NIHRDataInsights/HRCSData huggingface dataset:
Title: The Avon Longitudinal Study of Parents and Children: An international resource for population genomics and lifecourse epidemiology. Core Programme Support 2011-2015 and Core programme support 2014-2019
Funder: Medical Research Council

Abstract: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective cohort study with unprecedented scope and detail of information on thousands of people from before birth through to early adulthood, on their parents and now on their children. It is an internationally valued resource at the forefront of population-based research. ALSPAC allows the investigation of developmental trajectories marking critical periods in human life, the genetic and epigenetic factors contributing to health and disease and the environmental exposures which form the context within which these processes act. As ALSPAC participants enter adulthood and start having children, the study's potential to contribute to scientific discovery is expanding, giving a greater capacity to explore links between current and future health and the intergenerational components of health and disease. ALSPAC is unequivocally the richest open-access epidemiological resource in the world. Our goals are to ensure that ALSPAC (i) is sustained, (ii) has participation maximised and (iii) is enhanced. These goals will be delivered by follow-up of the original cohort through clinic assessment, questionnaires and record linkage, data collection on their children, consolidation of GWAS data on all participants and the development of epigenomics research.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: UK Biobank Imaging Enhancement Main phase
Funder: Medical Research Council

Abstract: UK Biobank has involved the collection of extensive baseline questionnaire data, physical measurements and biological samples from 500,000 men and women aged 40-69 at baseline in 2006-10, and their health is now being followed by linkage to health records and by web-based questionnaires. This proposal involves the enhancement of the phenotyping of 100,000 participants in UK Biobank with information from multiple imaging modalities involving the brain, heart, large blood vessels, body composition, and bone and joints. The large scale is intended to provide sufficient statistical power for reliable assessment of associations between these imaging phenotype measures and a wide range of incident diseases. As with the successful recruitment and baseline assessment phase, the application of highly efficient processes to optimise and manage these imaging assessments has been shown in the pilot phase to allow them to be conducted cost-effectively. The pilot phase has also demonstrated that non-imaging assessments could be conducted in parallel without interfering with the streamlined imaging process. The pilot phase has shown that high quality data can be obtained and that an increasing range of research-ready measures can be derived using automated analysis tools. These imaging data would be available to all bona fide researchers for health-related research that is in the public interest. During and after the main phase of imaging, these dedicated imaging centres could also be used for repeat imaging in subsets of participants to allow investigation of the relevance of changes in imaging measures to various outcomes (e.g. dementia).


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Maths, Engineering and Life Sciences: making connections for precision medicine
Funder: Medical Research Council

Abstract: A multitude of biological and environmental factors interact to mediate human development, health and disease. It follows that a number of data types are required to describe these factors; one-dimensional viewpoints – even omic datasets – are one-dimensional oversimplifications of extraordinarily complex multi-cellular systems. To power precision medicine, we must build a multi-dimensional picture, by integrating data from multiple viewpoints from the single-cell level upwards. Our overarching aim is to develop a step change in research capability towards precision medicine at the University of Southampton. We request funding for a microfluidic engineer, a systems biologist, to promote collaboration between mathematical, computational, engineering, biology and medical specialisms in a new interdisciplinary laboratory. We request equipment to develop new quantal microfluidic processes to increase information depth and resolution down to the single cell level, novel analytical methods will then model the complexity of human disease. This investment will produce new technology and methods to capture unique cross-cutting datasets in disease systems, and new multi-dimensional analytical strategies in molecular systems biology. It will not only uncover the spatiotemporal architecture of development in single cells and cell populations; it will promote an imaginative, systems-biological mind-set, and a common vocabulary of research and enquiry in microfluidics, data science, and medical research across rare, infectious, acquired and non-communicable disease. The lasting impact of this investment will be new tools and concepts for human development and disease, and resultant advances towards the personalised therapeutic and preventative strategies that are the vision of precision medicine.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE
Title: The Scottish Genomes Partnership
Funder: Medical Research Council

Abstract: As part of a strategy to deliver genomic medicine in the NHS, Genomics England (GeL) was allocated £100m by DH England to sequence 100,000 genomes. The MRC wished to partner the Devolved Governments of Northern Ireland, Scotland and Wales to help to develop their capabilities and support their engagement with this initiative through GeL, to help to establish a UK-wide partnership that builds and brings together larger assets of genomic data from across the UK, with the capability to link together and enhance genomic, phenotypic and health record assets. This award represents the MRC’s investment in the Scottish Genomes Partnership and complements partnership funding of £4,000,000 from the Scottish Government, and up to £3,500,000 from Scottish Enterprise, which will be awarded separately. Funds will be used to (1) support SGP's sequencing of genomes of individuals with rare diseases (1000 genomes, ca 330 trios) and (2) to support the development of federated analysis solutions for distributed genomic data, including through joint working with GeL.


