NIHRDataInsights/HRCSData huggingface dataset:
Title: Connecting Lung Structure and Function in Cystic Fibrosis Through Physiological Modelling, Image Analysis, and Uncertainty Quantification
Funder: Medical Research Council

Abstract: The goal of the proposed project is to use advanced computational modelling of gas transport and ventilation in the human airway tree to improve the early detection of Cystic Fibrosis (CF) in both adults and children. This will build on preliminary research employing a novel technique to simulate airway blockages/constrictions (due to mucus 'plugs') accurately, while accounting for uncertainty due to heterogeneity throughout the lung structure without simulating these in detail (greatly reducing the computational requirements). I will use these methods to infer the extent and distribution of lung blockages and the associated uncertainty in these predictions from patient data. I will analyse patient data on multiple breath inert gas washout (MBW), from the NIHR-funded LCI-SEARCH study. Using these studies alongside imaging data (where available) we will synthesise more information into CF diagnosis and early detection through the development and deployment of new clinical indices. I will also develop and incorporate mathematical models of the lung parenchyma that account for physiologically important effects of pulmonary surfactant dynamics and material heterogeneity. Improved measures of early lung physiology will lead to improved detection of disease and more targeted intervention. The lung model developed in CF will also be deployed to investigate early disease interventions in COPD and asthma in future.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CONGENITAL DISORDERS;RESPIRATORY
Title: Understanding the role of ionocytes in a cystic fibrosis (CF) context using human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (AECs).
Funder: Wellcome Trust

Abstract: Cystic Fibrosis (CF) affects over 10000 people in the UK. It is a recessive monogenic disease caused by a double mutation in the gene encoding for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) and it affects multiple tissues, especially the lung. There is still no cure for this disease and patients require life-long treatment and eventually lung transplantation. This projects aims to study a newly discovered cell type in the human airway epithelium. These cells have been called pulmonary ionocytes because of their ion-exchange function and their similarity to ionocytes in Xenopus and zebrafish. Because they express high levels of CFTR, they have been proposed to have a key role in CF. I will derive airway epithelial cells, including ionocytes, from iPSCs from healthy and CF patients. I will do an extensive characterisation of the cells and I will study their role in the healthy and diseased epithelium using approaches such as single cell RNA-seq and assessment of cilia dynamics and mucus clearance. Overall, this project will shed light into the role of pulmonary ionocytes in the epithelium and into the pathophysiology of CF. This will lead to the identification of potential therapeutic targets and future treatments for the disease.

Lay abstract: Cystic Fibrosis (CF) is a chronic genetic disease that affects over 10000 people in the UK. It is caused by a double mutation in a specific gene and it currently has no cure. Recently, a new cell type called pulmonary ionocyte has been discovered in the airway epithelium, highly affected in CF. Because these cells express high levels of the gene mutated in CF, it is thought that they might have an important role in this disease. I will use the latest stem cell technology to mimic the human airway epithelium in the lab. This will allow me to characterise this new type of cell and understand its function in healthy and CF contexts. This research will address a highly novel and unexplored field in both lung physiology and CF. The study will allow a better understanding of the disease, which will lead to the design of new therapeutic approaches.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CONGENITAL DISORDERS;RESPIRATORY
Title: Inflammatory regulation of cholesterol biosynthesis in a monogenic model of intracerebral haemorrhage
Funder: Medical Research Council

Abstract: Hypocholesterolemia is a clinical risk factor for intracerebral haemorrhage (ICH). It has been postulated that as cholesterol is an essential membrane component, a reduction in levels may lead to neurovascular instability and proneness to rupture. However, this potential mechanism has not been investigated to date and will be addressed in this proposal. Mutation of the SAMHD1 gene causes one of the seven genetic subtypes of Aicardi-Goutières syndrome (AGS), an inherited childhood brain disorder characterised by upregulation of type I interferon (IFN). Clinically, SAMHD1-patients differ from other AGS subtypes in that they carry a high risk of ICH, suggesting a discrete role for SAMHD1 in neurovascular homeostasis exists. We have generated a mutant samhd1 zebrafish line which exhibit a significant upregulation of type I IFN and susceptibility to ICH. Furthermore, transcriptomic analyses indicate that samhd1 mutant larvae exhibit a significant reduction in expression of 14 cholesterol biosynthesis genes. Analysis of the Genotype-Tissue Expression database reveals that 8 of these genes are also significantly downregulated in ICH patients. Taken together these data suggest that ICH occurrence in this model may be associated with increased type I IFN signalling and an impairment in de novo cholesterol synthesis. The aim of this proposal is to use this model to (i) determine whether the cholesterol biosynthesis defect occurs specifically within brain endothelial cells and (ii) whether vulnerability to ICH is dependent on type I IFN signalling. Furthermore, we will utilise an in vitro approach to determine if disruption of other AGS genes causes a cholesterol synthesis defect in human brain endothelial cells. This work will reveal a previously unrecognised role for SAMHD1 function in the context of AGS and will highlight the need to consider anti-viral signalling and cholesterol biosynthesis as possible intervention targets for future ICH prevention.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CONGENITAL DISORDERS;STROKE
Title: Over three years for investigation of manganese metabolism and treatment development for neurological childhood disorders associated with manganese accumulation using a zebrafish gene knockout model.
Funder: Action Medical Research

Abstract: Background Manganese is a metal that is normally found in the body and required by cells in small amounts to function normally. However, high levels are toxic and cause brain and liver damage. Manganese toxicity may occur in newborns and preterm babies who require intravenous feeds and in children with liver disease. Manganese toxicity can also contribute to cases of early onset Parkinson's disease seen in children or young adults and has recently been suggested to play a role in the development of attention deficit hyperactivity disorder (ADHD). These researchers have discovered a new cause of brain and liver disease in children caused by an inherited defect of a manganese transporter. This results in an inability of the body to excrete manganese and leads to damaging accumulation of manganese in the liver and brain. Affected children develop difficulties walking and often become wheelchair-bound. Some die of liver cirrhosis at a young age. Current treatments require children to attend hospital for one week every month to reduce manganese accumulation. The treatment is costly, time consuming and can only be given intravenously. It improves symptoms but does not fully cure the disability. It is likely that this condition is under diagnosed due to a current lack of awareness. The research project The aim of this project is to understand why manganese is toxic to the body and how it is involved in the development of movement disorders such as Parkinson's disease in children. The research also aims to identify better treatments for patients who accumulate manganese in the brain and liver, ideally, these treatments would be given by mouth to reduce the disease burden for affected families. New drug treatments could alleviate physical disability, maintain children's ability to walk and prevent death from liver damage. The research should also provide gene testing to help diagnose those patients that have a rare genetic disorder linked to errors in manganese metabolism. More will be learnt about the role of manganese in the development of diseases such as Parkinson's disease, ADHD and forms of liver disease. At the same time, the laboratory methods developed during this research project should aid in the investigation of the disease processes for other genetic disorders and help to develop new treatments.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Risk Objective Assessment for Discharge (ROAD): development of a fit for purpose risk assessment tool for patients entering hospital via an emergency care pathway.
Funder: Department of Health (England)

Abstract: To conduct all underpinning developmental work to create a risk assessment tool for patients who enter Hospital via an emergency care pathway. The developmental work will include three initial tests/refinements in practice within an Acute Medical Unit (AMU) with rigorous process and content evaluation at each stage. This tool will benefit patients by enhancing the usual admission/discharge process used in emergency care by providing a fit for purpose risk assessment tool, namely; appropriate for very short stay vulnerable older patients (up to 48 hours) before they are transferred to another in-patient ward for further comprehensive assessment or are discharged home.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Accident or design? Exploring regional variation in placement outcomes for young children in care.
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: The study looked at the experiences of birth parents and young people who returned from care (i.e. foster, residential and kinship care) to live with their birth parent/s while remaining subject to a Care Order. It commenced in 2010, and was funded by the Research and Development Division of the Public Health Agency (PHA). The research explored the processes, background characteristics, and perceived reasons why children and young people returned home while remaining in care, in the five HSC Trusts in Northern Ireland. It also focused on understanding the functions the Care Order had for social services, the birth parents, and young people involved. It was found that on 31st March 2009, there were 193 children/young people living with their birth parents on a Care Order in Northern Ireland. This is eight per cent of the total population of Looked After children, and is lower than had been anticipated from governmental statistics. In total, the case files of 47 of these young people (24% of total population) were reviewed, and interviews were conducted with ten of them and their birth parent/s. The analysis revealed that the majority had a parental background history of alcohol abuse and domestic violence, and most return breakdowns in the study were related to continuing parental alcohol and/or drugs misuse. While some children had a planned return home after parents had engaged in supports and completed assessments, many young people had returns that were not planned, as they initiated the move themselves, or previous foster placements had broken down and there were no alternative placements identified for them. Many of these young people essentially ‘voted with their feet’, and social services were required to ensure that they remained safe in often less than optimal circumstances. After returning home, for many, Care Orders remained for initially unintended lengthy periods because of the risks posed by parents’ intermittent alcohol abuse and their lifestyle, contact issues, and parents’ desire to ensure that their children were able to access the supports that they needed. Thus, Care Orders at home tended to serve two main functions: to either monitor and/or support the placement. This was a unique study in that these families’ experiences have often been missing from public care research literature as well as the public eye. It is hoped that the findings will help policy-makers and practitioners have a better understanding of these families, and the issues involved in working with them.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Police to Primary Care: Testing the feasibility and acceptability of a high risk domestic abuse notification pilot.
Funder: Chief Scientist Office (Scotland)

Abstract: A pilot project was commenced in 2012 by the then Strathclyde Police within which domestic abuse incidents, categorised by the police as carrying high risk to the victim, are notified to victims’ General Practitioners. The pilot aims to improve levels of disclosure of abuse within a primary care setting. This study aims to test the feasibility and acceptability of the pilot. The study will: assess the robustness of implementation processes within the pilot; determine the acceptability of referral from the perspective of the NHS, the police force and those who have been victims of domestic abuse; and, generate findings about the extent to which the pilot can be improved and tested more robustly as per the MRC guidance on evaluating complex interventions.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Utility of Adaptive Designs in Public Funded Clinical Trials
Funder: Department of Health (England)

Abstract: The objective is to explore the application of adaptive designs in publicly funded trials and provide guidance on their implementation. When planning a trial, we often have sub-optimal information to inform its design which could later undermine its validity. Furthermore, our assumptions are often overoptimistic. Adaptive designs, in which accumulating trial data may be used to modify key aspects of the trial may be beneficial but are not routinely applied in publicly funded trials despite their potential benefits. We will employ statistical literature review of potential adaptive designs, elicit views of experts and use case studies to illustrate their implementation.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Does a breathlessness intervention service ('CBIS') reduce stress significantly more than usual care in breathless patients with advanced non-malignant disease and their carers? A phase II feasibility study.
Funder: Department of Health (England)

Abstract: Breathlessness is common in people with serious heart and lung disease. Experts agree that using a number of treatments together (e.g. exercise, relaxation, education) brings the greatest improvement. The `Cambridge Breathlessness-Intervention Service (`CBIS')’ uses this approach in patients and their carers. We think that 'CBIS' works by reducing stress. Stress levels in the body can be assessed by measuring the amount of a hormone called `cortisol' in saliva. We want to know whether CBIS changes the levels of this hormone in patients and carers. This is a small pilot study testing our methods before doing a large study.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: How does Computerised Physician Order Entry (CPOE) with integrated clinical decision support (CDS) impact on pharmacist-physician communication in the hospital setting?
Funder: Department of Health (England)

Abstract: Pharmacists check prescriptions for safety and efficacy, and are vital in highlighting errors to the physician before they impact on patients. Paper-based prescribing is being phased out in hospitals and replaced with computers; this technology has the potential to change face-to-face communication. Evidence shows that errors in healthcare communication are a leading cause of error. With the use of focus groups and observation, I will examine the impact of computerised prescribing on pharmacist-physician communication. As a result, communication will be optimised so that critical information about the pharmaceutical management of the patient can be effectively exchanged and translated into practice.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: HbA1c testing in Primary Care
Funder: Department of Health (England)

Abstract: I propose research to understand and optimize HbA1c testing in primary care to benefit patients by carrying out the following: Database analysis to understand current practice for laboratory HbA1c requests in primary care. Survey of GPs to understand what the take up is and what barriers are to point-of-care devices in primary care. Systematic review of the literature to establish what is known about point-of-care HbA1c testing and to include a meta-analysis of diagnostic accuracy studies. Pilot study of point-of-care HbA1c testing in primary care. Interviews and questionnaire to understand patient and practitioner perceptions of point-of-care HbA1c tests


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Improving the quality of long-term care through the use of quality standards and best practice guidelines: a comparative study of approaches in residential care in England and Australia
Funder: Department of Health (England)

Abstract: Policy-makers struggle to find ways of improving quality in long-term care over and above minimum standards. There is a lack of evidence on which methods are most effective, with changes in regulation, the introduction of market reforms and public reporting all seen as potential tools for changing provider behaviour. Focusing on residential care for older people in England and Australia, this study aims to investigate and analyse the development and implementation of quality standards and best practice guidelines for improving quality, how and why approaches vary, and what opportunities exist to transfer learning between countries.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: 2013 Doctoral Fellowship: Promoting resiliency in parents of children with complex physical healthcare needs through the development of a structured parent support programme
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Caring for children with complex physical healthcare needs places considerable demands upon parents with regard to their physical and emotional health, parental relationships and economic welfare. While many parents exhibit negative consequences of caring, others cope well in similar circumstances and appear to thrive. Parental resilience has been linked to a range of factors including perceived social support, high family hardiness, active problem solving and the capacity to adapt. Policy and strategic direction in Northern Ireland confirms a commitment to supporting parents and recognises the impact that support groups may play in this process. Meta-reviews have confirmed the effectiveness of group based carer programmes in improving a range of factors including resilience, self efficacy, coping, family functioning and psycho-social health. This study aims to develop a structured programme to increase resiliency in parents of children with complex physical healthcare needs. The approach proposed fits with the core stages of the MRC Framework in terms of developing and exploring a complex intervention (MRC, 2000, 2008). This is a 4 phase study. Phase 1 will involve the development of the parent structured support programme through workshops with parents and professionals. Phase 2 will identify the research instruments and will determine their face validity for application in this study. Phase 3 will focus on the development of a training programme and the training of the course facilitators. The parent programme will be delivered twice in Phase 4 to test its feasibility and to inform its further refinement.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: United Kingdom Primary Sjogren's Syndrome Registry (UKPSSR)
Funder: Medical Research Council

Abstract: Primary Sjogren s syndrome (PSS) is a chronic multi-system disease that affect up to 3% of adults in the United Kingdom. Although sicca symptoms, joint pain and fatigue are the commonest symptoms of PSS, almost any organs can be affected and there is a 40-fold increased risk of developing lymphoma. However, little is known regarding the pathogenesis and effective treatment has not been identified. The recent development of standardised outcome measures by the UK Sjogren‘s Interest Group (UKSIG) and others have generated criteria by which the effectiveness of specific therapy can be judged and compared. Furthermore, emerging biological treatments, notably anti-B cell therapies, have shown promising results in improving fatigue, sicca symptoms and systemic features of PSS. These recent developments have provided the framework for testing new therapies in PSS and performing other clinical studies. The aim of this project is to create a cohort of 500 well-characterised PSS patients in order to facilitate such proof-of-concept clinical trials, observational and longitudinal studies in PSS. 500 patients is required because not all patients are suitable for all studies. PSS patients will be identified from existing databases of the 24 collaborating hospitals. After obtaining written consent, patients will be assessed for severity of the key symptoms, disease activity and organ damage and health-related quality of life. These assessments include patient-completed questionnaires, physical examination, bedside clinical tests, laboratory tests of peripheral blood and urine. All assessments will be completed in a single outpatient visit, and all laboratory tests are readily available in all recruiting hospitals. In addition, we will store serum, DNA and RNA samples from patients for future studies. We will develop a database software specifically for this registry. All clinical data and biological materials will be stored in anonymised-linked format. The proposed registry will provide a unique and valuable resource for clinical and academic studies as well as for identifying suitable patients for clinical trials and other clinical studies. The creation of a well-characterised cohort of PSS patients will significantly reduce the cost of screening patients for these studies and will increase the appeal for sponsorship from industry for these proof-of-concept studies. This project will also foster collaborative research between academia, National Health Service (NHS) and industry, and promote the use of standardised assessment tools in managing patients with PSS. Finally, since this cohort will be the largest of its kind, it will also generate invaluable epidemiological data.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: DISPUTED AETIOLOGY AND OTHER