? Statistics and Mathematical Modeling Core (Core 4) The Statistics and Mathematical Modeling Core (Core 4) will provide data management, statistical analysis and mathematical modeling support for the Program?s overall goal to understand the immunological and viral determinants of congenital CMV infection. The Core has worked with both projects to define a comprehensive sample size analysis for all experiments and will also analyze the data generated from those experiments to identify correlates of placental transmission and viral load using descriptive statistics and statistical visualization as well as univariate and multivariate regression modelling. Special attention is paid to the use of use of methods that optimize information extraction from small sample sizes in both the experimental design and subsequent analysis. An innovative aspect of the Core is the proposed development of mathematical models and computer simulations to explore how different mechanistic assumptions affect viral population growth and the likelihood of placental transmission under different immune control scenarios. These mathematical models will take advantage of and integrate the viral population genetics analyses (Core 3), host (Core 1) and CMV (Core 2) longitudinal measurements, and systematic experimental perturbations in nave and non-nave hosts (Projects 1 and 2) to evaluate and generate hypotheses about how host-CMV interactions modulate the risk of viral dissemination and placental transmission. The pharmacokinetics effort within the Core will develop a semi-physiologic based PK model to characterize the maternal, fetal, and maternal-fetal distribution of HIG after administration to RhCMV-infected rhesus dams or directly to RhCMV- infected fetuses to generate optimal dosing regimens of HIG for materno-fetal prevention and treatment of congenital CMV. Core 4 will also work with the Admin Core to define the schema to capture critical data summaries in a REDCap database, create templates to track versioning and experimental metadata in the Duke Box service used for data sharing across projects and cores. Finally, Core 4 will work with the Admin Core and in consultation with the Duke Office of Advancing Scientific Integrity, Services, and Training (ASIST) to establish Program-specific data management SOPs and Scientific Culture and Accountability Plan (SCAP) for the Program. Core 4 supports all components in this Program (Project 1, 2; Core 1, 2, 3; Admin Core), and provides a centralized resource for exploratory data analysis, statistical analysis, pharmacokinetics studies, mathematical modeling, and data management. Core 4 will be central to the preparation of all Program presentations, reports, and manuscripts that seek to establish the immunologic and virologic factors involved in placental transmission of CMV as a strategy to guide future vaccine design and evaluation
