180 research outputs found

    STAMINA: Stochastic Approximate Model-Checker for Infinite-State Analysis

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    Stochastic model checking is a technique for analyzing systems that possess probabilistic characteristics. However, its scalability is limited as probabilistic models of real-world applications typically have very large or infinite state space. This paper presents a new infinite state CTMC model checker, STAMINA, with improved scalability. It uses a novel state space approximation method to reduce large and possibly infinite state CTMC models to finite state representations that are amenable to existing stochastic model checkers. It is integrated with a new property-guided state expansion approach that improves the analysis accuracy. Demonstration of the tool on several benchmark examples shows promising results in terms of analysis efficiency and accuracy compared with a state-of-the-art CTMC model checker that deploys a similar approximation method

    Severe Coronavirus Disease 2019 Infection in an Adolescent Patient After Hematopoietic Stem Cell Transplantation

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    © 2020 American College of Chest Physicians Infection with the severe acute respiratory syndrome coronavirus 2 causes severe acute lung injury in approximately 5% of infected adults, but few reports have been made of severe pediatric disease. We present an adolescent patient who contracted severe acute respiratory syndrome coronavirus 2 one week after a paternal haplo-identical hematopoietic stem cell transplant, with development of severe hyperferritinemic acute lung injury and macrophage activation-like syndrome. We present her case and a comparison of her laboratory data with those of a cohort of pediatric patients with coronavirus disease 2019 without severe disease

    Approximation Techniques for Stochastic Analysis of Biological Systems

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    There has been an increasing demand for formal methods in the design process of safety-critical synthetic genetic circuits. Probabilistic model checking techniques have demonstrated significant potential in analyzing the intrinsic probabilistic behaviors of complex genetic circuit designs. However, its inability to scale limits its applicability in practice. This chapter addresses the scalability problem by presenting a state-space approximation method to remove unlikely states resulting in a reduced, finite state representation of the infinite-state continuous-time Markov chain that is amenable to probabilistic model checking. The proposed method is evaluated on a design of a genetic toggle switch. Comparisons with another state-of-art tool demonstrates both accuracy and efficiency of the presented method

    Characteristics and risk factors associated with critical illness in pediatric COVID-19

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    © 2020, The Author(s). Background: While much has been reported regarding the clinical course of COVID-19 in children, little is known regarding factors associated with organ dysfunction in pediatric COVID-19. We describe critical illness in pediatric patients with active COVID-19 and identify factors associated with PICU admission and organ dysfunction. This is a retrospective chart review of 77 pediatric patients age 1 day to 21 years admitted to two New York City pediatric hospitals within the Northwell Health system between February 1 and April 24, 2020 with PCR + SARS-CoV-2. Descriptive statistics were used to describe the hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. Results: Forty-seven patients (61%) were admitted to the general pediatric floor and thirty (39%) to the PICU. The majority (97%, n = 75) survived to discharge, 1.3% (n = 1) remain admitted, and 1.3% (n = 1) died. Common indications for PICU admission included hypoxia (50%), hemodynamic instability (20%), diabetic ketoacidosis (6.7%), mediastinal mass (6.7%), apnea (6.7%), acute chest syndrome in sickle cell disease (6.7%), and cardiac dysfunction (6.7%). Of PICU patients, 46.7% experienced any significant organ dysfunction (pSOFA \u3e = 2) during admission. Patients aged 12 years or greater were more likely to be admitted to a PICU compared to younger patients (p = 0.015). Presence of an underlying comorbidity was not associated with need for PICU admission (p = 0.227) or organ dysfunction (p = 0.87). Initial white blood cell count (WBC), platelet count, and ferritin were not associated with need for PICU admission. Initial C-reactive protein was associated with both need for PICU admission (p = 0.005) and presence of organ dysfunction (p = 0.001). Initial WBC and presenting thrombocytopenia were associated with organ dysfunction (p = 0.034 and p = 0.003, respectively). Conclusions: Age over 12 years and initial CRP were associated with need for PICU admission in COVID-19. Organ dysfunction was associated with elevated admission CRP, elevated WBC, and thrombocytopenia. These factors may be useful in determining risk for critical illness and organ dysfunction in pediatric COVID-19

    Specification and Verification of Synchronous Hardware using LOTOS

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    This paper investigates specification and verification of synchronous circuits using DILL (Digital Logic in LOTOS). After an overview of the DILL approach, the paper focuses on the characteristics of synchronous circuits. A more constrained model is presented for specifying digital components and verifying them. Two standard benchmark circuits are specified using this new model, and analysed by the CADP toolset (Cæsar/Aldébaran Development Package)

    Safety of low-carbohydrate diets

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    Low-carbohydrate diets have re-emerged into the public spotlight and are enjoying a high degree of popularity as people search for a solution to the population\u27s ever-expanding waistline. The current evidence though indicates that low-carbohydrate diets present no significant advantage over more traditional energy-restricted diets on long-term weight loss and maintenance. Furthermore, a higher rate of adverse side-effects can be attributed to low-carbohydrate dieting approaches. Short-term efficacy of low-carbohydrate diets has been demonstrated for some lipid parameters of cardiovascular risk and measures of glucose control and insulin sensitivity, but no studies have ascertained if these effects represent a change in primary outcome measures. Low-carbohydrate diets are likely effective and not harmful in the short term and may have therapeutic benefits for weight-related chronic diseases although weight loss on such a program should be undertaken under medical supervision. While new commercial incarnations of the low-carbohydrate diet are now addressing overall dietary adequacy by encouraging plenty of high-fibre vegetables, fruit, low-glycaemic-index carbohydrates and healthier fat sources, this is not the message that reaches the entire public nor is it the type of diet adopted by many people outside of the world of a well-designed clinical trial. Health effects of long-term ad hoc restriction of inherently beneficial food groups without a concomitant reduction in body weight remains unanswered.<br /

    Uncoupling proteins, dietary fat and the metabolic syndrome

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    There has been intense interest in defining the functions of UCP2 and UCP3 during the nine years since the cloning of these UCP1 homologues. Current data suggest that both UCP2 and UCP3 proteins share some features with UCP1, such as the ability to reduce mitochondrial membrane potential, but they also have distinctly different physiological roles. Human genetic studies consistently demonstrate the effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles influence body weight or body mass index (BMI) with many studies showing a positive effect while others do not. There is strong evidence that both UCP2 and UCP3 protect against mitochondrial oxidative damage by reducing the production of reactive oxygen species. The evidence that UCP2 protein is a negative regulator of insulin secretion by pancreatic β-cells is also strong: increased UCP2 decreases glucose stimulated insulin secretion ultimately leading to β-cell dysfunction. UCP2 is also neuroprotective, reducing oxidative stress in neurons. UCP3 may also transport fatty acids out of mitochondria thereby protecting the mitochondria from fatty acid anions or peroxides. Current data suggest that UCP2 plays a role in the metabolic syndrome through down-regulation of insulin secretion and development of type-2 diabetes. However, UCP2 may protect against atherosclerosis through reduction of oxidative stress and both UCP2 and UCP3 may protect against obesity. Thus, these UCP1 homologues may both contribute to and protect from the markers of the metabolic syndrome
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