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Objective To determine the balance of costs, risks, and benefits for different thromboprophylaxis strategies for medical patients during hospital admission.Design Decision analysis modelling study.Setting NHS hospitals in England.Population Eligible adult medical inpatients, excluding patients in critical care and pregnant women.Interventions Pharmacological thromboprophylaxis (low molecular weight heparin) for all medical inpatients, thromboprophylaxis for none, and thromboprophylaxis given to higher risk inpatients according to risk assessment models (Padua, Caprini, IMPROVE, Intermountain, Kucher, Geneva, and Rothberg) previously validated in medical cohorts.Main outcome measures Lifetime costs and quality adjusted life years (QALYs). Costs were assessed from the perspective of the NHS and Personal Social Services in England. Other outcomes assessed were incidence and treatment of venous thromboembolism, major bleeds including intracranial haemorrhage, chronic thromboembolic complications, and overall survival.Results Offering thromboprophylaxis to all medical inpatients had a high probability (>99%) of being the most cost effective strategy (at a threshold of £20 000 (€23 440; $25 270) per QALY) in the probabilistic sensitivity analysis, when applying performance data from the Padua risk assessment model, which was typical of that observed across several risk assessment models in a medical inpatient cohort. Thromboprophylaxis for all medical inpatients was estimated to result in 0.0552 additional QALYs (95% credible interval 0.0209 to 0.1111) while generating cost savings of £28.44 (−£47 to £105) compared with thromboprophylaxis for none. No other risk assessment model was more cost effective than thromboprophylaxis for all medical inpatients when assessed in deterministic analysis. Risk based thromboprophylaxis was found to have a high (76.6%) probability of being the most cost effective strategy only when assuming a risk assessment model with very high sensitivity is available (sensitivity 99.9% and specificity 23.7% v base case sensitivity 49.3% and specificity 73.0%).Conclusions Offering pharmacological thromboprophylaxis to all eligible medical inpatients appears to be the most cost effective strategy. To be cost effective, any risk assessment model would need to have a very high sensitivity resulting in widespread thromboprophylaxis in all patients except those at the very lowest risk, who could potentially avoid prophylactic anticoagulation during their hospital stay.

IntroductionAlthough evidence supports the effective use of a cue to forget an encoded stimulus, the mechanisms of this forgetting are not well understood. Evidence from item-method directed forgetting in long-term memory reveals greater prefrontal and parietal activation for information that is cued to be forgotten. Activation in those brain regions is typically associated with increased effort and cognitive control.MethodTo test the mechanism of directed forgetting in visual working memory, we used stimuli that rely on distinct brain regions such as faces and buildings and varied memory stability. Participants completed a directed forgetting task with faces and buildings, and memory stability was manipulated by presenting some stimuli repeatedly throughout the study, and other stimuli were only presented once.Results and discussionFunctional magnetic resonance imaging (fMRI) results from the parahippocampal place area suggest that to-be-remembered buildings elicit higher activation than to-be-forgotten buildings. In addition, dorsolateral prefrontal cortex activation changed throughout the trial period, possibly suggesting that the cue led to information being dropped from visual working memory, or through a shift in attention, as occurs with the retro-cue paradigm. Several explanations for these results are discussed.

The COVID-19 pandemic has led to many undergraduate medical programs shifting their preclinical curricula online— reducing access to clinical skills sessions and ultimately causing gaps in students’ knowledge. This study sought to better understand the impact and role of virtual clinical skills training sessions, using point-of-view (POV) livestreaming wearable technology, in supplementing medical students’ learning. 38 University of Ottawa medical students were recruited to participate in a 1.5-hour virtual clinical teaching session. An abdominal physical examination was broadcasted through two views (chest-mounted smartphone, room overview). Participants completed pre- and post-event questionnaires on their overall impression, satisfaction/challenges, and platform efficacy compared to other learning modalities. Improvements were noted in participants’ perspectives towards event engagement (p=0.042, Cohen’s d=0.48), comparability to in-person encounters (p=

IntroductionSpinal cord injury (SCI) animal models often utilize an open surgical laminectomy, which results in animal morbidity and also leads to changes in spinal canal diameter, spinal cord perfusion, cerebrospinal fluid flow dynamics, and spinal stability which may confound SCI research. Moreover, the use of open surgical laminectomy for injury creation lacks realism when considering human SCI scenarios.MethodsWe developed a novel, image-guided, minimally invasive, large animal model of SCI which utilizes a kyphoplasty balloon inserted into the epidural space via an interlaminar approach without the need for open surgery.ResultsThe model was validated in 5 Yucatán pigs with imaging, neurofunctional, histologic, and electrophysiologic findings consistent with a mild compression injury.DiscussionFew large animal models exist that have the potential to reproduce the mechanisms of spinal cord injury (SCI) commonly seen in humans, which in turn limits the relevance and applicability of SCI translational research. SCI research relies heavily on animal models, which typically involve an open surgical, dorsal laminectomy which is inherently invasive and may have untoward consequences on animal morbidity and spinal physiology that limit translational impact. We developed a minimally invasive, large animal model of spinal cord injury which utilizes a kyphoplasty balloon inserted percutaneously into the spinal epidural space. Balloon inflation results in a targeted, compressive spinal cord injury with histological and electrophysiological features directly relevant to human spinal cord injury cases without the need for invasive surgery. Balloon inflation pressure, length of time that balloon remains inflated, and speed of inflation may be modified to achieve variations in injury severity and subtype.

Enzymes catalyze key reactions within Earths life-sustaining biogeochemical cycles. Here, we use metaproteomics to examine the enzymatic capabilities of the microbial community (0.2 to 3 µm) along a 5,000-km-long, 1-km-deep transect in the central Pacific Ocean. Eighty-five percent of total protein abundance was of bacterial origin, with Archaea contributing 1.6%. Over 2,000 functional KEGG Ontology (KO) groups were identified, yet only 25 KO groups contributed over half of the protein abundance, simultaneously indicating abundant key functions and a long tail of diverse functions. Vertical attenuation of individual proteins displayed stratification of nutrient transport, carbon utilization, and environmental stress. The microbial community also varied along horizontal scales, shaped by environmental features specific to the oligotrophic North Pacific Subtropical Gyre, the oxygen-depleted Eastern Tropical North Pacific, and nutrient-rich equatorial upwelling. Some of the most abundant proteins were associated with nitrification and C1 metabolisms, with observed interactions between these pathways. The oxidoreductases nitrite oxidoreductase (NxrAB), nitrite reductase (NirK), ammonia monooxygenase (AmoABC), manganese oxidase (MnxG), formate dehydrogenase (FdoGH and FDH), and carbon monoxide dehydrogenase (CoxLM) displayed distributions indicative of biogeochemical status such as oxidative or nutritional stress, with the potential to be more sensitive than chemical sensors. Enzymes that mediate transformations of atmospheric gases like CO, CO2, NO, methanethiol, and methylamines were most abundant in the upwelling region. We identified hot spots of biochemical transformation in the central Pacific Ocean, highlighted previously understudied metabolic pathways in the environment, and provided rich empirical data for biogeochemical models critical for forecasting ecosystem response to climate change.

Abstract Background The International Psoriasis Council (IPC) recommends an approach that considers body surface area (BSA), involvement in special areas, and treatment history for classifying patients as candidates for topical or systemic treatment. This study aimed to quantify the burden of psoriasis by describing BSA distribution, special area involvement, and treatments in a real-world population. Methods This retrospective cohort study included patients with psoriasis from the Optum® deidentified Electronic Health Records database with a BSA value ( 10%) recorded between 1 March 2014 and 1 September 2020. Treatments and special area involvement (face, scalp, palms/soles, nails, genitals) were identified within 90 days of the BSA value and stratified by BSA category. Results Among eligible patients (N = 5120), mean age was 51.4 years and 49.3% were women. The majority of patients (78.9%) were treated with any topical. Proportions of patients with BSA 10% were 23.4%, 41.9%, and 34.6%, respectively; proportions with 0, 1, and 2+ special areas were 21.6%, 31.6%, and 45.7%, respectively; and 44.4%, 45.7%, and 45.9% of patients with BSA 10%, respectively, had 2+ special areas. Conclusion The IPC classification can likely identify many more patients who may benefit from systemic therapy than BSA alone. Graphical Abstract

This study estimates the effect of state appropriations on the graduation rates of freshman cohorts by race/ethnicity. Data were obtained for public four-year institutions (n = 415) representing six freshman cohorts between 2007 and 2012. Hybrid regression models indicated that a ten percent increase in appropriations would yield a percentage point increase in graduation rates of 0.59 for all students, 0.99 for Black students, 0.84 for Latinx students, and 0.59 for White students. However, the effect of state appropriations on graduation rates varied across institutions (-1.03 to 2.99 percentage point change) and was frequently larger at institutions with medium or high subsidy reliance (0.70 to 1.39 percentage point change). Also, the effect of state appropriations on Black student graduation rates was 2.48 times larger at HBCUs. This study suggests that state appropriations can be an effective instrument for raising the graduation rates of diverse students to help meet state attainment goals.

This qualitative study analyzes the relationship between two concepts from critical race theory -- counterspaces and community cultural wealth. Counterspaces are supportive, identity-affirming community spaces, while community cultural wealth highlights the importance of the knowledge, skills, and networks used by individuals belonging to marginalized groups to successfully navigate academia. This study investigates the hypothesis that the processes operating within counterspaces serve to strengthen an individual's access to their community cultural wealth. The study site is BRAINS, a U.S.-based professional development program for early-career academic neuroscientists from underrepresented groups. Findings revealed that two types of counterspace processes (narrative identity work and direct relational transactions) and three types of community cultural wealth (aspirational capital, social capital, and navigational capital) are most salient within BRAINS. After examining the complex interactions connecting counterspace processes and community cultural wealth, we offer recommendations for future professional development programs and research designed to broaden participation in academia.

This study inquired into the nature of identity among refugee youth living at Dzaleka Refugee Camp in Malawi. Aged between eighteen and twenty-four, the sample comprised of twenty-two female (m = 20.18, sd = 1.89) and thirty-eight male (m = 21.68, sd = 1.92) participants, from Burundi, the Democratic Republic of Congo, Rwanda, and Somalia. The study hypothesized that the organizing structure of education and its related experiences fostered identity formation for the youth. The questions asked were: 1. How do long-term refugee youth at the camp construct identity? 2. How does the process of identity formation facilitate the youth's socialization within the camp? The study used the inductive analytical approach of interpretive description. The methods of data collection were in-depth qualitative interviews, participant observations and fieldnotes. Findings from the study demonstrated how the participants filtered their identity formation vis-à-vis concepts of education, resulting in two categories: liminal and aspirational identities.

The extant literature highlights the impact principals have on daily operations, visioning, school climate, academic programming, instructional monitoring, and numerous other areas. The need for well-trained principals at the helm of schools, particularly those with large concentrations of at-risk students, has been identified as a critically important factor in improving academic outcomes. Underdeveloped leaders often struggle to improve schools and are unable to show adequate progress among the students they serve. They are also more prone to early burnout, increasing turnover rates. As such, the need to strengthen principal preparation programs has become even more evident in recent years. A number of states, including North Carolina, are exploring ways to encourage principal preparation providers to adopt leadership development approaches that are more responsive to evidenced-based research about effective school leadership. This article focuses on university-school partnerships as an emerging strategy for providing aspiring principals with a more authentic preparation experience.

First paragraphs: In May 2023, approximately 100 people gathered in Kansas City, Missouri, for a national conven­ing on scaling agroecology in what is now known as the United States. The gathering (referred to throughout this special issue as the Agroecology Summit or simply the Summit) was convened by people working at research institutions throughout the U.S. The organizing committee aimed to iden­tify how research can support the growers, organi­zations, and communities enacting agroecology in the U.S. Initially funded by a US$50,000 grant from the U.S. Department of Agriculture (USDA), the committee also hoped to create a “roadmap” for agroecological research in the U.S. While a co-created research agenda for agro­ecology is arguably an important long-term goal, what unfolded at the Summit indicates that pursu­ing this goal was premature—putting the research cart before the agroecology horse, so to speak. Many summit participants from civil society and social movement spaces pushed against the idea of a roadmap. Some pushed against the idea of work­ing collectively on a goal that was not collectively identified or co-designed; others, against the idea of engaging in collective work without first estab­lishing trust, especially where deep reparative work between and among communities and institutions is still needed. Bringing together people who span diverse identities, positionalities, and ways of knowing is both an epistemologically and ethically complex endeavor. Given the diversity of histori­cal, cultural, and practical orientations to agroecol­ogy, it is unsurprising that the Summit revealed tensions. Two editors on this special issue (Roman-Alcalá and Horner) were on the summit organizing committee. Roman-Alcalá and Horner shared that it was not always comfortable for Summit organiz­ers to receive some of the critiques voiced before the summit (as shared by Wills, Tovar-Aguilar, and Naylor in this issue), at the summit, and further articulated in this special issue. However, the necessity of ongoing dialogue—of engaging in gen­erative discussions across points of difference—was and is evident (Roman-Alcalá, 2022). Although the Summit did not ultimately yield a research agenda or roadmap, it was not an unfruitful event. Participants did not coalesce around a singular goal. Instead, they gave voice to the many goals, needs, and visions driving agroecology in the U.S. The commentaries in this special issue highlight some of the research, policy, organizing, and repar­ative priorities that emerged during and after the Summit. . . .

Introduction In February 2023, the Institute for Agroecology (IFA) was formally recognized by the University of Vermont. We are a group of scholars who aim to leverage our privileges and positions within the academy to support farmers, activists, and move­ments in the struggle for agroecology and food sovereignty. International collaborators have often asked us to consider how we can do more to build out agroecology in the United States—the so-called “belly of the beast” of industrial agriculture and racialized capitalism (Robinson, 2021)—and how we can act, from the U.S., to support the growth of agroecology in other places. As a newly formed institute, we are keen to engage with others working to advance agroecol­ogy in the U.S. This motivated us to accept an invitation to join a committee organizing a national convening on agroecology in May 2023. We viewed it as an opportunity to collectively iden­tify research that would support people, communi­ties, organizations, and movements aligning with agro­ecology in the U.S. The organizing committee named creation of a “roadmap” for agroecological research in the U.S. as the convening’s purpose. The plan was to create a space for listening to the needs of those working on the ground and to iden­tify ways to support their work via research and resources. . . .

Background Pharmacological prophylaxis during hospital admission can reduce the risk of acquired blood clots (venous thromboembolism) but may cause complications, such as bleeding. Using a risk assessment model to predict the risk of blood clots could facilitate selection of patients for prophylaxis and optimise the balance of benefits, risks and costs. Objectives We aimed to identify validated risk assessment models and estimate their prognostic accuracy, evaluate the cost-effectiveness of different strategies for selecting hospitalised patients for prophylaxis, assess the feasibility of using efficient research methods and estimate key parameters for future research. Design We undertook a systematic review, decision-analytic modelling and observational cohort study conducted in accordance with Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines. Setting NHS hospitals, with primary data collection at four sites. Participants Medical and surgical hospital inpatients, excluding paediatric, critical care and pregnancy-related admissions. Interventions Prophylaxis for all patients, none and according to selected risk assessment models. Main outcome measures Model accuracy for predicting blood clots, lifetime costs and quality-adjusted life-years associated with alternative strategies, accuracy of efficient methods for identifying key outcomes and proportion of inpatients recommended prophylaxis using different models. Results We identified 24 validated risk assessment models, but low-quality heterogeneous data suggested weak accuracy for prediction of blood clots and generally high risk of bias in all studies. Decision-analytic modelling showed that pharmacological prophylaxis for all eligible is generally more cost-effective than model-based strategies for both medical and surgical inpatients, when valuing a quality-adjusted life-year at £20,000. The findings were more sensitive to uncertainties in the surgical population; strategies using risk assessment models were more cost-effective if the model was assumed to have a very high sensitivity, or the long-term risks of post-thrombotic complications were lower. Efficient methods using routine data did not accurately identify blood clots or bleeding events and several pre-specified feasibility criteria were not met. Theoretical prophylaxis rates across an inpatient cohort based on existing risk assessment models ranged from 13% to 91%. Limitations Existing studies may underestimate the accuracy of risk assessment models, leading to underestimation of their cost-effectiveness. The cost-effectiveness findings do not apply to patients with an increased risk of bleeding. Mechanical thromboprophylaxis options were excluded from the modelling. Primary data collection was predominately retrospective, risking case ascertainment bias. Conclusions Thromboprophylaxis for all patients appears to be generally more cost-effective than using a risk assessment model, in hospitalised patients at low risk of bleeding. To be cost-effective, any risk assessment model would need to be highly sensitive. Current evidence on risk assessment models is at high risk of bias and our findings should be interpreted in this context. We were unable to demonstrate the feasibility of using efficient methods to accurately detect relevant outcomes for future research. Future work Further research should evaluate routine prophylaxis strategies for all eligible hospitalised patients. Models that could accurately identify individuals at very low risk of blood clots (who could discontinue prophylaxis) warrant further evaluation. Study registration This study is registered as PROSPERO CRD42020165778 and Researchregistry5216. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127454) and will be published in full in Health Technology Assessment; Vol. 28, No. 20. See the NIHR Funding and Awards website for further award information. Plain language summary People who are admitted to hospital are at risk of blood clots that can cause serious illness or death. Patients are often given low doses of blood-thinning drugs to reduce this risk. However, these drugs can cause side effects, such as bleeding. Hospitals currently use complex risk assessment models (risk scores, which usually include patient, disease, mobility and intervention factors) to determine the individual risk of blood clots and identify people most likely to benefit from blood-thinning drugs. There are a lot of different risk scores and we do not know which one is best. We also do not know how these scores compare to each other or whether using scores to decide who should get blood-thinning drugs provides good value for money to the NHS. We reviewed all previous studies of risk scores. We found that they did not predict blood clots very well and we could not recommend one score over another. We then created a mathematical model to simulate the use of blood-thinning drugs in people admitted to hospital. The model suggested that giving blood-thinning drugs to everyone who could have them would probably provide the best value for money, in medical patients. Our findings were the same, but less certain, for surgical patients. We also collected information from four NHS hospitals to explore possibilities for future research. Our work showed that routinely collected electronic data on blood clots and bleeding events is not very accurate and that using different scores could result in variable use of blood-thinning medications. Our findings suggest that it may be better value to the NHS and better for patients if we were to offer blood-thinning medications to everyone on admission to hospital, without using any risk score. However, this approach needs further research to ensure it is safe and effective. Such research would not be able to rely on routine electronic data to identify blood clots or bleeding events, in isolation. Scientific summary Background Venous thromboembolism (VTE) is a composite diagnosis including deep-vein thrombosis (DVT) and pulmonary embolism (PE). The condition is a global health burden, affecting over 1:1000 adults worldwide, every year. Previous epidemiological studies have shown more than half of all VTE events to be hospital-associated (or acquired) thrombosis (HAT), occurring during admission or within 90 days of discharge. Current evidence suggests that many HAT events are potentially preventable. Pharmacological prophylaxis in medical and surgical inpatients has been shown to be clinically effective in several large studies and meta-analyses. However, although prophylaxis reduces the risk of VTE for hospital inpatients, it also incurs costs and potentially increases the risk of bleeding. As such, international guidelines recommend a process of individualised VTE risk assessment at the point of hospital admission. Several risk assessment models (RAMs) have been developed to aid this process. The accuracy and cost-effectiveness of these models are uncertain. Further prospective studies in this area are challenging due to national guidance, contract standards and high rates of routine prescribing (> 70%). We sought to assess the clinical and cost-effectiveness of VTE RAMs through secondary research methods, by conducting a systematic review of RAM accuracy and subsequent decision-analytic modelling. In addition, we sought to evaluate the accuracy of routine data sources to identify core VTE and bleeding outcomes and estimate key clinical parameters for any future implementation study. Objectives The prespecified and combined project objectives were as follows: Update existing systematic reviews to identify VTE RAMs for hospital inpatients and determine their comparative accuracy for predicting the risk of VTE. Undertake decision-analytic modelling to determine the cost-effectiveness of pharmacological prophylaxis guided by a RAM, compared to prophylaxis for all and prophylaxis for none. Use the decision-analytic model to identify key areas of uncertainty and determine the value of gathering additional information to reduce uncertainty. Pilot the use and evaluate the accuracy of efficient methods to measure core clinical VTE and bleeding outcomes. Estimate key parameters for planning a future implementation study. Methods Workstream 1 used a systematic review and economic analysis to address objectives 1, 2 and 3. We extended and updated overlapping systematic reviews of available RAMs, performed quality assessment of relevant studies and synthesised performance measures (e.g. sensitivity, specificity and concordance (C) statistics) to evaluate the prognostic accuracy of individual RAMs. We subsequently used this information to inform decision-analytic modelling. The target population for the conceptual model was hospital inpatients, including medical, surgical and trauma patients but excluding critical care patients, children and women admitted to hospital for pregnancy-related reasons. Patients at increased risk of bleeding were assumed not to receive pharmacological prophylaxis under any strategy and were excluded from the model. We compared strategies of using no pharmacological prophylaxis, pharmacological prophylaxis for all and pharmacological prophylaxis given in accordance with validated RAMs. The use of mechanical prophylaxis was considered out of scope for the modelling. We used a lifetime horizon and reported primary outcomes of costs and quality-adjusted life-years (QALYs). Multiple scenario and sensitivity analyses were conducted by subgroup. Workstream two used primary research to address objectives four and five. We conducted a multicentre observational cohort study across four hospitals to compare prespecified methods of efficient data collection to formal case note review. We identified a target population hospitalised during 2019 and extracted data from prospectively completed VTE risk assessments, when available. Research assistants undertook further retrospective case note review for each patient episode. We used electronic health records to evaluate additional risk characteristics and record all relevant clinical outcomes, including the subsequent diagnosis of HAT, major bleeding and clinically relevant non-major bleeding events. We then collated multiple routine data sources for each patient episode to determine the accuracy of these methods in identifying relevant clinical outcomes, compared to a gold standard of case note review. The primary outcome measures for workstream two were contingency tables with sensitivity, specificity and predictive values. Feasibility criteria for any future study using efficient data methods were set a priori. We also estimated the potential variation in prescribing recommendations using multiple validated RAMs and estimated key parameters for any future implementation study. The Venous ThromboEmbolism Assessment Methods study received a favourable opinion from the Proportionate Review Sub-committee of the London – West London & Gene Therapy Advisory Committee (GTAC) Research Ethics Committee and approval from the Health Research Authority (HRA) and Care Research Wales (HCRW) on 18 September 2019 (reference 19/LO/1303, IRAS project ID 262220). Results Workstream 1 Our updated systematic review included 51 studies, comprising 24 unique validated RAMs. The vast majority of studies evaluated VTE RAMs in medical (n = 21), surgical (n = 15) or mixed (n = 4) cohorts of hospital inpatients. The most widely evaluated models were the Caprini RAM (22 studies), the Padua prediction score (16 studies), the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) models (8 studies), the Geneva Risk Score (4 studies) and the Kucher Score (4 studies). All studies had a high or unclear risk of bias, with the main issues related to patient selection, outcome and analysis factors. C-statistics varied markedly between these studies and between models, with no RAM performing obviously better than other models. Similarly, estimates for sensitivity and specificity were highly variable. In the decision analytic modelling, we estimate that in medical inpatients, prophylaxis reduces serious adverse outcomes [fatal PEs, fatal bleeding and non-fatal intracranial haemorrhage (ICH)] from 53 per 10,000 to 42 per 10,000, with a reduction in symptomatic DVTs and non-fatal PEs that is higher than the increase in other bleeds. In the long-term outcomes at 5 years, there is a large reduction in the number of patients experiencing post-thrombotic syndrome (PTS) following prophylaxis from 787 per 10,000 to 385 per 10,000, but minimal difference in overall survival. Modelling showed that thromboprophylaxis for all has a high probability (> 99%) of being the most cost-effective strategy (£20,000 per QALY threshold) based on the performance of existing RAMs in cohorts of medical inpatients. This finding was generally robust under the scenario and sensitivity analyses with one exception; targeting thromboprophylaxis using a Padua score ≥ 3 (84% of cohort) had a 76.6% probability of being the most cost-effective strategy when assuming higher RAM performance (sensitivity 99.9%; specificity 23.7%). The overall expected value of perfect information (EVPI) associated with all parameters included in the probabilistic sensitivity analysis (PSA) when valuing a QALY at £20,000 was £0.06 per patient per year due to the high probability that prophylaxis for all is the optimal strategy. However, the EVPI would be £2.42 per person per year if a more accurate RAM could be developed for medical inpatients. In surgical inpatients, the risk of a serious adverse outcome (as above) is low at 7 per 10,000 but it is increased slightly by prophylaxis to 11 per 10,000 due to the additional risk of fatal bleeding or non-fatal ICH. Although the risk of any symptomatic VTE is reduced form 140 per 10,000 to 41 per 10,000, the risk of any major bleeding is increased from 125 per 10,000 to 370 per 10,000. Prophylaxis still reduces the risk of PTS in surgical inpatients, from 367 per 10,000 to 107 per 10,000, but PTS is less common in the surgical cohort than in the medical cohort. Modelling showed that giving prophylaxis to all surgical inpatients has the highest probability of being cost-effective at £20,000 per QALY, with a 70% likelihood of being optimal, but there is also a 17% likelihood that using a Pannucci score of ≥ 3 would be optimal and a 9% likelihood that using a Pannucci score of ≥ 1 would be optimal. These findings were sensitive to some uncertainties explored in the scenario and sensitivity analyses. In particular, prophylaxis for all may no longer be the optimal strategy for surgical inpatients when the risk of PTS is lower, when using an extended duration of prophylaxis or where a RAM is assumed to have a very high sensitivity. The overall EVPI associated with all parameters included in the PSA when valuing a QALY at £20,000 was £16.35 per person. This does not include the uncertainty of considering which RAM to use as the EVPI and does not include any uncertainty not captured in the PSA, such as uncertainty around the model assumptions or the choice of data sources, or uncertainty around the estimates of sensitivity and specificity. In the analysis of parameter EVPI [expected value of partial perfect information (EVPPI)], the relative risk of VTE for patients having thromboprophylaxis compared to patients not having thromboprophylaxis was the parameter with the largest EVPPI. In specific surgical populations requiring longer durations of prophylaxis, we found that pharmacological prophylaxis for all eligible patients remained optimal in those having elective knee replacement. Offering prophylaxis at a Pannucci score of ≥ 3 (sensitivity of 84% and specificity of 49%) was optimal when prescribing 28 days of low-molecular-weight heparin (LMWH) to patients having elective hip replacement. These conclusions were sensitive to prophylaxis strategy; using direct oral anticoagulants (DOACs) rather than LMWH resulted in prophylaxis for all as the optimal strategy for both hip and knee patients. Workstream 2 The observational cohort study was conducted across all four sites, enrolling 2115 patient hospitalisation episodes, with 2008 eligible for analysis. Medical and surgical cases were evenly balanced, but with more emergency (73.7%) than elective (25.8%) admissions. The sensitivity of routine coding data for detection of HAT and major bleeding events was 62% [95% confidence interval (CI) 54 to 69] and 38% (95% CI 27 to 50), respectively. Local VTE data sets performed better, with sensitivity of 81% (95% CI 75 to 87). The specificity of routine coding data for VTE and bleeding was 98% (95% CI 97 to 99) and 95% (95% CI 94 to 96), respectively, and the specificity of local VTE data sets was 100% (95% CI 99 to 100). We were unable to demonstrate overall feasibility of using efficient outcome measures and did not meet several prespecified criteria. In a smaller subgroup of patients with prospectively collected data, we evaluated potential variation in pharmacological prophylaxis using different RAMs. We identified 543 hospital episodes with VTE risk assessment performed during 2019, with 254 episodes suitable for inclusion, data extraction and comparative analysis. Overall recommendations for pharmacological prophylaxis varied substantially between seven RAMs, ranging from 13% of admitted patients for the IMPROVE associative score (95% CI 9.4 to 17.7) to 91% (95% CI 86.3 to 93.6) for the Department of Health (now Department of Health and Social Care) VTE risk assessment tool. The latter tool resulted in an absolute increase of 28% for prophylaxis recommendation, compared to other RAMs. Within this multicentre cohort of hospitalised inpatients, the HAT event rate was 1.6% (95% CI 1.0 to 2.2) and the major bleeding event rate was 2.5% (95% CI 1.8 to 3.2). Conclusions We updated prior systematic reviews to conclude that that the available evidence has significant methodological limitations and demonstrates current RAMs to have weak predictive accuracy. Decision-analytic modelling showed that the balance of VTE or major bleeding risks, combined with the RAM performance in medical cohorts, means that thromboprophylaxis for all is the optimal strategy within our model for medical inpatients. These findings were robust to multiple scenarios and sensitivity analyses. The optimal strategy for surgical inpatients is to offer thromboprophylaxis to all. However, the scenario analyses for surgical inpatients found that the optimal strategy was sensitive to many of the individual model inputs and assumptions tested. In addition, the optimal strategy for surgical patients receiving extended duration thromboprophylaxis appeared dependent on duration of therapy and prophylaxis strategy. The findings from our cohort study suggest that efficient methods for identifying VTE or major bleeding events during hospital admission or within 90 days of discharge, are not sufficiently sensitive for use in a large data-enabled study. We did not reach several predefined feasibility metrics. We also found limitations in the ability of efficient methods to identify individual risk variables and facilitate RAM comparison in future work. The majority of our sites did not collect contemporaneous data on risk assessment in a digital, or easily accessible format. Implications for policy-makers If, despite drug costs and potential harms, pharmacological prophylaxis for all is the most cost-effective strategy, use of unvalidated RAMs may be suboptimal. Based on our findings, it may be preferable for policy-makers to consider evaluating a new paradigm of ‘opt-out’ VTE prevention, in which all eligible patients are routinely offered pharmacological prophylaxis on hospital admission without complex risk assessment. In this circumstance, patients who are ineligible for pharmacological prophylaxis due to high bleeding risk, specific contraindications or personal choice could opt out, but still utilise evidence-based mechanical thromboprophylaxis strategies. The findings from our cohort study have implications for funders looking to support further work in this area. These data suggest large studies entirely reliant on routine data collection methods for complex time-dependent outcome measures (such as HAT or major bleeding) are likely to be inaccurate. Recommendations for future research Further research should evaluate the following themes in this area of clinical care: Evaluation of routine pharmacological prophylaxis for all eligible medical and surgical patients on hospital admission, compared to current practice of risk assessment using a RAM. Such work would need to be conducted at scale and could not rely on efficient methods for outcome measurement in isolation. Development and validation of RAMs to identify individuals receiving prophylaxis at very low risk of blood clots, who could therefore potentially discontinue pharmacological prophylaxis early during hospital stay. Our analysis was inevitably limited in scope and did not examine the use of RAMs to identify accurate prediction of bleeding risk, the use of mechanical prophylaxis in medical patients with increased bleeding risk (or contraindications to pharmacological prophylaxis) or patients at risk of thromboprophylaxis failure. These issues could be priorities for future research. Study registration This study is registered as Research Registry 5216, PROSPERO CRD42020165778. Funding This award was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127454) and is published in full in Health Technology Assessment; Vol. 28, No. 20. See the NIHR Funding and Awards website for further award information.

This paper offers a reflexive analysis of an interdisciplinary and cross-race collaboration to advance equity in engineering called LATTICE (Launching Academics on the Tenure-Track: an Intentional Community in Engineering). We engage two bodies of scholarship—matters of care in feminist science and technology studies (STS) and critical race theory on counterspaces—to theorize on the data infrastructure and narrative practices that we developed when applying critical methodologies to collective action in technoscience. We discuss how our care practices conflicted with traditional ethnographic practices and thus, inspired us to innovate on methods. These methods—member-checking and polyvocal memo-ing—make transgressing the boundaries of LATTICE counterspaces for public dissemination possible by invoking caring as praxis. We conclude that using these methods to discuss the contradictions and challenges in STS collaborations is an opportunity for advancing mutual intelligibility among interdisciplinary scholars and a politics of knowledge production grounded in values of care and friendship that may contribute to equity and justice in technoscience.

Abstract Contemporary students increasingly benefit from non‐hierarchical education, including peer‐led work, which moves beyond more ridged traditional educational structures. Such approaches encourage engagement, two‐way communication, diversity of thought and collaboration. This piece shares the stories and experiences of students with a shared interest in health promotion and lifestyle medicine who took part in a peer‐led, internationally based online student group. The forum aimed to provide a space for students to explore and discuss diverse topics within the health sphere in an attempt to bridge the gap between areas of expertise and education. The group capitalised on the normalisation of remote video meetings following the COVID‐19 pandemic to bring together a small group of diverse students from across the globe on a weekly basis for journal clubs, presentations, debates and guest lectures. Group member feedback was obtained and highlighted key gaps in much traditional education, which the group addressed. These included moving beyond educational and research silos, the importance of preventative health approaches and the need for more judgement‐free and inclusive learning environments. Alignment with the current health landscape and potential for scaling the group format more widely is discussed. The article concludes by emphasising the advantages of this approach in fostering a network of learners prepared to tackle future health challenges.

Recently, 2D/3D direct laser writing has attracted increased attention due to its broad applications ranging from biomedical engineering to aerospace. 3D nanolithography of water-soluble protein-based scaffolds have been envisioned to provide a variety of tunable properties. In this paper, we present a functional protein-based photoresist with tunable mechanical properties that is suitable for multiphoton lithography (MPL). Through the use of methacrylated streptavidin or methacrylated bovine serum albumin in combination with polyethylene glycol diacrylate or methacrylated hyaluronic acid as crosslinkers and a vitamin-based photoinitiator, we were able to write two- and three-dimensional structures as small as 200 nm/600 nm lateral/axial features, respectively. We also demonstrated that Young's modulus can be tuned by the photoresist composition, and we were able to achieve values as low as 40 kPa. Furthermore, we showed that Young's modulus can be recovered after drying and rehydration (i.e. shelf time determination). The retained biological functionality of the streptavidin scaffolds was demonstrated using fluorescently labelled biotins. Using single-molecule fluorescence microscopy, we estimated the density of streptavidin in the written features (1.8 ± 0.2 × 105 streptavidins per 1.00 ± 0.05 μm³ of feature volume). Finally, we showed applicability of our 2D scaffold as a support for a fluorescence absorbance immuno-assay (FLISA), and as a delivery platform of extracellular vesicles to HeLa cells.

Venous thromboembolism is the third most common cause of cardiovascular death globally and many diagnoses are preventable. The UK NHS has led international efforts to reduce VTE, particularly hospital-associated VTE, through coordinated national policy action and world-leading research. Despite this, VTE remains an important cause of morbidity and mortality in the UK, as underlined by the recent COVID-19 pandemic. Future reductions in VTE incidence/deaths will require progress on several fronts: a better understanding of case mix; revisiting VTE risk assessment, focussing on thromboprophylaxis failure and improving awareness of VTE amongst clinicians and the public. Changes to healthcare delivery, with care increasingly delivered outside of hospital, alongside changing disease patterns, including the rise in obesity, have huge implications for VTE and will dramatically alter prevention. The UK, with its nationalised healthcare model and long history of policy action on VTE, provides a unique lens through which to study past successes and future priorities for VTE prevention.

Objective To explore whether large language models (LLMs) Generated Pre-trained Transformer (GPT)-3 and ChatGPT can write clinical letters and predict management plans for common orthopaedic scenarios.Design Fifteen scenarios were generated and ChatGPT and GPT-3 prompted to write clinical letters and separately generate management plans for identical scenarios with plans removed.Main outcome measures Letters were assessed for readability using the Readable Tool. Accuracy of letters and management plans were assessed by three independent orthopaedic surgery clinicians.Results Both models generated complete letters for all scenarios after single prompting. Readability was compared using Flesch-Kincade Grade Level (ChatGPT: 8.77 (SD 0.918); GPT-3: 8.47 (SD 0.982)), Flesch Readability Ease (ChatGPT: 58.2 (SD 4.00); GPT-3: 59.3 (SD 6.98)), Simple Measure of Gobbledygook (SMOG) Index (ChatGPT: 11.6 (SD 0.755); GPT-3: 11.4 (SD 1.01)), and reach (ChatGPT: 81.2%; GPT-3: 80.3%). ChatGPT produced more accurate letters (8.7/10 (SD 0.60) vs 7.3/10 (SD 1.41), p=0.024) and management plans (7.9/10 (SD 0.63) vs 6.8/10 (SD 1.06), p

Exclusionary discipline practices have a direct negative impact on individual students, schools, and society at large. To improve equity and cultural responsivity, active efforts to assess the contextual fit of effective strategies are necessary. The following study describes the Inclusive Skill-building Learning Approach (ISLA), an intervention designed to support school staff in carrying out preventative strategies and outlines instructional responses for educators and office staff. Additionally, an iterative approach to inform changes was used as part of the development process of ISLA. This paper aims to capture and incorporate the voices of students and staff using multiple methods to seek feedback for refining the quality, feasibility, and contextual fit of the ISLA intervention in middle schools. A total of 53 school staff provided feedback on the ISLA intervention. Further, Design Team members (n = 26) participated in semi-structured interview meetings to inform changes to ISLA. Last, student participants (n = 23) engaged in focus groups that were transcribed and coded via an independent co-coding strategy. The findings provide support for preventative school-based interventions that use alternatives to exclusionary discipline, as well as strategies for improving the ISLA intervention. [For the corresponding grantee submission, see ED618111.]

Andreas Horner,1 Horst Olschewski,2 Sylvia Hartl,3 Arschang Valipour,4 Georg-Christian Funk,5 Michael Studnicka,6 Monika Merkle,7 Bernhard Kaiser,1 Eva Maria Wallner,8 Stephan Brecht,8 Bernd Lamprecht1 1Johannes Kepler University Linz, Kepler University Hospital, Department of Pulmonology, Linz, Austria; 2Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, and Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; 3Department of Respiratory and Critical Care Medicine, Klinik Penzing and Sigmund Freud University, Medical School, Vienna, Austria; 4Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria; 5Department of Internal and Respiratory Medicine, Klinik Ottakring, Vienna, Austria; 6Department of Pulmonary Medicine, Paracelsus Medical University, Salzburg, Austria; 7Specialist Office for Pulmonology Dr. Merkle, Vienna, Austria; 8A. Menarini Pharma GmbH, Vienna, AustriaCorrespondence: Andreas Horner, Johannes Kepler University Linz, Kepler University Hospital, Department of Pulmonology, Altenberger Strasse, 69, 4040 Linz and Krankenhausstrasse 9, 4020 Linz, Austria, Email Andreas.Horner@kepleruniklinikum.atBackground: Symptoms of depression, pain and limitations in physical activity may affect quality of life in COPD patients independent from their respiratory burden. We aimed to analyze the associations of these factors in outpatients with COPD in Austria in a stable phase of disease.Methods: We conducted a national, cross-sectional study among patients with COPD. For depression, the Patient Health Questionnaire-9 (PHQ-9) and for respiratory symptoms the St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C) were used along with 10-point scales for physical activity and pain.Results: After exclusion of 211 patients due to non-obstructive spirometry or missing data, 630 patients (62.5% men; mean age 66.8 ± 8.6 (SD) years; mean FEV1%pred. 54.3 ± 16.5 (SD)) were analyzed. Of these, 47% reported one or more exacerbations in the previous year, 10.4% with hospitalization. A negative depression score was found in 54% and a score suggesting severe depression (PHQ-9 score ≥ 15) in 4.7%. In a multivariate linear regression model, self-reported pain, dyspnea, and number of exacerbations were predictors for higher PHQ-9-scores. A negative pain score was found in 43.8%, and a score suggesting severe pain in 2.9% (8– 10 points of 10-point scale). Patients reporting severe pain were more often female, had more exacerbations, and reported more respiratory and depressive symptoms, a lower quality of life, and less physical activity. About 46% of patients rated their physical activity as severely impaired. These patients were significantly older, had more exacerbations, concomitant heart disease, a higher pain and depression score, and a lower quality of life (SGRQ-C – total score and all subscores).Conclusions: In Austria, nearly half of stable COPD outpatients reported symptoms of depression, which were associated with lower levels of self-reported physical activity, more pain, and respiratory symptoms. The associations were particularly strong for depression with SGRQ-C.Keywords: chronic obstructive pulmonary disease, depression, PHQ-9, pain, quality of life, St. George’s Respiratory Questionnaire, physical activity

Tropical deep convective clouds, particularly their large cirrus outflows, play an important role in modulating the energy balance of the Earth's atmosphere. Whilst the cores of these deep convective clouds have a significant short-wave (SW) cooling effect, they dissipate quickly. Conversely, the thin cirrus that flow from these cores can persist for days after the core has dissipated, reaching hundreds of kilometres in extent. These thin cirrus have a potential for large warming in the tropics. Understanding the evolution of air parcels from deep convection, clouds along these trajectories, and how they change in response to anthropogenic emissions is therefore important to understand past and future climate change. This work uses a novel approach to investigate the evolution of tropical convective clouds by introducing the concept of “time since convection” (TSC). This is used to build a composite picture of the lifecycle of air parcels from deep convection. Cloud properties are a strong function of TSC, showing decreases in the optical thickness, cloud-top height, and cloud fraction over time, thereby driving the latitudinal structure of cloudiness. After an initial dissipation of the convective core, changes in thin cirrus cloud amount were seen beyond 200 h from convection. Changes in cloud are shown to be a strong function of TSC and not simply reflective of latitudinal changes as air moves from the tropics to the extratropics. Finally, in the initial stages of convection there was a large net negative cloud radiative effect (CRE). However, once the convective core had dissipated, the sign of the CRE flipped and there was a sustained net warming CRE beyond 120 h from the convective event. Changes are present in the cloud properties long after the main convective activities have dissipated, signalling the need to continue further analysis at longer timescales than previously studied.

Abstract The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young’s modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis.