NIHRDataInsights/HRCSData huggingface dataset:
Award Title: Multi-modal assessment of liver grafts undergoing normothermic machine perfusion to stratify quality and deliver therapy
Funder: Medical Research Council

Abstract: The perfusion programme has three key linked aims and is a preclinical, experimental study whereby human organs will be normothermically perfused. Up to 40 livers will undergo normothermic perfusion during the three year period of the study. Access to human organs discarded from transplantation is already in place through national approval from NHSBT and ethical committees. In addition access to the national organ donation biobank (QUOD) will provide control tissue samples from organs that are transplanted and linked clinical data to establish correlation of the biomarkers with clinical outcomes. We will analyse whole organs and cell subsets looking for injury, senescence and cell death using an array of cutting edge technologies (e.g. proteinomics, cell free DNA, Raman spectroscopy, multiplex multi-sensing fiber optics) together with point of care biochemical analysis. Perfusate, tissue, bile and urine samples will be taken for analysis across the course of the perfusion up to 48-72 hours (or longer if perfusion technology allows it). Using MR spectroscopy and Raman spectroscopy we will assess changes in the liver structure during machine perfusion. The biliary cellular compartment will be assessed in real time continuously using in vivo multicore fibre based multiparametric multiplexed sensing which will be confirmed with traditional biochemical parameters to determine accuracy. We will use machine learning and informatics to analyse data generated and if organs are used clinically, we will link the experimental data with the clinical outcomes using the QUOD and NHSBT If organs are not used clinically, cell populations will be rested in vivo/vitro and additional data generated as feedback on the predictive ability of the assays used. These cell populations will then be infused in the liver during normothermic machine perfusion and effects assessed using the above assays.


Research Activity Codes: 5.2 CELLULAR AND GENE THERAPIES;5.4 SURGERY
Health Categories: ORAL AND GASTROINTESTINAL
Award Title: Multimodal profiling of inflammatory and immune cells to determine stage and treatment response in non-alcoholic steatohepatitis and type II diabetes
Funder: Medical Research Council

Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide, affecting 2/3 of people living with type 2 diabetes in Europe. For most patients, NAFLD is a benign condition, but a minority of patients develop non-alcoholic steatohepatitis (NASH) and liver fibrosis which can progress to cirrhosis, liver failure and liver cancer. Currently the only means of distinguishing patients with NASH and fibrosis from those who have uncomplicated steatosis is to perform a liver biopsy. It is neither convenient nor desirable to use this invasive and costly procedure to risk-stratify patients. Non-invasive markers can help detect established advanced disease, but are not reliable at detecting patients with NASH and fibrosis at risk of progression. One reason for the absence of a reliable biomarker is our incomplete understanding of NASH pathogenesis, which we will address in the current proposal. Our preliminary data using cytometry by time of flight to study peripheral blood mononuclear cells has shown an increase in cytotoxic CD8+ T cells and Th1 cells in patients with NASH and significant fibrosis compared to patients with simple steatosis or healthy controls. We hypothesise that adaptive immune cells, specifically pro-inflammatory T cells, play a pathogenic role in NASH.  Single cell transcriptomics and downstream mechanistic studies will give us unique insights into the pathogenesis of NASH and inform biomarker selection and lead to novel treatment targets. We will: 1. Use cutting-edge CITE-Seq single cell RNA sequencing to determine type, activation status and clonality of T cells (and other immune cells), in liver, blood and adipose tissue sampled at the time of bariatric surgery from patients with type 2 diabetes, obesity and fatty liver.  2. Determine function of T cell subsets identified in Objective 1 in in vitro models of lipotoxicity and fibrosis. 3. Determine effect of treatment-induced NASH resolution on T and other immune cells.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: INFLAMMATORY AND IMMUNE SYSTEM;ORAL AND GASTROINTESTINAL
Award Title: Multiplication and sleep- does learning before sleep improve recall?
Funder: The British Academy

Abstract: Educators are becoming increasingly aware of the potential impact of sleep on learning.  Studies show that learning new vocabulary before sleep, rather than in the morning, leads to better memory in children and adults. However, no research has investigated whether the same improvement generalises to learning numerical facts. Being able to fluently recall multiplication tables is a key skill associated with success in mathematics, but many children and adults struggle with this [1]. Timing learning prior to sleep could be a simple intervention to help. Firstly, we will investigate whether timing the learning of complex multiplication facts prior to sleep improves undergraduate students' recall. This study will serve as a proof of principle for future studies with simple multiplication facts with children. Secondly, a focus group with parents of primary school-aged children will explore parents' acceptability of learning of multiplication facts around bedtime.


Research Activity Codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: NEUROLOGICAL
Award Title: Multiresolution predictive dynamics of COVID-19 risk and intervention effects
Funder: Medical Research Council

Abstract: SARS-CoV2 is a novel virus, and even as new data improves scientific insight, many uncertainties remain about key aspects of transmission. Throughout the pandemic, mathematical and statistical models of COVID-19 have had an important role in the analysis of epidemiological data, in forecasting incidence trends and in assessing the potential impact of different intervention strategies. Models developed by the Imperial College COVID-19 response team have been particularly influential, but the absence of detailed data on transmission patterns have necessitated important assumptions that limit their predictive performance. This project will (a) extend predictive models of transmission trends to include complex spatiotemporal correlation to better capture new seeding events and improve early identification of hotspots of transmission, (b) understand the causal effect of interventions on transmission and the limits to which this inference is possible, (c) systematically collate and analyse data on transmission in specific contexts (households, schools, workplaces and care homes) to derive specific transmission parameter estimates for those settings to be used to improve the ability of models to predict the impact of targeted non pharmaceutical interventions, (d) Understand how important epidemiological parameters are changing with time and what is driving these changes. This work will directly support the Imperial team's input into the UK COVID-19 response via the SPI-M, NERVTAG and SAGE committees and our partnerships with PHE and the Joint Biosecurity Centre (JBC).


Research Activity Codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health Categories: INFECTION
Award Title: Multiscale modelling of progression in Parkinson's disease
Funder: Medical Research Council

Abstract: Disease progression is a key feature of PD, defined in terms of pathology within a brain region (c.f., symptom severity) and the spread of pathology between regions (c.f., new symptoms). Progression is highly variable, and potential mechanisms span many biological scales: with differences in where the disease begins, pattern of damage across circuits, co-existing pathologies, abnormal neural dynamics, cellular vulnerability and organelle dysfunction all thought to contribute.  This project aims to map the mechanisms of disease progression in Parkinson's disease (PD) across multiple biological scales, from cells to circuits, in the same individuals. Framing PD progression as differences in the cortical burden of disease (cortical dominant = fast; brainstem dominant = slow), we will identify individuals with extreme phenotypes of progression from an existing cohort to:  (i) Define longitudinal changes in brain microstructure in vivo.  (ii) Map the molecular and cellular dynamics using in vitro human models from the same individuals.  (iii) We will integrate data (i) and (ii) to inform a deep generative model, where mechanisms at one scale-quantified via model parameters derived from experimental measures-provide information used by the next. This will characterise how these pathophysiological mechanisms at different scales interact to result in the clinical syndrome observed.  This program will  deliver an open framework of integrated resources that can then be used in a translational setting.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: NEUROLOGICAL
Award Title: Musculoskeletal functional ability in three diverse Sub-Saharan Africa Populations; assessing muscle strength & function to understand healthy ageing
Funder: Medical Research Council

Abstract: In sub-Saharan Africa (SSA) shifting demographics, rapid urbanization and associated lifestyle changes are generating an exponential rise in non-communicable diseases of ageing, of which musculoskeletal diseases are a significant proportion. There is an urgent need to reduce the time people spend living with locomotor disabilities and dependence, and to maximize functional ability amongst the growing ageing populations in resource poor countries in SSA. This proposal focuses on three countries, The Gambia, South Africa and Zimbabwe. Hypothesis: In the diverse ageing populations, high levels of adiposity and chronic infection with low levels of dietary diversity and physical activity are, in differing combinations, responsible for growing levels of sarcopenia and poor functional ability.  WP1: What is the epidemiology of muscle strength, mass and function in each country? We collaborate with a team currently planning extensive community-based population prevalence surveys in The Gambia, Zimbabwe and South Africa. We have a unique and time-limited opportunity to add to these surveys. We will collect data from questionnaires, DXA scans, muscle strength and function, physical performance and blood tests. We will quantify musculoskeletal multimorbidities including sarcopenia and determine associations with disability and HRQoL. WP2: What are the clinical, nutritional and metabolic risk factors for low muscle strength, mass and function? Identifying risk factors for muscle impairment will aid understanding of mechanisms underlying muscle dysfunction. We will examine clinical, nutritional and metabolomic markers, and determine predictors of sarcopenia. Findings fed-back to local communities, national health leads and policy makers. This project grant offers a highly-cost effective opportunity, taking advantage of a funded research platform. This MRC investment would permit detailed and novel study of muscle in some of the most rapidly ageing populations in the world.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health Categories: MUSCULOSKELETAL
Award Title: Museums, Crisis and Covid-19: Vitality and Vulnerabilities
Funder: Arts and Humanities Research Council

Abstract: The Covid-19 crisis is having a significant impact on the museum sector, nationally and globally. It is exposing the vulnerability of museums, their staff, projects and collections. Elsewhere, innovative programming is demonstrating the vitality and versatility of an engaged, responsive and participatory museum service, proving that museums are places of relevance even in a crisis. 

This research project focuses on how museums can continue to contribute to community resilience and wellbeing in a time of crisis. It addresses sector adaptability as it adjusts audience engagement and collaboration (such as new collecting practices, programming and exhibitions) in response to Covid-19. The differing responses during the Covid-19 crisis - in some museums staff were furloughed yet elsewhere they have been involved in responsive projects - uncovers deeper attitudes to the essential (or otherwise) nature of museum services. Going forward, this project will lead and inform the sector as it adapts to effective community-digital possibilities that still embraces new thinking in participation and engagement. Alongside this, the project evaluates how we adapt our practices to be mindful of audience diversity, digital poverty, and the isolation challenges for vulnerable audiences arising from Covid-19.

Rising to that challenge this project: 
1.	identifies how museum pedagogy and practices must adapt to new audience needs; 
2.	explores possibilities for co-produced community-digital innovation; and, 
3.	investigates the offer museums can make to support community resilience during and in the aftermath of the Covid-19 crisis.

The importance of this project lies in the following areas. Firstly, new knowledge about the understanding of the impact of Covid-19 on the museum sector in NI that will both inform the Department for Communities (DfC) and have national relevance. Secondly, by generating new thinking around the community-digital dynamic and leading innovation as museums adapt. Thirdly, understanding the new needs around community resilience and wellbeing, arising from Covid-19.

The Museums Association's response to the Covid-19 enquiry described museums as vital in supporting communities, promoting community cohesion, enabling wellbeing, and reflection on significant public issues. Many of our museums work with vulnerable groups, who will remain cautious/shielding post lockdown e.g. the Dementia Friendly Programme (NI Museums Council). This project will investigate the impact of putting such programmes on hold, how they can be effectively adapted/reinstated, and make recommendations for immediate application/future planning.


Research Activity Codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health Categories: INFECTION;GENERIC HEALTH RELEVANCE
Award Title: NHS productivity national assessment
Funder: Department of Health and Social Care

Abstract: This work will be measuring the growth in the productivity of the English National Health Service (NHS) across financial years. Productivity is defined as the ratio of the total amount of outputs produced by the NHS to the total amount of inputs used. The higher the amount of outputs produced for a given amount of inputs, the higher the productivity.  The NHS produces an array of diverse outputs in a number of different healthcare settings, e.g hospitals, which are included in our comprehensive measure, as well as adjusting, where possible, outputs for the quality of care and measures of success of treatments. NHS inputs include labour, materials and buildings/other assets.  Assessing the productivity of the NHS is important in the current economic environment, as resource (financial) constraints are putting ever more pressure on the NHS to realise significant efficiency improvements. Producing annual estimates of productivity growth for the NHS will provide policymakers with a thorough assessment of the achievement of the NHS.

Lay Abstract: This work will be measuring the growth in the productivity of the English National Health Service (NHS) across financial years. Productivity is defined as the ratio of the total amount of outputs produced by the NHS to the total amount of inputs used. The higher the amount of outputs produced for a given amount of inputs, the higher the productivity.  The NHS produces an array of diverse outputs in a number of different healthcare settings, e.g hospitals, which are included in our comprehensive measure, as well as adjusting, where possible, outputs for the quality of care and measures of success of treatments. NHS inputs include labour, materials and buildings/other assets.  Assessing the productivity of the NHS is important in the current economic environment, as resource (financial) constraints are putting ever more pressure on the NHS to realise significant efficiency improvements. Producing annual estimates of productivity growth for the NHS will provide policymakers with a thorough assessment of the achievement of the NHS.

Research Activity Codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: Nasal cathelicidin expression in protection against respiratory syncytial virus
Funder: Chief Scientist Office, Scotland

Abstract: Respiratory Syncytial Virus (RSV) is the biggest cause of lower airway infections in the world, killing ~100,000 children <5 years old every year, and affecting the elderly as severely as influenza. There are no effective treatments, and we don’t understand why these age-groups get lethal infections when healthy adults have only mild cold
symptoms. We discovered that an antimicrobial substance (cathelicidin), naturally-produced in our bodies, can protect against RSV. In humans and mice, cathelicidin stops RSV infection getting started, and, if infection does occur, it is less severe when more cathelicidin is made by the body. The amount of cathelicidin varies in different people’s noses, where RSV virus enters. We propose that infants and the elderly are lacking effective “cathelicidin-shields” in their noses. This missing anti-viral barrier, and its effect on the bacteria that live in the nose, may increase the risk of serious RSV infection. This research will examine those ideas, and test whether ways of boosting cathelicidin production can help to protect against RSV. This research may help us understand who is at risk of severe RSV disease and develop ways to use cathelicidins and/or boost the body’s production of cathelicidin, to prevent and/or treat this life-threatening infection.


Research Activity Codes: 5.1 PHARMACEUTICALS
Health Categories: INFECTION
Award Title: Network analysis of multimodal COVID-19 patient datasets
Funder: Wellcome Trust

Abstract: Over recent years there has been an enormous number of developments in the ways we obtain molecular information from patients with disease. This has resulted in the ability to generate multiple measurements per patient for large cohorts, including levels of various proteins in their blood stream, gene activity across multiple different cell types at the resolution of single cell as well as precise methods of counting the numbers of different cells present in the system of interest. At the same time, there is an acute need to integrate this information and enable using all the data at once and not one at a time. Multilayer networks which at each layer summarize information available from a single experiment and then connect these layers allow us to integrate molecular information across various molecular measurements. We aim to develop statistically robust network methods and apply them to a dataset of more than 100 hospitalized COVID-19 patients of different severities. We also aim to compare them with sepsis, hospitalized flu patients and COVID-19 non-hospitalized patients and healthy volunteers to discover better ways to stratify patients and understand the underlying biological mechanisms driving their disease.


Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: INFLAMMATORY AND IMMUNE SYSTEM
Award Title: Neural mechanisms of endogenous pain control
Funder: Wellcome Trust

Abstract: Pain plays a vital role in self-protection and injury avoidance, and my research to date has outlined a core learning and decision-making framework, based on reinforcement learning theory, that shows how this is achieved in the brain. Recently, I have shown that this controls not only actions, but also the intensity of perceived pain itself (endogenous pain control) - an effect related to predicted uncertainty. This leads to the underlying hypothesis that pain is actively tuned by the value of its information - a precise metric that derives from an estimate of the extra benefit to survival achieved through learning. This leads to a series of testable questions: i) how and where is this information computed, ii) is it opioid-dependent, iii) how is it maintained over time, iv) how and at what level does it control pain representations, v) and can it be targeted to reduce pain. The proposed research describes the series of behavioural and neuroimaging experiments that will answer these questions, aiming to provide a comprehensive circuit level account of the major endogenous pain control process in the brain. Ultimately, the results aim to provide a basis for developing precision interventions for chronic pain.

Lay Abstract: The magnitude of chronic pain as a global clinical problem is illustrated by the opioid crisis. Opioids work by activating the brain’s powerful endogenous pain-killing system, but cause problems due to co-activation of reward and addiction networks. My research aims to understand why we have such a powerful pain-killing system in the first place, and how it actually works to control pain. Recently, I have identified a specific brain signal in human frontal cortex that may act as a central decision-maker in turning down the level of experienced pain. My proposal involves a set of human experiments built around a core hypothesis about how this signal works: what are the inputs, how does it compute the decision, and where in the brain does it exert its effect on pain? The ultimate goal is to design precision, non-drug (e.g. biomedical engineering) approaches that selectively harness the system to provide pain relief.

Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: MENTAL HEALTH;NEUROLOGICAL