NIHRDataInsights/HRCSData huggingface dataset:
Title: Personalised social marketing of multi-dimensional physical activity profiles in at risk men & women
Funder: Medical Research Council

Abstract: The roll-out of the NHS Health Check through general practice represents a considerable investment of resource in order to identify at risk individuals. This public health initiative is underpinned by the relevance and power of personalised information and physical activity is advocated as a primary strategy for patients to reduce their risk. The major challenge is to develop approaches that are effective at changing behaviour in this priority group and that can be readily implemented in primary care. Physical activity is a rather complex behaviour. There are multiple dimensions (aspects) to physical activity behaviour that all have the potential to improve health. This can sometimes lead to confusion but it also means that there is the potential to generate novel and exploitable opportunities. We now have the technology to capture this information and thus provide patients with personalised feedback on the multiple dimensions of physical activity behaviour that they can change and use (harness) to play a role in reducing their risk (e.g., physical activity energy expenditure, time engaged in moderate intensity activity, sedentary time etc). We have piloted different formulations for integrated physical activity profiles that reflect various (multiple) physical activity dimensions. We will work with the users (patients and healthcare practitioners) to generate a preferred option (personalised and visual feedback in the form of a physical activity profile) that represents biologically important dimensions of physical activity behaviour. We will then determine whether we can use feedback from these profiles and social marketing techniques to help patients identified as at risk in the NHS Health Check to understand the problem (their low physical activity) as a step towards becoming self-determined in their engagement (i.e., autonomous). There is a direct route to implementation of the findings and a change in practice as an adjunct to NHS Health Checks.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Development and stage 2 RCT with internal pilot of a weight loss maintenance intervention for obese adults after clinically significant weight loss
Funder: Medical Research Council

Abstract: The NHS and the public invest considerably in weight loss interventions but most people regain weight rapidly. We propose developing the first WLM intervention meeting the MRC guidance for the development of complex interventions, based on evidence identified from a systematic review and configured through user-centred design. We will conduct the first UK based WLM RCT and the first such RCT conducted in Europe to recruit individuals in the community. The proposed intervention will combine automated intervention content provided through personal body weighing scales which communicate data wirelessly to a central server and tailored intervention content delivered through a mobile internet platform and personal contact. The detailed procedures of the intervention content, hardware and software will be developed in the first year using user-centred design and the evidence from our systematic review. We will conduct a series of small pilot studies to optimise acceptability and feasibility of the intervention. We will then conduct a two-arm RCT with randomisation of 144 participants each to the new intervention or a control condition with assessment of body weight and secondary outcomes prior to randomisation and one year later. Qualitative process evaluation will be conducted with 20 participants in both groups. We will integrate an 'internal pilot' into the trial to test in the first three months and with the first 60 participants if the trial procedures are feasible. If pre-set targets are not met, we will seek advice from the funder and the independent Trial Steering Committee about either discontinuing the trial or modifying the procedures. If these targets are met, we will continue the study and the pilot data will form part of the final trial data set. We will analyse the effectiveness and cost-effectiveness of the intervention and explore the association between socioeconomic status and other participant characteristics (e.g. age, gender, etc) with WLM.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: How can we help parents recognise unhealthy body weight in their children?
Funder: Medical Research Council

Abstract: Identifying effective preventive strategies for childhood obesity is a public health priority. Parents have a central role in their child's health-related behaviours but evidence shows that parents tend not recognise overweight (OW) in their own child. Parents do not use objective methods when identifying child weight status. Rather they use visual assessments such as comparing their child with others. The National Child Measurement Programme (NCMP) measures weight status in Reception and Year 6 children. Parents are informed of the results but anecdotal evidence suggests this fails to promote action. Parents who perceive their child's weight as a health issue are more likely to modify their child's lifestyle. This research will address the fundamental issue of recognition and awareness of a healthy body weight in children and therefore of childhood overweight. These are prerequisites to behaviour change. This multistage study will develop and test measures to improve parents' ability to assess their child's weight status (in line with NCMP criteria), increase their knowledge of the health consequences of childhood OW and intention to take action. Body image scales (BIS) are visual images of body shape but as yet none map onto commonly used body mass index cut-offs. In stage 1 3D body scans of 800 children will be used to create age and gender specific BIS for Reception and Year 6 children. The BIS, supporting information to increase parental knowledge of the consequences of childhood OW, and the approach to delivery will be further developed using extensive consultation with parents in stage 2. A feasibility study using the tool will follow (stage 3) with further user feedback. The final tool and methods of delivery will be tested in a cluster randomised trial in stage 4. Policy and practitioner partners in our team will ensure that the study outputs are directly transferable to practice and support the work of the National Obesity Observatory and NHS Choices.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Metabolomics for monitoring dietary exposure
Funder: Medical Research Council

Abstract: In collaboration with colleagues at the MRC Human Nutrition Research, we have identified a panel of foods of high public health importance suitable for exposure monitoring in urine using biomarker technology. Free-living volunteers will consume these specific foods as part of everyday eating patterns over 3 days before collection of urine and blood for identification of potential biomarkers. The timings of specific meals and of biofluid collection will be pre-determined to facilitate investigation of the duration of food-derived metabolite signals and the most informative urine collection strategies. In addition, 400 study participants consuming their usual diets will be recruited. We will estimate habitual dietary intake using the EPIC FFQ and collect "spot" urine samples. This population sample will be used to test the utility of putative metabolite biomarkers of dietary intake. NMR and LC-MS technology will be used to generate comprehensive metabolite profiles of urine samples. Supervised data mining methods will identify signals explanatory of exposure to specific foods. Targeted NMR and accurate mass FT-ICR-MS will be used to structurally annotate metabolites with biomarker potential. Targeted analytical methods will be established to simultaneously measure several biomarker signals (e.g. using MRM approaches) in urine. In controlled residential food intervention studies, volunteers will be asked to consume known amounts of test foods for which we have identified potential biomarkers and urine and blood will be collected at defined intervals for up to 3 days after consumption. We aim to describe the kinetics of signal decay and to determine the quantitative relationships between food intake and urinary metabolite concentrations. Biomarkers proving informative will be tested for utility using dietary data and urine samples from both recent National Diet and Nutrition Survey studies (24hr urines) and the 400 "spot" urines from the present study.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: The 'Medical Bypass': a new treatment for obesity and diabetes
Funder: Medical Research Council

Abstract: Obesity and Type 2 diabetes are massive health problems worldwide. There is no adequate medical treatment for obesity. Bariatric surgery is successful in reducing weight and producing remissions in diabetes by increasing the circulating levels of gut hormones which, acting in concert, suppress appetite, increase energy expenditure and improve carbohydrate metabolism. However, surgery is expensive and has high morbidity and mortality rates. I will test whether a 'medical bypass' combination of newly developed long-lasting analogues of the gut hormones, peptide YY(PYY), glucagon-like peptide-1 (GLP-1) and oxyntomodulin (OXM), can reproduce the effect of a surgical bypass and thus provide a medical treatment for obesity. I will use a validated animal model of obesity, the diet-induced obese Wistar rat. I will initially compare the effects of surgical bypass vs 'medical bypass' on food intake and body weight. Levels of GLP-1, OXM and PYY will be measured after surgical bypass in one group of animals. In another group, I will mimic these levels with an appropriate dose of analogue and then assess the effects of the two treatments on food intake and body weight. Three months treatment with the analogue combination will then be assessed for its effects on (a) food intake; (b) body weight; (c) energy expenditure as assessed by a Comprehensive Lab Animal Management system; (d) glucose tolerance; (e) body composition and (f) neuronal activation in the hypothalamus and brainstem, assessed by immunohistochemistry for the neuronal activation marker c-fos. By understanding the effects of the medical bypass, I will obtain proof-of-concept in animals that will enable this new therapy to be translated into a successful medical treatment for obesity and type 2 diabetes.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: The role of T1R1/T1R3 in satiety
Funder: Medical Research Council

Abstract: High protein diets inhibit food intake and facilitate weight loss in both animals and humans. This effect is not related to reduced palatability. However, these diets are difficult to adhere to and have therefore proved unsuccessful as treatments for obesity. The T1R1/T1R3 receptor is a promiscuous amino acid receptor expressed in the gastrointestinal tract that may mediate the effects of protein on appetite. My pilot data suggests that specific amino acids that bind to the T1R1/T1R3 stimulate the release of anorectic gut hormones and reduce appetite in rodents. This programme of work aims to: 1) Characterise the gut T1R1/T1R3 system. I will determine the expression pattern of T1R1/T1R3 in the mouse gastrointestinal tract, and investigate its co-localisation with the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). I will determine the effects of T1R1/T1R3 ligands on gut hormone release following direct administration into those regions of the gut showing the highest expression. 2) Determine the role of T1R1/T1R3 in gut hormone release. I will use mice globally lacking T1R1, and thus T1R1/T1R3 signalling, to confirm that T1R1 is necessary for the effects of specific amino acids on gut hormone release and food intake. I will then use mice specifically lacking T1R1 in the gut to determine whether it is T1R1/T1R3 signalling in the gastrointestinal tract that mediates these effects. 3) Determine the role of gut T1R1/T1R3 in mediating the effects of a high protein diet. I will use mice specifically lacking T1R1 in the gut to determine whether T1R1/T1R3 signalling in the gut mediates the well-characterised effects of a high protein diet on food intake and weight loss. These experiments will determine the importance of T1R1/T1R3 in amino acid sensing in the gut, and will assess the utility of targeting T1R1/T1R3 to treat obesity.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Investigation of genetic variation underlying central obesity amongst Indian Asians.
Funder: Medical Research Council

Abstract: Indian Asians have high prevalence of central obesity, which is causally linked to their 2-3 fold excess risk of the metabolic syndrome of insulin resistance, T2D and CHD, compared to Europeans. Improved understanding of the mechanisms underlying central obesity and associated diseases in Indian Asians is of great importance for improving health in this population. Central obesity has been shown to be heritable amongst Indian Asians though the underlying genetic mechanisms are not well understood. My preliminary studies in LOLIPOP show that genetic variants linked to obesity in Europeans do not account for the excess risk of central obesity in Indian Asians. The goal of my proposal is to investigate genetic variation underling central obesity in Indian Asians. I propose WES in 200+ Indian Asians at extremes of central obesity, selected as the top and bottom 0.5% of the population distribution for WHR in the LOLIPOP cohort (n~18,000). Genetic variants associated with WHR at P<10-3 will be taken forward for replication testing in a two stage design. In stage one, >100 genetic variants will be tested in ~1800 Indian Asians (selected as the top and bottom 5% of the population distribution for WHR among the remaining LOLIPOP participants). In stage two, variants identified from stage 1 at P<0.01 will be tested for association with WHR in the remaining ~16,000 Indian Asian participants in LOLIPOP. Significance will be inferred at P<5x10-8. The extent to which confirmed genetic variants contribute to the excess of central obesity and the increased risk of T2D and CHD in Indian Asians will be established. Indian Asian data will be compared with 1000 Genomes data to identify whether the associated variants in Indian Asians are population specific or cosmopolitan. Pathways to disease will be evaluated using bioinformatic approaches.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Targeting the aspartic protease BACE1 for inhibition in order to increase hypothalamic leptin sensitivity and reverse obesity.
Funder: Medical Research Council

Abstract: Part 1: We will perform a comparative study of C57BL/6 BACE1-/-, BACE1+/-, and wild type littermate (BACE1+/+) mice, in which all three genotypes will be fed on regular or high fat diet for 20 (or longer for BACE1+/- mice) weeks (for HF diet sufficient time to induce DIO in wild type mice). In this longitudinal study we will determine how loss (BACE1-/- mice), reduction (BACE1+/- mice) and increased (via high fat diet) BACE1 affects RMR, body composition, food intake (basal and MTII modified) and plasma glucose and hormone (leptin, insulin) levels. At the end of the dietary period all three genotypes will be injected with leptin to explore the role of BACE1 on hypothalamic leptin sensitivity (measuring changes in food intake, hypothalamic neuropeptide expression and signalling strength of various leptin receptor-mediated pathways). These will be compared using peripheral and central routes of leptin administration. Part 2: We will use the same criteria set out above to test the prediction that reduction of BACE1 activity in DIO wild type mice results in loss of body weight (reduced adiposity) concomitant with recovery of hypothalamic leptin sensitivity (i.e. reversal of high fat diet induced hypothalamic leptin resistance). Inhibition of BACE1 activity in mice will be induced through pharmacological inhibition by infusion or oral administration of small molecule non-peptide BACE1 inhibitors. Part 3: We will determine whether the effects of BACE1 inhibition require the presence of leptin by oral administration of BACE1 inhibitor to ob/ob mice using the same output measures described above. Additionally, we will analyse dietary-modified leptin- and BACE1 inhibitor-treated hypothalamic tissue for evidence of BACE1-mediated alterations in signalling pathway networks associated with obesity and diabetes and/or known components of leptin signalling pathways. Peripheral tissues will be examined for evidence of altered levels of energy expenditure markers.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Differences in growth and adiposity between UK Pakistani and White British children: the causes and consequences of smaller size and greater adiposity
Funder: Medical Research Council

Abstract: Aim To describe differences in growth and adiposity between Pakistani and White British children from birth to age 4/5, to examine maternal causes of any differences and to explore the consequences for child health and development. Objectives 1.To examine associations between maternal characteristics associated with developmental overnutrition and offspring size and adiposity at birth and age 4/5 years in Pakistani and White British children. 2.To develop growth trajectories from birth to age 4/5 and compare growth, adiposity and blood pressure between Pakistani and White British children 3.To examine whether size at birth and child growth are associated with health and educational outcomes in Pakistani and White British children. 4.To determine whether growth and fatness differ depending on whether the parents and grandparents of Pakistani infants were born in the UK or South Asia Methods This proposal will use new and existing data collected for the BiB study and will link with routine health information databases. New data collection will include skinfold and blood pressure measurements at age 4/5. Cord leptin assays will be completed on the whole BiB cohort and child health, hospital admission and education information will be extracted from routine health and education systems Existing data will include maternal measures of hyperglycaemia and offspring size measurements. Statistical analysis will include multivariable linear regression models and tests for statistical interaction. Growth trajectories will be estimated using linear spline mixed effects models for Pakistani and White British children. Scientifc and medical opportunities Recent studies draw attention to differences in adiposity between South Asian and White British infants and children. Understanding more about the causes and consequences of these differences is crucial for planning public health interventions to tackle ethnic inequalities in diabetes and cardiovascular disease.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Characterising patterns and changes in physical activity in older people and their determinants and consequences
Funder: Department of Health (England)

Abstract: We aim to contribute evidence to inform the development of interventions and policy to promote physical activity among older people and shift population distributions of physical activity behaviour. We will achieve our aim through interconnected components employing a range of methods (quantitative, qualitative and modelling) in the context of an ongoing, large population-based observational study. EPIC-Norfolk, a prospective cohort study, recruited 30,000 men and women aged 40-79 years at baseline (1993 to 1997) from 35 general practices in Norfolk. Participants have completed the previously validated EPAQ-2 physical activity questionnaire on two occasions and one round of measurement of potential determinants of physical activity by a modified NEWS questionnaire (Neighbourhood Environment Walkability Scale with inclusion of additional items based on the Theory of Planned Behaviour). In addition, over 4000 participants have undergone objective measurement of physical activity by accelerometry. The EPIC-Norfolk 4th health check has recently commenced, supported by MRC core funds, and includes measures of anthropometry, body composition and spirometry, a physical performance battery and self-report and objective (accelerometry) assessment of physical activity. In this project we will use home adDr.esses (available for all participants) to derive detailed characterisation of the environment using standard geographical information systems. We will also add tracking of participants' location and movements using GPS devices and qualitative interviews. This will enable us to better understand the levels and patterns of physical activity and sedentary behaviour, the change in these behaviours over time, and the determinants of these behaviours and their health consequences. We will also develop a Markov model to quantify the impact of changes in population patterns of physical activity on health outcomes.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL