Synthesis from Recursive-Components Libraries

Synthesis is the automatic construction of a system from its specification. In classical synthesis algorithms it is always assumed that the system is "constructed from scratch" rather than composed from reusable components. This, of course, rarely happens in real life. In real life, almost every non-trivial commercial software system relies heavily on using libraries of reusable components. Furthermore, other contexts, such as web-service orchestration, can be modeled as synthesis of a system from a library of components. In 2009 we introduced LTL synthesis from libraries of reusable components. Here, we extend the work and study synthesis from component libraries with "call and return"' control flow structure. Such control-flow structure is very common in software systems. We define the problem of Nested-Words Temporal Logic (NWTL) synthesis from recursive component libraries, where NWTL is a specification formalism, richer than LTL, that is suitable for "call and return" computations. We solve the problem, providing a synthesis algorithm, and show the problem is 2EXPTIME-complete, as standard synthesis.Comment: In Proceedings GandALF 2011, arXiv:1106.081

Towards Efficient Exact Synthesis for Linear Hybrid Systems

We study the problem of automatically computing the controllable region of a Linear Hybrid Automaton, with respect to a safety objective. We describe the techniques that are needed to effectively and efficiently implement a recently-proposed solution procedure, based on polyhedral abstractions of the state space. Supporting experimental results are presented, based on an implementation of the proposed techniques on top of the tool PHAVer.Comment: In Proceedings GandALF 2011, arXiv:1106.081

Verification and Control of Turn-Based Probabilistic Real-Time Games

Quantitative verification techniques have been developed for the formal analysis of a variety of probabilistic models, such as Markov chains, Markov decision process and their variants. They can be used to produce guarantees on quantitative aspects of system behaviour, for example safety, reliability and performance, or to help synthesise controllers that ensure such guarantees are met. We propose the model of turn-based probabilistic timed multi-player games, which incorporates probabilistic choice, real-time clocks and nondeterministic behaviour across multiple players. Building on the digital clocks approach for the simpler model of probabilistic timed automata, we show how to compute the key measures that underlie quantitative verification, namely the probability and expected cumulative price to reach a target. We illustrate this on case studies from computer security and task scheduling

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

On optimal timed strategies

Abstract. In this paper, we study timed games played on weighted timed automata. In this context, the reachability problem asks if, given a set T of locations and a cost C, Player 1 has a strategy to force the game into T with a cost less than C no matter how Player 2 behaves. Recently, this problem has been studied independently by Alur et al and by Bouyer et al. In those two works, a semi-algorithm is proposed to solve the reachability problem, which is proved to terminate under a condition imposing the non-zenoness of cost. In this paper, we show that in the general case the existence of a strategy for Player 1 to win the game with a bounded cost is undecidable. Our undecidability result holds for weighted timed game automata with five clocks. On the positive side, we show that if we restrict the number of clocks to one and we limit the form of the cost on locations, then the semi-algorithm proposed by Bouyer et al always terminates.

Beyond the Basics: Improving Information About Small-Scale Fisheries

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