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Background: The COVID-19 pandemic exposed critical gaps in health system preparedness. This study, guided by a critical ecological model, examines the experiences of primary health and community services in Aotearoa New Zealand during the pandemic, focusing on their response to older people and their unpaid caregivers. The study aims to identify effective strategies for health system resilience. It addresses the question, what can we learn from the experiences of organisations supporting older people and caregivers during COVID-19, to prepare for other similar (emergency health) situations?, Methods: A multidisciplinary research team conducted cross-sectional qualitative research through semi-structured telephone interviews with service providers (SPs) delivering primary or community home-based services to older people and caregivers across Aotearoa New Zealand. SPs included national organisations, Māori, Pacific, or rural providers and dementia services. Data were collected between July and October 2020. Notes were taken during interviews using a Rapid Appraisal Procedure grid, which were later revised and validated by participants. Data were analysed using a hybrid deductive-inductive thematic analysis, following COREQ guidelines., Results: Twenty staff (Chief Executive Officers and representatives) from national organisations (N = 4), Māori (N = 3), Pacific (N = 5), rural (N = 4), and regional dementia (N = 4) SPs were interviewed. SPs demonstrated resilience through collaboration, adapting delivery models, and upskilling staff. Key challenges involved inconsistent identification of vulnerable clients, limited access to aged residential care, and barriers relating to digital access which disproportionately affected older adults and staff, and clients in rural areas. Workforce shortages, and unclear public policy concerning travel across regions further complicated service delivery, highlighting the interaction between policy, community, interpersonal, and individual factors., Conclusions: Aotearoa New Zealand managed COVID-19 effectively, but the pandemic exposed areas for improvement in health system resilience. The government demonstrated absorptive resilience through swift actions, including lockdowns and clear communication, while SPs exhibited adaptive resilience by modifying service protocols. Knowledge gained from this study can contribute to transformative resilience. Long-term strategic changes are necessary to improve emergency planning, such as developing a unified framework to inform a 'Priority List', enhancing workforce capacity, and addressing digital exclusion. These steps can strengthen health system robustness and preparedness for future crises., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the University of Auckland Health Research Ethics Committee (Ref AH21966). Informed consent to participate in the study was obtained from all participants. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Cognitive impairment is common in haemodialysis patients with no known beneficial interventions. Cooler dialysate slows brain white-matter changes, but its effect on cognition is unknown. This feasibility trial was performed to inform a fully-powered, randomised trial to assess this., Methods: We aimed to randomise (1:1) 90 haemodialysis patients to this double-blinded, randomised controlled feasibility trial to standard care (dialysate-temperature 36.5 °C) or intervention (35 °C). Eligible patients were adult chronic haemodialysis recipients with no established diagnosis of dementia or psychiatric disease. The primary outcome was change in Montreal Cognitive Assessment (MoCA) score at 12-months. Secondary outcomes included recruitment and attrition rates, reasons for non-recruitment, intradialytic hypotension, depression, patient burden, computerised cognition test battery, and quality of life., Findings: Of 334 patients screened, 160 were eligible. 99 declined mainly for the extra non-dialysis day study visits. Sixty-one patients consented, 43 randomised - 20 in standard care, 23 in intervention arms; 13 withdrew for non-dialysis day visits and 5 without reason before randomisation. 27 patients (12 standard care, 15 intervention) completed the trial - 5 died, 1 transplanted, 4 withdrew consent, and 6 could not attend due to the pandemic. Low temperature dialysis was well tolerated. There was no difference in change in MoCA from baseline to 12 months between the standard and intervention arms; 1.0 (-2.8-3.0, p = 0.755) and - 2.0 (-1.0 - -4.0, p = 0.047) respectively. There were no differences between groups on any secondary measures. There were no significant adverse events reported., Discussion: The trial was significantly affected by the COVID-19 pandemic contributing to an attrition rate of 27%. The non-dialysis day research visits were mainly responsible for low recruitment and consent withdrawal. There are several learning points, described in the article, which will inform design of definitive trials in this area in the future., Trial Registration: ClinicalTrials.gov Identifier NCT03645733. Registration date 24/08/2018., Competing Interests: Declarations. Ethics approval and consent to participate: The trial was approved by the National Research Ethics Service Committee, West Midlands-South Birmingham (IRAS ID 234107). All participants provided informed consent. Consent for publication: Not applicable. Competing interests: Paul Maruff is an employee of Cogstate a cognitive instrument used in this study. The other authors have no relevant conflict of interest for the trial. Conflict of interest: Paul Maruff is an employee of Cogstate a cognitive instrument used in this study. The other authors have no relevant conflict of interest for the trial. The results presented in this paper have not been published previously in whole or part, except in abstract format., (© 2024. The Author(s).)

Background: Evidence suggests that prehabilitation interventions, which optimise physical and mental health prior to treatment, can improve outcomes for surgical cancer patients and save costs to the health system through faster recovery and fewer complications. However, robust, theory-based evaluations of these programmes are needed. Using a theory of change (ToC) approach can guide evaluation plans by describing how and why a programme is expected to work. Theories of Change have not been developed for cancer prehabilitation programmes in the literature to date. This paper aims to provide an overview of the methodological steps we used to retrospectively construct a ToC for Prehab2Rehab (P2R), a cancer prehabilitation programme being implemented by the Cardiff and Vale University Health Board., Methods: We used an iterative, participatory approach to develop the ToC. Following a literature review and document analysis, we facilitated a workshop with fourteen stakeholders from across the programme using a 'backwards mapping' approach. After the workshop, stakeholders had three additional opportunities to refine and validate a final working version of the ToC., Results: Our process resulted in the effective and timely development of a ToC. The ToC captures how P2R's interventions or activities are expected to bring about short, medium and long-term outcomes that, collectively, should result in the overarching desired impacts of the programme, which were improved patient flow and reduced costs to the health system. The process of developing a ToC also enabled us to have a better understanding of the programme and build rapport with key stakeholders., Conclusions: The ToC has guided the design of an evaluation that covers the complexity of P2R and will generate lessons for policy and clinical practice on supporting surgical cancer patients in Wales and beyond. We recommend that evaluators apply a ToC development process at the outset of evaluations to bring together stakeholders and enhance the utilisation of the findings. This paper details a pragmatic, efficient and replicable process that evaluators could adopt to develop a ToC. Theory-informed evaluations may provide better evidence to develop and refine cancer prehabilitation interventions and other complex public health interventions., Competing Interests: Declarations. Ethics approval and consent to participate: This project, including the Theory of Change workshop, was deemed to be a service evaluation to improve healthcare, undertaken as part of the establishment order for Public Health Wales NHS Trust under the National Health Service (Wales) Act 2006. As per Health Research Authority guidance, ethical approval was not required. This decision was ratified by the Public Health Wales Research and Development Office. An internal Data Protection Impact Assessment was completed to ensure that the evaluation activities adhered to Information Governance regulations. Only consensus data was collected (with no individual or personal data) and workshop participants provided verbal informed consent for the workshop outputs to be included in research outputs. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: This study outlines the initiation of an interprofessional education (IPE) program designed for optometry and education students. The program aimed to foster interdisciplinary collaboration and improve the management of eye health in children with special educational needs (SEN) - a vulnerable and underserved group., Methods: This program incorporated lectures and workshops to impart essential knowledge about SEN and to develop the necessary attitudes and skills for conducting eye examinations. A key component involved vision screenings at two special education schools, where optometry (n = 43) and education students (n = 39) collaborated to serve 170 children with mild to moderate intellectual disabilities. Quantitative data was gathered pre- and post-program using a single-stage, five-level Likert scale. Qualitative insights were drawn from students' reflective writings to evaluate their learning outcomes, understanding, and confidence in managing eye health for children with SEN., Results: Of the participants, 37 optometry and 21 education students completed the survey (70.7% response rate). The survey results indicated significant improvements in understanding SEN characteristics (p ≤ 0.013) and increased confidence when conducting eye examinations for children with SEN (p < 0.007) after the training program. The analysis of reflective writings highlighted the program's beneficial impacts on students. They recognized the value of interprofessional collaboration, reported enhanced professional competence, gained deeper insights into their own and their peers' roles within multidisciplinary teams, and developed a strengthened sense of social responsibility., Conclusion: This IPE program proved to be an effective method for enhancing optometry and education students' knowledge and confidence in managing eye health needs of children with SEN. The findings support the advocacy for continued collaborative efforts between healthcare providers and educators to ensure comprehensive care for this population. Such disciplinary collaboration provides positive evidence in early stages of training in both disciplines., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Human ethics and consent to participate: Written informed consent was obtained from the guardians through the schools. All screening procedures adhered to the tenets of the Declaration of Helsinki and were approved by The Hong Kong Polytechnic University Human Subjects Ethics Subcommittee (HSEARS20230104006). Consent to publish: The individual(s) depicted have been made aware of the intended use of the image and have provided their consent. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Adequate maternity care and appropriate clinical interventions during labour and delivery can reduce adverse perinatal outcomes, but unnecessary interventions may cause harm. While studies have shown that refugees and asylum seekers face important barriers when accessing maternity care, there is a lack of high-quality quantitative data on perinatal health interventions, such as induction of labour or caesarean sections, among refugees and asylum seekers and the findings reported in the literature tend to be inconsistent. Our goal was to examine and synthesise the evidence regarding the rates of intrapartum clinical interventions in women who are refugees and asylum seekers in high-income countries compared to other population groups., Methods: We conducted a scoping review of peer-reviewed studies published in English since 2011 that report original quantitative findings regarding intrapartum clinical interventions among refugees and asylum seekers in high-income countries compared to those in non refugee, non asylum seeker populations. We examined reported rates of clinical pain relief, labour induction and augmentation, episiotomies, instrumental deliveries, and caesarean sections., Results: Twenty-five papers were included in the review. Findings indicate that refugees and asylum seekers were less likely to receive pain relief, with 16 out of 20 data points showing unadjusted ORs ranging from 0.20 (CI: 0.10-0.60) to 0.96 (CI: 0.70-1.32). Similarly, findings indicate lower odds of instrumental delivery among refugees and asylum seekers with 14 of 21 data points showing unadjusted ORs between 0.25 (CI: 0.15-0.39) and 0.78 (CI: 0.47-1.30); the remaining papers report no statistically significant difference between groups. There was no discernable trend in rates of labour induction and episiotomies across studies., Conclusions: The studies included in this review suggest that asylum seekers and refugees are less likely to receive clinical pain relief and experience instrumental delivery than non-refugee groups in high-income countries. This review strengthens our understanding of the links between immigration status and maternity care, ultimately informing policy and practice to improve perinatal health and the provision of care for all., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The increasing prevalence of mental health disorders in the United Kingdom necessitates the exploration of novel treatment modalities. This study aimed to assess the feasibility and acceptability of conducting a randomised controlled trial (RCT) evaluating the efficacy of four osteopathic interventions on psychophysiological and mental health outcomes., Methods: A mixed-methods feasibility study with an explanatory sequential design was implemented. The quantitative phase involved randomising 42 participants into four intervention groups: (1) high-velocity and articulation techniques (HVAT), (2) soft-tissue massage (STM), (3) craniosacral therapy (CST), and (4) a combination approach. Primary outcome measures encompassed recruitment rate, assessment duration, questionnaire completion, intervention attrition, and adverse events. Secondary outcomes included validated assessments of depression, anxiety, stress, psychological flexibility, heart rate variability (HRV), and interoception, administered pre- and post-intervention. Analysis of variance (ANOVA) was employed to evaluate pre-post intervention changes. The qualitative phase comprised semi-structured interviews analysed using thematic analysis., Results: The study achieved a recruitment rate of 21 eligible participants per month, with 54.8% of respondents meeting eligibility criteria. All 33 participants who completed the study underwent interventions and assessments within the allocated one-hour timeframe, with full questionnaire completion. The attrition rate was 21%. No adverse events were reported. Qualitative analysis revealed positive participant experiences, with themes highlighting good practitioner communication, intervention accessibility, and increased bodily awareness. Some participants found the questionnaire battery burdensome. Exploratory quantitative analyses showed variations in effects across interventions for heart rate variability, interoceptive accuracy, and mental health measures, but these results should be interpreted cautiously due to the small sample size., Conclusions: This study provides evidence supporting the feasibility and acceptability of a larger-scale RCT investigating osteopathic interventions for individuals presenting with mild psychological symptoms. The preliminary findings suggest potential efficacy in improving mental health outcomes, warranting further investigation. Trial registration NCT05674071, registered 06/01/2023., (© 2024. The Author(s).)

Background: Great apes are a global conservation concern, with anthropogenic pressures threatening their survival. Genetic analysis can be used to assess the effects of reduced population sizes and the effectiveness of conservation measures. In humans, autosomal short tandem repeats (aSTRs) are widely used in population genetics and for forensic individual identification and kinship testing. Traditionally, genotyping is length-based via capillary electrophoresis (CE), but there is an increasing move to direct analysis by massively parallel sequencing (MPS). An example is the ForenSeq DNA Signature Prep Kit, which amplifies multiple loci including 27 aSTRs, prior to sequencing via Illumina technology. Here we assess the applicability of this human-based kit in African great apes. We ask whether cross-species genotyping of the orthologs of these loci can provide both individual and (sub)species identification., Results: The ForenSeq kit was used to amplify and sequence aSTRs in 52 individuals (14 chimpanzees; 4 bonobos; 16 western lowland, 6 eastern lowland, and 12 mountain gorillas). The orthologs of 24/27 human aSTRs amplified across species, and a core set of thirteen loci could be genotyped in all individuals. Genotypes were individually and (sub)species identifying. Both allelic diversity and the power to discriminate (sub)species were greater when considering STR sequences rather than allele lengths. Comparing human and African great-ape STR sequences with an orangutan outgroup showed general conservation of repeat types and allele size ranges. Variation in repeat array structures and a weak relationship with the known phylogeny suggests stochastic origins of mutations giving rise to diverse imperfect repeat arrays. Interruptions within long repeat arrays in African great apes do not appear to reduce allelic diversity., Conclusions: Orthologs of most human aSTRs in the ForenSeq DNA Signature Prep Kit can be analysed in African great apes. Primer redesign would reduce observed variability in amplification across some loci. MPS of the orthologs of human loci provides better resolution for both individual and (sub)species identification in great apes than standard CE-based approaches, and has the further advantage that there is no need to limit the number and size ranges of analysed loci., (© 2024. The Author(s).)

Background: Research consistently finds poorer health and educational outcomes for children who have experienced out-of-home care relative to the general population. Few studies have explored differences between those in care and those in receipt of intervention from social services but not in care. Children receiving social services interventions often experience Adverse Childhood Experiences (ACEs), and deprivation, which are known to negatively impact outcomes. We aimed to estimate the association of different social services interventions with educational outcomes and hospital admissions, while adjusting for ACEs and deprivation., Methods: We linked retrospective, routinely collected administrative records from health, education, and social care to create a cohort via the Secure Anonymised Information Linkage (SAIL) databank in Wales, UK. We analysed data for children and household members (N = 30,439) across four different groups: [1] no social care intervention; [2] children in need but not in care (CIN); [3] children on the Child Protection Register but not in care (CPR); [4] children in care - i.e. removed from the family home and looked after by the local authority (CLA). Our primary outcome was education outcomes at age 16 years. Secondary outcomes were all cause emergency hospital admissions, and emergency admissions for external causes/injuries., Results: Children in receipt of social services intervention were more likely to not attain the expected level upon leaving statutory education at age 16 after adjusting for ACEs and other characteristics (for children who had been in out-of-home care (conditional OR: 1·76, (95%CI) 1·25 - 2·48), in need (2·51, 2·00-3·15) and those at risk (i.e., on the child protection register) (4·04, 2·44 - 6·68). For all-cause emergency admissions, all social care groups were at greater risk compared to children in the general population (children in care (conditional HR: 1·31, 1·01-1·68), children in need (1·62, 1·38 - 1·90), and children at risk (1·51, 1·11 - 2·04)., Conclusions: All groups receiving social service intervention experience poorer educational and health outcomes than peers in the general population. Children who remain with their home parents or caregivers but are identified as 'in need' or 'at risk' by social care practitioners require further research. Integrated support is needed from multiple sectors, including health, educational and social care., (© 2024. The Author(s).)

Background: The aim of this systematic review was to investigate how clinical prediction models compare in terms of their methodological development, validation, and predictive capabilities, for patients with blunt chest trauma presenting to the Emergency Department., Methods: A systematic review was conducted across databases from 1st Jan 2000 until 1st April 2024. Studies were categorised into three types of multivariable prediction research and data extracted regarding methodological issues and the predictive capabilities of each model. Risk of bias and applicability were assessed., Results: 41 studies were included that discussed 22 different models. The most commonly observed study design was a single-centre, retrospective, chart review. The most widely externally validated clinical prediction models with moderate to good discrimination were the Thoracic Trauma Severity Score and the STUMBL Score., Discussion: This review demonstrates that the predictive ability of some of the existing clinical prediction models is acceptable, but high risk of bias and lack of subsequent external validation limits the extensive application of the models. The Thoracic Trauma Severity Score and STUMBL Score demonstrate better predictive accuracy in both development and external validation studies than the other models, but require recalibration and / or update and evaluation of their clinical and cost effectiveness., Review Registration: PROSPERO database ( https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=351638 )., (© 2024. The Author(s).)

Background: Recent trials suggest that more conservative resections such as segmentectomy are non-inferior to more radical approaches. Most segmentectomy can be safely performed using video-assisted thoracoscopic surgery (VATS). The clinical benefits of robotic-assisted thoracoscopic surgery (RATS) remain unclear. We aimed to perform a systematic review evaluating the outcome of open thoracotomy, VATS, and RATS for segmentectomy., Methods: A systematic database search was conducted of original articles exploring the outcome of open versus VATS versus RATS segmentectomy in PubMed, EMBASE and SCOPUS. The primary outcome was 30-day mortality. Secondary outcomes were hospital readmission, air leak, and post-operative pneumonia respectively., Results: 11 studies were included with a total patient sample size of 7280. There were no differences between the three approaches in terms of 30-day mortality, hospital readmission, air leak, and post-operative pneumonia., Conclusion: There are no significant differences between the three approaches in the clinical outcomes measured. While our analysis demonstrates the potential benefits of RATS, it is important to note that the steep learning curve associated with this technique may impact its wider adoption and efficacy in the community. Further randomised control studies are required to compare the short and long terms results of VATS and RATS approaches., (© 2024. The Author(s).)

Background: Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated., Methods: Three-dimensional co-culture models were used to explore adipocyte-EOC interactions. The impact of adipocytes on EOC proliferation, response to therapy and invasive capacity was assessed. Primary adipocytes and omental tissue were isolated from patients with ovarian malignancies and benign ovarian neoplasms. Exosomes were isolated from omentum tissue conditioned media and the effect of omentum-derived exosomes on EOC evaluated. Exosomal microRNA (miRNA) sequencing was used to identify miRNAs abundant in omental exosomes and EOC cells were transfected with highly abundant miRNAs miR-21, let-7b, miR-16 and miR-92a., Results: We demonstrate the capacity of adipocytes to induce an invasive phenotype in EOC populations through driving epithelial-to-mesenchymal transition (EMT). Exosomes secreted by omental tissue of ovarian cancer patients, as well as patients without malignancies, induced proliferation, upregulated EMT markers and reduced response to paclitaxel therapy in EOC cell lines and HGSOC patient samples. Analysis of the omentum-derived exosomes from cancer patients revealed highly abundant miRNAs that included miR-21, let-7b, miR-16 and miR-92a that promoted cancer cell proliferation and protection from chemotherapy when transfected in ovarian cancer cells., Conclusions: These observations highlight the capacity of omental adipocytes to generate a pro-tumorigenic and chemoprotective microenvironment in ovarian cancer and other adipose-related malignancies., (© 2024. The Author(s).)

Background: Natural language processing (NLP) is increasingly being used to extract structured information from unstructured text to assist clinical decision-making and aid healthcare research. The availability of expert-annotated documents for the development and validation of NLP applications is limited. We created synthetic clinical documents to address this, and to validate the Extraction of Epilepsy Clinical Text version 2 (ExECTv2) NLP pipeline., Methods: We created 200 synthetic clinic letters based on hospital outpatient consultations with epilepsy specialists. The letters were double annotated by trained clinicians and researchers according to agreed guidelines. We used the annotation tool, Markup, with an epilepsy concept list based on the Unified Medical Language System ontology. All annotations were reviewed, and a gold standard set of annotations was agreed and used to validate the performance of ExECTv2., Results: The overall inter-annotator agreement (IAA) between the two sets of annotations produced a per item F1 score of 0.73. Validating ExECTv2 using the gold standard gave an overall F1 score of 0.87 per item, and 0.90 per letter., Conclusion: The synthetic letters, annotations, and annotation guidelines have been made freely available. To our knowledge, this is the first publicly available set of annotated epilepsy clinic letters and guidelines that can be used for NLP researchers with minimum epilepsy knowledge. The IAA results show that clinical text annotation tasks are difficult and require a gold standard to be arranged by researcher consensus. The results for ExECTv2, our automated epilepsy NLP pipeline, extracted detailed epilepsy information from unstructured epilepsy letters with more accuracy than human annotators, further confirming the utility of NLP for clinical and research applications., (© 2024. The Author(s).)

Background: The All Wales Diabetes Prevention Programme (AWDPP) is a Wales wide, public health initiative designed to systematically identify adults at risk of developing type 2 diabetes and offer a 30-minute person-centred lifestyle conversation focused on diet and physical activity. An independent formative process and value-based evaluation was commissioned to examine the implementation of this programme in 14 primary care cluster areas across Wales during the initial roll-out., Methods: This evaluation was undertaken to ascertain the views on early implementation of the programme from service users, health care professionals and key stakeholders. The evaluation was informed by the Medical Research Council Framework for Process Evaluation and Wales Prudent Healthcare principles. As part of the value-based assessment, a preliminary cost-consequence analysis was conducted to understand the short-term economic impact of the implementation of the programme., Results: Service users who took part in the evaluation highly valued the programme and nearly half had been previously unaware that they were at risk of developing type 2 diabetes. Delivering the programme presented challenges but there was significant enthusiasm and support from all stakeholders. Overall, the programme was being delivered as intended albeit with evidence of some variation in the application of the programme eligibility criteria., Conclusions: In Wave 1 of the AWDPP roll-out, the intent to deliver the programme in line with Prudent Healthcare was successful and promising in terms of demonstrating value. Opinions expressed by service users suggest the AWDPP matters to them; raising awareness, promoting knowledge and capacity to change behaviours and motivate and raise confidence., (© 2024. The Author(s).)

Background: Veteran residents in Northern Ireland (NI) are an under-researched population. Little is known about their experiences of trauma and mental health management. The overall mental well-being of veterans living in NI may be poorer than other veteran populations, due to the challenges presented by the unique landscape. Understanding their experiences is crucial for providing appropriate, targeted support., Method: Six male veterans, who had received a mental health diagnosis, living in NI and all aged > 40 years participated. Semi-structured interviews, using open-ended questions, were conducted over the telephone. Interpretative phenomenological analysis was used to explore their experiences., Results: Two experiential themes were identified each containing three experiential statements. Statements for 'an extreme lack of' included: lack of mental health literacy/awareness; lack of expectations of official support; lack of a sense of perceived appreciation. Statements for 'an extreme abundance of' included: exacerbated exposure to a range of extreme environments; high levels of ruled-based living; high levels of engaging with informal/local level support., Conclusions: Several experiential statements aligned with existing literature, including having poor mental health literacy and problem recognition, and heavily utilising social support versus formal help-seeking. Some novel findings included bouncing between extreme positive and negative environments which could be as detrimental to mental health as experiencing conflict trauma. Heavy alcohol use was just another rule soldiers followed. Positive help-seeking experiences failed to improve poor opinions of support organisations. Finally, poor self-perceptions connected to military status are pertinent in NI, which seems to fuel self-marginalisation and distrust. A combination of factors likely contributes to many veterans living in NI having poorer mental well-being. Novel findings would benefit from further exploration as understanding how NI veterans interpret their experiences is key to providing adequate healthcare., (© 2024. The Author(s).)

Background: Network theory is largely applied in real-world systems to assess landscape connectivity using empirical or theoretical networks. Empirical networks are usually built from discontinuous individual movement trajectories without knowing the effect of relocation frequency on the assessment of landscape connectivity while theoretical networks generally rely on simple movement rules. We investigated the combined effects of relocation sampling frequency and landscape fragmentation on the assessment of landscape connectivity using simulated trajectories and empirical high-resolution (1 Hz) trajectories of Alpine ibex (Capra ibex). We also quantified the capacity of commonly used theoretical networks to accurately predict landscape connectivity from multiple movement processes., Methods: We simulated forager trajectories from continuous correlated biased random walks in simulated landscapes with three levels of landscape fragmentation. High-resolution ibex trajectories were reconstructed using GPS-enabled multi-sensor biologging data and the dead-reckoning technique. For both simulated and empirical trajectories, we generated spatial networks from regularly resampled trajectories and assessed changes in their topology and information loss depending on the resampling frequency and landscape fragmentation. We finally built commonly used theoretical networks in the same landscapes and compared their predictions to actual connectivity., Results: We demonstrated that an accurate assessment of landscape connectivity can be severely hampered (e.g., up to 66% of undetected visited patches and 29% of spurious links) when the relocation frequency is too coarse compared to the temporal dynamics of animal movement. However, the level of landscape fragmentation and underlying movement processes can both mitigate the effect of relocation sampling frequency. We also showed that network topologies emerging from different movement behaviours and a wide range of landscape fragmentation were complex, and that commonly used theoretical networks accurately predicted only 30-50% of landscape connectivity in such environments., Conclusions: Very high-resolution trajectories were generally necessary to accurately identify complex network topologies and avoid the generation of spurious information on landscape connectivity. New technologies providing such high-resolution datasets over long periods should thus grow in the movement ecology sphere. In addition, commonly used theoretical models should be applied with caution to the study of landscape connectivity in real-world systems as they did not perform well as predictive tools., (© 2024. The Author(s).)

Background: Recent technological advances have resulted in low-cost GPS loggers that are small enough to be used on a range of seabirds, producing accurate location estimates (± 5 m) at sampling intervals as low as 1 s. However, tradeoffs between battery life and sampling frequency result in studies using GPS loggers on flying seabirds yielding locational data at a wide range of sampling intervals. Metrics derived from these data are known to be scale-sensitive, but quantification of these errors is rarely available. Very frequent sampling, coupled with limited movement, can result in measurement error, overestimating movement, but a much more pervasive problem results from sampling at long intervals, which grossly underestimates path lengths., Methods: We use fine-scale (1 Hz) GPS data from a range of albatrosses and petrels to study the effect of sampling interval on metrics derived from the data. The GPS paths were sub-sampled at increasing intervals to show the effect on path length (i.e. ground speed), turning angles, total distance travelled, as well as inferred behavioural states., Results: We show that distances (and per implication ground speeds) are overestimated (4% on average, but up to 20%) at the shortest sampling intervals (1-5 s) and underestimated at longer intervals. The latter bias is greater for more sinuous flights (underestimated by on average 40% when sampling > 1-min intervals) as opposed to straight flight (11%). Although sample sizes were modest, the effect of the bias seemingly varied with species, where species with more sinuous flight modes had larger bias. Sampling intervals also played a large role when inferring behavioural states from path length and turning angles., Conclusions: Location estimates from low-cost GPS loggers are appropriate to study the large-scale movements of seabirds when using coarse sampling intervals, but actual flight distances are underestimated. When inferring behavioural states from path lengths and turning angles, moderate sampling intervals (10-30 min) may provide more stable models, but the accuracy of the inferred behavioural states will depend on the time period associated with specific behaviours. Sampling rates have to be considered when comparing behaviours derived using varying sampling intervals and the use of bias-informed analyses are encouraged., (© 2024. The Author(s).)

Background: Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT)., Methods: We undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019-2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events., Results: At two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported., Conclusion: Staff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned., Trial Registration: ISRCTN13232859 (Registered 16/02/2018)., (© 2024. The Author(s).)

Background: Teachers are recognized as 'key agents' for the delivery of physical activity programs and policies in schools. The aim of our study was to develop and evaluate a tool to assess teachers' capability, opportunity, and motivation to deliver school-based physical activity interventions., Methods: The development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS) involved three phases. In Phase 1, we invited academic experts to participate in a Delphi study to rate, provide recommendations, and achieve consensus on questionnaire items that were based on the Capability, Opportunity, and Motivation Behavior (COM-B) model. Each item was ranked on the degree to which it matched the content of the COM-B model, using a 5-point scale ranging from '1 = Poor match' to '5 = Excellent match'. In Phase 2, we interviewed primary and secondary school teachers using a 'think-aloud' approach to assess their understanding of the items. In Phase 3, teachers (n = 196) completed the COM-PASS to assess structural validity using confirmatory factor analysis (CFA)., Results: Thirty-eight academic experts from 14 countries completed three rounds of the Delphi study. In the first round, items had an average rating score of 4.04, in the second round 4.51, and in the third (final) round 4.78. The final tool included 14 items, which related to the six constructs of the COM-B model: physical capability, psychological capability, physical opportunity, social opportunity, reflective motivation, and automatic motivation. In Phase 2, ten teachers shared their interpretation of COM-PASS via a 20-min interview, which resulted in minor changes. In Phase 3, CFA of the 3-factor model (i.e., capability, opportunity, and motivation) revealed an adequate fit to the data (χ 2  = 122.6, p < .001, CFI = .945, TLI = .924, RMSEA = .066). The internal consistencies of the three subscale scores were acceptable (i.e., capability: α = .75, opportunity: α = .75, motivation: α = .81)., Conclusion: COM-PASS is a valid and reliable tool for assessing teachers' capability, opportunity, and motivation to deliver physical activity interventions in schools. Further studies examining additional psychometric properties of the COM-PASS are warranted., (© 2024. The Author(s).)

Background: Four out of five people living with osteoarthritis (OA) also suffer with at least one other long-term health condition. The complex interaction between OA and multiple long-term conditions (MLTCs) can result in difficulties with self-care, restricted mobility, pain, anxiety, depression and reduced quality of life. The aim of the MulTI-domain Self-management in Older People wiTh OstEoarthritis and Multi-Morbidities (TIPTOE) trial is to evaluate the clinical and cost-effectiveness of the Living Well self-management support intervention, co-designed with people living with OA, integrated into usual care, in comparison to usual care alone., Methods: TIPTOE is a multi-centre, two-arm, individually randomised controlled trial where 824 individuals over 65 years old with knee and/or hip joint pain from their OA affected joint and at least one other long-term health condition will be randomised to receive either the Living Well Self-Management support intervention or usual care. Eligible participants can self-refer onto the trial via a website or be referred via NHS services across Wales and England. Those randomised to receive the Living Well support intervention will be offered up to six one-to-one coaching sessions with a TIPTOE-trained healthcare practitioner and a co-designed book. Participants will be encouraged to nominate a support person to assist them throughout the study. All participants will complete a series of self-reported outcome measures at baseline and 6- and 12-month follow-up. The primary outcome is symptoms and quality of life as assessed by the Musculoskeletal Health Questionnaire (MSK-HQ). Routine data will be used to evaluate health resource use. A mixed methods process evaluation will be conducted alongside the trial to inform future implementation should the TIPTOE intervention be found both clinically and cost-effective. An embedded 'Study Within A Project' (SWAP) will explore and address barriers to the inclusion of under-served patient groups (e.g. oldest old, low socioeconomic groups, ethnic groups)., Discussion: TIPTOE will evaluate the clinical and cost-effectiveness of a co-designed, living well personalised self-management support intervention for older individuals with knee and/or hip OA and MLTCs. The trial has been designed to maximise inclusivity and access., Trial Registration: ISRCTN 16024745 . Registered on October 16, 2023., (© 2024. The Author(s).)

Background: Physical, affective and behavioural symptoms associated with the menstrual cycle are commonplace. Adolescents with problematic symptoms have reported a negative impact on school attendance, behaviour and participation in physical activity. In the United Kingdom, evidence suggests that menstrual health education delivered by teachers focusses on menstrual cycle biology as opposed to management of menstruation and menstrual cycle related symptoms. Through obtaining the pupil voice, this study aimed to understand young people's perceptions and experiences of menstrual education in schools and their experiences of menstruating whilst at school, including within Physical Education., Methods: To address the aims, a qualitative descriptive study was conducted. Nine focus groups with female pupils (n = 48; ages 10-15 years) were completed across six school locations in England and Wales, including primary and secondary schools. A range of elements relating to the menstrual cycle, education at school and PE were discussed by pupils., Results: Four main themes were developed (a) Education preferences, (b) Period positive environments, (c) Personal experiences and (d) Impact on school. Similarities were reflected across focus groups in terms of current (lacking) education, lesson style and preferences, comfort of conversations, lack of school support and impact on school and PE., Conclusion: The findings highlight the lack of menstrual education received and subsequent impact of menstruation and menstrual-related symptoms in school and PE. The abundance of information requested by pupils highlights the deficit in understanding about how to manage periods in school and remain engaged in physical activity. Schools can utilise information from the current study to; create period positive environments; consider lesson content and format; and explore how to support girls to stay physically active in PE., (© 2024. The Author(s).)

Background: Iron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments., Results: The optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM - 1 s - 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg., Conclusions: This study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application., (© 2024. The Author(s).)

Background: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease., Methods: Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma)., Results: Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC., Conclusions: This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence., (© 2024. The Author(s).)

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD).The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD., (© 2024. The Author(s).)

The application of supervised machine learning methods to identify behavioural modes from inertial measurements of bio-loggers has become a standard tool in behavioural ecology. Several design choices can affect the accuracy of identifying the behavioural modes. One such choice is the inclusion or exclusion of segments consisting of more than a single behaviour (mixed segments) in the machine learning model training data. Currently, the common practice is to ignore such segments during model training. In this paper we tested the hypothesis that including mixed segments in model training will improve accuracy, as the model would perform better in identifying them in the test data. We test this hypothesis using a series of data simulations on four datasets of accelerometer data coupled with behaviour observations, obtained from four study species (Damaraland mole-rats, meerkats, olive baboons, polar bears). Results show that when a substantial proportion of the test data are mixed behaviour segments (above ~ 10%), including mixed segments in machine learning model training improves the accuracy of classification. These results were consistent across the four study species, and robust to changes in segment length, sample size, and degree of mixture within the mixed segments. However, we also find that in some cases (particularly in baboons) models trained with mixed segments show reduced accuracy in classifying test data containing only single behaviour (pure) segments, compared to models trained without mixed segments. Based on these results, we recommend that when the classification model is expected to deal with a substantial proportion of mixed behaviour segments (> 10%), it is beneficial to include them in model training, otherwise, it is unnecessary but also not harmful. The exception is when there is a basis to assume that the training data contains a higher rate of mixed segments than the actual (unobserved) data to be classified-such a situation may occur particularly when training data are collected in captivity and used to classify data from the wild. In this case, excess inclusion of mixed segments in training data should probably be avoided., (© 2024. The Author(s).)

Background: Understanding and treating the harm caused by gambling is a growing international psychiatric and public health challenge. Treatment of gambling harm may involve psychological and pharmacological intervention, in conjunction with peer support. This scoping review was conducted to identify, for the first time, the characteristics and extent of United Kingdom (UK) based gambling treatment research. We reviewed studies conducted among people seeking treatment for disordered or harmful gambling in the UK, the settings, research designs, and outcome measures used, and to identify any treatment research gaps., Methods: Systematic searches of PsycInfo, PsycArticles, Scopus, PubMed, and Web of Science databases were carried out for gambling treatment research or evaluation studies conducted in the UK. Studies were included if they evaluated the effectiveness of an intervention or treatment designed to improve symptoms of harmful or problematic gambling, reported outcomes of interventions on treatment adherence, gambling symptoms, or behaviours using standardised measures, were conducted in the UK, and were published since 2000., Results: Eight studies met the inclusion criteria. Four were retrospective chart reviews, two were single-participant case reports, one described a retrospective case series, and one employed a cross-sectional design. None used an experimental design., Conclusion: The limited number of studies included in this review highlights a relative paucity of gambling treatment research conducted in UK settings. Further work should seek to identify potential barriers and obstacles to conducting gambling treatment research in the UK., (© 2024. The Author(s).)

Exposure to indoor air pollutants (IAP) has increased recently, with people spending more time indoors (i.e. homes, offices, schools and transportation). Increased exposures of IAP on a healthy population are poorly understood, and those with allergic respiratory conditions even less so. The objective of this study, therefore, was to implement a well-characterised in vitro model of the human alveolar epithelial barrier (A549 + PMA differentiated THP-1 incubated with and without IL-13, IL-5 and IL-4) to determine the effects of a standardised indoor particulate (NIST 2583) on both a healthy lung model and one modelling a type-II (stimulated with IL-13, IL-5 and IL-4) inflammatory response (such as asthma).Using concentrations from the literature, and an environmentally appropriate exposure we investigated 232, 464 and 608ng/cm 2 of NIST 2583 respectively. Membrane integrity (blue dextran), viability (trypan blue), genotoxicity (micronucleus (Mn) assay) and (pro-)/(anti-)inflammatory effects (IL-6, IL-8, IL-33, IL-10) were then assessed 24 h post exposure to both models. Models were exposed using a physiologically relevant aerosolisation method (VitroCell Cloud 12 exposure system).No changes in Mn frequency or membrane integrity in either model were noted when exposed to any of the tested concentrations of NIST 2583. A significant decrease (p < 0.05) in cell viability at the highest concentration was observed in the healthy model. Whilst cell viability in the "inflamed" model was decreased at the lower concentrations (significantly (p < 0.05) after 464ng/cm 2 ). A significant reduction (p < 0.05) in IL-10 and a significant increase in IL-33 was seen after 24 h exposure to NIST 2583 (464, 608ng/cm 2 ) in the "inflamed" model.Collectively, the results indicate the potential for IAP to cause the onset of a type II response as well as exacerbating pre-existing allergic conditions. Furthermore, the data imposes the importance of considering unhealthy individuals when investigating the potential health effects of IAP. It also highlights that even in a healthy population these particles have the potential to induce this type II response and initiate an immune response following exposure to IAP., (© 2024. The Author(s).)

Objective: Distribution of take-home naloxone (THN) by emergency services may increase access to THN and reduce deaths and morbidity from opioid overdose. As part of a feasibility study for a randomised controlled trial (RCT) of distribution of THN kits and education within ambulance services and Emergency Departments (EDs), we used qualitative methods to explore key stakeholders' perceptions of feasibility and acceptability of delivering the trial., Methods: We undertook semi-structured interviews and focus groups with 26 people who use opioids and with 20 paramedics and ED staff from two intervention sites between 2019 and 2021. Interviews and focus groups were recorded, transcribed verbatim and analysed using Framework Analysis., Results: People using opioids reported high awareness of overdose management, including personal experience of THN use. Staff perceived emergency service provision of THN as a low-cost, low-risk intervention with potential to reduce mortality, morbidity and health service use. Staff understood the trial aims and considered it compatible with their work. All participants supported widening access to THN but reported limited trial recruitment opportunities partly due to difficulties in consenting patients during overdose. Procedural problems, restrictive recruitment protocols, limited staff buy-in and patients already owning THN limited trial recruitment. Determining trial effectiveness was challenging due to high levels of alternative community provision of THN., Conclusions: Distribution of THN in emergency settings was considered feasible and acceptable for stakeholders but an RCT to establish the effectiveness of THN delivery is unlikely to generate further useful evidence due to difficulties in recruiting patients and assessing benefits., (© 2024. The Author(s).)

Introduction: Older individuals and, in particular, individuals at risk of recurrent stroke, may be susceptible to thrombosis when participating in exercise, however, this aspect has not been well investigated., Methods: Clot microstructure and conventional markers of thrombotic risk were determined in twenty lacunar stroke patients and fifteen healthy age-matched controls before, immediately after and 1 h after a bout of moderate intensity cycling exercise. Data were analyzed using a linear mixed model approach., Results: At rest, clot microstructure (1.69 ± 0.07 vs. 1.64 ± 0.05, corresponding to a difference of ~ 50% in normalized clot mass; p = 0.009) and thrombocyte count (73%; p < 0.0001) were higher, and activated partial thromboplastin time was lower (18%; p = 0.0001) in stroke patients compared to age-matched controls. Acute exercise increased thrombogenic markers similarly in the two groups: incipient clot microstructure (1.69 ± 0.07 vs. 1.74 ± 0.05; p = 0.0004 and 1.64 ± 0.05 vs. 1.71 ± 0.04; p < 0.0001, for stroke and controls respectively), plasma fibrinogen (12%; p < 0.0001 and 18%; p < 0.0001, for stroke and controls respectively) and the combined coagulation factors II, VII and X (p = 0.0001 and p < 0.0001, for stroke and controls respectively)., Conclusion: The results show that exercise transiently increases the risk of blood clot formation in both stroke patients and controls, however, due to the higher baseline thrombogenicity in stroke patients, the post exercise risk of forming blood clots may be higher in this group., Trial Registration: Registered at ClinicalTrials.gov (NCT03635177)., (© 2024. The Author(s).)

The Environmental Evidence for the Future (EEF) Initiative emerged in response to the challenges and opportunities presented by the UK's decision to leave the European Union and its associated Environmental Frameworks. The Natural Environment Research Council (NERC), working closely with the Collaboration for Environmental Evidence (CEE) and UK stakeholders, developed the initiative to identify and address crucial evidence gaps, offering a long-term vision for environmental policy and sustainability. The EEF Initiative progressed through three stages: strategic priority identification, NERC panel award selection, and the production of Systematic Maps of existing evidence. The first stage involved collaborative workshops across the UK to identify key knowledge gaps in environmental science. The subsequent prioritisation resulted in 65 challenges across 10 thematic areas. The second stage saw NERC initiating, with CEE support, an open call for research proposals emphasising the use of evidence synthesis methodology. The selection process, balancing topic importance and applicant expertise, led to funding for five projects. The final stage involved the production of Systematic Maps of existing evidence based on the CEE Guidelines and Standards, providing a structured overview of existing literature on specific topics. The EEF Initiative demonstrated effective collaboration between UKRI (NERC), an independent non-profit (CEE), academia, and government agencies, addressing critical environmental challenges through rigorous evidence synthesis methodologies. The programme enhanced understanding and utilisation of these methodologies within the research community. Key lessons include the importance of inclusive priority-setting, differentiation between broad policy questions and specific Systematic Map questions, recognition of the value of Systematic Maps, and the role of experience in evidence synthesis teams. As policymakers and researchers navigate environmental policies in a resource-constrained environment, the EEF Initiative highlights the cost-effectiveness and efficiency of systematic mapping and review processes for evidence-based decision-making. The success of funding through NERC sets a precedent for future thematic evidence focused programmes, emphasising the need for continued support in developing synthesis skills among researchers and encouraging direct government commissions for targeted and responsive evidence. The EEF Initiative serves as a model for effective collaboration, providing valuable insights into addressing evidence gaps and shaping evidence-based policymaking in an ever-evolving environmental landscape., (© 2024. The Author(s).)

Background: Forensic psychiatry is often associated with long admissions and has a high cost of care. There is little known about factors influencing length of stay (LOS), and no previous systematic review has synthesised the available data. This paper aims to identify factors influencing the LOS in forensic psychiatry hospitals to inform care and interventions that may reduce the length of admissions., Methodology: A systematic review was conducted by searching major databases, including PubMed, EMBASE and PsycInfo, from inception until May 2022. Observational studies conducted in forensic hospitals that examined associations between variables of interest and LOS were included. Following data extraction, the Newcastle‒Ottawa Scale was used for quality appraisal. No meta-analysis was conducted due to heterogeneity of information; a quantitative measure to assess the strength of evidence was developed and reported., Results: A total of 28 studies met the inclusion criteria out of 1606 citations. A detailed quantitative synthesis was performed using robust criteria. Having committed homicide/attempted homicide, a criminal legal status with restrictions, and a diagnosis of schizophrenia-spectrum disorders were all associated with longer LOS. Higher Global Assessment of Functioning (GAF) scores were associated with a shorter LOS., Conclusion: High-quality research examining factors associated with LOS in forensic psychiatry is lacking, and studies are heterogeneous. No modifiable characteristics were identified, and thus, practice recommendations were not made. There is an increasing necessity to understand the factors associated with longer admissions to inform care and increase success in reintegration and rehabilitation. This paper provides recommendations for future research., (© 2024. The Author(s).)

Background: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo., Results: The attenuated tumour targeting Salmonella typhimurium SL7207 strain was modified to carry chromosomally integrated shRNA expression cassettes at the xylA locus. The colorectal cancer cell lines SW480, HCT116 and breast cancer cell line MCF7 were used to demonstrate the ability of these modified strains to perform intracellular infection and deliver effective RNA and protein knockdown of the target gene c-Myc. In vivo therapeutic efficacy was demonstrated using the Lgr5creER T2 Apc flx/flx and BlgCreBrca2 flx/fl p53 flx/flx orthotopic immunocompetent mouse models of colorectal and breast cancer, respectively. In vitro co-cultures of breast and colorectal cancer cell lines with modified SL7207 demonstrated a significant 50-95% (P < 0.01) reduction in RNA and protein expression with SL7207/c-Myc targeted strains. In vivo, following establishment of tumour tissue, a single intra-peritoneal administration of 1 × 10 6 CFU of SL7207/c-Myc was sufficient to permit tumour colonisation and significantly extend survival with no overt toxicity in control animals., Conclusions: In summary we have demonstrated that tumour tropic bacteria can be modified to safely deliver therapeutic levels of gene knockdown. This technology has the potential to specifically target primary and secondary solid tumours with personalised therapeutic payloads, providing new multi-cancer detection and treatment options with minimal off-target effects. Further understanding of the tropism mechanisms and impact on host immunity and microbiome is required to progress to clinical translation., (© 2024. The Author(s).)

Background: The geographic distribution and host-parasite interaction networks of Sarcocystis spp. in small mammals in eastern Asia remain incompletely known., Methods: Experimental infections, morphological and molecular characterizations were used for discrimination of a new Sarcocystis species isolated from colubrid snakes and small mammals collected in Thailand, Borneo and China., Results: We identified a new species, Sarcocystis muricoelognathis sp. nov., that features a relatively wide geographic distribution and infects both commensal and forest-inhabiting intermediate hosts. Sarcocystis sporocysts collected from rat snakes (Coelognathus radiatus, C. flavolineatus) in Thailand induced development of sarcocysts in experimental SD rats showing a type 10a cyst wall ultrastructure that was identical with those found in Rattus norvegicus from China and the forest rat Maxomys whiteheadi in Borneo. Its cystozoites had equal sizes in all intermediate hosts and locations, while sporocysts and cystozoites were distinct from other Sarcocystis species. Partial 28S rRNA sequences of S. muricoelognathis from M. whiteheadi were largely identical to those from R. norvegicus in China but distinct from newly sequenced Sarcocystis zuoi. The phylogeny of the nuclear 18S rRNA gene placed S. muricoelognathis within the so-called S. zuoi complex, including Sarcocystis attenuati, S. kani, S. scandentiborneensis and S. zuoi, while the latter clustered with the new species. However, the phylogeny of the ITS1-region confirmed the distinction between S. muricoelognathis and S. zuoi. Moreover, all three gene trees suggested that an isolate previously addressed as S. zuoi from Thailand (KU341120) is conspecific with S. muricoelognathis. Partial mitochondrial cox1 sequences of S. muricoelognathis were almost identical with those from other members of the group suggesting a shared, recent ancestry. Additionally, we isolated two partial 28S rRNA Sarcocystis sequences from Low's squirrel Sundasciurus lowii that clustered with those of S. scandentiborneensis from treeshews., Conclusions: Our results provide strong evidence of broad geographic distributions of rodent-associated Sarcocystis and host shifts between commensal and forest small mammal species, even if the known host associations remain likely only snapshots of the true associations., (© 2024. The Author(s).)

Background: Acquired brain injury (ABI) and other chronic conditions are placing unprecedented pressure on healthcare systems. In the UK, 1.3 million people live with the effects of brain injury, costing the UK economy approximately £15 billion per year. As a result, there is an urgent need to adapt existing healthcare delivery to meet increasing current and future demands. A focus on wellbeing may provide an innovative opportunity to reduce the pressure on healthcare services while also supporting patients to live more meaningful lives. The overarching aims of the study are as follows: (1) evaluate the feasibility of conducting a positive psychotherapy intervention for individuals with ABI and (2) ascertain under what conditions such an intervention would merit a fully powered randomised controlled trial (RCT) compared to a standard control group (TAU)., Methods and Analysis: A randomised, two-arm feasibility trial involving allocation of patients to either a treatment group (positive psychotherapy) or control group (treatment as usual) group, according to a 1:1 ratio. A total of 60 participants at three sites will be recruited including 20 participants at each site. Assessments will be conducted at baseline, on completion of the 8-week intervention and 3 months following completion. These will include a range of questionnaire-based measures, psychophysiology and qualitative outcomes focusing on feasibility outcomes and participant experience. This study has been approved by the Wales Research Ethics Committee (IRAS project ID: 271,251, REC reference: 19/WA/0336)., Discussion: This study will be the first to examine the feasibility of an innovative, holistic positive psychotherapy intervention for people living with ABI, focused on individual, collective and planetary wellbeing, and will enable us to determine whether to proceed to a full randomised controlled trial., Trial Registration: ISRCTN12690685 , registered 11th November 2020., (© 2024. The Author(s).)

Introduction: People with Xeroderma Pigmentosum (XP) have a heightened sensitivity to ultraviolet radiation (UVR) and are advised to wear photoprotective clothing including a visor covering the face and neck. Photoprotective visors are homemade and predominately worn by children with decreasing frequency as age increases. To improve upon the current design and efficacy we were tasked with developing a prototype visor to meet patients' needs., Methods: Adopting a codesign methodology, patients' experiences of wearing a visor and patient and carer views of emerging prototypes were explored during interviews. A thematic analysis was conducted in parallel with data collection and themes were interpreted into design cues; desirable attributes of a visor that would counteract the negative user experiences and meet the requirements described by patients and carers. The design cues guided the iterative development of prototypes by academic engineers., Results: Twenty-four interviews were conducted with patients and carers. Thematic analysis resulted in the following five themes: Being safe from UVR exposure; self-consciousness; temperature effects; acoustic difficulties; and material properties. The following design cues were developed from the themes respectively; materials and design with high UVR protection; ability to customise with own headwear; ventilation to reduce steaming up; acoustic functionality to enable hearing and speech; foldable, portable, and easy to put on and take off., Conclusions: It is important to understand people's experiences of using medical devices to improve their safety, efficiency and user satisfaction. The user experience themes and design cues, informed the iterative development of low fidelity visor prototypes as part of a codesign process. These design cues and responses to the prototypes are guiding commercial manufacturing and regulatory approval. The visor can then be prescribed to patients, providing an equitable service of care., (© 2024. The Author(s).)

Background: Nurses play an important role in interprofessional pharmaceutical care. Curricula related to pharmaceutical care, however, vary a lot. Mapping the presence of pharmaceutical care related domains and competences in nurse educational programs can lead to a better understanding of the extent to which curricula fit expectations of the labour market. The aim of this study was to describe 1) the presence of pharmaceutical care oriented content in nursing curricula at different educational levels and 2) nursing students' perceived readiness to provide nurse pharmaceutical care in practice., Methods: A quantitative cross-sectional survey design was used. Nursing schools in 14 European countries offering educational programs for levels 4-7 students were approached between January and April 2021. Through an online survey final year students had to indicate to what extent pharmaceutical care topics were present in their curriculum., Results: A total of 1807 students participated, of whom 8% had level 4-5, 80% level 6, 12% level 7. Up to 84% of the students indicated that pharmaceutical care content was insufficiently addressed in their curriculum. On average 14% [range 0-30] felt sufficiently prepared to achieve the required pharmaceutical care competences in practice. In level 5 curricula more pharmaceutical care domains were absent compared with other levels., Conclusions: Although several pharmaceutical care related courses are present in current curricula of level 4-7 nurses, its embedding should be extended. Too many students perceive an insufficient preparation to achieve pharmaceutical care competences required in practice. Existing gaps in pharmaceutical care should be addressed to offer more thoroughly prepared nurses to the labour market., (© 2024. The Author(s).)

Background: Healthcare system data (HSD) are increasingly used in clinical trials, augmenting or replacing traditional methods of collecting outcome data. This study, PRIMORANT, set out to identify, in the UK context, issues to be considered before the decision to use HSD for outcome data in a clinical trial is finalised, a methodological question prioritised by the clinical trials community., Methods: The PRIMORANT study had three phases. First, an initial workshop was held to scope the issues faced by trialists when considering whether to use HSDs for trial outcomes. Second, a consultation exercise was undertaken with clinical trials unit (CTU) staff, trialists, methodologists, clinicians, funding panels and data providers. Third, a final discussion workshop was held, at which the results of the consultation were fed back, case studies presented, and issues considered in small breakout groups., Results: Key topics included in the consultation process were the validity of outcome data, timeliness of data capture, internal pilots, data-sharing, practical issues, and decision-making. A majority of consultation respondents (n = 78, 95%) considered the development of guidance for trialists to be feasible. Guidance was developed following the discussion workshop, for the five broad areas of terminology, feasibility, internal pilots, onward data sharing, and data archiving., Conclusions: We provide guidance to inform decisions about whether or not to use HSDs for outcomes, and if so, to assist trialists in working with registries and other HSD providers to improve the design and delivery of trials., (© 2024. The Author(s).)

Foraging is a key driver of animal movement patterns, with specific challenges for predators which must search for mobile prey. These patterns are increasingly impacted by global changes, principally in land use and climate. Understanding the degree of flexibility in predator foraging and social strategies is pertinent to wildlife conservation under global change, including potential top-down effects on wider ecosystems. Here we propose key future research directions to better understand foraging strategies and social flexibility in predators. In particular, rapid continued advances in biologging technology are helping to record and understand dynamic behavioural and movement responses of animals to environmental changes, and their energetic consequences. Data collection can be optimised by calibrating behavioural interpretation methods in captive settings and strategic tagging decisions within and between social groups. Importantly, many species' social systems are increasingly being found to be more flexible than originally described in the literature, which may be more readily detectable through biologging approaches than behavioural observation. Integrating the effects of the physical landscape and biotic interactions will be key to explaining and predicting animal movements and energetic balance in a changing world., (© 2024. The Author(s).)

Background: The number of older people in prison is growing. As a result, there will also be more prisoners suffering from dementia. The support and management of this population is likely to present multiple challenges to the prison system., Objectives: To examine the published literature on the care and supervision of people living in prison with dementia and on transitioning into the community; to identify good practice and recommendations that might inform the development of prison dementia care pathways., Methods: A scoping review methodology was adopted with reporting guided by the PRISMA extension for scoping reviews checklist and explanation., Results: Sixty-seven papers were included. Most of these were from high income countries, with the majority from the United Kingdom (n = 34), followed by the United States (n = 15), and Australia (n = 12). One further paper was from India., Discussion: The literature indicated that there were difficulties across the prison system for people with dementia along the pathway from reception to release and resettlement. These touched upon all aspects of prison life and its environment, including health and social care. A lack of resources and national and regional policies were identified as important barriers, although a number of solutions were also identified in the literature, including the development of locally tailored policies and increased collaboration with the voluntary sector., Conclusion: To our knowledge, this is the most comprehensive and inclusive review of the literature on dementia care pathways in prison to date. It has identified a number of important areas of concern and opportunities for future research across the prison system, and its operations. This will hopefully lead to the identification or adaptation of interventions to be implemented and evaluated, and facilitate the development of dementia care pathways in prisons., (© 2024. The Author(s).)

Objectives: To determine the feasibility and acceptability of implementing the Mini-AFTERc intervention., Design: Non-randomised cluster-controlled pilot trial., Setting: Four NHS out-patient breast cancer centres in Scotland., Participants: Ninety-two women who had successfully completed primary treatment for breast cancer were screened for moderate levels of fear of cancer recurrence (FCR). Forty-five were eligible (17 intervention and 28 control) and 34 completed 3-month follow-up (15 intervention and 21 control)., Intervention: Mini-AFTERc, a single brief (30 min) structured telephone discussion with a specialist breast cancer nurse (SBCN) trained to target the antecedents of FCR., Outcomes: Feasibility and acceptability of Mini-AFTERc and the study design were assessed via recruitment, consent, retention rates, patient outcomes (measured at baseline, 2, 4, and 12 weeks), and post-study interviews with participants and SBCNs, which were guided by Normalisation Process Theory., Results: Mini-AFTERc was acceptable to patients and SBCNs. SBCNs believe the implementation of Mini-AFTERc to be feasible and an extension of discussions that already happen routinely. SBCNs believe delivery, however, at the scale required would be challenging given current competing demands for their time. Recruitment was impacted by variability in the follow-up practices of cancer centres and COVID-19 lockdown. Consent and follow-up procedures worked well, and retention rates were high., Conclusions: The study provided invaluable information about the potential challenges and solutions for testing the Mini-AFTERc intervention more widely where limiting high FCR levels is an important goal following recovery from primary breast cancer treatment., Trial Registration: ClinicalTrials.gov, NCT0376382 . Registered on 4 December 2018., (© 2024. The Author(s).)

Objective: Frailty develops as a result of age-related decline in many physiological systems and is associated with increased vulnerability to adverse outcomes following thoracic surgery. We prospectively tested our hypothesis that pre-operative pulmonary rehabilitation (Prehab) improves frailty, as suggested by a frailty index > 3 (FI > 3) and fitness, and thereby reduces the risk of post-surgical complications and death in vulnerable elderly lung cancer patients., Methods: 221 surgical patients, 80 with FI > 3 vs. 141 patients with FI < 3, following Prehab proceeded to surgery. Their Frailty index (FI), dyspnoea scores, performance status (PS), level of activity (LOA) and six-minute walk test (6MWT) prior to and following Prehab were determined. The post-operative length of hospital stay (LOHS), complications, mortality and mid-term survival at 1100 days were compared. Similarly, outcomes for elderly patient ≥ 70 years with FI > 3 (≥ 70,FI > 3) were compared with younger patients < 70 years with FI ≤ 3 (< 70,FI ≤ 3)., Results: Patients with FI > 3 were significantly older, had lower 6MWT and higher thoracoscores hence, 82.5% of patients with FI > 3 vs. 33.3% (p = 0.02) with FI ≤ 3 were considered high risk for surgery and postoperative adverse events. With Prehab there was significant improvement in the FI, dyspnoea scores, PS, LOA and 6MWT. Following surgery, there were no differences in major complication rates (8.8% vs. 9.2% p = ns); LOHS median (IQR) [7 (6.8) vs. 8 (5.5) days]; mortality at 30-days (3.7% vs. 0.7%, p = ns); 90-days (6.3% vs. 2.8%, p = ns) and 1-year survival (81.1% vs. 83.7% p = ns). Survival at 1100 days was (63.2% vs. 71.1%, p = 0.19). Likewise, 87.7% elderly ≥ 70,FI > 3 patients were considered high-risk for surgery and postoperative adverse events vs. 35.1% younger patients < 70,FI ≤ 3 (p = 0.0001). Following Prehab and surgery, there were no significant differences in complications, LOHS, mortality at 365 days between the two groups. Survival at 1100 days for ≥ 70,FI > 3 was 55.2% vs. 79.96% for < 70,FI ≤ 3; (p = 0,01)., Conclusion: Our study suggests that Prehab optimises vulnerable high-risk elderly lung cancer patients with frailty allowing them to undergo surgery with outcomes of post-surgical complications, LOHS and mortality at 365 days no different to patients with no frailty. However, mid-term survival was lower for elderly patients with frailty., (© 2023. The Author(s).)

A cornerstone of asthma management is maintaining physical activity (PA), but this may lead to increased exposure to, and deeper inhalation of, pollutants. Furthermore, children and adolescents may be more susceptible to the deleterious impacts of such exposures. Despite the recent air quality campaigns and media coverage surrounding the dangers of air pollution to respiratory health, few target children and their understanding of such issues.Using semi structured interviews, understanding of PA, air pollution and their interaction was explored with 25 youth aged 7-17 years. Utilising NVIVO 12 software, an atheoretical, inductive thematic analysis was conducted to identify key themes which were subsequently presented as pen profiles with the number of common responses within a theme indicative of its strength.The majority (88%) of youth's indicated traffic-related air pollution and global manufacturing as key sources of air pollution. Whilst all youths were aware of outdoor pollution, only 52% were aware of indoor air pollutants, of which 62% had asthma. Despite some uncertainty, all youths described pollution in a negative fashion, with 52% linking air pollution to undesirable effects on health, specifically respiratory health. PA in a polluted area was thought to be more dangerous than beneficial by 44%, although 24% suggested the benefits of PA would outweigh any detriment from pollution.Youth are aware of, and potentially compensate for, the interaction between air pollution and PA. Strategies are needed to allow youth to make more informed decisions regarding how to promote PA whilst minimising exposure to air pollution., (© 2023. The Author(s).)

Background: The EVITE Immunity study investigated the effects of shielding Clinically Extremely Vulnerable (CEV) people during the COVID-19 pandemic on health outcomes and healthcare costs in Wales, United Kingdom, to help prepare for future pandemics. Shielding was intended to protect those at highest risk of serious harm from COVID-19. We report the cost of implementing shielding in Wales., Methods: The number of people shielding was extracted from the Secure Anonymised Information Linkage Databank. Resources supporting shielding between March and June 2020 were mapped using published reports, web pages, freedom of information requests to Welsh Government and personal communications (e.g. with the office of the Chief Medical Officer for Wales)., Results: At the beginning of shielding, 117,415 people were on the shielding list. The total additional cost to support those advised to stay home during the initial 14 weeks of the pandemic was £13,307,654 (£113 per person shielded). This included the new resources required to compile the shielding list, inform CEV people of the shielding intervention and provide medicine and food deliveries. The list was adjusted weekly over the 3-month period (130,000 people identified by June 2020). Therefore the cost per person shielded lies between £102 and £113 per person., Conclusion: This is the first evaluation of the cost of the measures put in place to support those identified to shield in Wales. However, no data on opportunity cost was available. The true costs of shielding including its budget impact and opportunity costs need to be investigated to decide whether shielding is a worthwhile policy for future health emergencies., (© 2023. The Author(s).)

Background: During the COVID-19 pandemic, clinical services were severely disrupted, restricted, or withdrawn across the country. People living with Inflammatory Bowel Disease (IBD) - an auto-immune disorder for which medical treatment often results in immunosuppression, thus requiring regular monitoring-may have struggled to access clinical support. As part of a larger qualitative study, we investigated experiences of access to clinical services during the pandemic, and patient concerns about and preferences for services in the future., Methods: This exploratory qualitative study used semi-structured interviews to explore participants' experiences of clinical services across the UK during the pandemic. All data were collected remotely (March - May 2021) using online video-calling platforms or by telephone. Audio files were transcribed professionally and anonymised for analysis. Data were analysed using thematic analysis., Results: Of the eight themes found across all data, four related specifically to accessing GP, local (district) hospital, and specialist (tertiary) referral services for IBD: 1) The Risk of Attending Hospital; 2) Missing Routine Monitoring or Treatment; 3) Accessing Care as Needed, and 4) Remote Access and The Future., Conclusions: Our findings support other studies reporting changes in use of health services, and concerns about future remote access methods. Maintenance of IBD services in some form is essential throughout crisis periods; newly diagnosed patients need additional support; future dependence on IBD services could be reduced through use of treatment / self-management plans. As the NHS digitalises it's future services, the mode of appointment-remote (telephone, video call), or in-person - needs to be flexible and suit the patient., (© 2023. The Author(s).)

Understanding the processes that determine how animals allocate time to space is a major challenge, although it is acknowledged that summed animal movement pathways over time must define space-time use. The critical question is then, what processes structure these pathways? Following the idea that turns within pathways might be based on environmentally determined decisions, we equipped Arabian oryx with head- and body-mounted tags to determine how they orientated their heads - which we posit is indicative of them assessing the environment - in relation to their movement paths, to investigate the role of environment scanning in path tortuosity. After simulating predators to verify that oryx look directly at objects of interest, we recorded that, during routine movement, > 60% of all turns in the animals' paths, before being executed, were preceded by a change in head heading that was not immediately mirrored by the body heading: The path turn angle (as indicated by the body heading) correlated with a prior change in head heading (with head heading being mirrored by subsequent turns in the path) twenty-one times more than when path turns occurred due to the animals adopting a body heading that went in the opposite direction to the change in head heading. Although we could not determine what the objects of interest were, and therefore the proposed reasons for turning, we suggest that this reflects the use of cephalic senses to detect advantageous environmental features (e.g. food) or to detect detrimental features (e.g. predators). The results of our pilot study suggest how turns might emerge in animal pathways and we propose that examination of points of inflection in highly resolved animal paths could represent decisions in landscapes and their examination could enhance our understanding of how animal pathways are structured., (© 2023. The Author(s).)

Background: To support proliferation and survival within a challenging microenvironment, cancer cells must reprogramme their metabolism. As such, targeting cancer cell metabolism is a promising therapeutic avenue. However, identifying tractable nodes of metabolic vulnerability in cancer cells is challenging due to their metabolic plasticity. Identification of effective treatment combinations to counter this is an active area of research. Aspirin has a well-established role in cancer prevention, particularly in colorectal cancer (CRC), although the mechanisms are not fully understood., Methods: We generated a model to investigate the impact of long-term (52 weeks) aspirin exposure on CRC cells, which has allowed us comprehensively characterise the metabolic impact of long-term aspirin exposure (2-4mM for 52 weeks) using proteomics, Seahorse Extracellular Flux Analysis and Stable Isotope Labelling (SIL). Using this information, we were able to identify nodes of metabolic vulnerability for further targeting, investigating the impact of combining aspirin with metabolic inhibitors in vitro and in vivo., Results: We show that aspirin regulates several enzymes and transporters of central carbon metabolism and results in a reduction in glutaminolysis and a concomitant increase in glucose metabolism, demonstrating reprogramming of nutrient utilisation. We show that aspirin causes likely compensatory changes that render the cells sensitive to the glutaminase 1 (GLS1) inhibitor-CB-839. Of note given the clinical interest, treatment with CB-839 alone had little effect on CRC cell growth or survival. However, in combination with aspirin, CB-839 inhibited CRC cell proliferation and induced apoptosis in vitro and, importantly, reduced crypt proliferation in Apc fl/fl mice in vivo., Conclusions: Together, these results show that aspirin leads to significant metabolic reprogramming in colorectal cancer cells and raises the possibility that aspirin could significantly increase the efficacy of metabolic cancer therapies in CRC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Socioeconomic differences in the impact of alcohol consumption on health have been consistently reported in the so-called "alcohol harm paradox" (i.e., individuals from higher socioeconomic backgrounds (SES) drink more alcohol than individuals from lower SES, but the latter accrue more alcohol-related harm). Despite the severe health risks of smoking however, there is a scarcity of studies examining a possible "smoking harm paradox" (SHP). We aim to fill this gap., Methods: We conducted a prospective cohort study with adolescents from the Norwegian Longitudinal Health Behaviour Study (NLHB). Our study used data from ages 13 to 30 years. To analyse our data, we used the random-intercept cross-lagged panel model (RI-CLPM) with smoking and self-reported health as mutual lagged predictors and outcomes as well as parental income and education as grouping variables. Parental income and education were used as proxies for adolescent socioeconomic status (SES). Smoking was examined through frequency of smoking (every day, every week, less than once a week, not at all). General health compared to others was measured by self-report., Results: Overall, we found inconclusive evidence of the smoking harm paradox, as not all effects from smoking to self-reported health were moderated by SES. Nevertheless, the findings do suggest that smoking predicted worse subjective health over time among individuals in the lower parental education group compared with those in the higher parental education group. This pattern was not found for parental income., Conclusions: While our results suggest limited evidence for a smoking harm paradox (SHP), they also suggest that the impact of adolescent smoking on later subjective health is significant for individuals with low parental education but not individuals with high parental education. This effect was not found for parental income, highlighting the potential influence of parental education over income as a determinant of subjective health outcomes in relation to smoking., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer., (© 2023. BioMed Central.)