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/vipgenerator. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In Silico Clinical Trials (ISCT), i.e. clinical experimental campaigns carried out by means of computer simulations, hold the promise to decrease time and cost for the safety and efficacy assessment of pharmacological treatments, reduce the need for animal and human testing, and enable precision medicine. In this paper we present methods and an algorithm that, by means of extensive computer simulation-based experimental campaigns (ISCT) guided by intelligent search, optimise a pharmacological treatment for an individual patient (precision medicine). We show the effectiveness of our approach on a case study involving a real pharmacological treatment, namely the downregulation phase of a complex clinical protocol for assisted reproduction in humans.

The SmartHG project goal is to develop a suite of integrated software services (the SmartHG Platform) aiming at steering residential users energy demand in order to: keep operating conditions of the electrical grid within given healthy bounds, minimize energy costs, and minimize CO2 emissions. This is achieved by exploiting knowledge (demand awareness) of electrical energy prosumption of residential users as gained from SmartHG sensing and communication infrastructure. This paper describes such an infrastructure along with user demand patterns emerging from the data gathered from ~600 sensors installed in ~40 homes participating in SmartHG test-beds.

Many Embedded Systems are indeed Software Based Control Systems (SBCSs), that is control systems whose controller consists of control software running on a microcontroller device. This motivates investigation on Formal Model Based Design approaches for control software. Given the formal model of a plant as a Discrete Time Linear Hybrid System and the implementation specifications (that is, number of bits in the Analog-to-Digital (AD) conversion) correct-by-construction control software can be automatically generated from System Level Formal Specifications of the closed loop system (that is, safety and liveness requirements), by computing a suitable finite abstraction of the plant.