NIHRDataInsights/HRCSData huggingface dataset:
Title: Using the National Endoscopy Database (NED) to evaluate endoscopy performance
Funder: The Health Foundation

Abstract: Colonoscopy is the key diagnostic investigation for colorectal cancer. However, international studies show a significant variation in quality between colonoscopists. Low polyp-detecting colonoscopists have higher post-procedure colorectal cancer incidence and mortality rates. It is not currently known what the extent of the variation is in the UK, nor what the optimal key performance indicators (KPIs) for colonoscopy polyp detection should be. This means underperformance can’t be easily identified. The National Endoscopy Database, overseen by the Joint Advisory Group on Gastrointestinal Endoscopy, will automatically captures real-time clinical data from each UK hospital’s Endoscopy Reporting System. This project will use the database to determine the optimal KPI for colonoscopy pathology detection. This involves reviewing the evidence base for various suggested KPIs in this domain, and determining the confounders and explanatory factors for variation in optimal detection. The project will also evaluate what the KPI minimum standard for proximal colon pathology detection should be. Proximal colorectal cancers are missed over twice as often as distal cancers. The extent of unwarranted variation in endoscopy performance will be assessed, and potentially remediable factors identified. High and low performing Trusts will be identified, and a health economic analysis will be carried out to assess the impact of this variation. A randomised controlled trial will be performed to find out what the impact of regular, unit-level performance data is. Automated KPI data reports will be produced and disseminated to the intervention group, including benchmarking against other endoscopists and units. These high-quality, benchmarked endoscopy performance reports will allow endoscopists, providers and commissioners to identify potential issues rapidly. Qualitative work will inform the design and implementation of the trial, to maximise the efficacy of the intervention. Additional interviews to be conducted after the trial will help with the interpretation of the findings.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL
Title: Strategies for the development and maturation of functional hepatocytes from hES cells
Funder: Medical Research Council

Abstract: Human ESCs self-renew and have the capacity to differentiate into a wide range of cell types. Harnessing these properties to generate specific cell types is very attractive and many groups have demonstrated the ability of hESCs to generate hepatocyte-like cells (HLCs). The scarcity of primary human liver material means that a renewable source of fully functional HLCs would be very valuable to the pharmaceutical industry for predictive toxicology, but also accelerate development and improvement in bioartifical liver technology for clinical use. However, HLCs generated from hESCs using current technologies are often not fully functional. In order to deliver functionally mature HLCs, that are scalable and suitable for pharmaceutical and eventual clinical use new approaches are required to improve and enhance (i) in vitro hepatic progenitor development and expansion and (ii) generation of functionally mature hepatocyte-like cells. We propose to address these issues here and our overall aim is to generate HLCs that exhibit a full range of mature hepatocyte functions from hESCs by cost-effective and robust means. To achieve our goals we will focus on the following specific aims: 1: Establishment of tools for the generation and validation of HLCs from hESCs 2: Optimisation of hepatic progenitor generation and expansion 3: Utilise innovative approaches to promote generation of functionally mature HLCs. In Aim 1 we will generate reporter lines for hepatic progenitors (HNF4A-eGFP) and mature HLCs (ASPGR1-mCherry) using zinc finger nuclease technology. Aim 2 will see us combine recent innovations, with combinatorial approaches (drawing from our understanding of normal development) to improve generation of hepatic progenitors and establish conditions that permit their expansion and maintenance. The focus of Aim 3 will be the generation of HLCs with a fully functional phenotype using approaches informed by hepatocyte physiology and liver maturation.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL
Title: The DEEP Study: Developing Effective and Efficient Care Pathways for Patients with Chronic Pain
Funder: Department of Health (England)

Abstract: Pain affecting the face or mouth and lasting longer than three months ("chronic orofacial pain", COFP) is a relatively common problem in the UK. Our previous research shows that: healthcare professionals are uncertain how to diagnose and manage it; sufferers experience negative impacts in their everyday lives because of it; patients experience multiple unhelpful referrals between different health professionals in an attempt to manage it. Our proposed research aims to identify, from both patient and financial perspectives, where and how we can make changes to the way patients with COFP are managed in the NHS. For example, why do we often get little improvement, yet a high cost personally or financially? Once this information is gathered we will be able to suggest potential new and improved care pathway(s) for COFP based on savings made by removing ineffective or inefficient aspects of the current care pathway and replacing them with something better. The new pathway(s) will be based on improving the quality of life of sufferers, decreasing their pain and providing efficiency for the patient and the NHS. Our team has diverse expertise: sociology, economics, psychology, specialist clinicians and health service policy. This will ensure that no single aspect of COFP’s impact on sufferers will be overlooked in favour of another, a common flaw in this area. The expected outcomes to the research are a more effective and efficient care pathway for those with COFP, which will be ready to trial or directly implement. The learning should also be relevant to other long-term pain conditions affecting other parts of the body.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL
Title: Store operated Ca2+ entry in apoptotic cells.
Funder: Wellcome Trust

Abstract: 1. To characterise apoptosis-induced changes in store-operated Ca2+ entry (SOCE) pathway including: 1.1) Changes of Ca2+ influx. 1.2) Modifications of proteins involved in SOCE. 1.3) Changes in cellular structures serving as platforms for SOCE. 2. To characterise the role of apoptosis-induced regulation of SOCE in determining the mode of cell death of pancreatic acinar cells triggered by inducers of acute pancreatitis.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL
Title: Genetic and functional mapping of gene deserts in complex disease.
Funder: Wellcome Trust

Abstract: Genetic mutations that cause rare human diseases have taught us much about the 1.5% of the genome made up of genes- DNA that encodes proteins. However we know very little about the remaining genome often referred to as junk DNA. It has been proposed to contain sequences essential for controlling when and where genes are switched on and off across the diverse cell types that make up the human body. Using newly developed technologies it is now possible to survey the genome for these functional s equences to determine their role in the cell and how their disruption may cause disease. Recently we have identified many regions of the genome that harbour DNA variations that cause Crohn s disease (CD), a common disorder of the gut. In some of these regions the underlying cause of CD is a mutation or DNA variant that directly disrupts a gene. However many other regions exist where we have not found a mutation, some of which have no genes at all. By directly analyzing gut tissues from CD patie nts we will identify the important functional sequences within these gene-less regions, confirm the DNA variants that disrupt them and which genes they switch on and off.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL
Title: Dental professionalism and ethics: what does it mean in practice?
Funder: Wellcome Trust

Abstract: This research proposal is a multi-stage combined qualitative/quantitative study of key stakeholders in the dental profession. The research consists of three stages: 1. In depth individual interviews with purposively sampled participants, exploring case studies which will be developed into fuller vignettes for part 2. 2. A series of homogenously sampled focus groups, framing discussion around the vignettes from part 1. 3. A quantitative survey of general dental practitioners designed in the light of conclusions drawn. Objectives: 1. To perform a literature review establishing existing work on professionalism within medicine and dentistry. 2. To obtain the views from key representatives on the important tenets and behaviours of professionalism in dentistry, as well as views from representatives of non-health professions. 3. To consider how these tenets and behaviours relate to teamwork and business. 4. To consider how these tenets and behaviours may be changing and the underlying reasons for these changes. 5. To use test case scenarios with focus groups to explore professionalism in practice. 6. To formulate a revised definition and make recommendations on the development of professionalism. The completed project will aim to inform policy in areas of undergraduate and postgraduate education, continuing professional development and professional remediation.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL
Title: Biofiltration by Biological Design
Funder: Royal Academy of Engineering

Abstract: Developing ways of producing low-cost, low-energy, sustainable drinking water for rural communities


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL;INFECTION
Title: Analysing the cellular basis of palate morphogenesis and clefting
Funder: Medical Research Council

Abstract: Formation of the palate is a good example of solid tissue morphogenesis and of significant clinical interest because cleft palate is one of the commonest human birth defects. Understanding the cellular mechanisms responsible for morphogenesis is a potential route to impact via regenerative therapies. Although cell proliferation is presumed important, contributions of cell rearrangement, division orientation, extracellular matrix expansion, apoptosis and cell size and shape changes in palatal mesenchyme are unknown and likely to be substantial, with failure of one or more leading to cleft palate independent of proliferation. This proposal aims to understand the cellular mechanisms of palatogenesis, focusing on outgrowth and elevation of the palatal shelves in wild type and mutant mice. Specifically, it will link cleft phenotypes with cellular function in Gas1 and Wnt5a mutant models, thought to represent different cellular mechanisms of cleft palate - affecting cell proliferation and planar cell polarity, respectively. We will use genetic lineage tracing to map local directional growth and clonal spread in these mice by crossing into tamoxifen-inducible labelled (mTmG and Confetti) strains, quantifying cell proliferation, apoptosis, polarity, shape, packing and spindle orientation by immunofluorescent labelling and confocal microscopy. Finally, we will use in-silico modelling and novel computational spatial registration of morphogenetic datasets to quantify and localise exactly which cellular processes are present during normal palatogenesis and deficient in mutants. Collectively, these analyses will provide a detailed composite map of directional tissue elongation during palatogenesis and cellular mechanisms underlying cleft palate. Using cleft palate as a model for comprehensive evaluation of mesenchymal morphogenesis, such integration methods and analyses may prove valuable in understanding genotype to phenotype correlation in other organ and tissue systems.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;ORAL AND GASTROINTESTINAL;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Efficient Algorithms for Mechanism Design Without Monetary Transfer
Funder: Engineering and Physical Sciences Research Council

Abstract: Matching problems involve assigning agents to commodities, such as junior doctors to hospitals, or kidney patients to donors, based on preference lists expressed by the agents. They have important large-scale practical applications in centralised matching schemes that perform allocations of these types in a number of countries._x000D_ _x000D_ When designing mechanisms for these matching problems, two issues present research challenges going forward: (i) optimality (based on the social welfare of the agents involved) and (ii) truthfulness._x000D_ _x000D_ These two desirable properties may be conflicting. This led Procaccia and Tennenholtz to introduce the idea of approximate mechanism design without money - this involves the design of truthful mechanisms which may lead to a loss of optimality in the constructed solutions, but such loss can be theoretically bounded._x000D_ _x000D_ In the above practical applications, monetary transfer is not appropriate. Two further applications that motivate optimal truthful mechanisms, where monetary transfer is not allowed, involve combinatorial auctions and facility location problems_x000D_ _x000D_ This proposal lies in the area of Algorithmic Mechanism Design (AMD), part of the wider field of Computational Social Choice Theory. We are interested in particular in mechanism design without money._x000D_ _x000D_ The famous Gibbard-Satterthwaite Theorem roughly states that, in environments without money, the only truthful mechanism is (the trivial) dictatorship. However, it does not apply whenever the domain of preferences of the individuals over the possible outcomes is restricted. That is the case in most real-world applications, where indeed more interesting mechanisms occur._x000D_ _x000D_ We plan to advance the area of AMD without payments by tackling combinatorial auctions, junior doctor placement and reviewer assignment, kidney exchange and facility location problems We will develop new truthful mechanisms whilst measuring their degradation in performance as compared to previous (non-truthful mechanisms). In particular, we will investigate the trade-off between truthfulness and optimality when considering approximate mechanism design._x000D_ _x000D_ New software will arise from this work and we have routes for exploiting it through existing University of Glasgow collaborations with the NHS (concerning the assignment of junior doctors to hospitals as part of the Scottish Foundation Allocation Scheme, and the assignment of kidney donors to patients via the National Living Donor Kidney Sharing Schemes).


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE;RENAL AND UROGENITAL
Title: Interrogating disease clusters, multimorbidity and adverse outcomes in chronic kidney disease
Funder: Medical Research Council

Abstract: Aim: To improve our understanding of the risks of adverse clinical outcomes associated with chronic kidney disease (CKD) and multimorbidity. Context: I have performed a systematic review on the area and identified an association between multimorbidity and mortality in patients with CKD. However, little is known about the risks in patients with mild to moderate CKD and about the risk of cardiovascular (CV) outcomes. Objectives: 1) To compare the characteristics of patients with CKD to those with normal kidney function. 2) To determine the associations between multimorbidity count (number of of Long Term Conditions (LTCs)) and adverse outcomes (mortality, hospitalisation and CV events) in patients with CKD. 3) To identify clusters of LTCs and patient factors in patients with CKD who are highest risk for adverse clinical outcomes. 4) To determine the most effective predictor of adverse outcomes in patients with CKD and multimorbidity: multimorbidity count or clusters of LTCs and patient factors. Methods: This Fellowship will use a data-driven approach in three large and high-quality datasets. UK Biobank has comprehensive data on 500,000 volunteers. Data are partly self-reported and are validated by linked health care records. The SAIL databank provides data from the routine care of 2.4 million patients in Wales. The SCREAM cohort is from the routine care of 1.2 million Swedish patients. Data from all three datasets will be analysed using survival analyses and clustering statistical techniques. Opportunities: It is well known that patients with CKD are at high risk of early mortality and CV events, but little is known about how multimorbidity influences different adverse clinical outcomes, especially in mild to moderate CKD. By targeting this evidence gap, this Fellowship will contribute to the development of clinical guidelines and direct future health policy and clinical trials.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE;RENAL AND UROGENITAL
Title: An investigation into the functional role of the RhoGAP protein SH3BP1/ARHGAP43 in Autosomal Dominant Polycystic Kidney Disease
Funder: Medical Research Council

Abstract: Autosomal Dominant Polycystic Kidney disease (ADPKD) is the most common monogenic kidney disease in man and a leading cause of end stage renal failure. It most commonly results from mutations in PKD1 or PKD2, encoding Polycystin 1 (PC1) and Polycystin 2 (PC2). Treatment for ADPKD is limited and hampered by side effects and reduced efficacy. The mechanisms behind cyst development in ADPKD are unclear but cellular hyperproliferation, reduced cell motility and impaired cell-cell junction formation. This project aims to evaluate the functional relevance of a recently identified interaction between PC1 and a Rho-GAP protein, SH3BP1. Through its GAP activity towards Cdc42 or Rac1, SH3BP1 regulates cell-cell adhesion, cell migration and actin cytoskeletal organisation. It has also been recently identified as a key regulator or a novel mechanism of endocytosis (Fast Endophilin Mediated Endocytosis, FEME). Important growth factor receptors such as EGFR can be internalised via FEME so thus the process may play a role in cellular proliferation. The SH3BP1-PC1 interaction may provide a mechanistic explanation to the cellular phenotypes observed in cystic cells. I will use a combination of co-IP, pull downs and mass spectrometry, we will evaluate the exact binding determinants between the PC1-SH3BP1 interaction. PC1 can dephosphorylate interacting proteins (such as PC2) and SH3BP1 is highly phosphorylated. Using phosphoproteomics, I will identify any specific phosphorylation sites on SH3BP1 before evaluating them for functional relevance in cystic cells and cyst development in vitro. Through live cell imaging I will evaluate the internalisation of specific growth factor receptors shown to drive hyperproliferation in ADPKD cells such as EGFR. Using markers of FEME and other forms of endocytosis, I will specify if any forms of endocytosis are deranged in ADPKD. Finally, the role of SH3BP1 in cyst development will be evaluated in vitro through use of 3D cystic cell models.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;RENAL AND UROGENITAL
Title: Improving the quality of care and outcomes in patients with chronic kidney disease.
Funder: Department of Health (England)

Abstract: Chronic kidney disease (CKD) affects about 10% of the adult population. CKD is associated with an increased risk of death mainly from cardiovascular (eg heart attacks) and cerebrovascular (stroke) causes. The little research that has been carried out in this condition has invariably produced negative results. The lack of data from pilot studies and the lack of good information on the specific population under study may be responsible for this. This NIHR Fellowship will fund a pilot trial, as well as epidemiological work using novel information technology systems to gain an in-depth understanding of the natural history of this condition.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE;RENAL AND UROGENITAL
Title: Developing Asset-Based Approaches to Appropriately Support Behaviour Change Among People During Times of Stress
Funder: Chief Scientist Office (Scotland)

Abstract: In order to improve health in Scotland people need to develop and maintain more positive health behaviours. Life events, such as the diagnosis of cancer in a loved one, or becoming a parent have been shown to be times when people become more responsive to positive behaviour change. These times then are ideal points for health professionals to introduce or support a health behaviour change. Many people, however, find these times extremely stressful and therefore maintaining positive behaviour change is a challenge. This PhD aims to identify behaviour change techniques (BCTs) that increase an individual’s resilience resources so they can cope better during these times of stress and in turn help maintain the desired positive behaviour during significant life events and beyond. Breastfeeding maintenance in early parenthood will be the behaviour targeted in this PhD. BCTs likely to be most effective will be identified using existing evidence (Systematic Review) and consensus amongst experts (Delphi exercise 1). The most appropriate form of delivery will then be developed by consensus amongst stakeholders (Delphi exercise 2). A pilot controlled trial of the developed intervention will then be carried out. Participants will be pregnant women who declare an intention to breastfeed. Participants will be randomised to intervention or usual care. Resilience and coping strategies will be measured at baseline and immediately after intervention. Breastfeeding behaviour will be collected at birth, 10days and six weeks postpartum. Analysis of the measures and in-depth interviews on acceptability of the intervention will also be carried out.


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