ORIGIN aims to deliver more effective, photonics-enabled, brachytherapy for cancer treatment through advanced real-time radiation dose imaging and source localisation. This will be achieved by the development of a new optical fibre based sensor system to support diagnostics-driven therapy through enhanced adaptive brachytherapy. A 16-point optical fibre sensors system will be developed, for Low Dose Rate (LDR) and High Dose Rate (HDR) Brachytherapy, with sensitivity of 150 counts/Gy for LDR- and 2500 counts/mGy for HDR- BT alongside a dedicated data acquisition system providing a dose mapping system with a spatial resolution of 0.5mm (HDR) and 3mm (LDR) and time resolution of 0.1s (HDR) and 0.5s (LDR), with 5% uncertainty. This is a 50% improvement in uncertainty over existing systems. Further interrogation of the optical signal will provide real-time monitoring of the radiation source location during treatment. The ORIGIN system will be integrated into existing clinical brachytherapy treatment planning and delivery systems to confirm that the dose prescribed to the tumour is achieved, whilst ensuring the dose to organs at risk (OARs) is within acceptable limits. This will provide for optimised dose-led, patient-oriented, personalised treatment plans leading to improved patient outcomes and prevention of treatment errors, with the potential to reduce the overall risk of treatment error by 55%. The optical fibre radiation dosimeters will be further optimised for improved optical signal collection efficiency, higher signal-to-noise ratio (SNR) and repeatable high volume fabrication. Taking manufacturability into consideration from the outset will ensure that ORIGIN establishes Europe at the fore of brachytherapy system development and photonics manufacturing.

Endocrine-disrupting chemicals (EDCs) disturb lipid and glucose metabolism in several metabolically active organs such as liver and pancreas besides being able to interfere with many aspects of hormonal action. There is accumulating evidence linking EDCs or their mixtures with an increased incidence of obesity, atherosclerosis, and type 2 diabetes. Developmental exposure to EDCs can exert life-long, even transgenerational effects and affects the susceptibility to many diseases. However, the metabolic effects of EDCs are still poorly understood and the lack of mechanistic data and predictive models of adverse metabolic outcomes of EDCs hinders their risk assessment. The “Novel Effect biomarkers for MEtabolic disruptorS: evidence on health Impacts to science and policy needS” (NEMESIS) consortium brings together experts in toxicology, medicine, risk assessment, and social sciences and humanities to respond to the unmet regulatory needs of EDCs within silico, in vitro, in vivo, epidemiological and systems biology data on EDC-mediated metabolic effects in multifactorial models. We will assess mechanistic data on metabolic disruption in liver and pancreas and how EDCs or their mixtures affect the microbiota, enhanced with data on dose-response relationships and the causality of these actions. In addition, NEMESIS will provide human exposure data of EDCs and explore effect biomarkers for metabolic disruption. NEMESIS’ results will improve assessment of metabolic endpoints in testing guidelines and adopt alternative models to animal testing. Adverse Outcome Pathways (AOP)s and Integrated Approaches to Testing and Assessment (IATA) approaches will be developed to assess adverse metabolic effects of EDCs and improve the risk assessment towards a more holistic approach. Citizens are engaged from the beginning of the project to develop effective risk communication practices on EDCs and to maximize the science-to-policy impact of NEMESIS together with relevant stakeholders.

Chronic infections represent a major cause of human cancer: on a global scale, they are responsible for an estimated 13% of human cancers. Helicobacter pylori (Hp), Hepatitis C virus (HCV), and Human Papilloma Virus (HPV) are responsible together for 75% of these cases, or 10% of total cancer burden [De Martel et al., 2020]. Occupation health surveillance is mandatory in all European countries: although the mechanisms of its implementation vary between the countries, these programs are in general aimed at diagnosing and preventing work-related diseases. Prevention of occupational cancers has therefore been a component of occupational health surveillance. In recent years, however, there has been a movement towards including in occupational health surveillance aspects of health promotion which are not occupational in a strict sense. This approach stems from several considerations: (i) the contact between the worker and the health professional in charge of the surveillance can be seen as a privileged opportunity for health promotion in general; (ii) through the worker, the health promotion initiative may reach other groups of the population; (iii) because of the periodic nature of the visits entailed by the occupational health surveillance, it is possible to efficiently implement follow-up mechanisms. The conceptual framework of the proposed research is based on the incorporation into on-going occupational surveillance schemes of primary prevention programs against infection with Hp, HCV and HPV. The overarching objectives of the proposed research are: - to conduct a series of pilot projects aimed at assessing the effectiveness (including cost-effectiveness) of incorporating primary prevention interventions against Hp, HCV and HPV into existing occupational surveillance systems in high-risk populations, including its impact beyond the workers directly involved in the pilot projects; - to identify barriers and bottlenecks for the implementation of such interventions. This action is part of the Cancer Mission cluster of projects on ‘Prevention and early detection'.