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Competency Based Medical Education (CBME) is pushing the medical profession to be more accountable in our standards of assessment. This has led us to focus our efforts at the top of Miller’s pyramid, where we aim to see what the trainee ‘does’ in the clinical environment. In Canadian Royal College specialty training, this has come in the form of workplace-based supervision of trainees performing Entrustable Professional Activities (EPAs). This is unfamiliar territory for many residents and faculty, and implementation of an additional assessment process into already busy clinical practice has been particularly challenging. Because EPA assessments serve as significant contributors in new programs of assessment, failure to collect high quality EPA assessments threaten the validity of this new system. Understanding the barriers to and enablers of EPA acquisition can inform faculty development initiatives to ensure success. Based on our previous work studying early experiences of EPA assessment acquisition in Emergency Medicine, we have identified eight key concepts to guide faculty development initiatives, namely: the rationale for CBME, the ‘behind the scenes’ of CBME, how to construct rich narrative comments, effective use of supervision scales, the tension of EPA assessments being both formative and summative, the importance of a shared responsibility between residents and faculty for EPA assessment completion, familiarity with the suite of EPAs, and tips and tricks for incorporating EPA assessment completion into busy clinical practice. These key concepts can be integrated into an overall faculty development strategy for building this now essential skill set.

Objective The objective of this review was to summarise the literature on the relationship between PD and arterial stiffness.Design Systematic scoping review.Data sources PubMed, Embase, SPORTDiscus with full text and CINALH+ with full text databases were searched from inception to 10 July 2023.Eligibility criteria Adults (≥18 years), arterial stiffness measured as pulse wave velocity (PWV), PD assessment, and randomised control trial or observational study designs.Data extraction and synthesis Of 453 articles identified, four studies were included. Two studies were cross-sectional (United States, Brazil), one was longitudinal (United Kingdom), and another was a randomized control trial (United States).Results The age of the study populations ranged from 18 years to 75 years and one study evaluated a clinical population. All studies used different PWV devices and PD assessments. Associations between PD and PWV varied by geographical region, sex, clinical status and study design.Conclusion Research evaluating the association between PD and PWV is scarce and heterogeneous in PD and PWV assessments. There is an inconclusive association between PD and PWV.

ABSTRACT Introduction The increasing prevalence of shiftwork among young adults poses significant health risks, primarily due to its disruptive effects on sleep, nutrition and physical activity. Addressing these risks necessitates the development of tailored, evidence‐based resources to support these key health behaviours. Participatory research approaches, engaging those with relevant lived experience (i.e., co‐design) are a novel and effective approach in developing these resources. As such, the aim of the present study was to explore whether sleep, nutrition and physical activity resources for young shiftworkers could be developed using participatory, co‐design approaches and how co‐designers would rate both the approaches used and the resulting resources. Methods A participatory approach engaged co‐designers (young, experienced or previous shiftworkers; workplace health and safety specialists; science communicators and academic experts) to complete 2–3 online questionnaires and participate in 1–2 online workshops, to co‐design sleep, nutrition and physical activity resources for young shiftworkers. Following resource development, co‐designers assessed both the participatory approach and the resulting resources, through an online questionnaire, which included the Public and Patient Engagement Evaluation Tool (PPEET). Results Co‐designers (n = 48) participated in the development of sleep, nutrition and physical activity resources for young shiftworkers. Co‐designers evaluated the participatory approach positively, with a mean rating across all PPEET items of 4.7 (±0.2) on a 5‐point Likert scale. Co‐designers also provided positive ratings for the resources, with the majority (91.7%) either agreeing or strongly agreeing that they were user‐friendly, valuable and informative for young shiftworkers and would serve as a credible source of health information. Conclusion By adopting a novel participatory approach, we successfully co‐designed sleep, nutrition and physical activity resources for young shiftworkers. Participatory approaches, including co‐design, should be considered when developing health interventions for shiftworkers, given the value of embedding lived experience to address their unique lifestyle challenges. Patient or Public Contribution Co‐designers and/or people with relevant lived experience were involved in all project activities: conceptualisation, design, recruitment, data collection, data analysis, knowledge translation and output generation.

Abstract Adversity early in life can modify the trajectory for disease risk extending decades beyond the event. Preterm birth produces persistent cardiovascular alterations that may appear maladaptive in adulthood. We have previously hypothesized that those born preterm may exhibit cardiovascular vulnerability in the climate change context. Further, this vulnerability may be present as early as childhood. We aimed to identify the early signs of cardiovascular dysfunction at childhood‐equivalent age using our animal model of preterm birth. Using a whole‐body thermal stress test, guinea pigs aged 35‐d and 38‐d (equivalent to 8–10‐year‐old children) and born at term or preterm gestations were exposed to progressive hyper‐ (TC = 41.5°C) and hypo‐thermia (TC = 34°C; normothermia TC = 39°C). Comprehensive cardiovascular monitoring included ECG, blood pressure, microvascular perfusion, blood gas, and catecholamine profile, as well as skin and core body temperature. Preterm‐born animals exhibited attenuated vascular responses to hyperthermic stress, and a significant elevation in systolic blood pressure in response to hypothermic stress. Such responses are similar to those observed in elderly populations and indicate the presence of cardiovascular dysfunction. This is the first study to demonstrate the impact of preterm birth on the cardiovascular response to both heat and cold stress. Further, this dysfunction has been observed at an earlier age than that achievable using traditional stress testing techniques. The present findings warrant further investigation.

Abstract Objective The objective of this scoping review is to identify and understand the available evidence on the delivery of dietary messages to patients with type 2 diabetes in a dental setting. The outcome of a scoping review in this area will inform the development of a clinical intervention for dietary counseling at the chairside. Introduction Diabetics are at a higher risk for developing periodontal disease, and the severity of periodontal disease can impact the ability to control glucose levels. Considering the prevalence of diabetes within the community, dental practitioners are well placed to provide dietary messages to support this cohort during the management of periodontal disease. Inclusion Criteria Studies that consider the population affected by type 2 diabetes and a dietary intervention in the context of a dental setting will be included. Methods The databases selected for sources of studies are MEDLINE, EMBASE, CINAHL and SCOPUS. The scoping review will be conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews. Only English language studies are eligible for inclusion in this review. Terms relating to dietary advice, diabetes, dental practitioner and health education will be used to search for related studies. Screening based on abstract, and titles will be followed by full text screening with results supplied in PRISMA‐SCR diagram. A data extraction tool will be used to chart the details of selected studies then presented in a venn diagram and word map along with a narrative synthesis of results.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Metal‐based nanoparticles (NPs) have entered clinical use for enhancing radiotherapy, but the underlying mechanisms remain ambiguous. Herein, single‐cell analysis of two cell lines in response to megavolt irradiation and a radiomimetic drug, neocarzinostatin (NCS) after coculture with gold NPs with different surface coatings, polyethylene glycol (AuPEG), PEG, and transferrin (AuT) or silica (AuSiO2), is reported. Different surface chemistry presents a major challenge for objective comparison between the biological impacts where major differences in cell‐uptake exist. AuSiO2 NPs are the most efficient for promoting radiosensitization despite being associated with cells 10 times less than the actively targeted AuT NPs. Conversely, for cells exposed to NCS, AuSiO2 NPs impede the radiomimetic action and promote cell survival. AuT NPs enhance death of cells in combination with NCS showing that NPs can sensitize against cytotoxic agents in addition to radiation. While NPs contribute to radiosensitization (or enhancing/impeding chemotherapeutic drug activity), due to cell and cell line heterogeneity, the ultimate radiosensitivity of a cell appears to be dominated by its inherent radiosensitivity and how this cell‐regulated response is manipulated by NPs. This is evidenced through comparison of radiobiological response of cells with equivalent NP association rather than equivalent coculture conditions.

Introduction Lower limb apophyseal injuries commonly occur in children and adolescents with unknown incidence and prevalence. These conditions are considered benign, but impact children and adolescents quality of life and can lead to sport withdrawal at a crucial time. The primary aim of this research was to develop self-administered tools for two of the most common apophyseal injuries. The secondary aim was to test the sensitivity and specificity of the tools. Methods Study 1 used a three round online Delphi panel (n = 8), with expert consensus supported by robust literature. This panel developed a self-administered screening tool for calcaneal (Sever’s disease) and tibial tuberosity (Osgood-Schlatter’s disease) apophysitis. Study 2 tested the sensitivity and specificity of these developed tools with parents and children (n = 63) with concurrent clinical examination by a health professional. An initial sample size for Study 2 was set at 155 children however this was impacted by COVID-19 and recruitment was halted. Results Both tools had excellent diagnostic accuracy with an area under the curve of 83% (95% confidence interval = 0.70 to 0.95) for the posterior heel (calcaneal apophysitis) tool and 93% (95% confidence interval = 0.80 to 1.00) for the anterior of knee (tibial tuberosity apophysitis) tool using the pilot data from the 63 children. Conclusions These tools may also enhance opportunities for clinicians and health service providers with pre-clinical screening to reduce wait list time and encourage low cost, self-administered management where indicated. These findings may enable large epidemiological studies to identify populations and calculate incidence and prevalence of these conditions using self report.

Background: Symptoms of emotional and physical stress near death may be related to previous experiences of trauma. Objective: To investigate current evidence regarding the following: (1) Is previous trauma identified in people who are dying, and if so, how? (2) How is previous trauma associated with the experience of death/dying in people with or without cognitive impairment? and (3) What palliative care interventions are available to people with previous trauma at the end of life? Design: This integrative review was conducted per Whittemore and Knafl’s guidelines, which involves a stepped approach, specifically (1) problem identification, (2) literature search, (3) data evaluation, (4) data analysis and (5) presentation. Methods: This integrative review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Electronic databases were searched in August 2021 and updated in August 2023. The articles were quality appraised, and narrative data were analysed using Grounded Theory (GT). Results: Of 1310 studies screened, 11 met the inclusion criteria (four qualitative and seven quantitative) conducted in Australia, Canada, Japan and the United States; and American studies accounted for 7/11 studies. Eight were focused on war veterans. Descriptive studies accounted for the majority, with only two publications testing interventions. Re-living trauma near death has additional features to a diagnosis of post-traumatic stress disorder alone, such as physical symptoms of uncontrolled, unexplained acute pain and this distress was reported in the last weeks of life. Conclusion: This study proposes that re-living trauma near death is a recognisable phenomenon with physical and psychological impacts that can be ameliorated with improved clinical knowledge and appropriate management as a new GT. Further research is needed to enable past trauma identification at the end of life, and trauma-informed safe interventions at the end of life are an urgent need.

Abstract In situ spacecraft observations are critical to our study and understanding of the various phenomena that couple mass, momentum, and energy throughout near‐Earth space and beyond. However, on‐orbit telemetry constraints can severely limit the capability of spacecraft to transmit high‐cadence data, and missions are often only able to telemeter a small percentage of their captured data at full rate. This presents a programmatic need to prioritize intervals with the highest probability of enabling the mission's science goals. Larger missions such as the Magnetospheric Multiscale mission (MMS) aim to solve this problem with a Scientist‐In‐The‐Loop (SITL), where a domain expert flags intervals of time with potentially interesting data for high‐cadence data downlink and subsequent study. Although suitable for some missions, the SITL solution is not always feasible, especially for low‐cost missions such as CubeSats and NanoSats. This manuscript presents a generalizable method for the detection of anomalous data points in spacecraft observations, enabling rapid data prioritization without substantial computational overhead or the need for additional infrastructure on the ground. Specifically, Principal Components Analysis and One‐Class Support Vector Machines are used to generate an alternative representation of the data and provide an indication, for each point, of the data's potential for scientific utility. The technique's performance and generalizability is demonstrated through application to intervals of observations, including magnetic field data and plasma moments, from the CASSIOPE e‐POP/Swarm‐Echo and MMS missions.

Transgender people across Canada face high rates of housing insecurity and homelessness compared to people whose gender identity matches the sex they were assigned at birth. Yet shelters and transitional housing meant to provide temporary places to stay do not always meet the needs of transgender people. This community-based study asked what can make transitional housing safer and more comfortable for transgender people, with a focus on the Westman region of Manitoba. In collaboration with YWCA Brandon, the first author interviewed nine service providers who work in housing organizations or in service provision for transgender people in Manitoba, to learn about good practices from their perspectives. In the process we learned about the factors that make transitional housing and shelters unsafe and unwelcoming for transgender people; these factors are the focus of this article. We highlight barriers to access to existing transitional housing, including the prevalence of faith-based shelters, gender segregation policies and practices, intake and referral procedures that create risks for transgender people, and insufficient training for organization leaders. These findings are relevant to shelter and transitional housing providers and to allies and advocates for the well-being of transgender people in Manitoba and beyond.

Abstract Introduction Midfoot osteoarthritis (OA) is a painful and disabling condition. Arch contouring foot orthoses have been recommended for midfoot OA, yet there is no high‐quality evidence from randomised controlled trials to support their use. This clinical trial aims to evaluate the efficacy of arch contouring foot orthoses for midfoot OA. Methods This will be a parallel‐group randomised controlled superiority trial. One‐hundred and forty community‐dwelling people with painful midfoot OA will be randomised to receive either arch contouring foot orthoses or flat sham inserts. Outcome measures will be obtained at baseline, 4, 8 and 12 weeks; the primary endpoint for assessing efficacy being 12 weeks. The primary outcome measure will be average midfoot pain whilst walking over the last 7 days on an 11‐point numerical rating scale. Secondary outcome measures include function (walking/standing subscale of the Manchester–Oxford Foot Questionnaire), participants' perception of overall treatment effect (self‐reported global rating of change on a 15‐point Likert scale), physical activity (Incidental and Planned Exercise Questionnaire), general health‐related quality of life (Short Form‐12 Version® 2.0), use of co‐interventions and adverse events. Discussion This trial will evaluate the efficacy of arch contouring foot orthoses for relieving pain and improving function, physical activity and health‐related quality of life in people with midfoot OA. The findings will provide high‐quality evidence as to whether arch contouring foot orthoses are efficacious and will help to inform clinical guidelines about the use of foot orthoses for midfoot OA. Trial registration Australian and New Zealand Clinical Trial Registry (ACTRN12623000953639).

Objective/Approach The Black Health Equity Working Group's Applied Health Research Question aimed to compare cancer screening rates and surgical wait times between community health centre (CHC) clients based on race-related data and non-CHC clients. CHC client data was categorized by self-identified racial groups, with Black self-identification compared to non-Black racialized, White, and missing racial self-identification, and non-CHC clients. Health card numbers were encrypted to link individuals to the Primary Care Population dataset for breast, cervical, and colorectal cancer screening rates. Surgical wait time indicators, such as the number of patients undergoing surgery and average wait times for initial consultation and completed surgeries, were derived from the Wait Time Information System. Assessments were conducted semi-annually from fiscal year 2018 to 2021. Results Following the onset of COVID-19, CHC clients self-identifying as Black experienced the most significant decrease (6.8%) in colorectal screenings compared to other groups. Mammogram screenings remained consistently higher for CHC clients self-identifying as Black pre- and post-pandemic. Average cervical cancer screening rates were approximately 8% higher among CHC clients compared to non-CHC clients, irrespective of racial self-identification. However, due to small sample sizes and missing data among self-identified racial groups, trends in surgical wait times for both CHC and non-CHC clients were unstable. Conclusion/Implications Tailored interventions targeting Black CHC clients can enhance cancer screening rates, particularly colorectal screenings. The analysis of CHC data offers valuable insights into race-based disparities in health outcomes. Improved data completeness is essential for accurately assessing health outcome variations among different racial groups.

Objective To provide an update on the key characteristics, refinements to project flow, and future opportunities for a program providing customized research evidence to health system policymakers and providers. Approach With a goal to inform health system decision making, the program answers research questions posed by health system requestors that can be answered with linked, population-based administrative data. Now in its 10th year of operation, the program has been refined over time to improve efficiency, usefulness of research products, and requestor satisfaction. Satisfaction surveys and individual-level engagements with requestors are used to collect feedback on the needs of an increasingly diverse group of requests. Results With 508 requests, 82 Data Sharing Agreements, and 257 unique requestors since its inception, the program informs governmental decision making, evaluates intervention effectiveness, and aids grassroots organizations’ planning for services. Notable updates to the program include, inserting multiple opportunities for connection between the program and requestors through the project life cycle to understand goals and needs; assigning staff scientists to shepherd projects and promote efficiency; training coordinators to review privacy impact assessments; and (soon) accepting a broader range of projects to include data beyond the health sector e.g. education. Conclusion This program continues to improve and is an exemplar of sustainable approaches to supporting health system requestors with evidence from administrative data in program evaluation, planning and policy change. Implications Being responsive to requestor needs has allowed the program to attract an increasingly diverse range of requesters who can obtain impactful and timely research evidence.

Objective To highlight progress in facilitating and supporting pan-Canadian data analysis research that is supported by a central coordinating center. This process will be illustrated with the use of a recently completed project that has been supported using data from Alberta, British Columbia, and Ontario. Approach The project represents a significant endeavor within the central coordinating center, as it necessitates coordination for data access, data importation and analytical support across three provinces. The focus will be on the administrative processes refined to support collaborative research endeavors. While specific project details will remain undisclosed, procedural enhancements within the central coordinating center framework will be highlighted. Key discussion points include standardized protocols for data access, collaborative efforts to streamline data importation, and facilitation of analytical support across jurisdictions. The type of cross-jurisdictional analytic support will as well be highlighted; data variables harmonization and sharing of data algorithms cohorts across the participating provincial data centers in support of the meta-analysis. Results The successful completion of the final data analysis underscores the effectiveness of a unified data access coordination center for researchers seeking multi-regional health data in Canada. By highlighting advancements enabled by the central coordinating center and provincial data centers, this submission aims to inform researchers about the current landscape of pan-Canadian research and foster opportunities for future collaboration. Implications Sharing insights and lessons from this project emphasizes the advancements facilitated by the central coordinating center and provincial data centers, informing researchers about the potential of pan-Canadian research, and encouraging future collaborative endeavors.

Objective Stewards of population-level data have an obligation to serve the public interest. As one such publicly funded data steward, our Public Advisory Council (PAC) co-led and determined the focus of an analysis project using population-level administrative health data. We describe our engagement strategies herein. Approach The 20-member PAC was involved in each stage of the project, from research question formulation to knowledge translation planning over 18 months, consisting of 12 meetings with both large and smaller groups. Our approach to engagement applied the International Association for Public Participation’s Framework as the foundation for an ‘empowerment’ level of engagement and adapted approaches from the James Lind Alliance and the ‘Plan-Do-Study-Act’ cycle. Results The PAC chose to focus their analysis project on factors related to mental health and addiction service use. Four strategies were used and co-designed by members to foster engagement throughout: providing education and guidance, shared and guided brainstorming, building consensus, and responsiveness to feedback and evaluation. PAC members directed how and when these strategies were used, with challenges and lessons learned currently being co-developed into a publicly accessible report. Conclusions Our work demonstrates the importance and value of public-driven research outputs and the feasibility of integrating public members in the work of data stewards. Implications The insights and practical strategies generated from this project will be used to guide effective engagement of the public for future analysis projects and to improve trust and social license for other initiatives using population-level data.

Objective There is growing recognition of the importance of community data governance to build accountability of research institutions to communities. Our organization, a steward of health and administrative population-level data, has previously implemented community governance structures for Indigenous data. This scoping initiative explores development and implementation of an additional community governance structure for race-related data. Approach We conducted a scoping review of peer-reviewed and grey literature to identify existing practices of community data governance. We also conducted key informant interviews with thirteen racialized community stakeholders, who addressed open-ended questions on potential co-design processes as well as governance mandates, scopes, barriers, and facilitators. Results The scoping review identified eight community data governance examples. Two of these pertained to race-related data, while the remaining six pertained to other data that identified “community” geographically, by disease condition, life stage, and/or economic circumstance. Governance structures were diverse, ranging from one-time crowd-design of a data-sharing agreement to quarterly meetings of a governing board to review project-level data requests. Key informant interviews provided four themes to guide implementation in the context of our organization: exploring organizational readiness, considering who should be involved, defining the scope and mandate, and drafting an approach and process. Conclusion We are committed to implementing a community governance structure for race-related, population-level data. However, there are limited examples of similar structures in the existing literature. Implications The identified examples and the advice of community stakeholders will guide co-design of a preliminary structure, scope, and mandate for community governance of race-related, population-level data.

Background The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. Objective To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department. Design Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone. Setting United Kingdom Major Trauma Centres. Participants Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta. Interventions Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta. Main outcome measures Primary: Mortality at 90 days. Secondary: Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. Health economic: Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon. Data sources Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data). Results Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at any time point. Death due to haemorrhage was more common in the standard care plus resuscitative endovascular balloon occlusion of the aorta group than in the standard care group. There were no serious adverse device effects. Resuscitative endovascular balloon occlusion of the aorta is less costly (probability 99%), due to the competing mortality risk but also substantially less effective in terms of lifetime quality-adjusted life-years (probability 91%). Limitations The size of the study reflects the relative infrequency of exsanguinating traumatic haemorrhage in the United Kingdom. There were some baseline imbalances between groups, but adjusted analyses had little effect on the estimates. Conclusions This is the first randomised trial of the addition of resuscitative endovascular balloon occlusion of the aorta to standard care in the management of exsanguinating haemorrhage. All the analyses suggest that a strategy of standard care plus resuscitative endovascular balloon occlusion of the aorta is potentially harmful. Future work The role (if any) of resuscitative endovascular balloon occlusion of the aorta in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and is published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information. Plain language summary Trauma (physical injury) is a major cause of death and disability. The most common cause of preventable death after injury is uncontrolled bleeding. Resuscitative endovascular balloon occlusion of the aorta is a technique whereby a small balloon is inflated in the aorta (main blood vessel) which aims to limit blood loss until an operation can be done to stop the bleeding. In this study, which is the first randomised trial in the world of this technique, we investigated whether adding resuscitative endovascular balloon occlusion of the aorta to the standard care received in a major trauma centre reduced the risk of death in trauma patients who had life-threatening uncontrolled bleeding. The study took place in 16 major trauma centres in the United Kingdom. Ninety adult trauma patients with confirmed or suspected uncontrolled bleeding took part and were randomly divided into two groups: (1) those who received standard care and (2) those who received standard care plus resuscitative endovascular balloon occlusion of the aorta. We followed participants for 6 months using routinely collected data from the National Health Service and from the Trauma Audit Research Network registry. We also contacted surviving patients at 6 months to ask about their quality of life. In the standard care group, 42% of participants died within 90 days of their injury compared to 54% of participants in the standard care plus resuscitative endovascular balloon occlusion of the aorta group. Risk of death was also higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group at all other time points (3, 6 and 24 hours, in hospital and at 6 months). Overall, the study showed that the use of resuscitative endovascular balloon occlusion of the aorta in hospital increased the risk of death. Scientific summary Background Trauma is a major cause of death and disability. Trauma (physical injury) disproportionately affects the young, killing those who might otherwise have lived long and productive lives. The most common cause of preventable death after injury is haemorrhage. The addition of resuscitative endovascular balloon occlusion of the aorta (REBOA) to current standard care is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite, for definitive haemostasis. Objectives The UK-REBOA trial was a pragmatic, multicentre, Bayesian, open-label, group-sequential, parallel-group randomised controlled trial comparing standard care plus REBOA versus standard care in patients with exsanguinating haemorrhage in the emergency room. The study included an elicitation exercise, an embedded mixed-methods process evaluation and a health economic evaluation. The primary clinical outcome was 90-day mortality (defined as death within 90 days of injury, before or after discharge from hospital). Secondary clinical outcomes included 3-, 6- and 24-hour mortality, in-hospital mortality, 6-month mortality, length of stay (in hospital and intensive care unit), 24-hour blood product use, need for haemorrhage control procedures (operation or angioembolisation), time to commencement of haemorrhage control procedure, complications/safety data and functional outcome [measured using the extended Glasgow Outcome Scale (GOS-E)] at discharge. Economic outcomes were 6-month (within trial) and lifetime (modelled) UK NHS perspective costs, life-years and quality-adjusted life-years (QALYs) [calculated using EuroQol Group’s 5-dimension health status 5-level questionnaire (EQ-5D-5L)], 6-month quality of life (measured using EQ-5D-5L). Methods Trauma patients were recruited in 16 UK major trauma centres. Trauma patients aged (or believed to be aged) 16 years or older, with confirmed or suspected life-threatening torso haemorrhage thought to be amenable to adjunctive treatment with REBOA were eligible. Women known (or thought to be) pregnant and those with injuries deemed unsurvivable were excluded. The trauma team leader assessed the patients for eligibility. Patients who were eligible for inclusion in the trial were incapacitated and unable to give consent at the time of eligibility assessment and randomisation. There was also not sufficient time to consult a surrogate decision-maker, or even an independent medical practitioner, for advice about including the patient. Enrolment therefore took place without prior consent following Research Ethics Committee approval for this approach. Consent for continuing participation (i.e. data collection) was sought by a member of the UK-REBOA trial team once patients were no longer in a critical condition (defined as being cared for in a ward area rather than an intensive care unit or high-dependency unit) or from a personal (or nominated professional) consultee. The trauma team leader enrolled the participant using a dedicated, secure website, available on a handheld device (smartphone, tablet) or desktop computer which is linked directly to the 24-hour randomisation system at the Centre for Healthcare Randomised Trials, based in the Health Services Research Unit, University of Aberdeen. Patients were randomised into one of the two intervention arms, in a 1 : 1 allocation ratio, in randomly generated blocks of two or four. Standard care: Patients allocated to the control group received ‘standard care’, as expected in a specialist major trauma centre. Such treatment typically included intubation, blood transfusion including blood products in a 1 : 1 : 1 ratio, interventions such as tourniquet application, and early operative or endovascular haemorrhage control. Treatment could also have included open aortic occlusion of the thoracic or abdominal aorta. Standard care plus REBOA: Patients allocated to this arm of the trial additionally received the technique of endovascular aortic occlusion, for the purpose of resuscitation, as part of an overall treatment strategy. The addition of REBOA to current standard care was intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. The trial sought to evaluate the technique of REBOA rather than a specific brand of device, and therefore permitted the use of any licensed occlusion balloon, and did not prescribe or mandate a particular product. The trial had an integrated training programme to ensure familiarity with the REBOA procedure. In patients who had been randomised to the standard care plus REBOA arm of the trial, clinicians could decide not to insert the balloon occlusion device if: the patient’s haemodynamic status improved (as a result of other resuscitative measures), if they were deemed to no longer have life-threatening torso haemorrhage requiring adjunctive treatment with REBOA; they deteriorated (to the point of imminent death); or there was technical difficulty in obtaining arterial access, and it was felt that operative control of haemorrhage could be obtained more quickly. The data collection strategy for the UK-REBOA trial was designed to minimise the burden on participants and clinicians, and for the avoidance of duplication. The randomisation system collected balloon inflation/deflation times. The trial drew on routinely collected data, primarily from the Trauma Audit and Research Network (TARN) registry which includes demographic, injury, treatment and outcome data (including the GOS-E and EQ-5D-5L). Mortality and hospital resource use data were also sought from NHS Digital. The main analysis was based on the intention-to-treat principle. There were two planned interim analyses of survival and a final analysis of all outcomes after follow-up was complete. Baseline and follow-up data were summarised using descriptive statistics and graphical summaries. Treatment effects are presented with 95% credible intervals for the primary and secondary outcomes. Elicitation exercise An elicitation exercise involving 20 subject matter experts (12 emergency medicine physicians, 3 pre-hospital care doctors, 4 surgeons and 1 intensivist) was undertaken to derive prior probability distributions to help contextualise the interpretation for the primary and secondary outcomes of the trial. Subject matter experts, on average, estimated in-hospital and 90-day mortality in this patient group, without the use of REBOA, to be in excess of 50%. Mortality at earlier time points (6 and 24 hours) was estimated to be closer to 25%. The elicited data, and the resulting prior probability distributions, indicate that the experts, on average, had a favourable opinion of REBOA, that is they expect the addition of REBOA to standard care to improve mortality at all time points. Clinical results Sixteen recruitment sites were opened in a staggered manner. Recruitment commenced in October 2017, was halted in March 2020 due to COVID-19, and restarted in July 2020. The second interim analysis (including 80 participants) triggered one of the pre-specified stopping rules, and recruitment closed in March 2022, by which time 90 participants had been recruited. Forty-four participants were randomised to standard care (2 of whom did receive REBOA) and 46 were randomised to standard care plus REBOA (19 of whom had the catheter inserted and balloon inserted and the remaining 27 progressed to different time points along this pathway). The groups were well-matched in terms of age, gender, comorbidities, mechanism of injury and injury severity. In the standard care arm, the median age was 39 years (interquartile range 30–56 years) and 77% were male. In the standard care plus REBOA arm, the median age was 46 years (interquartile range 33–62) and 61% were male. The median Injury Severity Score in both arms was 41 (interquartile range 29–50), with the majority classed as having very severe injury. Of the 46 patients allocated to standard care plus REBOA treatment, 25 (54%) died within 90 days. Of the 43 standard care patients for whom primary outcome data are available, 18 (42%) died within 90 days. Using the minimally informative prior, the odds of 90-day mortality were 1.58 for patients allocated to the standard care plus REBOA arm (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (i.e. that REBOA was harmful) was 86.9%. The direction of the estimate did not change when an enthusiastic (the elicited) prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3-, 6- and 24-hour mortality), the posterior probability that REBOA was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at 3, 6 and 24 hours, at 90 days or 6 months, or in-hospital mortality. Death due to haemorrhage was more common in the standard care plus REBOA group than in the standard care group. The mean number of days spent in intensive care and in hospital were lower in the standard care plus REBOA group compared to the standard care group, partly because of the higher number of earlier deaths in the standard care plus REBOA arm. There were no serious adverse device effects. Health economics We costed individual components of resources and summed these to generate a total cost for the whole initial hospitalisation admission period. Total NHS resource use for the index hospitalisation was obtained from patient-level data in TARN and the key resource use variables for costing included time of arrival, time of emergency department departure, time of first operation, time of death/discharge, number and type of operative procedures and volume of blood transfusions that were required. Secondary care contacts and episodes of care that were commenced between the date of discharge from the index hospitalisation through 6 months post randomisation were sourced, where available, through linkage of patient records to the Hospital Episode Statistics database. All costs are reported from a UK NHS perspective in Great British pounds (GBP) (year 2020-1). Quality of life was measured using the EQ-5D-5L prior to patient’s discharge from their index hospitalisation and at 6 months post admission. EQ-5D-5L asks respondents to report any problems on a given day across five dimensions of mobility, self-care, usual activities, anxiety/depression and pain. The data were available from TARN and supplemented with data collected by the local trial teams. EQ-5D-5L data were cross-walked to the 3L version and valued using UK general population preference tariffs. Baseline utility was set equal to the unconscious state (−0.402) and utility following death was set to 0. QALYs were calculated using an area under the curve approach assuming linear extrapolation between time points. From the within-trial health economic analysis, participants in the standard care plus REBOA arm of the study incurred lower costs {index hospital admission: mean cost £57,384 [standard deviation (SD) £62,863]} compared to those in standard care [mean cost £116,064 (SD £128,957)]. Lower costs in the standard care plus REBOA arm of the study were mainly due to lower use of hospital resources (length of stay, etc.) due to the competing risk of death (i.e. a higher number of deaths in the REBOA plus standard care group). Similarly, life-years accrued and QALYs over 6 months post randomisation were also lower in standard care plus REBOA compared to standard care due to a greater proportion of trial participants dying, with mortality also occurring earlier in the follow-up period for the REBOA arm. The mean life-years gained in the standard care plus REBOA arm was 0.232 (SD 0.247) compared to 0.305 (SD 0.236) in the standard care arm. When modelled over a full lifetime horizon, standard care plus REBOA is less costly (probability 99%), due to the competing risk of mortality but is also substantially less effective in terms of QALYs accrued over a lifetime horizon (probability 91%). The findings are robust to a range of scenario analyses undertaken, with the probability of standard care being the optimal treatment strategy ranging from 66% to 81% at a threshold value of a QALY = £50,000. Process evaluation The process evaluation was conducted in two phases; both phases involved interviews with clinical and research staff based at recruitment sites. Phase 1 was designed to identify barriers during trial initial and set-up; Phase 2 focused on exploring barriers and facilitators of recruitment into the trial and intervention delivery. A behavioural framework was used in Phase 2 to direct analysis and generate solutions designed to enhance trial practices, which included regular online meetings between the principal investigators from each site, updates to training materials and delivery, and e-mail/Twitter feedback on recruitment activity. Conclusions This is the first randomised trial ever to be conducted examining the potential clinical effectiveness of REBOA for the management of exsanguinating haemorrhage. All the analyses conducted suggest with high probability that a strategy of standard care plus REBOA is harmful. Implications for health care: The continuing use of REBOA, at least in the UK in-hospital setting, should be re-evaluated. Implications for research: The role (if any) of REBOA in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and will be published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information.

Background and purpose: Total hip arthroplasty (THA) can be performed through various surgical approaches, including direct anterior (DAA). DAA-THA may offer faster recovery but carries a higher risk of complications, which may be mitigated by surgeon volume and experience. We examined the association of surgeons’ annual surgical volume with major complications after DAA-THA in a population-based sample. Methods: A population-based retrospective cohort study was carried out on primary DAA-THA patients in Ontario between April 2016 and March 2021. We used restricted cubic splines to visually define the association between annual DAA surgeon volume and the risk of major surgical complications (fractures, dislocations, infections, and revisions) within 1 year of surgery. We further compared the complication rates amongst different DAA volume categories (< 30, 30–60, and > 60 cases/year). Results: The study encompassed 9,672 DAA-THA patients (52% female, median age 67 years). We showed a sharp decline in the probability of complications as the surgical volume of DAA-THA increased within the lower range of 0–30 cases/year; the probability slightly increased after the surgical volume exceeded 60 cases/year. The overall complication rates were 3.09%, 2.24%, and 2.18% for the surgical experience group of < 30 cases/year, 30–60 cases/year, and > 60 cases/year, respectively. Conclusion: There was an inverse relationship between surgical volume and complication rates in DAA-THA within the lower volume ranges. Maintaining a surgical volume of at least 30 DAA-THA cases/year can minimize complications, emphasizing the importance of surgical volume in this approach.

Background: As people age the risk of dementia increases. Balance and strength deteriorate with ageing, but their associations with dementia are not clear. We aimed to determine relationships of balance and strength performance with incident dementia in the Health in Men Study (HIMS) cohort. Methods: We used wave 4 of the HIMS as baseline for analyses (2011–2013), following 1261 men until December 2017 via data linkage to determine incident dementia. Balance was measured using a modified Balance Outcome Measure for Elder Rehabilitation (mBOOMER) Score and strength with the knee extension test. Cox proportional hazards regression was used, adjusting for sociodemographic and health data. Strength and balance scores were analysed non-linearly using restricted cubic splines. Results: 13.7% of men were diagnosed with dementia over a mean period of 4.7 (SD 1.5) years. Higher baseline mBOOMER scores were associated with a reduced risk of incident dementia, with greater changes in risk at higher mBOOMER scores (9 vs 8: HR 0.80, 95% CI 0.73–0.88; 12 vs 11: 0.49, 95% HR 0.36–0.68). Higher baseline lower limb strength was associated with a reduced risk of incident dementia, with greater changes occurring at lower scores, plateauing at around 25 kg (5 vs 4: HR 0.93, 95% CI 0.89–0.98; 25 vs 24: HR 0.99, 95% CI 0.95–1.03). Conclusions: This study demonstrated a non-linear association of better performance in both strength and balance with reduced likelihood of incident dementia. These results raise the hypothesis that strategies to improve strength and balance could reduce the incidence of dementia in older men.

Alcohol dependence (AD) and gambling disorder (GD) are common addiction disorders with significant physical and mental health consequences. AD and GD are associated with dysregulated responses to reward which could be due to a common mechanism of dysregulated endogenous opioid signalling. We explored associations between reward anticipation responses, using the Monetary Incentive Delay (MID) functional magnetic resonance imaging (fMRI) task, and mu-opioid receptor (MOR) availability and endogenous opioid release capacity using [11C]carfentanil positron emission tomography (PET), in 13 AD, 15 GD and 14 heathy control (HC) participants. We also examined differences in MID task reward anticipation responses between AD, GD and HC participants. These were secondary exploratory analysis of data collected to examine differences in MOR PET in addiction. We did not find significant differences in MID win > neutral anticipation BOLD responses compared between participant groups in a priori ROIs (ventral striatum, putamen, caudate) or whole brain analyses. We found no significant correlations between MID win > neutral anticipation BOLD responses and [11C]carfentanil PET measures, except for limited negative correlations between putamen MOR availability and MID win > neutral anticipation BOLD response in AD participants. Previous research has suggested a limited role of endogenous opioid signalling on MID task reward anticipation responses in AD and HCs as these responses are not modulated by opioid receptor blockade and this may explain our lack of significant correlations in HC and AD or GD participants. Our results, particularly the lack of differences in MID win > neutral anticipation BOLD responses across participants groups, may be limited due to only including AD or GD participants who are abstinent or in active treatment.

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects, ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in the life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nano-particle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration.

Abstract: We present the first survey of quiet Sun features observed in hard X-rays (HXRs), using the Nuclear Spectroscopic Telescope ARray (NuSTAR), a HXR focusing optics telescope. The recent solar minimum, combined with NuSTAR’s high sensitivity, has presented a unique opportunity to perform the first HXR imaging spectroscopy on a range of features in the quiet Sun. By studying the HXR emission of these features, we can detect or constrain the presence of high temperature (> 5 MK) or non-thermal sources, to help understand how they relate to larger, more energetic solar phenomena, and determine their contribution to heating the solar atmosphere. We report on several features observed in the 28 September 2018 NuSTAR full-disk quiet Sun mosaics, the first of the NuSTAR quiet Sun observing campaigns, which mostly include steady features of X-ray bright points and an emerging flux region, which later evolved into an active region, as well as a short-lived jet. We find that the features’ HXR spectra are well fitted with isothermal models with temperatures ranging between 2.0 – 3.2 MK. Combining the NuSTAR data with softer X-ray emission from Hinode/XRT and EUV from SDO/AIA, we recover the differential emission measures, confirming little significant emission above 4 MK. The NuSTAR HXR spectra allow us to constrain the possible non-thermal emission that would still be consistent with a null HXR detection. We found that for only one of the features (the jet) was there a potential non-thermal upper limit capable of powering the heating observed. However, even here, the non-thermal electron distribution had to be very steep (effectively mono-energetic) with a low energy cut-off between 3 – 4 keV.

Measurement-based care is an approach to clinical care that involves systematically evaluating patient-reported outcomes to guide clinical decision making with a strong evidence base in the general population; however, its use in autism is limited. As autistic people are more likely to be diagnosed with psychiatric disorders (e.g. depression, anxiety) and to use psychiatric services (e.g. psychotherapy) than the general population, efforts to enhance clinical care for this population are critical. The current proof-of-concept study presents the development and pilot administration of an autism-adapted measurement-based care (MBC-AUT) system for psychotherapy designed for and with autistic people, as well as preliminary data on the feasibility, acceptability, benefits, and barriers to the adoption of the system for clients and clinicians. Findings from the first 18 youth and adult clients to use the system suggest that the MBC-AUT system is feasible and acceptable. Important benefits of the MBC-AUT system for clients and clinicians were identified through semi-structured interviews, and some barriers to the use of the MBC-AUT system were raised. Potential solutions are presented to address these barriers and to reduce the client and clinician burden. As autistic clients continue to seek psychological services, efforts to enhance the delivery and quality of psychotherapy for this population are essential.

Multiple studies have shown that language learners and other students undertaking postsecondary studies in an additional language (L2) consult digital translation tools to complete course-related work despite general disapproval of their use by instructors. Significant improvements in the accuracy of machine translation (MT) along with their widespread use among students present ethical and pedagogical implications that have yet to be coherently addressed by instructors and institutions at the tertiary level. Recognizing MT as inextricable from L2 users' academic realities, this article reviews the current research on perceptions and purposes of its use in higher education institutions, discusses MT at the policy level (e.g., gaps in legislation related to academic integrity and, more broadly, inconsistencies between the aims of internationalization and the continued delegitimization of marginalized varieties of English), outlines various ways that MT can be harnessed to support learning (e.g., for vocabulary acquisition, writing, metalinguistic awareness, learner autonomy), and suggests ways forward in education, research, and theory on the intersection of MT and learning.

The escalating challenge of antimicrobial resistance (AMR) has led to a surge of global research and policy discourse on refilling an empty antibiotic pipeline. The empty pipeline metaphor is, however, wrought with paradoxes. Drawing on critical social sciences and humanities research on pharmaceutical innovation, this comment article presents five of the key paradoxes that structure contemporary innovation discourse: Was the so-called “Golden Age” of antibiotics really golden? Was rational drug design truly rational in terms of antibiotic development? Was the antibiotic pipeline really built on a foundation of scientific breakthroughs by an elite group of (male) inventors? How can antibiotics, powerful symbols of industrial power, be considered as market failures? How could the crisis of antibiotics become the golden hour of their policing? Rather than dissect each paradox, the article aims to complicate standard problem diagnoses and encourage creative new conceptualizations of inclusive antimicrobial innovation.

Abstract The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called ‘FLip’ mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.

Abstract Background Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes. Methods The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada. The program consisted of a one-time overview survey of physician practice to establish overall practice parameters, followed by a review of at least 5 severe asthma patients to establish the current landscape of severe asthma management. Results The program collected practice overview surveys from 78 specialists (52 Respirologists, 24 Allergists, and 2 General practice physicians with an interest in respiratory disease) in 8 provinces. Practices included a variety of types in both large metropolitan centres and smaller regional settings. There were 503 patients reviewed and included in the program. Most (65%) patients were currently using a biologic treatment, 30% were biologic naive, and 5% had used a biologic treatment in the past. Most patients (53%) were reported to have mixed allergic and eosinophilic phenotypes, despite a perception that allergic, eosinophilic and mixed phenotypes were evenly balanced in the physician practice. Overall, patients currently treated with biologic agents had parameters suggesting higher control and were more satisfied with treatment. However, there was less than optimal treatment satisfaction for more than half of all patients, particularly for those patients not treated with a biologic agent. Conclusions Phenotyping is hampered by poor availability for several assessments, and the full range of treatments are not currently fully utilized, partly due to physician familiarity with the agents and partly due to prescribing restrictions. Even when treated with biologic agents, patient satisfaction can still be improved.

Abstract Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B. anthracis Sterne strain, which is the strain used in the manufacture of the UK anthrax vaccine. Then, for the first time, we quantify PA production and degradation via mathematical modelling and Bayesian statistical techniques, making use of this new experimental data as well as two other independent published data sets. We propose a single mathematical model, in terms of delay differential equations (DDEs), which can explain the in vitro dynamics of all three data sets. Since we did not heat activate the B. anthracis spores prior to inoculation, germination occurred much slower in our experiments, allowing us to calibrate two additional parameters with respect to the other data sets. Our model is able to distinguish between natural PA decay and that triggered by bacteria via proteases. There is promising consistency between the different independent data sets for most of the parameter estimates. The quantitative characterisation of B. anthracis PA production and degradation obtained here will contribute towards the ambition to include a realistic description of toxin dynamics, the host immune response, and anti-toxin treatments in future mechanistic models of anthrax infection.