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    NIHR funding alert

    The following new funding opportunities are available:

    Clinician Scientist Award

    Round 18

    Efficacy and Mechanism Evaluation Programme An NIHR and MRC partnership

    18/55 Improving Safety and Efficacy Through Targeted Drug Delivery

    18/56 Neurodegenerative Disorders

    18/57 Type 2 Diabetes

    18/58 EME Researcher Led

    18/59 Mechanisms of action of health interventions

    Health Technology Assessment Programme

    18/24 Early reoperation for patients with residual glioblastoma

    18/25 Microstructural scaffold insertion following microfracture for chondral knee defects

    18/26 Surgical management of pressure ulcers

    18/27 Alternative bisphosphonate regimens for the prevention of osteoporotic fracture in adults

    18/28 Paediatric wrist fracture

    18/29 Preventing job loss in people with long term physical health conditions

    18/30 Hysteroscopic removal of retained placenta

    18/31 Discontinuation of growth hormone treatment in pubertal children

    18/32 Management of orthostatic hypotension

    18/33 Valuing the benefits and harms of antenatal and new born screening programmes in the UK

    18/34 Routinely used interventions for improving attachment in infants and young children

    18/35 Behavioural intervention to treat anxiety in adults with autism and  moderate to severe learning disabilities

    18/36 Anticonvulsant augmentation of antipsychotic medication in the management of psychosis

    18/37 Repair of digital nerve injury

    18/38 Selective serotonin reuptake inhibitor for the treatment of anxiety in adults with autism

    18/39 Earlier active management of ovarian hyperstimulation syndrome

    18/40 Short-term use of benzodiazepines for the acute management of acute low back pain

    18/41 Clinical and cost effectiveness of alternative urinary catheter design

    18/42 Cystic fibrosis 18/43 Rotation of the fetal head at full cervical dilatation

    18/44 Pre-hospital pain management

    18/45 Proton pump inhibitor therapy for refractory gastro-oesophageal reflux symptoms    

    18/46 Pharmacological management of post-traumatic seizures  

    18/47 Outpatient cervical ripening for induction of labour

    18/48 Radiotherapy in first-line treatment of diffuse large B-cell lymphoma

    18/49 Radiofrequency denervation for low back pain

    18/50 Frail older people in primary care

    18/51 Extended duration haemodialysis

    18/52 Management of isolated or incidental subsegmental pulmonary embolism

    18/53 Clozapine for children and young people with treatment resistant schizophrenia

    Integrated Clinical Academic Programme for non-medical healthcare professionals An NIHR and Health Education England partnership

    Round 4

    Public Health Research Programme

    18/60 Researcher-led (including complex health and care needs in older people and London Devolution Deal highlight notices)

    For more information and a list of all current funding opportunities, please visit the NIHR website.

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    Cancer Genome Atlas Update

    Cancer is caused by changes to DNA that affect the way cells grow and divide. There are at least 200 forms of cancer, with many subtypes. Identifying the changes in each cancer’s complete set of DNA—its genome—and understanding how these changes interact to drive the disease will lay the foundation for improving cancer prevention, early detection, and tailored treatments.

    The Cancer Genome Atlas (TCGA) was launched in 2005 by NIH’s National Human Genome Research Institute (NHGRI) and National Cancer Institute (NCI) to map the key genomic changes in 33 types of cancer. The multi-institution collaboration focused not only on cancer genome sequencing, but also on different types of molecular data collection and analysis, such as investigating gene and protein expression profiles (when they are turned on or off) and associating them with clinical and imaging data. With over $300 million in total funding, the project involved more than 150 researchers at more than two dozen institutions.

    The PanCancer Atlas sums up the work accomplished by TCGA in a collection of 27 papers across a suite of Cell journals. Three summary papers published on April 5, 2018, recap the core findings, and companion papers report more in-depth explorations.

    The first summary paper describes a technique called molecular clustering that groups cancers based on their molecular characteristics rather than their tissue of origin. The scientists analyzed gene expression, DNA modifications, protein expression, and other data from about 10,000 tissue samples representing 33 different types of cancer. The team identified 28 distinct clusters based on molecular similarities. Although most of these clusters could be linked to tissue of origin, many contained different cancer types. The most diverse group had 25 cancer types. These findings could help guide the treatment of many cancer patients whose tumors are of unknown origin.

    The second paper presents findings on oncogenesis, the processes that lead to cancer development and progression. The authors focused on three critical oncogenic processes: the DNA mutations that drive cancers; the influence of DNA alterations on gene and protein expression; and the interplay of tumors with their surroundings, particularly immune cells. The results will help in the development of new treatments for a wide range of cancers.

    The final paper details genomic alterations in 10 key signaling pathways that control the stages of the cell’s life cycle, growth, and death. The researchers found that 89% of tumors had at least one significant alteration in these pathways. About 57% of tumors had at least one alteration that could be targeted with currently known drugs and 30% had multiple targetable alterations. These findings will help researchers explore treatments with more tailored approaches, such as using a combination of drugs to target multiple pathways at the same time.

    “TCGA was the first project of its scale to characterize—at the molecular level—cancer across a breadth of cancer types,” says Dr. Carolyn Hutter, NHGRI team lead for TCGA. “At the project’s infancy 10 years ago, it wasn’t even possible, much less on such a scale, to do the types of characterization and analysis that were being proposed. It was a hugely ambitious project.”

    “The PanCancer Atlas effort complements the over 30 tumor-specific papers that have been published by TCGA in the last decade and expands upon earlier pan-cancer work that was published in 2013,” says Dr. Jean Claude Zenklusen, director of the TCGA Program Office at NCI.

    Read more at the National Institutes of Health website.

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    PHG joins University of Cambridge

    PHG Foundation is proud to​ announce that as of 1 April ​2018, it will be part of the University of Cambridge.

    The School of Clinical Medicine will host the PHG Foundation, a unique combination that will continue and strengthen the Foundation’s successful policy development work in the application of science to benefit health and society.

    Commenting on the new association, the Vice-Chancellor of the University of Cambridge Professor Stephen Toope said:

    This initiative brings together the unique research strengths of both the PHG Foundation, which has led such exemplary thinking around how science can best work for health, and the University’s world-leading School of Clinical Medicine…I am enormously grateful to the Hatton Trust for making this possible, and look forward to the University and the Foundation jointly addressing some of the major health challenges facing society today.

    The Foundation looks forward to working with the Clinical School, the PHG Foundation’s Director, Mark Kroese commented:

    The Clinical School is a world-leading source of medical excellence, research and leadership, and we are very much looking forward to working more closely with colleagues there as we continue to provide multidisciplinary perspectives on the policy issues around cutting-edge medical interventions and technologies.

    The association has been made possible by a philanthropic gift from the Hong Kong based Hatton Trust, which recognises the University’s global eminence in science, medicine and the humanities alongside the pioneering policy development work of the Foundation. The PHG Foundation has received major funding from the Hatton Trust.

    The Chair of the Trustees of the Foundation, Dr Ron Zimmern said:

    I am delighted to see the work of the PHG Foundation over the last twenty years recognised by the University of Cambridge, and I am sure that the unique combination of a policy think-tank and a Clinical School will be highly successful. 

    Looking ahead, the PHG Foundation will also build upon existing and new links with other parts of the University, including the Cambridge Institute of Public Health, the Centre of Law, Medicine and Society at the Faculty of Law, the Centre for Research in the Arts, Social Humanities, the Cambridge Institute for Public Policy and Hughes Hall. 

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    MRC to study childhood arthritis

    Medical Research Council-funded scientists are beginning a five-year study of childhood arthritis and its linked eye inflammation called uveitis, with the aim of better understanding how to treat the complex condition, which affects one in 1,000 under-16 year olds in the UK.

    With nearly £5 million in funding (including £0.5m from Arthritis Research UK), the CLUSTER childhood arthritis study will team scientists at the UCL Great Ormond Street Institute of Child Health (ICH) and other UK institutions* to follow the health trajectories of 5,000 children with the condition.

    The initiative is one of four ‘stratified medicine’ projects being funded by the MRC, which is investing £15 million in studies that will establish ground-breaking approaches in treating prostate cancer, kidney disease, alcoholic hepatitis and childhood arthritis. Stratified medicine, also referred to as personalised medicine or precision medicine, is an emerging approach for disease diagnosis and treatment that considers patients’ genes, environment and lifestyle to create tailored therapies instead of a one-size-fits-all approach.

    Childhood arthritis can cause long-term disability and poor quality of life – sometimes well into adulthood. If it isn’t diagnosed and treated early, patients may require hip and knee replacements, are significantly shorter than their peers, and some end up in wheelchairs. For those patients who also have uveitis, a condition where the inside of the eyes become inflamed, there is also a significant risk of vision loss and blindness.

    Currently, young people diagnosed with arthritis in the UK are given a single drug therapy, but it works in only about 50% of cases. The remaining half must try other treatments, one after the other, to find a therapy which works for them. Along the way, they may experience painful side effects, time out of school and even a worsening of their symptoms.

    Ultimately, the researchers in the trial hope to identify a simple biomarker test that will:

    • Pave the way to new treatment options, identifying potential new therapies and eventually the trialling of new drugs which work better with fewer side effects
    • Help doctors define the right medication for the right duration for each individual patient on the first try. Identifying the right treatment ensures symptoms are managed and that the condition doesn’t develop into lifelong disability
    • Identify which children are at risk of uveitis, a serious eye-inflammation which affects 15% those with childhood arthritis. Currently, patients visit eye specialists every three to six months to screen for this secondary condition that can lead to blindness
    • Project long-term outcomes for these children – scientists will track patient health over decades, so they can better predict what may be ahead for these children

    Lead researcher, Professor Lucy Wedderburn at the UCL ICH and Great Ormond Street Hospital, said: “Using a stratified medicine approach could be a gamechanger in childhood arthritis and its associated uveitis. A biomarker test could lead to methods for accurately predicting the right treatment for the right duration, halting the worsening of symptoms and leading to shorter time to remission. Nothing like that has been done before in this area of research.”

    Eilean MacDonald, an 18-year-old patient, who was diagnosed with childhood arthritis as an 18-month-old baby, is taking part in the study. It took years of trying various medications until she found the right treatment to alleviate her symptoms. She’s now on crutches and requires an ankle replacement this summer.

    MacDonald said: “When you think of arthritis you see a 70-year-old lady with stiff hands, not an 18-month-old baby or a teenager. People don’t believe children can get arthritis but we do. I’ve missed school and had to quit activities I loved because of my condition.

    “This research is so important – it could mean the next generation of kids with childhood arthritis won’t have to go through what I did. They could have the right therapy handpicked for them, reducing the impact it has on their lives. They could have even one piece of their life that’s more consistent and predictable while living with this disease.” 

    Professor Sir John Savill, Chief Executive Officer at the MRC, said: “Stratified medicine is reshaping the medical landscape by taking a patient-first approach that looks at how – and why – different groups of patients respond differently to therapies. Instead of looking for a ‘one-size-fits-all’ solution, stratified medicine is increasing what we know about diseases and how they affect individuals, and applying these findings to current tools in diagnostics and treatment to improve health outcomes. I am particularly pleased to see the potential benefits of this research approach extended to children with a life-changing condition.”

    Dr Natalie Carter, head of research liaison and evaluation at Arthritis Research UK, said: “Twelve thousand children in the UK have juvenile idiopathic arthritisopens in new window (JIA), and this can have a significant impact on their physical, emotional and social well-being. In addition to the pain they experience, over 50% of these children may go on to have severe limitations in movement as adults, limiting their ability to carry out every day tasks. By working in partnership, we can all make a bigger difference for these children living with such a debilitating condition. We are excited to see the results of this project in the future.”

    The Stratified Medicine Initiative is a major part of the MRC’s research strategy. Whether described as stratified, precision or personalised medicine, the research will provide new insights into disease mechanisms to enable better tailoring of existing treatments, and pave the way for the development of new treatments, diagnostics and care pathways.

    *The CLUSTER study includes collaboration with the UCL Institute of Ophthalmology, and scientists from Manchester, Liverpool, Cambridge, Bristol and London. CLUSTER is receiving additional co-funding from GOSH Children’s Charity and Olivia’s Vision, the sole UK charity dedicated to providing information and support to families and patients diagnosed with uveitis.

    The other funded projects include ReIMAGINE, which is developing better screening for prostate cancer; NURTuRE, which is building kidney disease-specific cohorts to rethink the way new drugs are developed and trialled; and a study on alcoholic hepatitis, which is aiming to develop biomarker tests to quantify risk and improve management of the disease.

    Learn more at the MRC website.

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