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Abstract In sub-Saharan Africa, young people are at high risk of HIV infection, representing nearly 4 out of 5 new infections. HIV self-testing (HIVST), a new and proactive testing scheme that involves self-collection of a specimen and interpretation of results, is deemed potentially helpful for increasing testing amongst population groups like young people who do not frequently use routine testing services. This study assessed young people’s intention to use HIVST in urban areas of southern Ethiopia drawing on the Theory of Planned Behaviour. A community-based cross-sectional study was conducted with 634 participants aged 15–24 years from six town administrations of two zones in January to February 2023. The participation rate was 634/636 yielding 99.7%. The OraQuick HIVST kit was demonstrated to young people recruited in a door-to-door survey with a face-to-face interview using an electronic questionnaire in a mobile phone-based application. Intention to use HIVST was measured from a 6-point Likert scale with scores of agreements ranging from 1 to 6. Descriptive statistics and ordinal logistic regression analysis were done using STATA version 18. Most of the participants agreed that they would use HIVST if it was available (86.3% agreeing or strongly agreeing). Interestingly, young people who perceived themselves at some to high risk were 0.51 times less likely to be in the higher order of intention to use when HIVST is available to them than those who perceived themselves at no to low risk. Intention to use HIVST increased by a factor of 1.29, 1.84 and 2.35 for every one-unit increase on the mean favourable attitude, perceived behavioural control, and acceptability scores, respectively. The majority of young people intended to use HIVST. Young people’s perceived behavioural control, and acceptability of HIVST affected their intention to use. Intention and subsequent use of HIVST can be enhanced through an understanding of the role of risk perception and positive attitude, confidence to perform and acceptance of the test. Implementation studies are required to examine the actual uptake of HIVST among young people.

Abstract 18F-GP1 is a novel highly specific radiotracer that binds to activated platelets and thrombus. We aimed to establish the observer repeatability of coronary, carotid and cerebral 18F-GP1 uptake in patients presenting with acute myocardial infarction or ischaemic stroke. Forty-three patients presenting with acute myocardial infarction or ischaemic stroke underwent hybrid positron emission tomography (PET) and computed tomography (CT) angiography. Qualitative and quantitative assessment of 18F-GP1 uptake was performed on coronary arteries, carotid arteries and brain parenchyma. Qualitative uptake of 18F-GP1 had excellent intraobserver and interobserver agreement, with complete agreement for the presence or absence of visual 18F-GP1 uptake. For quantitative analysis, there were excellent intraclass correlation coefficients for intraobserver repeatability for coronary artery, carotid artery and brain parenchymal SUVmax and TBRmax measurements (all ≥ 0.92). Coronary artery and brain parenchymal analyses showed the strongest agreement in SUVmax values with mean biases of − 0.04 (limits of agreement − 0.21 to 0.20) and 0.02 (limits of agreement − 0.29 to 0.32) respectively. There was good interclass correlation coefficients for interobserver repeatability for coronary artery, carotid artery and brain parenchymal SUVmax and TBRmax measurements (all ≥ 0.89). The strongest interobserver agreement was seen with brain parenchymal SUVmax (mean SUVmax 1.95 ± 0.94) and TBRmax (mean TBRmax 9.55 ± 6.56) with mean biases of − 0.05 (limits of agreement − 0.37 to 0.27) and 0.04 (limits of agreement − 0.59 to 0.52) respectively. Visual qualitative and quantitative 18F-GP1 PET-CT image analyses provide robust and repeatable measurements of activated platelets and thrombi within the coronary arteries, carotid arteries and brain parenchyma.

Abstract Racism is an insidious problem with far-reaching effects on the lives of Black, Indigenous, and People of Color (BIPOC). The pervasive negative impact of racism on mental health is well documented. However, less is known about the potential downstream impacts of maternal experiences of racism on offspring neurodevelopment. This study sought to examine evidence for a biological pathway of intergenerational transmission of racism-related trauma. This study examined the effects of self-reported maternal experiences of racism on resting state functional connectivity (rsFC) in n = 25 neonates (13 female, 12 male) birthed by BIPOC mothers. Amygdala and hippocampus are brain regions involved in fear, memory, and anxiety, and are central nodes in brain networks associated with trauma-related change. We used average scores on the Experiences of Racism Scale as a continuous, voxel-wise regressor in seed-based, whole-brain connectivity analysis of anatomically defined amygdala and hippocampus seed regions of interest. All analyses controlled for infant sex and gestational age at the 2-week scanning session. More maternal racism-related experiences were associated with (1) stronger right amygdala rsFC with visual cortex and thalamus; and (2) stronger hippocampus rsFC with visual cortex and a temporo-parietal network, in neonates. The results of this research have implications for understanding how maternal experiences of racism may alter neurodevelopment, and for related social policy.

Abstract Seaweed farming is widely promoted as an approach to mitigating climate change despite limited data on carbon removal pathways and uncertainty around benefits and risks at operational scales. We explored the feasibility of climate change mitigation from seaweed farming by constructing five scenarios spanning a range of industry development in coastal British Columbia, Canada, a temperate region identified as highly suitable for seaweed farming. Depending on growth rates and the fate of farmed seaweed, our scenarios sequestered or avoided between 0.20 and 8.2 Tg CO2e year−1, equivalent to 0.3% and 13% of annual greenhouse gas emissions in BC, respectively. Realisation of climate benefits required seaweed-based products to replace existing, more emissions-intensive products, as marine sequestration was relatively inefficient. Such products were also key to reducing the monetary cost of climate benefits, with product values exceeding production costs in only one of the scenarios we examined. However, model estimates have large uncertainties dominated by seaweed production and emissions avoided, making these key priorities for future research. Our results show that seaweed farming could make an economically feasible contribute to Canada’s climate goals if markets for value-added seaweed based products are developed. Moreover, our model demonstrates the possibility for farmers, regulators, and researchers to accurately quantify the climate benefits of seaweed farming in their regional contexts.

BackgroundSexual minority men are disproportionately affected by methamphetamine use, with recent studies suggesting an increase in use specifically among Black sexual minority men. Black sexual minority men face unique structural barriers to achieving optimal health. Given its harmful effects, and in light of existing health disparities, an increase in methamphetamine use among Black sexual minority men poses a significant public health concern. ObjectiveThe Health Impacts and Struggles to Overcome the Racial Discrimination of Yesterday (HISTORY) study is investigating the potential impacts of exposure to the census tract–level structural racism and discrimination (SRD) on methamphetamine use among Black sexual minority men in Atlanta, Georgia, and will identify intervention targets to improve prevention and treatment of methamphetamine use in this population. MethodsThis study uses a mixed methods and multilevel design over a 5-year period and incorporates participatory approaches. Individual-level quantitative data will be collected from a community-based cohort of Black sexual minority men (N=300) via periodic assessment surveys, ecological momentary assessments, and medical record abstractions. Census tract–level measures of SRD will be constructed using publicly available administrative data. Qualitative data collection will include longitudinal, repeated in-depth interviews with a subset (n=40) of study participants. Finally, using a participatory group model–building process, we will build on our qualitative and quantitative data to generate causal maps of SRD and methamphetamine use among Black sexual minority men, which in turn will be translated into actionable recommendations for structural intervention. ResultsEnrollment in the HISTORY study commenced in March 2023 and is anticipated to be completed by November 2024. ConclusionsThe HISTORY study will serve as a crucial background upon which future structural interventions can be built, to mitigate the effects of methamphetamine use and SRD among Black sexual minority men. International Registered Report Identifier (IRRID)DERR1-10.2196/63761

The reemergence of primitive reflexes (PRs) in older age is related to cognitive impairment. Currently, there are no means to prevent or slow their reappearance, but research evidence exists for their control in children. Therefore, this experiment investigated whether a 16-week special sensorimotor exercise program could benefit older adults and whether the intervention-induced changes (if any) may be associated with various indices of mental health. Of 115 adults over 60, 95 completed the study (mean age = 76.37 ± SD = 7.04 years, 22 % men). The experimental group (n = 38) showed an almost threefold decline in PRs compared to controls. In contrast, the control group (n = 57) exhibited a nearly threefold increase in PRs compared to the intervention group. Cognitive function increased in the experimental but not in the control group. Changes in PRs over the 16-week intervention were positively related to negative mental health indices (hopelessness and perceived stress) and negatively related to well-being. These findings suggest that the here-presented mild sensorimotor exercises could affect older adults' reemerging PRs and that changes in PRs are associated with mental health benefits. These results may open new research avenues toward preventing cognitive and psychological decline in older adults.

Starvation ketoacidosis represents one of the three forms of metabolic acidosis caused by the accumulation of ketone bodies within the blood stream. It can be easily missed in patients who present acutely and are found to have an unexplained or profound metabolic acidosis. Here, we present a life-threatening case of severe ketoacidosis in a breast-feeding mother without diabetes who was on a strict ketogenic diet. Although a ketogenic diet has been previously considered to be safe in non-pregnant individuals, its safety in breast-feeding mothers in the post-partum period is less known and may be associated with greater harm. Health professionals and mothers should be aware of the potential risks associated with a strict ketogenic diet when combined with breast-feeding, especially in the earlier stages of the post-partum period. Prompt investigation, diagnosis and immediate management is vital to avoid life-threatening complications. We report a case admitted on the acute medical take with starvation ketoacidosis associated with ketogenic diet and adequate calorie consumption who was breast-feeding at the time of admission.

Abstract Protected areas are traditionally the foundation of conservation strategy, but land not formally protected is of particular importance for the conservation of large carnivores because of their typically wide-ranging nature. In South Africa, leopard (Panthera pardus) population decreases are thought to be occurring in areas of human development and intense negative interactions, but research is biased towards protected areas, with quantitative information on population sizes and trends in non-protected areas severely lacking. Using Spatially Explicit Capture-Recapture and occupancy techniques including 10 environmental and anthropogenic covariates, we analysed camera trap data from commercial farmland in South Africa where negative human-wildlife interactions are reported to be high. Our findings demonstrate that leopards persist at a moderate density (2.21 /100 km2) and exhibit signs of avoidance from areas where lethal control measures are implemented. This suggests leopards have the potential to navigate mixed mosaic landscapes effectively, enhancing their chances of long-term survival and coexistence with humans. Mixed mosaics of agriculture that include crops, game and livestock farming should be encouraged and, providing lethal control is not ubiquitous in the landscape, chains of safer spaces should permit vital landscape connectivity. However, continuing to promote non-lethal mitigation techniques remains vital.

Abstract High grade serous carcinoma (HGSC) metastasises primarily intraperitoneally via cancer spheroids. Podocalyxin (PODXL), an anti-adhesive transmembrane protein, has been reported to promote cancer survival against chemotherapy, however its role in HGSC chemoresistance is unclear. This study investigated whether PODXL plays a role in promoting chemoresistance of HGSC spheroids. We first showed that PODXL was expressed variably in HGSC patient tissues (n = 17) as well as in ovarian cancer cell lines (n = 28) that are more likely categorised as HGSC. We next demonstrated that PODXL-knockout (KO) cells proliferated more slowly, formed less compact spheroids and were more fragile than control cells. Furthermore, when treated with carboplatin and examined for post-treatment recovery, PODXL-KO spheroids showed significantly poorer cell viability, lower number of live cells, and less Ki-67 staining than controls. A similar trend was also observed in ascites-derived primary HGSC cells (n = 6)—spheroids expressing lower PODXL formed looser spheroids, were more vulnerable to fragmentation and more sensitive to carboplatin than spheroids with higher PODXL. Our studies thus suggests that PODXL plays an important role in promoting the formation of compact/hardy HGSC spheroids which are more resilient to chemotherapy drugs; these characteristics may contribute to the chemoresistant nature of HGSC.

Abstract Repeated stress can predispose to substance abuse. However, behavioral and neurobiological adaptations that link stress to substance abuse remain unclear. This study investigates whether intermittent social defeat (ISD), a stress protocol that promotes drug-seeking behavior, alters intertemporal decision-making and cortical inhibitory function in the medial prefrontal cortex (mPFC). Male long evans rats were trained in a delay discounting task (DDT) where rats make a choice between a fast (1 s) small reward (1 sugar pellet) and a large reward (3 sugar pellets) that comes with a time delay (10 s or 20 s). A decreased preference for delayed rewards was used as an index of choice impulsivity. Rats were exposed to ISD and tested in the DDT 24 h after each stress episode, and one- and two-weeks after the last stress episode. Immunohistochemistry was performed in rat’s brains to evaluate perineuronal nets (PNNs) and parvalbumin GABA interneurons (PV) labeling as markers of inhibitory function in mPFC. ISD significantly decreased the preference for delayed large rewards in low impulsive, but not high impulsive, animals. ISD also increased the density of PNNs in the mPFC. These results suggest that increased choice impulsivity and cortical inhibition predispose animals to seek out rewards after stress.

This article discusses the different manner in which psychotropic medications and behavioral interventions can interact when treating dually diagnosed clients. Case examples representing possible illustrations of permutations of these interactions are discussed. It is argued that the potential effect of one treatment procedure on the efficacy of another should be considered. (Contains references.) (Author/CR)

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Abstract Recent work by our laboratory and others indicates that co-display of multiple antigens on protein-based nanoparticles may be key to induce cross-reactive antibodies that provide broad protection against disease. To reach the ultimate goal of a universal vaccine for seasonal influenza, a mosaic influenza nanoparticle vaccine (FluMos-v1) was developed for clinical trial (NCT04896086). FluMos-v1 is unique in that it is designed to co-display four recently circulating haemagglutinin (HA) strains; however, current vaccine analysis techniques are limited to nanoparticle population analysis, thus, are unable to determine the valency of an individual nanoparticle. For the first time, we demonstrate by total internal reflection fluorescence microscopy and supportive physical–chemical methods that the co-display of four antigens is indeed achieved in single nanoparticles. Additionally, we have determined percentages of multivalent (mosaic) nanoparticles with four, three, or two HA proteins. The integrated imaging and physicochemical methods we have developed for single nanoparticle multivalency will serve to further understand immunogenicity data from our current FluMos-v1 clinical trial.

Abstract Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death worldwide. Cigarette smoke which has approximately 2–3 µg of Cadmium (Cd) per cigarette contributes to the environmental exposure and development and severity of COPD. With the lack of a cadmium elimination mechanism in humans, the contribution of cadmium induced stress to lung epithelial cells remains unclear. Studies on cadmium responsive miRNAs suggest regulation of target genes with an emphasis on the critical role of miRNA–mRNA interaction for cellular homeostasis. Mir-381, the target miRNA in this study is negatively regulated by cadmium in airway epithelial cells. miR-381 is reported to also regulate ANO1 (Anoctamin 1) expression negatively and in this study low dose cadmium exposure to airway epithelial cells was observed to upregulate ANO1 mRNA expression via mir-381 inhibition. ANO1 which is a Ca2+-activated chloride channel has multiple effects on cellular functions such as proliferation, mucus hypersecretion and fibroblast differentiation in inflamed airways in chronic respiratory diseases. In vitro studies with cadmium at a high concentration range of 100–500 µM is reported to activate chloride channel, ANO1. The secretory epithelial cells are regulated by chloride channels like CFTR, ANO1 and SLC26A9. We examined “ever” smokers with COPD (n = 13) lung tissue sections compared to “never” smoker without COPD (n = 9). We found that “ever” smokers with COPD had higher ANO1 expression. Using mir-381 mimic to inhibit ANO1, we demonstrate here that ANO1 expression is significantly (p

Introduction Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not.Methods and analysis Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities.Ethics and dissemination This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.

BackgroundAcute mental health services report high levels of safety incidents that involve both patients and staff. The potential for patients to be involved in interventions to improve safety within a mental health setting is acknowledged, and there is a need for interventions that proactively seek the patient perspective of safety. Digital technologies may offer opportunities to address this need. ObjectiveThis research sought to design and develop a digital real-time monitoring tool (WardSonar) to collect and collate daily information from patients in acute mental health wards about their perceptions of safety. We present the design and development process and underpinning logic model and programme theory. MethodsThe first stage involved a synthesis of the findings from a systematic review and evidence scan, interviews with patients (n=8) and health professionals (n=17), and stakeholder engagement. Cycles of design activities and discussion followed with patients, staff, and stakeholder groups, to design and develop the prototype tool. ResultsWe drew on patient safety theory and the concepts of contagion and milieu. The data synthesis, design, and development process resulted in three prototype components of the digital monitoring tool (WardSonar): (1) a patient recording interface that asks patients to input their perceptions into a tablet computer, to assess how the ward feels and whether the direction is changing, that is, “getting worse” or “getting better”; (2) a staff dashboard and functionality to interrogate the data at different levels; and (3) a public-facing ward interface. The technology is available as open-source code. ConclusionsRecent patient safety policy and research priorities encourage innovative approaches to measuring and monitoring safety. We developed a digital real-time monitoring tool to collect information from patients in acute mental health wards about perceived safety, to support staff to respond and intervene to changes in the clinical environment more proactively.

Abstract Vascular congestion and coagulopathy have been shown to play a role in human and experimental cerebral malaria (eCM), but little is known about the role of microglia, or microglia-vascular interactions and hypercoagulation during disease progression in this fatal infection. Recent studies show microglia bind to fibrinogen, a glycoprotein involved in thrombosis. An eCM model of Plasmodium chabaudi infection in mice deficient in the regulatory cytokine IL-10 manifests neuropathology, including hypercoagulation with extensive fibrin(ogen) deposition and neuroinflammation. Intravital microscopy and immunofluorescence are applied to elucidate the role of microglia in eCM. Results show microgliosis and coagulopathy occur early in disease at 3 dpi (day post-infection), and both are exacerbated as disease progresses to 7dpi. Vessel associated microglia increase significantly at 7 dpi, and the expression of the microglial chemoattractant CCL5 (RANTES) is increased versus uninfected and localized with fibrin(ogen) in vessels. PLX3397 microglia depletion resulted in rapid behavioral decline, severe hypothermia, and greater increase in vascular coagulopathy. This study suggests that microglia play a prominent role in controlling infection-initiated coagulopathy and supports a model in which microglia play a protective role in cerebral malaria by migrating to and patrolling the cerebral vasculature, potentially regulating degree of coagulation during systemic inflammation.

The reported study compared the impact of four influence strategies (agency assignment, enhanced active choice, deviance regulation marking, and temporal framing) on English- and Spanish-speaking parents’ reported intention to vaccinate their children for HPV. An online experiment was conducted to examine the impact of the strategies. In a fractional factorial design, participating parents (N = 1663) were exposed to combinations of influence strategies in text messages presented as reminders they might receive from a healthcare provider about their child’s eligibility for the vaccine series. The results indicated small but significant impacts of agency assignment, enhanced active choice, and deviance regulation marking on parents’ reported vaccination intentions. The study adds to the research literature on HPV vaccination communication in two important respects. First, it demonstrated how incorporating evidence-based influence strategies into reminder messages can increase parents’ vaccination intentions, an important precursor and predictor of actual vaccine uptake. Second, it sets an important precedent by examining the effects of influence strategies on vaccination intentions across different languages.

Abstract Background Early phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists for clinical trial protocols and completed trial reports in the SPIRIT and CONSORT guidelines, respectively. However, both guidelines and their extensions do not adequately address the characteristics of EPDF trials. Building on the SPIRIT and CONSORT checklists, the DEFINE study aims to develop international consensus-driven guidelines for EPDF trial protocols (SPIRIT-DEFINE) and reports (CONSORT-DEFINE). Methods The initial generation of candidate items was informed by reviewing published EPDF trial reports. The early draft items were refined further through a review of the published and grey literature, analysis of real-world examples, citation and reference searches, and expert recommendations, followed by a two-round modified Delphi process. Patient and public involvement and engagement (PPIE) was pursued concurrently with the quantitative and thematic analysis of Delphi participants’ feedback. Results The Delphi survey included 79 new or modified SPIRIT-DEFINE (n = 36) and CONSORT-DEFINE (n = 43) extension candidate items. In Round One, 206 interdisciplinary stakeholders from 24 countries voted and 151 stakeholders voted in Round Two. Following Round One feedback, one item for CONSORT-DEFINE was added in Round Two. Of the 80 items, 60 met the threshold for inclusion (≥ 70% of respondents voted critical: 26 SPIRIT-DEFINE, 34 CONSORT-DEFINE), with the remaining 20 items to be further discussed at the consensus meeting. The parallel PPIE work resulted in the development of an EPDF lay summary toolkit consisting of a template with guidance notes and an exemplar. Conclusions By detailing the development journey of the DEFINE study and the decisions undertaken, we envision that this will enhance understanding and help researchers in the development of future guidelines. The SPIRIT-DEFINE and CONSORT-DEFINE guidelines will allow investigators to effectively address essential items that should be present in EPDF trial protocols and reports, thereby promoting transparency, comprehensiveness, and reproducibility. Trial registration SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network ( https://www.equator-network.org/ ).

Abstract Background Patient and public involvement in health economic evaluation is still relatively rare, compared to other areas of health and social care research. Developing stronger patient and public involvement in health economic evaluation will be important in the future because such evaluations can impact on the treatments and interventions that patients can access in routine care. Main text The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) is a reporting guideline for authors publishing health economic evaluations. We established an international group of public contributors who were involved in the update of the CHEERS 2022 reporting guidance, ensuring two items (areas of reporting) specifically about public involvement were included. In this commentary we focus on the development of a guide to support public involvement in reporting, a key suggestion made by the CHEERS 2022 Public Reference Group, who advocated for greater public involvement in health economic evaluation. This need for this guide was identified during the development of CHEERS 2022 when it became apparent that the language of health economic evaluation is complex and not always accessible, creating challenges for meaningful public involvement in key deliberation and discussion. We took the first step to more meaningful dialogue by creating a guide that patient organisations could use to support their members to become more involved in discussions about health economic evaluations. Conclusions CHEERS 2022 provides a new direction for health economic evaluation, encouraging researchers to undertake and report their public involvement to build the evidence base for practice and may provide some reassurance to the public that their voice has played a part in evidence development. The CHEERS 2022 guide for patient representatives and patient organisations aims to support that endeavour by enabling deliberative discussions among patient organisations and their members. We recognise it is only a first step and further discussion is needed about the best ways to involve public contributors in health economic evaluation.

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

Introduction Endovenous therapy is the first choice management for symptomatic varicose veins in NICE guidelines, with 56–70 000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a known complication of endovenous therapy, occurring at a rate of up to 3.4%. Despite 73% of UK practitioners administering pharmacological thromboprophylaxis to reduce VTE, no high-quality evidence supporting this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE; however, further evidence is needed. This study aims to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective.Methods and analysis A multi-centre, assessor-blind, randomised controlled trial (RCT) will recruit 6660 participants from 40 NHS and private sites across the UK. Participants will be randomised to intervention (single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21–28 days post-procedure to identify asymptomatic DVT. The duplex scan will be conducted locally by blinded assessors. Participants will be contacted remotely for follow-up at 7 days and 90 days post-procedure. The primary outcome is imaging-confirmed lower limb DVT with or without symptoms or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance, adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression.Ethics and dissemination Ethical approval was granted by Brent Research Ethics Committee (22/LO/0261). Results will be disseminated in a peer-reviewed journal and presented at national and international conferences.Trial registration number ISRCTN18501431.

While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work. The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed a baseline and three-month electronic survey. At three months post-infection, 40.8% of participants reported at least one SARS-CoV-2 symptom and 9.6% of participants reported five or more SARS-CoV-2 symptoms. When asked about missed work due to their SARS-CoV-2 infection at three months, 7.2% of participants reported missing ≥10 workdays and 13.9% of participants reported not returning to work since their infection. At three months, participants with ≥5 symptoms had a higher adjusted odds ratio of missing ≥10 workdays (2.96, 95% CI 1.81-4.83) and not returning to work (2.44, 95% CI 1.58-3.76) compared to those with no symptoms. Prolonged SARS-CoV-2 symptoms were common, affecting 4-in-10 participants at three-months post-infection, and were associated with increased odds of work loss, most pronounced among adults with ≥5 symptoms at three months. Despite the end of the federal Public Health Emergency for COVID-19 and efforts to "return to normal", policymakers must consider the clinical and economic implications of the COVID-19 pandemic on people's employment status and work absenteeism, particularly as data characterizing the numerous health and well-being impacts of Long COVID continue to emerge. Improved understanding of risk factors for lost work time may guide efforts to support people in returning to work.

Atlantic tarpon (Megalops atlanticus) are capable of long-distance migrations (hundreds of kilometers) but also exhibit resident behaviors in estuarine and coastal habitats. The aim of this study was to characterize the spatial distribution of juvenile tarpon and identify migration pathways of adult tarpon in the northern Gulf of Mexico. Spatial distribution of juvenile tarpon was investigated using gillnet data collected by Texas Parks and Wildlife Department (TPWD) over the past four decades. Generalized additive models (GAMs) indicated that salinity and water temperature played a significant role in tarpon presence, with tarpon occurrences peaking in the fall and increasing over the past four decades in this region. Adult tarpon caught off Texas (n = 40) and Louisiana (n = 4) were tagged with acoustic transmitters to characterize spatial and temporal trends in their movements and migrations. Of the 44 acoustic transmitters deployed, 18 of the individuals were detected (n = 16 west of the Mississippi River Delta and n = 2 east of the Mississippi River Delta). Tarpon tagged west of the Mississippi River Delta off Texas migrated south in the fall and winter into areas of south Texas and potentially into Mexico, while individuals tagged east of the delta migrated into Florida during the same time period, suggesting the presence of two unique migratory contingents or subpopulations in this region. An improved understanding of the habitat requirements and migratory patterns of tarpon inhabiting the Gulf of Mexico is critically needed by resource managers to assess the vulnerability of each contingent to fishing pressure, and this information will guide multi-state and multi-national conservation efforts to rebuild and sustain tarpon populations.

BackgroundSuicide rates in the United States have increased recently among Black men. To address this public health crisis, smartphone-based ecological momentary assessment (EMA) platforms are a promising way to collect dynamic, real-time data that can help improve suicide prevention efforts. Despite the promise of this methodology, little is known about its suitability in detecting experiences related to suicidal thoughts and behavior (STB) among Black men. ObjectiveThis study aims to clarify the acceptability and feasibility of using smartphone-based EMA through a pilot study that assesses the user experience among Black men. MethodsWe recruited Black men aged 18 years and older using the MyChart patient portal messaging (the patient-facing side of the Epic electronic medical record system) or outpatient provider referrals. Eligible participants self-identified as Black men with a previous history of STB and ownership of an Android or iOS smartphone. Eligible participants completed a 7-day smartphone-based EMA study. They received a prompt 4 times per day to complete a brief survey detailing their STB, as well as proximal risk factors, such as depression, social isolation, and feeling like a burden to others. At the conclusion of each day, participants also received a daily diary survey detailing their sleep quality and their daily experiences of everyday discrimination. Participants completed a semistructured exit interview of 60-90 minutes at the study’s conclusion. ResultsIn total, 10 participants completed 166 EMA surveys and 39 daily diary entries. A total of 4 of the 10 participants completed 75% (21/28) or more of the EMA surveys, while 9 (90%) out of 10 completed 25% (7/28) or more. The average completion rate of all surveys was 58% (20.3/35), with a minimum of 17% (6/35) and maximum of 100% (35/35). A total of 4 (40%) out of 10 participants completed daily diary entries for the full pilot study. No safety-related incidents were reported. On average, participants took 2.08 minutes to complete EMA prompts and 2.72 minutes for daily diary surveys. Our qualitative results generally affirm the acceptability and feasibility of the study procedures, but the participants noted difficulties with the technology and the redundancy of the survey questions. Emerging themes also addressed issues such as reduced EMA survey compliance and diminished mood related to deficit-framed questions related to suicide. ConclusionsFindings from this study will be used to clarify the suitability of EMA for Black men. Overall, our EMA pilot study demonstrated mixed feasibility and acceptability when delivered through smartphone-based apps to Black men. Specific recommendations are provided for managing safety within these study designs and for refinements in future intervention and implementation science research. International Registered Report Identifier (IRRID)RR2-10.2196/31241

Abstract Obesity is a result of a long-term energy imbalance due to decisions associated with energy intake and expenditure. Those decisions fit the definition of heuristics: cognitive processes with a rapid and effortless implementation which can be very effective in dealing with scenarios that threaten an organism’s viability. We study the implementation and evaluation of heuristics, and their associated actions, using agent-based simulations in environments where the distribution and degree of richness of energetic resources is varied in space and time. Artificial agents utilize foraging strategies, combining movement, active perception, and consumption, while also actively modifying their capacity to store energy—a “thrifty gene” effect—based on three different heuristics. We show that the selective advantage associated with higher energy storage capacity depends on both the agent’s foraging strategy and heuristic, as well as being sensitive to the distribution of resources, with the existence and duration of periods of food abundance and scarcity being crucial. We conclude that a ”thrifty genotype” is only beneficial in the presence of behavioral adaptations that encourage overconsumption and sedentariness, as well as seasonality and uncertainty in the food distribution.

Abstract Nuclear pore proteins (Nups) prominently are among the few genes linked to speciation from hybrid incompatibility in Drosophila. These studies have focused on coding sequence evolution of Nup96 and Nup160 and shown evidence of positive selection driving nucleoporin evolution. Intriguingly, channel Nup54 functionality is required for neuronal wiring underlying the female post-mating response induced by male-derived sex-peptide. A region of rapid evolution in the core promoter of Nup54 suggests a critical role for general transcriptional regulatory elements at the onset of speciation, but whether this is a general feature of Nup genes has not been determined. Consistent with findings for Nup54, additional channel Nup58 and Nup62 promoters also rapidly accumulate insertions/deletions (indels). Comprehensive examination of Nup upstream regions reveals that core Nup complex gene promoters accumulate indels rapidly. Since changes in promoters can drive changes in expression, these results indicate an evolutionary mechanism driven by indel accumulation in core Nup promoters. Compensation of such gene expression changes could lead to altered neuronal wiring, rapid fixation of traits caused by promoter changes and subsequently the rise of new species. Hence, the nuclear pore complex may act as a nexus for species-specific changes via nucleo-cytoplasmic transport regulated gene expression.

