Motivation: Model-based approaches to safety and efficacy assessment of pharmacological drugs, treatment strategies or medical devices (In Silico Clinical Trial, ISCT) aim to decrease time and cost for the needed experimentations, reduce animal and human testing, and enable precision medicine. Unfortunately, in presence of non-identifiable models (e.g. reaction networks), parameter estimation is not enough to generate complete populations of Virtual Patients (VPs), i.e. populations guaranteed to show the entire spectrum of model behaviours (phenotypes), thus ensuring representativeness of the trial.Results: We present methods and software based on global search driven by statistical model checking that, starting from a (non-identifiable) quantitative model of the human physiology (plus drugs PK/PD) and suitable biological and medical knowledge elicited from experts, compute a population of VPs whose behaviours are representative of the whole spectrum of phenotypes entailed by the model (completeness) and pairwise distinguishable according to user-provided criteria. This enables full granularity control on the size of the population to employ in an ISCT, guaranteeing representativeness while avoiding over-representation of behaviours. We proved the effectiveness of our algorithm on a non-identifiable ODE-based model of the female Hypothalamic-Pituitary-Gonadal axis, by generating a population of 4 830 264 VPs stratified into 7 levels (at different granularity of behaviours), and assessed its representativeness against 86 retrospective health records from Pfizer, Hannover Medical School and University Hospital of Lausanne. The datasets are respectively covered by our VPs within Average Normalized Mean Absolute Error of 15%, 20% and 35% (90% of the latter dataset is covered within 20% error).Availability and implementation. Our open-source software is available at https://bitbucket.org/mclab/vipgeneratorSupplementary information: Supplementary data are available at Bioinformatics online.

In management tasks for modern electricity networks the stakeholders face typically two conflicting objectives: maximization of income (increasing demand) and reduction of demand peaks (reducing costs). To improve management of electricity distribution networks, an integrated service-based methodology is presented in this paper. Namely, the proposed approach: i) computes the operational constraints in order to improve utilization of the whole network; ii) enforces those constraints by focusing on each network substation separately; iii) verifies that probability of violating those constraints in nonnominal cases is fairly low. The feasibility of the approach has been tested tested by using a realistic scenario taken from an existing medium voltage Danish distribution network. In such scenario, the proposed method improves the network utilization and offers economic benefits for all the principal participants, i.e. DSOs, retailers and end users.

The goal of System Level Formal Verification (SLFV) is to show system correctness notwithstanding uncontrollable events (such as: faults, variation in system parameters, external inputs, etc). Hardware In the Loop Simulation (HILS) based SLFV attains such a goal by considering exhaustively all relevant simulation scenarios. We present a distributed multi-core algorithm for HILS-based SLFV. Our experimental results on the Fuel Control System example in the Simulink distribution show that by using 64 machines with an 8 core processor each we can complete the SLFV activity in about 27 hours whereas a sequential approach would require more than 200 days. To the best of our knowledge this is the first time that a distributed multi-core algorithm for HILS-based SLFV is presented.