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As architects and designers, we face design challenges that are rooted in the built condition. In our collaboration with student activities professionals, the effective use of space to service, engage, and welcome the campus community is at the forefront of design and planning discussions. We must consider the social implications of our physical designs that evolve as social and cultural norms change. One such topic of extended conversation is the all-gender restroom which has been a topic of conversation in the projects we are designing over the last decade. This piece will help bridge the gap between student affairs practitioners and architectural designers with information and understanding of how code influences the design of all gender restrooms, so that campus communities are better prepared to advocate for their needs in building all gender restrooms.

Abstract An understanding of the extent to which target audiences consider different nutrition-related messages to be effective could assist campaign developers design more persuasive communications. Accordingly, this study sought to develop and assess the utility of the Perceived Effectiveness of Nutrition Messages Scale (PENMS). A longitudinal online survey was completed by Australian adults (n = 5,014 at Time 1 and 2,880 at Time 2). At T1, respondents saw one of two messages promoting healthy eating. They were then administered the PENMS, and asked how likely they were to engage in the behaviour specified in the message. Respondents completed the PENMS again at T2. An exploratory factor analysis was performed on PENMS scores and measures of reliability and validity obtained. Two factors were identified: ‘effects perceptions’ (Factor 1) and ‘message perceptions’ (Factor 2). Internal consistency of scores was 0.82 for Factor 1 and 0.70 for Factor 2. Test re-test reliability was 0.76 and 0.69 for Factors 1 and 2, respectively. Scores on both factors were moderately correlated with behavioural intentions. The favourable results for PENMS scores suggest the scale may be a useful tool for assessing the extent to which target audiences consider different nutrition-related messages to be effective.

A-Ching Chao,1,2 Tsong-Hai Lee,3 Luther C Pettigrew,4 Yousef Hannawi,5 Hung-Yu Huang,6 Nai-Fang Chi,7,8 Lung Chan,9,10 Po-Lin Chen,11 Thomas Devlin12,13 1Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 2College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Department of Neurology, University of Kentucky Chandler Medical Center, Lexington, KY, USA; 5Division of Cerebrovascular Diseases and Neurocritical Care, Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 7School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 8Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; 9Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 10Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 11Division of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan; 12CHI Memorial Neuroscience Institute, Chattanooga, TN, USA; 13Department of Neurology, Morehouse School of Medicine, Atlanta, GA, USACorrespondence: Thomas Devlin, Chattanooga Center for Neurological Research, 725 Glenwood Drive, Suite 880-A, Chattanooga, TN, 37404, USA, Email devlinmdphd@gmail.comPurpose: Odatroltide (LT3001), a novel small synthetic peptide molecule designed to recanalize occluded blood vessels and reduce reperfusion injury, is safe and efficacious in multiple embolic stroke animal models. This study aimed to investigate the safety and tolerability of intravenous administration of odatroltide in patients with acute ischemic stroke within 24 hours of onset.Patients and Methods: Patients with National Institutes of Health Stroke Scale (NIHSS 4– 30) who were untreated with intravenous thrombolysis or endovascular thrombectomy were randomized (2:1) to receive a single dose of odatroltide (0.025 mg/kg) or placebo within 24 hours of stroke symptom onset. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) occurrence within 36 hours.Results: Twenty-four patients were enrolled and randomized; of these 16 and 8 received intravenous odatroltide infusion and placebo, respectively. sICH did not occur in both groups, and other safety measures were comparable between the groups. The rate of excellent functional outcome (modified Rankin Scale score, 0– 1, at 90 days) was 21% and 14% in the odatroltide and placebo groups, respectively. Furthermore, 47% and 14% of patients in the odatroltide and placebo groups, respectively, showed major neurological improvement (NIHSS improvement ≥ 4 points from baseline to 30 days). Among the 9 odatroltide-treated patients with baseline NIHSS ≥ 6, 78% showed major neurological improvement.Conclusion: Compared with placebo, treatment with intravenous odatroltide within 24 hours following onset of ischemic stroke appears to be safe and may be associated with better neurological and functional outcomes. However, the efficacy and safety of odatroltide requires further confirmation in the next phase of clinical trials.Clinical Trial Registration: Clinicaltrials.gov identifier: NCT04091945.Keywords: LT3001, ischemic stroke, rtPA

Background. Preimplantation biopsy combines measurements of injury into a composite index to inform organ acceptance. The uncertainty in these measurements remains poorly characterized, raising concerns variability may contribute to inappropriate clinical decisions. Methods. We adopted a metrological approach to evaluate biopsy score reliability. Variability was assessed by performing repeat biopsies (n = 293) on discarded allografts (n = 16) using 3 methods (core, punch, and wedge). Uncertainty was quantified using a bootstrapping analysis. Observer effects were controlled by semi-blinded scoring, and the findings were validated by comparison with standard glass evaluation. Results. The surgical method strongly determined the size (core biopsy area 9.04 mm2, wedge 37.9 mm2) and, therefore, yield (glomerular yield r = 0.94, arterial r = 0.62) of each biopsy. Core biopsies yielded inadequate slides most frequently. Repeat biopsy of the same kidney led to marked variation in biopsy scores. In 10 of 16 cases, scores were contradictory, crossing at least 1 decision boundary (ie, to transplant or to discard). Bootstrapping demonstrated significant uncertainty associated with single-slide assessment; however, scores were similar for paired kidneys from the same donor. Conclusions. Our investigation highlights the risks of relying on single-slide assessment to quantify organ injury. Biopsy evaluation is subject to uncertainty, meaning each slide is better conceptualized as providing an estimate of the kidney’s condition rather than a definitive result. Pooling multiple assessments could improve the reliability of biopsy analysis, enhancing confidence. Where histological quantification is necessary, clinicians should seek to develop new protocols using more tissue and consider automated methods to assist pathologists in delivering analysis within clinical time frames.

The 2020 COVID-19 crisis forced universities to make a dramatic shift to emergency remote education (ERE). While the urgency of the pandemic is gone, schools continue implementing ERE, but more often on a short-notice, short-term basis in response to various situations. This research examines students’ suggestions for improving university transitions to ERE and applies them to post-pandemic use of ERE. Qualitative thematic analysis was used to analyze responses to an open-ended survey question answered by 2,751 students at a large Southeastern U.S. university. Responses identified main concerns as Grades and Grading (38%), Better University and Instructor Preparation (23%), Improved Learning Experience (18%), Meeting Student Needs (12%), and No Suggestions (9%). The study found that reducing the uncertainty students felt about ERE’s impact on grades, course content, class schedules, assignments, and communication with instructors would improve their online learning experience. Recommendations suggest preemptive steps universities can take to improve post-pandemic use of emergency remote education.

IntroductionRenal transplant biopsies provide insights into graft health and support decision making. The current evidence on links between biopsy scores and transplant outcomes suggests there may be numerous factors affecting biopsy scores. Here we adopt measurement science approach to investigate the sources of uncertainty in biopsy assessment and suggest techniques to improve its robustness.MethodsHistological assessments, Remuzzi scores, biopsy processing and clinical variables are obtained from 144 repeat biopsies originating from 16 deceased-donor kidneys. We conducted sensitivity analysis to find the morphometric features with highest discriminating power and studied the dependencies of these features on biopsy and stain type. The analysis results formed a basis for recommendations on reducing the assessment variability.ResultsMost morphometric variables are influenced by the biopsy and stain types. The variables with the highest discriminatory power are sclerotic glomeruli counts, healthy glomeruli counts per unit area, percentages of interstitial fibrosis and tubular atrophy as well as diameter and lumen of the worst artery. A revised glomeruli adequacy score is proposed to improve the robustness of the glomeruli statistics, whereby a minimum of 104 µm2 of cortex tissue is recommended to keep type 1 and type 2 error probabilities below 0.15 and 0.2.DiscussionThe findings are transferable to several biopsy scoring systems. We hope that this work will help practitioners to understand the sources of statistical uncertainty and improve the utility of renal biopsy.

The past several decades have seen rapid advances in diagnosis and treatment of cardiovascular diseases and stroke, enabled by technological breakthroughs in imaging, genomics, and physiological monitoring, coupled with therapeutic interventions. We now face the challenge of how to (1) rapidly process large, complex multimodal and multiscale medical measurements; (2) map all available data streams to the trajectories of disease states over the patient's lifetime; and (3) apply this information for optimal clinical interventions and outcomes. Here we review new advances that may address these challenges using digital twin technology to fulfill the promise of personalized cardiovascular medical practice. Rooted in engineering mechanics and manufacturing, the digital twin is a virtual representation engineered to model and simulate its physical counterpart. Recent breakthroughs in scientific computation, artificial intelligence, and sensor technology have enabled rapid bidirectional interactions between the virtual‐physical counterparts with measurements of the physical twin that inform and improve its virtual twin, which in turn provide updated virtual projections of disease trajectories and anticipated clinical outcomes. Verification, validation, and uncertainty quantification builds confidence and trust by clinicians and patients in the digital twin and establishes boundaries for the use of simulations in cardiovascular medicine. Mechanistic physiological models form the fundamental building blocks of the personalized digital twin that continuously forecast optimal management of cardiovascular health using individualized data streams. We present exemplars from the existing body of literature pertaining to mechanistic model development for cardiovascular dynamics and summarize existing technical challenges and opportunities pertaining to the foundation of a digital twin.

Objective To describe trends in the organisational structure, workforce and recorded appointments by role in English general practice.Design Retrospective longitudinal study.Setting English general practice.Data sources and participants NHS England, Office for Health Improvement and Disparities and Care Quality Commission national administrative datasets covering between 5 to 10 years from 2013 to 2023.Results Between 2013 and 2023, the number of general practices fell by 20% from 8044 to 6419; the average practice list size increase by 40% from 6967 to 9724 patients. The total population covered by providers with over 100 000 registered patients reached 2.3 million in 2023 compared to 0.5 million in 2017. The proportion of practices under individual ownership decreased from 13% to 11% between 2018 and 2023; there was little change in the proportion owned by partnerships, incorporated companies or NHS bodies, which respectively averaged around 80.3%, 6.9% and 0.7%. Between 2015 and 2022, there was a 20% rise in the total full-time equivalent (FTE) general practice workforce, including Primary Care Network staff, from 1.97 to 2.37 per 1000 patients because of an increase in multidisciplinary other 'Direct Patient Care' (DPC) and administrative roles. The number of nurses remained stable, and the number of qualified general practitioners (GPs) decreased by 15%. In September 2022, there were 0.45 FTE qualified GPs per 1000 patients; GPs and other DPC roles, excluding nurses, each represented 19% of the FTE per 1000 patients workforce; administrative roles represented 51%. The general practice workforce is predominantly female. A quarter of GPs qualified overseas. Between 2018 and 2023, there was no clear upward or downward trend in total appointments per 1000 patients with, on average, half provided by GPs.Conclusions Since 2013, there has been a shift in general practice towards larger practices with more multidisciplinary teams, alongside a reduction in the number of FTE qualified GPs per 1000 patients. We recommend that the impacts of these changes on access, quality and costs are closely monitored.

Abstract Data from commercial off-the-shelf (COTS) wearables leveraged with machine learning algorithms provide an unprecedented potential for the early detection of adverse physiological events. However, several challenges inhibit this potential, including (1) heterogeneity among and within participants that make scaling detection algorithms to a general population less precise, (2) confounders that lead to incorrect assumptions regarding a participant’s healthy state, (3) noise in the data at the sensor level that limits the sensitivity of detection algorithms, and (4) imprecision in self-reported labels that misrepresent the true data values associated with a given physiological event. The goal of this study was two-fold: (1) to characterize the performance of such algorithms in the presence of these challenges and provide insights to researchers on limitations and opportunities, and (2) to subsequently devise algorithms to address each challenge and offer insights on future opportunities for advancement. Our proposed algorithms include techniques that build on determining suitable baselines for each participant to capture important physiological changes and label correction techniques as it pertains to participant-reported identifiers. Our work is validated on potentially one of the largest datasets available, obtained with 8000+ participants and 1.3+ million hours of wearable data captured from Oura smart rings. Leveraging this extensive dataset, we achieve pre-symptomatic detection of COVID-19 with a performance receiver operator characteristic (ROC) area under the curve (AUC) of 0.725 without correction techniques, 0.739 with baseline correction, 0.740 with baseline correction and label correction on the training set, and 0.777 with baseline correction and label correction on both the training and the test set. Using the same respective paradigms, we achieve ROC AUCs of 0.919, 0.938, 0.943 and 0.994 for the detection of self-reported fever, and 0.574, 0.611, 0.601, and 0.635 for detection of self-reported shortness of breath. These techniques offer improvements across almost all metrics and events, including PR AUC, sensitivity at 75% specificity, and precision at 75% recall. The ring allows continuous monitoring for detection of event onset, and we further demonstrate an improvement in the early detection of COVID-19 from an average of 3.5 days to an average of 4.1 days before a reported positive test result.

University food environments have a strong influence on the dietary choices of students and staff. The aim of this study was to assess the food environment at a large university in Sydney, Australia. Data were collected between March and July 2022 from 27 fixed food outlets and 24 vending machines. The healthiness of the food environment was evaluated using the Healthy Food and Drink in NSW Health Facilities for Staff and Visitors Framework ('Framework'), which assesses food environment parameters including the availability, placement, and promotion of 'Everyday' (healthy) and 'Occasional' (less healthy) products. Each parameter was evaluated overall and across each food outlet type. Across all outlets, Everyday foods and drinks made up 43.9% of all products. Only two outlets met the Framework's product availability benchmark of ≥75% Everyday foods and drinks. A total of 43 outlets (84.3%) sold sugary drinks as part of their product range. Occasional products made up 68.4%, 53.3%, and 59.9% of all items for sale at checkout areas, countertops, and eye-level shelves, respectively. Finally, 79.7% of meal deals included Occasional products. Our findings highlight the need to improve the availability, placement, and promotion of foods and drinks sold at a major university campus in Sydney, Australia.

The quality assurance provided by preimplantation biopsy quantification of chronic damage may allow greater use of kidneys from expanded criteria donors, and thereby expand the deceased donor pool. Preimplantation biopsy may, however, identify additional acute or chronic pathologies not considered in the scoring of chronic damage, and these may influence the decision to implant or discard the kidney. This single-centre retrospective cohort study of a contemporary UK donor population systematically characterised the nature of additional findings in 1,046 preimplantation and implantation biopsies over an eight-year period. A diverse range of findings were identified in 111/1,046 (11%) organs; most frequently diabetic glomerulopathy, focal segmental glomerulosclerosis, (micro)thrombi, neutrophil casts, and immunoglobulin/complement staining. Seventy (63%) of these were transplanted, with subsequent biopsy in 41 (58%) cases confirming that 80% of the initial acute changes had spontaneously resolved, while there was no progression of diabetic glomerulopathy, and the lesions of focal segmental glomerulosclerosis were not identified. Over 75% of assessable grafts with additional histological findings at the time of transplant showed adequate function at one-year following transplant. In conclusion, most histological abnormalities that may be identified in addition to chronic scarring in preimplantation kidney biopsies would not preclude transplantation nor predict poor graft function.

Abstract Aim To explore how undergraduate nursing students are assessed on nursing numeracy and medication calculations from the perspective of Australian nurse education leaders. Design A qualitative study. Methods Semi‐structured interviews were conducted with 17 nurse education leaders between November 2022 and January 2023. Braun and Clarke's six phases of thematic analysis were used to analyse the data. Results Five key themes were identified: (i) high expectations to keep the public safe, (ii) diverse assessment formats, (iii) different ways of managing assessment integrity, (iv) assessment conditions incongruent to the clinical setting and (v) supporting struggling students. Conclusion Nurse education leaders set high standards requiring students to achieve 100% in numeracy and medication calculation assessments, thus maintaining the reputation of nursing and patient safety. However, students struggled to meet this expectation. Diverse assessment formats were implemented, with some examination conditions contrary to clinical practice. Currently, there is no benchmark or independent point of registration examination in Australia, hence the problem is each university had a different standard to judge students' competence. Gaining insight into how these assessments are conducted provides an opportunity to work towards an evidence‐based model or benchmark for the assessment of numeracy. Implications for the Profession Dosage errors in clinical practice threaten patient safety and the reputation of the nursing profession. The accuracy rate of calculations by undergraduate and registered nurses is deficient worldwide. This research highlights a major educational issue, that being the wide variation in how numeracy assessments are conducted with no clear pedagogical rationale for a standardised method. Such assessments would establish a national standard, contributing to quality assurance, the development of the nursing profession and improve patient safety.

Background and purpose: Radiomics analysis extracts quantitative data (features) from medical images. These features could potentially reflect biological characteristics and act as imaging biomarkers within precision medicine. However, there is a lack of cross-comparison and validation of radiomics outputs which is paramount for clinical implementation. In this study, we compared radiomics outputs across two computed tomography (CT)-based preclinical scanners. Materials and methods: Cone beam CT (CBCT) and µCT scans were acquired using different preclinical CT imaging platforms. The reproducibility of radiomics features on each scanner was assessed using a phantom across imaging energies (40 & 60 kVp) and segmentation volumes (44–238 mm3). Retrospective mouse scans were used to compare feature reliability across varying tissue densities (lung, heart, bone), scanners and after voxel size harmonisation. Reliable features had an intraclass correlation coefficient (ICC) > 0.8. Results: First order and GLCM features were the most reliable on both scanners across different volumes. There was an inverse relationship between tissue density and feature reliability, with the highest number of features in lung (CBCT=580, µCT=734) and lowest in bone (CBCT=110, µCT=560). Comparable features for lung and heart tissues increased when voxel sizes were harmonised. We have identified tissue-specific preclinical radiomics signatures in mice for the lung (133), heart (35), and bone (15). Conclusions: Preclinical CBCT and µCT scans can be used for radiomics analysis to support the development of meaningful radiomics signatures. This study demonstrates the importance of standardisation and emphasises the need for multi-centre studies.

BackgroundSocial media may be a useful method for research centers to deliver health messages, increase their visibility in the local community, and recruit study participants. Sharing examples of social media–based community outreach and educational programs, and evaluating their outcomes in this setting, is important for understanding whether these efforts have a measurable impact. ObjectiveThe aim of this study is to describe one center’s social media activities for community education on topics related to aging, memory loss, and Alzheimer disease and related dementias, and provide metrics related to recruitment into clinical research studies. MethodsSeveral social media platforms were used, including Facebook, X (formerly Twitter), and YouTube. Objective assessments quantified monthly, based on each platform’s native dashboard, included the number of followers, number of posts, post reach and engagement, post impressions, and video views. The number of participants volunteering for research during this period was additionally tracked using a secure database. Educational material posted to social media most frequently included content developed by center staff, content from partner organizations, and news articles or resources featuring center researchers. Multiple educational programs were developed, including social media series, web-based talks, Twitter chats, and webinars. In more recent years, Facebook content was occasionally boosted to increase visibility in the local geographical region. ResultsUp to 4 years of page metrics demonstrated continuing growth in reaching social media audiences, as indicated by increases over time in the numbers of likes or followers on Facebook and X/Twitter and views of YouTube videos (growth trajectories). While Facebook reach and X/Twitter impression rates were reasonable, Facebook engagement rates were more modest. Months that included boosted Facebook posts resulted in a greater change in page followers and page likes, and higher reach and engagement rates (all P≤.002). Recruitment of participants into center-affiliated research studies increased during this time frame, particularly in response to boosted Facebook posts. ConclusionsThese data demonstrate that social media activities can provide meaningful community educational opportunities focused on Alzheimer disease and related dementias and have a measurable impact on the recruitment of participants into research studies. Additionally, this study highlights the importance of tracking outreach program outcomes for evaluating return on investment.

Background and objectivesThis study aimed to examine whether baseline CSF measures of Alzheimer disease (AD)-related pathology are associated with the time to onset of mild cognitive impairment (MCI) and whether these associations differ by age, sex, Apolipoprotein E (ApoE4) status, and proximal (≤7 years) vs distal (>7 years) time to symptom onset.MethodsMeasures of amyloid (Aβ1-42 and Aβ1-40), phospho-tau (ptau181), and total tau (t-tau) were determined from CSF samples obtained at baseline from participants in an ongoing longitudinal project, known as the Biomarkers for Older Controls at Risk for Alzheimer Disease study (BIOCARD) study. The fully automated, Lumipulse G immunoassay was used to analyze the specimens. Cox regression models were used to examine the relationship of baseline biomarker levels with time to symptom onset of MCI and interactions with age, sex, and ApoE allelic status in subjects who progressed from normal cognition to MCI.ResultsAnalyses included 273 participants from the BIOCARD cohort, who were cognitively normal and predominantly middle-aged at baseline, and have been followed for an average of 16 years (max = 23.6). During follow-up, 94 progressed to MCI (median time to symptom onset = 6.9 years). In Cox regression models, elevated ptau181 and t-tau levels were associated with time to MCI symptom onset if it occurred within 7 years of baseline (HR 1.386 and 1.329; p = 0.009 and 0.017, respectively), while a lower Aβ42/Aβ40 ratio was associated with symptom onset if it occurred >7 years from baseline (HR 0.596, p = 0.003). There were also significant 3-way CSF × age × sex interactions for ptau181 and Aβ42/Aβ40, with follow-up analyses indicating that associations between these biomarkers and progression to MCI were stronger among men than among women, but this difference between sexes diminished with increasing age.DiscussionThe lengthy follow-up of BIOCARD participants permitted an examination of time-varying associations between CSF AD biomarkers with MCI symptom onset and the influence of sex, baseline age, and ApoE4 genotype on these associations. These factors may inform clinical trial enrollment strategies, or trial duration and outcomes, which may use these measures as surrogate markers of treatment response.

BACKGROUND: A lack of undergraduate medical curricula on providing healthcare to transgender and gender diverse (TGD) patients has contributed to significant health disparities for TGD communities. To address this gap, we designed and evaluated a novel curriculum to train Obstetrics and Gynecology (OB/GYN) clerkship students in caring for TGD patients. METHODS: Following Kerns 6-step method for curriculum development, we created a two-part curriculum on TGD healthcare topics - an online module on gender-affirming care, followed by a series of interactive cases on TGD-specific health topics. Undergraduate medical students completing their core OB/GYN clerkships at a university academic medical center (January-December 2021) were invited to complete this curriculum. Participants completed pre/post assessment surveys to assess their experience caring for TGD patients, as well as a scored knowledge assessment before and after completing the curriculum. RESULTS: Sixty-five students participated in this curricular assessment. Prior to completing the module, 45% agreed that they had received adequate TGD health training. Following module completion, students reported increased comfort in caring for transgender patients (49.2% vs. 81.5%; p

Abstract Canine personality and behavioural characteristics have a significant influence on relationships between domestic dogs and humans as well as determining the suitability of dogs for specific working roles. As a result, many researchers have attempted to develop reliable personality assessment tools for dogs. Most previous work has analysed dogs’ behavioural patterns collected via questionnaires using traditional statistical analytic approaches. Artificial Intelligence has been widely and successfully used for predicting human personality types. However, similar approaches have not been applied to data on canine personality. In this research, machine learning techniques were applied to the classification of canine personality types using behavioural data derived from the C-BARQ project. As the dataset was not labelled, in the first step, an unsupervised learning approach was adopted and K-Means algorithm was used to perform clustering and labelling of the data. Five distinct categories of dogs emerged from the K-Means clustering analysis of behavioural data, corresponding to five different personality types. Feature importance analysis was then conducted to identify the relative importance of each behavioural variable’s contribution to each cluster and descriptive labels were generated for each of the personality traits based on these associations. The five personality types identified in this paper were labelled: “Excitable/Hyperattached”, “Anxious/Fearful”, “Aloof/Predatory”, “Reactive/Assertive”, and “Calm/Agreeable”. Four machine learning models including Support Vector Machine (SVM), K-Nearest Neighbour (KNN), Naïve Bayes, and Decision Tree were implemented to predict the personality traits of dogs based on the labelled data. The performance of the models was evaluated using fivefold cross validation method and the results demonstrated that the Decision Tree model provided the best performance with a substantial accuracy of 99%. The novel AI-based methodology in this research may be useful in the future to enhance the selection and training of dogs for specific working and non-working roles.

Abstract Objective: The use of food packaging as a vehicle for marketing to children is under investigated. Our objective was to determine the prevalence and types of child-directed promotional techniques used on food packaging in Australia. Design: Based on existing literature and regulations, we developed a framework to classify on-pack child-directed promotional techniques involving the use of characters and other elements that appeal to children. We analysed the packaging of all products in eight food categories available for sale from supermarkets in 2019 and recorded the use of child-directed promotions on pack. We assessed the number and proportion of products displaying child-directed promotional techniques overall and assessed the healthiness of products using child-directed promotions against four indicators of healthiness to provide summary data overall and for the manufacturers who most frequently employed child-targeted strategies. Setting: Data were collected from the FoodSwitch database in Sydney, Australia. Results: 901/8006 (11·3 %) products displayed one or more child-directed on-pack element. Most frequent was on foods for infants and young children (n 315), confectionery (n 283), snack foods (n 172) and dairy (n 168). Personified characters were the most commonly used element (n 512). Products using child-directed promotional techniques scored poorly on all four indicators of healthiness: mean health star rating 2·34 (out of 5); 81 % ultra-processed and 6·1 % and 4·5 % products eligible to market to children under Western Pacific and Mexican nutrient profiling schemes, respectively. Conclusions: Australian children are targeted by promotional techniques on the packaging of unhealthy food products. Stronger regulation of these techniques is warranted to protect children’s health.

Objectives Electronic health record (EHR) systems are used extensively in healthcare; their design can influence clinicians’ behaviour. We conducted a systematic review of EHR-based interventions aimed at changing the clinical practice of general practitioners in the UK, assessed their effectiveness and applied behaviour change theory to identify lessons for other settings.Design Mixed methods systematic review.Data sources MEDLINE, EMBASE, CENTRAL and APA PsycINFO were searched up to March 2023.Eligibility criteria Quantitative and qualitative findings from randomised controlled trials (RCTs) controlled before-and-after studies and interrupted time series of EHR-based interventions in UK general practice were included.Data extraction and synthesis Quantitative synthesis was based on Cochrane’s Synthesis without Meta-analysis. Interventions were categorised using the Behaviour Change Wheel and MINDSPACE frameworks and effectiveness determined by vote-counting using direction of effect. Inductive thematic synthesis was used for qualitative studies.Results Database searching identified 3824 unique articles; 10 were included (from 2002 to 2021), comprising eight RCTs and two associated qualitative studies. Four of seven quantitative studies showed a positive effect on clinician behaviour and three on patient-level outcomes. Behaviour change techniques that may trigger emotions and required less cognitive engagement appeared to have positive effects. Qualitative findings indicated that interventions reassured clinicians of their decisions but were sometimes ignored.Conclusion Despite widespread use, there is little high quality, up-to-date experimental evidence evaluating the effectiveness of EHR-based interventions in UK general practice. The evidence suggested EHR-based interventions may be effective at changing behaviour. Persistent, simple action-oriented prompts appeared more effective than complex interventions requiring greater cognitive engagement. However, studies lacked detail in intervention design and theory behind design choices. Future research should seek to optimise EHR-based behaviour change intervention design and delineate limitations, providing theory-based justification for interventions. This will be of increasing importance with the growing use of EHRs to influence clinicians’ decisions.PROSPERO registration number CRD42022341009.

Background Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. Objective To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. Design A prospective multicentre observational cohort study (the ‘SONAR’ study). Setting Seventeen haemodialysis centres in the UK. Participants Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Intervention Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Main outcome measures Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. Results A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas’ non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Conclusions Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. Trial Registration This trial is registered as ISRCTN36033877 and ISRCTN17399438. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information. Plain language summary What was the problem? For people with advanced kidney disease, haemodialysis is best provided by an ‘arteriovenous fistula’, which is created surgically by joining a vein onto an artery at the wrist or elbow. However, these take about 2 months to develop fully (‘mature’), and as many as 3 out of 10 fail to do so. What was the question? We asked whether we could use early ultrasound scanning of the fistula to identify those that are unlikely to mature. This would allow us to decide whether it would be practical to run a large, randomised trial to find out if using early ultrasound allows us to ‘rescue’ fistulas that would otherwise fail. What did we do? We invited adults to undergo serial ultrasound scanning of their fistula in the first few weeks after it was created. We then analysed whether we could use the data from the early scans to identify those fistulas that were not going to mature by week 10. What did we find? Of the 333 fistulas that were created, about two-thirds reached maturity by week 10. We found that an ultrasound scan 4 weeks after fistula creation could reliably identify those fistulas that were going to mature. However, of those fistulas predicted to fail, about one-third did eventually mature without further intervention, and even without knowing what the early scans showed, another third were successfully rescued by surgery or X-ray-guided treatment at a later stage. What does this mean? Performing an early ultrasound scan on a fistula can provide reassurance that it will mature and deliver trouble-free dialysis. However, because scans are poor at identifying fistulas that are unlikely to mature, we would not recommend their use to justify early surgery or X-ray-guided treatment in the expectation that this will improve outcomes. Scientific summary Background Because of their favourable durability and low infection rates, arteriovenous fistulas (AVFs) are considered the best option for provision of haemodialysis, and they offer survival advantages compared to dialysis through a central venous catheter (CVC). Upon surgical creation, AVFs undergo a period of ‘maturation’, wherein the transit of high-pressure arterial flow through the anastomosis triggers compensatory dilatation and thickening of the draining fistula vein, with marked increases in blood flow through the AVF. This maturation, which generally takes about 2 months, is required to achieve functionality and enables the AVF to be used for dialysis. The main drawback with AVFs is that a large proportion (in excess of 30% in some series) do not develop fully, and either thrombose or remain patent in an immature state. This necessitates further surgical or radiological interventions to aid maturation, or formation of an entirely new fistula, thus potentially prolonging the requirement for dialysis through a CVC. Strategies to increase maturation rates and early patency of AVFs may therefore make a substantial difference to patient outcomes. In this respect, widespread patient and clinician consultation, supported by the James Lind Alliance, has identified the question, ‘What can be done to make fistulas or grafts last as long as possible?’ as one of the top 10 research priorities in vascular access provision. One possible approach to counter early fistula loss from non-maturation/thrombosis is to use Doppler ultrasound (US) surveillance in the first few weeks after creation to identify at-risk fistulas and to inform early radiological or surgical intervention, in anticipation that this improves longer-term fistula patency. This has, however, not yet been tested. The SONAR consortium, representing 17 UK centres that provide vascular access surgery, was established to test the hypothesis: Doppler US surveillance of AVFs immediately after creation improves longer-term AVF patency, by directing early and effective surgical or radiological salvage of those AVFs at risk of failing or not maturing. Objectives In considering the above hypothesis, several conditions must be met if US-guided early salvage intervention is to improve outcomes following AVF creation: that US can effectively distinguish those newly formed fistulas that are unlikely to mature that maturity failure occurs commonly enough that clinically meaningful improvements in fistula outcomes by early identification of at-risk fistulas are plausible that salvage interventions performed on those ‘at-risk’ fistulas are effective and improve fistula patency. The SONAR study thus aimed to address the following objectives sequentially, over a 5-year window: Run an observational cohort study in which consenting participants undergo serial US assessment of their AVF in the first 3 months after its formation (phase 1). Model whether features on early US can reliably identify those fistulas that will not mature or will fail early. Assess from the observational cohort study whether a randomised controlled trial (RCT) evaluating early US-guided salvage intervention is feasible. Run a multicentre RCT in which 1-year fistula patency in a treatment group receiving early US surveillance of their developing fistula is compared against standard care: monitoring of fistula maturation by clinical assessment only (phase 2). Progression to the phase 2 study depended upon accomplishing the first three objectives and, in particular, demonstrating that US surveillance could accurately predict fistula non-maturation. This manuscript will thus focus on the phase 1 study set-up and outcomes. Methods A prospective multicentre observational cohort study of adult patients undergoing formation of AVF for haemodialysis was performed to test the hypothesis: Doppler US surveillance early after AVF creation can reliably identify those AVFs that will not mature or will fail early. Criteria for participation were as follows: Adult, aged 16 years or older. The participant had end-stage renal disease and was either already established on haemodialysis or likely to start imminently. The participant was due creation of an arm AVF (either wrist or elbow) including the following types of fistula: radiocephalic, ulnobasilic, brachiocephalic and brachiobasilic (one- or two-stage) fistula, with a minimal acceptable threshold of 2 mm venous diameter at whatever site was chosen. Full informed consent to participate was provided. Consenting participants underwent serial US scanning at weeks 2, 4, 6 and 10 after fistula formation in addition to standard care (such as regular clinical assessment) as per local centre policy. Fistula flow rates, fistula venous diameter and resistance index were recorded, according to a standard study protocol, with clinical teams blinded to the US findings, unless a scan was simultaneously requested on clinical grounds or the scan confirmed thrombosis of the fistula. The primary outcome measure was fistula maturation at 10 weeks. To encompass participants who remained pre-dialysis, along with clinical examination, maturation was assessed at 10 weeks according to accepted surrogate US parameters: wrist fistula: representative venous diameter ≥ 4 mm, with flow > 400 ml/minute elbow fistula: representative venous fistula diameter ≥ 5 mm, with flow > 500 ml/minute. Three distinct outcomes defined fistula non-maturation: a fistula occlusion/thrombosis within the study period (76 days post AVF creation) fistula abandonment within the study period due to failure to mature or due to thrombosis/occlusion failure to achieve (either reported at the week 10 scan or imputed) maturation, according to the preset US parameters. The following secondary outcome measures were also recorded: for those patients established on dialysis, successful use of the fistula for dialysis on three successive occasions clinical suitability for dialysis 10 weeks after fistula creation based on examination alone according to local practice formation of a new fistula (including fashioning of proximal neoanastomosis) or radiological salvage procedure fistula thrombosis secondary fistula patency patient acceptability, based on the proportion of patients that complete their scans. Assuming that early US surveillance predicts fistula non-maturation/failure in 25% of AVFs, a total of 347 fistulas were required to achieve precision of ± 10% for an estimated 72% positive predictive value (PPV) for detecting non-maturation/failure. The total sample size allows for 10% dropout. Mixed multivariable logistic regression (binary-data population-average model with exchangeable correlation structure) of the early US scan data was then used to build separate models for wrist and elbow AVF that contained the minimum number of measurements required to predict AVF non-maturation by 10 weeks. Receiver operating characteristic curves of the developed risk scores were analysed to determine when surgical or radiological intervention on the developing AVF could be considered. The PPV and negative predictive value (NPV; the probability of AVF maturation given that the model predicts maturation) were calculated alongside a 95% confidence interval (CI) for the chosen risk-score cut-off. Additional modelling was then performed on a subset (n = 192) of the original SONAR cohort available for follow-up, to assess whether fistula failure at 6 and 12 months could be identified by analysis of early US characteristics. The primary outcome measure for the longer-term follow-up was primary fistula patency at 6 months, defined as ‘the interval between access creation to the earliest time of fistula thrombosis, abandonment (except abandonment because of steal), intervention on the fistula (to re-establish or maintain patency) or the time of measurement of patency’. Secondary outcome measures included assisted primary patency (the interval from access creation until access thrombosis or the time of measurement of patency, including any interventions to maintain patency) and secondary patency (the interval from access creation to time of measurement of patency or to abandonment of the fistula). Similar binary-data population-average modelling was performed as for predicting 10-week non-maturation, aiming to build parsimonious models that contained the minimum number of variables from one scan time point (at either week 4 or week 6) to effectively predict primary fistula non-patency at 6 months. Results Of 347 consents to participation (median age 65 years; interquartile range 52–74 years; 64.8% male; 43.2% diabetic; 55.0% pre-dialysis), 333 underwent AVF creation during the study window (47.7% wrist, 52.3% elbow fistula). Early failure before the first US scan occurred in 37 (11.1%) AVFs, but by 10 weeks, 219 of 333 (65.8%) created AVFs had reached maturity (67.2% elbow, 60.4% wrist). Of the remainder, by week 10 a further 20 had failed (57 failures in total; 17.1%), 29 (8.7%) remained patent but not mature and the status of 28 (8.4%) was unknown. Excluding those failures occurring within the first 2 weeks (because it would be impractical to organise salvage so quickly) results in a fistula maturation rate of 74.0% at 10 weeks. Serial US scanning revealed that maturation occurred rapidly (the vast majority of AVFs that were mature by 10 weeks had reached maturation by 2 weeks). Comparison of the early scan data in those AVFs that had matured by week 10 against those AVFs that remained immature (see Figure 4) revealed consistently lower fistula flow rates and fistula vein diameter in the latter. For example, the median blood flow at 2 weeks was 1135.5 and 691.0 ml/minute in those elbow and wrist fistulas, respectively, that reached maturation by week 10, whereas week 2 flows of 349.0 and 395.5 ml/minute were recorded in those elbow and wrist fistulas that did not reach maturation at week 10. Modelling to predict AVF non-maturation at week 10 was optimally built on the week 4 scan data but required separate algorithms for wrist and elbow fistulas, with fistula venous diameter and flow rate at week 4 identified as the most significant variables in explaining wrist fistula maturity failure (PPV 60.6%, 95% CI 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow fistula maturity failure (PPV 66.7%, 95% CI 48.9% to 84.4%). Diagnostic tests for model fit and influential observations were run on the optimum models for wrist and elbow AVFs, with both performing well, with area under the curve values of at least 0.90. Conversely, both models could predict fistula maturation much more reliably [NPVs of 95.4% (91.0–99.8) and 95.6% (91.8–99.4) for wrist and elbow, respectively]. Additional modelling was then performed on a subset (n = 192) of the original SONAR cohort available for follow-up, to assess whether fistula failure at 6 and 12 months could be identified by analysis of early US characteristics. Primary, assisted primary and secondary patency AVF rates at 6 months were 76.5%, 80.7% and 83.3%, respectively, and at 12 months were 68.3%, 74.1% and 79.5%, respectively. Broadly similar US characteristics (fistula vein size, flow rate and resistance index) were identified as the most significant variables predicting primary patency failure at 6 months, with similar predictive power as for 10-week AVF maturity failure, but with wide CIs (wrist AVF: PPV 72.7%, 95% CI 46.4% to 99.0%; elbow AVF: 57.1%, 95% CI 20.5% to 93.8%). Moreover, the models performed very poorly at identifying assisted primary and secondary patency failure, likely because a subset of those identified as liable to fail were instead successfully salvaged by radiological or surgical intervention. Conclusions Although early US can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those unlikely to mature or to fail within 6 months. Allied to the better than expected fistula patency rate achieved by the SONAR consortium (that is further improved by successful radiological or survival salvage without recourse to the early US data), we estimate that a prospective randomised trial comparing early US-guided intervention against standard care (observation only) would require at least 1300 fistulas and would only achieve a minimally clinically important difference in the intervention arm if virtually every intervention were successful in maintaining/restoring fistula patency. Limitations The US scan findings were generally not made available to the clinical teams, so as to avoid their influencing participant management. However, scan results were revealed to the responsible clinical team on 98 occasions (10.7% of all scans), either because an early US scan was standard care for that unit (76 occasions) or because unblinding was requested because of clinical concern relating to the fistula’s maturation. It is therefore possible that in a small number of cases, the study US scans triggered salvage procedures that would not otherwise have been performed on clinical grounds alone. This is particularly problematic for the 12-month follow-up study, because the intervention would mark the end of primary patency – the primary outcome measure for the 6-month analysis – and it would therefore provide false support for the statistical modelling. However, in the majority of cases, unblinding did not prompt further intervention (simply instead confirming fistula maturation), and thus is unlikely to have compromised the statistical modelling. Similarly, to include pre-dialysis patients in the study, it was necessary to adopt surrogate US markers to define fistula maturation, and it is perhaps not ideal to be using the same modality to delineate the maturation process as one uses to define maturation, particularly because fistula maturation is principally a functional concern relating to whether the fistula can be used to provide adequate dialysis. Repeat US was not performed at 6 months for the follow-up study, and the analysis of fistula patency, rather than maturation status, provides a better reflection of fistula functionality. This may partly explain the differences in the modelling findings between the 10-week and 6-month studies. Trial registration The SONAR study was approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234) and assigned ISRCTN36033877. The SONAR-12M study was approved by the West Midlands – Edgbaston Research Ethics Committee (REC 20/WM/0331) and assigned ISRCTN17399438. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

PurposeSepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a highly heterogeneous syndrome with distinct phenotypes that impact immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct functional phenotypes of immune cells. In this study, we utilized our Organ-on-Chip assay to categorize sepsis patients into distinct phenotypes using patient data, neutrophil functional analysis, and proteomics.MethodsFollowing informed consent, neutrophils and plasma were isolated from sepsis patients in the Temple University Hospital ICU (n=45) and healthy control donors (n=7). Human lung microvascular endothelial cells (HLMVEC) were cultured in the Organ-on-Chip and treated with buffer or cytomix ((TNF/IL-1β/IFNγ). Neutrophil adhesion and migration across HLMVEC in the Organ-on-Chip were used to categorize functional neutrophil phenotypes. Quantitative label-free global proteomics was performed on neutrophils to identify differentially expressed proteins. Plasma levels of sepsis biomarkers and neutrophil extracellular traps (NETs) were determined by ELISA.ResultsWe identified three functional phenotypes in critically ill ICU sepsis patients based on ex vivo neutrophil adhesion and migration patterns. The phenotypes were classified as: Hyperimmune characterized by enhanced neutrophil adhesion and migration, Hypoimmune that was unresponsive to stimulation, and Hybrid with increased adhesion but blunted migration. These functional phenotypes were associated with distinct proteomic signatures and differentiated sepsis patients by important clinical parameters related to disease severity. The Hyperimmune group demonstrated higher oxygen requirements, increased mechanical ventilation, and longer ICU length of stay compared to the Hypoimmune and Hybrid groups. Patients with the Hyperimmune neutrophil phenotype had significantly increased circulating neutrophils and elevated plasma levels NETs.ConclusionNeutrophils and NETs play a critical role in vascular barrier dysfunction in sepsis and elevated NETs may be a key biomarker identifying the Hyperimmune group. Our results establish significant associations between specific neutrophil functional phenotypes and disease severity and identify important functional parameters in sepsis pathophysiology that may provide a new approach to classify sepsis patients for specific therapeutic interventions.

Introduction The World Health Organization recommends banning all forms of e-cigarette advertising, promotion, and sponsorship. The aims of the present study were to: 1) examine young people’s exposure to e-cigarette advertising across a wide range of media in four diverse countries; and 2) identify any association between the number of different types of media exposures and e-cigarette use. Methods A cross-sectional online survey was administered to approximately 1000 people aged 15–30 years in Australia, China, India, and the United Kingdom (n=4107). The survey assessed demographic characteristics, e-cigarette and tobacco use, numbers of friends and family members who vape, and exposure to multiple forms of e-cigarette advertising (e.g. television, radio, print, and various types of social media). Descriptive analyses were conducted on those who had heard of e-cigarettes (n=3095, significance threshold p

Radiotherapy (RT) treatment is an important strategy for the management of non-small cell lung cancer (NSCLC). Local recurrence amongst patients with late-stage NSCLC remains a challenge. The loss of PTEN has been associated with radio-resistance. This study aimed to examine the efficacy of RT combined with ataxia telangiectasia-mutated Rad3-related (ATR) inhibition using Ceralasertib in phosphatase and tensin homolog (PTEN)-depleted NSCLC cells and to assess early inflammatory responses indicative of radiation pneumonitis (RP) after combined-modality treatment. Small hairpin RNA (shRNA) transfections were used to generate H460 and A549 PTEN-depleted models. Ceralasertib was evaluated as a single agent and in combination with RT in vitro and in vivo. Histological staining was used to assess immune cell infiltration in pneumonitis-prone C3H/NeJ mice. Here, we report that the inhibition of ATR in combination with RT caused a significant reduction in PTEN-depleted NSCLC cells, with delayed DNA repair and reduced cell viability, as shown by an increase in cells in Sub G1. Combination treatment in vivo significantly inhibited H460 PTEN-depleted tumour growth in comparison to H460 non-targeting PTEN-expressing (NT) cell-line-derived xenografts (CDXs). Additionally, there was no significant increase in infiltrating macrophages or neutrophils except at 4 weeks, whereby combination treatment significantly increased macrophage levels relative to RT alone. Overall, our study demonstrates that ceralasertib and RT combined preferentially sensitises PTEN-depleted NSCLC models in vitro and in vivo, with no impact on early inflammatory response indicative of RP. These findings provide a rationale for evaluating ATR inhibition in combination with RT in NSCLC patients with PTEN mutations.

Abstract Knowledge mobilisation can be achieved through various routes. This can include immersive, in-person time spent in a different workplace with people from other disciplines or sub-sectors. By doing so participants mobilise and exchange knowledge through observing the dynamics of a different workplace; by learning directly from others with different expertise and/or through sharing their own expertise. We have called this form of knowledge exchange ‘Workplace-based Knowledge Exchange Programmes’ (WKEPs) and have focused on their role in the health and care sector because of the importance of knowledge mobilisation in this field yet their relatively low profile in the literature. This study explores the main characteristics of WKEPs among academics, providers, and policymakers in the health and care sector in the United Kingdom (UK) through a scoping review and mapping exercise. We systematically identified 147 academic articles (between 2010 and 2022) and 74 websites which offered WKEPs as part of, or all of, their knowledge mobilisation activities (between 2020 and 2022). Characteristics were grouped into structures, processes, and outcomes. WKEPs lasted between one day and five years and were mostly uni-directional. Exchange ambitions varied, aiming to benefit both the participants and their working environments. They commonly aimed to build networks or collaborations, improve understanding of another field and bring back knowledge to their employer, as well as improve leadership and management skills. Almost all programmes were for healthcare providers and academics, rather than social care providers or policymakers. In-person WKEP activities could be categorised into four domains: ‘job shadowing’, ‘work placements’, ‘project-based collaborations’, and ‘secondments’. The aims of many of the WKEPs were not clearly described and formal evaluations were rare. We used the findings of this study to develop a framework to describe WKEP activities. We suggest the use of common language for these activities to aid participation and research, as well as recommending principles for the comprehensive advertising of WKEPs and reporting of experiences after participation in WKEPs. We recommend the establishment of an online repository to improve access to WKEPs. These resources are necessary to strengthen understanding and the effectiveness of WKEPs as a mechanism for knowledge mobilisation.

Purpose – Higher levels of participation in school are linked to greater academic performance, better health and well-being and positive long-term outcomes for young people. Evidence shows that for students with emotional and behavioural difficulties (EBD), participation in school-based occupations is often restricted in comparison to their peers. Given the recent advancements towards introducing a new model of school-based occupational therapy in Ireland, this paper aims to discuss how occupational therapy can support students with EBD to increase their participation within the post-primary school context. The opinions in this paper are derived from the authors’ experience in the development of this practice in the Republic of Ireland. Design/methodology/approach – The authors reviewed current literature and reflected on current practice to describe the unique role of occupational therapy in supporting students with EBD in the school environment. Findings – Occupational therapists have potential to play a key role in school-based support for students with EBD. The authors describe how occupational therapists can promote whole school understanding of EBD and enable skill development, self-regulation, participation and school belonging, among youths with EBD. There is a significant lack of literature guiding practice in this area. Further research is required to explore professional issues and identify best practice. Originality/value – This paper aims to provoke consideration of how school-based occupational therapists can play a crucial role in supporting students with EBD who are otherwise at risk of occupational injustice.

This study describes an effective protocol for naturalistic archaeological weapons experiments that improves cross-validation with controlled experiments and allows testing of multiple hypotheses. Stone-tipped atlatl darts and arrows were launched by skilled users against fresh carcasses, with high-speed cameras and radar guns capturing details of ballistic performance, impacts to bone and stone armatures, and other variables. The results pertaining to terminal ballistics in soft tissues are presented, with implications for what made ancient hunting projectiles effective and can be observed archaeologically. Fine-grained knappable stones seem to produce sharper armatures that can dramatically improve penetration, and presumably, lethality. Two commonly used metrics by archaeologists for estimating armature efficacy, tip cross-sectional area (TCSA), and perimeter (TCSP), are not among the significant variables for capturing penetration depth in soft tissues. However, armatures with larger TCSAs tend to be fitted to larger shafts that carry more energy and penetrate more deeply, providing one method for predicting wounding potential. The variability within weapon systems means that isolating efficacy to individual variables, such as tip cross-sectional size of stone armatures, can lead to erroneous interpretations.

Abstract The bold vision of AI-driven pervasive physiological monitoring, through the proliferation of off-the-shelf wearables that began a decade ago, has created immense opportunities to extract actionable information for precision medicine. These AI algorithms model input-output relationships of a system that, in many cases, exhibits complex nature and personalization requirements. A particular example is cuffless blood pressure estimation using wearable bioimpedance. However, these algorithms need training over significant amount of ground truth data. In the context of biomedical applications, collecting ground truth data, particularly at the personalized level is challenging, burdensome, and in some cases infeasible. Our objective is to establish physics-informed neural network (PINN) models for physiological time series data that would use minimal ground truth information to extract complex cardiovascular information. We achieve this by building Taylor’s approximation for gradually changing known cardiovascular relationships between input and output (e.g., sensor measurements to blood pressure) and incorporating this approximation into our proposed neural network training. The effectiveness of the framework is demonstrated through a case study: continuous cuffless BP estimation from time series bioimpedance data. We show that by using PINNs over the state-of-the-art time series models tested on the same datasets, we retain high correlations (systolic: 0.90, diastolic: 0.89) and low error (systolic: 1.3 ± 7.6 mmHg, diastolic: 0.6 ± 6.4 mmHg) while reducing the amount of ground truth training data on average by a factor of 15. This could be helpful in developing future AI algorithms to help interpret pervasive physiologic data using minimal amount of training data.

When they work, controlled experiments can efficiently and clearly reveal essential characteristics of the functions and performance of ancient hunting and fighting weapons. However, homogenous target media must be carefully validated to ensure that controlled tests capture the same variables that made weapons effective in their original application. Although homogenous flesh simulants have proven effective for studying firearms, the same simulants cannot be assumed to be effective when testing low-velocity cutting/piercing projectiles, which have significantly different performance characteristics than bullets. We build on past research showing that two flesh simulants that are commonly used by archaeologists, ballistics gelatin and pottery clay, fail to capture how atlatl darts and arrows perform when penetrating biological tissues. In accord with forensic research of knife-thrust attacks, natural and polymeric skin simulants may prove effective in future experiments, but this requires further research.

IntroductionThe accumulation of neurofibrillary tau tangles, a neuropathological hallmark of Alzheimer’s disease (AD), occurs in medial temporal lobe (MTL) regions early in the disease process, with some of the earliest deposits localized to subregions of the entorhinal cortex. Although functional specialization of entorhinal cortex subregions has been reported, few studies have considered functional associations with localized tau accumulation.MethodsIn this study, stepwise linear regressions were used to examine the contributions of regional tau burden in specific MTL subregions, as measured by 18F-MK6240 PET, to individual variability in cognition. Dependent measures of interest included the Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini Mental State Examination (MMSE), and composite scores of delayed episodic memory and language. Other model variables included age, sex, education, APOE4 status, and global amyloid burden, indexed by 11C-PiB.ResultsTau burden in right Brodmann area 35 (BA35), left and right Brodmann area 36 (BA36), and age each uniquely contributed to the proportion of explained variance in CDR-SB scores, while right BA36 and age were also significant predictors of MMSE scores, and right BA36 was significantly associated with delayed episodic memory performance. Tau burden in both left and right BA36, along with education, uniquely contributed to the proportion of explained variance in language composite scores. Importantly, the addition of more inclusive ROIs, encompassing less granular segmentation of the entorhinal cortex, did not significantly contribute to explained variance in cognition across any of the models.DiscussionThese findings suggest that the ability to quantify tau burden in more refined MTL subregions may better account for individual differences in cognition, which may improve the identification of non-demented older adults who are on a trajectory of decline due to AD.

Children's mobility and the opportunity to get around the city on their own has decreased and is today limited to a large extent by unsafe traffic situations. Due to their limited independent mobility, children are excluded from the urban space and its facilities. Independent mobility can be related to several dimensions of children's social, physical, mental and cognitive wellbeing. The purpose of this study is to investigate if and in what way autonomous buses can contribute to children's independent mobility and, using children's experiences, provide insights into this before the introduction of autonomous buses in cities and public transport systems. To do so, the two research questions ''How can autonomous buses in the transport system contribute to children's independent mobility?'' and ''What prerequisites are necessary for autonomous buses to contribute to children's independent mobility?'' are answered. The survey is based on a case of introduction of autonomous buses in urban environments. Three focus groups with students in a primary school were conducted with the aim of gaining the participants' experiences. The results indicate that the introduction of autonomous buses in an urban area can contribute to children's independent mobility in several ways and that the buses have certain characteristics that enable them to be adapted to children's conditions. The low speed of the shuttles, which is often seen as an obstacle when it comes to time efficiency, has a positive effect on perceived safety in this case. The mobility solution is also child-friendly in that it is accessible in terms of trip planning and payment. However, it is important to consider the risk that the bus might replace active transportation modes, like cycling. To avoid this, autonomous shuttles should be integrated in a way that complement, not compete with, active travel.

Abstract When compared to their temperate coastal counterparts, sediments deposited and preserved along arid aeolian to shallow‐marine margins remain relatively poorly understood, particularly at the scale of lithofacies units and architectural elements. These systems often record evidence for relative sea‐level change within sedimentary basins. This work focusses on the Entrada–Curtis–Summerville formations that crop out in central eastern Utah, USA, and provides a detailed analysis of the aeolian Moab Member of the Curtis Formation (informally known as the Moab Tongue) that was impacted by cycles of marine transgressions and regression in the late Jurassic. This study utilises photogrammetry, sedimentary logging and sequence‐stratigraphical analysis techniques. Results indicate that four short‐lived transgressive‐regressive cycles are preserved within the Moab Member, followed by a broad regressive event recorded at the transition between the Curtis and Summerville formations. These cycles relate to changes in the relative sea level of the Sundance Sea and the deflation and expansion of the neighbouring aeolian dune field. During periods of normal regression, marine sediments displayed evidence of tidal and wave action, whereas the continental domain was characterised by growth of the aeolian system. However, when regression occurred within optimal physiographic conditions such as a restricted, semi‐enclosed basin, and at sufficient magnitude to outpace erg expansion, this acted to shut‐down bedform development and preservation. A rapid restriction of aeolian sediment availability and the inability of the dune field to recover resulted in the formation of deflationary sandsheets, arid coastal plain strata and contemporaneous shallow‐marine deposits that are starved of wind‐sourced sediments. This study highlights how a rapidly developing high‐magnitude regression can lead to the overall retraction of the erg. Deciphering the evolution and sequence stratigraphical relationships of arid aeolian to shallow marine margins is important in both understanding environmental interactions and improving the characterisation of reservoir rocks deposited in these settings.

Abstract Background Both Alzheimer’s disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition. Methods Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by (i) apolipoprotein-E (APOE) genetic status (APOE-ε2 and APOE-ε4 vs. APOE-ε3; N = 1819) and (ii) AD polygenic risk scores (AD-PRS; N = 1175). A CR index was calculated by combining years of education and literacy scores. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, episodic memory, and executive function. Results In mixed-effects models, higher CR index scores were associated with better baseline cognitive performance for all cognitive outcomes. APOE-ε4 genotype and AD-PRS that included the APOE region (AD-PRSAPOE) were associated with declines in all cognitive domains, whereas AD-PRS that excluded the APOE region (AD-PRSw/oAPOE) was associated with declines in executive function and global cognition, but not memory. There were significant 3-way CR index score × APOE-ε4 × time interactions for the global (p = 0.04, effect size = 0.16) and memory scores (p = 0.01, effect size = 0.22), indicating the negative effect of APOE-ε4 genotype on global and episodic memory score change was attenuated among individuals with higher CR index scores. In contrast, levels of CR did not attenuate APOE-ε4-related declines in executive function or declines associated with higher AD-PRS. APOE-ε2 genotype was unrelated to cognition. Conclusions These results suggest that APOE-ε4 and non-APOE-ε4 AD polygenic risk are independently associated with global cognitive and executive function declines among individuals with normal cognition at baseline, but only APOE-ε4 is associated with declines in episodic memory. Importantly, higher levels of CR may mitigate APOE-ε4-related declines in some cognitive domains. Future research is needed to address study limitations, including generalizability due to cohort demographic characteristics.

Abstract Smart rings provide unique opportunities for continuous physiological measurement. They are easy to wear, provide little burden in comparison to other smart wearables, are suitable for nocturnal settings, and can be sized to provide ideal contact between the sensors and the skin at all times. Continuous measuring of blood pressure (BP) provides essential diagnostic and prognostic value for cardiovascular health management. However, conventional ambulatory BP measurement devices operate using an inflating cuff that is bulky, intrusive, and impractical for frequent or continuous measurements. We introduce ring-shaped bioimpedance sensors leveraging the deep tissue sensing ability of bioimpedance while introducing no sensitivity to skin tones, unlike optical modalities. We integrate unique human finger finite element model with exhaustive experimental data from participants and derive optimum design parameters for electrode placement and sizes that yields highest sensitivity to arterial volumetric changes, with no discrimination against varying skin tones. BP is constructed using machine learning algorithms. The ring sensors are used to estimate arterial BP showing peak correlations of 0.81, and low error (systolic BP: 0.11 ± 5.27 mmHg, diastolic BP: 0.11 ± 3.87 mmHg) for >2000 data points and wide BP ranges (systolic: 89–213 mmHg and diastolic: 42–122 mmHg), highlighting the significant potential use of bioimpedance ring for accurate and continuous estimation of BP.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

BackgroundOur previous study showed that 3 plant extracts enhanced the immune responses and growth efficiency of weaned pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV), which is one of the most economically important disease in swine industry. However, each plant extract differently effected on growth efficiency and immune responses. Therefore, the objective of this study was conducted to characterize the effects and investigate the potential underlying mechanisms of 3 plant extracts on gene expression of alveolar macrophages in weaned pigs experimentally infected with PRRSV.ResultsPRRSV infection altered (P

IntroductionSetting sodium targets for pre-packaged food has been a priority strategy for reducing population sodium intake. This study aims to explore the attitudes and considerations of researchers and key stakeholders toward implementing such policy in China.MethodsAn exploratory study comprising a survey and a focus group discussion was conducted among 27 purposively selected participants including 12 researchers, 5 consumers, 4 administrators, 3 industry association representatives and 3 food producers. The survey/discussion covered the key questions considered when developing/promoting sodium targets. Free-text responses were manually classified and summarized using thematic analysis.ResultsTwo-thirds of the participants supported target-setting policy. Researchers and administrators were most supportive, and food producers and associations were least supportive. Adapted WHO food categorization framework was well accepted to underpin target-setting to ensure international comparability and applicability for Chinese products. Maximum values were the most agreed target type. The WHO benchmarks were thought to be too ambitious to be feasible given the current food supply in China but can be regarded as long-term goals. Initially, a reduction of sodium content by 20% was mostly accepted to guide the development of maximum targets. Other recommendations included implementing a comprehensive strategy, strengthening research, engaging social resources, establishing a systematic monitoring/incentive system, maintaining a fair competitive environment, and developing a supportive information system. Target-setting policy was acceptable by most stakeholders and should be implemented alongside strategies to reduce discretionary salt use.DiscussionOur findings provide detailed guidance for the Chinese government when developing a target-setting strategy. The methods and results of this study also provide meaningful references for other countries to set sodium targets for pre-packaged foods and implement other salt reduction strategies simultaneously.