NIHRDataInsights/HRCSData huggingface dataset:
Title: Resolving a novel brain circuit controlling appetite and body weight
Funder: Medical Research Council

Abstract: Obesity has emerged as a primary healthcare challenge of the 21st century because of its prevalence, burden on human health/NHS and the paucity of effective medications. I recently discovered that the activation of a specific subset of cells within the nucleus of the solitary tract that synthesise cholecystokinin (NTS-CCK) and potently reduce food intake and body weight. Here I propose to extend this work by dissecting the discrete metabolic NTS-CCK network at the genetic, anatomical and behavioural level, and evaluating its therapeutic potential for the treatment of obesity. To achieve this, I will capitalise on the selectivity afforded by new technology for cell-specific activity manipulation and visualisation. To reveal specific NTS-CCK circuits modulating appetitive behaviour, I will rapidly and reversibly control NTS-CCK axon terminals using in vivo optogenetics. I will clarify the structural organisation of NTS-CCK circuits controlling appetite using Rabies-based retrograde labelling. Furthermore, I will characterise the transcriptional signature of appetite suppressing NTS-CCK neurons using RNASeq. To study the temporal dynamics by which signals of nutritional state recruit the NTS-CCK neurons, I will perform optical recording of their activity using in vivo calcium photometry. Finally, I will test the necessity of NTS-CCK neurotransmission for the maintenance of energy balance and how the lack of this circuitry impinges on the development and progression of diet-induced obesity and metabolic-like syndrome by site- and cell-specific ablation of NTS-CCK neurons. I anticipate that the proposed research will generate an evidence base for a novel and distinct circuit critically transmitting information about nutritional status to modulate energy balance and body weight, a circuit that has a strong translational potential for the treatment of obesity.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: The big breakfast study: chrono-nutrition influence on energy expenditure and body weight
Funder: Medical Research Council

Abstract: Energy balance may be influenced by timing of eating, such that weight loss is greater when consuming a relatively larger morning meal than a comparable evening meal. The mechanisms for this are not understood, but likely to be linked to either behavioral adaption in physical activity in response to time of eating, or, driven by biological circadian rhythms. After eating, a cascade of metabolites and hormones are released, which can influence energy expenditure through thermic effect of food. Neuronal and hormonal systems that are likely involved in driving the circadian rhythm in energy expenditure or TEF are the endocrine hormones (insulin) and metabolites (glucose); with diurnal variation also reported in a gastric emptying. Our hypothesis is that timing of eating influences energy balance, because morning energy expenditure is amplified in comparison to evening. The cause of the increased energy expenditure in the morning is unclear, whether this is linked to natural biological circadian rhythm in response to eating or behavioral adaption. Key objectives will be addressed through a research study program that involves two key experiments in overweight/obese subjects, to explore potential behavioral and circadian influences on energy expenditure and energy balance. Our first diet trial will examine the impact of calorie distribution as morning and evening eating on metabolic and behavioral regulation during weight loss. Finally, we will test whether meal consumption effects on energy balance are modulated though the normal circadian rhythms, by applying a phase delay protocol in a controlled environment. Together, these studies will elucidate how energy balance can be modulated by timing of eating.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: Improving healthy energy balance- and obesity-related behaviours among preschoolers in Malaysia: feasibility of adapting the ToyBox-Study
Funder: Medical Research Council

Abstract: This study will assess the feasibility of adapting the ToyBox-Study programme to the Malaysian kindergarten setting, and to conduct a pilot RCT, which will inform development of a full RCT. ToyBox-Study is an evidence-based intervention conducted in 6 European countries on 7000 children and their families, and over 100 kindergartens. The Toybox-Study programme is designed to improve four energy balance-related behaviours which impact on obesity in kindergarten children: water drinking, snacking, physical activity and sedentary behaviour. All materials (training manuals, questionnaires, caregiver information) from that study have been made available to the applicants. Stage I will apply a Theory of Change framework for complex behavioural interventions, initiated by a stakeholder workshop. Stage II is adaptation of ToyBox material to the Malaysian social and language contexts. Stage III is a pilot RCT in 10 kindergartens: 5 in Peninsular Malaysia and 5 in Sarawak, of which 2 in each region will be controls. 300 children will be recruited, with 200 in intervention kindergartens, from KEMAS (Community Development Department) kindergartens, so as to target more underprivileged families, as well as including a strong representation from Iban and Bidayuh ethnic groups, who may be particularly vulnerable to developing obesity. Experienced UK partners, who were involved in the original ToyBox-Study will train Malaysian research staff, who in turn will train kindergarten staff to carry out the intervention across the kindergarten year, with an additional 6-month follow-up for key outcomes. Emphasis will be placed on evaluation of intervention feasibility including assessing ease of adaptation, acceptability of ToyBox-Study to parents, facilitators, and kindergarten teachers; recruitment and retention rates; parental adherence to or engagement with ToyBox; intervention fidelity; and feasibility of collecting outcome measures.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: Diet, physical activity and cardiometabolic health in Malaysian adolescents: from epidemiology to intervention
Funder: Medical Research Council

Abstract: We propose a mixed methods approach including secondary analysis of MyHeARTs cohort data, conducting systematic reviews, metabolic analysis of stored serum samples, qualitative research with key stakeholders and full evaluation of a pilot intervention. We will use detailed data on health behaviours and intermediate risk factors from 1361 adolescents aged 13-17 years to generate behavioural patterns predictive of cardiometabolic risk. Patterns will incorporate diet, eating architecture, physical activity, and sedentary behaviours and key intermediate risk factors like high fat intake, low cardiorespiratory fitness or obesity. A hybrid of data-driven and hypothesis-based multivariate pattern analysis, RRR will be applied to generate different behavioural patterns that explain variation in hypothesised intermediate variables on the causal pathway from behaviour to disease. Patterns will reveal specific behaviours with the highest weights, thus explaining the highest variation in the pathway to disease, which should be the most promising targets for intervention. We will conduct prospective analyses of change in behavioural patterns with change in blood lipids, glucose and blood pressure from age 13-17 years using linear and logistic regression. We will then explore associations with metabolic health further by incorporating selected novel metabolites from lab-analysis of stored serum samples collected at age 15 and 17. Combining findings of the systematic review with MyHeART analyses, we will conduct semi-structured qualitative focus groups and interviews with adolescents and school staff to explore how health behaviours might be changed. After mapping intervention to behaviour change techniques, a pilot intervention will be run in 6 secondary schools (3 intervention and 3 control) with a comprehensive outcome and process evaluation. Based on experience in UK studies, we will pilot tools to assess costs associated with developing and delivering the intervention.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: How will the obesity epidemic influence healthy ageing? The potential for health behaviours to alleviate the obesity burden across generations
Funder: Medical Research Council

Abstract: Aim: Global population trends in obesity and ageing raise challenges for health and society. To address the potential of health behaviours to alleviate the obesity-related health burden, I aim to determine influences on health behaviours and adiposity, their interrelations and relationship to components of healthy ageing (physical and cognitive capability) across generations. Objectives: To establish (within and across generations) associations between: (1) early life factors and health behaviours, (2) time-varying behaviour and adiposity trajectories, (3) time-varying behaviours and components of healthy ageing; and to establish whether: (4) relationships between obesity trajectories and healthy ageing components are modified by time-varying behaviours, and (5) the influence of genetic variants on weight gain is modified by time-varying behaviours. Methods: The 1946, 1958 and 1970 British birth cohorts will be used. Prospective data include adiposity measures from early life onwards, health behaviours during adulthood and measures of healthy ageing. For each objective, within cohort analyses will be conducted; in cross-cohort analyses, comparability of measures will be considered. Relevant statistical methods (e.g. structural equation modelling, multilevel models, marginal structural models, g-estimation of structural nested models) will be used. Causal inference methods and sensitivity analysis will be applied to explore conclusion robustness to assumption violations. Scientific opportunities: The project will shed light on the influence of obesity trends on healthy ageing across generations, quantify the likely impact of intervening on behaviours at different life stages and contribute to the design of trials to reduce consequences of obesity and that promote uptake and maintenance of healthy behaviours. It will advance knowledge of healthy ageing by deepening our aetiological understanding of ageing processes and how these processes have changed over time.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: Role of food prices and food system changes in improving population health
Funder: Medical Research Council

Abstract: The CDA research programme uses advanced econometric methods to develop models and analyse dietary behaviour via food and beverage demand and linking to health outcomes by addressing four key gaps in current research: RQ1: What is the role of stock-piling (storing), habits and information asymmetry in influencing consumer response to price changes and the choice of foods and beverages? RQ2: What is the role of out-of-home food and beverage consumption in diets, and how does the demand for OOH foods and beverages respond to price changes, including substitution with foods eaten at home? RQ3: What is the impact of industry-led voluntary changes in food systems, to achieve healthier food environments, on consumer food and beverage choices and expenditures? RQ4: How can Discrete Choice Experiments (DCE) be effectively used in analysing the impact of food policies on consumer behaviour in the context of large numbers of alternatives and multiple choices? RQs1-3 will be answered by micro-econometric analysis of highly disaggregated longitudinal panel data on household food and beverage purchases. Planned methods range from discrete choice models (RQ1) and multi-stage demand systems (e.g. almost ideal demand system) (RQ1-2) to interrupted time series designs with control groups and multi-level hierarchical random effects models (RQ3). For RQ4, advanced DCE methods will be used, including Bayesian D-efficient designs, and allowing for large number of alternatives and multiple choices via menu based experiments or multiple discrete choice models. Two major innovations from the proposed programme include the use of newly available and highly disaggregated data for food and beverage consumption outside homes that will be linked to at-home consumption data, and an application of the DCE in the same sample meaning that stated preferences can be put into context with wider behaviour using large amounts of highly disaggregated observed behaviour (preference) data.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: Developing an area (street) based cash transfer scheme to promote healthy eating communities in areas of high deprivation (the FRESH Street Project)
Funder: Medical Research Council

Abstract: This project addresses an issue of major strategic public health importance - how to create sustainable and healthy diets, eating behaviours and food systems in areas of high deprivation. Many communities in the UK are in food poverty "the inability to afford, or have access to, food to make up a healthy diet" (DH 2005), with diets high in processed foods and low in fresh fruit and vegetables. Moreover, social eating patterns have changed with food often consumed in a rush, alone and while multi-tasking. The combination of what we eat and how we eat often leads to poor long term health including type 2 diabetes and obesity. The intervention to be developed in this project takes into account the fact that decisions about food are complex and not made in social isolation. The intervention (and the project) engages with this complexity, and as such is seeking to change social practices of eating and diet by helping alter the contexts and recognise the constraints on decision making. This public health intervention is seeking to achieve positive long term change at multiple levels of the socio-ecological model (Whitehead & Dahlgren, 1991). This public health intervention is a health behaviour change financial incentive voucher scheme for specific areas with high deprivation levels and low fruit and vegetable and high processed food consumption. The voucher scheme to be developed will be product specific (fresh fruit and vegetable) and supplier specific (local fresh fruit and vegetable market stalls and shops and fruit and vegetable delivery schemes e.g. box schemes), and delivered to all children and adults in the target communities (streets). In order to be sustainable in the long term the voucher scheme will need to be embedded within local communities, and multiple various organisations and infrastructures which provide services relating to the food system and healthy eating (education, production, preparation, consumption, waste management.)


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: Developing a theory of change, outcome measures and evaluation design for an evaluation of the impact of the Daily Mile on obesity and health
Funder: Medical Research Council

Abstract: The Daily Mile (TDM) is designed to get schoolchildren running for 15 minutes per day. It has proved acceptable to schools, with significant health benefits claimed. However, to date there have been no robust evaluations of its public health effectiveness. This represents an excellent opportunity for developing urgently-needed methodologies for evaluations of complex interventions in 'real life' settings. TDM is being implemented in a range of school settings, and usually as part of a range of broader measures: in Lewisham, for instance, within a Whole System approach. This presents evaluation challenges: identifying what 'the intervention' is; identifying effective intervention components; identifying what the necessary and sufficient conditions might be for it to have effects; identifying how these components relate to system-level change. We aim to first develop the DM as a public health intervention. We will map the scheme to the TIDieR checklist; develop a logic model to describe the theoretical pathways from intervention to outcomes, describe the full range of potential health outcomes, and identify potential costs. Second, we will develop urgently-needed methodologies for evaluating complex interventions in complex systems. Specifically, we aim to design an evaluation which combines quantitative analysis of secondary data sets (primarily BMI measures) with qualitative rapid ethnography within a quasi-experimental design. We will assess the feasibility of using Qualitative Comparative Analysis (QCA) (a mixed method approach that uses data about 'cases' - in our example schools - as well as variables) to investigate causality in complex systems. We will assess whether rapid appraisal techniques generate sufficient qualitative knowledge for a QCA. This early phase study will therefore inform an evaluation of: 1) the impact of TDM on participating children's health; and 2) the sufficient and necessary conditions for positive impact on public health.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: Self-monitoring of online food purchases: development of the myShop app
Funder: Medical Research Council

Abstract: Food purchasing environments are a prime setting for interventions aimed at improving diet. In the UK, online supermarket shopping is expanding at a rate of 14% per year. We have built a web browser extension called myShop which can be used in six UK online supermarkets to provide point-of-purchase cues towards healthier food purchasing, such as traffic light labelling of nutritional quality delivered at point of choice, review and checkout, and the option to block presentation of unhealthy foods. For this project, we will build a website (for use on smartphone, tablet or PC) which will support use of the myShop app by means of a range of behaviour change techniques including: self-monitoring the nutritional quality of purchases; goal-setting and tailored feedback; advice on healthy shopping and motivational reminders. We will use a theory, evidence and person-based approach to development. We will review the evidence on dietary behaviour change interventions to identify what features are successful at changing behaviour and to learn from user views of previous interventions. We will carry out a behavioural analysis and create a logic model and guiding principles for the design features of the website, which will be created by an experienced digital agency. We will carry out around 20 think aloud interviews with users recruited from the general population to elicit feedback which will inform improvements to the prototype website. To ensure the opinions of lower socioeconomic groups are included we will recruit using adverts in local buy-and-sell websites and face-to-face recruitment at discount supermarket chains. A further 20 participants will be asked to use the website for several weeks and will then be interviewed about their experiences to inform final modifications and to confirm accessibility, usability, acceptability and feasibility. This work will form the basis of a proposal for a trial to evaluate effectiveness at changing dietary behaviour.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE
Title: SurgiCal Obesity Treatment Study (SCOTS)
Funder: Chief Scientist Office, Scotland

Abstract: Bariatric surgery is an increasingly common procedure for the treatment of severe obesity and obesity-related disease. However there is variable evidence on the complications of bariatric surgery and which patient groups have the best improvements in clinical outcomes. We will recruit 2000 patients undergoing bariatric surgery in the NHS and private sector in Scotland, UK, over a 5 year period. We will follow them for a mean of 10 years. We will record mortality, weight, incident T2DM, CHD, CVD, cancer, fractures, nutritional blood markers, anxiety, depression, post-operative complications, revisional surgery rates, health related quality of life, glycaemic control, diabetic complications and diabetes medications.

Lay abstract: We will collect data on every patient in Scotland having weight loss surgery, to monitor their weight, nutrient levels in their blood, whether diabetes gets better or if they develop diabetes in the future, any complications such as wound infections or requiring a second operation, heart attacks, cancer or if they die, and if quality of life improves and they feel more or less anxious or depressed after the surgery. We will follow the patients for 10 years after their surgery. The surgical team will consent the patients and record height, weight, age, date and type of surgery. Weight and nutritional outcomes: the patients will be sent a blood form at 6 months then annually and attend local GP practice for bloods and weight. The results of the blood tests and weight will automatically download to the research IT system from the laboratory results database and if abnormal the surgeon informed and the patient sent a further form to get a full nutrient blood test. The results of these tests will be returned to the surgeons and GPs. Quality of life, psychological and surgical complications: these are outcomes that the patients report themselves. This will be done via phone, postal and on-line questionnaires. We will work closely with established bariatric surgery patient support groups to make these as simple as possible. We will trial a number of methods and also consider giving vouchers as an incentive to complete the questionnaires. Diabetes control and complications, heart attacks, cancers and whether people die: these are all collected using routine NHS data. In Scotland we have excellent, accurate IT health records that we can link to at minimal cost. This means that we can follow all these outcomes even if the patient never attends for any follow up or completes a questionnaire.

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE