Cost-effectiveness of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: an economic evaluation of the REACT (Retirement in Action) trial.

BACKGROUND: Mobility limitations in older populations have a substantial impact on health outcomes, quality of life, and social care costs. The Retirement in Action (REACT) randomised controlled trial assessed a 12-month community-based group physical activity and behaviour maintenance intervention to help prevent decline in physical functioning in older adults at increased risk of mobility limitation. We aimed to do an economic evaluation of the REACT trial to investigate whether the intervention is cost-effective. METHODS: In this health economic evaluation, we did cost-effectiveness and cost-utility analyses of the REACT programme versus standard care on the basis of resource use, primary outcome, and health-related quality-of-life data measured in the REACT trial. We also developed a decision analytic Markov model that forecasts the mobility of recipients beyond the 24-month follow-up of the trial and translated this into future costs and potential benefit to health-related quality of life using the National Health Service and Personal Social Services perspective. Participants completed questionnaire booklets at baseline, and at 6, 12, and 24 months after randomisation, which included a resource use questionnaire and the EQ-5D-5L and 36-item short-form survey (SF-36) health-related quality-of-life instruments. The cost of delivering the intervention was estimated by identifying key resources, such as REACT session leader time, time of an individual to coordinate the programme, and venue hire. EQ-5D-5L and SF-36 responses were converted to preference-based utility values, which were used to estimate quality-adjusted life-years (QALYs) over the 24-month trial follow-up using the area-under-the-curve method. We used generalised linear models to examine the effect of the REACT programme on costs and QALYs and adjust for baseline covariates. Costs and QALYs beyond 12 months were discounted at 3·5% per year. This is a pre-planned analysis of the REACT trial; the trial itself is registered with ISRCTN (ISRCTN45627165). FINDINGS: The 12-month REACT programme was estimated to cost £622 per recipient to deliver. The most substantial cost components are the REACT session leader time (£309 per participant), venue hire (£109), and the REACT coordinator time (£80). The base-case analysis of the trial-based economic evaluation showed that reductions in health and social care usage due to the REACT programme could offset the REACT delivery costs (£3943 in the intervention group vs £4043 in the control group; difference: -£103 [95% CI -£695 to £489]) with a health benefit of 0·04 QALYs (0·009-0·071; 1·354 QALYs in the intervention group vs 1·314 QALYs in the control group) within the 24-month timeframe of the trial. INTERPRETATION: The REACT programme could be considered a cost-effective approach for improving the health-related quality of life of older adults at risk of mobility limitations. FUNDING: National Institute for Health Research Public Health Research Programme.

Effect of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: the REACT (Retirement in Action) randomised controlled trial.

BACKGROUND: Mobility limitations in old age can greatly reduce quality of life, generate substantial health and social care costs, and increase mortality. Through the Retirement in Action (REACT) trial, we aimed to establish whether a community-based active ageing intervention could prevent decline in lower limb physical functioning in older adults already at increased risk of mobility limitation. METHODS: In this pragmatic, multicentre, two-arm, single-blind, parallel-group, randomised, controlled trial, we recruited older adults (aged 65 years or older and who are not in full-time employment) with reduced lower limb physical functioning (Short Physical Performance Battery [SPPB] score 4-9) from 35 primary care practices across three sites (Bristol and Bath; Birmingham; and Devon) in England. Participants were randomly assigned to receive brief advice (three healthy ageing education sessions) or a 12-month, group-based, multimodal physical activity (64 1-h exercise sessions) and behavioural maintenance (21 45-min sessions) programme delivered by charity and community or leisure centre staff in local communities. Randomisation was stratified by site and adopted a minimisation approach to balance groups by age, sex, and SPPB score, using a centralised, online, randomisation algorithm. Researchers involved in data collection and analysis were masked but participants were not because of the nature of the intervention. The primary outcome was change in SPPB score at 24 months, analysed by intention to treat. This trial is registered with ISRCTN, ISRCTN45627165. FINDINGS: Between June 20, 2016, and Oct 30, 2017, 777 participants (mean age 77·6 [SD 6·8] years; 66% female; mean SPPB score 7·37 [1·56]) were randomly assigned to the intervention (n=410) and control (n=367) groups. Primary outcome data at 24 months were provided by 628 (81%) participants (294 in the control group and 334 in the intervention group). At the 24-month follow-up, the SPPB score (adjusted for baseline SPPB score, age, sex, study site, and exercise group) was significantly greater in the intervention group (mean 8·08 [SD 2·87]) than in the control group (mean 7·59 [2·61]), with an adjusted mean difference of 0·49 (95% CI 0·06-0·92; p=0·014), which is just below our predefined clinically meaningful difference of 0·50. One adverse event was related to the intervention; the most common unrelated adverse events were heart conditions, strokes, and falls. INTERPRETATION: For older adults at risk of mobility limitations, the REACT intervention showed that a 12-month physical activity and behavioural maintenance programme could help prevent decline in physical function over a 24-month period. FUNDING: National Institute for Health Research Public Health Research Programme (13/164/51).

Exploring the views of planners and public health practitioners on integrating health evidence into spatial planning in England: a mixed-methods study.

BACKGROUND: This study explored barriers and facilitators to integrating health evidence into spatial planning at local authority levels and examined the awareness and use of the Public Health England 'Spatial Planning for Health' resource. METHODS: A sequential exploratory mixed-methods design utilized in-depth semi-structured interviews followed by an online survey of public health, planning and other built environment professionals in England. RESULTS: Views from 19 individuals and 162 survey responses revealed high awareness and use of the Spatial Planning for Health resource, although public health professionals reported greater awareness and use than other professionals. Key barriers to evidence implementation included differences in interpretation and the use of 'evidence' between public health and planning professionals, lack of practical evidence to apply locally and lack of resource and staff capacity in local authorities. Key facilitators included integrating health into the design of local plans, articulating wider benefits to multiple stakeholders and simplifying presenting evidence (regarding language and accessibility). CONCLUSION: The Spatial Planning for Health resource is a useful resource at local authority level. Further work is needed to maximize its use by built environment professionals. Public health teams need support, capacity and skills to ensure that local health and well-being priorities are integrated into local planning documents and decisions.

Exploring young people's interpretations of female genital mutilation in the UK using a community-based participatory research approach.

BACKGROUND: Female genital mutilation (FGM) is a deeply-rooted cultural practice mainly undertaken in Africa, the Middle East and Asian countries. Evidence to date suggests that although first-generation migrants to the West are abandoning FGM, the custom continues in some places, albeit in small numbers. This study examined how young people living in FGM affected communities in the United Kingdom (UK), interpreted and explained FGM. METHODS: A community-based participatory research (CBPR) approach was used to recruit and train nine young people aged 15-18 as co-researchers. These comprised eight females and one male from second-generation FGM affected communities, living in Bristol. The co-researchers then undertook focus groups and semi-structured interviews with twenty participants aged 13-15 living in Bristol, Cardiff and Milton Keynes. The qualitative data from the training workshops, interviews and focus groups were collected and analysed using thematic analysis. RESULTS: There were conflicting views among participants. Some perceived FGM as a historical tradition that was of very little, if any, relevance to them. In contrast, others perceived that the more archaic, cultural interpretation of FGM, more commonly shared by older generations, had been supplanted by a new form of FGM, which they believed to be a safe procedure, made so by the availability of highly-trained, qualified doctors and better equipment in the UK. Participants spoke of challenges encountered when attempting to raise the issue of FGM with parents. Nevertheless, they acknowledged that- being born and raised in the UK - enabled them to talk openly and to challenge others. CONCLUSION: Future strategies to address and prevent FGM in the UK will require a public health approach that is holistic, intersectional and empowering. Such measures should be relevant to young people born and raised in the UK who interpret FGM differently to previous first-generation migrant relatives and communities. Tackling FGM requires a shift away from a principal preoccupation with harm reduction and criminalisation towards collaboration and active dialogue with communities, in positive and productive ways that acknowledge and engage issues of identity, race, gender, and generation, enabling people affected by FGM to take control of their health and well-being.

The Tribulations of Trials: Lessons Learnt Recruiting 777 Older Adults Into REtirement in ACTion (REACT), a Trial of a Community, Group-Based Active Aging Intervention Targeting Mobility Disability.

BACKGROUND: Challenges of recruitment to randomized controlled trials (RCTs) and successful strategies to overcome them should be clearly reported to improve recruitment into future trials. REtirement in ACTion (REACT) is a United Kingdom-based multicenter RCT recruiting older adults at high risk of mobility disability to a 12-month group-based exercise and behavior maintenance program or to a minimal Healthy Aging control intervention. METHODS: The recruitment target was 768 adults, aged 65 years and older scoring 4-9 on the Short Physical Performance Battery (SPPB). Recruitment methods include the following: (a) invitations mailed by general practitioners (GPs); (b) invitations distributed via third-sector organizations; and (c) public relations (PR) campaign. Yields, efficiency, and costs were calculated. RESULTS: The study recruited 777 (33.9% men) community-dwelling, older adults (mean age 77.55 years (SD 6.79), mean SPPB score 7.37 (SD 1.56)), 95.11% white (n = 739) and broadly representative of UK quintiles of deprivation. Over a 20-month recruitment period, 25,559 invitations were issued. Eighty-eight percent of the participants were recruited via GP invitations, 5.4% via the PR campaign, 3% via word-of-mouth, and 2.5% via third-sector organizations. Mean recruitment cost per participant was £78.47, with an extra £26.54 per recruit paid to GPs to cover research costs. CONCLUSIONS: REACT successfully recruited to target. Response rates were lower than initially predicted and recruitment timescales required adjustment. Written invitations from GPs were the most efficient method for recruiting older adults at risk of mobility disability. Targeted efforts could achieve more ethnically diverse cohorts. All trials should be required to provide recruitment data to enable evidence-based planning of future trials.

Feasibility Trial Evaluation of a Peer Volunteering Active Aging Intervention: ACE (Active, Connected, Engaged).

BACKGROUND: ACE (Active, Connected, Engaged) is a theory-informed, pragmatic intervention using peer volunteering support to promote active ageing in socially disengaged, inactive older adults. This study aimed to establish ACE's feasibility and acceptability. METHODS: Fifty-four older adults were recruited as either peer volunteers (activators; n = 15) or participants (ACEs; n = 39). Participants were randomized to one-to-one support from an activator (ACEs-Intervention [ACEs-I]) or a waiting-list control group (ACEs-Control [ACEs-C]). Activators supported ACEs-I to get out more and engage with local activities. Objectively measured physical activity (PA), lower limb function, and number of out of house activities were assessed at baseline and post-intervention. A mixed-methods process evaluation assessed changes in confidence to get out and about, social support, autonomy, competence, and relatedness. RESULTS: Eighty-two percent of ACEs (mean age = 73.7 years [SD 7.3]) and all activators completed assessments at both baseline and post-intervention (6 months). ACEs-I reported more out of house activities (M [SD] = 6.34 [4.15]). ACEs-I increased physical function post-intervention (M [SD] = 9.8 [2.3]). ACEs-I reported improved well-being and vitality and increased confidence to get out and about, confidence in the face of specific barriers, knowledge of local initiatives, and perceived social support post-intervention. Activators, although sufficiently active at baseline, increased their PA further. ACE was well-accepted and easy to deliver. CONCLUSIONS: ACE is an acceptable and feasible intervention for helping socially disengaged older people to get out and about more, improve their confidence, and engage more with their community.

Influence of visual targets and landmarks on honey bee foraging and waggle dancing.

Animals use diverse sensory stimuli to navigate their environment and to recognize rewarding food sources. Honey bees use visual attributes of the targeted food source, such as its color, shape, size, direction and distance from the hive, and the landmarks around it to navigate during foraging. They transmit the location information of the food source to other bees if it is highly rewarding. To investigate the relative importance of these attributes, we trained bees to feeders in two different experiments. In the first experiment, we asked whether bees prefer to land on (a) a similar feeder at a different distance on the same heading or on (b) a visually distinct feeder located at the exact same location. We found that, within a short foraging range, bees relied heavily on the color and the shape of the food source and to a lesser extent on its distance from the hive. In the second experiment, we asked if moving the main landmark or the feeder (visual target) influenced recruitment dancing for the feeder. We found that foragers took longer to land and danced fewer circuits when the location of the food source, or a major landmark associated with it, changed. These results demonstrate that prominent visual attributes of food sources and landmarks are evidently more reliable than distance information and that foraging bees heavily utilize these visual cues at the later stages of their journey.

Methods of identifying and recruiting older people at risk of social isolation and loneliness: a mixed methods review.

BACKGROUND: Loneliness and social isolation are major determinants of mental wellbeing, especially among older adults. The effectiveness of interventions to address loneliness and social isolation among older adults has been questioned due to the lack of transparency in identifying and recruiting populations at risk. This paper aims to systematically review methods used to identify and recruit older people at risk of loneliness and social isolation into research studies that seek to address loneliness and social isolation. METHODS: In total, 751 studies were identified from a structured search of eleven electronic databases combined with hand searching of reference bibliography from identified studies for grey literature. Studies conducted between January 1995 and December 2017 were eligible provided they recruited community living individuals aged 50 and above at risk of social isolation or loneliness into an intervention study. RESULT: A total of 22 studies were deemed eligible for inclusion. Findings from these studies showed that the most common strategy for inviting people to participate in intervention studies were public-facing methods including mass media and local newspaper advertisements. The majority of participants identified this way were self-referred, and in many cases self-identified as lonely. In most cases, there was no standardised tool for defining loneliness or social isolation. However, studies that recruited via referral by recognised agencies reported higher rates of eligibility and enrolment. Referrals from primary care were only used in a few studies. Studies that included agency referral either alone or in combination with multiple forms of recruitment showed more promising recruitment rates than those that relied on only public facing methods. Further research is needed to establish the cost-effectiveness of multiple forms of referral. CONCLUSION: Findings from this study demonstrate the need for transparency in writing up the methods used to approach, assess and enrol older adults at risk of becoming socially isolated. None of the intervention studies included in this review justified their recruitment strategies. The ability of researchers to share best practice relies greatly on the transparency of research.

Barriers and facilitators of physical activity among adults and older adults from Black and Minority Ethnic groups in the UK: A systematic review of qualitative studies.

Older adults from Black and Minority Ethnic (BME) groups experience a relatively higher burden of physical inactivity compared with their counterparts from non-BME groups. Despite the increasing number of qualitative studies investigating the barriers and facilitators of physical activity among older adults from BME backgrounds in the UK, there is very limited review-level evidence. The aim of this review is to undertake a synthesis of existing qualitative studies, using a meta-ethnographic approach, to explore the barriers and opportunities for physical activity among adults and older adults from BME communities in the UK. Studies conducted between January 2007 and July 2017 were eligible if they met the following criteria: employed any qualitative method; included participants identified as being BME, aged 50 and above, and living in the UK. In total, 1036 studies were identified from a structured search of six electronic databases combined with hand searching of reference bibliographies. Ten studies met the inclusion criteria for the review and were included. Six key themes emerged from the data: awareness of the links between physical activity and health, interaction and engagement with health professionals, cultural expectations and social responsibilities, suitable environment for physical activity, religious fatalism and practical challenges. There was a substantial gap in research among Black African groups. Interventions aimed at improving physical activity participation among older adults should be acceptable and accessible to minority groups. Further research is needed to investigate the barriers and facilitators of physical activity among older adults from African backgrounds.

Building capacity to use and undertake applied health research: establishing a training programme for the health workforce in the West of England.

OBJECTIVES: Increasing research capacity is important for health services as part of improving the conduct of high-quality research, which addresses the needs of patients and the public. It is a core function of the 13 Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) established in England between 2008 and 2013. This article reports on the development of an innovative capacity building programme in CLAHRC West over an 18-month period (May 2015 to December 2016). It aims to disseminate the learning from the initiative and share our experience with other CLAHRCs. STUDY DESIGN: The study design was an evaluation of a training programme to build research capacity. METHODS: We carried out a training needs assessment among local stakeholders and scoped existing provision of research-related training. This informed the development of a programme of free short courses, which were targeted at health and social care professionals including those working in local authorities and the voluntary sector. We aimed to engage professionals working at all levels in these organisations and to promote interprofessional education, to build a research culture. We engaged a variety of educators to provide a range of 1-day courses at an introductory level, which were accessible to practitioners. RESULTS: During the first 18 months of the training programme, we delivered 31 courses and trained 350 participants. Attendees came from secondary care (20%), voluntary sector (18%) and local authorities (18%). Professionals working in the mental health sector comprised 11% and commissioning 6%. Less well represented were primary care (3%) and community care (4%). The largest professional group was public health, followed by medical, nursing and allied health professionals in approximately equal proportions. Courses were evaluated on a scale of 1 (poor) to 4 (excellent) with the mean being 3.6 (range 3.3-4.0). CONCLUSIONS: The training programme has been highly successful with many courses oversubscribed, and all courses being well evaluated by participants. It has met the needs of local professionals for brief, applied training in research, as well as attracting those from other parts of the United Kingdom, suggesting the courses are both appropriate and helping to fill a gap in provision. We are building on this work to further engage audiences working in areas such as the wider determinants of health and commissioning, as well as primary and community sectors. CLAHRCs are uniquely placed to drive a culture change in the use, understanding and application of research across the healthcare community.

Developing the public health workforce: training and recognizing specialists in public health from backgrounds other than medicine: experience in the UK.

BACKGROUND: There is increasing recognition that improving health and tackling inequalities requires a strong public health workforce capable of delivering key public health functions across systems. The World Health Organization in Europe has identified securing the delivery of the Essential Public Health Operations and strengthening public health capacities within this as a priority.It is acknowledged that current public health capacities and arrangements of public health services vary considerably across the World Health Organization in European Region, and investment in multidisciplinary workforce with new skills is essential if public health services are to be delivered. CASE PRESENTATION: This paper describes the current situation in the UK where there are nationally funded multidisciplinary programmes for training senior public health specialists. Uniquely, the UK provides public health registration for multidisciplinary as well as medical public health specialists. CONCLUSION: The transition from a predominantly medical to a multidisciplinary public health specialist workforce over a relatively short timescale is unprecedented globally and was the product of a sustained period of grass roots activism aligned with national policy innovation. the UK experience might provide a model for other countries seeking to develop public health specialist workforce capacity in line with the Essential Public Health Operations.

A community-based physical activity intervention to prevent mobility-related disability for retired older people (REtirement in ACTion (REACT)): study protocol for a randomised controlled trial.

BACKGROUND: The REtirement in ACTion (REACT) study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial (RCT) with an internal pilot phase. It aims to test the effectiveness and cost-effectiveness of a community, group-based physical activity intervention for reducing, or reversing, the progression of functional limitations in older people who are at high risk of mobility-related disability. METHODS/DESIGN: A sample of 768 sedentary, community-dwelling, older people aged 65 years and over with functional limitations, but who are still ambulatory (scores between 4 and 9 out of 12 in the Short Physical Performance Battery test (SPPB)) will be randomised to receive either the REACT intervention, delivered over a period of 12 months by trained facilitators, or a minimal control intervention. The REACT study incorporates comprehensive process and economic evaluation and a nested sub-study which will test the hypothesis that the REACT intervention will slow the rate of brain atrophy and of decline in cognitive function assessed using magnetic resonance imaging (MRI). Outcome data will be collected at baseline, 6, 12 and 24 months for the main study, with MRI sub-study data collected at baseline, 6 and 12 months. The primary outcome analysis (SPPB score at 24 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. DISCUSSION: REACT represents the first large-scale, pragmatic, community-based trial in the UK to target the non-disabled but high-risk segment of the older population with an intervention to reduce mobility-related disability. A programme that can successfully engage this population in sufficient activity to improve strength, aerobic capacity, coordination and balance would have a major impact on sustaining health and independence. REACT is also the first study of its kind to conduct a full economic and comprehensive process evaluation alongside the RCT. If effective and cost-effective, the REACT intervention has strong potential to be implemented widely in the UK and elsewhere. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN45627165 . Retrospectively registered on 13 June 2016. Trial sponsor: University of Bath. Protocol Version 1.5.

Inter-sectoral Transfer of the Food for Life Settings Framework in England.

Organisational settings such as schools, workplaces and hospitals are well recognised as key environments for health promotion. Whilst there is extensive literature on specific types of settings, little empirical research has investigated the transfer of frameworks between sectors. This study analyses Food for Life, an England-wide healthy and sustainable food programme that evolved in schools and is being adapted for children's centres, universities, care homes, and hospital settings. Following a case study design, we interviewed 85 stakeholders in nine settings. Food for Life's systemic framework of 'food education, skills and experience' 'food and catering quality', 'community and partnerships' and 'leadership' carried salience in all types of settings. These were perceived to act both as principles and operational priorities for driving systemic change. However, each setting type differed in terms of the mix of facilitating factors and appropriate indicators for change. Barriers in common included the level of culture-shift required, cost perceptions and organisational complexity. For settings based health promotion practice, this study points to the importance of 'frame-working' (the systematic activity of scoping and categorising the field of change) alongside the development and application of benchmarks to stimulate change. These processes are critical in the transfer of learning from between sectors in a form that balances commonality with sufficient flexibility to adapt to specific settings. Synergy between types of settings is an under-recognised, but critical, part of action to address complex issues such as those emerging from the intersection between food, health and sustainability.

Participant and Public Involvement in Refining a Peer-Volunteering Active Aging Intervention: Project ACE (Active, Connected, Engaged).

Background: Evidence for the health benefits of a physically active lifestyle among older adults is strong, yet only a small proportion of older people meet physical activity recommendations. A synthesis of evidence identified "best bet" approaches, and this study sought guidance from end-user representatives and stakeholders to refine one of these, a peer-volunteering active aging intervention. Methods: Focus groups with 28 older adults and four professional volunteer managers were conducted. Semi-structured interviews were conducted with 9 older volunteers. Framework analysis was used to gauge participants' views on the ACE intervention. Results: Motives for engaging in community groups and activities were almost entirely social. Barriers to participation were lack of someone to attend with, lack of confidence, fear of exclusion or "cliquiness" in established groups, bad weather, transport issues, inaccessibility of activities, ambivalence, and older adults being "set in their ways". Motives for volunteering included "something to do," avoiding loneliness, the need to feel needed, enjoyment, and altruism. Challenges included negative events between volunteer and recipient of volunteering support, childcare commitments, and high volunteering workload. Conclusion: Peer-volunteering approaches have great potential for promotion of active aging. The systematic multistakeholder approach adopted in this study led to important refinements of the original ACE intervention. The findings provide guidance for active aging community initiatives highlighting the importance of effective recruitment strategies and of tackling major barriers including lack of motivation, confidence, and readiness to change; transport issues; security concerns and cost; activity availability; and lack of social support.

Downregulation of Bit1 expression promotes growth, anoikis resistance, and transformation of immortalized human bronchial epithelial cells via Erk activation-dependent suppression of E-cadherin.

The mitochondrial Bit1 protein exerts tumor-suppressive function in NSCLC through induction of anoikis and inhibition of EMT. Having this dual tumor suppressive effect, its downregulation in the established human lung adenocarcinoma A549 cell line resulted in potentiation of tumorigenicity and metastasis in vivo. However, the exact role of Bit1 in regulating malignant growth and transformation of human lung epithelial cells, which are origin of most forms of human lung cancers, has not been examined. To this end, we have downregulated the endogenous Bit1 expression in the immortalized non-tumorigenic human bronchial epithelial BEAS-2B cells. Knockdown of Bit1 enhanced the growth and anoikis insensitivity of BEAS-2B cells. In line with their acquired anoikis resistance, the Bit1 knockdown BEAS-2B cells exhibited enhanced anchorage-independent growth in vitro but failed to form tumors in vivo. The loss of Bit1-induced transformed phenotypes was in part attributable to the repression of E-cadherin expression since forced exogenous E-cadherin expression attenuated the malignant phenotypes of the Bit1 knockdown cells. Importantly, we show that the loss of Bit1 expression in BEAS-2B cells resulted in increased Erk activation, which functions upstream to promote TLE1-mediated transcriptional repression of E-cadherin. These collective findings indicate that loss of Bit1 expression contributes to the acquisition of malignant phenotype of human lung epithelial cells via Erk activation-induced suppression of E-cadherin expression.

TLE1 inhibits anoikis and promotes tumorigenicity in human lung cancer cells through ZEB1-mediated E-cadherin repression.

The Transducin-like enhancer of split 1 (TLE1) corepressor protein is overexpressed in human lung tumors and is a putative lung-specific oncogene. However, the molecular mechanism underlying its oncogenic function remains to be delineated. Here, we report an important role of TLE1 in promoting lung tumorigenesis by a mechanism involving induction of anoikis resistance. Using the human lung adenocarcinoma A549 and immortalized bronchial epithelial BEAS-2B cell lines, we observed that TLE1 inhibits anoikis through transcriptional repression of E-cadherin gene. In support of E-cadherin as a downstream target of TLE1 to block anoikis, forced expression of E-cadherin attenuated TLE1-induced anoikis resistance while E-cadherin downregulation decreased the anoikis sensitivity of TLE1 knockdown cells. Furthermore, we determined that E-cadherin expression is transcriptionally induced upon loss of cell attachment and functions as an effector of anoikis. Loss of E-cadherin via the siRNA strategy or exogenous TLE1 expression was sufficient to attenuate anoikis in A549 and BEAS-2B cells. Importantly, we demonstrated that the ZEB1 transcriptional factor is required for TLE1-mediated E-cadherin repression and anoikis resistance. ZEB1 interacted with and recruited the TLE1 to the E-cadherin promoter to impose histone deacetylation and gene silencing. In vivo, TLE1 strongly promoted tumorigenicity of A549 cells in a ZEB1-dependent manner. Underscoring its role in anoikis insensitivity of lung cancer cells, the TLE1-mediated E-cadherin repression was negatively regulated by the tumor suppressor Bcl-2 inhibitor of transcription 1 (Bit1) to effect anoikis. These findings identify the ZEB1/TLE1/E-cadherin transcriptional mechanism as a novel pathway that promotes anoikis resistance and oncogenicity of lung cancer cells.

Food for Life: evaluation of the impact of the Hospital Food Programme in England using a case study approach.

OBJECTIVES: To evaluate the impact and challenges of implementing a Food for Life approach within three pilot NHS sites in 2014/2015 in England. Food for Life is an initiative led by the Soil Association, a non-governmental organisation in the UK that aims to encourage a healthy, sustainable food culture across communities. DESIGN: A case-study approach was undertaken using semi-structured interviews with staff and key stakeholders together with analysis of relevant documents such as meeting minutes, strategic plans and reports. SETTING: Three NHS Trusts in England. PARTICIPANTS: Staff and key stakeholders. MAIN OUTCOME MEASURES: Synthesis of key findings from semi-structured interviews and analysis of relevant documents. RESULTS: Key themes included the potential to influence contracting processes; measuring quality; food for staff and visitors; the role of food in hospitals, and longer term sustainability and impact. Participants reported that adopting the Food for Life approach had provided enormous scope to improve the quality of food in hospital settings and had provided levers and external benchmarks for use in contracting to help drive up standards of the food provided by external contractors for patients and staff. This was demonstrated by the achievement of an FFLCM for staff and visitor catering in all three organisations. CONCLUSIONS: Participants all felt that the importance of food in hospitals is not always recognised. Engagement with Food for Life can produce a significant change in the focus on food within hospitals, and help to improve the quality of food and mealtime experience for staff, visitors and patients.

Interventions Aimed at the Prevention of Childhood Injuries in the Indigenous Populations in Canada, Australia and New Zealand in the Last 20 Years: A Systematic Review.

Globally, Indigenous children are found to be at a significantly higher risk of injury compared to non-Indigenous children. It has been suggested that mainstream injury prevention strategies are ineffective within Indigenous communities. The aim of this review is to identify existing interventions aimed at preventing injury in Indigenous children in the hope that it guides future strategies. To the best of the authors' knowledge, no prior systematic reviews exist looking at interventions specifically aimed at preventing injury in Indigenous child populations in the three chosen countries. Electronic databases were systematically searched for relevant childhood interventions aimed at the prevention of injuries in Indigenous populations based in Canada, Australia and New Zealand from 1996 to 2016. A manual search of the reference lists of relevant articles and a manual search of relevant websites were also completed. After 191 records were screened, six interventions were identified meeting the criteria for inclusion. Eligible papers underwent a quality appraisal using adapted assessment checklists and key information was extracted. Findings were then synthesized using a narrative approach. The interventions mainly promoted child safety through activities focusing on education and awareness. Only three of the six studies measured changes in injury hospitalization rates, all but one evaluation reporting a significant decrease. Studies which measured awareness all demonstrated positive changes. Results suggest that interventions delivered in a culturally appropriate manner acted as a main success factor. Barriers identified as hindering intervention success included lack of cohesion within the intervention due to staff turnover and lack of experienced staff with Indigenous knowledge. This review revealed a limited amount of evaluated interventions for the prevention of Indigenous childhood injuries. Conclusive evidence of the effectiveness of existing interventions is lacking due to the predominantly small-scale evaluations of pilot interventions. Future research is needed to provide more rigorous evidence of the mechanisms driving the successful implementation, delivery and uptake of such strategies tailored to Indigenous children.