NIHRDataInsights/HRCSData huggingface dataset:
Title: Engineering vascularised and aligned tissues using ultrasound cell patterning
Funder: Medical Research Council

Abstract: It is imperative that bioengineering strategies incorporate structural organization into in vitro grown tissue. For example, cardiac contraction is mediated by the synchronous beating of aligned cardiomyocytes, while the anisotropic mechanical properties of musculoskeletal tissues (e.g. ligament, tendon, cartilage, skeletal muscle) are defined by the directional organization of cells and matrix fibres. It is technically challenging, however, to achieve such fine control over tissue microstructure. The resolution of bioprinting is insufficient to fabricate detailed tissue architecture, while materials-based approaches can be methodologically inflexible and difficult to translate into 3D. The aim of this research is to develop a new, versatile strategy, in which the structural elements of complex tissues are reproduced using ultrasound patterning. Ultrasound standing waves present negligible cytotoxicity and can be used to manipulate bulk cell populations over large areas without any pre-labelling, specialised media or complex equipment. Our preliminary results have shown that ultrasound fields can be used to align myoblasts into parallel lines. In this Fellowship, an advanced acoustic set-up will be developed to engineer 3D tissues with hierarchical and multicellular cell patterning. These patterning methodologies will be developed using cell lines derived from human induced pluripotent stem cells, to ensure biological relevance for the real-world applications (disease models, drug screens, tissue grafts). The patterned tissue constructs will be fully characterised using confocal reflectance microscopy, gene expression analysis, immunohistochemistry, Raman mapping, electron microscopy and spatial transcriptomics. The validated tissues will then be applied predominantly for the engineering of vascularised, aligned muscle, but will be developed as platform technologies to enable application towards different organised tissue structures.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Complex Systems Science: Applications to Health Behavior.
Funder: Medical Research Council

Abstract: Aims. The proposed research encompasses two primary objectives. First, the research will integrate multilevel modeling techniques with social network methods in order to answer complex questions regarding variation in health outcomes dependent on individual, social, and environmental factors. In particular, the research will examine variation at the individual, peer, and school level to determine the ways through which these interdependent factors contribute to health inequities (e.g., substance use) among adolescents. Secondly, the research aims to advance our understanding of network-based interventions by applying diffusion of innovation methods in order to determine for whom, in what way, and how these interventions impact health behavior change (e.g., smoking cessation, engagement in healthy sexual practices). Methodology. Multiple longitudinal extant datasets specific to social networks and health behavior will be used. A variety of rigorous social network methodologies, including Multiple Membership Multiple Classification models, stochastic actor-based models, agent based models, and models of behavioral diffusion, will be employed. Scientific and Medical Impact. The proposed research impacts science by disentangling critical interconnections between social networks and health across contexts. Findings will highlight the complex interdependencies between individual, social, and environmental determinants, and thus, inform the effective design of intervention efforts. Moreover, the proposed research will benefit public health and policy through the identification of specific targets for sociocontexual interventions, in addition to advancing our understanding of how and for whom network interventions exert influence on health behavior change.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE
Title: Data synthesis over a network of multiple treatment comparisons for joint longitudinal and event-time outcomes.
Funder: Medical Research Council

Abstract: Joint models of longitudinal and time-to-event data simultaneously model an outcome repeatedly measured over time, and a time to some event by quantifying the relationship between the outcomes. Traditionally, joint models involve two-level data (as event-times and longitudinal measurements are nested within individuals). However, data is increasingly available from multiple sources (hospitals, centres, studies etc.), which form a third level. In reality, multiple treatment options exist in most clinical areas. Methodology to simultaneously compare all options is essential to inform optimal healthcare. However, data sources can employ differing subsets of available treatments, meaning direct comparisons between pairs of treatments are unavailable from some data sources. Network Meta-Analyses allow simultaneous assessment of multiple treatment options by combining direct and indirect evidence, but the methodology has not been explored for joint analysis of longitudinal and event-time data. My project will develop flexible methodology and software to efficiently model joint longitudinal and time-to-event outcome data from multiple data sources, to compare multiple treatment options simultaneously. The developed methodology will exploit both direct and indirect evidence when comparing several treatment options, and will provide functionality to address and model heterogeneity and inconsistency across the network of treatments compared in a multi-source joint longitudinal and time-to-event analyses. Currently, joint modelling methods are time intensive. This project will employ recent advances to Monte Carlo Markov Chain methodology in Computer Sciences, such as Sequential Monte Carlo samplers, to provide significantly reduced model fitting times. The methodology and software developed will be used to assess treatment options in three clinical areas; relapse data in HIV, hypertension data, and data from intensive care units.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Training in single-cell sequencing analysis for the Human Cell Atlas
Funder: Medical Research Council

Abstract: We have identified a number of key elements of research support provision which can be delivered through training to enable greater impact of the HCA within the UK research community and beyond. - Good data management practices and high quality data submission to the HCA - Single-cell RNA sequence analysis - Biological interpretation of analysis outputs We will therefore be delivering both face to face and online training to researchers who are using scRNA-Sequencing in their studies who require support in developing sound data management practices when generating such data, upskilling them in the analysis of this data and enabling its submission, in high quality format, to the HCA for access by others in the wider biological / biomedical research communities. This will maximise the value of data submitted by UK researchers to the global research community.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Human Developmental Biology Resource: support for Human Cell Atlas
Funder: Medical Research Council

Abstract: The Human Developmental Biology Resource (HDBR) is an ethically-approved human fetal tissue bank that provides the national and international scientific community with embryonic and fetal samples (4 to 23 weeks gestation) for research. This stage range represents the period when congenital disorders arise and many diseases of childhood and adulthood originate. Fetal material is supplied to an average of 100 projects at any time, and has contributed to more than 240 research publications, including in Nature, Science and Cell. The HDBR proposes to extend its service to supply human developmental material to projects within the MRC Human Cell Atlas (HCA) initiative. This new funding stream will support single cell gene expression and image analysis studies in embryonic and fetal tissues, for comparison with adult tissues. To supply projects under the MRC HCA initiative, the HDBR requires additional resource to meet several challenges. These include: greater tissue demand in terms of sample numbers per year, a larger range of specialist dissections to supply particular tissues/organs, and the ability to adapt tissue supply to specific project and funding milestones within the MRC HCA research portfolio. To meet these challenges, the HDBR will: (i) attend additional clinics to substantially increase the number of samples collected; (ii) train new and existing staff in an extended range of specialist dissection procedures, where possible via collaborations with MRC HCA groups; (iii) improve operating efficiency by providing samples from each embryo/fetus to multiple projects, working closely with HCA groups to ensure tissue supply is coordinated with project needs, and exploring the use of archived frozen tissue as an alternative to fresh material. While meeting HCA project needs, the HDBR will also ensure that its existing and new non-HCA projects remain well provided for, and that the highest possible standard of fetal material supply is maintained.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE
Title: Protein Translation Dynamics in Response to DNA Damage
Funder: Medical Research Foundation

Abstract: Increased sensitivity to DNA damage is the hallmark of a variety of human diseases. The integrity of the DNA is remarkably maintained through a complex network of signalling pathways, each acting upon recognition of a specific class of DNA lesion. This maintenance apparatus is known collectively as the DNA damage response (DDR), to ensure that DNA damage is repaired before a cell propagates throughout subsequent cell generations. The expression and modifications of proteins play a key determinant role in sensing the DNA damage, recruitment of DNA repair factors and orchestrating the cell-cycle changes. The utility of a set of post-transcriptional and post-translational modification allows temporal and spatial control over protein stability, localization and interactions, and may represent a means for targeting diseases with diminished capacity for DNA repair including cancer, and diseases associated with aging (Hoeijmakers, 2009). A detailed picture of the intricate trans- and co- regulatory mechanisms of DDR is highly needed to ensure efficient activation of cellular response to genotoxic stress. To address this issue, we propose to perform the first spatiotemporal system-wide analysis of post transcriptional and translational modifications in response to DNA damage.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Characterisation of DVL 2 DEP domain swapping regulation
Funder: Medical Research Foundation

Abstract: Wnt signalling is an ancient pathway evolutionarily conserved in metazoan animals that controls numerous context-dependent transcriptional switches as well as planar cell polarity during animal development and in adult tissues. In the presence of a Wnt signal, cells respond via the so-called Wnt signalosome: a transient co-cluster of signal transducers and transmembrane receptors that forms following the binding of extracellular Wnt to transmembrane receptors. Dishevelled is the hub protein on the signalosome, and it homodimerizes via a domain swapping mechanism of its DEP domain, where a DEP monomer extends its N-terminal α-helix, called H1, to donate it to a second DEP recipient. My research project has been focused in studying the regulation of DEP domain swapping event, and specially, on the relevance of phosphorylation in two Serine residues located at each end of the H1 α-helix (S418 and S435) on this event. For this, I have used cell-based assays, to assess the phonotypical effects of phosphorylation of these residues. I have also taken a biophysical approach to further study the consequences that phosphorylation on these residues have on DEP behaviour in experiments such as SEC-MALS and NMR spectroscopy. I am currently using the CRISPR-Cas9 technology in Drosophila Melanogaster to study the effect of modification of these residues in vivo.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Policy Research Unit in Social Care Workforce
Funder: Department of Health and Social Care

Abstract: We focus on the adult social care workforce - people working in care homes, home care and day centres, including social workers working with older people and people with disabilities, as well as their family carers. For some studies we collect new material but for others we use existing information to be efficient and not to waste busy people's time. Many of our studies use different or multiple methods to seek several views of a subject. The main task of the Unit is to investigate changes and continuities in the social care workforce. We investigate what social care workers do and their different activities. We offer detailed information on the workforce to policy makers using independent, timely, robust and reliable data about the social care workforce.

Lay abstract: We focus on the adult social care workforce - people working in care homes, home care and day centres, including social workers working with older people and people with disabilities, as well as their family carers. For some studies we collect new material but for others we use existing information to be efficient and not to waste busy people's time. Many of our studies use different or multiple methods to seek several views of a subject. The main task of the Unit is to investigate changes and continuities in the social care workforce. We investigate what social care workers do and their different activities. We offer detailed information on the workforce to policy makers using independent, timely, robust and reliable data about the social care workforce.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Heparin versus 0.9% sodium chloride intermittent flushing for prevention of occlusion in central venous catheters in adults
Funder: Department of Health and Social Care

Abstract: Central venous catheters (CVCs) are commonly used in health care, allowing delivery of blood, medication and nutritional support that cannot be given peripherally. 95% of the approximately 238,000 adult critical care episodes recorded in England each year for patients admitted into intensive care units or other critical care settings require a CVC, but their use is an important source of morbidity and mortality due to infectious complications and a thrombosis rate of between 5% and 18%. Flushing with heparin has been the most commonly used procedure to avoid thrombus formation and to prolong the duration of catheter patency in CVCs. However, use of heparin is not free of risk and has a considerable economic impact. Based on the 2014 version of this review, NICE concluded there was no good evidence that flushing with heparin was better than flushing with normal saline. Given that heparin may cause side effects while normal saline has virtually no side effects, NICE subsequently recommended flushing with saline instead of heparin, thereby enabling considerable savings for the NHS. However, certainty of evidence in the 2014 review was low, and an update is urgently required to ensure current clinical recommendations accurately reflect the totality of available evidence.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Colloids versus crystalloids for fluid resuscitation in critically ill patients
Funder: Department of Health and Social Care

Abstract: More than 90 000 people are admitted to critical care units in England every year, whether it is following injury, major surgery or life-threatening illness [1]. In policy terms, prompt and effective treatment of critically ill people would be expected to speed their recovery and avoid complications; thus this review helps fulfil the aims of two of the domains in the 2016-7 NHS Outcomes Framework, namely ‘Preventing people from dying prematurely’ (Domain 1) and ‘Helping people to recover from episodes of ill health or following injury’ (Domain 3). Scientifically, whilst a number of relevant, non-Cochrane systematic reviews have been published since 2013, when the last update of this Cochrane review appeared [2-7], they vary in scope, patient population and methodological approach. The 2013 version was referred to in the 2016 NICE guideline on intravenous fluids [8], but the guideline authors commented: ‘Despite the years of debate [about the best type of fluid to use, and the optimal volume and rates of delivery], uncertainty remains about the best fluid to use and many decisions are actually based on personal preferences.’ Given the continuing controversy, it is vital that the Cochrane review is updated, to the highest current methodological standards.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE
Title: English Longitudinal Study of Ageing (ELSA)
Funder: Department of Health and Social Care

Abstract: Background This is a longitudinal study of ageing. Data will be collected by following up respondents to the 1998, 2000, and 2001 Health Surveys for England (HSE) making it very cost-effective. The first round of the study will interview a representative sample of 13,000 English people aged 50 years or more in 2001/2. The primary objective is to collect longitudinal data that will provide a crucial resource for exploring issues related to ageing and enable a better understanding of the dynamics of ageing and the implications for policy and service provision in the future. The LSA will provide the following health and biomedical information: * Self-reported physical health - to assess changes over time with regard to specific illnesses and general health; * Prevalence of cardiovascular disease - as one of the most important cause of mortality and a key component in diseases related to stress which contributes to inequalities in health; * Prevalence of particular diseases - whether and how they lead to disability; * Cognitive processes, ageing and early stage dementia; * Psychological health; * Physical measurements and biological samples eg lipid profiles - to predict decrements in physical functioning such as CHD and stroke; * Contact with primary and secondary health services and receipt of formal and informal care. Data collected from ELSA will be deposited in the ESRC Data Archive. It's website is www.ifs.org.uk/index.shtml. Aims HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Plan of Investigation HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Potential Impact HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Policy Relevance Longitudinal panel data such as this will contribute at a number of levels to the policy-making of various government departments.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: GENERIC HEALTH RELEVANCE
Title: An exploration of the views of disabled children and their parents on the extent to which nurses meet their needs during acute emergency and inpatient admissions.
Funder: Health Education England

Abstract: Children with disabilities account for a higher number of acute emergency admissions and remain as inpatients for a longer period of time, compared to children without disability. Nurses in the acute setting are not meeting the needs of disabled children and their families adequately during these admissions. This PhD study proposes the use of semi-structured interviews to explore the views of disabled children and their parents regarding the nursing care received during acute hospital admissions. Results will be presented to focus groups of nursing staff for their reflections on how models of care can be improved to this vulnerable group.

Lay abstract: Children with disabilities account for a higher number of acute emergency admissions and remain as inpatients for a longer period of time, compared to children without disability. Nurses in the acute setting are not meeting the needs of disabled children and their families adequately during these admissions. This PhD study proposes the use of semi-structured interviews to explore the views of disabled children and their parents regarding the nursing care received during acute hospital admissions. Results will be presented to focus groups of nursing staff for their reflections on how models of care can be improved to this vulnerable group.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Incorporating Emerging Therapies into Open Randomised Clinical Trials
Funder: Department of Health and Social Care

Abstract: This research will identify, assess and investigate statistical considerations when incorporating an emerging therapy as a new randomisation arm into an ongoing clinical trial. Adding a treatment arm mid-trial is desirable to researchers, regulators and patients to ensure that new treatments are evaluated as quickly as possible, and resources are optimised. There is currently very little literature regarding statistical methods and design considerations to ensure that the research integrity is not compromised when adapting a trial in this way. The planned outcomes will recommend when and how this adaptation is possible and advantageous, comprehensively detailing the necessary considerations and methodology.

Lay abstract: This research will identify, assess and investigate statistical considerations when incorporating an emerging therapy as a new randomisation arm into an ongoing clinical trial. Adding a treatment arm mid-trial is desirable to researchers, regulators and patients to ensure that new treatments are evaluated as quickly as possible, and resources are optimised. There is currently very little literature regarding statistical methods and design considerations to ensure that the research integrity is not compromised when adapting a trial in this way. The planned outcomes will recommend when and how this adaptation is possible and advantageous, comprehensively detailing the necessary considerations and methodology.

Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE