NIHRDataInsights/HRCSData huggingface dataset:
Title: Biobank Re-imaging Study co-funded by Medical Research Council (MRC), Chan Zuckerberg Initiative (CZI) and Calico Life Sciences LLC (Calico)
Funder: Medical Research Council

Abstract: Re-imaging Study co-funded by Medical Research Council (MRC), Chan Zuckerberg Initiative (CZI) and Calico Life Sciences LLC (Calico) The MRC Contribution to the study is £10m out of a total investment between the funders of £30m. The investment is to support:- UK Biobank is a large, prospective cohort study that enrolled 500,000 men and women aged 40 to 69 from across the UK during 2006-10. At recruitment, they answered a large number of questions about their lifestyle, environment and other exposures, had a series of physical measurements (including eye imaging in a subset of about 100,000) and provided samples of blood and urine (and saliva in a subset of about 100,000) for both immediate haematological assays and frozen archiving for subsequent assays (including genotyping and genetic sequencing of the whole cohort). UK Biobank has become the pre-eminent biomedical research platform for studying the aetiology of common diseases of middle and later life (Sudlow et al. 2015), with over 20,000 registered researchers conducting over 2,000 approved research projects, leading to over 2,500 publications by mid-2021.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE;CARDIOVASCULAR;NEUROLOGICAL
Title: Evidence Synthesis as a tool for the Evaluation of Therapeutic Medical Devices
Funder: Medical Research Council

Abstract: The research objectives are to: (i) investigate the methods for generating cost effectiveness evidence for therapeutic medical devices. (ii) test out evidence synthesis methods to investigate the relative cost-effectiveness of medical devices using chronic venous leg ulceration as a tracer condition. (iii) explore alternative methods of evidence synthesis to integrate summary data with patient level economic and clinical data. The research methods include systematic review of the literature, comparative analysis, qualitative research with healthcare policy makers involving semi-structured interviews, and Bayesian evidence synthesis methods (among them mixed treatment comparisons; generalised evidence synthesis; multi-parameter evidence synthesis; comprehensive decision analytic modelling) using summary and patient level data. The delivery of this project will provide a formal framework for the evaluation of medical devices for the treatment of specific health conditions which can be used to inform healthcare decision making regarding adoption decisions.


Research activity codes: 6.3 MEDICAL DEVICES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: GENERIC HEALTH RELEVANCE;CARDIOVASCULAR;SKIN
Title: The Human Gut Microbiome as a Modifier of Human Health
Funder: Wellcome Trust

Abstract: My project will aim to investigate the role of the human gut microbiome in health and disease outcomes, in particular to assess its role in the link between dietary composition and obesity. The human gut microbiome is a huge community of microorganisms that exist within our digestive systems that interact to aid digestion, protect against pathogens and create metabolites. Although previous evidence suggests the gut microbiome plays a role in health and diseases, much of the literature (arising from animal or observational human studies) attempting to assess this relationship has so far been inconsistent and unable to prove cause-and-effect relationships. I aim to combine epidemiological, genetic and causal inference methods to establish relationships between dietary composition and the microbiome and between the microbiome and health outcomes (focusing on obesity). Dietary composition is one of the key exposures dominating the literature as a likely regulator of the gut microbiome, with a diet high in dietary fibre for example being correlated with high microbial diversity. Lower microbial diversity has been observed in the gut of people with obesity, amongst other diseases. By filling the gaps in the evidence, this research has the potential to be translated into clinical practice and industry.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE;CARDIOVASCULAR;STROKE;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL
Title: Incidental findings (Ifs) from genetic tests: exploring the ethical issues and implications for practice
Funder: Department of Health (England)

Abstract: Genetic testing techniques have advanced enormously over the past few decades. It is now possible to examine large potions of a person’s genetic code at costs manageable to routine NHS services. As well as diagnosing the cause of specific clinical signs and symptoms, or family histories of disease, such genetic testing will also at times find entirely unexpected, but clinical relevant information about a person, such as a future disease likelihood. This research fellowship aims to gain an empirical and ethical insight into the experiences and attitudes of healthcare users and professionals towards incidental findings (IFs) from genetic testing, using both quantitative and qualitative research methods. This together with an analysis of relevant literature will provide novel insights into the practical and ethical issues surrounding IFs in genetic practice and allow the development of guidance on how practice should evolve as technologies increase the likelihood of IFs.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;CONGENITAL DISORDERS
Title: Investigating the role of DNA methylation in human growth disorders
Funder: Medical Research Council

Abstract: Understanding the basis of inherited disease remains an important and substantial goal in human health research. Mutations in the DNA sequence account for inherited disease in the large part, but increasingly it is being recognised that epigenetic factors such as DNA methylation play an important role. Identifying and understanding the interplay between genetic and epigenetic mutations is important for elucidating disease mechanisms and for developing strategies to identify biomarkers, diagnostic tools and treatments. We present data showing that we can interrogate human DNA methylation genome-wide and we have used bioinformatic tools to confirm known regions of hypomethylation in patients with a well-characterised human growth disorder, Silver Russell Syndrome (SRS). We propose to mine high-resolution methylation data generated by next generation sequencing methods from SRS patients who lack known methylation defects for novel epimutations. Furthermore, we will examine the methylomes and exomes of a group of rare, extreme syndromic growth disorders and a group of common non-syndromic (interuterine growth retardation-IUGR) growth disorders for which the underlying aetiology is poorly understood. With this strategy we will identify novel epimutations and disease genes and characterise associations between methylation variation and genetic variation.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;CONGENITAL DISORDERS
Title: How are centrosomes/SPBs licensed at the meiosis I to meiosis II transition?.
Funder: Wellcome Trust

Abstract: The growth of all living things depends on the duplication and subsequent division of cellular material. Of utmost importance in the generation of healthy new cells is the accurate partitioning of the genetic material that is contained on the chromosomes. This will ensure that each new cell inherits all the information it needs to grow and prosper. Sometimes errors are made during cell division that result in the unequal distribution of the chromosomes to the new cells. These cells with too few or too many chromosomes are said to be aneuploid, a condition that is associated with diseases such as cancer and Down s syndrome. To understand how these defects arise we are studying the cellular machinery that partitions the chromosomes. The pairs of newly duplicated chromosomes are pulled apart by a structure known as the spindle. The spindle forces are counteracted by glue, known as cohesion, between each chromosome pair. This ensures that chromosome pairs do not separate until all chromoso mes are in place. Our goal is to understand the establishment and regulation of cohesion at the site of spindle attachment and to understand how linkages in this region contributes to the generation of healthy daughter cells.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;CONGENITAL DISORDERS
Title: Deciphering the function of GORAB and how its loss leads to Gerdoderma Osteodysplastica
Funder: Wellcome Trust

Abstract: Geroderma osteodystplastica (GO) is an autosomal recessive disorder with hallmark symptoms of lax skin, precocious skin aging, osteoporosis, and growthretardation. It was recently demonstrated that GO is caused by mutation of GORAB (Golgin, Rab6 interacting), a protein localised to the Golgi apparatus. However, the cellular function of GORAB and mechanisms underlying GO pathogenesis are currently unknown. The goals of this project are to define GORAB function at the cellular level and to decipher how loss of GORAB leads to the clinical manifestations of GO. Our preliminary work suggests a role forGORAB in exocytic membrane traffic, and we hypothesise that defects in this process leads to defective deposition of the extracellular matrix of skin and bone. The specific aims are to: 1) Determine the role of GORAB in exocytic membrane traffic 2) Identify and functionally characterise GORAB interacting proteins 3) Investigate how loss of GORAB results in extracellular matrix defects seen in geroderma osteodysplastica patients


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;CONGENITAL DISORDERS
Title: Health Care Innovations from Policy to Practice: A Case study of Rapid HIV testing in General Practice
Funder: Department of Health (England)

Abstract: Health Care Innovations from Policy to Practice: A Case Study of Rapid HIV Testing in General Practice. Population-wide testing for HIV is UK policy where background HIV prevalence is >2 per 1000 (1). The RHIVA 2 Trial of Rapid HIV Testing in General Practice saw wide variations in implementation. This research aims to explore the policy-practice gap in implementing rapid HIV testing. It is a mixed method, multi-level case study linked to an ongoing cluster randomised trial (RHIVA2). Analysis will include individual, organisational and policy level data with an aim to provide insights into why an evidence based national police is implemented widely in some settings but a to a limited extent in others.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: Streamlining Galen: Medical Summaries and the Transmission of Medicine in Medieval Islam
Funder: Wellcome Trust

Abstract: We propose to study medical teaching and practice and the changing face of Galenic medicine in Islam through the medium of a prolific but largely unstudied genre of writings, Arabic summaries of Galen. A fundamental re-evaluation of these sources will show how they served as primary learning tools for medical students and doctors, a means of demonstrating medical credentials, and as instruments for the reconfiguration of the ancient medical heritage. In addition to a comprehensive survey of Arabic Galenic summaries, we will compile and digitise a select corpus of such texts, and analyse and compare them with the Galen treatises in Arabic translation that formed the basis of the summaries, using digital tools and techniques of close reading. The proposed outcomes include (1) a study of the history, nature and purposes of summaries in Arabic medical literature; (2) monograph studies, editions and translations of a number of these works; (3) articles on individual authors of summaries and their working methods; (4) the proceedings of a conference on the role of auxiliary texts in the evolution of Galenic medicine in antiquity and the Middle Ages; and (5) a publicly available digital corpus of summaries and related texts.

Lay abstract: What makes a doctor in medieval Islam? To answer this crucial question of medical authority and legitimacy, we propose to study the production, transmission and control of medical knowledge through a ubiquitous but overlooked genre of medical writings: Arabic summaries of Galen. In late antiquity and medieval Islam, the writings of the Roman physician Galen (d.216 CE) formed the basis of professional medicine. Most were translated into Arabic. Arabic-speaking doctors produced a flood of summaries to help their readers learn and reproduce Galenic science. These reflected both the changing methods and priorities of their authors and the changing face of Galenic medicine itself and its role in Islamic society. Some authorities commended summaries as study tools, while others condemned them as illegitimate shortcuts. This project will study the training and legitimisation of physicians, and the transmission and transformation of medical knowledge in the Islamic world.

Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: “The palliative care needs of Palestinians in the Gaza Strip: a community-based study”
Funder: The Academy of Medical Sciences

Abstract: Gaza Strip is a tiny piece of land with 2 million individuals with fragile Health services which was further damaged with prolonged siege and frequent episodes of violence. Gaza strip suffers a high prevalence of cancer and chronic illnesses compared to other cities inside Palestine and globally. The lack of freedom of movement between the two main geographical zones makes the job of health care professional doctors harder and the demands for creating context-specific training centers rather than one or two strong centers a necessity and challenge. The vast majority of cancer patients and suffers from chronic illnesses complain of poor services and many complications and no one has ever looked at the real needs of those people and how to meet them and offer help. Therefore, Scoping study of palliative care needs and serviecs is needed to help decision-makers and health professionals better plan for the future with a hope to improve health care delivery and quality of life of needy people. Conducting such comprehensive and high-quality research requires good planning and training with experts in the field and capacity building through better international collaboration.


Research activity codes: 7.2 END OF LIFE CARE
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: The Intersectional Effects of Disability and Social Class on Becoming NEET
Funder: The British Academy

Abstract: Disabled children and young people are at high risk of becoming NEET (Not in Education, Employment, or Training) in early adulthood. Persisting medical understandings of disability typically interpret this risk as an inevitable consequence of individual conditions and/or impairments. As a result, we know little surrounding the social processes that are implicated in disability-related educational and occupational disadvantage experienced by disabled young people. Furthermore, existing studies have largely adopted monolithic understandings of disability, disregarding impairment-specific barriers and stigmas, as well as intersections with social class status, which may have critical implications for NEET outcomes. Adopting an intersectional lens, this project will rectify omissions in existing research by investigating processes of becoming NEET among physically disabled young people from low social class backgrounds. We will will highlight overlooked processes of social reproduction, whilst encouraging a move beyond single-axis analyses of disability-related inequalities in future social stratification and employment research.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: Care Beyond the Family? British South Asians and Ageing in Scotland
Funder: The British Academy

Abstract: The UK population is ageing and the ‘challenges’ this poses have been recognised by academics and policy makers alike. Discussion, however, has primarily focused on the UK population as a whole, with insufficient attention paid to ethnic minority populations, especially in Scotland. This study will serve as a corrective. It focuses on British South Asians in Edinburgh and Glasgow to interrogate aged care within a context of cultural heterogeneity. It will demonstrate that, just like British families, British South Asian families are undergoing change. It will address the implications of cultural diversity and social change for the future of ageing and the allocation of care. The proposed research will challenge common assumptions that South Asians ‘care for their own’ by exploring care beyond the family. It will thus generate new insights on how the needs of a diverse ageing population can best be addressed in planning and service provision.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: Protecting survivors of torture and ill treatment: dignity, violence and human rights in poor communities
Funder: The British Academy

Abstract: This project examines the attempts of human rights groups to promote the dignity of people living in poverty in the face of violence. It does so through an interdisciplinary study of the challenges involved in protecting survivors of torture and ill-treatment in low-income countries. People living in poor and marginal communities are often particularly vulnerable to torture and ill-treatment, but at the same time, face serious obstacles accessing justice. Above all, they can fear reprisals and stigmatisation if they seek legal redress. Adequate protection mechanisms are therefore a crucial part of ensuring the dignity of survivors. The project engages with human rights activists, lawyers and policy makers, and focuses initially on two country case studies, Kenya and Sri Lanka, before broadening out to draw more global lessons for the protection of survivors living in poor communities. It is based on long standing research collaborations and experience of practitioner engagement.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: Visualizing Gender-Based Violence in Graphic Awareness Campaigns in Nepal
Funder: The British Academy

Abstract: This project investigates representations of gender-based violence (GBV) in graphic art forms in Kathmandu and Pokhara, Nepal. Using interdisciplinary research methods, we will study how four types of violence – domestic abuse, trafficking, street harassment, menstruation-based discrimination – are portrayed in graphic print publications (comics, zines) and public graphic expressions (murals, graffiti, street art), and how stakeholders (NGOs, activists, artists) use graphic art as an awareness-raising tool. Our research will foster knowledge exchange via local research hubs, and result in two creative initiatives with local arts organizations and NGOs: (1) an open-access digital archive of graphic representations of GBV and (2) a series of graphic art workshops for 600 girls (aged 12-17). The project builds on an existing seed-funded collaboration, exploring representations of GBV in murals in Kathmandu, and develops strategies for producing inclusive, effective, and culturally sensitive messaging in GBV awareness campaigns.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: Decision making under uncertainty in a complex world. Determining when a health economic decision model is good enough for a complex decision problem via quantification of model uncertainty.
Funder: Department of Health (England)

Abstract: This project will develop methods for quantifying uncertainty about health economic decision model structure. This will allow us to determine when a model is “good enough” to support a decision, reducing the risk that the model is either too complex (and therefore a waste of resources), or too simple (leading to an unacceptable risk of the wrong decision). Models that are built to be “good enough” for a decision problem will lead to the best trade-off between model complexity and model cost. Avoiding inadequate models will lead to better decisions and a more efficient allocation of resources.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);8.2 HEALTH AND WELFARE ECONOMICS
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER
Title: Dissecting the mechanisms of fibril-mediated amyloid toxicity
Funder: Wellcome Trust

Abstract: Amyloid-forming proteins chiefly recognised for their association with age-related neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are also responsible for a host of debilitating systemic and localised amyloidoses, including Diabetes Mellitus Type 2 and Dialysis Related Amyloidosis (DRA). Despite the frequency of these disorders within human populations, no effective cures are currently available for these conditions. Decades of research have established two main hypotheses for amyloid-associated cytotoxicity which implicates either soluble oligomers or mature amyloid fibrils as the primary determinants of cell death. However, recent data suggest the two may be linked. Several experiments have shown that mature fibrils are dynamic entities, releasing soluble material with cytotoxic potential. Others have highlighted that increasing the surface hydrophobicity of soluble toxic oligomers while maintaining a high degree of intermolecular beta-sheet structure greatly enhances their cytotoxic potential. Surface hydrophobicity is also increased among shorter B2m amyloid fibrils (Fig. 1a), which are known to be more cytotoxic than their longer counterparts. This raises the possibility that toxic oligomers and mature amyloid fibrils share common structural and/or chemical/physical properties that endow their cytotoxic potential. In this proposal, we will investigate whether fibril hydrophobicity and dynamics are key mediators of amyloid-associated toxicity. By using four different amyloid-forming sequences including AB1-40/42, B2-microglobulin (B2m) and ccB-p, we will determine: 1. Accurate fibril length distributions of AB1-40/42 and ccB-p amyloid fibrils 2. The role of hydrophobicity in fibril-associated cytotoxicity 3. How 'molecular recycling' properties of fibrils affect cytotoxicity 4. Structural elucidation of fibril-cell interactions This project will take a multidisciplinary approach, combining biophysical and cell biological experiments under the leadership of Prof. S.E. Radford and Dr E.W. Hewitt. Cryo-tomography techniques will be developed with Prof. H. Saibil (Birkbeck College, London) and mass spectrometry will be performed in collaboration with Prof. A.E. Ashcroft.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;DISPUTED AETIOLOGY AND OTHER