NIHRDataInsights/HRCSData huggingface dataset:
Title: Ultrasound mediated bioluminescence tomography for high sensitivity, high spatial resolution 3D imaging
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: An imaging system that combines ultrasound and optical techniques will be developed with the capability to significantly improve the spatial resolution and quantitative accuracy of bioluminescence imaging (BLI). Enhancement of the information obtainable from current BLI systems will be achieved by first modulating the bioluminescent light emitted in the tissue with a focused ultrasound beam. This produces an ultrasound modulated light 'beacon' within the tissue in the region of the ultrasound focus which can be used to reduce the effects of light scattering and improve the image spatial resolution. To provide an added layer of information conventional ultrasound imaging will be carried out enabling images of tissue structure to be co-registered. Both modulated light beacons and structural information will inform a reconstruction algorithm based on our widely used NIRFAST reconstruction code enabling the two datasets to be merged. The potential of the system to outperform current state of the art BLI will be demonstrated through a number of exemplar pre-clinical 3D imaging studies, including tracking of mesenchymal stem cells in nude mice. Based on our proof of concept data the 3D image spatial resolution will be improved by at least a factor of 5 (500 um compared with 2.5 mm) enabling more accurate and consistent clinical data to be obtained from a smaller set of animals. This will contribute to a significant impact on the 3Rs. Replacement: better imaging will inform more accurate computational models; Reduction: imaging enables longitudinal studies on the same cohort, more accurate quantitative imaging allows fewer animals to be used in a study; Refinement: through the improved quality of research findings.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: EFucci an atlas of proliferation to reduce mouse usage in embryonic proliferation assays
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: The study of proliferation is key to the characterisation of many models of human disease especially in the developing embryo. There were over 3000 academic papers published in the field in 2013 alone. Often these studies use the incorporation of thymidine analogues into the DNA of dividing cells to identify sub-populations of cycling cells. This approach usually requires either multiple intraperitoneal injections of the thymidine analogue or the surgical implantation of mini osmotic pumps to slowly release the analogue. The Fucci system is an alternative to this approach that uses two genetically encoded biosensors of cell cycle phase to label cells and therefore does not require surgical intervention. We have developed an alternative mouse model that incorporates the Fucci probes into a single construct driven by a strong ubiquitously active promoter (R26Fucci2a). This has allowed us to reduce animal usage in our own experiments by abrogating the need to use two mouse lines, one expressing each Fucci probe. #The atlas will also help to promote the use of our alternative R26Fucci2 model thus reducing the number of surgical procedures required to carry out the experiments.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: ClearfLo: Clean Air for London
Funder: Natural Environment Research Council

Abstract: Poor air quality, particularly in urban areas, has a demonstrable effect on human health, but the processes responsible for producing the main pollutants, namely particulate matter, ozone, nitrogen dioxide and heat are not well understood and are poorly predicted. The ambition of ClearfLo is to provide integrated measurements of the meteorology, composition and particulate loading of London's urban atmosphere, made at street level and at elevated sites, complemented by modelling, to improve predictive capability for air quality. This ambition will be addressed by establishing new measurement capabilities in London, which will be used for long-term measurements and intensive observation periods, and by analysis and modelling of the measurements to establish key processes.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC)
Funder: Natural Environment Research Council

Abstract: Most recent scientific efforts have focused on examining toxicities of manufactured nano-particles (MNPs) only in source materials. By not evaluating MNPs at the point of exposure, these efforts fail to address the relevant question of whether or not consumer-product-derived MNPs are of concern to public health and the environment. The proposed US-UK consortium, 'Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC)', provides a systematic, multidisciplinary approach, including both experimental and computational tools and projects, for predicting potential human and environmental risks associated with the use of selected consumer products that respectively incorporatezinc oxide, silver, and cerium dioxide nanoparticles. The overall hypothesis of the RAMNUC project is that MNPs at the point of exposure for both humans and aquatic animals will substantially differ in both physicochemical and toxicological properties from MNPs at the source (synthesized in the laboratory or acquired commercially). These differences may have significant consequences with respect to MNPs' bioavailability, alterations of immunity, induction of oxidative stress, inflammation, disease processes, and other toxicity measures. We will assess intracellular and extracellular bioavailability and toxicity of the selected MNPs, as synthesized and as incorporated in consumer products, using both in vitro and in vivo experiments. Tested MNPs will be controlled or well characterized for their physical (e.g., size, shape, state of agglomeration/aggregation) and chemical properties (e.g., composition, functionalization, surface chemistry). Hence, our proposed in vitro and in vivo studies will produce mechanism-based results relating toxic effects to MNP physicochemical properties. The RAMNUC Consortium will also include a novel human exposure simulation study that will produce realistic estimates of MNP exposures to consumers. Data generated from these mechanistic experiments will be integrated into the mechanism-based computational modules of two existing source-to-exposure-dose-to-effects modeling systems, allowing for rational extrapolation and generalization in MNP risk assessment. Built upon the inter-institutional expert structure, the RAMNUC consortium serves as a model for systematically addressing complex problems associated with MNP risk assessment and will generate results that will contribute to our very limited knowledge about health risks associated with the use of nano-technology based consumer products.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: GENERIC HEALTH RELEVANCE
Title: [WATER] Management and Control of Taste and Odour Problems associated with Geosmin and 2-MIB in drinking Water Supplies
Funder: Natural Environment Research Council

Abstract: In this CASE Studentship PhD project we aim to understand the drivers of elevated VOC production (Geosmin and 2-MIB) in drinking water reservoirs within the Wessex Water catchment. Episodic outbreaks of Geosmin and 2-MIB have occasionally, though not always, been associated with planktonic cyanobacterial blooms in Wessex reservoirs, but more recently, benthic communities have been identified as potential and significant sources of the VOCs, (Wessex Water, unpublished data). Focussing on three reservoirs and their associated catchments, we will analyse the distribution, transport and fate of these VOCs and their response to water treatment processes. The specific aims are: i) to isolate potential VOC producing microorganisms from the benthic and pelagic regions of the three reservoirs (and from the immediate catchment); ii) to examine intra-and interspecific variability in Geosmin and 2-MIB production under a range of experimental regimes; iii) to determine the degree of compartmentalisation between dissolved and particulate fractions of VOCs; iv) identify conditions that lead to the exudation of VOCs with a specific focus on the role(s) of viral lysis, protozoan and crustacean grazers, using isolated benthic and pelagic VOC-producing microorganisms


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: GENERIC HEALTH RELEVANCE
Title: BACCUS: Big data for atmospheric chemistry and composition: Understanding and Science
Funder: Natural Environment Research Council

Abstract: The atmosphere is composed to millions of chemical compounds. Each of these compounds can have distinct properties chemical and physical but also biological and medical. Our ability to understand these compounds is dependent upon the instrumentation available to us. New advances in instrumentation (high resolution GC-TOF systems) allow us to investigate the composition of the atmosphere in unprecedented detail. However, these new instruments provide a deluge of data that needs to be stored and process. By storing all of the data, rather than throwing away the data that is not yet understood we will create a virtual air archive which can be exploited into the future as our ability to understand the complex instrumentation and chemistry involved becomes more refined. BACCUS provides hardware to deal with this data deluge, provide software and computers to support to analyse and visualise the data and provides some computation to initially interpret the results.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: The Exploratory Map: developing and evaluating a complex intervention to support generalist care of complex needs.
Funder: Department of Health (England)

Abstract: This proposal aims to optimise the delivery and evaluation of the Exploratory Map as a complex intervention supporting generalist care for people with complex, chronic illness.General Practice provides holistic care supporting individuals in living their daily lives. A single, disease-focused explanatory framework is inadequate to explain much of the illness needs presented to General Practice; complexity is a function of diversity and uncertainty. Practitioner and patient engage in a dynamic process of shared exploration and interpretation of illness experience. The Exploratory Map describes this process: the integration of biotechnical and biographical knowledge to generate an individualised account of need. However neither the profession, nor the processes of evidence-based practice, have described a framework by which the impact of this activity can be evaluated.This proposal describes 3 steps in the delivery of this complex intervention. An ethnographic longitudinal study explores individual efforts to maintain continuity of daily life in the face of chronic complex illness, including the impact of health care on this creative capacity. Analysis of consultations with patients with complex problems, supported by interviews with both parties, will explore the interpretive process: defining the core components, drivers and barriers to delivery, markers of quality, and impact on patients. Two survey tools will be developed: an outcome measure of creative capacity; and an assessment of consultation type and quality. Tools will be validated within a pilot longitudinal cohort study to assess the impact of an interpretive model of care on patient outcomes.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Improving the management of long term conditions with the clinical use of patient reported outcome measures in Primary Care.
Funder: Department of Health (England)

Abstract: Current reforms of the NHS aim at making it easier for patients to know how the health services can improve their health. There is particular interest in using information based on what patients say about their own health using questionnaires. In this study we want to know whether passing this information on each patient to their General Practitioners can be used to make sure that patient's needs and priorities are taken into account. If that was the case, patients might feel more motivated to take care of their own health and this may result in better health and more satisfaction with the health services. We will develop an intervention with the help of patients and health professionals using methods that we have used previously. We will use a type of questionnaire in which patients are asked what activities or areas they consider most important to them. Patients then rate their health based on those areas. We will do an experiment to see whether the intervention can be used in real life and whether it does what we expect it to do. This experiment will also tell us more about whether (and how) further research needs to be done.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: GENERIC HEALTH RELEVANCE
Title: Methods for the assessment of the effectiveness of treatment sequences for clinical and economic decision making in the NHS
Funder: Division for Social Care and Health Research (Wales)

Abstract: Background Synthesising and interpreting evidence in order to make an informed decision regarding the effectiveness of a sequence of treatment options is not straightforward. Objectives To develop a framework for quantitative evidence synthesis to estimate the effectiveness of sequential treatment options in the context of decision analysis. Design Explore, develop and compare methods (including clinical decision analysis) for estimating treatment effect for an intervention in a population conditional on the previous treatments administered. The added value of using complex methods over more simplistic approaches will also be explored. Expected outcomes Framework which provides guidance on quantitative evidence synthesis of sequential treatment.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: GENERIC HEALTH RELEVANCE
Title: Supervised pharmacy student led medication review in primary care: A pilot study to ascertain the potential costs and effects
Funder: Department of Health (England)

Abstract: Background Level 3 clinical medication reviews (with patient and notes) are recommended by the Department of Health for specific patient groups. Pharmacy graduates acquire robust therapeutic knowledge and are trained to optimise drug therapy and patient medicine behaviour. Unlike other health care practitioners they have minimal patient contact during training and research has demonstrated a need for improvements in pharmacist consultation skills. To address this issue the current government agenda is to increase patient contact within the pharmacy undergraduate curriculum. Delivery of level 3 medication reviews by pharmacy undergraduates under close supervision has the potential for patient benefit, developing pharmacist consultation skills and providing a potential education model for the future. Aims By replicating the process of delivering NHS services under clinical supervision, utilised by all undergraduate schools of Optometry and Dentistry within the UK the study aims to • Determine the potential patient benefit arising from supervised pharmacy student led level 3 medication reviews • Determine the effect size of the intervention and its potential cost-effectiveness from an NHS perspective • Develop and describe a novel model for the training and delivery of pharmacy student led medication review clinics utilising consultations with patients with Type 2 Diabetes. Plan of Investigation Phase 1 Development Literature review & stakeholder focus groups undertaken to develop intervention Phase 2 Intervention Appropriately prepared 4th year pharmacy students invited to participate Patients with type II diabetes, identified via their medical practices, recruited and randomised to intervention or control Students allocated 2 Intervention patients (IPs) to review, undertake a notes review at medical practice under supervision and discuss with the general practitioner Student undertakes consultation at a later date with IP to discuss information needs and identify any adherence or safety issues Patient outcomes measured at baseline and end, and compared to determine effect size and potential cost-effectiveness Phase 3 Review Focus groups repeated to review the process Potential Impact In addition to meeting a number of current government agendas this project will potentially: Improve both patient knowledge of their medicines and patient adherence Result in large numbers of medication reviews being undertaken relatively inexpensively Improve adherence to national standards for diabetes prescribing and monitoring Improve patient outcomes Improve pharmacist consultation and medication review skills Improve working relationships between pharmacists and doctors Positively affect patient opinions of the pharmacist leading to greater future utilisation of this NHS resource


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: A randomised controlled trial of early mobilisation therapy in the Critically Ill
Funder: Department of Health (England)

Abstract: Background Quality of life (QOL), in terms of both Physical and Mental Health, is significantly reduced following a prolonged admission to Critical Care (Intensive Care). In survivors, there is a slow and incomplete recovery in QOL over the next 6 to 12 months. There is some evidence that early physiotherapy in this group of severely ill patients may improve both the rate and magnitude of recovery from critical illness. However the evidence base is very incomplete and in particular the relationship between the amount of physiotherapy given and the rate of recovery is unknown. We intend to examine this relationship in a randomised controlled trial. Aims The primary aim of this study is to test the hypothesis that an increased intensity of physiotherapy, started at an early stage of admission to critical care, will lead to better functional outcomes in critically ill patients. We will test this hypothesis by comparing outcomes at 6 months in two groups of severely ill patients, randomised to different intensities of physiotherapy. The primary outcome will be physical quality of life. Our secondary aims are to examine changes in mental health and the economic costs of the interventions including an analysis of costs against gain in quality of life. Plan of Investigation We will conduct a patient randomised, parallel group, controlled trial comparing two intensities of physiotherapy. Adult, critically ill patients, ventilated for more than 48 hours will be randomised to two groups. Group 1 (control patients) will receive usual care, including a once daily physiotherapy treatment session. Group 2 (intervention group) will receive a more intense twice daily programme. The primary outcome measure will be physical quality of life at 6 months (as measured by the SF-36 Physical Component Summary (PCS) measure). Secondary measures will include: exercise capacity as recorded by the 6 minute walk test; a composite score measuring activities of daily living; mental health QOL (SF-36 measure) and a cost-effectiveness evaluation of the intervention. Potential Impact Each year more than 100,000 patients require admission to Intensive Care units (ICU) in the United Kingdom. NICE have recently produced guidelines on rehabilitation after critical illness. The evidence base that underpins this guidance is acknowledged to be incomplete. The proposed trial would significantly add to the evidence regarding phyiotherapy-led, early mobilisation therapy. It would have an immediate impact on current practice in either confirming that current service provision (as defined by the usual level of practice) for physiotherapy is adequate or in supporting a change in provision to support twice daily interventions. The study would also examine the economic consequences of increased service provision in order to inform health providers and commissioners.


Research activity codes: 6.7 PHYSICAL
Health categories: GENERIC HEALTH RELEVANCE
Title: Rehabilitating muscle after intensive care (REMAIC)
Funder: Department of Health (England)

Abstract: Background Critically ill patients lose skeletal muscle at 2-4% per day. Muscle weakness is the most important determinant of health outcome. The elderly have reduced muscle mass and regain it slower and recovery may take a year. We have contributed to the evidence in new NICE guidance that early physiotherapy within intensive care and a self-guided rehabilitation programme in the first few months may aid recovery. Our pilot of a more intensive early physiotherapy led exercise programme suggests faster recovery. Elderly patients have anabolic resistance and when they are patients post ICU it may be exacerbated by a degree of insulin resistance. Skeletal muscle anabolic resistance may be overcome by the provision of appropriate supplementary essential amino acids if combined with physical exercise. Aims The study will examine the effect of amino acid supplements & physiotherapy on physical recovery in rehabilitating critically ill patients. Specifically we will address the following questions: 1) Does a specific nutrient supplement improve physical recovery over and above current care & physical therapy? 2) Does a specific nutrient supplement improve long-term glucose tolerance over and above current physical therapy? 3) Does a program of enhanced physiotherapy and structured exercise improve physical recovery quicker than conventional physiotherapy? 4) Is there a further additive effect of the specific nutrient supplement upon a program of enhanced physical therapy? Plan of Investigation Critically ill patients aged over 50 years will be recruited during recovery after intensive care. The aims will be addressed in a randomised controlled clinical outcome study where the control is best standard care as prescribed in new NICE clinical guideline 83 (early physiotherapy and self-help guide). Two factors will be tested in a 2x2 factorial design: 1) an essential amino acid drink twice daily just after exercise in between meals for 3 months 2) a Program of Enhanced Physiotherapy and Structured Exercise (PEPSE) of 6 weeks within the first 3 months. Primary efficacy outcome will be the improvement in six minute walking test a valid measure of exercise capacity measured at 3/12. Secondary efficacy parameters will be assessed using HOMA-IR, SF-36, DEXA, EQ6 at 3 month and 1 year. Potential Impact Nationally many critically ill patients currently receive inadequate rehabilitation and this prompted new NICE guidance on the rehabilitation of the critically ill patient. However key questions on additional nutrient provision and the amount of physical therapy are unknown. This clinical study with meaningful outcome measures including quality of life will provide key additional practical and outcome data to inform service provision in the NHS. Our previous pioneering work is internationally recognised and this study will have great international impact as it uniquely tests the combination of nutrient and exercise for the benefit of critically ill patients.


Research activity codes: 6.7 PHYSICAL
Health categories: GENERIC HEALTH RELEVANCE