Young people's experiences of physical activity insecurity: a qualitative study highlighting intersectional disadvantage in the UK.

BACKGROUND: Intersecting socioeconomic and demographic reasons for physical activity (PA) inequalities are not well understood for young people at risk of experiencing marginalisation and living with disadvantage. This study explored young people's experiences of PA in their local area, and the associated impacts on opportunities for good physical and emotional health and wellbeing. METHODS: Seven local youth groups were purposefully sampled from disadvantaged areas across urban, rural and coastal areas of England, including two that were specifically for LGBTQ + young people. Each group engaged in three interlinked focus groups which explored young people's perceptions and lived experience of PA inequalities. Data were analysed using an inductive, reflexive thematic approach to allow for flexibility in coding. RESULTS: Fifty five young people aged 12-21 years of different sexualities, gender and ethnicity took part. Analysis yielded four themes: PA experiences across spaces; resigned to a lack of inclusivity and 'belonging'; safety first; complexities in access and accessibility. Young people felt more comfortable to be active in spaces that were simpler to navigate, particularly outdoor locations largely based in nature. In contrast, local gyms and sports clubs, and the school environment in general, were spoken about often in negative terms and as spaces where they experienced insecurity, unsafety or discomfort. It was common for these young people to feel excluded from PA, often linked to their gender and sexuality. Lived experiences or fears of being bullied and harassed in many activity spaces was a powerful message, but in contrast, young people perceived their local youth club as a safe space. Intersecting barriers related to deprivation, gender and sexuality, accessibility, disability, Covid-19, affordability, ethnicity, and proximity of social networks. A need emerged for safe spaces in which young people can come together, within the local community and choose to be active. CONCLUSIONS: The overarching concept of 'physical activity insecurity' emerged as a significant concern for the young people in this study. We posit that PA insecurity in this context can be described as a limited or restricted ability to be active, reinforced by worries and lived experiences of feeling uncomfortable, insecure, or unsafe.

Impact of clinicians' behavior, an educational intervention with mandated blood pressure and the hypotension prediction index software on intraoperative hypotension: a mixed methods study.

PURPOSE: Intraoperative hypotension (IOH) is associated with adverse outcomes. We therefore explored beliefs regarding IOH and barriers to its treatment. Secondarily, we assessed if an educational intervention and mandated mean arterial pressure (MAP), or the implementation of the Hypotension Prediction Index-software (HPI) were associated with a reduction in IOH. METHODS: Structured interviews (n = 27) and questionnaires (n = 84) were conducted to explore clinicians' beliefs and barriers to IOH treatment, in addition to usefulness of HPI questionnaires (n = 14). 150 elective major surgical patients who required invasive blood pressure monitoring were included in three cohorts to assess incidence and time-weighted average (TWA) of hypotension (MAP < 65 mmHg). Cohort one received standard care (baseline), the clinicians of cohort two had a training on hypotension and a mandated MAP > 65 mmHg, and patients of the third cohort received protocolized care using the HPI. RESULTS: Clinicians felt challenged to manage IOH in some patients, yet they reported sufficient knowledge and skills. HPI-software was considered useful and beneficial. No difference was found in incidence of IOH between cohorts. TWA was comparable between baseline and education cohort (0.15 mmHg [0.05-0.41] vs. 0.11 mmHg [0.02-0.37]), but was significantly lower in the HPI cohort (0.04 mmHg [0.00 to 0.11], p < 0.05 compared to both). CONCLUSIONS: Clinicians believed they had sufficient knowledge and skills, which could explain why no difference was found after the educational intervention. In the HPI cohort, IOH was significantly reduced compared to baseline, therefore HPI-software may help prevent IOH. TRIAL REGISTRATION: ISRCTN 17,085,700 on May 9th, 2019.

Chronic nSMase inhibition suppresses neuronal exosome spreading and sex-specifically attenuates amyloid pathology in APP knock-in Alzheimer's disease mice.

Female biased pathology and cognitive decline in Alzheimer's disease (AD) have been consistently observed with unclear underlying mechanisms. Although brain sphingolipid ceramide is elevated in AD patients, whether and how ceramide may contribute to sex-specific differences in amyloid pathology is unknown. Here we investigated the sex-specific impact of chronic pharmacological inhibition of neutral sphingomyelinase (nSMase), a key enzyme responsible for ceramide metabolism, on in vivo neuron-derived exosome dynamics, Aß plaque load, and cognitive function in the APPNL-F/NL-F knock-in (APP NL-F) AD mouse model. Our results found sex-specific increase of cortical C20:0 ceramide and brain exosome levels only in APP NL-F but not in age-matched WT mice. Although nSMase inhibition similarly blocks exosome spreading in male and female mice, significantly reduced amyloid pathology was mostly observed in cortex and hippocampus of female APP NL-F mice with only modest effect found on male APP NL-F mice. Consistently, T maze test to examine spatial working memory revealed a female-specific reduction in spontaneous alternation rate in APP NL-F mice, which was fully reversed with chronic nSMase inhibition. Together, our results suggest that disease induced changes in ceramide and exosome pathways contribute to the progression of female-specific amyloid pathology in APP NL-F AD models.

The understanding, application and influence of complexity in national physical activity policy-making.

BACKGROUND: Complexity theory and systems-thinking are increasingly popular in physical activity (PA) research and policy discourse. The impact of this perspective shift, across many sectors, may be underwhelming. We explore why, by focusing on how these concepts are understood and applied by PA policy-makers. This is of particular interest given the challenges of multisectoral interest and poorly defined stakeholder boundaries that are associated with PA promotion. In this study, we critique key elements of complexity theory and consider how it is understood and put into practice in PA policy-making. METHODS: We adopted a complex realist position. Ten semi-structured interviews were conducted with national-level policy-makers from United Kingdom government settings (five civil servants, three politicians, two policy advisors). An inductive thematic analysis was conducted, and managed with NVivo 10 software. RESULTS: Three overarching themes were constructed to reflect policy-makers' uncertainty about complexity and the application of such perspectives to this policy space, their sense that PA was an unexceptionable yet unclaimed policy issue, and their desire for influence and change. Participants discussed complexity in contrasting ways. Its meaning was context-dependent and dynamic, which generated uncertainty about applying the concept. Participants also perceived an increasingly diverse but ill-defined PA policy system that spans the domains of expertise and responsibility. Collaborative practices may contribute to a previously unobserved sense of detachment from the systems' complexity. Nevertheless, participants suggested potentially effective ways to stimulate system change, which require passionate and enterprising leadership, and included varied evidence use, a focus on localised implementation and different ways to connect people. CONCLUSIONS: This research highlighted the importance of extending complexity theory and systems-thinking. While emphasizing the prevalence of these ideas across the PA sector, there is uncertainty as to their meaning and implications. This may prevent their use in ways that enhance PA policies and programmes. Participants conceptualised PA as a tool, which was imposed on the system. While this may support participative decision-making and localised implementation, further research is needed to understand how local systems foster leadership, the practical application of complexity and systems-thinking, and how to support system-wide change in the development and implementation of PA policies.

The Shared Safety Net Action Plan (SSNAP): a co-designed intervention to reduce delays in cancer diagnosis.

BACKGROUND: Safety netting in primary care may help diagnose cancer earlier, but it is unclear what the format and content of an acceptable safety-netting intervention would be. This project aimed to co-design a safety-netting intervention with and for primary care patients and staff. AIM: This work sought to address how a safety-netting intervention would be implemented in practice; and, if and how a safety-netting intervention would be acceptable to all stakeholders. DESIGN AND SETTING: Patient representatives, GPs, and nurse practitioners were invited to a series of co-design workshops. Patients who had and had not received a diagnosis of cancer and primary care practices took part in separate focus groups. METHOD: Three workshops using creative co-design processes developed the format and content of the intervention prototype. The COM-B Framework underpinned five focus groups to establish views on capability, opportunity, and motivation to use the intervention to assist with prototype refinement. RESULTS: Workshops and focus groups suggested the intervention format and content should incorporate visual and written communication specifying clear timelines for monitoring symptoms and when to present back; be available in paper and electronic forms linked to existing computer systems; and be able to be delivered within a 10-minute consultation. Intervention use themes included 'building confidence through partnership', 'using familiar and current procedures and systems', and 'seeing value'. CONCLUSION: The Shared Safety Net Action Plan (SSNAP) - a safety-netting intervention to assist the timely diagnosis of cancer in primary care, was successfully co-designed with and for patients and primary care staff.

'It All Kind of Links Really': Young People's Perspectives on the Relationship between Socioeconomic Circumstances and Health.

Meaningful inclusion of young people's perceptions and experiences of inequalities is argued to be critical in the development of pro-equity policies. Our study explored young people's perceptions of what influences their opportunities to be healthy within their local area and their understandings of health inequalities. Three interlinked qualitative focus group discussions, each lasting 90 to 100 min, with the same six groups of young people (n = 42) aged 13-21, were conducted between February and June 2021. Participants were recruited from six youth groups in areas of high deprivation across three geographical locations in England (South Yorkshire, the North East and London). Our study demonstrates that young people understand that health inequalities are generated by social determinants of health, which in turn influence behaviours. They highlight a complex interweaving of pathways between social determinants and health outcomes. However, they do not tend to think in terms of the social determinants and their distribution as resulting from the power and influence of those who create and benefit from health and social inequalities. An informed understanding of the causes of health inequalities, influenced by their own unique generational experiences, is important to help young people contribute to the development of pro-equity policies of the future.

Inequalities and Inclusion in Exercise Referral Schemes: A Mixed-Method Multi-Scheme Analysis.

Physical activity prescription, commonly through exercise referral schemes, is an established disease prevention and management pathway. There is considerable heterogeneity in terms of uptake, adherence, and outcomes, but because within-scheme analyses dominate previous research, there is limited contextual understanding of this variance. Both the impact of schemes on health inequalities and best practices for inclusion of at-risk groups are unclear. To address this, we modelled secondary data from the multi-scheme National Referral Database, comprising 23,782 individuals across 14 referral schemes, using a multilevel Bayesian inference approach. Scheme-level local demographics identified over-sampling in uptake; on the basis of uptake and completion data, more inclusive schemes (n = 4) were identified. Scheme coordinators were interviewed, and data were analyzed using a grounded theory approach. Inequalities presented in a nuanced way. Schemes showed promise for engaging populations at greater risk of poor health (e.g., those from more deprived areas or of an ethnic minority background). However, the completion odds were lower for those with a range of complex circumstances (e.g., a mental health-related referral). We identified creative best practices for widening access (e.g., partnership building), maintaining engagement (e.g., workforce diversity), and tailoring support, but recommend changes to wider operational contexts to ensure such approaches are viable.

A modified Delphi study to gain consensus for a taxonomy to report and classify physical activity referral schemes (PARS).

BACKGROUND: Physical Activity Referral Schemes (PARS), including exercise referral schemes, are a popular approach to health improvement, but understanding of effectiveness is limited by considerable heterogeneity in reporting and evaluation. We aimed to gain consensus for a PARS taxonomy as a comprehensive method for reporting and recording of such schemes. METHODS: We invited 62 experts from PARS policy, research and practice to complete a modified Delphi study. In round one, participants rated the need for a PARS taxonomy, the suitability of three proposed classification levels and commented on proposed elements. In round two, participants rated proposed taxonomy elements on an 11-point Likert scale. Elements scoring a median of ≥7, indicating high agreement, were included in the final taxonomy. RESULTS: Of those invited, 47 (75.8%) participated in round one, with high retention in round two (n = 43; 91.5%). 42 were UK-based, meaning the resultant taxonomy has been scrutinised for fit to the UK context only. The study gained consensus for a three-level taxonomy: Level 1: PARS classification (primary classification, provider, setting, conditions accepted [have or at risk of], activity type and funding). Level 2: scheme characteristics (staff structure, staff qualifications, behaviour change theories, behaviour change techniques, referral source, referrers, referral process, scheme duration, session frequency, session length, session times, session type, exit routes, action in case of non-attendance, baseline assessment, exit assessment, feedback to referrer and exclusion criteria) and Level 3: participant measures (demographics, monitoring and evaluation, and measures of change). CONCLUSION: Using a modified Delphi method, this study developed UK-based consensus on a PARS classification taxonomy. We encourage PARS practitioners and public health colleagues, especially those working with similar service models internationally, to test, refine and use this taxonomy to inform policy and practice.

Challenges, opportunities and solutions for local physical activity stakeholders: an implementation case study from a cross-sectoral physical activity network in Northeast England.

BACKGROUND: Increasingly, national policy initiatives and programmes have been developed to increase physical activity (PA). However, challenges in implementing and translating these policies into effective local-level programmes have persisted, and change in population PA levels has been small. This may be due to insufficient attention given to the implementation context, and the limited interactions between local policy-makers, practitioners and researchers. In this paper we use a case study of a cross-sectoral network in Northeast England, to identify the local-level challenges and opportunities for implementing PA policies and programmes, particularly the updated 2019 UK PA guidelines. METHODS: Five focus groups (n = 59) were conducted with practice partners, local policy-makers and researchers during an initial workshop in April 2018. Through facilitated discussion, participants considered regional priorities for research and practice, along with barriers to implementing this agenda and how these may be overcome. During a second workshop in December 2018, overarching findings from workshop one were fedback to a similar group of stakeholders, along with national policy-makers, to stimulate feedback from delegates on experiences that may support the implementation of the UK PA guidelines locally, focusing on specific considerations for research, evidence and knowledge exchange. RESULTS: In workshop one, three overarching themes were developed to capture local challenges and needs: (i) understanding complexity and context; (ii) addressing the knowledge and skills gap; and (iii) mismatched timescales and practices. In workshop two, participants' implementation plans encompassed: (i) exploring a systems approach to implementation; (ii) adapting policy to context; and (iii) local prioritising. CONCLUSIONS: Our findings suggest that academics, practitioners and policy-makers understand the complexities of implementing PA strategies, and the challenges of knowledge exchange. The updated UK PA guidelines policy presented an opportunity for multiple agencies to consider context-specific implementation and address enduring tensions between stakeholders. An organically derived implementation plan that prioritises PA, maps links to relevant local policies and supports a context-appropriate communication strategy, within local policy, practice and research networks, will help address these. We present 10 guiding principles to support transferable knowledge exchange activities within networks to facilitate implementation of national PA policy in local contexts.

Aging lowers PEX5 levels in cortical neurons in male and female mouse brains.

Peroxisomes exist in nearly every cell, oxidizing fats, synthesizing lipids and maintaining redox balance. As the brain ages, multiple pathways are negatively affected, but it is currently unknown if peroxisomal proteins are affected by aging in the brain. While recent studies have investigated a PEX5 homolog in aging C. elegans models and found that it is reduced in aging, it is unclear if PEX5, a mammalian peroxisomal protein that plays a role in peroxisomal homeostasis and degradation, is affected in the aging brain. To answer this question, we first determined the amount of PEX5, in brain homogenates from young (3 months) and aged (26 through 32+ months of age) wild-type mice of both sexes. PEX5 protein was decreased in aged male brains, but this reduction was not significant in female brains. RNAScope and real-time qPCR analyses showed that Pex5 mRNA was also reduced in aged male brain cortices, but not in females. Immunohistochemistry assays of cortical neurons in young and aged male brains showed that the amount of neuronal PEX5 was reduced in aged male brains. Cortical neurons in aged female mice also had reduced PEX5 levels in comparison to younger female mice. In conclusion, total PEX5 levels and Pex5 gene expression both decrease with age in male brains, and neuronal PEX5 levels lower in an age-dependent manner in the cortices of animals of both sexes.

The Northumberland Exercise Referral Scheme as a Universal Community Weight Management Programme: A Mixed Methods Exploration of Outcomes, Expectations and Experiences across a Social Gradient.

Exercise referral schemes (ERS) are internationally recognised, yet little attention has been paid to discrete referral groups or the influence of wider social determinants of health. The primary quantitative element of this mixed methods study used a mixed effects linear model to examine associations of sociodemographic predictors, obesity class and profession of referrer on weight and physical activity (PA) variables for weight-related referrals (n = 3624) to an established 24-week ERS. Chained equations modelling imputed missing data. The embedded qualitative element (n = 7) used individual semi-structured interviews to explore participant weight-related expectations and experiences. Age, gender and profession of referrer influenced weight loss. PA increased and was influenced by age and gender. The weight gap between the most and least obese narrowed over time but the PA gap between most and least widened. Age, employment and obesity class were most predictive of missing data but would unlikely alter overall conclusions. Qualitative themes were weight-loss support, personal circumstances and strategies, and weight expectations versus wellbeing rewards. This ERS worked, did not widen existing obesity inequalities, but demonstrated evidence of PA inequalities for those living with deprivation. To improve equity of experience, we recommend further stakeholder dialogue around referral experience and ongoing support needs.

Inequities and inequalities in outdoor walking groups: a scoping review.

BACKGROUND: Outdoor walking groups are widely-used programmes aimed at improving physical activity and health outcomes. Despite being promoted as accessible and inclusive, emerging work highlights participation biases based on gender, age and socioeconomic status, for example. To explicate the impact of outdoor walking groups on physical activity inequities, we conducted a scoping review of published outdoor walking group literatures. Specifically, we critically examined: (a) equity integration strategies; (b) intervention reach; (c) effectiveness; and (d) potential social determinants of engagement relating to the World Health Organization's conceptual framework. METHODS: Arksey and O'Malley's scoping review protocol was used to develop a comprehensive search strategy and identify relevant academic and grey literatures, which were screened using pre-defined inclusion and exclusion criteria. Data were organised by Cochrane PROGRESS-Plus equity characteristics and a narrative summary was presented for each thematic area. FINDINGS: Sixty-two publications were included. Key findings were: (a) some evidence of targeted intervention trials. Large-scale national programmes were tailored to regional activity and health needs, which may contribute toward addressing inequities. However, participant demographics seldom informed reported analyses; (b) participation was more likely among white, more socioeconomically advantaged, middle-to-older aged, female and able-bodied adults; (c) positive physical and psychological outcomes were unlikely to extend along social gradients; and (d) interventions primarily addressed intermediary determinants (e.g. psychosocial barriers; material resource). Social capital (e.g. friend-making) was identified as potentially important for addressing physical activity inequalities. CONCLUSIONS: The published literature on outdoor walking groups leaves unanswered questions regarding participation inequalities, with implications for future physical activity promotion. Currently, participation in outdoor walking groups is typically more prevalent among advantaged subpopulations. We make recommendations for research and practice to address these issues, as well as aid the translation of existing knowledge into practice. We advocate increased focus on the social determinants of engagement. A more consistent approach to collecting and analysing participant socio-demographic data is required. Our findings also support recommendations that appropriate tailoring of universal programmes to community needs and embedding strategies to increase social cohesion are important in developing equitable programmes.

Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-ß in Tg2576 Mice.

Amyloid plaques in Alzheimer's disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (Aß) pathogenesis; however, the mechanisms are still not well understood. We hypothesize that the gut bears the Aß burden prior to brain, highlighting gut-brain axis (GBA) interaction in neurodegenerative disorders. We used pre-symptomatic (6-months) and symptomatic (15-months) Tg2576 mouse model of AD compared to their age-matched littermate WT control. We identified that dysfunction of intestinal epithelial barrier (IEB), dysregulation of absorption, and vascular Aß deposition in the IEB occur before cerebral Aß aggregation is detectible. These changes in the GBA were associated with elevated inflammatory plasma cytokines including IL-9, VEGF and IP-10. In association with reduced cerebral myelin tight junction proteins, we identified reduced levels of systemic vitamin B12 and decrease cubilin, an intestinal B12 transporter, after the development of cerebral Aß pathology. Lastly, we report Aß deposition in the intestinal autopsy from AD patients with confirmed cerebral Aß pathology that is not present in intestine from non-AD controls. Our data provide evidence that gut dysfunction occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve the early manipulation of gut physiology and its microbiota.

The early diagnosis of cancer in primary care: A qualitative exploration of the patient's role and acceptable safety-netting strategies.

OBJECTIVES: The study had two aims-to assess the components considered important for patient involvement in diagnosing cancer earlier in primary care and to assess the acceptability, feasibility, cost and burden of three safety-netting interventions in terms of their potential to become a sustainable component of standard care and improve diagnostic outcomes for cancer in a primary care setting. METHOD: Fifteen interviews were conducted with patients and GPs/Nurse Practitioners. Findings were fed back at a workshop with 18 stakeholders who helped to conceptualise an intervention. Interviews were analysed using thematic analysis. Stakeholder discussions were captured through group feedback sessions. RESULTS: Three key themes around stakeholders' views on patient involvement emerged from the interviews. These were keeping the door open, roles and responsibilities and fear of cancer. Interview findings and workshop feedback identified the intervention should include a verbal discussion and plan, written information and a patient prompt option. CONCLUSION: Patient involvement in diagnosing cancer in primary care is considered acceptable to patients and HCPs. Factors that facilitate or hinder involvement have been identified. Components deemed important in a safety-netting intervention, and potential costs and benefits were established. This knowledge can direct future research and the development of safety-netting interventions.

Validation of revised patient measures of safety: PMOS-30 and PMOS-10.

OBJECTIVES: There is growing evidence that patients can provide feedback on the safety of their care. The 44-item Patient Measure of Safety (PMOS) was developed for this purpose. While valid and reliable, the length of this questionnaire makes it potentially challenging for routine use. Our study aimed to produce revised, shortened versions of PMOS (PMOS-30 and PMOS-10), which retained the psychometric properties of the longer version. PARTICIPANTS: To produce a shortened diagnostic measure, we analysed data from 2002 patients who completed PMOS-44, and examined the reliability of the revised measure (PMOS-30) in a sample of 751 patients. To produce a brief standalone measure, we again analysed data from 2002 patients who completed PMOS-44, and tested the reliability and validity of the brief standalone measure (PMOS-10) in a sample of 165 patients. METHODS: The process of shortening the questionnaire involved a combination of secondary data analysis (eg, Standard Deviation and inter-item correlations) and a consensus group exercise to produce PMOS-30 and examine face validity. Analysis of PMOS-30 data examined reliability (eg, Cronbach's alpha). Further secondary data analysis (ie, corrected item-total correlations) produced PMOS-10, and primary data collection assessed its reliability and validity (eg, Cronbach's alpha, analysis of variance). RESULTS: Fourteen items were removed to produce PMOS-30 and the percentage of negatively worded items was reduced from 57% to 33%. PMOS-30 demonstrated good internal reliability (α=0.89). The 10 items with the highest corrected item-total correlations across both PMOS-44 and PMOS-30 composed PMOS-10. PMOS-10 had good internal reliability (α=0.79), demonstrated convergent validity; however, discriminant validity was not established. CONCLUSIONS: Two revised, shortened versions of the original PMOS-44 (PMOS-30 and PMOS-10) were produced to capture patient feedback about safety in hospital. The measures demonstrated good reliability and validity, and preserved the psychometric properties of the original measure.

Prototyping for public health in a local context: a streamlined evaluation of a community-based weight management programme (Momenta), Northumberland, UK.

OBJECTIVES: Stakeholder co-production in design of public health programmes may reduce the 'implementation gap' but can be time-consuming and costly. Prototyping, iterative refining relevant to delivery context, offers a potential solution. This evaluation explored implementation and lessons learnt for a 12-week referral-based weight-management programme, 'Momenta', along with feasibility of an iterative prototyping evaluation framework. DESIGN: Mixed methods evaluation: Qualitative implementation exploration with referrers and service users; preliminary analysis of anonymised quantitative service data (12 and 52 weeks). SETTING: Two leisure centres in Northumberland, North East England. PARTICIPANTS: Individual interviews with referring professionals (n=5) and focus groups with service users (n=13). Individuals (n=182) referred by healthcare professionals (quantitative data). INTERVENTIONS: Three 12-week programme iterations: Momenta (n=59), Momenta-Fitness membership (n=58) and Fitness membership only (n=65). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: Qualitative themes developed through stakeholder-engagement. Secondary outcomes included preliminary exploration of recruitment, uptake, retention, and changes in weight, body mass index, waist circumference and psychological well-being. RESULTS: Service users reported positive experiences of Momenta. Implementation gaps were revealed around the referral process and practitioner knowledge. Prototyping enabled iterative refinements such as broadening inclusion criteria. Uptake and 12-week retention were higher for Momenta (84.7%, 45.8%) and Momenta-Fitness (93.1%, 60.3%) versus Fitness only (75.4%, 24.6%). Exploration of other preliminary outcomes (completers only) suggested potential for within-group weight loss and increased psychological well-being for Momenta and Momenta-Fitness at 12 weeks. 52 week follow-up data were limited (32%, 33% and 6% retention for those who started Momenta, Momenta-Fitness and Fitness, respectively) but suggested potential weight loss maintenance for Momenta-Fitness. CONCLUSIONS: Identification of issues within the referral process enabled real-time iterative refinement, while lessons learnt may be of value for local implementation of 'off-the-shelf' weight management packages more generally. Our preliminary data for completers suggest Momenta may have potential for weight loss, particularly when offered with a fitness membership.

Individual Sea Urchin Coelomocytes Undergo Somatic Immune Gene Diversification.

The adaptive immune response in jawed vertebrates is marked by the ability to diversify somatically specific immune receptor genes. Somatic recombination and hypermutation of gene segments are used to generate extensive repertoires of T and B cell receptors. In contrast, jawless vertebrates utilize a distinct diversification system based on copy choice to assemble their variable lymphocyte receptors. To date, very little evidence for somatic immune gene diversification has been reported in invertebrate species. Here we show that the SpTransformer (SpTrf ; formerly Sp185/333) immune effector gene family members from individual coelomocytes from purple sea urchins undergo somatic diversification by means of gene deletions, duplications, and acquisitions of single nucleotide polymorphisms. While sperm cells from an individual sea urchin have identical SpTrf gene repertoires, single cells from two distinct coelomocyte subpopulations from the same sea urchin exhibit significant variation in the SpTrf gene repertoires. Moreover, the highly diverse gene sequences derived from single coelomocytes are all in-frame, suggesting that an unknown mechanism(s) driving these somatic changes involve stringent selection or correction processes for expression of productive SpTrf transcripts. Together, our findings infer somatic immune gene diversification strategy in an invertebrate.

The Axial Organ and the Pharynx Are Sites of Hematopoiesis in the Sea Urchin.

Background: The location of coelomocyte proliferation in adult sea urchins is unknown and speculations since the early 1800s have been based on microanatomy and tracer uptake studies. In adult sea urchins (Strongylocentrotus purpuratus) with down-regulated immune systems, coelomocyte numbers increase in response to immune challenge, and whether some or all of these cells are newly proliferated is not known. The gene regulatory network that encodes transcription factors that control hematopoiesis in embryonic and larval sea urchins has not been investigated in adults. Hence, to identify the hematopoietic tissue in adult sea urchins, cell proliferation, expression of phagocyte specific genes, and expression of genes encoding transcription factors that function in the conserved regulatory network that controls hematopoiesis in embryonic and larval sea urchins were investigated for several tissues. Results: Cell proliferation was induced in adult sea urchins either by immune challenge through injection of heat-killed Vibrio diazotrophicus or by cell depletion through aspiration of coelomic fluid. In response to either of these stimuli, newly proliferated coelomocytes constitute only about 10% of the cells in the coelomic fluid. In tissues, newly proliferated cells and cells that express SpTransformer proteins (formerly Sp185/333) that are markers for phagocytes are present in the axial organ, gonad, pharynx, esophagus, and gut with no differences among tissues. The expression level of genes encoding transcription factors that regulate hematopoiesis show that both the axial organ and the pharynx have elevated expression compared to coelomocytes, esophagus, gut, and gonad. Similarly, an RNAseq dataset shows similar results for the axial organ and pharynx, but also suggests that the axial organ may be a site for removal and recycling of cells in the coelomic cavity. Conclusions: Results presented here are consistent with previous speculations that the axial organ may be a site of coelomocyte proliferation and that it may also be a center for cellular removal and recycling. A second site, the pharynx, may also have hematopoietic activity, a tissue that has been assumed to function only as part of the intestinal tract.

How do participant experiences and characteristics influence engagement in exercise referral? A qualitative longitudinal study of a scheme in Northumberland, UK.

OBJECTIVES: Exercise referral schemes (ERSs) are internationally widespread. This study aimed to gain an insight into differential engagement through understanding participant experiences of patients referred by healthcare professionals to one such scheme in the UK. DESIGN: The study employed a qualitative longitudinal approach using semistructured interviews, with results reported using Consolidated criteria for Reporting Qualitative research guidelines. SETTING: Two leisure centres providing an 'emerging best-practice' ERS in northeast England. PARTICIPANTS: Referred patients (n=11), who had not yet commenced the scheme, were recruited on a voluntary basis. Seven females and four males, with a range of non-communicable diseases, such as cardiovascular disease, mental health issues, diabetes, overweight/obesity and musculoskeletal problems, participated. INTERVENTION: 24-weeks, two times per week, of supervised exercise sessions and three one-to-one assessments (prescheme, 12 weeks and 24 weeks) for patients referred from primary and secondary care. PRIMARY OUTCOME MEASURES: Two longitudinal semistructured interviews, prior to commencement and 12-20 weeks later, were thematically analysed using the framework approach. Analysis comprised seven stages: transcription, familiarisation, coding, development and application of an analytical framework, charting data using a matrix and interpretation of data. Interpretation went beyond descriptions of individual cases to develop themes, which identified and offered possible explanations for differing participant experiences. RESULTS: Three overarching themes emerged. First, 'success', with engaged participants focused on health outcomes and reported increases in physical activity. Second, 'struggle', with short-term success but concerns regarding continued engagement. Participants reported scheme dependency and cyclical needs. Finally, 'defeat', where ill health, social anxiety and/or poor participation experience made engagement difficult. CONCLUSION: Some success in engaging those with non-communicable diseases was reported, resulting in positive effects on health and well-being. The study highlights complexity within ERSs and inequality of access for those with challenging health and social circumstances. Improved, or different, behaviour change support is required for referrals finding engagement difficult.