Comparing the Impact of Control Strategies on Mathematical Models of \u3ci\u3eClostridium difficile\u3c/i\u3e Transmission

The spore-forming, gram-positive bacteria Clostridium difficile can cause severe intestinal illness. A striking increase in the number of cases of C. difficile infection (CDI) among hospitals has highlighted the need to better understand how to prevent its spread. In this dissertation, I discuss the development and structure of two different models of nosocomial C. difficile transmission that we used to evaluate the efficacy of various control strategies and to determine optimal interventions.We begin with an update and modification of a compartmental model of nosocomial C. difficile transmission to include vaccination. We then apply optimal control theory on this epidemiological model to determine the time-varying optimal vaccination rate that minimizes a combination of (1) disease prevalence and spread in the hospital population and (2) the cost, in terms of time and money, associated with vaccination. Various hospital scenarios are considered, such as times of increased antibiotic prescription rates and periods of outbreak, to see how such scenarios affect the optimal vaccination rate. By comparing the values of our objective functional with constant vaccination rates to those with time-varying optimal vaccination rates, we illustrate the benefits of time-varying controls.The second model is an agent-based model that also simulates the transmission of C. difficile in a healthcare setting. This model explicitly incorporates healthcare workers (HCWs) as vectors of transmission, tracks individual patient antibiotic histories, incorporates varying risk levels of antibiotics with respect to CDI, and tracks contamination levels of ward rooms by C. difficile. Using this model, we evaluated the efficacy of a variety of control interventions and combinations of interventions on reducing C. difficile nosocomial colonizations and infections. The control techniques included two forms of antimicrobial stewardship, increased environmental decontamination through room cleaning, improved HCW compliance, and a preliminary assessment of vaccination

PaPaS: A Portable, Lightweight, and Generic Framework for Parallel Parameter Studies

The current landscape of scientific research is widely based on modeling and simulation, typically with complexity in the simulation's flow of execution and parameterization properties. Execution flows are not necessarily straightforward since they may need multiple processing tasks and iterations. Furthermore, parameter and performance studies are common approaches used to characterize a simulation, often requiring traversal of a large parameter space. High-performance computers offer practical resources at the expense of users handling the setup, submission, and management of jobs. This work presents the design of PaPaS, a portable, lightweight, and generic workflow framework for conducting parallel parameter and performance studies. Workflows are defined using parameter files based on keyword-value pairs syntax, thus removing from the user the overhead of creating complex scripts to manage the workflow. A parameter set consists of any combination of environment variables, files, partial file contents, and command line arguments. PaPaS is being developed in Python 3 with support for distributed parallelization using SSH, batch systems, and C++ MPI. The PaPaS framework will run as user processes, and can be used in single/multi-node and multi-tenant computing systems. An example simulation using the BehaviorSpace tool from NetLogo and a matrix multiply using OpenMP are presented as parameter and performance studies, respectively. The results demonstrate that the PaPaS framework offers a simple method for defining and managing parameter studies, while increasing resource utilization.Comment: 8 pages, 6 figures, PEARC '18: Practice and Experience in Advanced Research Computing, July 22--26, 2018, Pittsburgh, PA, US

Analyzing the Impact of Active Learning in General Education Mathematics Courses

This talk shares the preliminary results of a study that explores the general perceptions and attitudes of students in general education mathematics courses taught using primarily active learning- based methods (like group work, projects, and discovery learning), and compares them with those enrolled in a general education mathematics course taught in a more traditional and lecture-based method. We present an analysis of survey data collected throughout the semester, which explores the disposition and mindset of students, their mathematical confidence and anxiety, and perceptions of pedagogical methods used for the teaching of mathematics. We also explored how these perceptions and dispositions changed throughout the course by comparing pre, mid, and post surveys

Comparing intervention strategies for reducing Clostridioides difficile transmission in acute healthcare settings: An agent-based modeling study

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common healthcare infections. Common strategies aiming at controlling CDI include antibiotic stewardship, environmental decontamination, and improved hand hygiene and contact precautions. Mathematical models provide a framework to evaluate control strategies. Our objective is to evaluate the effectiveness of control strategies in decreasing C. difficile colonization and infection using an agent-based model in an acute healthcare setting. METHODS: We developed an agent-based model that simulates the transmission of C. difficile in medical wards. This model explicitly incorporates healthcare workers (HCWs) as vectors of transmission, tracks individual patient antibiotic histories, incorporates varying risk levels of antibiotics with respect to CDI susceptibility, and tracks contamination levels of ward rooms by C. difficile. Interventions include two forms of antimicrobial stewardship, increased environmental decontamination through room cleaning, improved HCW compliance, and a preliminary assessment of vaccination. RESULTS: Increased HCW compliance with CDI patients was ranked as the most effective intervention in decreasing colonizations, with reductions up to 56%. Antibiotic stewardship practices were highly ranked after contact precaution compliance. Vaccination and reduction of high-risk antibiotics were the most effective intervention in decreasing CDI. Vaccination reduced CDI cases to up to 90%, and the reduction of high-risk antibiotics decreased CDI cases up to 23%. CONCLUSIONS: Overall, interventions that decrease patient susceptibility to colonization by C. difficile, such as antibiotic stewardship, were the most effective interventions in reducing both colonizations and CDI cases

Muscle Fiber Type-Dependent Differences in the Regulation of Protein Synthesis

This study examined fiber type-dependent differences in the regulation of protein synthesis in individual muscle fibers found within the same whole muscle. Specifically, the in vivo SUrface SEnsing of Translation (SUnSET) methodology was used to measure protein synthesis in type 1, 2A, 2X and 2B fibers of the mouse plantaris muscle, in response to food deprivation (FD), and mechanical overload induced by synergist ablation (SA). The results show that 48 h of FD induced a greater decrease in protein synthesis in type 2X and 2B fibers compared to type 1 and 2A fibers. Type 2X and 2B fibers also had the largest FD-induced decrease in total S6 protein and Ser240/244 S6 phosphorylation, respectively. Moreover, only type 2X and 2B fibers displayed a FD-induced decrease in cross-sectional area (CSA). Ten days of SA also induced fiber type-dependent responses, with type 2B fibers having the smallest SA-induced increases in protein synthesis, CSA and Ser240/244 S6 phosphorylation, but the largest increase in total S6 protein. Embryonic myosin heavy chain (MHCEmb) positive fibers were also found in SA muscles and the protein synthesis rates, levels of S6 Ser240/244 phosphorylation, and total S6 protein content, were 3.6-, 6.1- and 2.9-fold greater than that found in fibers from control muscles, respectively. Overall, these results reveal differential responses in the regulation of protein synthesis and fiber size between fiber types found within the same whole muscle. Moreover, these findings demonstrate that changes found at the whole muscle level do not necessarily reflect changes in individual fiber types