52 research outputs found

    Abstracting strings for model checking of C programs

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    Data type abstraction plays a crucial role in software verification. In this paper, we introduce a domain for abstracting strings in the C programming language, where strings are managed as null-terminated arrays of characters. The new domain M-String is parametrized on an index (bound) domain and a character domain. By means of these different constituent domains, M-Strings captures shape information on the array structure as well as value information on the characters occurring in the string. By tuning these two parameters, M-String can be easily tailored for specific verification tasks, balancing precision against complexity. The concrete and the abstract semantics of basic operations on strings are carefully formalized, and soundness proofs are fully detailed. Moreover, for a selection of functions contained in the standard C library, we provide the semantics for character access and update, enabling an automatic lifting of arbitrary string-manipulating code into our new domain. An implementation of abstract operations is provided within a tool that automatically lifts existing programs into the M-String domain along with an explicit-state model checker. The accuracy of the proposed domain is experimentally evaluated on real-case test programs, showing that M-String can efficiently detect real-world bugs as well as to prove that program does not contain them after they are fixed

    Stochastic Game Approach to Air Operations

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    A Command and Control (C2) problem for Military Air Operations is addressed. Specifically, we consider C2 problems for air vehicles against ground based targets and defensive systems. The problem is viewed as a stochastic game. In this paper, we restrict our attention to the C2 level where the problem may consist of a few UCAVs or aircraft (or possibly teams of vehicles); less than say, a half-dozen enemy SAMs; a few enemy assets (viewed as targets from our standpoint); and some enemy decoys (assumed to mimic SAM radar signatures). At this low level, some targets are mapped out and possible SAM sites that are unavoidably part of the situation are known. One may then employ a discrete stochastic game problem formulation to determine which of these SAMs should optimally be engaged (if any), and by what series of air vehicle operations. Since this is a game model, the optimal opponent strategy is also determined. We provide analysis, numerical implementation, and simulation for full state feedback and measurement feedback control within this C2 context

    Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

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    Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p \u3c 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials

    Production of D+(2010)D^{*+}(2010) mesons by high energy neutrinos from the Tevatron

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    Charged vector D+(2010)D^{*+}(2010) meson production is studied in a high energy neutrino bubble chamber experiment with mean neutrino energy of 141 GeV. The D+D^{*+} are produced in (5.6±1.8)%(5.6 \pm 1.8)\% of the neutrino charged current interactions, indicating a steep increase of cross section with energy. The mean fractional hadronic energy of the D+D^{*+} meson is 0.55±0.060.55 \pm 0.06

    SerpinB3 Drives Cancer Stem Cell Survival in Glioblastoma

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    Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced with radiation. Finally, we found that SerpinB3 knockdown increased the efficacy of radiation in pre-clinical models. Taken together, our findings identify a GBM CSC-specific survival mechanism involving a cysteine protease inhibitor, SerpinB3, and provide a potential target to improve the efficacy of GBM therapies against therapeutically resistant CSCs

    Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

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    Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

    Prospective cohort study of patients with COVID-19 hospitalized in the Internal Medicine ward of Hospital Durand: study protocol

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    Fil: Melendi, Santiago E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pérez, María M. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Salas, Cintia E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Aguirre, Camila. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Baleta, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Balsano, Facundo J. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Caldano, Mariano G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Colignon, María G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Oliveira Brasil, Thayana De. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Wolodimeroff, Nicolás de. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Déramo Aquino, Andrea I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fernández de Córdova, Ana G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fontan, María B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Galvagno, Florencia I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Haedo, Mariana F. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Iturrieta Araya, Noelia S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Mollinedo Cruz,Volga S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Olivero, Agustín. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pestalardo, Ignacio. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ricciardi, María. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Saltos Navarrete, Jandry D. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Vera Rueda, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Villaverde, María C. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Xavier, Franco B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Lauko, Marcela. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ujeda, Carlos. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Leis, Rocío. Hospital General de Agudos Carlos G. Durand; Argentina.INTRODUCCIÓN: Conocer los predictores de mala evolución en pacientes con Enfermedad por Coronavirus 2019 (COVID-19) permite identificar de forma temprana a los pacientes con peor pronóstico, aportando mejores herramientas a la hora de tomar decisiones clínicas. Se presenta el protocolo de un estudio de cohorte cuyo objetivo principal es identificar factores de riesgo de infección severa, critica y mortalidad en pacientes con COVID-19 internados en el Servicio de Clínica Médica del Hospital Durand (Buenos Aires, Argentina). MÉTODOS: Estudio de cohorte prospectivo con base en un único centro. Se incluirá a todos los pacientes que ingresen al servicio de Clínica Médica con diagnóstico de COVID-19 durante el periodo de estudio. Se recolectarán las características epidemiológicas, clínicas, de laboratorio, radiológicas y los datos de tratamiento, al ingreso y al momento del alta o muerte hospitalaria. El evento final primario es la muerte en la internación; los eventos secundarios son el desarrollo de enfermedad grave y enfermedad crítica, la internación en unidad cerrada y el requerimiento de asistencia respiratoria mecánica

    Prospective cohort study of patients with COVID-19 hospitalized in the Internal Medicine ward of Hospital Durand: study protocol

    Get PDF
    Fil: Melendi, Santiago E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pérez, María M. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Salas, Cintia E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Aguirre, Camila. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Baleta, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Balsano, Facundo J. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Caldano, Mariano G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Colignon, María G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Oliveira Brasil, Thayana De. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Wolodimeroff, Nicolás de. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Déramo Aquino, Andrea I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fernández de Córdova, Ana G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fontan, María B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Galvagno, Florencia I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Haedo, Mariana F. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Iturrieta Araya, Noelia S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Mollinedo Cruz,Volga S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Olivero, Agustín. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pestalardo, Ignacio. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ricciardi, María. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Saltos Navarrete, Jandry D. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Vera Rueda, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Villaverde, María C. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Xavier, Franco B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Lauko, Marcela. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ujeda, Carlos. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Leis, Rocío. Hospital General de Agudos Carlos G. Durand; Argentina.INTRODUCCIÓN: Conocer los predictores de mala evolución en pacientes con Enfermedad por Coronavirus 2019 (COVID-19) permite identificar de forma temprana a los pacientes con peor pronóstico, aportando mejores herramientas a la hora de tomar decisiones clínicas. Se presenta el protocolo de un estudio de cohorte cuyo objetivo principal es identificar factores de riesgo de infección severa, critica y mortalidad en pacientes con COVID-19 internados en el Servicio de Clínica Médica del Hospital Durand (Buenos Aires, Argentina). MÉTODOS: Estudio de cohorte prospectivo con base en un único centro. Se incluirá a todos los pacientes que ingresen al servicio de Clínica Médica con diagnóstico de COVID-19 durante el periodo de estudio. Se recolectarán las características epidemiológicas, clínicas, de laboratorio, radiológicas y los datos de tratamiento, al ingreso y al momento del alta o muerte hospitalaria. El evento final primario es la muerte en la internación; los eventos secundarios son el desarrollo de enfermedad grave y enfermedad crítica, la internación en unidad cerrada y el requerimiento de asistencia respiratoria mecánica

    Comparison of numerical and analytical approximations of the early exercise boundary of American put options

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    We present qualitative and quantitative comparisons of various analytical and numerical approximation methods for calculating a position of the early exercise boundary of American put options paying zero dividends. We analyse the asymptotic behaviour of these methods close to expiration, and introduce a new numerical scheme for computing the early exercise boundary. Our local iterative numerical scheme is based on a solution to a nonlinear integral equation. We compare numerical results obtained by the new method to those of the projected successive over-relaxation method and the analytical approximation formula recently derived by Zhu [‘A new analytical approximation formula for the optimal exercise boundary of American put options’, Int. J. Theor. Appl. Finance 9 (2006) 1141–1177]. doi:10.1017/S144618111000085
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