NIHRDataInsights/HRCSData huggingface dataset:
Title: Lymphocyte Development
Funder: Medical Research Council

Abstract: "A central question in biology is how genetic information is interpreted to direct the ordered formation of different cell types within an organism.||Our group studies the molecular events that underlie co-ordinate gene activation and gene gene silencing, and how cell identity is conveyed through division, particularly in lymphocytes. ||These studies focus on understanding how key factors such as Ikaros regulate gene expression, the spatial position of loci in the nucleus and whether gene activity status is heritable.||We are examining the epigenetic regulation of stem cells, including the roles of non coding RNA, chromatin and Polycomb proteins in ES pluripotency and lineage-specific differentiation. This research programme uses replication timing, Chromatin (histone modification) profiling and ChIP analysis to map large-scale epigenetic changes that occur during development and ES cell differentiation.||We are evaluating the role of non-coding RNAs in transcriptional and post transcriptional gene silencing using mice carrying conditional alleles of the RNAseIII enzyme Dicer.||We are also investigating how cellular reprogramming is achieved using experimental heterokaryons, nuclear transfer and in trans-differentiating model systems."


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: The "Irie Classrooms Toolbox": a cluster randomised trial of a universal violence prevention programme in Jamaican preschools.
Funder: Medical Research Council

Abstract: Aim: To determine the effects of school-based violence prevention programme, implemented in Jamaican preschools, on the levels of aggression among children in school and violence against children by teachers. Study Design: Cluster randomized controlled trial Sample: 76 preschools in urban areas of Kingston, Jamaica will be randomly assigned to intervention (n = 38) or control (n = 38). Each preschool comprises three classrooms (one 3, 4 and 5 year old class) and all teachers and classrooms will be included in the study (228 teachers/classrooms: 114 in each group). In addition, a random sample of 6 children in the 4 and 5-year old classes will be selected for evaluation of child-level outcomes (912 children: 456 children in each group). Intervention: The intervention involves training teachers in classroom behaviour management and in strategies to promote children's social-emotional competence. Training is delivered through 5 full-day workshops, monthly in-class coaching over two school terms and weekly text messages. Measurements: The primary outcome measures are: i) observed violence against children by teachers and ii) observed levels of child aggression in the classroom. Secondary outcomes include observations of the quality of the classroom environment, teachers' reports of their mental health, teacher reported child mental health, direct tests of child self-regulation, child reports of teachers' use of corporal punishment and child attendance. Economic, Social, Qualitative Measures: Implementation science is incorporated throughout the study to determine the factors affecting the quality of implementation and how implementation is associated with outcomes. An economic evaluation will also be conducted. Implications: This study involves integrating an intervention into an existing service that is universally accessed by young Jamaican children. The intervention thus has the potential to make an enormous public health impact at the population level.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Strengthening the primary care system for adolescent indigenous health in Brazil: Integrating community health workers into the school setting
Funder: Medical Research Council

Abstract: There is global recognition of the social injustices and poor health that indigenous people endure. Health priorities for Brazil focus on several Sustainable Development Goals realted to non-communicable diseases and poverty. There are ~1 million indigenous people in Brazil, of which ~50% is <24y. Mato Grosso do Sul, the location for the proposed intervention, contains the 2nd largest concentration of indigenous people (70,000), 70% are <20y. Adolescence is a crucial period for developing health or disease risk trajectories. There is strong evidence for a pivotal role of community health workers (CHWs) in primary care but their effectiveness in secondary schools has not been evaluated. A feasibility study will explore whether CHWs can be trained to deliver universal and targeted services for health promotion, risk screening, and early intervention. We will work with local indigenous adolescents and parents, teachers and health professionals to ensure adaptability in delivery to best suit the needs of the pupils in different schools but all CHWs will have the same roles and responsibilities to promote adolescent health and use evidence-based materials. Based on the principles of realist evaluation and MRC guidelines for the evaluation of complex interventions, we will use a mixed methods approach including: 1) concept mapping with stakeholders to develop a model of factors that could affect implementation in the primary health care system and schools; 2) interviews with pupils, teachers, CHWs, and supervising nurses to understand the barriers and facilitators of implementation and 3) quantitative surveys to obtain useful data for needs assessments, and also examine likely influence of the intervention on adolescent health literacy and satisfaction with the intervention. If the findings are favourable, we will conduct wider testing of the intervention in collaboration with the indigenous communities and the health secretariat.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Strengthening the inclusion of persons with disabilities in the health system in Brazi
Funder: Medical Research Council

Abstract: A multi-disciplinary health system analysis will be undertaken to assess the inclusion of people with disabilities in the health system in Brazil and inform how this can be improved. This research will take a person-centred approach throughout. At the national level, we will conduct a policy analysis on the provision of healthcare for people with disabilities. We will review relevant national strategic plans and policy documents and interview key informants. We will also conduct a rehabilitation health system assessment using the WHO Tool. We will undertake detailed investigation in three States: Pernambuco, District Federal and Sao Paulo. In each, we will conduct a network analysis to map key stakeholders in the rehabilitation system and investigate what relevant information is available through the Health Management Information Systems Data. We will use a case-study approach to develop a comprehensive picture of operational reality. In each state, we will purposively select 2-3 rural and urban Primary Health Care facilities, one rural and one urban secondary level facilities, and one hospital where rehabilitation services are offered. We will use mixed methods to collect a range of data, including: an accessibility audit of the facilities, structured-observations of patients' visits, and in-depth interviews with health professionals (selected from different cadres). We will conduct interviews and focus-group discussions with people with disabilities and carers, selecting people with a range of impairment types, men and women, and different ages. Qualitative data collected will be thematically analysed. Triangulation of data will be conducted to synthesise and integrate data from different sources in order to address research objectives. Last, we will use participatory methods to formulate policy and programme recommendations, working with key stakeholders. People with disabilities will play a central role in formulating these recommendations.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Patients, the public and the uses of big data; practical engagement, education, scrutiny and leadership
Funder: Medical Research Council

Abstract: I will build the evidence base to inform best practice in this area. I will undertake research (using methods such as discrete choice experiments) to generate a better understanding of the views of patients and the public about how data are used. A significant benefit of the links to the use MY data patient movement is that we will have a range of patients and advocates who have already been through a range of training and education (which will continue). Their skills, experience and views will be a unique resource to the project, providing ready access to a specialist advisory and reference group. Using real life examples and clinical scenarios I will ask patient groups to look at the types and levels of data required, and how they would need to be used, to answer specific research questions. This will generate evidence to strengthen our understanding of what the public would, and would not, be happy for data to be used for. Key points here are that the scenarios would be based on actual patient experience, and the process would be patient-led and reported so ensuring the public credibility and maximum impact of research work across HDR-UK. Much of the research will be qualitative in nature, with a key focus on the development of lay summaries to encapsulate and communicate learning.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: The Refining Dog Care online learning platform - a modular learning resource for those working with dogs in research.
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: We will provide an Online Modular Learning Platform (OMLP) to improve the welfare of dogs and consequently the validity and reliability of data from their use in research and testing. The welfare of animals in scientific establishments is mediated by humans and we have previously demonstrated the impact of practices on welfare, behaviour, physiology and cardiology. Given the necessity of animal use as models we have a moral obligation to ensure that their welfare is optimised and their use results in valid and reliable scientific outcomes. Harmonisation of study outcomes between and within companies has proved challenging in animal research, particularly in multinational companies. There is a considerable need to provide science-based resources for training staff in order to address poor study outcomes. The successful translation of animal welfare research is dependent upon human behaviour change (HBC) interventions. Using a participatory approach, which will allow us to gather qualitative and quantitative data from partner staff, we will assess motivation, barriers and limitations to behaviour and attitude change. We will use semi-structured interviews to gain insight into our partners' expertise to inform the design of the OMLP. Changes in practice will be assessed using Knowledge, Attitude and Practices surveys. The principles of HBC, underpinned by evidence-based theories, eg Theory of Behaviour Change, Self-efficacy Theory, will be embedded into the design of the resources to impact learners, stimulating practical and sustained animal welfare improvements. Once launched, we will to assess longitudinally knowledge against learning outcomes, and changes in attitude and behaviour via surveys and assessments embedded in the platform. The design of the OMLP will provide an evidence base for learning resources rooted in the science of HBC which will lead to measurable improvements in Refinement and Reduction techniques applied to dogs in scientific research.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Investigating the treatment of paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME).
Funder: Department of Health and Social Care

Abstract: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is common and disabling yet little is known about recovery, whether Graded Exercise Therapy (GET) is effective, or what treatment strategies might work in children who are severely affected by CFS/ME. This programme of work will: determine what is known about recovery and how to define it; investigate the Minimal Clinically Important Difference in outcomes; study how to deliver GET; conduct a multicentre trial investigating the effectiveness of GET compared with activity management for mildly and moderately affected children, and start the work needed to establish a trial for severely affected children.

Lay abstract: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is common and disabling yet little is known about recovery, whether Graded Exercise Therapy (GET) is effective, or what treatment strategies might work in children who are severely affected by CFS/ME. This programme of work will: determine what is known about recovery and how to define it; investigate the Minimal Clinically Important Difference in outcomes; study how to deliver GET; conduct a multicentre trial investigating the effectiveness of GET compared with activity management for mildly and moderately affected children, and start the work needed to establish a trial for severely affected children.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: A genome-wide association study of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)
Funder: Medical Research Council

Abstract: "ME/CFS is a chronic and fluctuating condition that may affect many body systems. People with ME/CFS experience severe, persistent fatigue associated with post-exertional malaise. Few recover, most remain ill for many years. Risk for ME/CFS is known, in part, to be inherited. Biomolecular research into the causes of ME/CFS has long suffered from a replication crisis caused by most studies being considerably underpowered. Studies also often suffer from ill-defined disease criteria, cohort heterogeneity and failure to distinguish aetiology from symptomology. Our Partnership aims to reveal causal biomolecular mechanisms of ME/CFS and to create focused opportunities for development of diagnostic tests and targeted treatments. We will build a re-contactable research cohort of 20,000 people – each clinically diagnosed with ME/CFS and who meet either Canadian Consensus or IOM/NAM criteria – with DNA genotypes obtained by spit-and-post to allow a case-control genome-wide association study. Genotypes of control individuals will be obtained primarily from UK Biobank. Statistically significant association of loci to ME/CFS status would then provide objective and testable hypotheses with which to illuminate ME/CFS disease aetiology. We will also test for genetic concordance with other complex traits. Importantly, we expect genetic associations to provide the evidence base necessary to substantially improve the perception of ME/CFS among health care professionals and the general public, and reduce some of the stigma currently experienced by pwME. Our expertise ranges from interdisciplinary science (cohort building, genomics and statistical genetics) to the lived experience of ME/CFS of patients and carers. The considerable reach of our Patient and Public Involvement team (containing representatives of ten UK charities and from Science for ME) and our planned marketing and PR campaigns will optimise recruitment of the 20,000 ME/CFS cases."


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: New technology to improve capability for clinical radiopharmaceutical production
Funder: Medical Research Council

Abstract: There is a roadblock in the availability of new molecular imaging agents for clinical use. The demand for enabling technology is driven by the expansion in agents that have been validated as gold standard in patient care but do not yet have sufficient clinical availability. There is a challenge in delivery of these new diagnostic drugs at an appropriate cost point with minimal impact on staff training and infrastructure. This is an issue affecting health service provision worldwide. The key complexity in producing the radiopharmaceuticals is the infrastructure required on clinical sites (GMP facilities and highly trained staff on each site due to the short half-life of the drug). This increases cost above that incurred for routinely used agents in nuclear imaging such as fluorodeoxyglucose (FDG), a standard radiopharmaceutical used in positron emission tomography imaging. The most important recent example is the development of gallium-68 PSMA imaging which has become a key driver in the expansion of the market. This agent offers unrivalled capability in the detection and therapy response of prostate cancers but only has limited availability. Most hospitals lack the infrastructure and trained staff to produce the agent. The gallium-68 generator has only recently been approved for routine clinical use (2014) and so this is an ideal time to enter the market with demand on a sharp upward trend. This may also link to theranostic developments that are expected to increase over the next 10 years. The technology that we have developed is a microfluidic device that allows efficient processing of the generator eluent and brings synthetic capabilities to operate "at generator", increasing production efficiency with a strategy to provide tracer in a "patient ready" form for administration. This requires limited intervention by the radiopharmacist and can also produce the tracer in a "dose-on-demand" model that is a better fit with clinical need.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Lending a hand: developing a support structure for young migrants in South Africa and Uganda
Funder: Medical Research Council

Abstract: We will develop and test the acceptability and feasibility of a protective support structure for young migrants (aged 14-24 years old) in urban settings in South Africa and Uganda as means of early intervention to reduce the harm of patterns of risk behaviour (sexual risk and violence) associated with youth migration. We will 1) establish a peer-supporter network in three sites (a small town in Uganda and in South Africa and part of the capital city in Uganda) to provide advice and support over the telephone to individual young migrants; 2) offer a drop-in centre (a rented shop or similar) staffed by a peer-supporter during the day and early evening who can provide information and onward referral to local health and social services, free condoms, access to a counsellor/nurse for advice and the use of a computer/printer; 3) identify local champions and resources to enable a more supportive environment for youth. Our plans draw from evidence gained through prior research in the two settings, and a Theory of Change which draws on a `protection-risk' conceptual framework. Our focus is young people who have migrated, particularly new migrants within six months of their move to the new location, while still providing advice to migrants of longer standing, who may be planning a further move or change in their employment. We will use mixed-methods to adapt, implement and evaluate the feasibility of an intervention. We will use participatory methods working with youth advisory groups in both countries already engaged in the design of this project, to develop and implement the intervention. We will assess which facets of the package are valued and test our assumptions about the challenges young migrants face and the appropriateness of the intervention offered. Finally, we will design a full-scale evaluation of the effectiveness and cost effectiveness of the feasible and acceptable elements of the intervention, which we anticipate will be a randomised control trial.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Preventing violence against adolescents in schools: understanding implementation of the Empateach intervention in Nyarugusu refugee camp
Funder: Medical Research Council

Abstract: We will conduct a process evaluation of the Empateach intervention, which leverages behavioural science techniques to change teachers' beliefs and behaviours around corporal punishment, in Nyarugusu refugee camp in Tanzania. This study will run alongside a randomised controlled trial to assess the effectiveness of the intervention. We will conduct quantitative analyses of survey data from n=1250 students and n=500 teachers, and routine data collected from 27 schools, to explore whether school level background characteristics are associated with levels of intervention implementation and levels of violence; we will examine what was and was not implemented (fidelity), the exposure of individual teachers and schools (dose), and which individual teachers participated in the intervention and which completed a high proportion of activities (reach); finally, we will investigate pathways of change in individual teachers' and students outcomes using causal mediation analysis. We will also conduct qualitative analyses of data from approximately 200 individual interviews and 20 focus groups, drawing on techniques from Grounded Theory, including constant comparison and searching for deviant cases. We will explore conceptualizations of 'violence' and 'discipline' among students, parents, teachers and administration; assess the intervention implementation from the perspective of school administrators and management inside and outside schools, to inform scale up (including what aspects of the intervention were easy and more difficult to implement, what changes were made during implementation, and any patterns noted in participation); and we will delve into the experience of teachers, students and school administration with the intervention to understand what participants felt 'worked' and 'didn't work' and to gain insight into the mechanisms of action. The study will also include an economic evaluation to estimate the costs and cost-effectiveness of the Empateach intervention.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Refining weaning age in macaques destined for neuroscience research
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Rhesus macaques (Macaca mulatta) are an important animal model in neuroscience research and there is no immediate prospect of their replacement with less sentient species or in vitro models. The long-term, invasive nature of neuroscience research places substantial demands on macaques, raising valid concerns about cumulative severity. For these reasons, refinements to macaque husbandry that improve tolerance of laboratory housing, improve compliance with experimental procedures and/or reduce infection rates could have a significant positive impact on the welfare of macaques involved in neuroscience research.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: DISPUTED AETIOLOGY AND OTHER