NIHRDataInsights/HRCSData huggingface dataset:
Title: Effect of d-cycloserine on brain processing of breathlessness in COPD patients undergoing pulmonary rehabilitation
Funder: Dunhill Medical Trust

Abstract: Breathlessness is the major cause of suffering in chronic obstructive pulmonary disease (COPD). The most effective treatment is pulmonary rehabilitation (PR) where patients learn to fear breathlessness less. Unfortunately the beneficial effects of PR diminish with time and individual response varies. Hence the need to enhance its efficacy. D-cycloserine enhances neural plasticity in the hippocampus and prefrontal cortex, facilitating emotional learning. It augments fear extinction and enhances psychotherapy in anxiety disorders. Recent neuroimaging evidence implicates these brain regions in the improvements in breathlessness from PR.


Research activity codes: 6.1 PHARMACEUTICALS;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;RESPIRATORY
Title: Novel therapies for respiratory complications of organophosphorus pesticide poisoning in a minipig model
Funder: Wellcome Trust

Abstract: Over 200,000 people die every year from self-poisoning with agricultural formulations of OP pesticides. Current treatments are frequently ineffective, with over 20% of patients admitted to hospital dying. Many patients die from breathing problems caused by the poisoning. In this work, we will test whether new drugs affecting the lung can prevent lung damage caused by blood-borne OP or by pesticide breathed in as patients fall unconscious. We will also test the ability of a drug called rocuron ium to block the pesticide s effects on the nerve-muscle junction the pesticide usually causes disruption that prevents the chest expanding to draw air into the lungs. If animal studies are promising, their results will be used to help design human studies. One reason for the ineffectiveness of treatment may be the toxicity of other components in the agricultural pesticides. We have shown that the major solvent in one OP pesticide increases the toxicity of the OP itself. We will therefore a ssess the role of solvent and the OP active ingredient in causing lung damage. If solvents are found to cause damage, it should be possible to replace them with safer solvents, making OP pesticides safer and ultimately preventing thousands of deaths.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH;RESPIRATORY
Title: Mindfulness Based Stress Reduction to support self management of anxiety and depression following stroke: development and feasibility study
Funder: Chief Scientist Office, Scotland

Abstract: Anxiety and depression are common after stroke, but people do not always have the skills they need to cope with the symptoms. Mindfulness Based Stress Reduction (MBSR) is a standardised, 8-week course that teaches people with long-term conditions skills, including meditation and mindfulness breathing, to help them to self-manage symptoms of anxiety and depression. Skills taught during the course are practiced at home . Although some people find MBSR helpful, many people do not complete the whole course or find it difficult to practice at home. Using ‘taster sessions’ and focus groups we will work with stroke survivors and other experts to make changes to the standard course. Together we will look at what is taught and how it is taught. We will try to identify changes that will help stroke survivors follow the whole course and practice their new skills, and use them to self-manage symptoms of anxiety and depression. When we have made the changes, we will apply for funding for a research project that will help us to find out if stroke survivors follow the adapted course, including the home practice. We will also find out whether stroke survivors think that the planned research methods are acceptable


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;STROKE
Title: Jargon busting: The cognitive and neurobiological mechanisms underpinning Jargon Aphasia and preservation
Funder: Stroke Association

Abstract: Jargon speech and perseverations are a severe form of speech production impairment which can occur in aphasia. Computational psycholinguistics implicates a weak phonological system as the cause of jargon aphasia. An alternatively (but not mutually exclusive) hypothesis, implicates a reduction of within system inhibitory processes as playing a role in sustaining jargon and stimulating perseveration. Importantly, neither of these hypotheses have taken into account the wider cognitive networks involved in speech production. Neurobiological models emphasise an interaction between language, motor and somatosensory systems in speech production. This fellowship will combine these theoretical perspectives to enhance our understanding of the basis of jargon and perseveration and investigate mechanisms of manipulating the degree of speech disruption. Building on psycholinguistic models and pilot data, initial studies will use experimental neuropsychology to investigate psycholinguistic and external factors which facilitate and disrupt jargon production. The results from these studies will be used to develop subsequent electrophysiology studies investigating processing differences (ERP analysis) and functional connectivity changes (phase coherence analysis) associated with jargon production. These studies aim to establish jargon reducing mechanisms which can be incorporated into existing therapy protocols and enhance our understanding of the neurobiological basis of jargon and open new avenues for research.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH;STROKE
Title: Reader Award - Audrey Bowen - Strategies to COPE with cognitive difficulties after stroke (SCOPE)
Funder: Stroke Association

Abstract: A Stroke Association survey highlighted service users’ calls for improved access to psychological support and high levels of unmet need for cognitive difficulties. Additionally, the number one research priority for service users and providers, recently identified by the James Lind Alliance, was ‘what are the best ways to improve cognition after stroke?’ In response, this award will prepare the groundwork for funding applications for definitive, multicentre, pragmatic trials of interventions for stroke survivors with cognitive difficulties, through partnership working with key stakeholders to ensure research translates into practice. We will: recruit and train two leverage-funded PhD students; design targeted interventions for coping with cognitive difficulties, e.g. apraxia, based on a synthesis of systematic reviews, clinical guidelines and expert advisory consultation; test interventions for acceptability to service users and carers, and feasibility for delivery by NHS/3rd sector providers across the pathway within acute and community settings, through observational research; build collaborations; obtain additional PhD & postdoctoral funding; submit funding applications for feasibility/pilot randomised trials with low risk of bias that produce outcome measurements valued by service users and, submit applications for a stepped care, comprehensive service delivery model for cognitive difficulties that allows for the common co-morbidities ensuring good inclusivity/generalisability. Lay title: How to cope with cognitive difficulties, such as planning and concentration, after a stroke.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;STROKE
Title: Stroke Association / Chief Scientist Office Senior Clinical Lectureship - Terence Quinn - Improving our understanding and assessment of post stroke cognitive and mood problems
Funder: Stroke Association

Abstract: Post stroke neuropsychological problems have been chosen by stroke survivors and Stroke Association as priority areas for research. National guidance recommends early cognitive and mood screening but this policy lacks a robust evidence-base. I will build on my systematic review, PhD supervision and pilot data around neuropsychological aspects of stroke to create a multidisciplinary programme of research that will inform practice and policy in this area. I will create an inception cohort, recruited in first days post stroke with detailed phenotyping including cognitive and mood assessment. Feasibility; acceptability and accuracy of various screening tools will be described. Prospective follow up will use multi-domain cognitive and mood assessment at one, six, twelve and eighteen months. Outcomes of interest will be cognitive decline and incident post-stroke cognitive/mood disorder. I will describe the natural history of early cognitive and mood problems and independent predictors of neuropsychological “trajectory”. Creation of the cohort will provide excellent substrate for other relevant studies. The anticipation is to offer MD and PhD research projects with a view to creating a new research team and fostering greater collaboration between centres. Exemplar studies will focus on imaging biomarkers and qualitative research looking at the experience of cognitive and mood assessment.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH;STROKE
Title: Improving Patient Physical Rehabilitation Outcomes Though Mental Wellbeing Using Mobile VR - Concept Validation and Scoping
Funder: Innovate UK

Abstract: "Sound mental and physical wellbeing is essential to leading a happy and fulfilling life and contributing to positive social and economic outcomes. There is a strong link between physical and mental health, whereby the status of each influences the other yet we often address each in isolation. Through this feasibility study AppAttic will assess the concept of using mobile Virtual Reality (VR) to improve patient outcomes by uniting physical rehabilitation and mental wellbeing. The initial area of focus is on improving the mental and psychological aspects of stroke rehabilitation. This area was chosen due to AppAttic's existing research into the home-based physical rehabilitation of stroke patients using VR and the observation during this research that the psychological wellbeing aspects of recovery are often unmet. This funding will enable us build on the existing physical stroke rehabilitation project (which will already be developed by the time this project commences) and use it as a basis for validating the concept. The project will enable the concept of using mobile VR to improve the mental and psychological aspects of rehabilitation and ultimately improve patient outcomes to be assessed, validated and scoped for further development."


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;STROKE;GENERIC HEALTH RELEVANCE
Title: Explaining Language Outcome and Recovery After Stroke (ELORAS)
Funder: Wellcome Trust

Abstract: My aim is to develop a theoretical model of language processing that explains inter-patient variability in outcome after stroke. My hypotheses are that the same language task (e.g. describing a picture) can be sustained by different sets of brain regions (and neuronal pathways) and that inter-subject variability in neuronal pathways for the same language task reflect an individual’s inherent potential and prior experience. My investigations will (1) use functional neuroimaging to characterize inter-subject variability in neuronal pathways in a range of language tasks; (2) cluster healthy individuals and stroke patients into different groups according to the neural systems used for the same task; and (3) compare the identified groups on a multitude of demographic, behavioural and structural imaging measures. The results will identify the factors that distinguish which neuronal pathways a subject typically uses and which neural pathways are available to support recovery. The work will provide: (i) greater understanding of the neuronal pathways sustaining recovery; (ii) improved accuracy and precision in our prognoses for whether and when patients with aphasia will recover after stroke, and (iii) a new patient stratification system that can be used to design effective, individualised therapeutic interventions.

Lay abstract: The aim of the proposed research is to explain whether, when and how speech and language abilities can be recovered after stroke. My experimental plans are based on two decades of experience with functional and structural neuroimaging of language processing in the human brain which has shown that, although there is a great deal of consistency in the brain areas that different patients use when performing specific tasks (e.g. describing a picture), there is also variance that indicates that the same task can be supported by different anatomical brain systems. Understanding this variance is essential for improving our predictions for outcome after stroke because the effect of damage to one system will depend on whether all, some or none of the other possible systems have also been damaged. Our research will therefore (1) use functional neuroimaging of both healthy controls and stroke patients to identify different neural systems for specific language tasks; and (2) identify behavioural, demographic and neuroimaging markers that distinguish which patients do and don't recover. We will then use this information to improve confidence and precision of our predictions for language outcome and provide new ways to test a patient’s response to different types of treatment.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH;STROKE;NEUROLOGICAL
Title: An incident and high risk Type 1 diabetes research cohort
Funder: Diabetes UK

Abstract: The cohort will be incident cases of Type 1 diabetes and their siblings, characterised on the basis of clinical and demographic features and islet-specific antibody status. A repository will be created for DNA analysis and biomarker measurements to understand aetiology, and patients and their high risk siblings will be offered entry into trials of early intervention to limit beta cell destruction and diabetes prevention respectively. Both groups will be eligible to participate in epidemiological studies.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: METABOLIC AND ENDOCRINE
Title: Cell-cell communication and the regulation of islet function
Funder: Diabetes UK

Abstract: Insulin-secreting beta-cells exist within the complex anatomical structure of the islet, and the intra-islet environment regulates beta-cell expansion, survival and secretory function. This Fellowship will build on my past and current research experience to assess the importance of intra-islet communication in the (patho)physiology of beta-cell function. Work will focus on how interactions between islet cells regulate hormone synthesis and secretion, and on the role of cell-cell communication within islets in regulating beta-cell mass by modifying beta-cell proliferation and/or survival. The proposed experiments will use a combination of in vitro and in vivo models, including rodent and human primary islets, MIN6 pseudoislets, and a mouse model for islet transplantation. Islet-like structures will be generated in vitro using FACS purified primary islet cells or islet cell lines, and used to assess the functional consequences of islet cell composition and architecture, and of manipulating communication between islet cells. In parallel studies genomic and proteomic analysis will be used to identify novel elements involved in maintaining islet architecture and function. Defining the mechanisms and consequences of intra-islet cell-cell communication is important for identifying novel therapeutic targets for Type 2 diabetes, and for designing effective graft material for transplantation therapy of Type 1 diabetes


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: METABOLIC AND ENDOCRINE
Title: Glomerular endothelial glycocalyx and its dysregulation in diabetes
Funder: Diabetes UK

Abstract: The surface coat, or glycocalyx, found on all endothelial cells is critical for vascular health and the regulation of permeability both in systemic and glomerular circulations. In diabetes glycocalyx damage promotes vascular disease, proteinuria and diabetic nephropathy. This study will define the components of the glomerular endothelial glycocalyx which contribute to the permeability barrier to protein and how these are damaged in diabetes. This work will lead to novel therapies for treatment and prevention of renal and vascular disease in diabetes. Glycocalyx components and biosynthetic enzymes expressed by unique conditionally immortalised human glomerular endothelial cells will be analysed by focused qPCR arrays, western blotting and immunofluorescence for protein components and sophisticated size exclusion and HPLC for glycosaminoglycans. Findings will be validated by comparison with ex-vivo human glomeruli. Those components contributing to barrier properties will be identified by selective enzymatic removal, as we have previously performed for heparan sulphates, or by siRNA knock-down of biosynthetic enzymes or core proteins in conjunction with established permeability assays. Effects of diabetes on glycocalyx components important in the permeability barrier will be defined by exposing cultured GEnC to diabetic milieu and confirmed in ex-vivo human glomeruli and in a mouse model of type-1 diabetes


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: METABOLIC AND ENDOCRINE
Title: Action in diabetes and vascular disease preterax and diamicron MR controlled evaluation post trial observational study (ADVANCE-ON)
Funder: Diabetes UK

Abstract: Recent trials of intensive glucose lowering have not demonstrated significant reductions in macrovascular events and the premature termination of ACCORD have raised questions around the safety of intensive glucose lowering in Type 2 diabetes. Yet longterm results from the UKPDS have demonstrated macrovascular benefits possibly due to a ‘memory effect’ or perhaps a lower incidence of diabetic nephropathy. It remains unclear whether similar benefits might accrue in established Type 2 diabetes as opposed to those newly diagnosed. Our primary aim is to define the long-term, post-trial effects of intensive glucose control (compared to standard) on major cardiovascular events in 11,140 patients with type 2 diabetes. Secondary aims are to determine the long-term, post-trial effects on the same events of routine additional blood pressure lowering. The study comprises the long-term post-trial follow-up of participants in the ADVANCE study which completed in 2008. We will determine whether there is a convergence of the levels of cardiovascular risk that matches the convergence of these exposure levels in the 5 years following completion of the trial. This objective will be achieved by seeking 5 years of post-trial follow-up information for all ADVANCE study participants that were alive at the completion of the trial Yet longter


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: METABOLIC AND ENDOCRINE
Title: Patients’ expectations, beliefs and attitudes towards glucose-lowering drugs and their effects on body weight in Type 2 diabetes: a prospective study and pilot intervention.
Funder: Diabetes UK

Abstract: Type 2 diabetes (T2D) patients rarely fully comply with glucose-lowering medication, partly due to fear of weight gain. Increased body weight adversely affects diabetes control, yet many diabetes treatments, including insulin, promote weight gain. Orlistat and GLP-1 analogues may help with weight loss, but their widespread use is limited by tolerability and/or cost. Little is known about individuals’ experiences of these drugs. Furthermore, there is no validated educational intervention that focuses on body weight to optimise adherence. I will (i) measure the expectations, beliefs and attitudes of obese T2D patients towards their medication, with particular focus on body weight effects and association with adherence; (ii) test whether a pilot intervention focussing on the effects of body weight is acceptable to patients and improves understanding of their diabetes treatment and subsequent adherence. Phase 1: Postal questionnaires and qualitative interviews will be administered pre-/post- commencement of glucose-lowering drugs. Phase 2: An intervention will be developed and piloted based on data collected from phase 1 and evaluated using the same tools. Understanding obese T2D patients’ beliefs and experience of glucose-lowering drugs and their body weight effects will help development of an intervention to support these patients. This should promote diabetes and body weight awareness and allow patients to make more informed choices about treatment options with a view to improving adherence


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: METABOLIC AND ENDOCRINE
Title: v-SNARE requirements for entry of GLUT4 into the insulin-responsive compartment.
Funder: Diabetes UK

Abstract: Insulin stimulates glucose transport in fat and muscle by inducing translocation of the facilitative glucose transporter GLUT4 from intracellular vesicles to the cell surface. In the absence of insulin, the majority of GLUT4 is retained intracellularly by continually cycling through the endosomal system. A crucial facet of this trafficking itinerary is the existence specialised GLUT4 storage vesicles (GSVs) in fat and muscle cells. It is from these GSVs that GLUT4 is mobilised to the cell surface in response to insulin. Individuals with insulin resistance and type 2 diabetes exhibit defective regulation of blood glucose levels, and this is a result, at least in part, of reduced GLUT4 translocation. Understanding the molecular mechanism(s) involved in GLUT4 trafficking therefore represents an important step in the development of rational therapies for this disease. This project addresses two key questions in GLUT4 trafficking: (i) how are the GLUT4 vesicles formed and (ii) what is the molecular machinery involved? This proposal will capitalise upon methodology in our laboratories to define the v-SNARE requirements for GLUT4 sorting into GSVs, and characterise the role of specific v-SNAREs on GLUT4 trafficking in adipocytes.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: METABOLIC AND ENDOCRINE
Title: Understanding the mechanism of declining insulin sensitivity in the development of Type 2 diabetes.
Funder: Diabetes UK

Abstract: Recently, an unusual modification of the protein PPARgamma (the target of thiazolidinediones) was found in people with obesity and T2DM. The modification (phosphorylation at Ser273) alters cellular metabolism, promoting insulin resistance. We aim to devel


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: METABOLIC AND ENDOCRINE