NIHRDataInsights/HRCSData huggingface dataset:
Award Title: Clinical Training Award Cycle 4 2018
Funder: Cancer Research UK

Abstract: Clinical Training Award: The Cancer Research UK Cambridge Centre will bring together the diverse strengths of Cambridge to create novel practical applications that will improve the detection and treatment of cancer. The Centre will develop programmes in early detection, and integrative cancer medicine with the aim of developing new therapeutic approaches (http://www.cruk.cam.ac.uk/).


Research Activity Codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health Categories: CANCER AND NEOPLASMS
Award Title: Clonal dynamics and mutational landscape of normal and cancerous tissues in cancer predisposition syndromes
Funder: Medical Research Council

Abstract: This study aims to investigate the consequences of TP53 inactivation in malignant transformation, as well as in the development and maintenance of healthy tissues, using tumour and histologically-normal samples from Li-Fraumeni syndrome (LFS) individuals. LFS is a rare familial cancer syndrome caused by heterozygous germline pathogenic variants in TP53, which confer an increased risk of early onset cancer in diverse tissues of origin. Specifically, we will implement a multidisciplinary approach combining spatially-resolved, multi-omic technologies with single-clone and single-molecule resolution to delineate the patterns of mutations and mutational processes, clonal evolution and phylogenetic relationships of cells in LFS individuals. In Work Package (WP) 1 we will analyse samples from diverse histological structures (at least 25) collected post-mortem from ~10 LFS individuals. We will perform laser capture microdissection (LCM) combined with low-input whole-genome sequencing (WGS) on clonal structures, and NanoSeq on non-clonal tissues. The resulting data will allow us to study the consequences of pathogenic TP53 variants on the behaviour of normal cells and clones during life across diverse tissues. In WP2, we will apply WGS on multiple regions extracted using LCM from diverse tumours arising in LFS patients. We will primarily focus on studying the early events triggering the clonal expansion of malignant clones in an LFS background, and will compare the patterns of somatic alterations observed in benign clonal expansions with those leading to malignant transformation in LFS individuals, and in sporadic tumours driven by TP53 inactivation. In WP3, we will perform RNAseq and EMseq (low-input bisulfite sequencing) on the LCM samples collected in WP1 and WP2 to study transcriptional changes and epigenetic modifications in both histologically-normal tissues and tumour samples from LFS individuals.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: CANCER AND NEOPLASMS
Award Title: Co-design and feasibility testing of an Holistic Approach for Rehabilitation and Medical OptimisatioN after IntenSivE care (HARMONISE)
Funder: Public Health Agency, NI

Abstract: Background: People experience a variety of physical, psychological and cognitive complications following discharge home after critical illness. Rehabilitation may be able to address these problems, however there is currently no standard evidenced-based approach for rehabilitation following discharge home after critical illness in the UK, and the level of support people receive depends on where they live. People may also have new clinical needs following ICU admission, including multimorbidity and polypharmacy which are strongly associated with readmission and mortality risk. They may also experience social problems, including unemployment and the need for additional support at home from family or carers. Remote rehabilitation programmes have been shown to be clinically- and cost-effective in settings outside critical illness. However, emerging evidence indicates some people may be unable to participate in a fully remote intervention due to logistical and personal factors. Research questions: Is it possible to 1) co-design a feasible and acceptable personalised multicomponent intervention which addresses rehabilitation, clinical and social needs of patients after critical illness, and 2) deliver the intervention through a hybrid of remote and face-to-face care based on individual patient needs? Methods: Two scoping reviews will inform intervention development by identifying 1) clinical conditions following critical illness which are amenable to treatment (treatable traits) and 2) factors impacting participation in rehabilitation programmes following critical illness. I will then work with patients, relatives and healthcare professionals to co-design a multicomponent intervention, (called HARMONISE) with a personalised hybrid of face-to-face and remote delivery. Using a mixed methods approach, the feasibility and acceptability of the HARMONISE multicomponent intervention will be evaluated. Anticipated impact and dissemination: I will share the findings with patient groups, healthcare professionals, and researchers. If the HARMONISE intervention is feasible and acceptable, it will lead to a trial to evaluate clinical- and cost-effectiveness.


Research Activity Codes: 7.1 INDIVIDUAL CARE NEEDS
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: Communication-centered Parent-mediated treatment for Autism Spectrum Disorder in South Asia (COMPASS).
Funder: Medical Research Council

Abstract: Objectives: Phase 3 trial of the clinical and cost-effectiveness of the 'Parent-mediated intervention for Autism Spectrum Disorders in South Asia-Plus' (PASS+) intervention in addition to treatment as usual (TAU) compared to treatment as usual (TAU) alone in India. The study will take the already successfully piloted PASS+ intervention to scale.  Design: Two centre, two arm single (rater) blinded random allocation parallel group study of experimental treatment plus TAU against TAU alone. Primary endpoint 9 months, follow-up 15 months. Primary outcome: autism symptom severity (blind-rated Brief Observation of Social Communication Change). Secondary outcomes: include parent-child communication, child adaptation and QoL, parental wellbeing. Primary analysis intention to treat; planned secondary analysis of proposed mediators of treatment effect. Health Economic evaluation will estimate the cost-effectiveness of the intervention from a societal perspective using a QoL index valued to allow calculation of QALYs. Participants: 240 children aged 2 to 9 years with ASD, recruited from Autism clinics in two tertiary government hospitals in New Delhi, India.  Treatments: PASS+ is a manualised and piloted adaptation of the UK Pre-school Autism Communication Therapy (PACT), that uses video-feedback with parents to help them enhance social communication in their autistic child. It will be delivered by existing health system frontline workers, in 12 home-based sessions. TAU in the two recruitment centres is delivered through weekly autism clinics, an eclectic mix of behavioural therapy approaches which are delivered once a month delivered by specialists. The duration of therapy is based on the families' ability to follow up, adherence is under 50%.  Outcome: Generalizability and policy impact will be maximized through embedding the trial in routine facilities with embedded primary health-care workers, and using our policy influence to disseminate the findings.


Research Activity Codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: MENTAL HEALTH
Award Title: Community based interventions to improve HIV outcomes in adolescents: a cluster randomised trial in Zimbabwe
Funder: Wellcome Trust

Abstract: HIV infection is the leading cause of mortality among adolescents in sub-Saharan Africa. Adolescents are the only group in which HIV-associated mortality is rising despite the global scale-up of antiretroviral therapy (ART). Adolescents fare disproportionately poorly across the HIV care continuum compared to other age-groups: the prevalence of undiagnosed HIV is substantially higher, and coverage of and adherence to ART is lower, resulting overall in worse virological outcomes. Current services are thus insufficient for achieving optimal outcomes, and complementary strategies are required to meet the UNAIDS 90-90-90 targets.
 
 
 
The aim is to investigate whether a community-based, multi-component intervention incorporating HIV prevention, HIV testing, ART initiation, and ongoing adherence support, can improve virological suppression rates among HIV-infected adolescents in a high HIV prevalence setting
 
 
 
The objectives are to:
 
 1. Carry out a cluster-randomised trial in Zimbabwe comparing a) facility level HIV services with b) facility-based services plus the community-based intervention. The primary outcome will be proportion of HIV-infected adolescents in the community with an HIV viral load <1000copies/ml
 2. Evaluate the cost and cost-effectiveness of the intervention.
 3. To conduct a process evaluation of the intervention’s implementation, to inform components required for sustainability and scalability

Lay Abstract: HIV is the leading cause of death among adolescents in Africa. There are many reasons for this, including difficulties in getting HIV testing and in taking treatment. Current HIV services, which are mainly delivered in healthcare facilities, are clearly not sufficient, and additional strategies are required to help adolescents living with HIV to get diagnosed, and to support them to take their HIV treatment.
 
 
 
The proposed project will evaluate an approach that will incorporate HIV testing, facilitate linkage to HIV treatment services for adolescents (aged 12-20 years) who test HIV-positive, and provide support to improve their capacity to take HIV treatment. The intervention will be delivered in communities in Zimbabwe, which has a high prevalence of HIV, and will complement existing services in health facilities.
 
 
 
The study objectives are:
 
 1. To carry out a trial to investigate whether the intervention is effective at improving the proportion of HIV-infected adolescents in the community whose HIV is well-controlled with treatment.
 2. To investigate how cost-effective the intervention is in improving the number of years lived in full health by the beneficiaries of the intervention.
 3. To carry out a process evaluation to understand how well the intervention is implemented

Research Activity Codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health Categories: INFECTION
Award Title: Complete humanisation of adaptive cellular immunity in the mouse: Vaccine and therapeutic TCR discovery
Funder: Wellcome Trust

Abstract: Adaptive cell mediated immunity is one of the central components of immunological homeostasis. While the basic mechanisms are conserved the components that encounter antigen are subject to rapid evolutionary change driven by species specific pathogens co-evolving with the host and divergence of the host genome against which antigen receptors are negatively selected. Thus, epitopes that direct protective immunological responses differ between species. Consequently, translation of results obtained from immunisations conducted in model organisms to humans
 
remains a pernicious issue.
 
 
 
The long term goals of this proposal are to identify and validate vaccine candidates and discover therapeutic T cell receptors
 
 
 
To achieve these goals we will build mice in which all components of adaptive cellular immunity have been humanised, building on the technical success, biological insights and health-care benefits accrued from the construction of a mouse with a complete human immunoglobulin repertoire. We will use this humanised mouse as platform to isolate therapeutic T cell receptors for acute myeloid leukaemia in which the nucleophosmin gene has been mutated. In an independent and parallel work stream we will systematically explore the Plasmodium falciparum genome to identify vaccine candidates protective against the liver stage of the pathogen.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: INFLAMMATORY AND IMMUNE SYSTEM;GENERIC HEALTH RELEVANCE;INFECTION
Award Title: Comprehensive workplace intervention for cancer prevention in China
Funder: Medical Research Council

Abstract: Workplace cancer prevention interventions have been widely conducted in some high-income countries. However, the effective implementation of these evidence-based strategies is lacking in low- and middle-income countries (LMICs). It is an urgent task for LMICs to overcome the implementation barriers to reduce the cancer burden.   This research aims to adapt existing strategies of workplace health promotion in the prevention and control of cancer and build a scalable model in China. The research is designed as a stepped wedge cluster randomised controlled trial. We will recruit 15 workplaces with approximately 1500 employees across three low and middle economic cities of China. All the workplaces will be staggered into intervention stage randomly for three steps and will receive a 12-months' intervention and then maintain to the end of the project. The duration of the project is 48 months. A comprehensive workplace intervention package addressing major behaviour risks of cancer for the employees, such as tobacco and alcohol use, unhealthy diet, obesity and lack of physical activity, will be developed and implemented through multilevel involvement strategies covering individual programmes, organizational policies and supportive environment with the support of a mobile application. The primary outcome is the change in modifiable behaviour risk factors of cancer after the intervention. The research will also assess the changes of attendance of employees, the healthcare costs of organizations and the occurrence of cancer of employees in the long term.  The comprehensive workplace intervention for cancer prevention in low- and middle-income regions of China, if proven to be effective and cost-effective, will not only provide evidence and recommendations to the national policies on cancer prevention in China, but also have a great potential to be adapted by other LMICs.


Research Activity Codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health Categories: CANCER AND NEOPLASMS
Award Title: Computational models of dynamics in brain networks underlying action selection
Funder: Medical Research Council

Abstract: Recent advances in brain computer interfaces open new possibilities of normalizing pathological neural activity underlying symptoms of Parkinson’s disease. For example, patients are now implanted with closed-loop DBS systems including multiple recording and stimulation contacts, allowing the independent control of multiple neural populations. However, to take advantage of this technology, it needs to be understood what patterns of activity are produced during action selection in the healthy brain, because restoring such patterns should be a goal of closed-loop DBS systems. Furthermore, we need to understand how to stimulate with multiple contacts to achieve desired neural dynamics. Such insights are currently missing, so there is a need to develop a theory providing them. The overall aim of the programme is to provide mathematical description of the dynamics of brain networks underlying action selection and to understand how these dynamics can be modified by treatments for disorders affecting the system. The programme has three specific goals that focus on the three neural signals are particularly distorted in Parkinson’s disease. The first goal is to develop a theory of dopamine function in learning and action planning. Understanding its function is important because Parkinson’s disease is caused primarily by the dysfunction and death of neurons releasing dopamine, and medications increasing dopamine level are the most common treatment for Parkinson’s disease and many psychiatric conditions. The second goal is to describe the dynamics of beta oscillations during action planning. These oscillations are thought to be related with the symptoms of Parkinson’s disease, because in Parkinson’s disease the duration of intervals with high beta oscillations is longer when patients are off medications and their movement difficulties are more pronounced. The third goal is to identify control policy supressing tremor for closed-loop DBS with multiple contacts. To achieve these goals, the computational models will be developed based on data gathered in experimental neuroscience and neurology groups within our MRC Unit, and the models will inform development and refinement of interventions, through a collaboration with the neural engineering group.


Research Activity Codes: 1.4 METHODOLOGIES AND MEASUREMENTS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: NEUROLOGICAL
Award Title: Computer Vision and IoT for Personalised Site Monitoring Analytics in Real-Time (CV-SMART) towards Behaviour-Based Safety
Funder: Innovate UK

Abstract: The "One Death is too Many" (Donaghy, 2009) catchphrase for the UK zero-harm agenda shows that no fatal accident is admissible on construction sites. Modern H&S problems can only be solved from a combination of cultural, social and technical perspectives. A lot of work has been done from cultural and social perspectives, but the technical perspective has been massively ignored (particularly the use of digital technologies). There is a need to take a closer look at how social and technical systems overlap, and how the growing overlap influences H&S on construction sites. However, current approaches address the socio-technical overlap of H&S management separately despite the evidence that suggests that the Zero Harm target and H&S best practices cannot be achieved without effective digitisation in addition to appropriate social interventions (NBS, 2018). The consortium will, therefore, leverage state-of-the-art in computer vision and deep learning (convolutional neural networks and recurrent neural networks) to develop a Computer Vision and IoT for Personalised Site Monitoring Analytics in Real-Time (CV-SMART) for behaviour-based safety in confined construction sites.



CV-SMART will automatically detect, recognise and track diverse interacting heavy machines, building components, site activities, and site workers in real-time to (i) enforce H&S best practices and (ii) identify H&S risks and unsafe site practices such as failure to wear safety gadgets (helmets, harness, and personal protective equipment PPE), congested work areas, improper movement of heavy equipment, and improper working positions). CV-SMART will provide a digital visualisation platform, which will employ state-of-the-art in advanced visualisation for Intuitive user interaction and reporting. CV-SMART will alert on-site workers, safety managers, and site managers of H&S best practices and impending risks at the forefront of onsite operations with a minimal human intervention using IoT-enabled devices.


Research Activity Codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health Categories: INJURIES AND ACCIDENTS
Award Title: Control of patterning, growth and apoptosis by developmental signals
Funder: The Francis Crick Institute

Abstract: My lab investigates how signalling landscapes are established in a developing epithelium and how they are coordinated to control patterning, growth and apoptosis. The signals we are studying include Wnts, TGF-, Hedgehog, EGFR, JNK and steroid hormones. Most of our work uses the Drosophila wing as a model system. Our activities focus on the following specific projects. (1) We study how signalling gradients are formed, paying particular attention to Wnts and TGF-, as they exemplify two classes of morphogens, hydrophobic (Wnts) and water soluble (TGF-). We are devoting significant energy to understand how Wnts, which are appended with palmitoloeate are handed over from secreting to receiving cells. At the same time, we are reconstituting a morphogen gradient from an inert molecule (GFP) to identify, in combination with mathematical modelling, the basic features that allow the spread of morphogens in epithelia. (2) Our studies of Wnts have led us to characterise Notum, a deacylase that inactivate Wnts. In order to identify areas where Notum might be a good drug target, we are studying the phenotype of mice lacking Notum, with a focus on neurodegeneration, blood brain barrier maintenance, bone homeostasis and metabolism. This work is in close collaboration with others who are devising small molecule inhibitors of Notum. (3) We are dissecting (experimentally and through modelling) the signalling network that enable cell fate adjustments during tissue morphogenesis. (4) We study how tissue growth if modulated during development. We are analysing how patterning signals (Wingless, a Wnt and Dpp, a TGF-) control the cellular growth control machinery. To this end, we are developing optogenetic and thermo-sensitive means of controlling signal transduction so that we can identify the immediate early targets that promote growth. In addition, we are investigating whether the activity of these patterning signals might be affected by growth, as this could account for scaling (the coordination of pattern information and tissue size). Tissue growth is not only regulated by patterning signals. It is also modulated by tissue architecture and nutritional status. We are investigating how these pro-growth inputs are coordinated with those from patterning signals. (5) Finally, upon the request of a patient, we are modeling a ribosomopathy in flies and are well on the way to uncover the basis on cellular stress in conditions of inadequate ribosome activity.


Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: Controlling COVID19 through enhanced population surveillance and intervention (Con-COV): a platform approach
Funder: Medical Research Council

Abstract: Con-COV Technical Summary. Background: COVID19 is a rapidly evolving complex issue that requires near real time data, analyses and multidisciplinary team science to devise, implement and evaluate a wide variety of inter- and cross-sectoral interventions in order to minimise population harm.   Aims: to integrate multiple sources of data to produce timely and responsive analyses to:  1) provide detailed insight into the evolving pandemic in the general population, vulnerable groups and diverse settings (health care workers, social care workers, care homes and schools); 2) support and undertake evaluations of the effectiveness of adopted counter measures as these evolve; 3) rapidly inform policy and practice decision makers; and 4) communicate effectively with the general public. Methods: We will build on the existing total population 3.2 million Wales Multimorbidity Cohort funded by HDRUK/MRC to create the greatest in-depth COVID19 population study with data enhancements on vulnerable groups and settings, serology and viral genomics, scale the breadth and depth of disciplines involved and support embedded evaluations of countermeasures.  Our multi-agency team includes individuals from Welsh Government, Public Health Wales, academics from multiple disciplines and members of the public.  Deliverables: Reports on exposure risks, incidence and outcomes to Welsh Government COVID19 Technical Advisory Group (TAG) and onwards to SAGE; share models with multiple UK groups including SPI-M, triallists, and the Royal Society DELVE initiative; and provide evaluations of natural experiments in policy and practice. Timeline: We will report weekly to TAG and monthly to funders, recognising the time-sensitive requirements needed to inform evidence-based control and exit strategies.


Research Activity Codes: 7.3 MANAGEMENT AND DECISION MAKING
Health Categories: INFECTION