Abstract The pancreatic islet β-cell’s preference for release of newly synthesized insulin requires careful coordination of insulin exocytosis with sufficient insulin granule production to ensure that insulin stores exceed peripheral demands for glucose homeostasis. Thus, the cellular mechanisms regulating insulin granule production are critical to maintaining β-cell function. In this report, we utilized the synchronous protein trafficking system, RUSH, in primary β-cells to evaluate proinsulin transit through the secretory pathway leading to insulin granule formation. We demonstrate that the trafficking, processing, and secretion of the proinsulin RUSH reporter, proCpepRUSH, are consistent with current models of insulin maturation and release. Using both a rodent dietary and genetic model of hyperglycemia and β-cell dysfunction, we show that proinsulin trafficking is impeded at the Golgi and coincides with the decreased appearance of nascent insulin granules at the plasma membrane. Ultrastructural analysis of β-cells from diabetic leptin receptor deficient mice revealed gross morphological changes in Golgi structure, including shortened and swollen cisternae, and partial Golgi vesiculation, which are consistent with defects in secretory protein export. Collectively, this work highlights the utility of the proCpepRUSH reporter in studying proinsulin trafficking dynamics and suggests that altered Golgi export function contributes to β-cell secretory defects in the pathogenesis of Type 2 diabetes.

Plain English summary The Rising Tide Foundation for Clinical Cancer Research (RTFCCR), a private philanthropy that funds academic research, has developed a novel approach for requiring and supporting partnerships among grantees (scientists) and patients in designing and conducting research projects. The decision to focus on patient involvement stems from an expressed focus area established by the RTFCCR board of directors. In conducting this work, RTFCCR partnered with Patvocates, a patient advocacy and engagement network. Patvocates conducted a landscape assessment, interviews with experts, and their collective experience as patient advocates. This work generated a set of guiding documents and resources. These resources are to help public and private health research funders to better understand current challenges and support scientists and patients through their funding mechanisms. Three guiding documents, one for funders, one for grant applicants, and one for patient advocates are now available for download at the RTFCCR website: https://www.risingtide-foundation.org/clinical-cancer-research/patient-engagement#start Delivering a paradigm change involves not only the introduction of additional requirements and rules, but also enhanced education of patients and investigators. By using its grantmaking function and developing standardized approaches for implementation of patient involvement, RTFCCR is seeking to advance patient-centric cancer clinical research. Development and implementation of consistent policies and procedures for the integration of the patients’ view in the design and review of research proposals is needed for funders as well as for research institutes, both public and private.

OBJECTIVES/GOALS: To examine the individual and combined association between preoperative sleep disturbance (SD) and depression and 12-month disability, back pain, and leg pain after lumbar spine surgery (LSS). METHODS/STUDY POPULATION: We analyzed prospectively collected multi-center registry data from 700 patients undergoing LSS (mean age=60.9 years, 37% female, 89% white). Preoperative SD and depression were assessed with PROMIS measures. Established thresholds defined patients with moderate/severe symptoms. Disability (Oswestry Disability Index) and back and leg pain (Numeric Rating Scales) were assessed preoperatively and at 12 months. We conducted separate regressions to examine the influence of SD and depression on each outcome. Regressions examined each factor with and without accounting for the other and in combination as a 4-level variable. Covariates included age, sex, race, education, insurance, body mass index, smoking status, preoperative opioid use, fusion status, revision status, and preoperative outcome score. RESULTS/ANTICIPATED RESULTS: One hundred thirteen (17%) patients reported moderate/severe SD alone, 70 (10%) reported moderate/severe depression alone, and 57 (8%) reported both moderate/severe SD and depression. In independent models, preoperative SD and depression were significantly associated with 12-month outcomes (all p’s

# Background Swearing deserves attention in the physical therapy setting due to its potential positive effects on pain, physical performance, and therapeutic alliance. The purpose of this case report is to describe the strategic use of swearing in the clinical setting. # Case Presentation A 44-year-old female completed an episode of physical therapy after undergoing patellofemoral arthroplasty. Swearing was formally included into the plan of care, and the patient swore out loud during the most challenging and painful interventions. # Results The patient reported that repeating a swear word was funny, distracted the patient, and made the patient feel more confident. The patient and physical therapist self-reported a strong therapeutic alliance. # Conclusion There is evidence repeating a swear word out loud can strengthen the therapeutic alliance, improve physical performance, and decrease pain. This is, to our knowledge, the first report of a patient swearing during an episode of physical therapy care.

Objectives Juvenile idiopathic arthritis (JIA) is a common chronic childhood disease and chronic pain is a debilitating feature. A strong link has been shown between poor sleep and pain in JIA. However, the causal direction is unknown. This study’s aim was to determine if, in adolescents with JIA, a recommended healthful sleep duration leads to reductions in pain when compared with the restricted sleep (RS) duration that is commonly seen.Methods Patients with JIA (12–18 years old; pain score of ≥1 on a visual analogue scale) participated in a randomised, crossover sleep manipulation protocol. The 3-week protocol comprised a baseline week (BL), a week with healthy sleep duration (HSD; 9.5 hours in bed/night) and a RS week (RS; 6.5 hours in bed/night). After BL, participants were randomly assigned to either HSD or RS, and then crossed over to the other condition. Pain was self-assessed using the iCanCope with Pain app. We used Bayesian hierarchical models to estimate the effect of sleep duration on pain.Results Participants (n=31; mean age=15.0±1.8 years) averaged 1.4 (95% credible interval (CrI) 1.2–1.6) more hours of sleep per night during HSD relative to RS. Compared with RS, HSD resulted in a favourable effect on pain scores (OR 0.61, 95% CrI 0.39–0.95).Conclusion It is possible to have adolescents with childhood arthritis get a healthier sleep duration, and this longer sleep results in reduced pain. These findings complement prior correlational studies and confirm a causal relationship between reduced sleep duration and increased pain.Trial registration number NCT04133662.

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.

Plain English summary The goal of comparative clinical effectiveness research is to compare healthcare options and learn which work best for patients depending on their preferences and circumstances. Research efforts can be more effective when researchers engage stakeholders, such as patients, healthcare providers, and other members of the community—especially those communities or groups targeted by the planned research. Stakeholders can give their input throughout the research process to make sure the study will address questions and concerns that are most important and useful for participants. In 2014, the PCORI funded eight research studies that evaluated various ways to help African Americans and Hispanics/Latinos with poorly controlled asthma. These groups are underrepresented in asthma research but have higher rates of and more severe asthma for reasons that are poorly understood. The goal of this report is to show how stakeholders—including patients with asthma from these underrepresented groups, healthcare providers who care for patients with asthma, key representatives from the communities and others—participated as full partners in the eight studies and helped to improve the overall quality of the research and the relationship between the researchers and the community.

Abstract The Australian dingo is a recent anthropogenic addition to the Australian fauna, which spread rapidly across the continent and has since widely interbred with modern dogs. Genetic studies of dingoes have given rise to speculation about their entry to the continent and subsequent biogeographic effects, but few studies of their contemporary population structure have been conducted. Here we investigated the dingo ancestry and population structure of free-living dogs in western Victoria and contrasted it with a wider southern Australian sample. We wished to determine whether their geographic isolation was mirrored in genetic isolation. To address this question, we analysed 34 microsatellite markers using Bayesian clustering and discriminant analysis of principal components, and summarised genetic diversity at the population and individual level. The broader southern Australia sample (n = 1138) comprised mostly hybrid animals, with 30% considered pure dingoes. All western Victorian individuals (n = 59) appeared to be hybrids with high dingo ancestry. The population showed no evidence of admixture with other populations and low genetic diversity on all measures tested. Based upon our characterisation of this unusual mainland population, we advise against assuming homogeneity of dingoes across the continent.

Introduction: Non-specialist emergency medicine qualifications are an important step in developing the specialty of emergency medicine. The Diploma in Primary Emergency Care (Dip PEC) of the Colleges of Medicine of South Africa is one of the oldest registrable qualifications. Reviewing its changing role over time has lessons for academics developing Emergency Medicine training in Africa. Methods: Through a series of meetings and stakeholder engagements, the Council of the College of Emergency Medicine conducted a three year review of the qualification focusing on the curriculum, assessment processes, success rate and role of the qualification in the South African medical context. A survey of the perceptions of graduates over the last six years was also conducted. Results: The survey showed candidate numbers increased dramatically from 2011 to 2017, resulting in an entry cap. Lessons identified included ensuring that the qualification is responsive to the state of development of emergency medicine in the country, needing aligned and valid assessment processes and maintaining the value of the qualification in context. Discussion: Emergency medicine qualifications are dynamic in and of themselves and how they relate to their context. Program designers must prioritize ongoing evaluation from the start.

Background: Ambulatory electroencephalography (AEEG) recording is an essential aid for detecting interictal discharges and providing a clinical diagnosis. This study aimed to describe long-term outcomes among a cohort of patients who yielded negative results on AEEG at the time of assessment and identify factors associated with contemporary quality of life (QOL) and ultimate epilepsy diagnosis. Methods: This cross-sectional telephone follow-up study was conducted in June-November 2021 at the Neurology Department in a metropolitan hospital in Sydney, Australia. Results: Forty-seven of 105 eligible (45%) participants were enrolled. Twenty-one (45%) participants had been diagnosed with epilepsy at a 12-year follow-up. Taking anti-seizure medication, having experienced a seizure event, and having marriage and education-related characteristics were associated with an epilepsy diagnosis. QOL was found to be associated with age, employment status and history of experience of a seizure event. QOL and an epilepsy diagnosis were not shown to be statistically related. Conclusion: Nearly half of the participants had received an epilepsy diagnosis at long-term follow-up, despite having tested negative on AEEG at the time of assessment. Prolonged AEEG testing is an important tool to aid the diagnostic process. However, clinical examination, including accurate history taking, is vital in establishing an epilepsy diagnosis.

Introduction The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was ‘Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?’ This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.Methods and analysis We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress.Ethics and dissemination This study was approved by the Yorkshire and The Humber—Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group.Trial registration number ISRCTN41647111.

Introduction Decisions regarding the optimal vascular access for haemodialysis patients are becoming increasingly complex, and the provision of vascular access is open to variations in systems of care as well as surgical experience and practice. Two main surgical options are recognised: arteriovenous fistula and arteriovenous graft (AVG). All recommendations regarding AVG are based on a limited number of randomised controlled trials (RCTs). It is essential that when considering an RCT of a surgical procedure, an appropriate definition of quality assurance (QA) is made for both the new approach and the comparator, otherwise replication of results or implementation into clinical practice may differ from published results. The aim of this systematic review will be to assess the methodological quality of RCT involving AVG, and the QA measures implemented in delivering interventions in these trials.Methods and analysis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A systematic search will be performed of the MEDLINE, Embase and Cochrane databases to identify relevant literature. Studies will be selected by title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data collected will pertain to generic measures of QA, credentialing of investigators, procedural standardisation and performance monitoring. Trial methodology will be compared against a standardised template developed by a multinational, multispecialty review body with experience in vascular access. A narrative approach will be taken to synthesise and report data.Ethics and dissemination Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations, with the ultimate aim of providing recommendations for future RCT of AVG design.

Abstract Coral bleaching, precipitated by the expulsion of the algal symbionts that provide colonies with fixed carbon is a global threat to reef survival. To protect corals from anthropogenic stress, portable tools are needed to detect and diagnose stress syndromes and assess population health prior to extensive bleaching. Here, medical grade Urinalysis strips, used to detect an array of disease markers in humans, were tested on the lab stressed Hawaiian coral species, Montipora capitata (stress resistant) and Pocillopora acuta (stress sensitive), as well as samples from nature that also included Porites compressa. Of the 10 diagnostic reagent tests on these strips, two appear most applicable to corals: ketone and leukocytes. The test strip results from M. capitata were explored using existing transcriptomic data from the same samples and provided evidence of the stress syndromes detected by the strips. We designed a 3D printed smartphone holder and image processing software for field analysis of test strips (TestStripDX) and devised a simple strategy to generate color scores for corals (reflecting extent of bleaching) using a smartphone camera (CoralDX). Our approaches provide field deployable methods, that can be improved in the future (e.g., coral-specific stress test strips) to assess reef health using inexpensive tools and freely available software.

Plain English Summary All major problems, including complex global problems such as air pollution and pandemics, require reliable data sharing between disciplines in order to respond effectively. Such problems require evidence-informed collaborative methods, multidisciplinary research and interventions in which the people who are affected are involved in every stage. However, there is currently no standardised way to share information about initiatives and problem-solving across and between fields such as health, environment, basic science, manufacturing, education, media and international development. A multi-disciplinary international team of over 100 citizens, experts and data-users has been involved in co-creating STARDIT to help everyone in the world share, find and understand information about collective human actions, which are referred to as ‘initiatives’. STARDIT is an open access data-sharing system to standardise the way that information about initiatives is reported, including information about which tasks were done by different people. Reports can be updated at all stages, from planning to evaluation, and can report impacts in many languages, using Wikidata. STARDIT is free to use, and data can be submitted by anyone. Report authors can be verified to improve trust and transparency, and data checked for quality. STARDIT can help create high-quality standardised information on initiatives trying to solve complex multidisciplinary global problems. Among its main benefits, STARDIT offers those carrying out research and interventions access to standardised information which enables well-founded comparisons of the effectiveness of different methods. This article outlines progress to date; current usage; information about submitting reports; planned next steps and how anyone can become involved.

Background Clinical prediction rules (CPRs) developed to predict adverse outcomes of suspected pulmonary embolism (PE) and facilitate outpatient management have limitations in discriminating outcomes for ambulatory cancer patients with unsuspected PE (UPE). The HULL Score CPR uses a 5‑point scoring system incorporating performance status and self-reported new or recently evolving symptoms at UPE diagnosis. It stratifies patients into low, intermediate and high risk for proximate mortality. This study aimed to validate the HULL Score CPR in ambulatory cancer patients with UPE. Patients and methods 282 consecutive patients managed under the UPE-acute oncology service in Hull University Teaching Hospitals NHS Trust were included from January 2015 to March 2020. The primary end-point was all-cause mortality, and outcome measures were proximate mortality for the three risk categories of the HULL Score CPR. Results 30-day, 90-day and 180-day mortality rates for the whole cohort were 3.4% (n=7), 21.1% (n=43) and 39.2% (n=80), respectively. The HULL Score CPR stratified patients into low-risk (n=100, 35.5%), intermediate-risk (n=95, 33.7%) and high-risk (n=81, 28.7%) categories. Correlation of the risk categories with 30-day mortality (area under the curve (AUC) 0.717, 95% CI 0.522–0.912), 90-day mortality (AUC 0.772, 95% CI 0.707–0.838), 180-day mortality (AUC 0.751, 95% CI 0.692–0.809) and overall survival (AUC 0.749, 95% CI 0.686–0.811) was consistent with the derivation cohort. Conclusion This study validates the capacity of the HULL Score CPR to stratify proximate mortality risk in ambulatory cancer patients with UPE. The score uses immediately available clinical parameters and is easy to integrate into an acute outpatient oncology setting.

Objectives The overdose epidemic was designated a ‘Public Health Emergency’ in the USA on 26 October 2017, bringing attention to the severity of this public health problem. The Appalachian region remains substantially impacted by the effects from years of overprescription of opioids, and subsequently opioid non-medical use and addiction. This study aims to examine the utility of the PRECEDE–PROCEED model constructs (ie, predisposing, reinforcing and enabling factors) to explain opioid addiction helping behaviour (ie, helping someone who has an opioid addiction) among members of the public living in tri-state Appalachian counties.Design Cross-sectional study.Setting Rural county in the Appalachian region of the USA.Participants A total of 213 participants from a retail mall in a rural Appalachian Kentucky county completed the survey. Most participants were between the ages of 18 and 30 years (n=68; 31.9%) and identified as men (n=139; 65.3%).Primary outcome measure Opioid addiction helping behaviour.Results The regression model was significant (F(6, 180)=26.191, p

Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellyfish), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.

Objective: Swearing deserves attention in the physical therapy setting due to its potential positive psychological, physiological, and social effects. The purpose of this case series is to describe 2 cases in which a physical therapist swears in the clinical setting and its effect on therapeutic alliance. Patients: Case 1 is a 19-year-old male treated for a hamstring strain, and case 2 is a 23-year-old male treated post-operatively for anterior cruciate ligament reconstruction. The physical therapist utilized social swearing in the clinic with the goal of motivating the patient and enhancing the social connection with the patient, to improve therapeutic alliance. Results: The patient in case 1 reported a decrease in therapeutic alliance after the physical therapist began swearing during physical therapy treatments, whereas the patient in case 2 reported an increase in therapeutic alliance. Both patients disagreed that physical therapist swearing is unprofessional and disagreed that swearing is offensive, and both patients agreed physical therapists should be able to swear around their patients. Conclusion: Physical therapist swearing may have positive and negative influences in the clinic setting and may not be considered unprofessional. These are, to our knowledge, the first published cases of a physical therapist swearing in the clinical setting. LAY ABSTRACT Swearing produces positive effects that cannot be achieved with any other forms of language. Quite simply, swearing is powerful and deserves attention in the physical therapy setting. Swearing can lead to tighter human bonds, thereby enhancing the social connection between a patient and a physical therapist. This case series describes 2 cases where a physical therapist swears with patients in the clinical setting and its effect on their social connection. While swearing increased the social connection in 1 case, it decreased it in the other case. None of the patients thought that physical therapist swearing was unprofessional, and both patients believe physical therapists should be able to swear around their patients. The results of these cases indicate that physical therapist swearing can have positive and negative influences in the clinic. More studies are needed to help determine when, how, and if to swear in the physical therapy setting.