Dynamic modeling of antagonism between enteric infection and undernutritionin infancy

婴儿期肠道感染与营养不良拮抗的动态模型

• 批准号: 10767667
• 负责人: GWENYTH O'NEILL LEE
• 金额: $ 11.41万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-25 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10767667
• 关键词: Address; Adult; Affect; Age; Age Months; Area; Award; Behavior; Biological; Biological Models; Birth; Calibration; Campylobacter; Child; Childhood; Chronic; Communicable Diseases; Communities; Complex; Computer Models; Data; Data Set; Development; Diet; Dietary Factors; Disease; Ecuadorian; Elements; Ensure; Enteral; Epidemiology; Exposure to; Fatty acid glycerol esters; Feedback; Funding; Giardia; Goals; Growth; Height; Human; Immunity; In Situ; Income; Individual; Infant; Infant Development; Infant Health; Infection; Intake; Interdisciplinary Study; Intervention; Knowledge; Leadership; Life; Malnutrition; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolism; Methodology; Methods; Michigan; Modeling; National Institute of Allergy and Infectious Disease; Nutrient; Nutritional; Nutritional status; Outcome; Output; Pattern; Positioning Attribute; Poverty; Process; Proteins; Regulation; Reporting; Research; Research Personnel; Resources; Rotavirus; Rural; Sampling; Social Conditions; System; Testing; Time; Training; Universities; Update; Vitamin A; Work; Zinc; antagonist; bridge program; career; cognitive development; cohort; community based research; deprivation; design; dietary; dynamic system; early childhood; energy balance; enteric infection; enteric pathogen; epidemiology study; experience; feeding; girls; global health; improved; indexing; infancy; infection risk; innovation; interest; low and middle-income countries; maternal outcome; mathematical model; nutritional epidemiology; pathogen; prevent; programs; tool; training project

PROJECT SUMMARY The goal of this NIAID Mentored Research Scientist Development Award (K01) is to provide the candidate, Gwenyth O. Lee, with the training and protected time to build an independent, interdisciplinary research program. This program would bridge computational modeling methods and community-based research to address key questions in the field of enteric disease epidemiology. Stunted growth is a significant negative outcome of frequent enteric infection among children under five years in low and middle- income countries (LMICs). A major obstacle to the development of impactful interventions to prevent stunting has been methodological. Growth faltering in children is the cumulative result of complex interactions between infectious exposures and dietary inadequacies. Conventional statistical approaches are capable of, but not well-suited to, disentangling these interactions to identify those modifiable factors with the greatest potential impact. On the other hand, systems approaches are explicitly designed to capture complex interactions between multiple causal relationships. Therefore, the overall objective of this proposal is to develop a mechanistic model that captures patterns of feedback between infection, diet, and short-term growth dynamics and predicts how an individual infant might grow, given different patterns of infection experienced in the first two years of life. This model will be used to test whether feedback between infection and undernutrition has the potential to result in a ‘tipping point’, such that enteric infections impact stunting only when the negative effect of these infections outpaces the infant’s biological capacity for catch-up growth. The model will also be used to investigate mechanisms by which dietary inadequacies modify the relationship between enteric infections and growth and to compare enteropathogen- specific growth impacts. The model will be empirically based in 1) data from three Ecuadorian birth cohorts, sampled across rural-urban gradient with variable burdens of enteric exposures but relatively homogenous infant feeding practices and 2) data from six birth cohorts from multiple LMIC contexts (‘MAL-ED’ study), where enteric exposures but also dietary and social conditions are heterogeneous between cohorts. To match the proposed scientific work, the candidate will seek to integrate her experience in community-based enteric disease research with the following training areas: computational modeling, including 1) system dynamics and 2) agent-based modeling, and 3) the nutritional regulation of child growth. This training will be augmented with 4) career-building activities to acquire essential tools for leadership and professional growth. Experts have emphasized the need to better integrate computational modeling into applied epidemiology research, thereby creating models that can better predict contextually-tailored intervention strategies. The project builds upon the unique resources and mentoring available to the candidate through the University of Michigan to provide advanced methodological training, bolster applications for competitive funding, disseminate findings across the wider research community and attain research independence.

项目摘要 这个NIAID指导的研究科学家发展奖（K01）的目标是为候选人提供， Gwenyth O. Lee，培训和受保护的时间来建立独立的跨学科研究计划。 该计划将桥接计算建模方法和基于社区的研究以解决关键 进入疾病流行病学领域的问题。发育不良的增长是显着的负面结果 低收入和中等收入国家（LMIC）的五年儿童经常感染。专业 制定有影响力的干预措施以防止发育迟缓的障碍是方法论上的。生长 儿童步履蹒跚是感染性暴露与饮食中复杂相互作用的累积结果 不足。传统的统计方法能够但不适合将这些方法解散 相互作用以确定具有最大潜在影响的那些可修改因素。另一方面，系统 明确设计的方法是为了捕获多个因果关系之间的复杂相互作用。 因此，该提案的总体目标是开发一种机械模型，以捕获模式 感染，饮食和短期生长动态之间的反馈，并预测单个婴儿如何可能 鉴于生命的头两年中经历的不同感染模式。该模型将用于测试 感染和营养不良之间的反馈是否有可能导致“转折点”，以便 仅当这些感染的负面影响超过婴儿的生物学时，肠感染才会影响阻碍 追赶增长的能力。该模型还将用于研究饮食的机制 不足修改肠道感染与生长之间的关系，并比较肠病 - 特定的增长影响。该模型将基于1）来自三个厄瓜多尔出生队列的数据， 在肠道暴露的可变伯元中，在粗大城市的梯度上取样，但相对同质的婴儿 喂养实践和2）来自多个LMIC环境（“ Mal-Ed”研究）的六个出生队列的数据，其中 同类人群之间的暴露和饮食和社会状况是异质的。匹配提议的 科学工作，候选人将寻求将她在基于社区的促进疾病研究中的经验融合 在以下培训领域：计算建模，包括1）系统动力学和2）基于代理的动态 建模和3）儿童生长的营养调节。 该培训将通过4）职业建设进行增强 为领导和专业成长获得基本工具的活动。专家强调了需求 更好地集成计算建模到应用流行病学研究中，从而创建可以 更好地预测上下文规范的干预策略。该项目以独特的资源为基础 候选人通过密歇根大学提供指导，以提供先进的方法论 培训，支持竞争资金的申请，在更广泛的研究社区中传播发现 并获得研究独立性。