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Abstract Ocean ecosystems have been subjected to anthropogenic influences for centuries, but the scale of past ecosystem changes is often unknown. For centuries, the European flat oyster (Ostrea edulis), an ecosystem engineer providing biogenic reef habitats, was a culturally and economically significant source of food and trade. These reef habitats are now functionally extinct, and almost no memory of where or at what scales this ecosystem once existed, or its past form, remains. The described datasets present qualitative and quantitative extracts from written records published between 1524 and 2022. These show: (1) locations of past flat oyster fisheries and/or oyster reef habitat described across its biogeographical range, with associated levels of confidence; (2) reported extent of past oyster reef habitats, and; (3) species associated with these habitats. These datasets will be of use to inform accelerating flat oyster restoration activities, to establish reference models for anchoring adaptive management of restoration action, and in contributing to global efforts to recover records on the hidden history of anthropogenic-driven ocean ecosystem degradation.

Primary endometrial serous carcinoma, known for its aggressive nature and poor prognosis, shares similarities with breast and gastric cancers in terms of potential HER2 overexpression as a therapeutic target. Assessing HER expression is complicated by tumor heterogeneity and discrepancies between primary and metastatic sites. In this study, we retrospectively analyzed HER amplification and expression in 16 pairs of primary endometrial serous carcinoma resections and corresponding metastases. HER2 status was determined using immunohistochemistry (IHC), with criteria based on the percentage and intensity of tumor cell staining. Confirmatory techniques, such as dual in situ hybridization (DISH) and fluorescence in situ hybridization (FISH), were also employed. This study reports on the concordance rates and the presence and pattern of HER2 heterogeneity. Our results showed an 87.5% concordance rate in HER2 amplification status between primary and metastatic sites, with 33% of cases scored as 2+ being amplified. Heterogeneity was observed in 100% of amplified cases and 95% of non-amplified cases on in situ testing, with variations in heterogeneity patterns between techniques. In conclusion, our findings emphasize the importance of testing both primary and metastatic sites or recurrences, with a concordance rate of 87.5%. In addition, a review of the literature and combining the results showed a concordance rate of up to 68%. The presence and pattern of heterogeneity, particularly in cases of mosaic or clustered heterogeneity in the primary tumor, may serve as reliable indicators of concordance, predicting a non-amplified HER2 status in corresponding metastases.

Abstract Year 12 students in Big Picture Learning schools across Australia now use portfolios and interviews to apply for and gain entry to their first choice of university degree. They receive admission on the strength of portfolio evidence mapped to a new non-ATAR qualification, known as the International Big Picture Learning Credential (IBPLC). Since 2020, 270 graduates have received offers to university using the Credential, growing from 3 in 2017. Like other Big Picture graduates who went before them, they are continuing a trajectory of passion-based learning that began in Year 9 or 10 at one of 45 Australian Big Picture Learning schools. All IBPLC graduates begin tertiary study equipped with experiences in the real world, support systems with a range of community mentors and teachers, specialist knowledge in their chosen field, and a set of independent learning skills intended to give them the opportunity to thrive in the university setting. In this article we share the preliminary findings of a study of graduates of Big Picture Learning Australia secondary schools who have matriculated using the IBPLC. Findings from our surveys and interviews show promise that the learning design of Big Picture, which starts with an internship in a passion area, is the key factor in enabling the success of graduates both from high school and into their university studies.

Abstract Background The ongoing global crisis of Higher Education (HE) institutions during the post-COVID-19 pandemic period has increased the likelihood of enduring psychological stressors for staff. This study aimed to identify factors associated with job insecurity, burnout, psychological distress and coping amongst staff working at HE institutions globally. Methods An anonymous cross-sectional study was conducted in 2023 with staff at HE institutions across 16 countries. Job insecurity was measured using the Job Insecurity Scale (JIS), burnout using the Perceived Burnout measure question, psychological distress using the Kessler Psychological Distress Scale (K10), and coping using the Brief Resilient Coping Scale. Multivariable logistic regression with a stepwise variable selection method was used to identify associations. Results A total of 2,353 staff participated; the mean age (± SD) was 43(± 10) years and 61% were females. Most staff (85%) did not feel job insecurity, one-third (29%) perceived burnout in their jobs, more than two-thirds (73%) experienced moderate to very high levels of psychological distress, and more than half (58%) exhibited medium to high resilient coping. Perceived job insecurity was associated with staff working part-time [Adjusted Odds Ratio 1.53 (95% Confidence Intervals 1.15–2.02)], having an academic appointment [2.45 (1.78–3.27)], having multiple co-morbidities [1.86 (1.41–2.48)], perceived burnout [1.99 (1.54–2.56)] and moderate to very high level of psychological distress [1.68 (1.18–2.39)]. Perceived burnout was associated with being female [1.35 (1.12–1.63)], having multiple co-morbidities [1.53 (1.20–1.97)], perceived job insecurity [1.99 (1.55–2.57)], and moderate to very high levels of psychological distress [3.23 (2.42–4.30)]. Staff with multiple co-morbidities [1.46 (1.11–1.92)], mental health issues [2.73 (1.79–4.15)], perceived job insecurity [1.61 (1.13–2.30)], and perceived burnout [3.22 (2.41–4.31)] were associated with moderate to very high levels of psychological distress. Staff who perceived their mental health as good to excellent [3.36 (2.69–4.19)] were more likely to have medium to high resilient coping. Conclusions Factors identified in this study should be considered in reviewing and updating current support strategies for staff at HE institutions across all countries to reduce stress and burnout and improve wellbeing.

The mammalian gastrointestinal tract provides a habitat for multiple commensal and pathogenic organisms spanning all three domains of life. Both positive and negative interactions occur between gut inhabitants, with potential consequences for host health. Studies of parasite–microbiota associations in natural systems remain scarce, yet are important for understanding how parasite communities and commensal microbiota shape each other, and how these interactions influence host health. Here, we characterize associations between helminth and coccidial infections and gut microbiota profiles in a wild population of wood mice (Apodemus sylvaticus) over 3 years, using two complementary approaches. We first examined parasite–microbiota associations along the length of the gastrointestinal tract through destructive sampling. Then, in a larger non-invasive capture mark-recapture study, we assessed whether gut parasitic infections detected in feces predicted fecal microbiota diversity and composition. We found that while overall microbiota composition was not associated with infection by any common gut parasite species, microbiota richness was associated with gut parasitism in two ways: (i) infection by the trematode Corrigia vitta in the small intestine predicted higher microbiota diversity in the caecum; (ii) there was a negative relationship between gut parasite richness and fecal microbiota richness in the non-invasive study. As our results identified associations between gastrointestinal parasites and microbiota alpha diversity, a future experimental study in this tractable wild mammalian system would be valuable to definitively test the directionality of these interactions.

Seagrass carbon sequestration is known to be an accumulative process of both autochthonous and allochthonous carbon sequestration, however, carbon accreditation focuses on increasing autochthonous organic carbon only. In seagrass carbon accreditation methodologies peer-reviewed published data may be utilised as evidence for the deduction of a percentage of allochthonous carbon from the total seagrass sediment organic carbon. These literature-based proxies are often derived from stable isotope mixing models, which utilise seagrass and sediment δ13C values. This study looks at global seagrass sediment and leaf δ13C analyses, and demonstrates that climatic bioregion, geomorphology and seagrass morphological traits explain global patterns in seagrass leaf and sediment isotope δ13C ratios. Multi-factor analysis of mixed data shows a separation between seagrass bioregions and different leaf-size populations, specifically; north temperate regions from tropical and south temperate regions; medium leaf-size individuals to all others. Analysis of variance confirmed a significant difference (p

IntroductionSeveral current therapies for autoimmune diseases do not provide sustained remission. Therapies that focus on the restoration of homeostasis within the immune system (i.e., immune resolution) could overcome the limitations of current therapies and provide more durable remission. However, there is no established consensus on appropriate clinical trial designs and endpoints to evaluate such therapies. Therefore, we conducted a systematic literature review (SLR) focusing on five index diseases (asthma, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus [SLE], and ulcerative colitis) to explore published literature on 1) expert opinion on immune-resolution outcomes that should be measured in clinical trials; and 2) quantification of immune resolution in previous clinical trials.MethodsThe SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase and MEDLINE databases were systematically searched (2013–2023) for published English language articles. Conference proceedings (2020–2022) from American Academy of Dermatology, American College of Rheumatology, Digestive Disease Week, European Alliance of Associations for Rheumatology, and European Academy of Dermatology and Venereology were searched to include relevant abstracts. The study protocol was registered in PROSPERO (CRD42023406489).ResultsThe SLR included 26 publications on 20 trials and 12 expert opinions. Expert opinions generally lacked specific recommendations on the assessment of immune resolution in clinical trials and instead suggested targets or biomarkers for future therapies. The targets included thymic stromal lymphopoietin (TSLP) in asthma; T helper (Th)2 and Th22 cells and their respective cytokines (interleukin [IL]-4R and IL-22) in atopic dermatitis; inhibitory/regulatory molecules involved in T-cell modulation, and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) in rheumatoid arthritis; low-dose IL-2 therapy in SLE; and pro-resolution mediators in ulcerative colitis and asthma. In the interventional studies, direct biomarker assessments of immune resolution were the number/proportion of regulatory T-cells (Treg) and the ratio Th17/Treg in SLE and rheumatoid arthritis; the number of T follicular helper cells (Tfh), Th1, Th2, Th17, and Th22 in atopic dermatitis, rheumatoid arthritis, and SLE; and mucosal proinflammatory gene signatures (tumor necrosis factor [TNF], interleukin 1 alpha [IL1A], regenerating family member 1 alpha [REG1A], IL8, interleukin 1 beta [IL1B], and leukocyte immunoglobulin-like receptors A [LILRA]) in ulcerative colitis. Several studies reported a statistically significant relationship between clinical remission and immune-resolution biomarkers, suggesting a link between T-cell homeostasis, cytokine production, and disease activity in autoimmune diseases.DiscussionExisting literature does not offer clear guidance on the evaluation of immune resolution in interventional studies. Further research and consensus are needed to assess a treatment’s ability to induce long-term remission or low disease activity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023406489, identifier CRD42023406489.

Background Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person’s life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations. Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. Methods The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. Discussion The iFraP trial will answer important questions about the effectiveness of the new ‘iFraP’ osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. Trial registration ISRCTN 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407

Abstract Circulating tumor cells (CTCs) have gathered attention as a biomarker for carcinomas. However, CTCs in sarcomas have received little attention. In this work, we investigated cell surface proteins and antibody combinations for immunofluorescence detection of sarcoma CTCs. A microfluidic device that combines filtration and immunoaffinity using gangliosides 2 and cell surface vimentin (CSV) antibodies was employed to capture CTCs. For CTC detection, antibodies against cytokeratins 7 and 8 (CK), pan-cytokeratin (panCK), or a combination of panCK and CSV were used. Thirty-nine blood samples were collected from 21 patients of various sarcoma subtypes. In the independent samples study, samples were subjected to one of three antibody combination choices. Significant difference in CTC enumeration was found between CK and panCK + CSV, and between panCK and panCK + CSV. Upon stratification of CK + samples, those of metastatic disease had a higher CTC number than those of localized disease. In the paired samples study involving cytokeratin-positive sarcoma subtypes, using panCK antibody detected more CTCs than CK. Similarly, for osteosarcoma, using panCK + CSV combination resulted in a higher CTC count than panCK. This study emphasized deliberate selection of cell surface proteins for sarcoma CTC detection and subtype stratification for studying cancers as heterogeneous as sarcomas.

Background: Childhood maltreatment (CM) can be divided into: emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN). CM is associated with (Complex)Posttraumatic stress disorder (PTSD/CPTSD) and substance use disorder (SUD).Objective: This cross-sectional study examined the relationships between CM-subtypes with PTSD-severity and CPTSD in patients with SUD-PTSD.Method: Participants (N = 209) were treatment-seeking SUD-PTSD patients who completed the Childhood Trauma Questionnaire-short form, the Clinician-Administered PTSD Scale for DSM-5 and the International Trauma Questionnaire. Regression analyses and a model selection procedure to select an optimal model were used to examine CM-subtypes as predictors of (C)PTSD, adjusted for sex and age.Results: Total CM and all CM-types significantly predicted PTSD-severity in the univariate regression analysis, with EA begin the strongest predictor. In the multiple regression only SA predicted PTSD-severity. Subsequently, model selection indicated that the optimal model to predict PTSD-severity included EA and SA. In the univariate analyses total CM, EA, and PN significantly predicted CPTSD-classification, and total CM and all CM-types significantly predicted CPTSD-severity. In the multiple regression for CPTSD-classification only EA and PA were significant predictors and for CPTSD-severity EA, PA and SA were significant predictors. In post-hoc multiple regression analyses, only EA was a significant predictor of CPTSD-classification and CPTSD-severity. Finally, in the model selection the most parsimonious model only included EA for both CPTSD-classification and CPTSD-severity. Sex was not a moderator in the relationship between CM and PTSD, nor in CM and CPTSD.Conclusions: These findings indicate that for SUD-PTSD patients, several CM-types have predictive value for (C)PTSD-severity, however SA and especially EA appear to contribute to these complaints. Since EA does not constitute an A-criterion, it is generally more overlooked in PTSD treatment. Its impact should therefore be underlined, and clinicians should be attentive to EA in their treatment.

Aims The key aim of this project was to update and modernise the hospital procedure on how patients access pornographic material whilst detained at Wathwood Hospital. Within the update, we aimed to promote inclusivity and acceptance of all patients’ sexual identities as well as utilising the opportunity to emphasise healthy consenting sexual relationships. Patients in Forensic Mental Health settings are often inpatients for a significant amount of time, with multiple restrictions imposed on their private and family life. Current policy allows patients to purchase pornography for private use in their own room. It must be material of the same nature available in a main street outlet. In practice, material is usually purchased in DVD format from the Amazon website and subsequently screened for suitability by Security staff and finally approval by the Responsible Clinician. There have been numerous incident reports involving the trading of pornographic material. Methods Qualitative semi-structured group interviews (up to 5 people at a time) were conducted with patients in the medium-secure forensic services of Wathwood Hospital. They were recruited from the fortnightly Patient Forum. Anonymised questionnaires involving Likert scales and free text response spaces were also distributed at the Patient Forum. Data gathered investigated the percentage of patients who were aware of the current procedure, if they felt it worked well and what they thought the impact of accessing pornographic material might be. Staff were invited to complete a similar anonymised questionnaire, again considering their opinions on the positive or negative impacts of pornography for patients. In addition, we gathered data on whether there was a difference on the degree of comfort/discomfort about pornography, depending on whether the material involved opposite sex or same sex couples. In total, there were 40 survey participants. Results Some key areas for concern were found, for example, only 17% of staff and 16% of patients thought the current policy works well despite 69% of staff and 84% of patients feeling it is a patient's right to access pornography. Free text and focus group feedback established many benefits to it. It was clear that there were some areas of difficulty in the hospital policy, which would benefit from being refreshed. Conclusion Staff and patients overall feel that access to pornography is important for many of the patients. We identified areas for improvement in how this is accessed and a need to continually be considering the need to consider meeting the holistic needs for the patients.

Abstract Increasing attention has been drawn to the misuse of statistical methods over recent years, with particular concern about the prevalence of practices such as poor experimental design, cherry picking and inadequate reporting. These failures are largely unintentional and no more common in ecology than in other scientific disciplines, with many of them easily remedied given the right guidance. Originating from a discussion at the 2020 International Statistical Ecology Conference, we show how ecologists can build their research following four guiding principles for impactful statistical research practices: (1) define a focussed research question, then plan sampling and analysis to answer it; (2) develop a model that accounts for the distribution and dependence of your data; (3) emphasise effect sizes to replace statistical significance with ecological relevance; and (4) report your methods and findings in sufficient detail so that your research is valid and reproducible. These principles provide a framework for experimental design and reporting that guards against unsound practices. Starting with a well‐defined research question allows researchers to create an efficient study to answer it, and guards against poor research practices that lead to poor estimation of the direction, magnitude, and uncertainty of ecological relationships, and to poor replicability. Correct and appropriate statistical models give sound conclusions. Good reporting practices and a focus on ecological relevance make results impactful and replicable. Illustrated with two examples—an experiment to study the impact of disturbance on upland wetlands, and an observational study on blue tit colouring—this paper explains the rationale for the selection and use of effective statistical practices and provides practical guidance for ecologists seeking to improve their use of statistical methods.

Abstract Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.

Background Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person’s life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations. Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. Methods The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. Discussion The iFraP trial will answer important questions about the effectiveness of the new ‘iFraP’ osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. Trial registration: ISRCTN 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407

On-ice skating sprint performance is a significant predictor and requirement for playing at the highest levels of hockey. The purpose of this study was to determine the relationship between maximum and dynamic strength measures and on-ice sprint performance in university level ice hockey athletes. Both male (n=18) and female (n=13) hockey players participated in this study. The off-ice measures included two assessment procedures utilizing a force plate; an isometric mid-thigh pull (IMTP) to assess maximum strength and a countermovement jump (CMJ) to assess dynamic strength. Both off-ice measures were analyzed from both a relative (CMJr and IMTPr) and absolute (CMJa and IMTPa) perspective. The on-ice measures were 7.71m and 15.42m sprint times. Pearson product moment correlations were used to quantify the relationships between variables. CMJa (r = -0.56 to -0.61), IMTPa (r = -0.65 to -0.67) and IMTPr (r = -0.55) were significantly correlated (p < 0.05) with on-ice sprint performance. When analyzed by sex, no significant relationships (p > 0.05) were observed between CMJ measures and on-ice sprint times. No significant relationships (p > 0.05) were observed between IMTP measures and on-ice sprint times when individually analyzing male participants, while significant relationships (p < 0.05) were observed in females between IMTPa (r = -0.70 to -0.71) and IMTPr (r = -0.68 to -0.71) and on-ice sprint times. It is concluded that both maximum and dynamic strength are important factors in on-ice sprint performance in hockey players. Furthermore, maximum strength seems to be an important characteristic in on-ice sprint ability in females.

Abstract Background Globally, it is estimated that one in three adults live with two or more long‐term conditions (multiple long‐term conditions, MLTCs), that require self‐management. People who experience socioeconomic deprivation face significant health inequalities due to a range of interrelated characteristics that lead to a lack of resources and opportunities. Previous research with underserved populations indicate low levels of trust towards primary care providers and potential barriers for developing patient‐healthcare professional relationships. The purpose of this paper is to explore the barriers and facilitators to self‐managing MLTCs, amongst people who experience socioeconomic deprivation. Methods Semistructured one‐to‐one interviews with adults (n = 28) living in London and Sheffield, United Kingdom with MLTCs who are experiencing socioeconomic deprivation. Participants were recruited through general practices, community channels and social media. Data were analysed in NVivo using reflexive thematic analysis methods. Findings Four analytical themes were developed: (1) challenges in accessing healthcare services, financial assistance, and cultural awareness; (2) empowerment and disempowerment through technology, including digital exclusion, and use of technology; (3) impact and causes of exclusion on self‐management, including social isolation, area‐based and economic exclusion, and health‐related stigma and (4) adapting self‐management strategies, including cost‐effective, and culturally/lifestyle appropriate strategies. Conclusions Future health interventions and services need to be developed with consideration of the combined complexities of managing MLTCs while experiencing socioeconomic deprivation. Increased awareness in practitioners and commissioners of the complexities surrounding the lives of people experiencing socioeconomic deprivation, and the need for targeted strategies to promote self‐management of MLTCs are of great importance. Patient or Public Contribution A patient advisory group contributed to all stages of the study, including providing important feedback on study documents (topic guides and recruitment materials), as well as providing critical insights surrounding the interpretation of interview data.

Objective To explore eating and drinking experiences of patients with idiopathic pulmonary fibrosis (IPF), the impact of any changes associated with their diagnosis and any coping mechanisms developed by patients.Setting Pulmonary fibrosis support groups around the UK and the regional Interstitial Lung Diseases Clinic, Newcastle upon Tyne.Participants 15 patients with IPF (9 men, 6 women), median age 71 years, range (54–92) years, were interviewed. Inclusion criteria included competent adults (over the age of 18 years) with a secure diagnosis of IPF as defined by international consensus guidelines. Patients were required to have sufficient English language competence to consent and participate in an interview. Exclusion criteria were a history of other lung diseases, a history of pre-existing swallowing problem of other causes that may be associated with dysphagia and individuals with significant communication or other memory difficulties that render them unable to participate in an interview.Design A qualitative study based on semistructured interviews used purpose sampling conducted between February 2021 and November 2021. Interviews were conducted via video videoconferencing call platform or telephone call, transcribed and data coded and analysed using a reflexive thematic analysis.Results Three main themes were identified, along with several subthemes, which were: (1) Eating, as such, is no longer a pleasure. This theme mainly focused on the physical and sensory changes associated with eating and drinking and their effects and the subsequent emotional and social impact of these changes; (2) It is something that happens naturally and just try and get on with it. This theme centred on the self-determined strategies employed to manage changes to eating and drinking; and (3) What is normal. This theme focused on patients seeking information to better understand the changes in their eating and drinking and the patients’ beliefs about what has changed their eating and drinking.Conclusions To our knowledge, this is the first study to report on IPF patients’ lived experience of eating and drinking changes associated with their diagnosis. Findings demonstrate that some patients have substantial struggles and challenges with eating and drinking, affecting them physically, emotionally and socially. There is a need to provide better patient information for this area and further study.

Objectives There has been a rapid shift from face-to-face to remote consultation across healthcare settings. 90% of patients with mental health conditions are cared for entirely in primary care. Remote consultation can present challenges and benefits for patients with mental health conditions. The aim of this systematic review was to collate and examine the evidence relating to remote consultation in UK primary care on the experiences of patients with mental health conditions. Methods Six major databases were searched for empirical studies published in the English language between 1 January 2010 and 21 October 2022. Studies were included where remote consultation occurred between a patient and primary care clinician. Outcomes of interest include mode of remote consultation, patient experiences and characteristics. Final included studies were assessed for quality, and results analysed with narrative synthesis. Results Six studies met the inclusion criteria, covering a range of mental health conditions and remote consultation modalities (telephone, video, online, email, text-based). Patients were overall satisfied with remote consultation, with particular benefit for certain mental health conditions or anxious patients. However, several studies found that face-to-face was the preferred method, with highlighted negatives to remote consultation, such as inflexibility of online formats. Acceptability of remote consultation is context specific and influenced by the purpose of the consultation and individual patient. Remote consultation may reduce anxiety in some patients, but is potentially less acceptable than face-to-face for relational appointments. Conclusions Acceptability of remote consultation is context dependent. There is a lack of evidence surrounding patient characteristics and access to remote consultation.

Abstract Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. Conclusion UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Abstract Background Supported self-management interventions for patients with musculoskeletal (MSK) conditions may not adequately support those with limited health literacy, leading to inequalities in care and variable outcomes. The aim of this study was to develop a model for inclusive supported self-management intervention(s) for MSK pain that take account of health literacy. Methods A mixed methods study with four work-packages was conducted: work package 1: secondary analysis of existing data to identify potential targets for intervention; work package 2: evidence synthesis to assess effective components of self-management interventions taking into account health literacy; work package 3: views of community members and healthcare professionals (HCPs) on essential components; work package 4: triangulation of findings and an online modified Delphi approach to reach consensus on key components of a logic model. Findings Findings identified targets for intervention as self-efficacy, illness perceptions, and pain catastrophizing. A range of intervention components were identified (e.g. information in diverse formats offered at specific times, action planning and visual demonstrations of exercise). Support should be multi-professional using a combination of delivery modes (e.g. remote, face-to-face). Conclusions This research has developed a patient-centred model for a multi-disciplinary, multi-modal approach to supported self-management for patients with MSK pain and varying levels of health literacy. The model is evidence-based and acceptable to both patients and HCPs, with potential for significant impact on the management of MSK pain and for improving patient health outcomes. Further work is needed to establish its efficacy.

Opioid-induced respiratory depression (OIRD) deaths are ~80,000 a year in the US and are a major public health issue. Approximately 90% of fatal opioid-related deaths are due to synthetic opioids such as fentanyl, most of which is illicitly manufactured and distributed either on its own or as an adulterant to other drugs of abuse such as cocaine or methamphetamine. Other potent opioids such as nitazenes are also increasingly present in the illicit drug supply, and xylazine, a veterinary tranquilizer, is a prevalent additive to opioids and other drugs of abuse. Naloxone is the main treatment used to reverse OIRD and is available as nasal sprays, prefilled naloxone injection devices, and generic naloxone for injection. An overdose needs to be treated as soon as possible to avoid death, and synthetic opioids such as fentanyl are up to 50 times more potent than heroin, so the availability of new, higher-dose, 5-mg prefilled injection or 8-mg intranasal spray naloxone preparations are important additions for emergency treatment of OIRDs, especially by lay people in the community. Higher naloxone doses are expected to reverse a synthetic overdose more rapidly and the current formulations are ideal for use by untrained lay people in the community. There are potential concerns about severe withdrawal symptoms, or pulmonary edema from treatment with high-dose naloxone. However, from the perspective of first responders, the balance of risks would point to administration of naloxone at the dose required to combat the overdose where the risk of death is very high. The presence of xylazines as an adulterant complicates the treatment of OIRDs, as naloxone is probably ineffective, although it will reverse the respiratory depression due to the opioid. For these patients, hospitalization is particularly vital. Education about the benefits of naloxone remains important not only in informing people about how to treat emergency OIRDs but also how to obtain naloxone. A call to emergency services is also essential after administering naloxone because, although the patient may revive, they may overdose again later because of the short half-life of naloxone and the long-lasting potency of fentanyl and its analogs.

BackgroundThe well-established inverse relationship between socioeconomic status (SES) and risk of developing coronary heart disease (CHD) cannot be explained solely by differences in traditional risk factors.ObjectiveTo model the role SES plays in the burden of premature CHD in Argentina.Materials and methodsWe used the Cardiovascular Disease Policy Model-Argentina to project incident CHD events and mortality in low and high-SES Argentinean adults 35 to 64 years of age from 2015 to 2024. Using data from the 2018 National Risk Factor Survey, we defined low SES as not finishing high-school and/or reporting a household income in quintiles 1 or 2. We designed simulations to apportion CHD outcomes in low SES adults to: (1) differences in the prevalence of traditional risk factors between low and high SES adults; (2) nontraditional risk associated with low SES status; (3) preventable events if risk factors were improved to ideal levels; and (4) underlying age- and sex-based risk.Results56% of Argentina´s 35- to 64-year-old population has low SES. Both high and low SES groups have poor control of traditional risk factors. Compared with high SES population, low SES population had nearly 2-fold higher rates of incident CHD and CHD deaths per 10 000 person-years (incident CHD: men 80.8 [95%CI 76.6-84.9] vs 42.9 [95%CI 37.4-48.1], women 39.0 [95%CI 36.-41.2] vs 18.6 [95%CI 16.3-20.9]; CHD deaths: men 10.0 [95%CI 9.5-10.5] vs 6.0 [95%CI 5.6-6.4], women 3.2 [95%CI 3.0-3.4] vs 1.8 [95%CI 1.7-1.9]). Nontraditional low SES risk accounts for 73.5% and 70.4% of the event rate gap between SES levels for incident CHD and CHD mortality rates, respectively.DiscussionCHD prevention policies in Argentina should address contextual aspects linked to SES, such as access to education or healthcare, and should also aim to implement known clinical strategies to achieve better control of CHD risk factors in all socioeconomic levels.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) with limited treatment options. Interleukin-33 (IL-33) is proposed to play a role in the development of IPF however the exclusive use of prophylactic dosing regimens means that the therapeutic benefit of targeting this cytokine in IPF is unclear. Methods IL-33 expression was assessed in ILD lung sections and human lung fibroblasts (HLFs) by immunohistochemistry and gene/protein expression and responses of HLFs to IL-33 stimulation measured by qPCR. In vivo, the fibrotic potential of IL-33:ST2 signalling was assessed using a murine model of bleomycin (BLM)-induced pulmonary fibrosis and therapeutic dosing with an ST2-Fc fusion protein. Lung and bronchoalveolar lavage fluid were collected for measurement of inflammatory and fibrotic endpoints. Human precision-cut lung slices (PCLS) were stimulated with transforming growth factor-β (TGFβ) or IL-33 and fibrotic readouts assessed. Results IL-33 was expressed by fibrotic fibroblasts in situ and was increased by TGFβ treatment in vitro. IL-33 treatment of HLFs did not induce IL6, CXCL8, ACTA2 and COL1A1 mRNA expression with these cells found to lack the IL-33 receptor ST2. Similarly, IL-33 stimulation had no effect on ACTA2, COL1A1, FN1 and fibronectin expression by PCLS. Despite having effects on inflammation suggestive of target engagement, therapeutic dosing with the ST2-Fc fusion protein failed to reduce BLM-induced fibrosis measured by hydroxyproline content or Ashcroft score. Conclusions Together these findings suggest the IL-33:ST2 axis does not play a central fibrogenic role in the lungs with therapeutic blockade of this pathway unlikely to surpass the current standard of care for IPF.

Abstract Background Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host’s immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated. Methods SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity. Results Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host’s ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host’s immune system. Conclusion Whilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development. Graphical abstract

Abstract Background Therapeutic footwear and insoles are preventative strategies to reduce elevated plantar pressures associated with diabetic foot ulcer risk. An insole intervention appropriate for chairside delivery optimising plantar foot pressure reduction in people with diabetes has been developed. Aim To explore the feasibility and acceptability of testing an optimised insole compared with an active control insole to reduce plantar pressures for people with diabetic peripheral neuropathy. Methods A double-blinded multi-centre feasibility RCT with an embedded qualitative study. Participants were randomised to either an optimised insole group (intervention) or a standard cushioned insole group (active control). Participants were assessed at baseline, 3, 6, and 12 months with clinical outcomes of foot ulceration and mean peak plantar pressure (MPPP) reduction. An embedded qualitative study involved semi-structured interviews with 12 study participants and three podiatrists to explore their experiences of the intervention and trial procedures. Data were analysed using descriptive statistics (quantitative data) and thematic analysis (qualitative data). Results Screened were142 patients from which 61 were recruited; 30 participants were randomised to the intervention group and 31 to the active control group. Forty-two participants completed the study. At 12 months, 69% of the patient-reported questionnaires were returned and 68% of the clinical outcomes were collected. There were 17 incidences of foot ulceration occurring in 7/31 of the active control group and 10/30 in the intervention group. Mean difference in MPPP between the intervention and active control groups for all regions-of-interest combined favoured the intervention. Thematic analysis revealed three themes; accepting the study, behaviour and support during study procedures, and impact from study participation. Conclusion The results of the feasibility RCT suggest that the optimised insole holds promise as an intervention, and that a full RCT to evaluate the clinical and cost-effectiveness of this intervention is feasible and warranted for people with diabetic peripheral neuropathy. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN16011830 . Registered 9th October 2017.

The use of alternative proteins is becoming more common in pet feed, and insect-based dog foods (IBDFs) are becoming more widely available. However, little research has been conducted to date in respect of the drivers for consumers’ acceptance of IBDF. This study aimed to investigate the acceptance of IBDF among adult UK dog owners and the factors influencing the decision to try and buy such products. A theoretical model was developed following a review of the existing literature. An online survey of 280 participants was carried out and the results were analysed using structural equation modelling (SEM) to test the theoretical model. The following constructs all had a significant impact on attitudes towards IBDF and/or intentions to try and buy IBDF: food preferences for animal welfare, health and environment; attitudes towards uses of animals; beliefs about insect sentience; disgust; perceptions of benefits and risks; and social norms. Social norms had the strongest influence of any single construct. Consumer acceptance of IBDF is multi-faceted including social, cultural and ethical components, and it is likely that the better availability of information and opportunities for consumers to familiarise themselves with IBDF would help to drive consumer acceptance. In order to allow dog owners to make informed decisions in line with their ethical preferences, further research is needed to establish the overall health and welfare implications of IBDF on the animals involved in production, as well as the companion animals, who are the ultimate consumers.

Introduction & Background Netflix now has a consumer base of over 230 million worldwide. During the pandemic, its customers watched 203.8 million hours of content daily, with their activity, content choices and preferences being continually logged. The digital footprint data amassed in this process underpins a symbiotic relationship between supplier and consumer. Black-box algorithms convert these logs into personalised functionality and recommendations, producing improved customer experiences while generating revenue for the business. Whether the consumer willingly accepts this trade-off or not, it’s now almost impossible to use online services without leaving digital traces. But how representative of an individual’s actual preferences and behaviours are these? What biases exist in such datasets? And to what degree are consumers cognisant of how these datasets are being used? Objectives & Approach This study surveyed participants to interrogate their understanding of the data Netflix makes available to its subscribers. The objectives were to explore their perceptions relating to the data collected about them and encourage them to think critically about their digital footprint. It was also the intention of the research group that participants feel a sense of empowerment / control over the data made available to them. UK-based participants were provided with instructions on how to access their viewing history (programme titles, dates of access) and invited to inspect it. 61 participants opted to donate their data to the study, along with responses to a survey reflecting their understanding of what they had retrieved. Relevance to Digital Footprints While it may have been possible to work with Netflix to retrieve viewer data, by accessing via the participants instead, the researchers were enabling them to review and make informed choices about what they shared. One of the potential issues with this approach is that it provides an opportunity for participants to curate their data, should there be content that they would be uncomfortable sharing. Alternately, they may choose to withdraw from the study altogether based on what they see. While this has its drawbacks in terms of data inaccuracies and self-selection effect, it was felt important to the research team to prioritise the participants autonomy, encouraging them to be candid and share. If nothing else, it is hoped that by taking part in the study, there is the potential for participants to be inspired to think about the footprints they leave every time they go online so that they might be more mindful of them in future. Results In terms of bias, using only the Netflix data meant that the researchers were only accessing participants who pay for that service. Further, the researchers would only be accessing what would be a proportion of the participants’ viewing. If only using one service however, Netflix is arguably the service to use as according to statistica©, In 2021 it was the most subscribed (paid) supplier in the UK. 76% of respondents view more streamed content than terrestrial broadcast content and utilise an average of 3.5 streaming services. 36% of respondents also stated that they share their Netflix user profiles with at least one other person. Despite these limitations, 84% of respondents nonetheless considered that the captured content was representative of their ‘personal tastes and viewing habits.’ 76% were not aware until participating in the study that it was possible to extract their viewing data from Netflix, and 34% said they’d likely review it again. 33% indicated surprise as to the extent of information captured about them; but 91% believed that the streaming platform collected more information than was made available. Conclusions & Implications This study shows the potential of data donation to understand viewing habits, binge watching and related well-being indicators, with 43% of surveyed individuals offering their data for research. What has not been established in this study is why 57% of the group declined to share their data. It can be speculated that it may have been a reluctance to share once the data was inspected or that the process to access and then upload it may have been too much of a hurdle. An implication for this type of study may include a requirement to over-recruit in anticipation of a high drop-out rate or that data extraction and sharing needs to be made as simple and convenient as practicable for the participant. Given that one of the objectives of the research was to encourage participants to have more curiosity in and awareness / control of their digital footprints, consideration should be given to seeing if participant interest in further exploration of their data could be increased from the 24% seen here. This might be driven by the data type, any perceived utility it might have for the participant or any perceived ways in which it might be used to impact / influence them in some way by a 3rd party.

Abstract Archival (data-storage) and telemetry (acoustic and radio) tags are commonly used to provide data on the behavior and physiology of organisms, as well as data on their surrounding environment. For fishes, it is often advantageous to implant tags in the peritoneal cavity (i.e., intracoelomic implantation). The literature on best practices is limited for marine species, and near absent for tunas despite their regular application. We identify recommended practices using laparotomy in tropical tuna species following observations from thousands of tags implantations undertaken during implementation of several tagging programs across the Pacific. These recommended practices include descriptions of preferred tagging stations and equipment, fish selection, surgical procedures, and return of the fish to the wild. While these recommended practices were developed specifically for tropical tuna species, they are also likely applicable for other pelagic fishes. We present these guidelines to guide and promote the development of best practices for such procedures on pelagic species.

In this study, we assessed a highly structured, yearlong, case-based course designed for undergraduate pre-health students. We incorporated both content learning assessments and developed a novel method called Multiple Mini Exams for assessing course impact on the development of skills that professional schools often seek in pre-health students, focusing on students' abilities to collaborate with others, display bedside manners, synthesize patient case details, appropriately use scientific and medical language, and effectively attain patients' medical histories. This novel method utilized a rubric based on desired medical student skills to score videotaped behaviors and interactions of students role playing as doctors in a hypothetical patient case study scenario. Overall, our findings demonstrate that a highly structured course, incorporating weekly student performance and presentation of patient cases encompassing history taking, diagnosis, and treatment, can result in content learning, as well as improve desired skills specific for success in medical fields.

Abstract Background The STarT MSK cluster randomised controlled trial (RCT) investigated the clinical- and cost-effectiveness of risk-based stratified primary care versus usual care for patients with back, neck, shoulder, knee or multi-site pain. Trial quantitative results showed risk-based stratified care was not superior to usual care for patients’ clinical outcomes, but the intervention led to some changes in GP clinical decision-making. This paper reports a linked qualitative study exploring how risk-based stratified care was perceived and used in the trial, from the perspectives of clinicians and patients. Methods Semi-structured interviews were conducted with 27 patients, and focus groups and interviews with 20 clinicians (GPs and physiotherapists) in the intervention arm of the trial. Data were analysed thematically and findings explored using Normalisation Process Theory (NPT) and the COM-B model. Main findings Risk-based stratified care (subgrouping and matching treatments) was found to have ‘coherence’ (i.e. made sense) to several clinicians and patients, in that it was well-integrated in practice, and supported clinical decision-making. However, for some GPs stratified care was less ‘meaningful’, as the risk-stratification tool did not fit with usual ways of consulting and added to already time-pressured consultations. GPs reported giving more patients written information/advice due to easier access to electronic information leaflets through the trial template and were motivated to refer patients to physiotherapy as they believed the trial resulted in faster physiotherapy access (although this was not the case). Patients and clinicians reported that risk-based stratified care influenced conversations in the consultation, prompting greater attention to psychosocial factors, and facilitating negotiation of treatment options. Physiotherapists saw benefits in receiving information about patients’ risk subgroup on referral forms. Conclusion These findings provide context for interpreting some of the trial outcomes, particularly in relation to changes in clinical decision-making when risk-based stratified care was used. Findings also indicate potential reasons for lack of GP engagement with risk-based stratified care. Positive outcomes were identified that were not captured in the quantitative data, specifically that risk-based stratified care positively influenced some GP-patient conversations and facilitated negotiation of treatment options. Trial registration ISRCTN15366334 (26/04/2016).

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

La formación investigativa desde el pregrado es indispensable para la preparación del estudiante de la carrera de Medicina. La investigación se realizó con el propósito de caracterizar el proceso antes citado en la formación del médico general. Se utilizaron los métodos teóricos histórico-lógico, analítico-sintético e inductivo-deductivo. Asimismo, para el análisis de los fundamentos teóricos de la formación investigativa se empleó la revisión documental para el análisis de los planes de estudio D y E de esa carrera. Se encontró que los planes de formación del médico general han sufrido modificaciones para lograr mayor pertinencia y calidad del egresado, sin embargo, aún persisten insuficiencias en la concepción de la formación investigativa del Médico General.

Abstract Background Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are the most common prostate disorders in the UK, which cause considerable ill health in older men. Transperineal template prostate biopsy (TTPB) has emerged as a reliable procedure for the histopathological diagnosis of PCa and BPH due to its higher cancer detection rates. Although antiseptic preparation and antibiotic prophylaxis are used to ensure safety in patients undergoing surgical intervention, post-operative complications, such as infection and bleeding are still unavoidable, resulting in re-admissions, with resource implications. Currently, there is no biomarker profile to predict outcomes or monitor patients during the post-operative course. The main aim of this single-centre observational clinical pilot-study was to investigate the role of inflammatory and infection biomarkers following TTPB and their association with post-operative complications. Methods Forty-five patients scheduled for elective TTPB were recruited after informed consent at the Wrexham Maelor and Glan Clwyd Hospitals, North Wales, UK (n = 45). Prior to surgery, venous blood samples were collected at baseline and subsequently at 30, 120, and 240 min post-operatively. Urine samples were collected before and 120 min after the procedure. Serum procalcitonin (PCT), serum ferritin, and urine B2MG analysis were done using enzyme-linked fluorescent assay (ELFA) and the magnetic Luminex® multiplex performance assay was used to analyse IL-6, IL-8, IL-10 and TNF-α plasma concentrations. Data on clinical outcomes were collected from patients’ medical records. Results Following TTPB, significant (p ≤ 0.05) increases were observed in uB2MG, IL-6, IL-8, IL-10 and TNF-α. Significant decreases were observed in ferritin (p ≤ 0.05). No significant change was observed in PCT concentration (p ≥ 0.05). One patient developed an infection and severe haematuria post-operatively following TTPB. Conclusion Although not confirmative, changes seen in biomarkers such as uB2MG, IL-10 and TNF-α in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications such as infection and bleeding which can develop following TTPB for the diagnosis of PCa and BPH.

Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in the Afrotropical region has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. As stressed within the recent WHO NTD 2021-2030 Roadmap and Revised Guideline for schistosomiasis, inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes. The aim of this study was to assess the sensitivity and specificity of the currently available point-of-care circulating cathodic antigen test (POC-CCA), designed for Schistosoma mansoni detection in humans, for the detection of intestinal livestock schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. POC-CCA, together with the circulating anodic antigen (CAA) test, miracidial hatching technique (MHT), Kato-Katz (KK) and organ and mesentery inspection (for animals from abattoirs only), were applied to samples collected from 195 animals (56 cattle and 139 small ruminants (goats and sheep) from abattoirs and living populations) from Senegal. POC-CCA sensitivity was greater in the S. curassoni-dominated Barkedji livestock, both for cattle (median 81%; 95% credible interval (CrI): 55%-98%) and small ruminants (49%; CrI: 29%-87%), than in the S. bovis-dominated Richard Toll ruminants (cattle: 62%; CrI: 41%-84%; small ruminants: 12%, CrI: 1%-37%). Overall, sensitivity was greater in cattle than in small ruminants. Small ruminants POC-CCA specificity was similar in both locations (91%; CrI: 77%-99%), whilst cattle POC-CCA specificity could not be assessed owing to the low number of uninfected cattle surveyed. Our results indicate that, whilst the current POC-CCA does represent a potential diagnostic tool for cattle and possibly for predominantly S. curassoni-infected livestock, future work is needed to develop parasite- and/or livestock-specific affordable and field-applicable diagnostic tests to enable determination of the true extent of livestock schistosomiasis.

Background: Up to 20% of women diagnosed with tubo-ovarian carcinoma carry a germline pathogenic variant in a cancer-predisposing gene (e.g., BRCA1/BRCA2). Identifying these variants can help to inform eligibility for therapies, guide surveillance and prevention of new primary cancers, and assess risk to family members. The Gynecologic Oncology-Initiated Genetic Testing Model (GOIGT) was initiated at the McGill University Health Centre (MUHC) to streamline universal germline genetic testing for this population, while addressing the limited resources in the public healthcare system. This study aimed to evaluate the patient experience of participating in this model. Methods: Study participants were patients diagnosed with high-grade non-mucinous epithelial tubo-ovarian cancer who underwent genetic testing through the GOIGT model between 1 January 2017 and 31 December 2020. Eligible participants completed the retrospective questionnaires at least one month after result disclosure. Results: A total of 126 patients were tested through the GOIGT model during the study period, of which 56 were invited to participate. Thirty-four participants returned the study questionnaire. Overall, participants did not report decision regret following the genetic testing and were satisfied with the GOIGT model. Participants reported low levels of uncertainty and distress related to the implications of their test results for themselves and their family members. Conclusions: The results of this study support the continued implementation of mainstreamed genetic testing models for women with high-grade non-mucinous tubo-ovarian cancer. Further studies are required to compare experiences for patients with different genetic test results.

Abstract Context Too many people living with chronic kidney disease are opting for and starting on hospital‐based dialysis compared to a home‐based kidney replacement therapy. Dialysis services are becoming financially unsustainable. Objective This study aimed to assess the efficacy of coproductive research in chronic kidney disease service improvement to achieve greater sustainability. Design A 2‐year coproductive service improvement study was conducted with multiple stakeholders with the specific intention of maximizing engagement with the national health kidney services, patients and public. Setting and Participants A national health kidney service (3 health boards, 18 dialysis units), patients and families (n = 50), multidisciplinary teams including doctors, nurses, psychologists, social workers, and so forth (n = 68), kidney charities, independent dialysis service providers and wider social services were part of this study. Findings Coproductive research identified underutilized resources (e.g., patients on home dialysis and social services) and their potential, highlighted unmet social care needs for patients and families and informed service redesign. Education packages were reimagined to support the home dialysis agenda including opportunities for wider service input. The impacts of one size fits all approaches to dialysis on specialist workforce skills were made clearer and also professional, patient and public perceptions of key sustainability policies. Discussion and Conclusions Patient and key stakeholders mapped out new ways to link services to create more sustainable models of kidney health and social care. Maintaining principles of knowledge coproduction could help achieve financial sustainability and move towards more prudent adult chronic kidney disease services. Patient or Public Contribution Involved in developing research questions, study design, management and conduct, interpretation of evidence and dissemination.

Abstract Background Angular cheilitis, an infection mainly caused by Candida yeasts, is featured by the appearance of inflammatory lesions at the bilateral corners of the mouth, particularly in patients with poor oral hygiene, ill-fitting dentures and old age. The first isolation of an atypical yeast, Cystobasidium calyptogenae, from oral samples of a patient presenting with angular cheilitis is discussed in this study. Case presentation Angular cheilitis was diagnosed in a 60-year-old denture-wearing woman who presented with an irritation fibroma on her right lower buccal sulcus over the premolar region. Primary cultures of her oral swab and oral rinse samples grew a pure culture of an uncommon yeast strain resembling Rhodotorula sp. Sequence analysis of the yeast internal transcribed spacer (ITS) gene region and D1D2 domain showed highest similarity (99.6% and 100%, respectively) to C. calyptogenae CBS 9125 type strain. Following 2 weeks of treatment with miconazole/fusidic acid and mouthwash, the oral lesion showed improvement with less erythema. C. calyptogenae was not isolated from the patient’s oral samples upon repeat sampling. Conclusion This is the first report on the isolation of C. calyptogenae from human oral samples. The ability of C. calyptogenae to grow at 37 °C and the fact that it was the only yeast species isolated from the patient’s oral samples suggests its pathogenic potential and possible involvement in angular cheilitis. The ubiquitous nature of the Cystobasidium yeast is believed to increase the likelihood of opportunistic infections among immunocompromised individuals. As Cystobasidium is phenotypically indistinguishable from Rhodotorula, an emerging opportunistic pathogen, surveillance using molecular identification in clinical settings is essential in providing accurate diagnosis and treatment of uncommon yeast infections.

Abstract Background Schistosomiasis is a disease that poses major threats to human and animal health, as well as the economy, especially in sub-Saharan Africa (SSA). Whilst many studies have evaluated the economic impact of schistosomiasis in humans, to date only one has been performed in livestock in SSA and none in Senegal. This study aimed to estimate the financial impact of livestock schistosomiasis in selected regions of Senegal. Methods Stochastic partial budget models were developed for traditional ruminant farmers in 12 villages in northern Senegal. The models were parameterised using data from a cross-sectional survey, focus group discussions, scientific literature and available statistics. Two scenarios were defined: scenario 1 modelled a situation in which farmers tested and treated their livestock for schistosomiasis, whilst scenario 2 modelled a situation in which there were no tests or treatment. The model was run with 10,000 iterations for 1 year; results were expressed in West African CFA francs (XOF; 1 XOF was equivalent to 0.0014 GBP at the time of analysis). Sensitivity analyses were conducted to assess the impact of uncertain variables on the disease costs. Results Farmers surveyed were aware of schistosomiasis in their ruminant livestock and reported hollowing around the eyes, diarrhoea and weight loss as the most common clinical signs in all species. For scenario 1, the median disease costs per year and head of cattle, sheep and goats were estimated at 13,408 XOF, 27,227 XOF and 27,694 XOF, respectively. For scenario 2, the disease costs per year and head of cattle, sheep and goats were estimated at 49,296 XOF, 70,072 XOF and 70,281 XOF, respectively. Conclusions Our findings suggest that the financial impact of livestock schistosomiasis on traditional subsistence and transhumance farmers is substantial. Consequently, treating livestock schistosomiasis has the potential to generate considerable benefits to farmers and their families. Given the dearth of data in this region, our study serves as a foundation for further in-depth studies to provide estimates of disease impact and as a baseline for future economic analyses. This will also enable One Health economic studies where the burden on both humans and animals is estimated and included in cross-sectoral cost–benefit and cost-effectiveness analyses of disease control strategies. Graphical Abstract

ObjectivesThis study aimed to explore experiences of women with anal incontinence following a childbirth injury, and to identify areas of missed opportunities within care they received.DesignThis is a qualitative study involving semi-structured interviews.SettingParticipants were recruited via five hospitals in the UK, and via social media adverts and communication from charity organisations.ParticipantsWomen who have experienced anal incontinence following a childbirth injury, either within 7 years of sustaining the injury, or if they identified new, or worsening symptoms of AI at the time of menopause.Main outcome measuresMain outcomes are experiences of women with anal incontinence following childbirth injury, and missed opportunities within the care they received.ResultsThe following main themes were identified: opportunities for diagnosis missed, missed opportunities for information sharing and continuity and timeliness of care.ConclusionsAnal Incontinence following a childbirth injury has a profound impact on women. Lack of information and awareness both amongst women and healthcare professionals contributes to delays in accurate diagnosis and appropriate treatment.

Abstract Introduction People with diabetic peripheral neuropathy (DPN) and limited joint mobility syndrome (LJMS) can experience increased forefoot peak plantar pressures (PPPs), a known risk factor for ulceration. The aim of this study was to investigate whether ankle and 1st metatarsophalangeal (MTP) joint mobilisations and home‐based stretches in people with DPN improve joint range of motion (ROM) and reduce forefoot PPPs. Design and methods Sixty‐one people with DPN (IWGDF risk 2), were randomly assigned to a 6‐week programme of ankle and 1st MTP joint mobilisations (n = 31) and home‐based stretches or standard care only (n = 30). At baseline (T0); 6‐week post intervention (T1) and at 3 months follow‐up (T2), a blinded assessor recorded dynamic ankle dorsiflexion range using 3D (Codamotion) motion analysis and the weight bearing lunge test, static 1st MTP joint dorsiflexion ROM, dynamic plantar pressure and balance. Results At T1 and T2 there was no difference between both groups in ankle dorsiflexion in stance phase, plantar pressure and balance. Compared to the control group, the intervention group showed a statistically significant increase in static ankle dorsiflexion range (Left 1.52 cm and 2.9cms, Right 1.62 cm and 2.7 cm) at 6 (T1) and 18 weeks (T2) respectively p

Wild capture fisheries are of economic and social importance, providing a primary source of protein to people globally. There is a broad research base on the environmental impacts of fishing gears and processing methods yet, the impact on the global CO2 budget is less well studied. Evaluating the risk that wild capture fisheries pose to ecosystem health is vital to sustainably managing fishing practices to meet increasing global nutritional needs and reverse declines in marine biodiversity. At the same time meeting net-zero ambitions by reducing direct and indirect GHG emissions is vital. Ecological risk assessments, trait-based assessments, and vulnerability assessments have long supported fisheries management systems globally but do not yet provide any representation regarding the impacts that fishing gears have on the ability of the habitat to capture and store carbon. Considering the importance of accessibility and transparency in approaches necessary for fisheries sustainability certifications, this paper describes a method to integrate habitat carbon capacity attributes into the Marine Stewardship Council (MSC) Consequence and Spatial Analysis (CSA) framework. Applying the CSA carbon extension developed herein produces different CSA risk scores compared to the MSC CSA that does not account for carbon. This has potential consequences for certification schemes as carbon becomes more important in the fisheries sustainability conversation. The CSA carbon extension tool developed here is an important first step in incorporating carbon indicators into evaluations of fisheries that consider fishery carbon impacts.