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Objective: This scoping review aimed to map how occupational therapists evaluate the outcomes of services they provide within primary care. This evidence was considered in relation to how identified outcome evaluation methods align to principles of value-based health care., Introduction: Primary care services are experiencing unprecedented demands. Occupational therapy is an allied health profession that supports health and care provision in primary care, using a timely and proactive approach. There has been a notable increase in occupational therapy roles across primary care services in the past decade; however, the mechanisms for evaluating outcomes and the wider impact of these services remain under-researched. The aim of value-based health care, a global transformative approach, is to establish better health outcomes for individuals and communities through addressing value in system-wide care. However, it is not yet clear how evaluation methods used within occupational therapy align to the principles of a value-based agenda., Inclusion Criteria: Peer-reviewed journal articles and gray literature written in English were included to identify outcome evaluation methods used by occupational therapists to evaluate the effectiveness and impact of occupational therapy services provided in a primary care setting. Outcome evaluation methods used exclusively for the purpose of conducting research and not for capturing data within an occupational therapy primary care setting as part of routine clinical practice were excluded., Methods: This review followed JBI methodology for scoping reviews. The literature search was undertaken during June and July 2022. The following databases were searched from their earliest dates of availability: Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL via EBSCOhost, Scopus, AMED, and Web of Science. Two reviewers extracted data, supported by use of an extraction form developed by the reviewers. Findings were mapped using a framework developed based on key principles of value-based health care., Results: From 2394 articles, 16 eligible studies were included in the review. Of these, 9 were quantitative and 7 were of mixed methods design. Studies were from the UK, USA, Sweden, Spain, and Canada. The occupational therapy services represented were mainly heterogeneous. Four services were part of multidisciplinary programs of care and 12 services were specific to occupational therapy. Identified outcome evaluation methods broadly aligned to principles of value-based health care, with most alignment noted for measures demonstrating the aim of establishing better health. A wide range of evaluation methods were described to address both individual-level and service-level outcomes, with the use of patient-reported outcome measures identified in 13 studies. To capture patient experience, most studies reported a variety of methods. The aim of reducing the per capita cost of health care was least represented in the literature., Conclusion: This scoping review highlights a multifaceted but inconsistent approach to measuring the outcomes of occupational therapy provided in primary care. This has implications for establishing effectiveness and capturing data at scale to assist with wider planning of care and to enable the profession to demonstrate its contribution to value-based health care., Review Registration: Open Science Framework https://osf.io/hnaq4/., Competing Interests: DE is an associate editor of JBI Evidence Synthesis but was not involved in the editorial processing of this manuscript. The other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on Behalf of JBI.)

Objectives: To explore the priorities and directions of athlete upper and lower limb pain assessment by facilitating shared understandings of athletes and sport physiotherapists., Design: Qualitative research using a hermeneutic phenomenological approach., Methods: We carried out focus groups comprising a deliberate criterion sample using a constructivist perspective. At the end of each focus group, we used the nominal group technique method to generate a list of consensus-based priorities for future pain assessment. Our paper follows the consolidated criteria for reporting qualitative research (COREQ) guidelines., Results: We completed five focus groups, comprising twelve athletes (female, n = 5, male, n = 7) and four sport physiotherapists (male, n = 4). Two final themes (and six subthemes) were developed; I Enhanced Communication and Pain Descriptions (describing and representing pain, better communication, the role of technology, providing direction and setting the pace), and II Integrating Sport Specific and Multidimensional Assessments (broadening the pain assessment toolkit, the role of technology). We developed a set of thirteen practical priorities for pain assessment that span the subjective, objective, and general aspects of the athlete pain assessment., Conclusions: We have presented stakeholder-generated perspectives, direction and priorities for athlete pain assessment. Athletes and physiotherapists must continue to work together to achieve a comprehensive sport-specific multidimensional pain assessment experience alongside their wider support networks to ensure optimal representation and communication. We have highlighted some available pain assessment tools and strategies and outlined how novel tools may address certain gaps. Researchers, clinicians, and athletes can consider the practical guidance we have provided to address these priorities., Competing Interests: Declaration of interest statement The authors have no competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Active travel offers many societal benefits, including improving people's mental and physical health and minimising our impacts on the environment. Increasing active travel is particularly important amongst children and young people (CYP), who are building habits which they will carry into adulthood. Studies on active travel amongst CYP are limited, however, with most research focusing on adult participants or on adult perceptions of children. This study sought to understand CYP's interactions with the built and natural environment-and therefore their access to active travel-through the Capability, Opportunity, Motivation, Behaviour (COM-B) model. With a stakeholder group representing local government, youth organisations and active travel organisations, we co-created two bilingual questionnaires-one for young people aged 12-16 years living in Wales and the other for parents of young people aged 12-16 years living in Wales. Both questionnaires collected information on behaviour and perceived capability, opportunity and motivation of CYP to engage with their natural and built environments. The questionnaires included a discrete choice experiment (DCE), which proposed a series of binary choice questions indicating preferences based on landscape, journey time and type of travel. A total of 124 questionnaires (38 young people and 86 parents) were returned for analysis. These data indicate that CYP's time spent outdoors is not dependent upon geography (rural/urban/suburban), season, or school holidays. There was a significant difference in capability, opportunity and motivation between parents and CYP, with parents over-estimating the psychological capability of CYP to engage outdoors. The preference data indicate that active travel is the favoured mode of transport, with both CYP and parents stating that they would increase travel time in order to travel actively. While this response is not consistent with respondent's day-to-day travel choices, it suggests that the limitations to active travel may be psychological capability and automatic motivation, rather than a lack of opportunity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Holmes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene. This combinatorial approach achieved correction of ornithine transcarbamylase deficiency in the neonatal Spf ash mouse model following a single delivery to dividing hepatocytes in the newborn liver. Correction remained stable into adulthood, while a conventional rAAV approach resulted in a return to the disease state. In non-human primates, integration by transposition, mediated by this technology, improved gene expression 10-fold over conventional rAAV-mediated gene transfer while requiring 5-fold less vector. Additionally, integration site analysis confirmed a random profile while specifically targeting TA dinucleotides across the genome. Together, these findings demonstrate that transposable elements can improve rAAV-delivered therapies by lowering the vector dose requirement and associated toxicity while expanding target cell types., Competing Interests: Declaration of interests All authors except for S.C.C., E.B.v.D., and I.E.A. are or were employees of Tessera Therapeutics and currently receive or previously received salary along with stock options as compensation for their employment. I.E.A. is a consultant of Tessera Therapeutics, and this work was performed under a Tessera Therapeutics-sponsored research agreement., (Copyright © 2024 The American Society of Gene and Cell Therapy. All rights reserved.)

Our objective was to explore athlete's and sports physiotherapists' experiences of sports-related pain in the upper and lower limb. Using a constructivist and pragmatic perspective, we carried out focus groups comprising a deliberate criterion sample of athletes and sports physiotherapists. We used a topic guide that moved from open exploratory questions to questions focusing on the phenomena of sports-related pain in athletes. We coded, developed candidate themes and refined finalised themes using reflexive thematic analysis. A member of our research team acted as a critical friend adding additional perspectives. We followed the Consolidated Criteria for Reporting Qualitative Research (COREQ). We completed five focus groups comprising 12 athletes (n=5 female, n=7 male) and four sports physiotherapists (n=4 male) including one initial pilot (two athletes). We developed four final themes (1-4) and nine subthemes (1.1-4.3): (1) Athlete Pain Lens (1.1-pain is part of being an athlete and 1.2-pain shapes the life of an athlete), (2) Exploring And Navigating Pain (2.1-the sports-related pain spectrum and 2.2-making sense of pain), (3) The Emotional Toll of Pain (3.1-challenging emotions and 3.2-the impact of time) and (4) Coping, Community and Communication (4.1-coping with pain, 4.2-influence of community and support network and 4.3-communication, the broken key). We highlighted the distinct and challenging phenomenon of sports-related pain experienced by athletes and physiotherapists. Through effective communication, members of the athlete's community may recognise, and adjust to these challenges., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore experiences of pain in the context of early medical abortion (EMA) in the UK and to guide best practice around anticipatory guidance on pain., Methods: From late 2020 to early 2021, we recruited individuals from across the UK who had undergone abortion during the COVID-19 pandemic to participate in in-depth, semi-structured telephone interviews. A storytelling approach was used and data were analysed thematically using NVivo 12 software., Results: Focused coding and thematic analysis addressed accounts of pain, which were prominent in many interviews. We constructed the following subthemes: expected pain is manageable for some; the problem with unexpected pain; pain (co)produces fear; and problematising 'period-like pain'. The key issue which our analysis draws out is that while EMA pain experience might vary, for some it may be much worse than anticipated. Moreover, the common trope of likening it to 'period pain' can be misleading and a source of additional uncertainty at a potentially already challenging time., Conclusions: For some individuals, pain experienced in EMA will be severe and/or worse than expected. Insufficient preparation for pain can result in extremely negative experiences of EMA. Alongside development of improved analgesia, improvements should be made to anticipatory guidance on pain, particularly for those self-manging EMA at home. Framings of 'period-like pain' do not clarify expectations and should be avoided., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS). We present a novel approach to estimate the effect of exposure to health interventions on the severity of low back pain by country and over time., Methods: We extracted treatment effects for ten low back pain interventions from the Cochrane Database, combining these with coverage data from the MEPS to estimate the hypothetical severity in the absence of treatment in the USA. Severity across countries was then graded using the Health Access and Quality Index, allowing estimates of averted and avoidable burden under various treatment scenarios., Findings: We included 210 trials from 36 Cochrane systematic reviews in the network analysis. The pooled effect sizes (measured as a standardised mean difference) for the most effective intervention classes were -0·460 (95% uncertainty interval -0·606 to -0·309) for a combination of psychological and physical interventions and -0·366 (-0·525 to -0·207) for surgery. Globally, access to treatment averted an estimated 17·6% (14·8 to 23·8) of the low back pain burden in 2020. If all countries had provided access to treatment at a level estimated for Iceland with the highest Health Access and Quality Index score, an extra 9·1% (6·4 to 11·2) of the burden of low back pain could be avoided. Even with full coverage of optimal treatment, a large proportion (65·9% [56·9 to 70·4]) of the low back pain burden is unavoidable., Interpretation: This methodology fills an important shortcoming in the GBD by accounting for low back pain severity variations over time and between countries. Assumptions of unequal treatment access increased YLD estimates in resource-poor settings, with a modest decrease in countries with higher Health Access and Quality Index scores. Nonetheless, the large proportion of unavoidable burden indicates poor intervention efficacy. This method, applicable to other GBD conditions, provides policy makers with insights into health gains from improved treatment and underscores the importance of investing in research for new interventions., Funding: Bill and Melinda Gates Foundation and Queensland Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Prostate cancer (PCa) neuroendocrine tumor (NET)-like cells with low or absent androgen receptor (AR) signaling cause hormone therapy resistance and poor prognosis. Small cell lung carcinoma (SCLC), a high-grade NET, presents with metastasis early and has poor survival. ONC201/TIC10 is a first-in-class cancer therapeutic with clinical activity in diffuse gliomas and neuroendocrine tumors. We hypothesized that markers of neuroendocrine differentiation, activation of the integrated stress response (ISR) and the TRAIL pathway, as well as the expression of ClpP, contribute to neuroendocrine tumor cell death and sensitivity to ONC201. We show that PCa and SCLC cell lines (N=6) are sensitive to ONC201, regardless of the extent of neuroendocrine differentiation. Endogenous levels of some NET markers (CgA, FoxO1, ENO2, PGP9.5, SOX2) are present in a spectrum in PCa and SCLC cell lines. Overexpression of neural transcription factor BRN2 in DU145 PCa cells does not increase expression of NET differentiation markers FoxO1, ENO2, PGP9.5, and CgA at 48 hours. However, the transient BRN2 overexpression showed slight decreases in some NET markers on the spectrum while maintaining sensitivity of PCa cells to ONC201 before any phenotypic change related to NET differentiation. Our results show that ONC201 has preclinical activity against PCa including those without NET markers or in PCa cells with transient overexpression of neural transcription factor BRN2. Our results have relevance to activity of ONC201 in PCa where most castrate-resistant androgen-independent cancers are not therapy resistant due to NET differentiation. Importantly, NET differentiation does not promote resistance to ONC201 supporting further clinical investigations across the spectrum of PCa., Competing Interests: Declaration of conflict of interest W.S.E-D. is a co-founder of Oncoceutics, Inc., a subsidiary of Chimerix. Dr. El-Deiry has disclosed his relationship with Oncoceutics/Chimerix and potential conflict of interest to his academic institution/employer and is fully compliant with NIH and institutional policy that is managing this potential conflict of interest.

Prostate cancer (PCa) is the leading cause death from cancer in men worldwide. Approximately 30% of castrate-resistant PCa's become refractory to therapy due to neuroendocrine differentiation (NED) that is present in <1% of androgen-sensitive tumors. First-in-class imipridone ONC201/TIC10 has shown clinical activity against midline gliomas, neuroendocrine tumors and PCa. We explored the question of whether NED promotes sensitivity to imipridones ONC201 and ONC206 by inducible overexpression of SOX2 and BRN2, well-known neuroendocrine drivers, in human PCa cell lines DU145 or LNCaP. Slight protection from ONC201 or ONC206 with SOX2 and BRN2 overexpression was observed in the inducible LNCaP cells but not in the DU145 cells. At 2 months, there was an apparent increase in CLpP expression in LNCaP SOX2-overexpressing cells but this did not confer enhanced sensitivity to ONC201. DU145 SOX2-overexpressing cells had a significantly reduced ONC201 sensitivity than DU145 control cells. The results support the idea that treatment of castrate-resistant prostate cancer by imipridones may not be significantly impacted by neuroendocrine differentiation as a therapy-resistance mechanism. The results support further testing of imipridones across subtypes of androgen-sensitive and castrate-resistant prostate cancer., Competing Interests: Declaration of conflict of interest W.S.E-D. is a co-founder of Oncoceutics, Inc., a subsidiary of Chimerix. Dr. El-Deiry has disclosed his relationship with Oncoceutics/Chimerix and potential conflict of interest to his academic institution/employer and is fully compliant with NIH and institutional policy that is managing this potential conflict of interest.

Skin conditions carry a significant physical, psychological, and social burden. People with skin conditions often engage in health-threatening behaviours that can worsen symptoms and increase cardiovascular disease risk. However, access to dedicated psychological and behaviour-change support is limited. The impact, management, and existing psychological support available to adults living with skin conditions was qualitatively explored to inform the development of a psychologically supportive digital intervention. Qualitative research involving a hybrid inductive- deductive approach was performed. Data collection and analysis were theoretically informed by the Common-Sense Model of Self-Regulation. Eight synchronous online group interviews with 43 English-speaking adults (≥ 18 years) with a range of skin conditions were conducted. Data were analysed using Reflexive Thematic Analysis. Three superordinate themes are outlined: (i) visibility underpinning life course impairment, (ii) seeking control amid uncertainty, and (iii) existing support for people with skin conditions. Skin conditions carry a substantial psychological burden, yet dermatology service provision is sub-optimal and patients often resort to seeking support from unreliable sources. Psychological support can have benefits, but barriers exist. This study reinforces the need for high-quality psychological support, and that patients wanted digital means to support effective self- management.

Competing Interests: Conflicts of interest RMH has received financial support for research from Beiersdorf AG. Over the last 3 years CB has received funds for research, honoraria or consultancy from the following pharmaceutical companies: Abbvie, Almirall, Amgen (was Celgene), Beiersdorf AG, Janssen, Novartis, Pfizer and UCB.

Introduction: Social support can mitigate the impact of stress and stigma before or after an abortion. However, stigma anticipation can limit access to in-person support. Informal online spaces can offer opportunities to address unmet support needs including supplementing in-person support lacking within stigmatised contexts. While earlier studies have explored content of posts comprising personal accounts of abortion, little is known about the nuances of how and to what end online spaces are navigated., Methods: Semi-structured interviews were conducted remotely (online or by telephone) with 23 women living in Scotland (aged 20-54 years) recruited through social media and online advertisements. Reflexive thematic analysis was supported by NVivo12 software., Results: Key themes: obtaining support that was unavailable from in-person networks; preparation for abortion; reducing feelings of isolation. The majority of participants independently searched online for accounts of abortion, with only three receiving any signposting to specific resources. Without guidance, finding relevant, supportive content was not straightforward. The search process was additionally complicated by the prevalence of abortion stigma online, which generated an additional burden at a potentially challenging time. Those who received direction towards particular resources reported primarily positive online experiences., Conclusions: While online content could address perceived in-person support gaps, the process of finding supportive content without guidance can be complex. Online searching may also expose women to stigmatising material and interactions. Signposting by abortion services towards well-moderated and trustworthy online resources could be constructive in limiting exposure to stigma and misinformation, while allowing those seeking it to access better support., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Medication abortion has been established globally as safe and effective. This modality has increased accessibility and the opportunity to centre individual autonomy at the heart of abortion care, by facilitating self-managed abortion. Previous research has shown how self-managed abortion is beneficial in myriad settings ranging from problematic to (relatively) unproblematic contexts of access. In this paper we explore the relationship between self-management and sources of support (including health professionals, family, and friends); as well as considering issues of reproductive control and autonomy. Drawing on qualitative, experience-centred interviews, we utilise the concept of social connectedness to examine how supported self-managed abortion was experienced in the United Kingdom during the COVID-19 pandemic. Overall, self-management was welcomed, with participants speaking positively about managing their own abortion at home. However, a sense of connectedness was crucial in helping participants deal with difficult experiences; and functioned to support individual autonomy in self-care. This paper is the first to examine factors of connection, support, and isolation, as experienced by those undergoing self-managed abortion in the UK in detail. Our research suggests a continued need to advocate for high quality support for self-managed abortion, as well as for choice of abortion method, to support patient-centered care.

Healthcare is undergoing a fundamental shift in which digital health tools are becoming ubiquitous, with the promise of improved outcomes, reduced costs, and greater efficiency. Healthcare professionals, patients, and the wider public are faced with a paradox of choice regarding technologies across multiple domains. Research is continuing to look for methods and tools to further revolutionise all aspects of health from prediction, diagnosis, treatment, and monitoring. However, despite its promise, the reality of implementing digital health tools in practice, and the scalability of innovations, remains stunted. Digital health is approaching a crossroads where we need to shift our focus away from simply looking at developing new innovations to seriously considering how we overcome the barriers that currently limit its impact. This paper summarises over 10 years of digital health experiences from a group of researchers with backgrounds in physical therapy-in order to highlight and discuss some of these key lessons-in the areas of validity, patient and public involvement, privacy, reimbursement, and interoperability. Practical learnings from this collective experience across patient cohorts are leveraged to propose a list of recommendations to enable researchers to bridge the gap between the development and implementation of digital health tools.

Background: Children with Developmental Coordination Disorder (DCD) can experience sensory differences. There has been limited exploration of these differences and their impact on children with DCD., Aims: i) To explore the presence and impact of sensory differences in children with DCD compared to children without DCD; ii) To examine whether sensory differences are related to motor ability, attention deficit hyperactivity disorder (ADHD), or autistic traits., Method: Parents of children (8-12 years) with (n = 23) and without (n = 33) DCD used standardised questionnaires to report on their children's sensory differences, autistic traits, and ADHD traits. Motor abilities were assessed through the Movement Assessment Battery for Children-2. Data were explored both categorically (between-groups) and dimensionally., Results: Children with DCD had significantly higher levels of sensory differences than children without DCD. Sensory differences also had a significantly greater impact on daily activities for children with DCD. Higher levels of ADHD and autistic traits, but not motor ability, were significant independent predictors of higher levels of sensory difference., Conclusion: Children with DCD experience high levels of sensory differences, which impact on their daily lives. These sensory differences may be a marker for additional neurodivergence in children with DCD. Practitioners should consider the sensory needs of children with DCD., What This Paper Adds: This paper provides insight into the sensory features of children with DCD and the impact that sensory differences can have on daily living. Using parent-report, we found that children with DCD had increased sensory differences relative to children without DCD. These included increased hyperresponsiveness, increased hyporesponsiveness, and increased sensory interests, repetitions, and seeking behaviours (SIRS). We also found that sensory differences had a greater impact on daily living for children with DCD compared to children without DCD. Across the whole sample, autistic traits predicted hyperresponsivity and hyporesponsivity patterns; whereas traits of hyperactivity and impulsivity predicted SIRS. Motor abilities did not uniquely predict sensory differences, suggesting that other traits of neurodivergence may contribute to the sensory differences in DCD. Taken together, these findings highlight the necessity of considering sensory needs when supporting children with DCD. They also suggest that if sensory differences are identified in children with DCD, it may be due to the presence of co-occurring neurodivergent traits or conditions., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Pedestrians are a vulnerable group at the roadside and previous research has identified that children with DCD and ADHD are at a heightened risk of pedestrian injuries. Despite this, limited research has explored parental perspectives of the pedestrian risks faced by children with DCD and/or ADHD. Understanding parents' perspectives provides a unique insight into the challenges children face every day and the concerns that parents perceive regarding their children's safety as pedestrians. Therefore, the aim of this study was to explore parents' perspectives of the pedestrian risks faced by their children with DCD and/or ADHD., Methods: Semi-structured interviews were conducted with 14 parents of primary school and early secondary school aged children with age range 7-17. The participants were divided into three groups based on their children's conditions: DCD group (10-17 years, n  = 3), ADHD group (7-13 years, n  = 5), and co-occurring group (7-16 years, n  = 6). All parents confirmed an existing diagnosis and completed the SNAP-IV and DCDQ as screening tools. The interviews explored parents' perspectives regarding their children's pedestrian behaviors, parents' concerns and preventative measures taken to improve the pedestrian safety of their children with DCD and/or ADHD. Reflexive thematic analysis was undertaken to analyze the interviews, from which three themes were developed., Results: The first theme related to the challenges experienced by children at the roadside; parents emphasized the significance of structured and controlled pedestrian crossing sites, underlining their preference for designated crossings as safer options due to their heightened perceptions of risk associated with other road-crossing locations. The second theme: parental concerns and influences on children's road safety referred to their children's performance and safety at the roadside, leading to increased monitoring and a more protective approach to road crossing. The third theme: road safety education related to various strategies parents implemented to mitigate risks, while balancing independence and prioritizing their safety., Discussion: While there were commonalities in the challenges faced by children with DCD and/or ADHD at the roadside, there were also notable differences. Parents of children with DCD discussed challenges with spatial awareness and motor skills, whereas parents of children with ADHD discussed challenges with impulsivity and inattention. Parents of children with co-occurring DCD and ADHD described a complex interplay of these challenges. It is evident from the interviews that children with DCD and/or ADHD require a distinct approach to develop their pedestrian skills effectively and parents reported specific strategies they used to address the risks associated with their children's roadside behavior. Promoting pedestrian safety for children with DCD and/or ADHD necessitates collaboration among parents, schools and local authorities to implement comprehensive measures ensuring their safety. These findings contribute to understanding parental experiences and needs, providing valuable guidance for targeted interventions and policies to enhance the road safety of children with DCD and/or ADHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Falemban, Wilmut, Hurst and Purcell.)

Introduction: Gender affirming surgeries (GAS), such as phalloplasty (PLPs) and vaginoplasty (VGPs), are important aspects of medical care for transgender patients. Here, we aim to better characterize patient demographics and surgical outcomes for PLPs and VGPs using the National Surgical Quality Improvement Program (NSQIP). We hypothesized that frailty indices would be predictive of perioperative PLP and VGP risk and outcomes for PLPs and VGPs., Materials and Methods: Primary GAS, specifically PLPs and VGPs performed from 2006-2020 were identified in NSQIP. Baseline frailty was based on NSQIP's modified frailty index (mFI) and preoperative morbidity probability (morbprob) variable., Results: Fifty-eight PLPs and 468 VGPs were identified. The overall 30-day complication rate for PLP was 26%, with 17% of total patients experiencing minor complications and 16% experiencing major complications. The overall, minor, and major complication rates for VGP were 14%, 7%, and 9% respectively. Readmissions and reoperations occurred in 7% PLP and 5% VGP patients. No deaths occurred in either group within 30 days. The mFI scores were not predictive of 30-day complications or LOS. NSQIP morbprob was predictive of 30-day complications for both PLP (OR 4.0, 95% CI 1.08-19.59, p = 0.038) and VGP (OR 2.39, 95% CI 1.46-3.97, p = 0.0005). NSQIP's morbprob was also predictive of extended LOS for PLP patients (6.3 ± 1.3 days, p = 0.03)., Conclusions: This study describes patient characteristics and complication rates of PLPs and VGPs. The NSQIP preoperative morbprob is an effective predictor of surgical complications and is better than the mFI.

Data were charted as part of a scoping review which followed the Joanna Briggs Institute (JBI) evidence synthesis guidelines and the Preferred Reporting Items for Systematic Reviews and Meta Analysis Scoping Review extension (PRISMA-SCr) guidelines. Data was extracted from 470 articles that met the inclusion criteria for the scoping review; primary research articles of athletes where upper and/or lower limb pain since database inception. A draft data charting tool was developed by the research team and piloted for feasibility, accuracy and agreement. The charting tool was updated accordingly before being applied to the entire data set. Data collected included citation details, research context, participant information and pain assessment and classification tools, categories, and additional relevant information. The raw data set was filtered, and descriptive analysis of frequencies and counts were conducted. Researchers and clinicians interested in the range and applications of different pain assessment practices in athletes may reuse this data set. Data charting was comprehensive including aspects beyond the scope of the original research that offer clinical and research potential. These include information around recommended practice, (International Olympic Committee guidance) pain classifications and definitions and the use of multi-domain pain assessment tools., (© 2024 The Author(s).)

Aims: Alternative models of cardiac rehabilitation (CR) are required to improve CR access and uptake. Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) is a comprehensive home-based rehabilitation and self-management programme, facilitated by trained health professionals, for people with heart failure (HF) and their caregivers. REACH-HF was shown to be clinically effective and cost-effective in a multi-centre randomized trial. The SCOT:REACH-HF study assessed implementation of REACH-HF in routine clinical practice in NHS Scotland., Methods and Results: A mixed-method implementation study was conducted across six regional Health Boards. Of 136 people with HF and 56 caregivers recruited, 101 people with HF and 26 caregivers provided 4-month follow-up data, after participating in the 12-week programme. Compared with baseline, REACH-HF participation resulted in substantial gains in the primary outcome of health-related quality of life, as assessed by the Minnesota Living with Heart Failure Questionnaire (mean difference: -9.8, 95% CI: -13.2 to -6.4, P < 0.001). Improvements were also seen in secondary outcomes (PROM-CR+; EQ-5D-5L; Self-Care of Heart Failure Index (SCHFI) domains of maintenance and symptom perception; Caregiver Contribution to Self-Care domains of symptom perception and management). Twenty qualitative interviews were conducted with 11 REACH-HF facilitators, five supporting clinicians, and four national stakeholders. Interviewees were largely positive about REACH-HF, considering it to have 'filled a gap' where centre-based CR was not an option. Key issues to support future roll-out were also identified., Conclusion: Our findings support wider roll-out of REACH-HF as an alternative to centre-based models, to improve CR access and uptake for people with HF., Competing Interests: Conflict of interest: These affiliations had no influence on the interpretation or presentation of the results of the presentstudy. J.G.F.C. is supported by a British Heart Foundation Centre of Research Excellence award RE/18/6/34217. J.G.F.C. reports research funding and personal honoraria from Abbott, Amgen, Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cytokinetics, Idorsia, Johnson & Johnson, Medtronic, Myokardia, Novartis, NI Medical, Pharmacosmos, Pharma Nord, Philips, Respicardia, Servier, Torrent, Vifor, Viscardia. The other authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This systematic review synthesizes the literature on physical activity amongst people with DCD using the COM-B framework. The review questions were: (1) what is the Capability (C), Opportunity (O) and Motivation (M) for physical activity and (2) what does physical activity behavior (B) look like? A mixed-methods systematic review was conducted by searching eight databases (PubMed, APA PsycINFO, EMBASE, Scopus, Child Development and Adolescent Studies, Cochrane Library, Web of Science, CINAHL) up to July 2023. Data were extracted, thematically analyzed, and mapped to the COM-B model. The quality of studies was assessed with the Joanna Briggs Institute (JBI) critical appraisal tool. The protocol was registered with PROSPERO (CRD42022319127). Forty-three papers, 42 of which related to children, were included. Fifteen aligned with physical activity behavior, nine with physical capability, thirteen with psychological capability, one with social opportunity, one with physical opportunity, one with reflective motivation and three with automatic motivation. Pre-school-aged children with DCD engage in comparable levels of physical activity behavior, but differences emerge from 6 years of age. Characteristics of DCD result in reduced physical capability and less varied participation in physical activity. This impacts psychological capability, whereby lower self-perceptions result in a negative feedback loop and reduce the motivation to participate. Barriers relating to social opportunities may result in poor reflective and automatic motivation, although there is evidence that interventions can enhance enjoyment in the short term., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Purcell, Schott, Rapos, Zwicker and Wilmut.)

Floods are among the most destructive extreme events that exist, being the main cause of people affected by natural disasters. In the near future, estimated flood intensity and frequency are projected to increase. In this context, automatic and accurate satellite-derived flood maps are key for fast emergency response and damage assessment. However, current approaches for operational flood mapping present limitations due to cloud coverage on acquired satellite images, the accuracy of flood detection, and the generalization of methods across different geographies. In this work, a machine learning framework for operational flood mapping from optical satellite images addressing these problems is presented. It is based on a clouds-aware segmentation model trained in an extended version of the WorldFloods dataset. The model produces accurate and fast water segmentation masks even in areas covered by semitransparent clouds, increasing the coverage for emergency response scenarios. The proposed approach can be applied to both Sentinel-2 and Landsat 8/9 data, which enables a much higher revisit of the damaged region, also key for operational purposes. Detection accuracy and generalization of proposed model is carefully evaluated in a novel global dataset composed of manually labeled flood maps. We provide evidence of better performance than current operational methods based on thresholding spectral indices. Moreover, we demonstrate the applicability of our pipeline to map recent large flood events that occurred in Pakistan, between June and September 2022, and in Australia, between February and April 2022. Finally, the high-resolution (10-30m) flood extent maps are intersected with other high-resolution layers of cropland, building delineations, and population density. Using this workflow, we estimated that approximately 10 million people were affected and 700k buildings and 25,000 km[Formula: see text] of cropland were flooded in 2022 Pakistan floods., (© 2023. The Author(s).)

Aim: There is emerging evidence that the Mirror Neuron System (MNS) might contribute to the motor learning difficulties characteristic of Developmental Coordination Disorder (DCD). This study aimed to identify whether MNS activity differed between children with and without DCD during action observation, action execution and during a non-action baseline., Methods: Electroencephalography (EEG) was used to measure mu rhythm (a proxy for MNS activation) in 8-12-year-old children either with (n = 20) or without (n = 19) a diagnosis of DCD. The mu rhythm was recorded at rest and during five experimental conditions: (1) observation of gross motor and (2) fine motor actions; (3) execution of gross motor and (4) fine motor actions; and (5) non-biological movement. To address whether potential co-occurring traits of other neurodevelopmental conditions were associated with differences in mu rhythm, parents reported their child's attention and social communication skills. Mixed and repeated measure ANOVAs were conducted to examine differences in mu desynchronization and mu power respectively., Results: The non-DCD group showed greater mu rhythm desynchronization than children with DCD (i.e., more MNS activity), with both groups demonstrating increasing desynchronization from observation of fine actions to execution of gross actions. However, we also found that the children with DCD had less mu power during the non-biological movement condition than the non-DCD children, although mu power did not differ between groups during the resting condition. Correlations between mu desynchronization and children's attention and motor skills showed that poorer attention and motor abilities were associated with reduced MNS activity., Conclusion: Compared to children without DCD, the MNS in children with DCD did not distinguish between biological and non-biological movement. It is possible that the reduced specificity of the MNS in children with DCD is an underlying factor in the motor impairments observed in the disorder. The differential MNS activity could reflect broader atypical activity in perceptual networks that feed into the MNS in DCD., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Globally, cardiovascular diseases (CVD, that is, coronary heart (CHD) and circulatory diseases combined) contribute to 31% of all deaths, more than any other cause. In line with guidance in the UK and globally, cardiac rehabilitation programmes are widely offered to people with heart disease, and include psychosocial, educational, health behaviour change, and risk management components. Social support and social network interventions have potential to improve outcomes of these programmes, but whether and how these interventions work is poorly understood.  OBJECTIVES: To assess the effectiveness of social network and social support interventions to support cardiac rehabilitation and secondary prevention in the management of people with heart disease. The comparator was usual care with no element of social support (i.e. secondary prevention alone or with cardiac rehabilitation).  SEARCH METHODS: We undertook a systematic search of the following databases on 9 August 2022: CENTRAL, MEDLINE, Embase, and the Web of Science. We also searched ClinicalTrials.gov and the WHO ICTRP. We reviewed the reference lists of relevant systematic reviews and included primary studies, and we contacted experts to identify additional studies.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) of social network or social support interventions for people with heart disease. We included studies regardless of their duration of follow-up, and included those reported as full text, published as abstract only, and unpublished data., Data Collection and Analysis: Using Covidence, two review authors independently screened all identified titles. We retrieved full-text study reports and publications marked 'included', and two review authors independently screened these, and conducted data extraction. Two authors independently assessed risk of bias, and assessed the certainty of the evidence using GRADE. Primary outcomes were all-cause mortality, cardiovascular-related mortality, all-cause hospital admission, cardiovascular-related hospital admission, and health-related quality of life (HRQoL) measured at > 12 months follow-up.  MAIN RESULTS: We included 54 RCTs (126 publications) reporting data for a total of 11,445 people with heart disease. The median follow-up was seven months and median sample size was 96 participants. Of included study participants, 6414 (56%) were male, and the mean age ranged from 48.6 to 76.3 years. Studies included heart failure (41%), mixed cardiac disease (31%), post-myocardial infarction (13%), post-revascularisation (7%), CHD (7%), and cardiac X syndrome (1%) patients. The median intervention duration was 12 weeks. We identified notable diversity in social network and social support interventions, across what was delivered, how, and by whom.  We assessed risk of bias (RoB) in primary outcomes at > 12 months follow-up as either 'low' (2/15 studies), 'some concerns' (11/15), or 'high' (2/15). 'Some concerns' or 'high' RoB resulted from insufficient detail on blinding of outcome assessors, data missingness, and absence of pre-agreed statistical analysis plans. In particular, HRQoL outcomes were at high RoB. Using the GRADE method, we assessed the certainty of evidence as low or very low across outcomes. Social network or social support interventions had no clear effect on all-cause mortality (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.49 to 1.13, I 2 = 40%) or cardiovascular-related mortality (RR 0.85, 95% CI 0.66 to 1.10, I 2 = 0%) at > 12 months follow-up. The evidence suggests that social network or social support interventions for heart disease may result in little to no difference in all-cause hospital admission (RR 1.03, 95% CI 0.86 to 1.22, I 2 = 0%), or cardiovascular-related hospital admission (RR 0.92, 95% CI 0.77 to 1.10, I 2 = 16%), with a low level of certainty. The evidence was very uncertain regarding the impact of social network interventions on HRQoL at > 12 months follow-up (SF-36 physical component score: mean difference (MD) 31.53, 95% CI -28.65 to 91.71, I 2 = 100%, 2 trials/comparisons, 166 participants; mental component score MD 30.62, 95% CI -33.88 to 95.13, I 2 = 100%, 2 trials/comparisons, 166 participants).  Regarding secondary outcomes, there may be a decrease in both systolic and diastolic blood pressure with social network or social support interventions. There was no evidence of impact found on psychological well-being, smoking, cholesterol, myocardial infarction, revascularisation, return to work/education, social isolation or connectedness, patient satisfaction, or adverse events.  Results of meta-regression did not suggest that the intervention effect was related to risk of bias, intervention type, duration, setting, and delivery mode, population type, study location, participant age, or percentage of male participants.  AUTHORS' CONCLUSIONS: We found no strong evidence for the effectiveness of such interventions, although modest effects were identified in relation to blood pressure. While the data presented in this review are indicative of potential for positive effects, the review also highlights the lack of sufficient evidence to conclusively support such interventions for people with heart disease. Further high-quality, well-reported RCTs are required to fully explore the potential of social support interventions in this context. Future reporting of social network and social support interventions for people with heart disease needs to be significantly clearer, and more effectively theorised, in order to ascertain causal pathways and effect on outcomes., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Cognitive cloud computing in space (3CS) describes a new frontier of space innovation powered by Artificial Intelligence, enabling an explosion of new applications in observing our planet and enabling deep space exploration. In this framework, machine learning (ML) payloads-isolated software capable of extracting high level information from onboard sensors-are key to accomplish this vision. In this work we demonstrate, in a satellite deployed in orbit, a ML payload called 'WorldFloods' that is able to send compressed flood maps from sensed images. In particular, we perform a set of experiments to: (1) compare different segmentation models on different processing variables critical for onboard deployment, (2) show that we can produce, onboard, vectorised polygons delineating the detected flood water from a full Sentinel-2 tile, (3) retrain the model with few images of the onboard sensor downlinked to Earth and (4) demonstrate that this new model can be uplinked to the satellite and run on new images acquired by its camera. Overall our work demonstrates that ML-based models deployed in orbit can be updated if new information is available, paving the way for agile integration of onboard and onground processing and "on the fly" continuous learning., (© 2023. The Author(s).)

Background: Young people with Special Educational Needs and Disabilities (SEND) are especially vulnerable to physical inactivity. Research has demonstrated the effectiveness of tailored cycle training for children with SEND, however, it is unclear whether this then results in a greater uptake of cycling., Aims: To determine parent based perceptions of a SEND cycle training programme, factors which predict intention to cycle more and ongoing barriers to cycling., Methods: A tailored questionnaire was distributed to parents of children who took part in the cycle training., Results: Parents reported increased confidence in their child's ability to cycle independently with many also highlighting improvements in confidence and resilience. The outcome of the cycle training (level of enjoyment and change in cycling ability) had a positive influence on intention to cycle more while cycling frequency prior to training had a negative influence. Continuing barriers to cycling were identified which included difficulties accessing specialised equipment and a need for additional on-road cycle training., Conclusions and Implications: This study demonstrates the success of a specialised cycle training programme for children with SEND in terms of improvement to cycling and influences on the intention to cycle more., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors. Published by Elsevier Ltd.)

Background: Upper and lower limb (peripheral) pain is prevalent in athletes. Contemporary research prioritises multidimensional pain assessment and classification. This study aims to review comprehensive athlete pain assessment practices against the reference standard (International Olympic Committee, IOC Athlete Pain framework), identifying trends and highlighting gaps., Methods and Analysis: Six databases were searched using a comprehensive search strategy. This review followed the Joanna Briggs Institute standardised methodology for scoping reviews and is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Title and abstract, full-text screening and data charting were completed by two independent reviewers., Inclusion Criteria: Original research, systematic reviews and clinical practice guidelines reporting assessment or classification of pain in athletes of any age with chronic or acute peripheral pain in English on human participants from database inception., Results: 470 studies with 175 different pain assessment tools were mapped against the IOC Athlete Pain Framework. Papers included tools from neurophysiological (470/100%), biomechanical (425/90%), affective (103/22%), cognitive (59/13%) and socioenvironmental (182/39%) domains. Pain classification was included in 108 studies (23%). 4 studies (0.85%) defined pain. Athletes with physical disability were included in 13 (3%) studies and no studies included athletes with intellectual disabilities. Socioeconomic factors were addressed in 29 (6%) studies., Discussion: Neurophysiological and biomechanical domains are frequently addressed. Affective, socioenvironmental and cognitive tools are under-represented. Potential tools for use by researchers and clinicians are highlighted. Defining and classifying pain and determining predominant pain mechanisms is needed in both research and clinical practice. More work on underrepresented populations is needed., Conclusion: This review informs researchers and clinicians working with athletes in pain how pain assessment and classification is currently conducted and highlights future priorities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The quality of school-based sex and relationships education (SRE) is variable in the UK. Digitally-based interventions can usefully supplement teacher-delivered lessons and positively impact sexual health knowledge. Designed to address gaps in core SRE knowledge, STASH (Sexually Transmitted infections And Sexual Health) is a peer-led social network intervention adapted from the successful ASSIST (A Stop Smoking in Schools Trial) model, and based on Diffusion of Innovation theory. This paper describes how the STASH intervention was developed and refined., Methods: Drawing on the Six Steps in Quality Intervention Development (6SQuID) framework, we tested a provisional programme theory through three iterative stages -: 1) evidence synthesis; 2) intervention co-production; and 3) adaptation - which incorporated evidence review, stakeholder consultation, and website co-development and piloting with young people, sexual health specialists, and educators. Multi-method results were analysed in a matrix of commonalities and differences., Results: Over 21 months, intervention development comprised 20 activities within the three stages. 1) We identified gaps in SRE provision and online resources (e.g. around sexual consent, pleasure, digital literacy), and confirmed critical components including the core ASSIST peer nomination process, the support of schools, and alignment to the national curriculum. We reviewed candidate social media platforms, ruling out all except Facebook on basis of functionality restrictions which precluded their use for our purposes. 2) Drawing on these findings, as well as relevant behaviour change theories and core elements of the ASSIST model, we co-developed new content with young people and other stakeholders, tailored to sexual health and to delivery via closed Facebook groups, as well as face-to-face conversations. 3) A pilot in one school highlighted practical considerations, including around peer nomination, recruitment, awareness raising, and boundaries to message sharing. From this, a revised STASH intervention and programme theory were co-developed with stakeholders., Conclusions: STASH intervention development required extensive adaptation from the ASSIST model. Although labour intensive, our robust co-development approach ensured that an optimised intervention was taken forward for feasibility testing. Evidencing a rigorous approach to operationalising existing intervention development guidance, this paper also highlights the significance of balancing competing stakeholder concerns, resource availability, and an ever-changing landscape for implementation., Trial Registration: ISRCTN97369178., (© 2023. The Author(s).)

Background: The Global Burden of Disease Study (GBD) estimates burden by cause with major relevance for resource allocators globally. Non-fatal burden estimates are influenced by disorder severity. However, for many disorders, global severity is sourced from a single high-income country survey. We aimed to estimate severity distributions that vary by Healthcare Access Quality Index (HAQI) using anxiety disorders as a case study and present the usefulness of this method in simulating averted and avoidable burden globally., Methods: In this case study, we estimated treatment use among respondents with anxiety disorder in the 1997 Australian National Survey of Mental Health and Wellbeing (NSMHWB), the source used to estimate severity of anxiety disorders in GBD. Treatment effects were sourced from the Cochrane Database of Systematic Reviews and pooled via network meta-analysis. Severity distribution was established via a meta-regression of their disability weights, derived from 12-item short form survey scores. We simulated the shift in severity across scenarios without access to treatment and with full access to optimal treatment (cognitive behavioural therapy and antidepressants). We interpolated this shift linearly along the HAQI, extrapolated country-specific severity from HAQI scores, and calculated averted and avoidable burden., Findings: The database review sourced 56 reviews, of which eight were eligible for inclusion. These eight reviews reported on 156 randomised controlled trials, with 194 treatment effects. Respondents to the 1997 NSMHWB consisted of 5936 women (55·8%) and 4705 (44·2%) men aged 18 years or older (mean age and ethnicity data not available). The survey-weighted treatment effect size was -0·28 (95% uncertainty interval -0·45 to -0·12). The pooled treatment effect for full coverage optimal treatment was -1·07 (-1·47 to -0·64). The sequela-weighted disability weight among people with anxiety disorder in the NSMHWB was 0·141 (0·042 to 0·275). The estimated disability weight was 0·188 (0·070 to 0·341) after removing the benefits of treatment and 0·056 (0·013 to 0·140) after providing all people with anxiety disorder access to optimal treatment. Globally, 12·5% (4·6 to 21·5) of anxiety disorder burden was averted because of available treatment. However, 71·1% (46·2 to 87·6) of global anxiety disorder burden could be averted if all people with anxiety disorders had access to optimal treatment., Interpretation: Because it is based on guidance from a single survey done in one high-income country, the burden of anxiety disorders in low-income and middle-income countries is probably underestimated by GBD. Despite the availability of effective treatments, low use of these treatments means that most burden is still avoidable. Most of the burden could be averted if all people with anxiety disorders had access to optimal treatment, highlighting the importance of public promotion and referral pathways of treatment for anxiety disorders. Location-specific severity distributions in GBD would greatly increase precision in burden estimates and highlight avertable burden to clinicians, public health practitioners, and policy makers., Funding: Queensland Health and Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Verotoxin-producing Escherichia coli (VTEC) causes zoonotic infections, with potentially devastating complications, and children under 5 years old are particularly susceptible. Antibiotic treatment is contraindicated, and due to the high proportion of infected children that suffer from severe and life-changing complications, there is an unmet need for a vaccine to prevent VTEC infections. Bacterial adhesins represent promising candidates for the successful development of a vaccine against VTEC. Using a proteomic approach to identify bacterial proteins interacting with human gastrointestinal epithelial Caco-2 and HT-29 cells, we identified eleven proteins by mass spectrometry. These included a glutamine-binding periplasmic protein, GlnH, a member of the ABC transporter family. The glnH gene was identified in 13 of the 15 bovine and all 5 human patient samples tested, suggesting that it is prevalent. We confirmed that GlnH is involved in the host cell attachment of an O157:H7 prototype E. coli strain to gastrointestinal cells in vitro. Recombinant GlnH was expressed and purified prior to the immunisation of mice. When alum was used as an adjuvant, GlnH was highly immunogenic, stimulating strong serological responses in immunised mice, and it resulted in a modest reduction in faecal shedding but did not reduce colonisation. GlnH immunisation with a T-cell-inducing adjuvant (SAS) also showed comparable antibody responses and an IgG1/IgG2a ratio suggestive of a mixed Th1/Th2 response but was partially protective, with a 1.5-log reduction in colonisation of the colon and caecum at 7 days relative to the adjuvant only ( p = 0.0280). It is clear that future VTEC vaccine developments should consider the contribution of adjuvants in addition to antigens. Moreover, it is likely that a combined cellular and humoral response may prove more beneficial in providing protective interventions against VTEC.

Objective: To explore factors that could explain why older adults are more at risk at the roadside., Background: The physical and psychological health benefits of walking have been well-established, leading to the widespread promotion of walking amongst older adults. However, walking can result in an increased risk of injury as a pedestrian at the roadside, which is a greater risk for older adults who are overrepresented in pedestrian casualty figures., Method: Relevant databases were searched up to January 2020. All peer-reviewed journals that presented data on healthy older adults and some aspect of road crossing or roadside behavior were included. A total of 142 papers were assessed and 60 met the inclusion criteria., Results: Identified papers could be grouped into three areas: crossing at a designated crossing place; crossing with no designated crossing place; perceptions or behaviors., Conclusion: Multiple individual (attitudes, perceived behavioral control, walking time, time-to-arrival judgments, waiting endurance, cognitive ability), task (vehicle size, vehicle speed, traffic volume), and environmental (road layout, time of day, weather) constraints influence road crossing in older adulthood., Application: Accessibility of designated crossing areas needs to be addressed by ensuring sufficient time to cross and nonrestrictive waiting times. Signalized crossings need to be simplified and visibility increased. Where there is no designated crossing place, a reduction in speed limit alongside the provision of pedestrian islands to provide "pause" places are needed. Educational-based programs may also help ensure safety of older adults where there is no designated crossing place.

KRAS-LKB1 (KL) mutant lung cancers silence STING owing to intrinsic mitochondrial dysfunction, resulting in T cell exclusion and resistance to programmed cell death (ligand) 1 (PD-[L]1) blockade. Here we discover that KL cells also minimize intracellular accumulation of 2'3'-cyclic GMP-AMP (2'3'-cGAMP) to further avoid downstream STING and STAT1 activation. An unbiased screen to co-opt this vulnerability reveals that transient MPS1 inhibition (MPS1i) potently re-engages this pathway in KL cells via micronuclei generation. This effect is markedly amplified by epigenetic de-repression of STING and only requires pulse MPS1i treatment, creating a therapeutic window compared with non-dividing cells. A single course of decitabine treatment followed by pulse MPS1i therapy restores T cell infiltration in vivo, enhances anti-PD-1 efficacy, and results in a durable response without evidence of significant toxicity., Competing Interests: Declaration of interests S.K., T.T., D.A.B., C.P.P, and P.G. are inventors on a pending patent for combination DAC and MPS1 inhibitor therapy to prime cancer immunogenicity. D.A.B. is a consultant for N of One/Qiagen and Tango Therapeutics; is a founder and shareholder in Xsphera Biosciences; has received honoraria from Merck, H3 Biomedicine/Esai, EMD Serono, Gilead Sciences, Abbvie, and Madalon Consulting; and has received research grants from BMS, Takeda, Novartis, Gilead, and Lilly. T.U.B is a consultant for N of One/Qiagen. P.C.G. has sponsored research agreements with Marengo Therapeutics, Epizyme, Daiichi Sankyo, and Foghorn Therapeutics. C.P.P is a consultant for DropWorks and Xsphera Biosciences; has stock and other ownership interests in Xsphera Biosciences; received honoraria from Bio-Rad; and has sponsored research agreements with Daiichi Sankyo, Bicycle Therapeutics, Transcenta, Bicara Therapeutics, AstraZeneca, Intellia Therapeutics, Janssen Pharmaceuticals, and Array Biopharma. S.K. has a sponsored research agreement with Boehringer-Ingelheim. E.H.K. is an employee and stockholder of Merck & Co. and previously had a Sponsored Research Agreement with Takeda Pharmaceuticals. H.K. has a Sponsored Research Agreement with Takeda Pharmaceuticals. P.A.J. has received consulting fees from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche/Genentech, Takeda Oncology, ACEA Biosciences, Eli Lilly and Company, Araxes Pharma, Ignyta, Mirati Therapeutics, Novartis, LOXO Oncology, Daiichi Sankyo, Sanofi Oncology, Voronoi, SFJ Pharmaceuticals, Takeda Oncology, Transcenta, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Esai, Biocartis, Allorion Therapeutics, Accutar Biotech, and Abbvie; receives post-marketing royalties from DFCI; owned intellectual property on EGFR mutations licensed to Lab Corp; has sponsored research agreements with AstraZeneca, Daichi-Sankyo, PUMA, Boehringer Ingelheim, Eli Lilly and Company, Revolution Medicines; and Astellas Pharmaceuticals; and has stock ownership in LOXO Oncology and Gatekeeper Pharmaceuticals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Pain is often presumed to be part of the sport injury experience. The time-loss definition of injury leads to under-reported athletic pain impacting performance and quality of life. Whilst research regarding the assessment and classification of back pain in athletes is emerging, little has been reported regarding how peripheral pain is assessed and classified in research and practice. Six databases will be searched for relevant articles. Title and abstract screening followed by full-text screening will be completed by two independent reviewers. Data charting will be carried out using a modified standardised form. Descriptive results and frequencies will be reported. Pain measures identified in the studies will be mapped against the IOC Athlete Pain Framework alongside a narrative summary. Published peer-reviewed primary research studies alongside systematic reviews and clinical practice guidelines reporting the assessment or classification of pain in athletes of any age with chronic or acute peripheral pain across all study contexts in the English language on human participants from inception of the databases will be included. The results of this study are part of a body of research which will be used to inform the development of a pain assessment framework. The scoping review will be submitted for peer-reviewed journal publication and presented at sports medicine conferences. This review will inform researchers and clinicians working with athletes in pain how pain assessment and classification is currently conducted and positioned against the IOC Athlete Pain Framework., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Interactions between the inhibitor of apoptosis protein antagonist LCL161 and the histone deacetylase inhibitor panobinostat (LBH589) were examined in human multiple myeloma (MM) cells. LCL161 and panobinostat interacted synergistically to induce apoptosis in diverse MM cell lines, including those resistant to bortezomib (PS-R). Similar interactions were observed with other histone deacetylase inhibitors (MS-275) or inhibitors of apoptosis protein antagonists (birinapant). These events were associated with downregulation of the noncanonical (but not the canonical) NF-κB pathway and activation of the extrinsic, caspase-8-related apoptotic cascade. Coexposure of MM cells to LCL161/LBH589 induced TRAF3 upregulation and led to TRAF2 and NIK downregulation, diminished expression of BCL-XL, and induction of γH2A.X. Ectopic expression of TRAF2, NIK, or BCL-XL, or short hairpin RNA TRAF3 knock-down, significantly reduced LCL161/LBH589 lethality, as did ectopic expression of dominant-negative FADD. Stromal/microenvironmental factors failed to diminish LCL161/LBH589-induced cell death. The LCL161/LBH589 regimen significantly increased cell killing in primary CD138+ cells (N = 31) and was particularly effective in diminishing the primitive progenitor cell-enriched CD138-/19+/20+/27+ population (N = 23) but was nontoxic to normal CD34+ cells. Finally, combined LCL161/LBH589 treatment significantly increased survival compared with single-agent treatment in an immunocompetent 5TGM1 murine MM model. Together, these findings argue that LCL161 interacts synergistically with LBH589 in MM cells through a process involving inactivation of the noncanonical NF-κB pathway and activation of the extrinsic apoptotic pathway, upregulation of TRAF3, and downregulation of TRAF2/BCL-XL. Notably, this regimen overcomes various forms of resistance, is active against primary MM cells, and displays significant in vivo activity. This strategy warrants further consideration in MM., (© 2021 by The American Society of Hematology.)

The Centers for Disease Control and Prevention reports that one-third of all Americans have not done any advance care planning, which is essential for maintaining autonomy when people are no longer able to communicate wishes directly at the end of life. The Institute of Medicine reports that providers have limited training in communication techniques and low confidence in holding advance care planning conversations. Forty-four family nurse practitioner students received classroom communication training using evidence-based end-of-life nursing education consortium materials and role-play opportunities. One month later, students participated in a palliative care simulation experience in a high-fidelity simulated medical office environment with standardized patient. The family practice nurse practitioner students were required to communicate bad news of a poor diagnosis to a family member and begin the advance care planning conversation using the SPIKES protocol. Findings include a significant increase in postintervention advance care planning communication knowledge scores and self-confidence in holding these conversations (mean, 30.55 [SD, 2.992]; 95% confidence interval, 29.64-31.46; median, 31; range, 11-35) and satisfaction with the learning experience (mean, 18.14 [SD, 2.11]; 95% confidence interval, 17.50-18.78; median, 19; with range between 13 and 20)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 by The Hospice and Palliative Nurses Association. All rights reserved.)

Background: Effective sex education is the key to good sexual health. Peer-led approaches can augment teacher-delivered sex education, but many fail to capitalise on mechanisms of social influence. We assessed the feasibility of a novel intervention (STASH) in which students (aged 14-16) nominated as influential by their peers were recruited and trained as Peer Supporters (PS). Over a 5-10-week period, they spread positive sexual health messages to friends in their year group, both in-person and via social media, and were supported to do so via weekly trainer-facilitated meetings. The aims of the study were to assess the feasibility of STASH (acceptability, fidelity and reach), to test and refine the programme theory and to establish whether the study met pre-set progression criteria for continuation to larger-scale evaluation., Methods: The overall design was a non-randomised feasibility study of the STASH intervention in 6 schools in Scotland. Baseline (n=680) and follow-up questionnaires (approx. 6 months later; n=603) were administered to the intervention year group. The control group (students in year above) completed the follow-up questionnaire only (n=696), 1 year before the intervention group. The PS (n=88) completed a brief web survey about their experience of the role; researchers interviewed participants in key roles (PS (n=20); PS friends (n=22); teachers (n=8); trainers (n=3)) and observed 20 intervention activities. Activity evaluation forms and project monitoring data also contributed information. We performed descriptive quantitative analysis and thematic qualitative analysis., Results: The PS role was acceptable; on average across schools >50% of students nominated as influential by their friends, signed up and were trained (n=104). This equated to 13% of the year group. Trained PS rarely dropped out (97% completion rate) and 85% said they liked the role. Fidelity was good (all bar one trainer-led activity carried out; PS were active). The intervention had good reach; PS were reasonably well connected and perceived as 'a good mix' and 58% of students reported exposure to STASH. Hypothesised pre-conditions, contextual influences and mechanisms of change for the intervention were largely confirmed. All bar one of the progression criteria was met., Conclusion: The weight of evidence supports continuation to full-scale evaluation., Trial Registration: Current controlled trials ISRCTN97369178.

Background: Healthcare systems generate substantial carbon footprints that may be targeted to decrease greenhouse gas emissions. Outreach clinics may represent tools to assist in this reduction by optimizing patient related travel. Therefore, we sought to estimate the carbon footprint savings associated with a head and neck surgery outreach clinic., Methods: This study was a cross-sectional survey of patient travel patterns to a surgical outreach clinic compared to a regional cancer treatment centre from December 2019 to February 2020. Participants completed a self-administered survey of 12 items eliciting travel distance, vehicle details, and ability to combine medical appointments. Canadian datasets of manufacturer provided vehicular efficiency were used to estimate carbon emissions for each participant. Geographic information systems were used for analyses., Results: One hundred thirteen patients were included for analysis. The majority of patients (85.8%) used their own personal vehicle to travel to the outreach clinic. The median distance to the clinic and regional centre were 29.0 km (IQR 6.0-51.9) and 327.0 km (IQR 309.0-337.0) respectively. The mean carbon emission reduction per person was therefore 117,495.4 g (SD: 29,040.0) to 143,570.9 g (SD: 40,236.0). This represents up to 2.5% of an average individual's yearly carbon footprint. Fewer than 10% of patients indicated they were able to carpool or group their appointments., Conclusion: Surgical outreach clinics decrease carbon footprints associated with patient travel compared to continued care at a regional centre. Further research is needed to determine possible interventions to further reduce carbon emissions associated with the surgical care of patients.

Background: There is a strong interest in the use of social media to spread positive sexual health messages through social networks of young people. However, research suggests that this potential may be limited by a reluctance to be visibly associated with sexual health content on the web or social media and by the lack of trust in the veracity of peer sources., Objective: The aim of this study was to investigate opportunities and challenges of using social media to facilitate peer-to-peer sharing of sexual health messages within the context of STASH (Sexually Transmitted Infections and Sexual Health), a secondary school-based and peer-led sexual health intervention., Methods: Following training, and as a part of their role, student-nominated peer supporters (aged 14-16 years) invited school friends to trainer-monitored, private Facebook groups. Peer supporters posted curated educational sex and relationship content within these groups. Data came from a feasibility study of the STASH intervention in 6 UK schools. To understand student experiences of the social media component, we used data from 11 semistructured paired and group interviews with peer supporters and their friends (collectively termed students; n=42, aged 14-16 years), a web-based postintervention questionnaire administered to peer supporters (n=88), and baseline and follow-up questionnaires administered to students in the intervention year group (n=680 and n=603, respectively). We carried out a thematic analysis of qualitative data and a descriptive analysis of quantitative data., Results: Message sharing by peer supporters was hindered by variable engagement with Facebook. The trainer-monitored and private Facebook groups were acceptable to student members (peer supporters and their friends) and reassuring to peer supporters but led to engagement that ran parallel to-rather than embedded in-their routine social media use. The offline context of a school-based intervention helped legitimate and augment Facebook posts; however, even where friends were receptive to STASH messages, they did not necessarily engage visibly on social media. Preferences for content design varied; however, humor, color, and text brevity were important. Preferences for social media versus offline message sharing varied., Conclusions: Invitation-only social media groups formed around peer supporters' existing friendship networks hold potential for diffusing messages in peer-based sexual health interventions. Ideally, interactive opportunities should not be limited to single social media platforms and should run alongside offline conversations. There are tensions between offering young people autonomy to engage flexibly and authentically and the need for adult oversight of activities for information accuracy and safeguarding., (©Maija Hirvonen, Carrie Purcell, Lawrie Elliott, Julia V Bailey, Sharon Anne Simpson, Lisa McDaid, Laurence Moore, Kirstin Rebecca Mitchell, The STASH Study Team. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 16.02.2021.)

During postnatal development, colostrum and breastmilk are sequentially the first sources of nutrition with protein components and bioactive molecules that confer protection and immunostimulatory function to the gut. Caseins, whey proteins, secretory immunoglobulin A (sIgA), mucins, tryptophan, and growth factors are among milk-borne elements that are directly important in the control of mucosa development and protection. Consequently, breastfeeding is associated with the low incidence of gastrointestinal inflammation and with the decrease in respiratory diseases during postnatal period. The novel coronavirus (SARS-CoV-2) binds to angiotensin II-converting enzyme (ACE2) on the cell membrane, allowing virus entrance, replication, and host commitment. ACE2 is expressed by different cell types, which include ciliated cells in the lungs and enterocytes in the intestine. Such cells are highly active in metabolism, as they internalize molecules to be processed and used by the organism. The disruption of ACE2 impairs leads to intestinal inflammation and decreased synthesis of serotonin, affecting motility. By reviewing the effects of SARS-CoV-2 in the gastrointestinal and respiratory tracts in infants, and gut responses to breastfeeding interruption, we suggest that it is important to maintain breastfeeding during SARS-CoV-2 infection, as it might be essential to protect newborns from gastrointestinal-associated disorders and relieve disease symptoms., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)