NIHRDataInsights/HRCSData huggingface dataset:
Title: Social Patterning of Health over the Lifecourse
Funder: Medical Research Council

Abstract: Reducing social inequalities in health is a key policy goal in the UK as well as a significant focus for major international agencies such the World Health Organisation. This programme aims to investigate the creation and maintenance of poor physical and mental health and wellbeing over the lifecourse and across time in order to identify tractable entry points and mechanisms for reducing social inequalities in health. We have four broad objectives. To track changes in social circumstances and health over the lifecourse (within cohorts) and across time (between cohorts). To investigate specific pathways – social, biological, behavioural, psychosocial and cognitive - between social position and health. To explore the transmission of socioeconomic and health inequalities between generations. To examine the role of macro influences on health inequalities by undertaking cross-cohort comparisons between different places (nationally and internationally) and at different points in history. The core of this programme is the analysis of longitudinal data from the Twenty-07 Study, which has been following three cohorts of people - born around 1932, 1952, and 1972 – since 1987, collecting a wide range of information from them about their health and everyday lives, every five years, including on the most recent occasion biological samples. With these samples we are currently investigating the social patterning of different biomarkers to help us understand the biological processes that link socioeconomic factors with health outcomes. The three-cohort design of the Twenty-07 Study enables us to compare relationships at different life stages and sensitises us to their historical specificity in ways it is difficult for single birth cohorts and all-age studies to do. To complement this, we are conducting orals histories with a small number of respondents to gain a more indepth understanding of their experiences and health through different historical periods. Our analyses address issues of attrition and employ appropriate longitudinal techniques. In doing this, we plan to build capacity for longitudinal research in public health through studentships and postdoctoral fellowships.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: GENERIC HEALTH RELEVANCE
Title: Children, Young People, Families and Health Programme
Funder: Medical Research Council

Abstract: Our overall aim is to understand better the key social factors that shape the health of children and young people, with particular focus on the family, and through these understandings to develop and evaluate preventative interventions. There is increasing recognition that families, and in particular parent-child relationships, are a fundamental influence on young people’s health-related behaviours and health, especially in the early years. Although there is growing evidence that interventions with parents can have positive outcomes for their children, it has proved particularly challenging to recruit the parents of the most vulnerable children. Peers, schools and the mass media are other important influences on young people, though assessing their impact is complex. Schools and the mass media provide opportunities to promote health and, potentially, reach children and young people not readily accessed through parents. We have four broad objectives: • to understand better the influence of family life on health-related outcomes and how this varies socio-culturally, with particular focus on authoritarian parenting in east Africa • to understand better how the influence of families is interrelated with that of peers, schools and the media • to understand how these influences might be improved by developing and evaluating interventions, with particular focus on reaching the most vulnerable children and young people and on clarifying the causal pathways of interventions at both an individual and collective level • to strengthen research capacity, particularly in east Africa. Original observational and intervention studies are being conducted in the UK and east Africa, primarily Tanzania and Uganda, using both qualitative and quantitative methods. We use formative, process and outcome evaluations as appropriate, and where possible conduct randomised controlled trials. We are currently engaged in two large scale trials, one of a primary school social and emotional wellbeing programme, the other of early years interventions with vulnerable pregnant women. We are also bringing together existing research findings by systematically reviewing the published literature.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: GENERIC HEALTH RELEVANCE
Title: Chemical compatibility of drugs administered by continuous subcutaneous infusion for end of life care
Funder: Marie Curie

Abstract: Background In 2007, the National Patient Safety Agency (NPSA) issued an alert about injectable medicines after receiving reports of medication errors. Subsequent guidance recommended the compatibility of commonly used mixtures should be readily available. In 2008, the Medicines and Healthcare products Regulatory Agency (MHRA) stated that research should be commissioned to develop authoritative national advice on the compatibility and stability of medicines delivered via continuous subcutaneous infusions (CSCIs) for pain and symptom control at the end of life palliative care. Pilot chemical analysis has been performed during the past year to ensure feasibility. Aims and Objectives This study aims to develop an authoritative national guide detailing the chemical compatibility of a selection of drug combinations commonly used for symptom management during the last months and days of life. While many mixtures appear physically compatible (i.e. clear, colourless and free from precipitation) chemical incompatibilities cannot be discounted. It is unknown whether symptom deterioration that may occur in some patients is due to disease progression, or chemical incompatibilities reducing the availability of active drugs. Methods Initially, the development of a list of commonly used drug mixtures will be determined. This will be achieved through analysis of a database which will incorporate data generated by a national survey. Drug mixtures will be prepared in duplicate and will be attached to a syringe driver programmed to deliver the contents over a 24 hour period, simulating clinical use. Samples will be taken from the giving set at four set time points over the 24 hour infusion period. At each time point the appearance of the contents of the syringe and giving set will be monitored visually, pH will be measured and individual drug concentrations will be assayed by high performance liquid chromatography diode array detection (HPLC-DAD). The appearance of any degradation is also monitored by HPLC-DAD. Further techniques that may be employed include Liquid Chromatography Mass Spectrometry (LCMS) and Ion Mobility Spectrometry (IMS). How the results of this research will be used There is a definite need for chemical compatibility data of drug mixtures commonly used for pain and symptom control at the end-of-life. Healthcare professionals will be able to use such data to inform their clinical decision making and ensure the best possible care for patients as they approach the end of life. The information gained by undertaking this work would have both national and international application and has the potential to be of great importance for palliative medicine.


Research activity codes: 7.2 END OF LIFE CARE;6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE
Title: Identifying patients who would benefit from palliative care, irrespective of diagnosis: the development and feasibility testing of a primary care-based intervention
Funder: Marie Curie

Abstract: Background People’s experience of care at the end of life varies greatly by diagnosis. Recognising when patients with non-malignant illness need supportive and palliative care is a prerequisite for effective and equitable end of life care for this disadvantaged group. Primary care teams are well placed to use their increasingly sophisticated computerised databases and search facilities to identify and consider all such patients for palliative care based on pragmatic clinical and other criteria. Aims To develop and test a primary-care based intervention to identify patients who might benefit from earlier supportive and palliative care Methods We will develop a two-stage identification process: 1) Development and running of GP computer searches to identify patients with supportive and palliative care needs using criteria in the refined SPICT, as recorded in patient electronic records (VISION and EMIS): Patients will be purposively selected across the cancer, organ failure and frailty trajectories; 2) Refinement of the shortlist through discussion of the search results at Practice Team Meetings. We will carry out interviews with health professionals and focus groups with patients and carers. We will then test the feasibility of implementation of the intervention in six general practices with a range of socio-demographic characteristics. The intervention will be implemented over four months in each practice, and will include 1) running the searches once a month 2) discussion of the search-generated lists at practice team meetings. Further qualitative work with staff and patients will be carried out. The changes in the numbers of patients on the Palliative Care Register on a month-by month basis will be recorded: for those on the PCR, the number of OOH calls, and unplanned hospital admissions will also be recorded. How the results of this research will be used The results will inform the design of a future randomised controlled study to assess the impact of early supportive and palliative care for people with cancer and nonmalignant illnesses. This intervention if found useful has great potential for widespread applicability.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.2 END OF LIFE CARE
Health categories: GENERIC HEALTH RELEVANCE
Title: End of life care: the experiences and needs of lesbian, gay, bisexual and trans (LGBT) elders
Funder: Marie Curie

Abstract: Background While it is well known that end of life care needs are most common among older age groups (whether as patients or carers), there has been little research exploring particular sub groups and a lack of understanding of the heterogeneous needs of ‘older people’, particularly those living in non traditional family forms This study addresses the needs and experiences of lesbian, gay, bisexual and trans older people (LGBT elders) in relation to end of life care (EoLC) to assist the development of equitable service provision in EoLC that addresses core principles of dignity and respect for all. Aims 1. To identify particular needs and preferences salient to sexual/gender orientation relating to EoLC as identified by LGBT elders. 2. To examine ways in which sexual/gender orientation may impact on experiences of EoLC for LGBT elders 3. To explore LGBT elders' familial and friendship networks and the ways in which these personal networks may influence later life experiences towards and at end of life. 4. To identify recommendations for good practice in EoLC issues addressing issues for LGBT elders. Methods A mixed methods study with three phases: 1. A survey (n = up to 300) of LGBT elders experiences and needs in relation to EoLC across England and Wales 2. In-depth interviews with a sub-sample of the survey respondents (n = up to 60) to examine in-depth issues highlighted from the survey and incorporating 'eco-maps' (a participatory visual technique to map out and prompt discussions about respondents' supportive networks). 3. A public engagement workshop to feedback findings and to collaboratively develop recommendations to contribute to outcomes of the study. How the results of this research will be used. The research team have an excellent reputation for translating research findings to inform and shape policy and practice in end of life care. We will utilise our networks to reach a broad range of policy makers and service providers in EoLC. Specific impacts on policy and practice will include: • Development of a series of best practice guidelines for policy makers, commissioners and service delivery, identifying ways to address issues of equality and diversity and to improve access to / delivery of EoLC services to LGBT elders. • Feeding our findings into evidence based teaching for practitioners. • Development of materials to assist in raising public awareness of the issues for use at practitioner and user-led conferences.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.2 END OF LIFE CARE
Health categories: GENERIC HEALTH RELEVANCE
Title: Supporting family carers to enable patient discharge from acute care at end of life: qualitative study with carers and professionals to adapt evidence-based carer assessment to acute care settings
Funder: Marie Curie

Abstract: Background Discharge from hospital at end of life relies heavily on family carers’ ability and willingness to help care for the patient. The purpose of the project is to investigate how support for carers at discharge may facilitate successful discharge for the patient. Aims To improve carer support to facilitate successful patient discharge by • investigating the content, timing and format of support required by carers at patient discharge • using findings to adapt an evidence-based carer support needs assessment tool to the acute care setting and integrate it into a pathway to facilitate timely and appropriate patient discharge Methods Qualitative study investigating carers’ and professionals’ perspectives on carer support needs at discharge and the utility and role of a Carer Support Needs Assessment Tool (CSNAT) in supporting carers, conducted within the catchment area of three NHS Trusts serving a diverse demographic population. Carer sample: A purposive sample of 30-36 bereaved and current carers will be recruited to provide both retrospective reflections and immediate perspectives on discharge. Bereaved carers will be identified through retrospective linkage of data on planned discharge and patient deaths. Carers will be contacted by letter and interviewed 6-9 months post bereavement. Current carers will be identified through palliative and complex discharge teams, approached and interviewed on the wards and followed up in the community. Professional sample: A purposive sample of 48 hospital and community staff will be recruited via the three NHS Trusts from identified, key informants involved in discharge. To improve access and participation we will offer several focus groups, local to participants (up to 10), and telephone interviews for those unable to attend the groups. Interview and focus group protocols: Protocols will move from (a) broad exploration of carer-related concerns surrounding discharge to (b) investigation of CSNAT’s ability to encompass these concerns, and when and how it may be used in the process of discharge to improve carer support, preparation and involvement in decision making. How the results will be used Four workshops will bring together hospital and community staff and carers to discuss preliminary findings and assist in the adaptation of CSNAT for acute care and the development of a protocol that can be integrated into a pathway procedure for acute care discharge. In addition to general dissemination, the amended CSNAT and protocol will be further piloted and evaluated in acute care in planned, future projects.


Research activity codes: 7.2 END OF LIFE CARE;7.3 MANAGEMENT AND DECISION MAKING
Health categories: GENERIC HEALTH RELEVANCE
Title: Ubiquitination as a transient modification in regulated protein trafficking
Funder: Medical Research Council

Abstract: This project aims to further our knowledge of the role that ubiquitin plays as a trafficking signal through the endosomal system. Ubiquitination is a post translational modification that can alter a protein's fate. Ubiquitination targets proteins to the degradative lysosome, both from the cell surface and from the trans Golgi network (TGN). This pathway serves to attenuate many signalling pathways by down-regulating ubiquitinated cell surface receptors. In some cases, deubiquitinating enzymes (DUBs) serve to fine-tune this down regulation by rescuing some receptors from this fate allowing them to recycle to the plasma membrane. We have recently demonstrated that ubiquitination is required for the regulated trafficking of the facilitative glucose transporter GLUT4. Ubiquitination does not result in GLUT4 being delivered to the lysosome, but rather its sequestration away from the general endosomal system, in a specialised store, from where it is delivered to the cell surface in response to an insulin signal. We now aim to build on this study, our unpublished data, and work from others to test a novel hypothesis describing a cycle of ubiquitination/deubiquitination that serves to divert GLUT4 from the TGN to lysosome pathway into its specialised store. This work will not only further our understanding of GLUT4 traffic and ubiquitin as a sorting signal, but will also serve as a paradigm for other regulated trafficking pathways that underpin many physiological processes, such as those involved in hormone secretion, neurotransmission, antigen presentation and cell division. This study will be performed in the model 3T3-L1 adipocyte cell line using widely used cell biology approaches and will pursue 3 main objectives. 1. Characterisation of the ubiquitin-dependent trafficking step of GLUT4. 2. Characterisation of the role of the deubiquitinating enzyme USP25 in GLUT4 traffic. 3. Identification of the ubiquitin ligase responsible for ubiquitinating GLUT4.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Mechanism and function of organization of secretory cargo export from the endoplasmic reticulum.
Funder: Medical Research Council

Abstract: This proposal seeks to define the molecular basis of the organization of the exit point for secretory cargo from the endoplasmic reticulum. We have identified two key proteins that interdependently function in this step and propose to define their relationship using a combination of molecular cell biology and in vitro approaches. Our background in imaging underpins both sides of this proposal and we have engaged key collaborators to advance those aspects with which we are less familiar. COPII-dependent trafficking of secretory cargo from the ER to the Golgi represents the first membrane trafficking step in eukaryotic cells. In metazoan, this event is organized spatially at discrete sites on the endoplasmic reticulum (ER) membrane called transitional ER (tER). In recent years, we showed that these sites are defines in mammalian cells by Sec16. This protein serves as an organizer defining the site of assembly or other COPII proteins during vesicle formation. The lab of Jon Audhya has now identified TFG as a direct mediator of Sec16 clustering at tER sites. Audhya's initial work from C elegans leaves many questions as to the role of TFG - whether at the tER itself of further downstream in directed movement of vesicles. We propose to define the interdependent roles of TFG and Sec16 in mammalian cells - our hypothesis is that they act together to define the tER both functionally but also structurally. We propose to reconstitute this in vitro to determine the molecular basis for tER site assembly. We also have evidence that these proteins act in concert to direct collagen secretion and we will explore this avenue using a series of well established assays. Together these experiments will define the molecular basis for the organization of the transitional ER and to address why this organization relates to function.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Fascin-dependent control of nuclear plasticity in invading cells
Funder: Medical Research Council

Abstract: Cell migration is fundamental in the control of embryonic morphogenesis, tissue homeostasis, repair and inflammatory responses. Consequently, inappropriate migratory movements can result in autoimmune diseases, defective wound repair, or tumor cell metastasis. Cancer cells migrate alone or in small groups to spread from the primary tumour and are able to migrate to distal organs where they can continue to proliferate to form a second tumor mass. Cancer cell migration is regulated by adhesion signalling to drive dynamic actin remodelling. Fascin is an actin-bundling protein that is low or absent in normal human epithelia; its up-regulation correlates with poor prognosis in human carcinomas. Fascin localizes to and stabilizes actin-rich protrusions to promote cell migration. We have previously shown that the actin-bundling and pro-migratory properties of fascin are in part regulated by protein kinase C and the small GTPase Rac. However, very little is known about other regulators of fascin function or activity. Through a mass spec screen we have identified the nuclear envelope protein nesprin-1 as a novel binding partner for fascin. Our preliminary data supports a role for this complex in regulating nuclear shape in cells invading in 3D matrices. We hypothesise that this novel complex acts to control nuclear rigidity and plasticity, thus enabling tumour cells to navigate through complex tissues during invasion. Using a combination of biochemical and state-of-the-art microscopy approaches we aim to characterize the nesprin-fascin interaction further at the molecular level and to determine the upstream regulators responsible for dictating assembly of the complex. We will also define the role of the nesprin-fascin interaction in regulating nuclear shape, actin assembly and cell invasion in 3D matrices. Data arising from this study will provide important novel insight into the regulation of fascin and targets for future design of therapies to target invasive tumour cells.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE