Assessment of a Novel Newborn Screening Tool for Biliary Atresia

项目总结 这项提议旨在为候选人在临床和医学领域的独立学术生涯做好准备。 翻译研究。候选人的长期目标是为胆道疾病儿童找到创新的解决方案 闭锁和其他肝脏疾病。这位候选人受过基础科学研究方面的博士培训，他关心 在刺激的环境中，他接触到了各种儿科肝病。现在是 应聘者寻求在临床和翻译研究技术方面的正式培训，以使他能够综合 临床观察和患者数据，并开发新的诊断、治疗和预防策略。 该项目的近期目标有三个： 1)通过正规的课程学习、研究经验和 导师指导下的教学； 2)为未来的研究开发思路，可作为R03或R01拨款申请的基础 开始独立的事业；以及 3)从有成就的导师那里学习分析、沟通和决策的技能， 儿科肝病专业的成功职业道路将作为模板。 为了实现这一点，应聘者创建了一份严格的职业发展计划，同时进行 同时评估一种新的新生儿胆道闭锁筛查。BA是一种严重的肝脏疾病，具有显著的 发病率和死亡率，是美国儿科肝移植的主要适应症。如果英航是 早期诊断和治疗，患病的婴儿可以推迟甚至避免需要肝移植； 然而，婴儿通常在较晚的时候被诊断出来，因为这种疾病在出生后的头几周很难识别。 在此之前，候选人观察到患有BA的婴儿的直接或结合胆红素水平在 出生，并提出这种简单的测试可以用来筛查新生儿的疾病。 职业发展计划将使应聘者具备必要的知识和技能，以便充分评估 新生儿直接/结合胆红素筛查BA。应聘者将学习如何进行多中心 研究和解释大量的人口数据，通过对10个不同出生的102,000名新生儿进行筛查 医院。应聘者还将参加正式课程，以学习成本效益的理论和实践 研究，然后创建复杂的模型，模拟有和没有筛查的结果，这也 合并屏幕的相关成本。最后，应聘者将学习临床专业技能。 化学实验室以及如何评估其实用性，在测试血斑样本是否可以 用于BA筛选试验。 在培训结束时，应聘者应接受良好的培训，以解决以下方面的复杂问题 临床和转化性研究水平的儿科肝病。他应该有很多潜在的途径 进一步的研究，包括描述胆道闭锁的早期阶段，生成有效的算法 用于诊断胆道闭锁，从国家新生儿筛查中大规模检测血斑样本 实验室，并可能在国家一级为BA实施普遍的新生儿筛查计划。 他还将受益于该领域一位久经考验的领导者多年的密切指导。这些经历 应该为候选人申请独立资金做好准备，并帮助他作为一名 一位成功的内科科学家致力于改善患有肝病的儿童的生活。

PROJECT SUMMARY This proposal is designed to prepare the candidate for an independent academic career in clinical and translational research. The candidate’s long term goal is to discover innovative solutions for children with biliary atresia and other liver diseases. The candidate has PhD training in basic science research, and he cares for patients in a stimulating environment that exposes him to the full spectrum of pediatric liver disorders. Now the candidate seeks formal training in clinical and translational research techniques, to allow him to synthesize clinical observations and patient data and develop novel diagnostic, treatment, and prevention strategies. The immediate goals of this project are threefold: 1) Acquire clinical and translational research skills through formal coursework, research experience, and mentor-guided instruction; 2) Develop ideas for future research, which can serve as the basis for a R03 or R01 grant application to initiate an independent career; and 3) Learn analytical, communication, and decision-making skills from an accomplished mentor, whose successful career path in pediatric hepatology will serve as a template. To accomplish this, the candidate has created a rigorous career developmental plan to occur concurrently while assessing a novel newborn screen for biliary atresia (BA). BA is a serious liver condition with significant morbidity and mortality, and is the leading indication for pediatric liver transplantation in the US. If BA is diagnosed and treated early, infants with disease can delay or even avoid need for liver transplantation; however, infants are often diagnosed later because the disease is difficult to recognize in the first weeks of life. Previously, the candidate observed that infants with BA have elevated direct or conjugated bilirubin levels at birth, and proposed that this simple test could be used to screen newborns for disease. The career development plan will equip the candidate with the necessary knowledge and skills to fully assess newborn direct/conjugated bilirubin screening for BA. The candidate will learn how to conduct multi-center studies and interpret large amounts of population data, by screening 102,000 newborns from 10 different birth hospitals. The candidate will also take formal coursework to learn the theory and practice of cost-effective studies, and then create sophisticated models simulating outcomes with and without screening which also incorporate the screen’s associated costs. Finally, the candidate will learn specialized techniques in the clinical chemistry laboratory and how to evaluate their utility, in the context of testing whether blood spot samples can be used for the BA screening test. At the conclusion of the training period, the candidate should be well trained to address complex problems in pediatric hepatology at a clinical and translational research level. He should have many potential avenues of further investigation, including characterizing the early stages of biliary atresia, generating efficient algorithms for diagnosing biliary atreia, testing blood spot samples on a large scale from state newborn screening laboratories, and potentially implementing a universal newborn screening program for BA at the national level. He will also have benefitted from years of close instruction by a proven leader in the field. These experiences should prepare the candidate to apply for independent funding, and help launch his research career as a successful physician scientist focused on improving the lives of children with liver diseases.