Abstract Contract Synthesis and Verification in the Symbolic K Framework

[EN] In this article, we propose a symbolic technique that can be used for automatically inferring software contracts from programs that are written in a non-trivial fragment of C, called KERNELC, that supports pointer-based structures and heap manipulation. Starting from the semantic definition of KERNELC in the K semantic framework, we enrich the symbolic execution facilities recently provided by K with novel capabilities for contract synthesis that are based on abstract subsumption. Roughly speaking, we define an abstract symbolic technique that axiomatically explains the execution of any (modifier) C function by using other (observer) routines in the same program. We implemented our technique in the automated tool KINDSPEC 2.1, which generates logical axioms that express pre- and post-condition assertions which define the precise input/output behavior of the C routines. Thanks to the integrated support for symbolic execution and deductive verification provided by K, some synthesized axioms that cannot be guaranteed to be correct by construction due to abstraction can finally be verified in our setting with little effort.This work has been partially supported by the EC H2020-EU grant agreement No. 952215 (TAILOR), the EU (FEDER) and the Spanish MCIU under grant RTI2018-094403-B-C32, by Generalitat Valenciana under grant PROMETEO/2019/098.Alpuente Frasnedo, M.; Pardo, D.; Villanueva, A. (2020). Abstract Contract Synthesis and Verification in the Symbolic K Framework. Fundamenta Informaticae. 177(3-4):235-273. https://doi.org/10.3233/FI-2020-1989S2352731773-

Abstract Diagnosis for Timed Concurrent Constraint programs

The Timed Concurrent Constraint Language (tccp in short) is a concurrent logic language based on the simple but powerful concurrent constraint paradigm of Saraswat. In this paradigm, the notion of store-as-value is replaced by the notion of store-as-constraint, which introduces some differences w.r.t. other approaches to concurrency. In this paper, we provide a general framework for the debugging of tccp programs. To this end, we first present a new compact, bottom-up semantics for the language that is well suited for debugging and verification purposes in the context of reactive systems. We also provide an abstract semantics that allows us to effectively implement debugging algorithms based on abstract interpretation. Given a tccp program and a behavior specification, our debugging approach automatically detects whether the program satisfies the specification. This differs from other semiautomatic approaches to debugging and avoids the need to provide symptoms in advance. We show the efficacy of our approach by introducing two illustrative examples. We choose a specific abstract domain and show how we can detect that a program is erroneous.Comment: 16 page

Preventive CGRP-targeted therapies for chronic migraine with and without medication-overuse headache

Chronic migraine; Medication-overuse; Monoclonal antibodiesMigranya crònica; Abús de medicaments; Anticossos monoclonalsMigraña crónica; Abuso de medicamentos; Anticuerpos monoclonalesBackground: Calcitonin gene-related peptide (CGRP) targeted therapies are an important breakthrough in migraine prevention. Randomized clinical trials, post-hoc analyses, and phase IV studies have demonstrated their efficacy and safety in chronic migraine patients, including those with concomitant medication-overuse and medication-overuse headache. Real world evidence studies support these findings and provide realistic endpoints for estimation of effect. Methods and results We have performed a narrative review including results from double-blind placebo-controlled randomized clinical trials and real-world evidence studies regarding efficacy of the CGRP(-receptor) monoclonal antibodies and CGRP-receptor antagonists (gepants) in patients with chronic migraine with concomitant medication overuse (headache). We have included patient profiles and main efficacy endpoints (monthly migraine days, monthly headache days, monthly acute medication days and percentage responder rates). Conclusion The results of this review show that CGRP monoclonal antibodies are effective in chronic migraine patients, also in those with medication overuse (headache). At the time of this review, atogepant clinical trials in chronic migraine have not been communicated. Direct comparative studies are needed for comparison with other treatment options

Abstract Contract Synthesis and Verification in the Symbolic K Framework

[EN] In this article, we propose a symbolic technique that can be used for automatically inferring software contracts from programs that are written in a non-trivial fragment of C, called KernelC, that supports pointer-based structures and heap manipulation. Starting from the semantic definition of KernelC in the K semantic framework, we enrich the symbolic execution facilities recently provided by K with novel capabilities for contract synthesis that are based on abstract subsumption. Roughly speaking, we define an abstract symbolic technique that axiomatically explains the execution of any (modifier) C function by using other (observer) routines in the same program. We implemented our technique in the automated tool KindSpec 2.1, which generates logical axioms that express pre- and postcondition assertions which define the precise input/output behavior of the C routines. Thanks to the integrated support for symbolic execution and deductive verification provided by K, some synthesized axioms that cannot be guaranteed to be correct by construction due to abstraction can finally be verified in our framework with little effort.This work has been partially supported by the EU (FEDER) and Spanish MINECO under grant TIN2015-69175-C4-1-R, and and TIN2013-45732-C4-1-P, and by Generalitat Valenciana PROMETEOII/2015/013. Daniel Pardo was supported by FPU-ME grant FPU14/01830.Alpuente Frasnedo, M.; Pardo Pont, D.; Villanueva García, A. (2018). Abstract Contract Synthesis and Verification in the Symbolic K Framework. Universitat Politècnica de València. http://hdl.handle.net/10251/10030

Automatic inference of specifications using matching logic

Formal specifications can be used for various software engineering activities ranging from finding errors to documenting software and automatic test-case generation. Automatically discovering specifications for heap-manipulating programs is a challenging task. In this paper, we propose a technique for automatically inferring formal specifications from C code which is based on the symbolic execution and automated reasoning tandem "MATCHING LOGIC /K framework". We implemented our technique for a fragment of C, called KERNELC, in the automated tool KINDSPEC, which generates axioms that describe the precise input/output behavior of C routines that handle pointer-based structures, i.e., result values and state change. These specifications can be written either in MATCHING LOGIC itself, which is useful for further automated analysis within the K formal environment, or in sugared axiomatic form, which favors better human inspection. Since we rely on rewriting logic K semantics specification of programming languages, our approach can be easily extended to any language for which a formal semantics in K is given.This work has been partially supported by the EU (FEDER) and the Spanish MEC/MICINN, ref. TIN 2010-21062-C02-0, and by Generalitat Valenciana, ref. PROMETEO 2011/052.Alpuente Frasnedo, M.; Feliú Gabaldón, MA.; Villanueva García, A. (2013). Automatic inference of specifications using matching logic. En Proceeding PEPM '13 Proceedings of the ACM SIGPLAN 2013 workshop on Partial evaluation and program manipulation. Association for Computing Machinery (ACM). 127-136. https://doi.org/10.1145/2426890.2426914S12713

Abstract Diagnosis for tccp using a Linear Temporal Logic

Automatic techniques for program verification usually suffer the well-known state explosion problem. Most of the classical approaches are based on browsing the structure of some form of model (which rep- resents the behavior of the program) to check if a given specification is valid. This implies that a part of the model has to be built, and some- times the needed fragment is quite huge. In this work, we provide an alternative automatic decision method to check whether a given property, specified in a linear temporal logic, is valid w.r.t. a tccp program. Our proposal (based on abstract interpreta- tion techniques) does not require to build any model at all. Our results guarantee correctness but, as usual when using an abstract semantics, completeness is lost.Comini, M.; Titolo, L.; Villanueva García, A. (2014). Abstract Diagnosis for tccp using a Linear Temporal Logic. http://hdl.handle.net/10251/3569

Inferring Specifications in the K Framework

[EN] Despite its many unquestionable benefits, formal specifications are not widely used in industrial software development. In order to reduce the time and effort required to write formal specifications, in this paper we propose a technique for automatically discovering specifications from real code. The proposed methodology relies on the symbolic execution capabilities recently provided by the K framework that we exploit to automatically infer formal specifications from programs that are written in a non trivial fragment of C, called KERNELC. Roughly speaking, our symbolic analysis of KERNELC programs explains the execution of a (modifier) function by using other (observer) routines in the program. We implemented our technique in the automated tool KINDSPEC 2.0, which generates axioms that describe the precise input/output behavior of C routines that handle pointer- based structures (i.e., result values and state change). We describe the implementation of our system and discuss the differences w.r.t. our previous work on inferring specifications from C code.This work has been partially supported by the EU (FEDER) and the Spanish MINECO ref. TIN2013-45732-C4 (DAMAS), and by Generalitat Valenciana ref. PROMETEOII/2015/013. D. Pardo is supported by FPU-ME grant FPU14/01830.Alpuente Frasnedo, M.; Pardo Pont, D.; Villanueva, A. (2015). Inferring Specifications in the K Framework. Electronic Proceedings in Theoretical Computer Science. 1-16. http://hdl.handle.net/10251/74186S11

Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months

Erenumab; Migranya; Anticossos monoclonalsErenumab; Migraña; Anticuerpos monoclonicosErenumab; Migraine; Monoclonal antibodiesBackground In daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited. We evaluated their effectiveness in a real-life clinical cohort. Methods This is a prospective study conducted in CM patients with and without medication overuse treated with monthly MAbs during 6 months (erenumab/galcanezumab). We collected headache characteristics, including acute medication intake, through an electronic diary. We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment. Results Of 139 CM patients completing 6-month treatment with anti-CGRP MAbs, 71.2% (99/139) had MO at baseline. After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500). 60.6% (60/99) no longer satisfied MO definition. Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: − 13.4 ± 7.6 vs. -7.8 ± 7.2, p < 0.0001). No differences in MO resolution were observed according to the MAbs used. Baseline lower pain severity was associated with MO resolution (OR [95%]:0.236[0.054–0.975]; p = 0.049). Conclusions In real-life anti-CGRP MAbs are as effective in CM patients with MO as in patients without it and facilitate MO cessation. Reduction in headache frequency and acute medication days/month occurs regardless of whether patients stop overusing or not.No funding was received for this study

Automatic Inference of Specifications in the K Framework

[EN] Despite its many unquestionable benefits, formal specifications are not widely used in industrial software development. In order to reduce the time and effort required to write formal specifications, in this paper we propose a technique for automatically discovering specifications from real code. The proposed methodology relies on the symbolic execution capabilities recently provided by the K framework that we exploit to automatically infer formal specifications from programs that are written in a non–trivial fragment of C, called KERNELC. Roughly speaking, our symbolic analysis of KERNELC programs explains the execution of a (modifier) function by using other (observer) routines in the program. We implemented our technique in the automated tool KINDSPEC 2.0, which generates axioms that describe the precise input/output behavior of C routines that handle pointerbased structures (i.e., result values and state change). We describe the implementation of our system and discuss the differences w.r.t. our previous work on inferring specifications from C code.This work has been partially supported by the EU (FEDER) and Spanish MINECO under grants TIN2015-69175-C4-1-R and TIN2013-45732-C4-1-P, and by Generalitat Valenciana ref. PROMETEOII/2015/013.Alpuente Frasnedo, M.; Pardo Pont, D.; Villanueva García, A. (2015). Automatic Inference of Specifications in the K Framework. Electronic Proceedings in Theoretical Computer Science. (200):1-17. https://doi.org/10.4204/EPTCS.200.1S11720

In search of a gold standard patient-reported outcome measure to use in the evaluation and treatment-decision making in migraine prevention: A real-world evidence study

Efficacy; Headache; Health-related quality of lifeEficàcia; Mal de cap; Qualitat de vida relacionada amb la salutEficacia; Dolor de cabeza; Calidad de vida relacionada con la saludBackground Patient-Reported Outcomes (PROs) have been developed to numerically quantify disability, impact and quality of life. They have been widely used in migraine clinical trials. However, we still do not know which PRO more accurately reflects preventive treatment response from a patient’s perspective or which one may help us with treatment decisions in clinical practice. They have been used to enforce the efficacy results in clinical trials and real-world evidence so far. The aim of this study was to analyze which PROM is (1) better correlated with all primary efficacy endpoints and (2) which one is better associated with treatment continuation with CGRP-mAbs at week-12, which is usually the moment when this decision is made. Methods Patients with migraine who had received 3 administrations of CGRP-mAbs were evaluated in this prospective cohort study. Primary efficacy outcomes considered: a change in migraine days (MMD), headache days (MHD), pain intensity (INT), acute medication days (AMD) and 50% responder rate. The Spearman coefficient (rs) was the measure used for quantify the strength of the correlation between PROMs and treatment efficacy outcomes changes. A stepwise logistic regression identified which PROM was independently associated with treatment continuation at week-12. Results 263 patients completed 12 weeks of treatment. The efficacy outcomes and PROMs scores were statistically significantly reduced at week-12 for all patients. The role function-restrictive (RFR) domain of the Migraine-Specific Quality of Life (MSQ) questionnaire was statistically significantly correlated with all primary efficacy outcomes. Relative changes in MSQ total score (OR[95%]: 0.840[0.619-0.973]; p=0.037) and Patient Global Impression of Change (PGIC) scale (OR[95%]: 15.569[6.254-31.533]; p<0.001) were the PROMs associated with treatment continuation as independent factors at week-12. Conclusions Changes in MSQ questionnaire and PGIC scale at week-12 were the PROMs with higher association with CGRP-mAbs response from a patient’s perspective and medical decision-taking.The authors received no financial support for the research, authorship, and/or publication