Core-004

核心004

• 批准号: 10662365
• 负责人: Sallie R. Permar
• 金额: $ 20.43万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-24 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662365
• 关键词: Core; 004

ABSTRACT – 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 naïve and non-naïve 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 RhCMVinfected 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

摘要 - 统计和数学建模核心（核心4） 统计和数学建模核心（核心4）将提供数据管理，统计分析 以及对计划了解免疫学和病毒的​​总体目标的数学建模支持 先天性CMV感染的决定因素。核心都与两个项目合作，以定义一个全面的 所有实验的样本量分析，还将分析这些实验生成的数据 使用描述性统计数据和统计 可视化以及单变量和多元回归建模。特别注意使用 在两个实验设计中优化从小样本大小中提取信息的方法 和随后的分析。核心的创新方面是拟议的数学发展 模型和计算机模拟，以探讨不同的机械假设如何影响病毒种群 在不同的免疫控制场景下生长和位置传播的可能性。这些 数学模型将利用并整合病毒种群遗传学分析（核心3），宿主 （CORE 1）和CMV（CORE 2）纵向测量以及幼稚的系统扰动 和非遗产的宿主（项目1和2），以评估和生成有关宿主CMV的假设 相互作用调节病毒传播和占位段传播的风险。药代动力学的工作 核心内将开发一个基于半生理的PK模型，以表征孕产妇，胎儿和 给予RHCMV感染的恒河花大坝或直接向RHCMV感染的胎儿使用HIG的母亲及其分布，以生成HIG的最佳剂量方案，以预防Materno-Fetal 先天CMV。 Core 4还将与Admin Core一起定义模式以捕获关键数据 REDCAP数据库中的摘要，创建模板以跟踪版本和实验元数据 杜克盒服务用于跨项目和核心的数据共享。最后，核心4将与管理员一起工作 核心并与杜克大学促进科学诚信，服务和培训（ASIST）协商 建立特定计划的数据管理SOP和科学文化和问责制计划（SCAP） 为程序。核心4支持此程序中的所有组件（项目1，2; core 1，2，3; admin core）， 并提供了用于探索性数据分析，统计分析，药代动力学的集中资源 研究，数学建模和数据管理。核心4将是准备所有程序的核心 试图建立涉及的免疫和病毒学因素的演示，报告和手稿 CMV的胎盘传输作为指导未来疫苗设计和评估的策略