IJMSSC

DEVS is a sound Modeling and Simulation (M&S) framework that describes a model in a modular and hierarchical way. It comes along with an abstract simulation algorithm which defines its operational semantics. Many variants of such an algorithm have been proposed by DEVS researchers. Yet, the proper interpretation and analysis of the computational complexity of such approaches have not been systematically addressed and defined. As systems become larger and more complex, the efficiency of the DEVS simulation algorithms in terms of time complexity measure becomes a major issue. Therefore, it is necessary to devise a method for computing this complexity. This paper proposes a generic method to address such an issue, taking advantage of the recursion embedded in the triggered-by-message principle of the DEVS simulation protocol. The applicability of the method is shown through the complexity analysis of various DEVS simulation algorithms

A DEVS-based pivotal modeling formalism and its verification and validation framework

System verification is an ever-lasting system engineering challenge. The increasing complexity in system simulation requires some level of expertise in handling the idioms of logic and discrete mathematics to correctly drive a full verification process. It is recognized that visual modeling can help to fill the knowledge gap between system experts and analysis experts. However, such an approach has been used on the one hand to specify the behavior of complex systems, and on the other hand to specify complex requirement properties, but not simultaneously. This paper proposes a framework that is unique in supporting a full system verification process based on the graphical modeling of both the system of interest and the requirements to be checked. Patterns are defined to transform the resulting models to formal specifications that a model checker can manipulate. A real-time crossing system is used to illustrate the proposed framework

Gallstones: Management of the Sickle Cell Child

Gallstone is rare in children; however, sickle cell disease is associated with an increased risk of gallstone formation. We aimed to report particularity of diagnosis and management of gallstones in sickle cell children. We conducted a cross-sectional multicentric study in four hospitals of Dakar, in Senegal, during 18 years. We studied frequency, diagnostic particularities, management, and outcome. Among the 105 pediatric patients managed for gallstones, 87 (82.85%) had sickle cell disease. Among the latter, 18 (17.14%) were asymptomatic. Laparoscopic cholecystectomy was performed in 71 patients (67.62%). Following surgery, sickle cell patients were systematically hospitalized in the intensive care unit for 24 hours. Complications occurred in 7.6% and mortality in 1.9%. Gallstone is frequent in sickle cell children. Its management has good outcomes when taking in account particularities of these patients

Overall and Gender-Specific Effects of Intermittent Preventive Treatment of Malaria with Artemisinin-Based Combination Therapies among Schoolchildren in Mali: A Three-Group Open Label Randomized Controlled Trial.

Intermittent preventive treatment of malaria among schoolchildren (IPTsc) reduces clinical malaria, asymptomatic parasitemia, and anemia. The effects of IPTsc by gender have not been studied longitudinally. We investigated overall IPTsc efficacy and conducted a secondary analysis to explore gender-specific differences. We enrolled schoolchildren aged 6-13 years in an open-label, rolling-cohort randomized controlled trial between September 2007 and February 2013 in Kolle, Mali. Annually, schoolchildren received two full-treatment courses of sulfadoxine-pyrimethamine (SP) plus artesunate, or amodiaquine (AQ) plus artesunate, or no malaria treatment as control. We used mixed-effects generalized linear models to estimate differences in treatment outcomes across groups with interaction terms to explore gender-specific differences associated with Plasmodium falciparum infection, hemoglobin, and grade point averages (GPA) based on standardized testing. Overall, 305 students contributed 4,564 observations. Compared with the control, SP plus artesunate and AQ plus artesunate reduced the odds of P. falciparum infection (odds ratio [OR]: 0.33, 95% CI: 0.26-0.43; OR: 0.46, 95% CI: 0.36-0.59). We found strong evidence of increased mean hemoglobin concentrations (g/dL) in the SP plus artesunate group versus control (difference +0.37, 95% CI: 0.13-0.58). Collectively, schoolchildren given AQ plus artesunate had higher mean GPA (difference +0.36, 95% CI: 0.02-0.69) relative to control. Schoolgirls, compared with schoolboys, given SP plus artesunate had greater improvement in GPA (+0.50, 95% CI: -0.02 to 1.02 versus -0.27, 95% CI: -0.71 to 0.16); interaction P = 0.048, respectively. The IPTsc decreases P. falciparum infections in schoolchildren. Treatment regimens that include longer-acting drugs may be more effective at decreasing malaria-related anemia and improving educational outcomes as observed among girls in this setting

Expanding Research Capacity in Sub-Saharan Africa Through Informatics, Bioinformatics, and Data Science Training Programs in Mali

Bioinformatics and data science research have boundless potential across Africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, HIV and AIDS, Ebola virus disease, and Lassa fever. This work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. Two global health informatics training programs sponsored by the Fogarty International Center (FIC) were carried out at the University of Sciences, Techniques and Technologies of Bamako, Mali (USTTB) between 1999 and 2011. Together with capacity building efforts through the West Africa International Centers of Excellence in Malaria Research (ICEMR), this progress laid the groundwork for a bioinformatics and data science training program launched at USTTB as part of the Human Heredity and Health in Africa (H3Africa) initiative. Prior to the global health informatics training, its trainees published first or second authorship and third or higher authorship manuscripts at rates of 0.40 and 0.10 per year, respectively. Following the training, these rates increased to 0.70 and 1.23 per year, respectively, which was a statistically significant increase (p < 0.001). The bioinformatics and data science training program at USTTB commenced in 2017 focusing on student, faculty, and curriculum tiers of enhancement. The program’s sustainable measures included institutional support for core elements, university tuition and fees, resource sharing and coordination with local research projects and companion training programs, increased student and faculty publication rates, and increased research proposal submissions. Challenges reliance of high-speed bandwidth availability on short-term funding, lack of a discounted software portal for basic software applications, protracted application processes for United States visas, lack of industry job positions, and low publication rates in the areas of bioinformatics and data science. Long-term, incremental processes are necessary for engaging historically underserved countries in bioinformatics and data science research. The multi-tiered enhancement approach laid out here provides a platform for generating bioinformatics and data science technicians, teachers, researchers, and program managers. Increased literature on bioinformatics and data science training approaches and progress is needed to provide a framework for establishing benchmarks on the topics

Quinine Treatment Selects the pfnhe-1 ms4760-1 Polymorphism in Malian Patients with Falciparum Malaria

Background. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kolle and Faladie, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.Howard Hughes Medical Institute [55005502]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; European and Developing Countries Clinical Trials Partnership [EDCTP IP_07_31060_002]info:eu-repo/semantics/publishedVersio

Subclinical Cardiac Dysfunction Is Associated With Extracardiac Organ Damages

Background: Several studies conducted in America or Europe have described major cardiac remodeling and diastolic dysfunction in patients with sickle cell disease (SCD). We aimed at assessing cardiac involvement in SCD in sub-Saharan Africa where SCD is the most prevalent.Methods: In Cameroon, Mali and Senegal, SCD patients and healthy controls of the CADRE study underwent transthoracic echocardiography if aged ≥10 years. The comparison of clinical and echocardiographic features between patients and controls, and the associations between echocardiographic features and the vascular complications of SCD were assessed.Results: 612 SCD patients (483 SS or Sβ0, 99 SC, and 19 Sβ+) and 149 controls were included. The prevalence of dyspnea and congestive heart failure was low and did not differ significantly between patients and controls. While left ventricular ejection fraction did not differ between controls and patients, left and right cardiac chambers were homogeneously more dilated and hypertrophic in patients compared to controls and systemic vascular resistances were lower (p < 0.001 for all comparisons). Three hundred and forty nine SCD patients had extra-cardiac organ damages (stroke, leg ulcer, priapism, microalbuminuria or osteonecrosis). Increased left ventricular mass index, cardiac dilatation, cardiac output, and decreased systemic vascular resistances were associated with a history of at least one SCD-related organ damage after adjustment for confounders.Conclusions: Cardiac dilatation, cardiac output, left ventricular hypertrophy, and systemic vascular resistance are associated with extracardiac SCD complications in patients from sub-Saharan Africa despite a low prevalence of clinical heart failure. The prognostic value of cardiac subclinical involvement in SCD patients deserves further studies

Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study

Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6–35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior

Controllability of nonlinear degenerate parabolic cascade systems

This article studies of null controllability property of nonlinear coupled one dimensional degenerate parabolic equations. These equations form a cascade system, that is, the solution of the first equation acts as a control in the second equation and the control function acts only directly on the first equation. We prove positive null controllability results when the control and a coupling set have nonempty intersection

A generic learning simulation framework to assess security strategies in cyber-physical production systems

Connected systems through computerized networks are at the heart of the Industry of the future. As they merge physical entities with cyber spaces, they fall under the paradigm of cyber-physical production systems. Cybersecurity is a key challenge for such systems, as they are subject to daily attempts of intruders to gain unauthorized access to their internal resources or to compromise their integrity. The fast increase of new attack strategies requires the rapid design and assessment of new defense strategies. It entails a complex, error-prone and time-consuming process, including the clear specification of the attack and defense strategies involved, and the design and implementation of the simulation model allowing to evaluate the performances of the defense strategy. This work intends to make such a process transparent to cybersecurity managers by limiting their workload to the sole specification of the characteristics of the system and the logic of the attack and the defense. It provides a generic hybrid simulation framework for flexible evaluation of cybersecurity policies, which is demonstrated on a SYN flooding application. Therefore, the contribution is twofold: (1) The proposed framework offers a high-level environment allowing various experts to collaborate by graphically modeling a given attack strategy and the envisioned defense strategy, without engaging in heavy implementation efforts. Then the framework's executable infrastructure, which combines simulation with machine learning to understanding the interactions between the attackers & the defender, will allow them assessing the performances of these strategies. The proposed framework differs from state-of-the-art cybersecurity simulation environments in its uniqueness to combining the expressive power of a universal simulation modeling formalism with the user-friendliness of a visual simulation tool. Therefore, it offers at one side, a very high modeling flexibility for easy exploration of various cybersecurity strategies, and at the other side, integrated learning capabilities for allowing self-adaptive user-based cybersecurity strategy design. (2) The application demonstrating the framework focuses on the most encountered and still uncontrolled threats in cybersecurity, i.e. the SYN-Flooding based Denial of Service (DoS) attack. The application targeted is not meant to propose yet another SYN flood detection algorithm or to improve the state-of-the-art in that domain, but to prove the framework operationality. The experimental results obtained showcase the ability of the framework to support learning simulation-based SYN flood defense algorithm design and validation