Between 3 and 42% of patients do not initiate their treatments. Non-initiation and non-adherence are associated with poorer clinical outcomes, more days of sick leave and higher costs. The aim of this research project is to generate an effective, efficient and feasible intervention that improve initiation and adherence and improves clinical symptoms. The long-term benefits in terms of improved health and reduced costs will be evaluated. The results will be disseminated to stakeholders, decision-makers and the scientific community to promote implementation. The intervention is expected to improve the clinical practice, empowering the patient. The project develops an innovative approach to the design and evaluation of behavioural interventions that uses the principles of complex interventions, pragmatic trials and implementation research. Nine interventions to reduce non-initiation have been tested. The interventions were not theory-based and most used simple reminders. The evidence supporting these interventions was low and their impact on clinical symptoms and cost-effectiveness was not assessed. The strengths of the IMA-cRCT study are: 1) the main stakeholders are involved in the design and assessment; 2) IMA intervention is theory-based and has been optimized; 3) the study will assess the impact of the intervention on clinical parameters and cost-effectiveness, which is key to guarantee its transferability; 4) the project involves decision-makers; 5) the pragmatic design increases generalisation and 6) the intervention is easily transferable to other pathologies, populations and countries. As part of the ERC research project, a pragmatic cluster randomized controlled trial (cRCT) will evaluate the short-term effects of the IMA intervention and its cost-effectiveness and Markov models will be constructed to estimate its long-term cost-effectiveness. The results will be disseminated to facilitate its transferability to clinical practice in Spain and Europe.

Childhood cancers are believed to be rooted in aberrant development, a notion supported by their (i) generally low mutational burden, (ii) high prevalence of single (often epigenetic) driver events and (iii) occurrence during confined developmental periods. Yet, the exact origins of developmental tumours remain one of the principal enigmas of pediatric oncology. A prime example are malignant rhabdoid tumours (MRTs): they are astoundingly genomically simple but extremely deadly childhood cancers that arise almost exclusively in the first two years of life, and are driven by biallelic inactivation of the SWI/SNF chromatin remodelling complex subunit SMARCB1 (>95% of cases). We still do not know what determines oncogenic competence upon SMARCB1 loss. In particular we wonder: (1) What are the cell(s)-of-origin of rhabdoid tumours and what is their normal differentiation potential? (2) What is the molecular framework that facilitates oncogenic transformation upon SMARCB1 loss? (3) What is the contribution of the niche (local and systemic) to the acquisition of oncogenic competence? And, considering the epigenetic nature of the oncogenic event, (4) is the oncogenic MRT state reversible, and how? To answer these questions, we will combine state-of-the-art lineage-barcoded single-cell genomics, spatial transcriptomics, single-cell resolution wholemount imaging, CRISPR/Cas9 and epigenomic approaches, as well as integrative computational analyses, using transgenic mouse, induced pluripotent stem cell and patient-derived xenograft rhabdoid tumour models. This project will provide fundamental insights into the cell autonomous and non-autonomous determinants of oncogenic competence upon SMARCB1 loss. Based on our findings we hope to unlock targeted treatments for MRT patients. Importantly, the conceptual and experimental framework we establish will open up new investigative opportunities for a multitude of developmental cancers.

Language is perhaps the most prominent feature that distinguishes humans from the rest of the animal kingdom. Nevertheless, many perceptual and learning mechanisms serving language acquisition are not tailored specifically to language nor to humans. Decades of research have shown that several animal species are equipped with perceptual, cognitive and neural architectures that allow to learn language but only humans end up doing so. The key features and mechanisms that make language learnable by very young humans are still unclear. The GALA project focuses on how humans begin to learn language, exploring the biological nature of the mechanisms at the ‘entry-gate’ of language through a comparative-developmental approach involving nonhuman species, human newborns, infants and adults. Syllables are essential processing units of speech at the onset of language acquisition, through which newborns and infants preferentially encode and organize the speech signal. My proposal is that the mechanisms that allow to parse syllables from speech emerge from evolutionary-ancient sensory processes that likely evolved to compute different inputs in different species. I will explore two alleged universal linguistic constraints responsible for parsing syllables, and shaping the syllabic structure: Maximal Onset Principle (Research Line 1) and Sonority Hierarchy (Research Line 2). I will test such constraints across species, and at distinct stages of human development as well as in distinct sensory modalities, with behavioral and neuroimaging techniques. The GALA project will shed light on the ontogenetic and phylogenetic origins of the mechanisms through which humans access language, and will provide invaluable new knowledge that will bring us closer to understand why are humans the only species so far able to learn language.

Intravenous (IV) therapy is the most performed invasive treatment with 3.8 bn disposables tubes used annually. This procedure is not safe, neither for healthcare personnel nor patients, with serious consequences such as accidental IV dislodgement and Vascular Air Embolism (VAE) generating additional healthcare costs of €43b every year. In addition, there is a growing trend to administer IV infusion at home presenting social and economic benefits to patients with chronic diseases, cancer and, being especially important, to the current aging European population. In views of the situation, there is an urgent need for IV therapy risk reduction by preventing dislodgement, VAE and spill of hazardous fluids/vapours, while simultaneously supporting the ‘bringing care home initiative’. In response, we have developed ReAL, a weak-link tube connection and air removal devices that will make IV therapy more accurate and safer for healthcare personnel and patients by i) preventing accidental dislodgement, and ii) removing harmful air bubbles in a closed system,. ReAL helps patients to receive a more accurate dose with faster recovery, while healthcare providers save money. Providing IV therapy at home has shown a 90% potential cost saving compared to corresponding care provided in the hospital. In this SAFE-Infusion project we aim to disrupt the IV tube market by maturing, testing, and launching the next- generation tube connection and air removal device. Within the first five years post project, we estimate total accident-related cost-savings of €3.3bn for healthcare (i.e., €28 for each €1 spent in ReAL), 57 tonnes of plastic waste saved, €114m in accumulated revenues and €44m in accumulated operating profit for the SAFE-Infusion industry partners together.

Attention Deficit Hyperactivity Disorder (ADHD) affects a significant part of the population and causes considerable behavioural problems, learning limitations in the context of the formal education system and increased chances for social exclusion. Current treatment approaches induce high costs to welfare systems and individuals, while the widespread usage of stimulant medication remains a subject of controversy due to undesirable side-effects. FocusLocus brings together a multidisciplinary Consortium of partners aiming to design and produce market-oriented products and services for ADHD management by leveraging knowledge and technology from previous research and innovation activities. FocusLocus proposes a highly disruptive and innovative game-based intervention, relying on agent-based game mechanics that incorporate learning schemes for mental and motor skill acquisition and behavioural change, adopting multisensory user interaction, featuring personalisation, adaptation, performance analytics and monitoring features, delivered in a dual User Experience (UX) mode. Even though FocusLocus will be designed, tested and evaluated specifically for the case of ADHD management, it is expected that it will also be beneficial to a number of other associated mental, psychological and cognitive disorders and learning disabilities, thus generating a substantial marketing potential. FocusLocus activities will include the deployment of a pilot study for the extensive assessment of the proposed gaming system, the generation of evidence regarding its performance, the documentation of results for further ADHD research purposes and the creation of solid foundations for a marketable product.