Generalized Craig Interpolation for Stochastic Boolean Satisfiability Problems with Applications to Probabilistic State Reachability and Region Stability

The stochastic Boolean satisfiability (SSAT) problem has been introduced by Papadimitriou in 1985 when adding a probabilistic model of uncertainty to propositional satisfiability through randomized quantification. SSAT has many applications, among them probabilistic bounded model checking (PBMC) of symbolically represented Markov decision processes. This article identifies a notion of Craig interpolant for the SSAT framework and develops an algorithm for computing such interpolants based on a resolution calculus for SSAT. As a potential application area of this novel concept of Craig interpolation, we address the symbolic analysis of probabilistic systems. We first investigate the use of interpolation in probabilistic state reachability analysis, turning the falsification procedure employing PBMC into a verification technique for probabilistic safety properties. We furthermore propose an interpolation-based approach to probabilistic region stability, being able to verify that the probability of stabilizing within some region is sufficiently large

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Stanley Kubrick and the Internationalisation of Postwar Hollywood

This essay examines the early career, up to 1960, of the Jewish-American filmmaker Stanley Kubrick, covering his first five features as well as his short films, his unrealised projects and also, very briefly, his initial work as a photojournalist. With detailed references to Fear and Desire (1953), Paths of Glory (1957) and The German Lieutenant (a script that came close to production in 1959), it discusses Kubrick’s strong interest in twentieth-century German and Austrian culture and history, his ‘procedural’ approach to stories about World Wars I and II, and the increasing internationalisation of the content and production circumstances of his work. These developments are discussed in relation to box office trends and public opinion in the United States as well as to changes in Hollywood’s mode of production and key markets in the post-war era

How Leaders' Motivation Transfers to Customer Service Representatives

Motivating customer service representatives (CSRs) to their highest performance levels is major task of service unit managers. However, previous studies focused on the impact of leader behavior on follower motivation, while the influence of leader motivation on follower motivation has not been investigated yet. Thus, the authors develop and test a multilevel framework for the motivation spillover principle, which holds that the three components of Vroom’s motivation theory transfer from managers to CSRs. The authors apply this framework to the context of service technology adoption and test it with a matched multilevel sample of 387 service unit managers, 1,018 CSRs, and objective company records. The results support the notion of a motivation spillover from managers to CSRs, which exists incrementally beyond the direct effect of manager’s adoption behavior on CSR’s adoption. However, not all motivation components transfer unconditionally but are contingent on charismatic leadership and manager-CSR similarity - a finding that implies for researchers that an undifferentiated view of motivation in multilevel settings might not suffice. For organizations, the findings suggest that managers are important multipliers of motivation and thus organizations should direct their motivation efforts toward middle-level managers, as they might turn into serious roadblocks to CSR motivation

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (∣r̂ g∣ ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance