Find out about the winners of the 2019 grant round and their projects by clicking through the tabs below.
Dawkins & Strutt grant to assist research in the field of gastroenterology
Professor Mark McAlindon BM BS, B Med Sci, MRCP, DM
Sheffield Teaching Hospitals NHS Trust
Non-invasive assessment of the upper gastrointestinal tract using a joystick-controlled magnet robot and capsule endoscopy
Dyspeptic symptoms (indigestion) are amongst the most common encountered in general practice. A diagnosis may be sought by performing gastroscopy, a procedure involving the insertion of a flexible endoscope through the mouth and into the upper gastrointestinal tract, which is performed in over 1% of the population per annum. It is invasive, uncomfortable and patients may be given intravenous sedatives for the procedure to be performed. Yet most gastroscopy procedures identify no minor or irrelevant abnormalities. A non-invasive test which is able to identify the minority of patients who need gastroscopy to obtain samples may be better tolerated, performed without sedation and potentially outside the hospital setting.
A capsule endoscope is a small device which can be swallowed. It contains batteries, light emitting diodes and an imaging device which takes pictures as the natural contractions of the gastrointestinal tract propel it onwards. In this study, we will use a robot magnet suspended above the patient to steer a capsule around the stomach using two joysticks. We will compare patient tolerance and overall acceptability of capsule endoscopy with gastroscopy and perform an economic analysis to see if this new technology could reduce the cost of investigation of patients with dyspepsia.
Doris Hillier grant to assist research into rheumatism and athritis
Mr Benjamin Dean BM BCh PhD FRCS
Towards better treatment for people with base of thumb osteoarthritis
Around 6% of people aged 45 and over in the UK have sought treatment about osteoarthritis of the hand, and base of thumb osteoarthritis makes up a significant proportion of this burden. Patients typically complain of pain at the base of the thumb, dysfunction, and difficulty participating in certain activities occupationally, domestically and recreationally. There is a lack of evidence on how best to treat people with this condition and this includes the widely used intra-articular steroid injection.
This project aims to gather information upon which future research can be carried out to better enable effective treatment of people with this condition. This will include a systematic review of what is known about the effectiveness of injection therapy, a service evaluation project to define current pathways and treatments, and qualitative work to explore the attitude of both patients and clinicians to future research in this area. These findings will inform the development of a study protocol which will be co-designed with patient and public volunteers. We believe this work will lead to a successful funding application to conduct a large multicentre randomised controlled trial which will ultimately lead to better evidence to guide patient-centred care in people with thumb osteoarthritis.
H C Roscoe grant to assist research into the elimination of the common cold and/or other viral diseases of the human respiratory system
Mrs Shadia Khandaker
University of Liverpool
Immune profiling and high-throughput taxonomic analysis of the nasopharyngeal microbiota of infants presenting with acute viral respiratory tract infection.
Research in the past decade has convincingly shown that the bacterial communities found in the nasopharynx have an important contributory effect to upper respiratory tract infections (URTIs). However, it remains unclear how exactly the nasopharyngeal bacterial microbiota might influence the course of viral illnesses, and vice versa. In the current study, we bring the focus on Respiratory syncytial virus (RSV) and Human Rhino virus (HRV) – the two most common global causes of acute respiratory tract infections (ARIs) in paediatric patients.
We propose to exploit high-throughput species-level metagenomic sequencing in a large sample collection of nasopharyngeal isolates collected from a UK-based cohort of infants younger than 6 months of age. In addition to metagenomics analysis, we planned to perform a comprehensive immune profiling using highly sensitive multiplex immunoassays. We anticipate that our investigations will help identify differences in bacterial population diversity at the species level between mono-infected, co-infected and uninfected patients, in association with specific immune biomarkers.
The outcome of our proposal includes the discovery of a microbial fingerprint protective of URTI and/or the concomitant discovery of immune traits that either abate or enforce homeostasis in the nasopharyngeal mucosa.
Helen H Lawson grant to assist paediatric research
Dr Tamsin Newlove-Delgado MBChB, MPH, MRCPsych, MFPH, PhD
University of Exeter
& Dr Oana Mitrofan PhD
East Devon Child & Adolescent Community Mental Health Services
Understanding the journey of children with Sydenham’s chorea: Surveillance study of Sydenham's chorea presenting to paediatricians and child and adolescent psychiatrists in the UK and the Republic of Ireland
Sydenham’s chorea (SC) is a complex neuropsychiatric condition largely affecting children and adolescents. Symptoms include abnormal body movements (known as chorea), which range from mild to severe and may affect a child’s ability to carry out activities of daily living such as eating and walking. Children with SC also often experience emotional and behavioural symptoms, such as anxiety, obsessions and compulsions, which may be long-lasting and disabling.
SC is currently considered a ‘rare disease’ in developed countries; but little is known about how many children nowadays are affected by the disorder, what happens to them after diagnosis, or about their needs. Given the impact on the lives of patients and families, there is a clear need for a study of new cases to fill this gap.
In this study we will collect data on the numbers, characteristics, management and outcomes of new cases of SC in children in the UK and Republic of Ireland, using the British Paediatric Surveillance Unit and the Child and Adolescent Psychiatry Surveillance Service.
We hope that our findings will contribute to raising awareness amongst clinicians, speeding up diagnosis, planning effective services, providing better information for families, and ultimately, to improving patient care.
Dr Claire Meek MBChB, BSc, MSc, MRCP, FRCPath, PhD
& Dr Kathryn Beardsall MBBS, DCH, MRCP, MD, FRCPCH
University of Cambridge
Can continuous glucose monitoring improve the identification of neonatal hypoglycaemia after gestational diabetes? A pilot study
Children born to women with diabetes in pregnancy have a difficult start in life, due to the high frequency of perinatal complications including neonatal hypoglycaemia. Neonatal hypoglycaemia impacts on acute care after birth and prolonged or occult neonatal hypoglycaemia can cause neurocognitive impairment, including long-term deficits in cognition, visual acuity and executive function.
Current protocols to identify neonatal hypoglycaemia are based on intermittent heel-prick glucose tests and are known to substantially underdiagnose clinically-important episodes of neonatal hypoglycaemia. This pilot study aims to assess if continuous glucose monitoring [CGM] of babies can improve identification of neonatal hypoglycaemia after pregnancy complicated by gestational diabetes, and whether maternal CGM during labour can identify infants at particular risk of neonatal hypoglycaemia. Improving the detection of neonatal hypoglycaemia may help to reduce the long-term neurocognitive burden for these children.
This study will recruit women who are enrolled on the DiGest Study, a randomised controlled trial of calorie intake in pregnancy complicated by gestational diabetes in overweight and obese women taking place in the East of England. The information obtained will be used to plan a larger study of neonatal hypoglycaemia after gestational diabetes such as a randomised controlled trial of intrapartum or neonatal CGM versus standard care to reduce perinatal morbidity after gestational diabetes.
Josephine Landsell grant to assist research into heart disease
Dr Elaine Soon MBBChir, MRCP, PhD
University of Cambridge
Investigating the role of GCN2 in the pathogenesis of pulmonary vascular disease: Creating disease-specific cell models
Pulmonary hypertension is an umbrella term covering a host of deadly diseases characterised by an increase in the blood pressures of the blood vessels supplying the lungs. If left unchecked, the median survival of patients with idiopathic pulmonary arterial hypertension is less than 3 years. The classic gene defect associated with pulmonary hypertension is in bone morphogenetic protein (BMP) receptor type II. More recently, mutations in other genes have also been implicated in pulmonary hypertension. I am investigating how mutations in a particular gene coding for a protein called general control nonderepressible 2 (GCN2) cause pulmonary hypertension. GCN2 normally responds to amino acid starvation to activate the Integrated Stress Response. There has been no previous indication that GCN2 is involved in human cardio-pulmonary disease. My hypothesis is that GCN2 deficiency promotes the development of PAH via dysregulated BMP and/or inflammatory signalling. My overarching project involves determining the mechanism linking GCN2 and BMP signalling and exploring the consequences of GCN2 deficiency on vascular cell behaviour and cardiopulmonary physiology.
The Josephine Lansdell grant will allow us to employ a research assistant to develop vascular cell models bearing disease-causing mutations in GCN2 and BMPR2. If successful, this will aid in the understanding of the mechanisms by which GCN2 and BMPR2 deficiency lead to pulmonary vascular disease and will help test potential ways to treat GCN2 and BMPR2 deficiency. If there is a demand for these cell lines from other pulmonary vascular research centres we may eventually be able to create a depository to share these resources.
J Moulton grant to assist research into mental health through clinical trials
Dr Golam Khandaker MBBChir, MRCP, PhD
University of Cambridge
& Professor Nicholas Barnes BSc (Hons), PhD
University of Birmingham
A Randomised Controlled Trial of Tocilizumab in Patients with Depression and Low-grade Inflammation: The Insight Study.
Epidemiological and genetic studies suggest that low-grade inflammation, particularly a proinflammatory cytokine called interleukin 6 (IL-6), could play a role in the development of depression. Cytokines are protein molecules that act as mediators of immune response and are key to fighting infection, but chronic increase in these protein levels can be harmful.
This research will focus on the interactions between the immune system, brain and mind. We will be supporting the Insight study – a proof-of-concept randomised controlled trial of a novel anti-inflammatory drug – to test the idea that reducing inflammation in a sub-group of patients with depression could help to improve mood and memory.
The study will provide evidence that the IL-6 is linked with causing depression, so could be a treatment target, and generate vital data to inform assessment in a larger trial. The findings could potentially transform our understanding of the causes for depression and current approaches to treatment and prevention of the illness.
The James Trust grant for research into asthma
Dr Hans Michael Haitchi
& Dr Matthew Coleman
University Hospital Southampton
Multiomic approach to study the impact of maternal allergic asthma during pregnancy on asthma related mediators including ADAM33 in biologic samples collected during caesarean sections
Asthma is common and affects about 4.3 million adults and 1.1 million children in the UK. Maternal asthma during pregnancy is a strong risk factor for development of asthma in children and the asthma gene ADAM33 (A Disintegrin and Metalloproteinase 33) is associated with asthma, airway twitchiness and decline in lung function in children in early life.
Previous mouse studies by our group have discovered that a soluble form of the ADAM33 protein is increased in fluid that surrounds the baby in the womb (amniotic fluid) and in the lungs from newborn mouse pups from dams with an allergic airway inflammation during pregnancy.
This study will now test how the mothers’ asthma during pregnancy changes asthma related mediators such as ADAM33 in amniotic fluid, blood and placenta, collected during elective caesarean birth that may explain why children born to asthmatic mothers have an increased risk of developing asthma. Several possible asthma mediators will be measured using multiple novel research techniques.
Work from our group suggests that if ADAM33 is switched off or prevented from being released, the features of asthma will be suppressed, making ADAM33 a novel target as new therapy to prevent or treat asthma.
Kathleen Harper to assist research into antimicrobials
Dr Maria Dudareva & Dr Matthew Scarborough
Oxford University Hospitals NHS Foundation Trust
Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): A Randomised Open Label Multi-Centre Clinical Trial
Adults with bone or joint infections usually receive very long courses of antibiotics by mouth (oral) or into a vein (intravenous) following surgery. Overusing oral and intravenous antibiotics is harmful, because bacteria become resistant to antibiotics, people react to antibiotics (allergies, diarrhoea and vomiting), and because of the cost of providing long antibiotic courses.
It is safe to give antibiotics directly into the bone or joint, as a paste or beads, during surgery. This is called local antibiotic therapy. Local antibiotic therapy may mean that long treatment with oral or intravenous antibiotics is not needed to cure infection.
The SOLARIO randomised controlled trial aims to compare short and long courses of oral or
intravenous antibiotics for patients already having local antibiotic therapy to treat bone
and joint infection. The main aim is to see whether local antibiotic therapy with short courses of oral or intravenous antibiotics is as effective at preventing infection coming back. The trial will also allow other unanswered questions about bone and joint infection to be investigated. If short oral or intravenous antibiotic courses are enough to treat bone and joint infections, this will make treatment easier for patients in future.
Lift into Research grant to support at their inception innovative ideas that may progress to an application for funding to support a research project
Dr Hannat Akintomide MBBS, MFSRH, MSc (Hons), PgCert (MedEd)
Newcastle upon Tyne Hospitals NHS Foundation Trust
Copper intrauterine contraception discontinuation in women aged under 30
Women aged under 30 experience poorer sexual health contributed by higher rates of contraceptive non-use, failure and discontinuation. Copper intrauterine contraceptives (IUDs) are discontinued by up to 70% of younger women in the first year of use, significantly greater than the 30% discontinuation rate in older age groups. Identifying which IUDs currently in use are associated with better outcomes could reduce discontinuation in younger women.
This research will investigate the problems younger IUD users report, subsequent healthcare they require, and associated healthcare costs based on IUD type that may lead to their higher discontinuation rates. It will analyse evidence in the public domain and unpublished data to identify the types of IUDs that are associated with better outcomes in younger women.
The research findings are expected to be the first of its kind to support improvement, innovation and cost savings in IUD provision. Identifying IUDs associated with better continuation rates, fewer adverse effects and lower cost consequences could inform clinical decision and policy making that will potentially benefit thousands of younger women. This could also improve contraceptive choice, care provision, method continuation and ultimately public health.
Dr William Bolton
Low-cost wire-tension sensing technology to improve the use of Ilizarov circular frame fixators for long bone fractures
To manage long bone leg fractures, surgeons can use circular ring fixators called Ilizarov frames. During use it is important to know how the bones are healing over time. One way to do this is to measure the tension in the wires used to hold the bones in place. This is useful to monitor healing, but also, if the wires are too tight, the wires may snap, too loose, and the patient has increased pain and risk of pin site infection. This pre-clinical study that the Lift into Research grant will support aims to answer the following research question: What is the relationship between Ilizarov wire tension and the physical wire vibration (the analogue of audio ‘pitch’), and can appropriate tension be directly measured and quantified using a novel vibration sensor. Ensuring the correct tension is used when the frame is deployed may reduce the incidence of complications, and during the use of the frame (which may be on the patient for many months) these sensors may be able to tell surgeons more about how the fracture is healing.
Dr Aidan Hanrath
Royal Victoria Infirmary Newcastle
Characterising the interaction between Zika virus and type I interferon in CNS cells
Zika virus is increasingly recognised as an important global health concern. It is linked to severe problems in pregnancy such as abortions, poor foetal growth and reduced brain development causing microcephaly. There are no known effective medications to treat or prevent Zika virus infection.
Neural progenitor cells are brain stem cells which are crucial for developing healthy brain tissue in the growing foetus. These cells are very vulnerable to cell death when infected with Zika virus compared to other human cells, but it is unclear why this is. I hypothesise that they are vulnerable because they have a less active basic infection defence mechanism called type I interferon, compared to other cells.
To investigate this, I will study the effects of Zika virus on normal cells compared to cells which have a disabled type I interferon receptor, in neural progenitor cells and other types of human cell. I will also try to find out the reason these cells die, and whether they can be protected if given extra type I interferon.
Medicines which affect type I interferon in humans are already available, finding out its role could identify new options for the treatment and prevention of Zika virus disease.
Dr Anthony Thaventhiran
Barts and the London School of Medicine and Dentistry
Discovering novel therapeutics for Acute Traumatic Coagulopathy
Approximately 17,000 people in the UK die from injury each year, and uncontrolled bleeding is the most significant cause of preventable death. Most of these patients are under the age of 40. Acute Traumatic Coagulopathy (ATC) can exacerbate bleeding and is present in 25% of trauma patients. Current non-specific treatment with blood components and tranexamic acid is ineffective, with mortality over 45% higher in those affected.
The protein C pathway is immediately activated in trauma patients, causing ATC and leading to a failure of blood-clotting or the clots breaking-down too quickly (systemic anticoagulation and fibrinolysis). Through understanding the mechanism by which this problem occurs, new drug treatments can be developed to directly target the effects of protein C. I have established a preclinical model to act as a platform to test candidate drugs that increase clot stability. Pilot experiments have already identified initial drug candidates that will be validated before use in bleeding trauma patients.
Novel therapeutics which target the underlying pathology of ATC have the potential to improve outcomes from trauma haemorrhage.
Dr Samuel Tingle
2,4-Dinitrophenol treatment during Normothermic Machine Perfusion to optimise steatotic livers prior to transplant
Liver transplant is a lifesaving treatment for hundreds of people in the UK each year. However, a lack of optimal donated organs remains a major hurdle. The most common reason for a liver to go unused for transplant is increased levels of fat (termed steatosis). The increased levels of fat make the liver unhealthy and more sensitive to the damage caused by storing an organ outside of the body.
One attempt to increase the quality of donated livers has been the use of machines which can pump blood based solutions through the liver whilst it remains outside of the body (‘normothermic machine perfusion’). Our research will use machine perfusion to deliver a fat shedding drug (2,4-dinitrophenol; DNP) to donated human livers which have been deemed too fatty for transplant. We will investigate liver fat levels, alongside markers of liver injury and organ viability.
If DNP is able to defat steatotic human livers and improve their viability, this could improve outcomes for patients who would receive a steatotic graft. In addition it could safely expand the donor pool by allowing the transplant of livers currently deemed too fatty for transplant.
Dr James van Oppen
University Hospitals Leicester NHS Trust
Development and evaluation of face and content validity of a preliminary Patient-Reported Outcome Measure for the emergency care of older people with frailty (PROM-ECOP)
Older people living with frailty are better-served by the incorporation of holistic, person-centred approaches into existing fast-flowing and protocolised emergency care. A Patient-Reported Outcome Measure (PROM) would embed a person-centred ‘patient voice’ into research and quality improvement initiatives. This could also support the communication of individuals’ preferred healthcare outcomes to emergency care professionals in order to inform clinical consultations and management plans.
Research describing the preferred emergency care outcomes of older people has often excluded those who have frailty. A framework of expectations among older people in general is focussed on person-centred approaches rather than technological innovation, and includes comfort, symptom-relief, security, explanations, autonomy in decision-making and involvement of relatives. This work will use interviews and qualitative analysis to expand the framework to include perceptions from people with frailty. The expanded framework will be used as a reference to assimilate and devise a preliminary PROM, which will be iteratively improved and tested in future work.
Margaret Temple grant to assist research into schizophrenia
Dr Jyothika Kumar & Dr Mohammad Katshu
University of Nottingham
Towards precision treatment in schizophrenia: investigating the role of glutamate and glutathione in persisting deficits
Schizophrenia and related disorders, with a prevalence of about 5 per 1000, are estimated to cost £6.5 billion to the UK by 2026, nearly half of which is due to lost employment costs. Interestingly, the functional outcome and quality of life of patients with schizophrenia is predicted by persistent negative symptoms, for which there are currently no treatments available. Our previous work suggests that the levels of neurochemicals involved in long-range neurotransmission and inflammation, glutamate and glutathione, are low in patients with predominantly negative symptoms.
This project will use high-resolution (7 Tesla) Magnetic Resonance Spectroscopy, a non-invasive brain imaging technique, to measure the levels of glutamate and glutathione in a large cohort of patients with schizophrenia with varying degrees of persisting symptom dimensions: positive, negative and disorganised. The aim is to examine the relationship between these different symptom dimensions and glutamate/glutathione levels in the brain to improve our understanding of the underlying neurobiological mechanisms. This will help us identify any sub-group/s of patients who show the most prominent neurochemical abnormalities and are, hence, more likely to benefit from interventions that modulate glutamate/glutathione levels allowing for effective stratification of patient groups in future clinical trials.
Scholarship Grant to assist research into the mental health of medical students
Dr Antonia Rich BSc, MSc, DPsych (Health), FHEA
& Dr Asta Medisauskaite BSc, MS (distinction), PhD, AFHEA
University College London
Deconstructing the wounded learner: a mixed-methods exploration of medical students’ mental health
The prevalence of mental health issues in medical students is of great concern, with research showing that 27.2% of medical students are depressed or have depressive symptoms. Understanding the causes of medical students’ distress in order to develop solutions to remedy the situation is of paramount importance. In addition, previous studies focus mainly on depression and burnout, so finding out more about the different types of mental health issues students experience is necessary as required support might differ depending on the specific mental health issue.
We will recruit a geographically diverse group of medical students from Great Britain for our mixed-methods (longitudinal survey, documentary analysis, and interviews) study. This study will measure the types and prevalence of mental health issues in medical students and identify learning and environment factors that provoke or prevent mental health issues. The research will identify medical school factors which are associated with mental health issues, from the findings we will develop recommendations for Medical Schools in Great Britain to promote a culture that enhances wellbeing.
TP Gunton grant to assist research into public health relating to cancer
Dr Amitava Banerjee
University College London
Using large-scale routine data to monitor and improve ethnic inequalities in cancer and cardiovascular disease
Ethnic inequalities have been identified in both cardiovascular diseases (CVD) and cancer, which frequently coexist, eg treatment for cancer may be associated with heart disease. National cancer and CVD registries have been linked to electronic health records in the VICORI (Virtual Cardio-Oncology Research Institute) programme. The Global Burden of Disease (GBD) Study has allowed estimation of current and future burden for cancer and CVD, among other diseases, in England and globally. For ethnicity, quality of reporting and impact on disease burden, as well as healthcare, across cancer and CVD is not well-studied.
We will assess whether individuals from BME (black and minority ethnic groups) with overlapping cancer (lung, colorectal and breast cancers) and CVD (heart attacks and coronary bypass surgery) are less likely to have access to healthcare and worse outcomes than white British individuals. First, we will study quality of ethnicity reporting in VICORI/GBD databases, comparing with routine hospital data. Second, we will use VICORI and GBD to identify disease burden and access to services by ethnic groups. By highlighting reporting of ethnicity in healthcare data, and burden of cancer and CVD in BME groups, we will identify health inequalities and future targets for public health improvement.
Vera Down grant to assist research into neurological disorders
Dr Rimona Weil
University College London Hospital
Markers of disease activity in Dementia with Lewy Bodies
Dementia with Lewy bodies (DLB) is a common and debilitating form of dementia with prominent falls, visual hallucinations and slowness of movement. Estimated prevalence is 20% of all cases of dementia. DLB shares many clinical and pathological features with Parkinson’s disease and Parkinson’s disease dementia and the conditions are widely considered either end of a spectrum of one disease. Disease modifying treatments are emerging, but a critical gap is the lack of quantitative metrics of disease activity. These will be vital for clinical trials of emerging therapies to be tested in DLB.
This project will use a multimodal approach to identify markers of disease activity in DLB. We have previously shown that quantitative visual measures and retinal thickness are linked with risk of dementia in Parkinson’s disease. Here we will test these measures alongside advanced neuroimaging and blood biomarkers in DLB. This research will enable us to validate these quantitative measures as markers of disease activity to enable clinical trials to slow progression of DLB.
BMA Foundation for Medical Research
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