NIHRDataInsights/HRCSData huggingface dataset:
Title: Finding effective analgesics in zebrafish by analysing effects on the nervous system (CNS)
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: The zebrafish is increasingly being used in biomedical research, because it is a cost-effective vertebrate model organism. However, most of the more than 400.000 procedures per year are performed without analgesia, because there is a lack of knowledge regarding nociception and effective analgesics in this important laboratory species. Efforts are underway to establish non-invasive measures of nociception, such as altered behaviour and cortisol measurements. To firmly link such measures to nociception, changes in genes expression elicited by noxious stimuli in the CNS need to be established. In this pilot project, we propose to analyse gene expression changes of immediate early genes and endogenous opiates in the dorsal horn of the spinal cord, where primary nociception processing takes place, and in higher brain centres. Our preliminary findings indicate that c-fos expression is selectively increased in the dorsal horn and pro-enkephalin expression is increased in the brainstem of adult fish that received an intramuscular injection of mustard oil, compared to those that received a vehicle injection. This suggests that gene expression changes specifically related to nociception and not just to handling stress can be measured. We will conduct similar experiments in larval zebrafish and, importantly, will determine how potential analgesics reduce nociception-related gene expression. Our experiments will elucidate central nociception in zebrafish and will inform other studies using non-invasive measurements regarding the relevance of these measures to nociception. Our ultimate goal is to contribute to the refinement of procedures conducted on zebrafish by devising effective ways of analgesia and validating non-invasive measurements of these.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Attention Bias: A novel method to assess psychological well being in group-housed non-human primates.
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Aim: The aim of this pilot study is to contribute to the NC3Rs objective of refinement by developing and validating a state-of-the-art technological tool for assessing psychological wellbeing in captive non-human primates. This novel method focuses on quantifying attention bias - a bias in visual attention that has been linked to underlying emotional state in both humans and (recently by our research group) captive rhesus macaques. Objectives: 1. Adapt methods we recently developed to assess attention bias in captive and free-ranging male rhesus macaques, for use with group-housed female rhesus macaques. 2. Validate attention bias as a measure of psychological state, by triangulating attention bias scores with behavioural and physiological state indicators, and genetic trait indicators of emotion and wellbeing. 3. Develop a 'quick and easy' attention bias assessment tool that can be applied widely and inexpensively by care staff, to reliably determine individual attention bias scores. 4. Assess the extent to which baseline attention bias scores predict the nature and degree of change in behavioural, physiological and attentional responses of animals to (preexisting) stressful husbandry procedures. Methodology: Primarily, we will film eye gaze to social stimuli for blind coding from video (Objective 1), and trial development of a flash card assessment tool using remote off-theshelf computer eye-tracking technology (Objective 3). To address Objectives 2 and 4, we will conduct focal animal behavioural observations, enzymeimmunoassay (EIA) of salivary hormones and genetic analyses of 5-HTTLPR serial repeat polymorphisms Scientific opportunities: The assessment tool will provide staff at research facilities with an open access resource to maintain high standards of welfare. Breeding and supplying psychologically healthy animals to research facilities provides a grass-roots approach to improving quality of science conducted using these animals.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Refining the mouse model of footpad immunisation and infection
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Our aim is to REFINE the 'traditional' model of footpad immunisation and infection in order to improve animal welfare. We will use a combination of immunological and cutting-edge imaging methods to define the key parameters associated with the administration of antigens, cells or parasites in the dorsal aspect to the foot, comparing it to the established footpad model. We will also assess development of Leishmania infection at this alternative site to establish whether parasite growth and ease of monitoring lesion development are comparable. Critically, we will use a combination of methods to assess any improvement in animal welfare in order to determine whether our proposal truly represents a refinement to currently used methods.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Graded Exercise Therapy guided SElf-help Treatment (GETSET) for patients with chronic fatigue syndrome: a randomised controlled trial in secondary care
Funder: Department of Health (England)

Abstract: Background The chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterised by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. The prognosis is poor and patient management consumes significant NHS resources. NICE recommend graded exercise therapy (GET) as one of two effective and safe treatments (cognitive behaviour therapy (CBT) being the other). But surveys of ME charity members suggest that GET is unacceptable and harmful, and that they prefer self-help. GET and CBT are also therapist intensive and thus expensive. Self-help based on CBT seems helpful, but GET self-help has not been tested. Aims The main aim of this pragmatic two arm trial is to determine the acceptability, efficacy and safety of specialist medical care (SMC) supplemented by Graded Exercise Therapy guided SElf-help Treatment (GETSET), compared to SMC alone, for patients diagnosed with CFS/ME attending secondary care specialist CFS/ME clinics. The secondary aim is to determine whether GETSET is as cost-effective as having SMC alone. The tertiary aim is to examine moderators of efficacy. Plan of Investigation This is a pragmatic, two arms, observer blinded, randomised controlled trial of patients with a clinical diagnosis of CFS/ME, attending two specialist CFS/ME clinics who have been referred for practitioner delivered therapy. Trial follow-up will be 12 weeks after randomisation or at the start of therapy, whichever is sooner. We will compare SMC plus Graded Exercise Therapy guided SElf-help Treatment (GETSET) to SMC alone. GETSET will consist of a booklet describing a six-step programme of graded exercise self-help, and two telephone consultations with a GETSET-trained physiotherapist. The control group will continue to receive SMC. The primary outcome will be self-rated physical disability. Secondary outcomes will include overall change, symptoms, global function and healthcare costs. Potential Impact This will directly benefit patients who, once diagnosed, often spend many months waiting for rehabilitative therapy with little or no progress being made during that time. A clinically useful self-help approach provides advantages to both the patient and the NHS, since patient outcomes will improve while healthcare costs are reduced. If this trial shows GETSET to be acceptable, safe and comparatively effective, then the GETSET booklet could be made freely and publically available by website with the knowledge that clinics can recommend it with minimal guidance. The pragmatic approach (almost all clinically diagnosed patients being eligible) in this trial mean that GETSET will be generalisable to usual NHS practice.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.7 PHYSICAL
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Early Intervention In Fatigue: A Feasibility Study
Funder: Department of Health (England)

Abstract: Background Chronic fatigue, of over one months duration, is reported by 10-24% of attendees in General Practice (1;2;3;4) The prevalence of Chronic Fatigue Syndrome/Myalgic Encephalopathy (CFS/ME) is 0.2-2.7% (3; 5-8), it is a significant health burden (2) , consumes significant health resources with poor prognosis (9-11). There is some evidence that early intervention reduces the development of CFS/ME (12) but this is restricted to a sub-set of at risk patients. This study will investigate the feasibility and efficacy of an intervention for any patient presenting with unexplained fatigue of Aims The overall aim of this study is to investigate the feasibility and acceptability of conducting a Randomised Controlled Trial (RCT) to determine the effectiveness and cost effectiveness of early intervention for fatigue compared with standard medical care in primary care. The feasibility trial objectives are to: 1. Investigate the feasibility of recruiting patients presenting to their GP with disabling fatigue lasting 1 to 4 months; 2. Evaluate the recruitment process to a randomised trial; 3. Assess the utility and acceptability of health resource use questionnaires; 4. Provide estimates of sample size required for a full scale study; 5. Investigate issues of retention in the RCT, including the acceptability of the care provided and reasons for any drop outs. Plan of Investigation Adult patients presenting with unexplained fatigue will be identified at GP assessment. Eligible patients who consent to take part will be contacted at home and the study explained in detail. Patients will be randomised to 1. Standard medical care or 2. Standard medical care plus early intervention (EI). The EI will include a face to face individual session, which is supported with an education booklet, and 3 telephone follow ups. The feasibility and acceptability of the study will be documented. An integrated qualitative study will explore the acceptability of randomisation, the suitability of the intervention and health economic tools and the feasibility of the study. Potential Impact This feasibility study will inform a large RCT which will be sufficiently powered to test whether early intervention offered in primary care can prevent the development/severity of chronic fatigue syndrome. Up to half of patients who go on to develop CFS/ME are unemployed, use an annual average of 13 visits to their general practitioner and average 5 visits to secondary care (10). If early intervention strategies are successful this could reduce the number of adults developing CFS/ME with significant impact on health service use, health care burden and loss of earnings.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Understanding how changes to the environment may promote walking, cycling and physical activity
Funder: Department of Health (England)

Abstract: Guidance from NICE suggests that supportive physical environments encourage walking and cycling; however few studies have shown that changing the environment actually changes behaviour. This project aims to investigate the short and longer term effects of environmental changes on walking and cycling, the impacts on physical activity, and the mechanisms by which behaviour change is brought about. These aims will be achieved by conducting new analyses of existing data, and by combining evidence from these and other studies on how specific environmental changes are linked to specific behavioural changes and impacts on physical activity, for whom and in what circumstances.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: CFS in the NHS: diagnosis of Chronic Fatigue Syndrome in primary care and outcomes after treatment by specialist services
Funder: Department of Health (England)

Abstract: The objectives of my proposed research are: i) to obtain an up-to-date estimate of the incidence of Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), diagnosed in primary care in England; ii) to document different approaches to treating CFS by NHS specialist services and to measure and compare long-term treatment outcomes; and iii) to investigate the economic impact of diagnosing and treating CFS. I will analyse data from the Clinical Practice Research Database and the CFS National Outcomes Database. My research findings will be important for the planning and improvement of NHS specialist services for adults with CFS/ME.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Adaptive Tests for Long-Term Conditions (ATLanTiC): supporting patient-centred care for patients with long-term conditions.
Funder: Department of Health (England)

Abstract: Long-term conditions including arthritis and diabetes are increasingly common. These conditions are related to a number of problems including psychological distress or loneliness, which can reduce patient quality of life. However, these issues do not always receive enough attention in busy primary care settings. This study will develop and test a computer system to make quick assessments of quality of life and patient experience which will help patients report, discuss and evaluate quality of life issues with staff in primary care. The system will be tested by comparison with paper-based questionnaires and interviews with patients and professionals.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Development of an intervention to improve appropriate polypharmacy in older people in primary care
Funder: The Dunhill Medical Trust

Abstract: Inappropriate polypharmacy has been described as a major public health problem. However, polypharmacy has been proposed as the “new paradigm”, due to the ageing population with multimorbidities. There is limited evidence to support effectiveness of interventions to improve polypharmacy, possibly due to omission of health care professionals (HCPs) and patients in intervention design. This study aims to develop an intervention to improve appropriate polypharmacy for older people in primary care, with a patient-HCP partnership at its foundation. The study will comprise three parts: (i) the evidence base for the intervention will be identified from literature and by conducting semi-structured, theoretically-based interviews with HCPs (general practitioners and community pharmacists) and focus groups with patients; (ii) development of an intervention, to overcome barriers, enhance facilitators and achieve priority outcomes using evidence identified; (iii) test the intervention for feasibility and acceptability and refine further using feedback from HCPs and patients.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Mean, Moody and Monthly': Women, Medicine and Premenstrual Syndrome in Twentieth-Century Britain.
Funder: Wellcome Trust

Abstract: Premenstrual syndrome is a complex, ill-understood, idiosyncratic condition in which many combinations of symptoms of varying severity are reported and experienced. Recent estimates suggest that while 95 per cent of women of childbearing age experience some symptoms, only 5 per cent have them severely and yet the labelling of women as premenstrual and moody is ubiquitous in contemporary popular culture. My project examines the history of this medical category, and uses its story to explore t he medicalisation of everyday life in Britain. How and why did the term premenstrual syndrome , and its precursor, premenstrual tension , evolve? How did these terms shift from expert into popular usage? What roles have doctors, other health professionals, and women played in constructing, sustaining and challenging the diagnosis and treatment of premenstrual syndrome? And what were the implications of this disorder for women s roles and social status? I use a range of historical sources, fr om gynaecological textbooks to women s magazines, to explore how and why medical understandings and popular meanings of the premenstrual woman changed in Britain over the course of the twentieth century.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Envisioning Migraine and the Migraineur , c. 1873 2004.
Funder: Wellcome Trust

Abstract: In 1873 Edward Liveing wrote the first book on migraine. Describing migraines as 'nerve storms', he and and his contemporaries suggested that it was wealthy, intellectual men who primarily suffered from acute, episodic migraine attacks that affected their vision. By the twenty-first century migraine handbooks portray migraine as a disorder most often suffered by women, related to diet, mental health and the menstrual cycle. How did these switches happen, under what influences, and with what effe cts? Looking at changing ideas about class, gender, the nervous system, hormones, and psychology, this project will broaden our knowledge of a disease that continues to defy complete explanation, cure and prevention. By focusing on the migraine sufferer, it will use history to show that the our knowledge of migraine is shaped by more than the current neurological paradigm. More broadly, this study will also contribute to current attempts by historians and practitioners to understand the hi storical growth of the chronic disease burden in our contemporary society.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Understanding foot-and-mouth disease virus persistence in African buffalo.
Funder: Wellcome Trust

Abstract: Foot-and-mouth disease (FDM) affects livestock and wild animals, buffalo especially. The disease is widely distributed in the developing world. This highly contagious viral disease causes a fever and painful blisters on the feet, teats and in the mouth, leading to lameness, a drop in milk production, loss of appetite and condition. As a consequence, FMD is considered to be the most economically important disease of livestock. In southern Africa, buffalo maintain virus for long periods of tim e and act as a source of infection for cattle and other buffalo. We do not understand how the virus is maintained in buffalo and how the virus is transmitted from these carrier buffalo, to other animals. In addition, the vaccines used to protect cattle are not very effective for the types of viruses present in buffalo. This situation creates a problem in developing countries between the livestock producers, which need an efficient livestock production system to alleviate poverty, and conservatio nists which want to preserve the wildlife population. Understanding how virus is maintained in buffalo and transmitted to cattle will allow us to develop better vaccines and control policies to support economic development and preserve wildlife in Africa.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Validating a combined geo-epidemiological approach to sampling for a geo-chemical disease
Funder: Wellcome Trust

Abstract: Podoconiosis (endemic, non-filarial elephantiasis) is a common but under-researched condition found predominantly in tropical Africa. A strong research program has been developed over six years through collaboration between academics from Addis Ababa University and Brighton & Sussex Medical School, and a podoconiosis Patient Association in southern Ethiopia. Through the research described below, we intend to expand the program to include geological and mineralogical research into the environmental trigger to complement further genetic studies. We plan first to use stored blood samples from patients and controls in southern Ethiopia to confirm the association between Class II HLA genes and susceptibility to podoconiosis. In parallel with this, we will collect salivary DNA samples from400 cases and 400 controls in a recently described endemic site in North West Cameroon. We will genotype the top 80 single nucleotide polymorphisms (SNPs) identified by our earlier GWAS and perform HLA fine mapping on all samples, and do HLA typing and sequencing in a subset. Finally, in an eight-site comparative study in four regions of Ethiopia, clinical, epidemiological, geological and topographical informationwill be gathered and linked using GIS methods, and soil and water samples taken for mineralogical and chemical analysis.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER
Title: Gene-environment studies in podoconiosis.
Funder: Wellcome Trust

Abstract: Podoconiosis (from the Greek for 'foot' and 'dust') is a severely neglected non-infectious form of elephantiasis which we estimate affects approximately 4 million people (predominantly subsistence farmers) across tropical Africa. Irritant particles from volcanic clay soils cause lymph vessel damage in the lower leg, resulting in unsightly swelling (lymphoedema) in about 1 in 20 people who work this soil barefoot. A Wellcome Trust-funded study conducted recently provides strong evidence that ge netic susceptibility to podoconiosis lies in an area of our chromosomes responsible for proteins that process particles foreign to the body. In this study, we propose to confirm this in a second group of Ethiopian patients, and among podoconiosis patients from Cameroon. We also intend to identify which component(s) of the irritant soil is/are responsible for triggering disease in susceptible people. We anticipate that the study proposed will benefit patients with podoconiosis in at least two wa ys. First, simply through completing and publishing high quality research, awareness of this condition will be increased in scientific and public health arenas. Second, understanding more about how podoconiosis is triggered by soil particles will enable us to fine-tune community-led interventions (such as provision of shoes to high risk children) to control the disease.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: DISPUTED AETIOLOGY AND OTHER