Research activity codes: 4.4 POPULATION SCREENING;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: The Wales Genomic Medicine Centre
Funder: Medical Research Council

Abstract: The overall vision of the Wales GeMeC is to bring benefit to patients through improved diagnosis, together with improved understanding of rare diseases through the contribution of samples from patients in Wales. The award will contribute to the development of a UK-wide resource of linked genomic, phenotypic and health record information that would be a key asset driving patient care and directing key research programmes at a local, national and international level. It will harness and enhance existing regional capability in genomic medicine and research and also build the capacity of the Welsh NHS, Universities and Industry to translate research into patient benefits, through active participation in the UK 100,000 Genomes Initiative and beyond.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: A Midlands Regional Cryo-EM facility
Funder: Medical Research Council

Abstract: We are seeking to establish a regional cryo-Electron Microscopy facility in the Midlands. This will serve the needs of a large community of structural and cell biologists, enabling them to take advantage of the revolution in this technology. The facility will comprise a high-end 300kV instrument in Leicester and a 200kV feeder instrument in Warwick. Together with existing feeder instruments, this will establish an ecosystem (with both shared equipment, expertise and training) that will transform structural biology in the Midlands. The facility will support the research of more than 37 researchers studying complexes involved in gene regulation, DNA replication and repair, cellular organisation and communication. In addition, we will use the instrument to develop methods for time resolved cryo-EM and imaging membrane proteins using SMALP technology. In recognition of the strategic value of this facility, the regional Institutions have together committed to making a substantial financial contribution (>40%). There is a strong track record of collaboration and expertise sharing between the Midlands structural biologists. This will ensure effective use of the facility, accelerating our world-class research into the structure and mechanism of the molecular machinery that drives cellular function.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: The Scottish Macromolecular Imaging Centre (SMIC)
Funder: Medical Research Council

Abstract: Cryogenic transmission electron microscopy is revolutionising the field of structural biology, allowing researchers to determine rapidly the structures of macromolecular assemblies at close to atomic resolution. Furthermore, developments in cryogenic imaging of the cell are beginning to realise the exciting prospect of in-situ structure determination. We propose to establish a world-class centre for CryoEM with the primary objective of supporting macromolecular structure determination for life-science researchers in Scotland and northern England. Based in the Medical Research Council - University of Glasgow Centre for Virus Research (CVR), the Scottish Macromolecular Imaging Centre (SMIC) will be equipped with a 300 keV automated cryo-transmission electron microscope that is fitted with a direct electron detection camera, an energy filter and phase plates for high-contrast imaging. The centre will be founded by a consortium of Scottish Universities and serve as the hub for a network of structural biology researchers, fostering collaborations, training programmes and mutual support. Existing cryoEM resources at Glasgow, Dundee and Edinburgh will act as feeder sites with expert technical support to facilitate project development before presentation at SMIC. Oversight of SMIC by a management group will ensure that highest quality outputs are achieved and that the facility is operated with maximum efficiency.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Cryo-Electron Microscopy Research Infrastructure
Funder: Medical Research Council

Abstract: The Oxford Centre for Particle Imaging (OPIC) at the Wellcome Trust Centre for Human Genetics (WTCHG) plays the leading role for biological cryo electron microscopy and tomography (cryoEM and cryoET) at Oxford University. OPIC also offers a unique capability of contained microscopy as part of eBIC, the national facility. The high-end cryoEM instrument in OPIC is a 12-year-old FEI F30 ‘Polara’, which has become a bottleneck for our science due to its unreliability, low throughput and lack of ability to integrate latest technologies. The requested Krios cryoEM will: - Underpin the research of multiple groups within the WTCHG, that of the Structural Genomics Consortium (SGC) and other neighbouring biomedical researchers on the Old Road Campus. - Serve as a lynch pin in the pan-departmental strategy for biological cryoEM across the University of Oxford. - Provide access to high-end cryoEM and cryoET for eBIC users with projects requiring ACDP category 3 and DEFRA 4 levels of containment. Research that will benefit includes: - ‘structural vaccinology’ combining deep/single cell sequencing of the humoral response to emergent viruses with cryoEM mapping of epitopes. - analyses of cell-cell signalling systems and virus-cell interactions using sub-tomogram averaging and whole cell cryoET combined with correlative light microscopy.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: State-of-the-art workshop: Methods for placebo comparator group selection and use in surgical trials
Funder: Medical Research Council

Abstract: Leading national and international experts will produce state of the art thinking and knowledge on placebo control in surgical evaluation. It could be argued that placebo designs are especially important for surgery for two main reasons. Firstly, surgical interventions have undergone far less rigorous evaluation, often being the treatment of last resort. Secondly, bias is particularly high for surgery with surgical interventions anticipated to have a larger placebo effect than other treatments, given the orchestration and personalisation around the intervention delivery. Indeed, recent work we and another group have undertaken has shown the substantial magnitude and duration of surgical placebo effects. Previous reviews of placebo-controlled surgical trials have examined the characteristics of such studies, and some of the issues related to recruitment and feasibility, impact on outcome and serious adverse events. These reviews however, have not considered in detail trial design issues such as when it is appropriate to use a placebo control in a surgical trial, what factors should guide the choice of a placebo design and how that choice influences intervention standardisation (and fidelity assessment), selection and use of co-interventions. Further practical consideration of ethics is needed. Additionally, how placebo comparators are developed and piloted before use in a main trial has not been considered. Furthermore, beyond placebo analgesia studies using neuroimaging, there is little information on the neurophysiology of placebo in other contexts and little support to help recruitment to placebo surgical trials. Guidance around these core methodological considerations is urgently required to ensure that trialists can design (and funders can appropriately assess and fund) the optimal placebo controlled surgical trials of the future. Workpackage 1: Summary of current position for placebo control relating to surgery. Aim: To generate an overview of the state-of-the-art thinking on the placebo phenomenon as it applies to surgical research (incorporating ethical perspectives, neurophysiology, clinical frameworks and the regulatory/governance contexts). Workpackage 2: Systematic review of the use of a surgical placebo in trials. Aim: To identify new studies and key literature on surgical placebo control and review with specific attention on the rationale for placebo use, the type of placebo control used and any methodological/trial conduct implications these raise. Workpackage 3: Modified Delphi process to achieve consensus on the structure and content of the Workshop. Aim: To determine the scope of the workshop, optimise the programme, and ensure the output/guidance reflects stakeholders needs (focusing on subjects for which consensus is least well developed and for which open debate is needed).


Research activity codes: 6.4 SURGERY;6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: UK Biobank (core renewal)
Funder: Medical Research Council

Abstract: The UK Biobank resource has been established primarily for the conduct of prospective studies investigating the relevance of a wide range of exposures to health outcomes that occur during long-term follow-up. By 2022, there will start to be sufficient numbers of incident cases of the commoner conditions to support extensive and powerful research into their determinants (although research related to conditions present at baseline has already started). Hence, the chief emphasis for the past 5 years has been on preparing UK Biobank for effective use as a prospective resource by the widest possible range of researchers. This activity has included: developing resource access management systems; conducting repeat assessments in 20,000 participants; establishing record linkage for death, cancer and hospitalisation; piloting large-scale characterisation of commoner conditions; enhancing participant phenotyping; preparing for imaging assessments; and turning biological samples into genotypic and biomarker data to make the resource more accessible to researchers studying a wide range of different conditions. During the next few years, it is intended to: extend cohort-wide record linkage to primary care health records and conduct direct participant follow-up (e.g. for cognitive function); further develop and implement large-scale identification and characterisation of many different types of health outcome; streamline the research access systems, and improve methods for processing, presenting and providing linked healthcare data to researchers; conduct imaging assessments in 100,000 participants; develop and implement further enhancements (such as cardiac monitoring and further sample collection and assays); and make increasing amounts of genotype and biomarker data available. Efforts will also be made to ensure that researchers from around the world are suitably well informed about these developments so that use of the resource increases substantially over the next few years.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Methodology State-of-the-art workshop: management of measurement reactivity in trials of interventions to improve health
Funder: Medical Research Council

Abstract: Measurement reactivity has been defined as being present where measurement results in changes in the people being measured. The clearest evidence for this comes from a number of systematic reviews which show that asking people to complete questionnaires can result in changes in behaviour. In addition, there is ample other evidence that measurement other than questionnaire effects on behaviour can produce reactivity specifically in medical and healthcare contexts. This workshop will examine how these measurement reactivity effects can result in bias in trials in medical and healthcare contexts. The potential for bias exists where measurement differentially affects intervention and control groups. There are at least two situations where this is likely to occur: where interventions and measurements interact, and where measurement is unbalanced across randomised groups. There is a rapidly increasing literature which aims to identify why measurement can affect behaviour. Despite this, to date there appears to have been little systematic consideration given to which other situations exist where the effects of measurement interact with the mechanisms by which interventions are supposed to produce effects. There is a lack of consensus on the situations where one would expect measurement reactivity effects to occur, and little discussion of when one would expect these measurement reactivity effects to interact with other interventions. In sum, although there is now good evidence that measurement is not an inert procedure, it has generally been ignored in discussions of how to reduce bias in trials. There is no agreed set of practices for conduct, reporting or analysis of measurements that allow these patterns of responding to be understood or controlled for. Therefore, a set of guidance statements on how best to reduce bias due to measurement reactivity in studies of interventions to improve health, with a particular focus on bias in RCTs, will be produced. This focus is necessary, given the huge literature on measurement reactivity that sprawls across multiple disciplines, and the central importance of trials evidence for healthcare decision-making. To achieve the overall aim, the present research has the following objectives: a. identify key background literature examining measurement reactivity b. determine the scope of the guidance that would best meet stakeholder needs c. achieve consensus on guidance statements, and produce a guidance document based on this consensus d. disseminate key messages of guidance


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: ActEarly: a City Collaboratory approach to early promotion of good health and wellbeing
Funder: Medical Research Council

Abstract: This grant is funded by the UK Prevention Research Partnership (UKPRP) which is administered by the Medical Research Council on behalf of the UKPRP’s 12 funding partners: British Heart Foundation; Cancer Research UK; Chief Scientist Office of the Scottish Government Health and Social Care Directorates; Engineering and Physical Sciences Research Council; Economic and Social Research Council; Health and Social Care Research and Development Division, Welsh Government; Health and Social Care Public Health Agency, Northern Ireland; Medical Research Council; Natural Environment Research Council; National Institute for Health Research; The Health Foundation; The Wellcome Trust. Our vision is to promote a healthier, fairer future for children, young people and their communities by addressing the social and environmental determinants of health. We will create a ‘City Collaboratory’ (an open space or creative process where people work together to generate solutions) to co-produce and evaluate upstream interventions. Prevention research has tended to focus on ‘downstream’ interventions aimed at changing individual behaviours, frequently increasing inequalities. Our approach is to align our research expertise with the knowledge and experience of families, children, communities, local authorities, voluntary sector and industry to identify preventive pathways and implement and evaluate upstream interventions. Our collaboratory will take a lifecourse approach, focusing initially on the improvement of child health and development to improve health and wellbeing in young people so that they enter adult life with optimal health and ultimately improve the health of the whole population. We will evaluate impact on level and inequalities of a broad mix of outcomes such as education, physical activity, healthy growth and development (motor, cognitive) and longer term evaluate impact on adolescent/early adulthood obesity, mental health, cardiometabolic and respiratory outcomes. We propose a City Collaboratory model for whole system prevention. Our initial focus will be in Bradford, building on established, community-embedded research platforms and substantial planned investment in interventions to improve child health. We will then replicate the Collaboratory approach in a deprived area of London to test replicability in other UK populations. Researchers and stakeholders too often operate in disciplinary, sectorial and geographical silos. Our consortium development grant will bring together extensive international transdisciplinary, trans-sectoral expertise working across Yorkshire and London with local and national stakeholders to strengthen existing partnerships, recruit new partners, agree on priorities and develop long-term models whereby our City Collaboratory can maximise impact.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE