A Metric for Linear Temporal Logic

We propose a measure and a metric on the sets of infinite traces generated by a set of atomic propositions. To compute these quantities, we first map properties to subsets of the real numbers and then take the Lebesgue measure of the resulting sets. We analyze how this measure is computed for Linear Temporal Logic (LTL) formulas. An implementation for computing the measure of bounded LTL properties is provided and explained. This implementation leverages SAT model counting and effects independence checks on subexpressions to compute the measure and metric compositionally

The Role of Cerebral Embolic Protection Devices During Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement is the therapy of choice for patients with severe aortic stenosis who have prohibitive or high surgical risk. However, the benefit of TAVR is attenuated by the occurrence of major disabling stroke which is associated with increased mortality and early-reduced quality of life. Despite advances in TAVR technology, stroke remains a serious complication that is associated with significant negative outcomes. The majority of these occur in the acute phase following TAVR where cerebral embolic events are frequent. Cerebral embolic protection devices (CEPD) have been developed to minimize the risk of peri-procedural ischemic stroke during TAVR. CEPD have the potential to reduce intraprocedural burden of new silent ischemic injury. In this review we outline the etiology and incidence of stroke in TAVR population, and systematically review current evidence for cerebral embolic protection devices

Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression

Background: The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients. Methods: Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses. Gene variants were classified accordingly to the ESCAT score. Results: A total of 106 patients were included in this study; 44 % of cases were requested because of tissue unavailability at the diagnosis and 56 % were requested at the PD. At least one driver alteration was observed in 62 % of cases at diagnosis. Driver druggable variants classified as ESCAT level I were detected in 34 % of patients, including ALK-EML4, ROS1-CD74, EGFR, BRAF, KRAS p.G12C, PI3KCA. In the PD group, most patients were EGFR-positive, progressing to a first line-therapy. Sixty-three percent of patients had at least one driver alteration detected in blood and 17 % of patients had a known biological mechanism of resistance allowing further therapeutic decisions. Conclusions: The present study confirms the potential of liquid biopsy to detect tumour molecular heterogeneity in NSCLC patients at the diagnosis and at PD, demonstrating that a significant number of druggable mutations and mechanisms of resistance can be detected by NGS analysis on ctDNA

A Platform-Based Approach to Verification and Synthesis of Linear Temporal Logic Specifications

The design of Cyber-Physical Systems (CPS) is challenging as it requires coordination across several domains (e.g., functional, temporal, mechanical). To cope with complexity, rarely a CPS is built from scratch. Instead, it is assembled by reusing available components and subsystems. If a component is not available, then it is made to order according to a specification which ensures its compatibility with the rest of the system.To achieve design goals faster while guaranteeing system safety, the correct instantiation of modules and subsystems is essential. Formal specifications, such as those expressed in Linear Temporal Logic (LTL), have the potential to drastically reduce design and implementation efforts by enabling rigorous requirement analysis and ensuring the correct composition of reusable designs. Composing formal specifications, however, is a tedious and error-prone activity, and the scalability of existing formal analysis techniques is still an issue. In this dissertation, we present a set of techniques and algorithms that leverage compositional design principles to enable faster verification and correct-by-construction, platform-based synthesis of LTL specifications. In our framework, a design is a composition of several components (which could describe both hardware and software elements) represented through their specifications, expressed as LTL assume/guarantee interfaces, or contracts. The collection of all the available contracts, i.e., a library, describes the design platform. The contracts in the library are the building blocks of different possible designs, and they are simple enough that their correctness can be easily verified, yet complete enough to guarantee the correct and safe use of the components they represent. Our contribution is two-fold. On the one hand, we address the verification task: given an existing composition of contracts from the library, we want to check whether it satisfies a set of desired requirements. We improve the scalability of existing verification techniques by leveraging pre-verified relations between contracts in the library. On the other hand, we enable specification synthesis: given a (possibly incomplete) set of desired system properties, we are able to automatically generate a composition of contracts, chosen from a library, that satisfies them. We do so by devising a set of algorithms based on formal inductive synthesis, where a candidate is either accepted as correct or is used to infer new constraints and guide the synthesis process towards a solution. Additionally, we show how to increase the scalability of our approach by leveraging principles from the contract framework to decompose a synthesis problem into several independent tasks, which are simpler than the original problem. We validate our work by applying it to several industrial-relevant case studies, including the problem of verification and synthesis of a controller for the electrical power system of an aircraft

A Platform-Based Approach to Verification and Synthesis of Linear Temporal Logic Specifications

The design of Cyber-Physical Systems (CPS) is challenging as it requires coordination across several domains (e.g., functional, temporal, mechanical). To cope with complexity, rarely a CPS is built from scratch. Instead, it is assembled by reusing available components and subsystems. If a component is not available, then it is made to order according to a specification which ensures its compatibility with the rest of the system.To achieve design goals faster while guaranteeing system safety, the correct instantiation of modules and subsystems is essential. Formal specifications, such as those expressed in Linear Temporal Logic (LTL), have the potential to drastically reduce design and implementation efforts by enabling rigorous requirement analysis and ensuring the correct composition of reusable designs. Composing formal specifications, however, is a tedious and error-prone activity, and the scalability of existing formal analysis techniques is still an issue. In this dissertation, we present a set of techniques and algorithms that leverage compositional design principles to enable faster verification and correct-by-construction, platform-based synthesis of LTL specifications. In our framework, a design is a composition of several components (which could describe both hardware and software elements) represented through their specifications, expressed as LTL assume/guarantee interfaces, or contracts. The collection of all the available contracts, i.e., a library, describes the design platform. The contracts in the library are the building blocks of different possible designs, and they are simple enough that their correctness can be easily verified, yet complete enough to guarantee the correct and safe use of the components they represent. Our contribution is two-fold. On the one hand, we address the verification task: given an existing composition of contracts from the library, we want to check whether it satisfies a set of desired requirements. We improve the scalability of existing verification techniques by leveraging pre-verified relations between contracts in the library. On the other hand, we enable specification synthesis: given a (possibly incomplete) set of desired system properties, we are able to automatically generate a composition of contracts, chosen from a library, that satisfies them. We do so by devising a set of algorithms based on formal inductive synthesis, where a candidate is either accepted as correct or is used to infer new constraints and guide the synthesis process towards a solution. Additionally, we show how to increase the scalability of our approach by leveraging principles from the contract framework to decompose a synthesis problem into several independent tasks, which are simpler than the original problem. We validate our work by applying it to several industrial-relevant case studies, including the problem of verification and synthesis of a controller for the electrical power system of an aircraft

Constrained synthesis from component libraries

Embargo 24 kkSynthesis from component libraries is the problem of building a network of components from a given library, such that the network realizes a given specification. This problem is undecidable in general. It becomes decidable if we impose a bound on the number of chosen components. However, the bounded problem remains computationally hard and brute-force approaches do not scale. In this paper, we study scalable methods for solving the problem of bounded synthesis from libraries, proposing a solution based on the Counterexample-Guided Inductive Synthesis paradigm. Although our synthesis algorithm does not assume a specific formalism a priori, we present a parallel implementation which instantiates components defined as Linear Temporal Logic-based Assume/Guarantee Contracts. We show the potential of our approach and evaluate our implementation by applying it to two industrial-relevant case studies.Peer reviewe

Incidence and characterization of acute pulmonary embolism in patients with SARS-CoV-2 pneumonia: A multicenter Italian experience.

Background and aimsSeveral studies reported a high incidence of pulmonary embolism (PE) among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but detailed data about clinical characteristics, risk factors of these patients and prognostic role of PE are still lacking. We aim to evaluate the occurrence of pulmonary embolism among patients with SARS-CoV-2 infection, and to describe their risk factors, clinical characteristics, and in-hospital clinical outcomes.MethodsThis is a multicenter Italian study including 333 consecutive SARS-CoV-2 patients admitted to seven hospitals from February 22 to May 15, 2020. All the patients underwent computed tomography pulmonary angiography (CTPA) for PE detection. In particular, CTPA was performed in case of inadequate response to high-flow oxygen therapy (Fi02≥0.4 to maintain Sp02≥92%), elevated D-dimer (>0.5μg/mL), or echocardiographic signs of right ventricular dysfunction. Clinical, laboratory and radiological data were also analyzed.ResultsAmong 333 patients with laboratory confirmed SARS-CoV-2 pneumonia and undergoing CTPA, PE was detected in 109 (33%) cases. At CTPA, subsegmental, segmental, lobar and central thrombi were detected in 31 (29%), 50 (46%), 20 (18%) and 8 (7%) cases, respectively. In-hospital death occurred in 29 (27%) patients in the PE-group and in 47 (21%) patients in the non-PE group (p = 0.25). Patients in PE-group had a low rate of traditional risk factors and deep vein thrombosis was detected in 29% of patients undergoing compression ultrasonography. In 71% of cases with documented PE, the thrombotic lesions were located in the correspondence of parenchymal consolidation areas.ConclusionsDespite a low rate of risk factors for venous thromboembolism, PE is present in about 1 out 3 patients with SARS-CoV-2 pneumonia undergoing CTPA for inadequate response to oxygen therapy, elevated D-dimer level, or echocardiographic signs of right ventricular dysfunction. In most of the cases, the thromboses were located distally in the pulmonary tree and were mainly confined within pneumonia areas