The stated goal of RHAPSODY is to define a molecular taxonomy of type 2 diabetes mellitus (T2D) that will support patient segmentation, inform clinical trial design, and the establishment of regulatory paths for the adoption of novel strategies for diabetes prevention and treatment. To address these goals, RHAPSODY will bring together prominent European experts, including the leaders of the diabetes-relevant IMI1 projects to identify, validate and characterize causal biomarkers for T2D subtypes and progression. Our plans are built upon: (a) access to large European cohorts with comprehensive genetic analyses and rich longitudinal clinical and biochemical data and samples; (b) detailed multi-omic maps of key T2D-relevant tissues and organs; (c) large expertise in the development and use of novel genetic, epigenetic, biochemical and physiological experimental approaches; (d) the ability to combine existing and novel data sets through effective data federation and use of these datasets in systems biology approaches towards precision medicine; and (e) expertise in regulatory approval, health economics and patient engagement. These activities will lead to the discovery of novel biomarkers for improved T2D taxonomy, to support development of pharmaceutical activities, and for use in precision medicine to improve health in Europe and worldwide.

Ventricular tachycardia (VT) is an unpredictable and potentially deadly condition and should be promptly treated with catheter ablation and medication, before irreversible and potentially fatal organ damage follows. Unfortunately, this combination of treatments does not prevent VT reoccurrence in 30-50% of VT patients and while they can undergo multiple invasive ablations, technical difficulties or refusal of the patient can lead to a lack of effective treatment options. A promising novel, non-invasive treatment option for VT is stereotactic arrhythmia radioablation (STAR). Besides being non-invasive, STAR can also be used to reach locations that are inaccessible for catheter ablation, which may potentially improve effectiveness of overall VT treatment. Small scale first in men/early phase trials have been performed for STAR, providing proof-of-concept for clinical safety and efficacy. However, patients with recurrent VT are not a homogenous group and each center deals with different inclusion criteria, imaging and/or target definition. Many questions remain and the available studies lack the power to clinically validate the approach and prepare for late stage phase III trials. The STOPSTORM consortium sets out to consolidate all current and future European efforts to clinically validate STAR treatment by merging all data in a validation cohort study, standardising pre-treatment and follow-up, in order to collect the data sets and statistical power needed to unanimously establish clinical safety, efficacy and benefit for STAR. The STOPSTORM consortium also sets out to refine protocols and guidelines, determine volumes of interest, define and model the optimal target region and target dose, also in relation to surrounding healthy tissues (i.e. organs at risk) and determine which patient population and underlying cardiopathies respond best to STAR. By doing so the STOPSTORM consortium paves the way to consensus and future late stage clinical trials for STAR.

Eversince, the study of symmetry in mathematics and mathematical physics has been fundamental to a thourough understanding of most of the fundamental notions. Group theory in all its forms is the theory of symmetry and thus an indispensible tool in many of the basic theoretical sciences. The study of infinite symmetry groups is especially challenging, since most of the tools from the sophisticated theory of finite groups break down and new global methods of study have to be found. In that respect, the interaction of group theory and the study of group rings with methods from ring theory, probability, Riemannian geometry, functional analyis, and the theory of dynamical systems has been extremely fruitful in a variety of situations. In this proposal, I want to extend this line of approach and introduce novel approaches to longstanding and fundamental problems. There are four main interacting themes that I want to pursue: (i) Groups and their study using ergodic theory of group actions (ii) Approximation theorems for totally disconnected groups (iii) Kaplansky’s Direct Finiteness Conjecture and p-adic analysis (iv) Kervaire-Laudenbach Conjecture and topological methods in combinatorial group theory The theory of `2-homology and `2-torsion of groups has provided a fruitful context to study global properties of infinite groups. The relationship of these homological invariants with ergodic theory of group actions will be part of the content of Part (i). In Part (ii) we seek for generalizations of `2-methods to a context of locally compact groups and study the asymptotic invariants of sequences of lattices (or more generally invariant random subgroups). Part (iii) tries to lay the foundation of a padic analogue of the `2-theory, where we study novel aspects of p-adic functional analysis which help to clarify the approximation properties of (Z/pZ)-Betti numbers. Finally, in Part (iv), we try to attack various longstanding combinatorial problems in group theory with tools from algebraic topology and p-local homotopy theory.