NIHRDataInsights/HRCSData huggingface dataset:
Title: DISSSECT – Dementia: Improving Staff Stress & Satisfaction – Evaluation by Cluster Trial
Funder: Division for Social Care and Health Research (Wales)

Abstract: Caring for people with dementia in care home facilities can be stressful and challenging for staff. Challenging resident behaviours (such as using inappropriate language, agitation, aggression, wandering, vocal outbursts) contribute to staff strain at work. Staff become emotionally exhausted and work-stress may also contribute to high staff turnover rates (which are very high in private homes). Without help, staff can become less willing to care, develop pessimism and negative emotional responses. In addition, there may be emotional costs to work colleagues and economic costs to the provider due to sickness and absence. Ironically, some forms of dementia training for staff may increase stress levels in younger care workers and care staff from minority groups (of which there are large numbers in Wales). A systematic review will be undertaken of forms of help that have been shown to reduce stress in workers, especially those working in close contact with people with dementia in care facilities. The best evidenced forms of intervention will be used in a randomised trial to see if staff can better protect themselves against work stress, and which forms of help have positive impact on stress levels, sickness rates, and job satisfaction.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: NEUROLOGICAL
Title: Can an arts programme increase quality of life and well-being of care home residents with dementia? An exploratory study
Funder: Division for Social Care and Health Research (Wales)

Abstract: In the UK there are 700,000 people with dementia (just under 40,000 in Wales). Estimates anticipate a doubling of dementia sufferers in the next generation [1]. Symptoms of dementia include a decline in cognitive ability, memory, language and orientation. It is a progressive disease, and as yet there are no known cures. Therefore it is important that as well as researching prevention or cure, researchers also focus on promoting the quality of life and well being of people with dementia. Some research studies have shown that involvement in an arts programme increase the quality of life and well being of people with dementia. However, the majority of evidence is anecdotal. The aim of this exploratory study is to develop and evaluate an arts programme for people with dementia living in a care home. The study will be in 3 stages, where the arts programme is refined at each stage, based on feedback and results from the previous stage. A multidisciplinary advisory group, the people with dementia, and carers will be consulted at each stage. The results will inform the development of a future definitive trial to evaluate the effectiveness and wider implementation into practice in care homes.


Research activity codes: 6.8 COMPLEMENTARY
Health categories: NEUROLOGICAL
Title: Is ALS/FTD neuropsychologically distinct from FTD?
Funder: Motor Neurone Disease Association

Abstract: It is now recognised that some people with the amyotrophic form of motor neuron disease (ALS) develop a form of dementia known as frontotemporal dementia (FTD). The main symptoms are alterations in the person’s behaviour, difficulties in reasoning and judgement and problems in language. The precise nature of the relationship between ALS and FTD is not fully understood. Many people with FTD do not have ALS, just as many people with ALS do not have FTD. The project proposes to compare behaviour and thinking (cognitive) skills in patients clinically diagnosed with ALS/FTD and with FTD alone with the aim of determining whether there are behavioural and/or cognitive characteristics that distinguish the two. Patients will undergo a series of short tasks that look at a range of skills normally thought to depend on the workings of the frontal and temporal lobes of the brain. These include the ability to recognise emotions, to draw inferences about other people’s thoughts and intentions, to concentrate, organise actions and to understand and produce language. Carers will be asked about alterations in behaviour and emotions. A direct comparison of the findings in ALS/FTD and FTD will allow us to address the question whether the precise nature of the dementia in ALS/FTD is different from that of FTD alone. The study offers the opportunity to improve early recognition of ALS/FTD by better understanding of its clinical characteristics. In dementia clinics, it offers the potential to improve identification of those people with FTD who are at risk of developing ALS. In the longer term, the findings may have relevance for future treatment studies. There is good evidence that FTD has different underlying causes, so it will be necessary for future treatments to be targeted appropriately. Improved characterisation of ALS/FTD may help contribute to that endeavour.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: NEUROLOGICAL
Title: Over three years for improving epilepsy surgery in childhood using functional magnetic resonance imaging and electroencephalography
Funder: Action Medical Research

Abstract: Background Epilepsy is a disorder of the brain which causes seizures. Epilepsy can cause physical injury and even death but is also strongly associated with behavioural and developmental problems when suffered in childhood. In the UK alone there are an estimated 58,000 children under 18 with epilepsy. Surgery in childhood can dramatically improve the lives of epilepsy sufferers by stopping seizures. Before surgery, tests are carried out which distinguish brain areas which cause seizures from those which are necessary for functions such as walking and talking. However certain tests, such as recording from electrodes implanted in the brain and awake surgical procedures, can be difficult to carry out in children. The research project These researchers aim to develop a better, more child-friendly method of identifying brain areas for surgery. They will use EEG-fMRI, a method which measures both electrical activity and blood flow in the brain. The researchers want to study whether EEG-fMRI can be used to assess the surgical suitability of children with epilepsy before surgery. They will also find out if it is possible to perform the assessment while children watch a cartoon rather than lying still within a scanner. The researchers also want to see if fMRI alone, which only measures blood flow, and is more widely available, can give similar information on specific brain areas.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: A Programme of Diagnostic Test Accuracy Reviews and of Updates of Intervention Reviews in Dementia
Funder: Department of Health (England)

Abstract: The personal social and economic burden of dementia is huge. It accounts for more years lived with disability than any other condition. Through its rigorous methods The Cochrane Collaboration has improved the quality of primary research into clinical interventions for dementia. Through a programme of Cochrane DTA reviews we now have a similar opportunity to tighten the intellectual framework for the evaluation of diagnostic tests in dementia.The scope of the programme is twofold. A series of Diagnostic Test Accuracy (DTA) reviews will cover the full range of important imaging and laboratory biomarkers and of simple clinical tests. A series of updates will focus on interventions both pharmacological and non-pharmacological which are currently in clinical use in the NHS. In addition to the publication of high quality reviews in the Cochrane Collaboration database a strong emphasis will be put on integrating the results of the reviews in digested reports for policy development health technology appraisal and commissioning in the NHS. This will be feasible thanks to the intimate involvement of the Cambridgeshire & Peterborough Collaborations for Leadership in Applied Health Research and Care (CLAHRC CP) whose raison d’être is to support the translation of research evidence into practice.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL
Title: Psychological therapies for the management of chronic pain (internet delivered) in adults
Funder: Department of Health (England)

Abstract: Chronic pain is major source of distress and disability in the UK with as many as 40% of those attending general practice in the UK self-reporting chronic pain (http://dx.doi.org/10.1016/S0140-6736(99)03057-3). It is a personal and economic burden one of the major causes of years lived in disability and severe pain is now also considered a life limiting condition (http://dx.doi.org/10.1016/j.ejpain.2009.07.006). Psychosocial treatments focussed on behavioural change and self-management are considered primary treatment options (see NICE guidance on low back pain neuropathic pain and headache) but are limited by scare resources principally in expertise). Telemedicine solutions have been actively promoted as credible sources of delivery of behavioural change interventions. Patient groups have given a cautious welcome to the idea. The evidence for psychological interventions delivered remotely using computer technology is unknown. This CSR was designed to establish the efficacy of telemedicine solutions for chronic pain in adults. This is an active area of research and there are approximately 20 RCTs of reasonable size. This review will also be a companion review for a title we have on face-to-face psychological treatments. There is significant interest in the pain community of the specific pain management treatments because pain is unresponsive to generic self-management interventions.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: iPS transgenic models to better understand the molecular mechanisms of TDP-43 pathology
Funder: Motor Neurone Disease Association

Abstract: The aim of this project is to continue the development of cell lines from skin cells donated by people with MND, via induced pluripotential stem cell (iPSC) methodology. The student funded by grant Wade-Martins/Mar10/6262 successfully created and characterised cell lines from control (non MND) donors. However, the follow-up work using skin cells from people with MND was not completed, due to delays in obtaining ethical approval for skin biopsies from patients. With all necessary ethical permissions now obtained, cells from six MND patients are now stored in the Oxford group's stem cell bank, including two lines with C9orf72 mutations. During this project, and using the skills and experience obtained during her studentship, the post-doc will characterise these cell lines in great detail, with particular analysis on the actions of a panel of 30 key genes believed to be involved in motor neurone degeneration. The Oxford group also intend to add further cell lines to the collection, including some derieved from cells donated by participants in the BioMOx study, so these will be accompanied by an unprecedented level of clinical information. The work therefore forms a natural extension to the studies performed to date, with a firm platform already established. Other funding has been obtained to provide the salary costs for the post-doc for two years. MND Association funds will support the costs of laboratory consumables. This project is also closely linked to the Clinical Fellowship Scaber/July13/6508.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Mouse models of TDP-43 motor neurone disease as a tool to explore pathogenesis and generate new biomarkers
Funder: Motor Neurone Disease Association

Abstract: Motor neuron disease is currently untreatable. The cause of MND in a small proportion of patients is the mutation of a specific gene. Recently a new MND gene, TDP-43, has emerged as a potentially important contribution to the disease. One way in which to understand the function of a gene and how this goes wrong in disease is to create a model in mice. In this project we will create a mouse model of TDP-43 related motor neuron disease by inserting the human gene into a mouse. We will then study the mouse for signs of motor neuron degeneration and perform a variety of biochemical experiments to understand if the faulty copy of the gene affects the way that other genes are processed. An important difference between our model and others that are being developed is that we will insert the gene together with all of its regulatory and controlling elements, using a technology called BAC trangenesis, so that the pattern of expression of the resulting protein will mimic the human situation as closely as possible. A BAC transgenic model of TDP-43 MND would serve as a very important complementary tool for the improved understanding of why motor neurons die in this disease. We also believe that such a model will allow improved testing of potential therapies and improve the way that treatments are translated from the laboratory into the clinic.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: NEUROLOGICAL
Title: Cell-targeted phenotyping: using optogenetics to study ALS patient-derived motor neurons
Funder: Motor Neurone Disease Association

Abstract: Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease that results in the loss of motor neurons. The majority of ALS cases are sporadic in nature, however 5-10% have a known genetic cause with the most common abnormality recently identified as a repeat expansion in C9ORF72. We will take advantage of new technology that has enabled the production of stem cells from skin biopsies, termed induced pluripotent stem cells (iPSCs), which can be used to produce motor neurons from ALS patient with the C9ORF72 expansion. These cells provide a highly relevant human model of ALS and have the advantage of retaining the patient’s full genetic background including currently unknown factors that may play an important role in the disease. We will engineer the motor neurons to produce channelrhodopsin-2 (ChR2)-a protein that activates neurons when stimulated by light. This approach will enable us to selectively study the functional properties of motor neurons and systematically compare cells from patients and healthy individuals. Studies in ALS patients and animals with ALS associated mutations have shown alterations in neuronal communication, excitability and regulation of calcium that are a likely cause of fasciculations and muscle fatigue and may contribute to the demise of motor neurons. We will examine these aspects in the engineered iPSC-derived motor neurons that provide a more efficient method of ascertaining motor neuron specific properties. This study will provide insight into disease pathophysiology and enable the development of new therapeutic molecules that slow disease progression or provide better symptomatic relief.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: The X11 adaptor proteins and Alzheimer's disease.
Funder: Wellcome Trust

Abstract: One of the hallmark pathologies of Alzheimer's disease is deposition in the brain of Ab peptide within amyloid plaques. Increased production and deposition of Ab is believed to be a central aspect of the disease process. Indeed, many of the therapeutic approaches aimed at treating Alzheimer's disease involve inhibiting Ab production and deposition. Ab is derived by cleavage from a larger protein termed the "amyloid precursor protein" (APP) and we have shown that APP binds to proteins called the X11s. Moreover, we have demonstrated that the X11s inhibit Ab production. Many other research groups have obtained similar results. What is not known is how the X11s inhibit Ab production and this is the purpose of this programme of studies. Understanding the mechanisms by which the X11s exert their effect on APP and Ab production may well reveal new therapeutic targets for treatment of Alzheimer's disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: The role of retinoic acid in the spatiotemporal patterning of dorsal embryonic hindbrain.
Funder: Wellcome Trust

Abstract: Vitamin A is broken down in the body to make retinoic acid. This biologically active molecule has multiple, important roles in normal embryonic development. Too much or too little retinoic acid can have serious consequences for the developing foetus. In humans, damaging effects are concentrated in a few important groups of neurons in the cerebellum and hindbrain. While much of how retinoic acid affects early embryonic development is known, its role in the normal development of these relatively l ate forming brain structures is unclear. We will use a battery of highly focused molecular techniques to specifically answer this question. We also aim to test whether the involvement of retinoic acid in the development of these nuclei predisposes them to be sensitive to Vitamin A levels in adulthood. The importance of these studies is far-reaching. Defects in cerebellum development are implicated in a wide range of conditions; from relatively mild cognitive disorders such as dyslexia, through t o severe conditions such as medulloblastoma, a devastating childhood brain cancer. By contrast, developmental defects in hindbrain nuclei are specifically implicated Sudden Infant Death Syndrome.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL
Title: Deciphering the fundamental roles of two proteins involved in neurodegenerative disease.
Funder: Wellcome Trust

Abstract: The experiments in the present proposal are designed to understand the structure and the mechanism of action of a novel class of protein-cleaving enzymes. These unusual enzymes play an essential role in many physiological processes in living organisms, ranging from yeast to mankind. These normal biological processes included vitally important events such as signalling between cells during embryonic development, signalling between nerve cells in the brain, and signalling between immune cells during inflammation. These enzymes are also involved in several common diseases including Alzheimer's disease and Hepatitis C infection. We will use a variety of techniques including sophisticated electron microscopic and X-ray crystallographic studies to: 1) discover the normal three-dimensional structure and function of these enzymes; and 2) understand how these enzymes are usurped by disease-causing processes. The resulting knowledge will: 1) lead to a better understanding of several biological processes that are essential for life; and 2) will serve as a tool for the subsequent creation of medicines to stop the disease-causing processesin which these enzymes are involved. Such medicines will be designed, based onknowledge of the enzymes' shape, so that they block the disease-causing eventsbut still allow the normal enzymatic functions to continue unabated.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Cys-loop neurotransmitter receptors: molecular mechanisms underlying function.
Funder: Wellcome Trust

Abstract: Rapid communication between cells in the nervous system usually occurs at specialised junctions called synapses, by the release of specific chemical neurotransmitters that bind selectively to specific proteins (neurotransmitter-gated ion channels) embedded in the membrane of the adjacent cell. The binding of these neurotransmitters causes opening of an integral ion channel, which is located some distance (> 50 angstroms) from the binding site. We aim to understand the specificity of the binding event, and how the binding event is transduced to the pore region, by probing the specific chemical and conformational changes that occur both within the binding site, and between the binding site and the pore region. The former will be achieved by making subtle changes to the amino acid residues that define the structure and chemistry of the binding site, while the latter will predominantly involve incorporation of fluorescent probes that will allow changes in the environment of particular parts of the protein (especially the pore and the binding site) to be correlated with opening or closing of the ion channel.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL
Title: Molecular cell biology and pathology of hereditary spastic paraplegia.
Funder: Wellcome Trust

Abstract: Our overall goal is to understand better the molecular processes involved in axonal maintenance and degeneration. We will do this by studying the hereditary spastic paraplegias (HSPs), genetic conditions in which long axons in the spinal cord degenerate. We will analyse the normal and pathological functions of two HSP proteins that we have identified as binding-partners, spastin and atlastin. These proteins are involved in processes at the interface between membrane traffic and microtubule re gulation. We will examine functional assays for selected membrane traffic pathways in cell models of spastin- and atlastin- HSP. We will explore a potential mechanism by which abnormal traffic in these pathways may cause axonal degeneration, by analysing whether defects in axonal transport of cargoes derived from them are an early feature in cellular models of spastin- and atlastin-HSP. In the light of our preliminary work suggesting its importance in one type of HSP, we will determine whether abnormalities in BMP signalling are a unifying pathological feature of a group of HSPs, including spastin- and atlastin- HSP. Finally, we will use yeast-two hybrid screening as a basis to identify unrecognised HSP protein interactions, to extend the HSP protein interaction network and to identify new HSP candidate genes.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Molecular mechanisms of Schwann cell differentiation and growth.
Funder: Wellcome Trust

Abstract: Myelin has an essential role in insulating nerves and in promoting rapid nerve conduction. Loss of myelin in certain diseases causes reduced rates of nerve conduction and secondarily leads to nerve degeneration. The commonest inherited neurological disease is called Charcot-Marie-Tooth disease and its prime target is the Schwann cell, which is responsible for myelinating peripheral nerves. This disease affects about 1 person in 1000. We have identified a gene called the Periaxin gene that i s mutated in one form of this disease and we hope to understand why the loss of the protein that it encodes leads to such devastating consequences. An important aspect of understanding the function of genes like Periaxin is that it is has the potential to provide extremely valuable information about what these genes do normally in Schwann cells. For example in the case of the Periaxin protein we have discovered that it helps to form a structure in Schwann cells that allows them to grow during peripheral nerve development. In the proposed work we hope to build on these discoveries to provide further insights into what goes wrong in Charcot-Marie-Tooth disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL