The Dynamic Fault Tree Rare Event Simulator

The dynamic-fault-tree rare event simulator, DFTRES, is a statistical model checker for dynamic fault trees (DFTs), supporting the analysis of highly dependable systems, e.g. with unavailability or unreliability under 10^(-30). To efficiently estimate such low probabilities, we apply the Path-ZVA algorithm to implement Importance Sampling with minimal user input. Calculation speed is further improved by selective automata composition and bisimulation reduction. DFTRES reads DFTs in the Galileo or JANI textual formats. The tool is written in Java 11 with multi-platform support, and it is released under the GPLv3. In this paper we describe the architecture, setup, and input language of DFTRES, and showcase its accurate estimation of dependability metrics of (resilient) repairable DFTs from the FFORT benchmark suite.</p

The quantitative verification benchmark set

We present an extensive collection of quantitative models to facilitate the development, comparison, and benchmarking of new verification algorithms and tools. All models have a formal semantics in terms of extensions of Markov chains, are provided in the Jani format, and are documented by a comprehensive set of metadata. The collection is highly diverse: it includes established probabilistic verification and planning benchmarks, industrial case studies, models of biological systems, dynamic fault trees, and Petri net examples, all originally specified in a variety of modelling languages. It archives detailed tool performance data for each model, enabling immediate comparisons between tools and among tool versions over time. The collection is easy to access via a client-side web application at qcomp.org with powerful search and visualisation features. It can be extended via a Git-based submission process, and is openly accessible according to the terms of the CC-BY license

Lightweight Statistical Model Checking in Nondeterministic Continuous Time

Lightweight scheduler sampling brings statistical model checking to nondeterministic formalisms with undiscounted properties, in constant memory. Its direct application to continuous-time models is rendered ineffective by their dense concrete state spaces and the need to consider continuous input for optimal decisions. In this paper we describe the challenges and state of the art in applying lightweight scheduler sampling to three continuous-time formalisms: After a review of recent work on exploiting discrete abstractions for probabilistic timed automata, we discuss scheduler sampling for Markov automata and apply it on two case studies. We provide further insights into the tradeoffs between scheduler classes for stochastic automata. Throughout, we present extended experiments and new visualisations of the distribution of schedulers.</p

The direct healthcare costs associated with psychological distress and major depression : A population-based cohort study in Ontario, Canada

The objective of our study was to estimate direct healthcare costs incurred by a population-based sample of people with psychological distress or depression. We used the 2002 Canadian Community Health Survey on Mental Health and Well Being and categorized individuals as having psychological distress using the Kessler-6, major depressive disorder (MDD) using DSM-IV criteria and a comparison group of participants without MDD or psychological distress. Costs in 2013 USD were estimated by linking individuals to health administrative databases and following them until March 31, 2013. Our sample consisted of 9,965 individuals, of whom 651 and 409 had psychological distress and MDD, respectively. Although the age-and-sex adjusted per-capita costs were similarly high among the psychologically distressed ($3,364, 95$2,791, $3,937) and those with MDD ($3,210, 95% CI: $2,413,$4,008) compared to the comparison group ($2,629, 95$2,312, $2,945), the population-wide excess costs for psychological distress ($441 million) were more than twice that for MDD ($210 million) as there was a greater number of people with psychological distress than depression. We found substantial healthcare costs associated with psychological distress and depression, suggesting that psychological distress and MDD have a high cost burden and there may be public health intervention opportunities to relieve distress. Further research examining how individuals with these conditions use the healthcare system may provide insight into the allocation of limited healthcare resources while maintaining high quality care

Activation of PPARγ in Myeloid Cells Promotes Lung Cancer Progression and Metastasis

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits growth of cancer cells including non-small cell lung cancer (NSCLC). Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγflox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Macneg), or control PPARγflox/flox mice. In both models, mice receiving PPARγ-Macneg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells

Environmental and Genetic Preconditioning for Long-Term Anoxia Responses Requires AMPK in Caenorhabditis elegans

Article on environmental and genetic preconditioning for long-term anoxia responses requires AMPK in Caenorhabditis elegans