Recent evidence demonstrates that cancer is overtaking cardiovascular disease as the number one cause of mortality in Europe. This is largely due to the lack of preventative measures for common (e.g. breast) or highly fatal (e.g. ovarian) human cancers. Most cancers are multifactorial in origin. The core hypothesis of this research programme is that the extremely high risk of BRCA1/2 germline mutation carriers to develop breast and ovarian cancer is a net consequence of cell-autonomous (direct effect of BRCA mutation in cells at risk) and cell non-autonomous (produced in distant organs and affecting organs at risk) factors which both trigger epigenetic, cancer-initiating effects. The project’s aims are centered around the principles of systems medicine and built on a large cohort of BRCA mutation carriers and controls who will be offered newly established cancer screening programmes. We will uncover how ‘cell non-autonomous’ factors work, provide detail on the epigenetic changes in at-risk tissues and investigate whether these changes are mechanistically linked to cancer, study whether we can neutralise this process and measure success in the organs at risk, and ideally in easy to access samples such as blood, buccal and cervical cells. In my Department for Women’s Cancer we have assembled a powerful interdisciplinary team including computational biologists, functionalists, immunologists and clinician scientists linked to leading patient advocacy groups which is extremely well placed to lead this pioneering project to develop the fundamental understanding of cancer development in women with BRCA mutations. To reset the epigenome, re-establishing normal cell identity and consequently reducing cancer risk without the need for surgery and being able to monitor the efficacy using multicellular epigenetic outcome predictors will be a major scientific and medical breakthrough and possibly applicable to other chronic diseases.

We aim to reduce the burden of tobacco-related lung diseases. Our approach is to integrate inexpensive tobacco cessation strategies of proven efficacy into TB control programmes. This has three advantages: a) Preventing non-communicable diseases as well as reducing TB-related deaths; b) TB patients are more likely to quit tobacco than healthy smokers – ‘teachable moments’; and c) in the absence of specialist infrastructure, an approach to ‘piggyback’ cessation on existing programmes is a desirable policy imperative. We will first assess the effectiveness and cost-effectiveness of tobacco cessation strategies in helping TB patients to quit and improving their TB outcomes - the effectiveness goal; and then explore how best these strategies can be delivered, sustained and scaled-up – the implementation goal. We propose six work packages for Bangladesh, Nepal and Pakistan - high TB and tobacco burden countries. WP1 Development & Feasibility: To optimise the delivery of tobacco cessation strategies within TB programmes (focus group discussions [FGD], interviews, surveys, expert panel workshops) WP2 & 3 Effect and economic evaluation: To assess the effectiveness and cost effectiveness of cytisine with behavioural support vs. behavioural support alone on tobacco cessation and TB outcomes (randomised controlled trial [RCT]) WP4 Process evaluation: To study the design and delivery of the tobacco cessation strategies (FGD, observations, exit interviews) WP5 Context evaluation: To study the influence of contextual factors on the RCT outcomes (lit. review, interviews, surveys, analysis) WP6 Scale up & Sustainability: To assess sustainability of the cessation strategies and identify the likely costs, obstacles and opportunities for scaling these up (FGD, interviews, cost and outcomes analysis) Our ambition is that by studying the ‘real world’ influences on the implementation and success of tobacco cessation we will be able to translate our findings into benefits for patients

While Cardiovascular diseases (CVD) are the main cause of death worldwide, they are responsible for half of all deaths in Europe. The overall ageing of the European population and improving survival of patients with coronary heart disease has created a large population of older adults eligible for secondary prevention. Despite the established efficacy of cardiovascular medications, suboptimal adherence reduces their effectiveness and is the primary reason for suboptimal clinical benefit, contributing significantly to worsening of diseases and deaths at the population level. SECURE will be the first trial testing the efficacy of a fixed dose combination (FDC) polypill for secondary cardiovascular prevention in the elderly population (≥ 65 years old). The main objective is to evaluate the potential benefit of the FDC as a component of a cost-effective, globally available and comprehensive treatment strategy for secondary prevention of cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, stroke, and hospitalisation requiring revascularisation) as compared to standard therapy (the three components of the polypill given separately). As part of the secondary endpoints, SECURE will compare the effect of both strategies on adherence and intermediate measures of risk factor control such as lipids and blood pressure. Importantly, it will also measure the pharmacoeconomic impact of the FDC intervention as well as regional differences in all outcomes. The five-year project will thus involve subjects from seven different countries: Spain, Italy, France, Germany, Hungary, Poland and the Czech Republic. The findings and conclusions obtained in SECURE will allow the drafting of clinical guidelines and recommendations that will provide useful guidance and will serve as a reference framework for all stakeholders involved in tackling major challenges related to secondary prevention and treatment of chronic diseases in the elderly population.

The prevention and care of chronic diseases are among the priorities of the EU's current health strategy. Chronic Kidney Disease (CKD), one of the most common chronic degenerative diseases, is often accompanied by high mortality and morbidity, and it has a high socio-economic impact. On the other hand, with the incidence rate of 13,3 million cases per year, Acute Kidney Injury (AKI) is a major contributor to the global health burden and the global death toll of this disease is 1,7 million deaths yearly. Amidst the rising tide of AKI and CKD burden, the global nephrology workforce has failed to expand in order to meet the growing healthcare needs of this vulnerable patient population, thus cooperation at an international level would be necessary to boost workforce and sustainable models of healthcare delivery. The Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) will develop a European Strategic Partnership between Universities and clinic centres specialized in diagnostic and interventional nephrology with the overall objective (1) to stimulate the appeal in nephrology among learners at European level and (2) to improve the educational continuum, in order to respond to the unmet need to develop a policy framework for the provision of high-quality services within European health system.SPECIFIC OBJECTIVES developing innovative and multidisciplinary educational path with a patient-centered approach focusing on diagnostic and interventional nephrologyfostering the knowledge transfer from research to clinical practice in order to tackle risk management in health carestrengthening the cooperation among Universities and clinical centres in order to boost innovation and exchange of best practicespromoting the positive aspects of nephrology careers at European levelThe present proposal will jointly develop 4 curricula: Molecular Pathology, Vascular Access, Ultrasound and Peritoneal Dialysis.TARGET: 40 junior nephrologists (≤ 40 years old)