The STOP project will bring together a range of key health and food sector actors to generate scientifically sound and policy-relevant evidence on the factors that have contributed to the spread of childhood obesity in European Countries and on the effects of alternative policy options available to address the problem. This evidence will complement, systematise and partly reframe the findings of an established body of prior research by leveraging the latest scientific findings. The STOP project will translate the evidence gathered and generated into: a. A comprehensive set of indicators and a measurement framework for the regular monitoring of relevant dimensions of childhood obesity, its determinants and actions to address it in all European Countries; b. Policy toolkits, providing practical guidance and tools for the design and the implementation of effective and sustainable policies and actions by governments and private sector stakeholders; c. A novel, evidence-based, multi-stakeholder framework, to enable and promote a shared understanding of problems and solutions by key actors, relying on a structured process leveraging cognitive mapping and policy simulations validated by empirical data and empowering individual actors to take action within an agreed accountability and monitoring framework. STOP will generate timely, comprehensive and policy-relevant measures of childhood obesity in all European countries; it will generate new trans-disciplinary evidence of the role of key determinants of childhood obesity, emphasising the role of different environments surrounding children, from analyses of detailed multi-dimensional measurements taken on several established EU children cohorts, including epigenetic and biological mediators of obesity; it will assess the impacts of policies and actions to address childhood obesity based on observations in the same children cohorts and policy simulations of the health, social and economic outcomes of policies.

URBANE addresses an important and timely question: how does the urban environment impact the developmental origins of multimorbidity? Neurodevelopmental, cardiometabolic and respiratory adverse health outcomes are increasingly prevalent at young ages, with diseases such as obesity and asthma affecting up to four out of ten children in Europe. Multimorbidity, the co-occurrence of two or more health conditions, in childhood is thus becoming a major public health problem with short- and long-term consequences. Although it is well known that environmental hazards play a role in the development of diseases, the contribution of the complex environment in which we grow up and live on the development of multimorbidity remains unclear. URBANE addresses this knowledge gap. The project will leverage the resources of the Portuguese population-based birth cohort Generation XXI and follow an exposome-wide approach to the study of urban environmental impact on childhood multimorbidity. For that, the project will use a wide range of geospatial urban exposure data (e.g., air pollution, and characteristics of the urban natural and built environment) and multiple adverse health outcomes (e.g., high blood pressure, obesity, asthma, behavioral problems) collected at the vulnerable early stages of the lifecourse (pregnancy and childhood). The project will explore socioeconomic status and gender differences and also assess whether DNA methylation changes and dysregulation of hormone leptin explain the urban environmental impact on multimorbidity. URBANE will contribute to the discovery of urban environmental priorities, vulnerable subpopulations and aid in the identification of underlying mechanisms. URBANE is highly interdisciplinary, and fosters knowledge exchange. The project aligns with major EU strategies related to the urban environment and non-communicable diseases prevention, and thus its results are expected to be of high relevance for researchers, policy makers, and society.

ATHLETE aims to develop a toolbox of advanced, next-generation, exposome tools and a prospective exposome cohort, which will be used to systematically quantify the effects of a wide range of community-level and individual-level environmental risk factors on mental, cardiometabolic, and respiratory health outcomes and associated biological pathways during the first 2 decades of life, to implement acceptable and feasible exposome interventions, and to translate the resulting evidence to policy recommendations and prevention strategies. ATHLETE will establish a prospective exposome cohort, including FAIR data infrastructure, building on Europe’s most comprehensive already existing exposome data (18 cohorts in 12 European countries). ATHLETE will systematically characterise the effects of the exposome on early organ development, health trajectories, and biological pathways (metagenomic, metabolomic, epigenetic, ageing, and stress pathways), longitudinally from early pregnancy through adolescence. Innovative tool development will focus on: 1) complete and accurate measurement of multiple environmental risk factors (external/urban, chemical, physical, behavioural, social) through new targeted and untargeted exposure science approaches, 2) development of advanced statistical and toxicological strategies to analyse complex multi-dimensional exposome data, 3) development of interventions to reduce personal exposures, co-produced with the community, and 4) estimation of the societal impact of the exposome by calculating costs and child health impacts. ATHLETE’s strong focus on the vulnerable early stages of the life course, widespread general population exposures and common non-communicable diseases, its use of a large body of existing exposome data and expertise, its strong emphasis on knowledge translation, its development of an open online toolbox and its close collaboration in the European Human Exposome Network ensure that the objectives are achievable and highly relevant for future research and policy. ATHLETE is part of the European Human Exposome Network comprised of 9 projects selected from this same call.

Current anti-tuberculosis (TB) drug regimens face serious limitations at times of increasing antimicrobial drug resistance. Fortunately, for the first time for centuries, several novel anti-TB compounds are available for clinical evaluation. As the traditional approach to testing these in multiple combination regimens is too slow and inefficient new approaches of clinical phase 2 study designs are required if we are to meet the targets of the WHO EndTB strategy to save the lives of millions into the near future. Our consortium brings together a unique group of European and international leaders in TB research and leading industry partners. Together we will provide the necessary comprehensive range of expertise to meet the demands of the UNITE4TB scientific research agenda. Specifically, we will develop a new global standard for phase 2 TB clinical trial designs, utilising simulation tools to identify optimal doses in phase 2A trials and apply a multi-arm multi-stage adaptive randomised controlled 2B/C trial design capable of rapid and simultaneous evaluation of the best candidate regimens. Our innovative phase 2 trials will be performed to the highest regulatory standards, incorporating state-of-the-art microbiology, biomarker investigation and clinical pharmacology. We will take advantage of existing global TB clinical trial networks with the capacity to enrol patients at an unprecedented pace and number across four continents. Artificial intelligence/machine learning technologies will be applied to validate state-of-the art molecular and imaging tools as treatment decision biomarkers with the aim of establishing new, real-time outcome measures. Our consortium will evaluate 3-5 new chemical entities (NCEs) at phase 2A and up to 17 novel combination regimens in phase 2B/C. Our objective is to identify those that have the greatest chance of success in subsequent definitive phase 3 clinical trials and of becoming the global gold-standard TB regimens of the future.

Rapid progress in information and biotechnologies offers the promise of better, personalized health strategies using rich phenotypic, environmental and molecular (omics) profiles of every individual. To capitalize on this great promise, key challenge is to relate these profiles to health and disease while accounting for high diversity in individuals, populations and environments. Both Europe and Canada have long-term investments in population-based prospective cohort studies providing essential longitudinal data. These data must be analysed in unison to reach statistical power, however, presently cohort data repositories are scattered, hard to search and integrate, and data protection and governance rules discourage central pooling. EUCAN-Connect will enable large-scale integrated cohort data analysis for personalized and preventive healthcare across EU and Canada. This will be based on an open, scalable data platform for cohorts, researchers and networks, incorporating FAIR principles (Findable, Accessible, Interoperable, Reusable) for optimal reuse of existing data, and building on maturing federated technologies, with sensitive data kept locally and only results being shared and integrated, in line with key ELSI and governance guidelines. Widespread uptake will be promoted via beyond state-of-the-art research in close collaboration with leading cohort networks, focused on early-life origins of cardio-metabolic, developmental, musculoskeletal and respiratory health and disease impacting human life course. To address challenges of sustainability and curation, we will deliver innovative solutions for distributed, low-cost data harvesting and preservation, community curation/harmonization, privacy protection, open source bioinformatics toolbox development, and international governance. EUCAN-Connect platform and collaborations will be coordinated through BBMRI-ERIC (EU) and Maelstrom Research (Canada) to sustain long-term benefits to science and citizens worldwide.