Verifying Class Invariants in Concurrent Programs

Class invariants are a highly useful feature for the verification of object-oriented programs, because they can be used to capture all valid object states. In a sequential program setting, the validity of class invariants is typically described in terms of a visible state semantics, i.e., invariants only have to hold whenever a method begins or ends execution, and they may be broken inside a method body. However, in a concurrent setting, this restriction is no longer usable, because due to thread interleavings, any program state is potentially a visible state. In this paper we present a new approach for reasoning about class invariants in multithreaded programs. We allow a thread to explicitly break an invariant at specific program locations, while ensuring that no other thread can observe the broken invariant. We develop our technique in a permission-based separation logic environment. However, we deviate from separation logic's standard rules and allow a class invariant to express properties over shared memory locations (the invariant footprint), independently of the permissions on these locations. In this way, a thread may break or reestablish an invariant without holding permissions to all locations in its footprint. To enable modular verification, we adopt the restrictions of Muller's ownership-based type system

Symbolic Reachability Analysis of B through ProB and LTSmin

We present a symbolic reachability analysis approach for B that can provide a significant speedup over traditional explicit state model checking. The symbolic analysis is implemented by linking ProB to LTSmin, a high-performance language independent model checker. The link is achieved via LTSmin's PINS interface, allowing ProB to benefit from LTSmin's analysis algorithms, while only writing a few hundred lines of glue-code, along with a bridge between ProB and C using ZeroMQ. ProB supports model checking of several formal specification languages such as B, Event-B, Z and TLA. Our experiments are based on a wide variety of B-Method and Event-B models to demonstrate the efficiency of the new link. Among the tested categories are state space generation and deadlock detection; but action detection and invariant checking are also feasible in principle. In many cases we observe speedups of several orders of magnitude. We also compare the results with other approaches for improving model checking, such as partial order reduction or symmetry reduction. We thus provide a new scalable, symbolic analysis algorithm for the B-Method and Event-B, along with a platform to integrate other model checking improvements via LTSmin in the future

VerifyThis 2015 A program verification competition

VerifyThis 2015 was a one-day program verification competition which took place on April 12th, 2015 in London, UK, as part of the European Joint Conferences on Theory and Practice of Software (ETAPS 2015). It was the fourth instalment in the VerifyThis competition series. This article provides an overview of the VerifyThis 2015 event, the challenges that were posed during the competition, and a high-level overview of the solutions to these challenges. It concludes with the results of the competition and some ideas and thoughts for future instalments of VerifyThis

Outcome of intracranial bleeding managed with prothrombin complex concentrate in patients on direct factor Xa inhibitors or vitamin K antagonists

Intracranial hemorrhage (ICH) is the most feared complication of anticoagulation with a high mortality and morbidity. Before registration of a specific reversal agent for factor Xa inhibitors (FXa-I), international guidelines recommended prothrombin complex concentrate (PCC), which also is the specific reversal agent for vitamin K antagonists (VKA). In two contemporary cohorts, we compared clinical outcomes between patients with FXa-I and VKA related ICH treated with PCC between 2014 and 2018. Primary outcome was effective hemostasis after 24 h, according to the International Society of Thrombosis and Hemostasis definition. Safety outcomes were defined as venous and arterial thromboembolic complications and death within 30 days. Thirty-six patients with FXa-I-ICH and 39 patients with VKA-ICH were available for analysis. Baseline characteristics were comparable between both groups, except for time from start of symptoms to presentation at the hospital. In the FXa-I-ICH cohort, 24 (73%) patients achieved effective hemostasis compared to 23 (62%) patients in the VKA-ICH cohort (crude odds ratio [OR] 1.62 [95%CI 0.59–4.48], adjusted OR 1.45 [95%CI 0.44–4.83]). Eight (24%) patients with FXa-I-ICH deceased compared to 17 (45%) patients with VKA-ICH (crude OR 0.38 [95%CI 0.14–1.24], adjusted OR 0.41 [95%CI 0.12–1.24]). In this observational cohort study, the outcome of ICH managed with PCC was similar in patients with FXa-I-ICH and in patients with VKA-ICH

Increase in venous thromboembolism in SARS-CoV-2 infected lung tissue:proteome analysis of lung parenchyma, isolated endothelium, and thrombi

Aims: COVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue. Methods: Liquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls. Results: Compared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins. Conclusions: The decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.</p

Short-term prognosis of breakthrough venous thromboembolism in anticoagulated patients

Background: Evidence for guideline recommendations for the treatment of venous thromboembolism (VTE) during anticoagulant therapy is scarce. We aimed to observe and to describe the management of VTE occurring during anticoagulant therapy. Methods: This prospective multi-center, observational study included patients with objectively confirmed VTE during anticoagulant therapy (breakthrough event), with a follow-up of 3 months, after the breakthrough event. Results: We registered 121 patients with a breakthrough event, with a mean age of 56 years (range, 19 to 90); 61 were male (50%). Fifty-eight patients (48%) had an active malignancy. At the time of the breakthrough event, 57 patients (47%) were treated with a vitamin K antagonist (VKA), 53 patients (44%) with low-molecular-weight heparin (LMWH) and 11 patients (9%) with direct oral anticoagulants, unfractionated heparin, or VKA plu