Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome.

摘要： 乔纳森·桑托罗博士是一名临床科学家，专注于探索血管疾病、 唐氏综合征(DS)患者的脑血管疾病(CeVD)和炎症。这个五年计划 指导职业发展奖将为他提供以人口为基础的高级培训和技能 数据分析、生物统计学、神经成像和临床试验开发，以确保成功过渡到 独立的研究生涯。概述的提案建立在桑托罗博士之前发表的工作和 利用DS、神经发育、血管疾病和脑血管方面的专家导师团队- 在他的家庭机构和其他大型学术DS中心，DS患者的炎性障碍。 研究背景：DS患者早期CEVD的风险增加，特别是烟雾综合征， 而首发症状往往是继发于脑血管意外的不可逆转的神经损害。为 对于DS患者，目前还没有有效的方法来评估CEVD的风险。这是K23职业发展 建立在桑托罗博士之前工作的基础上，桑托罗博士发现了非侵入性方法来筛查患有脑血管病的儿童 DS.这项研究将前瞻性地评估DS患者的血压(BP)，并随后将其用于 预测有症状前的CeVD(目标1)。接下来，这项研究将比较金标准CeVD神经成像 研究各种非侵入性、低成本的生物测量工具，如重复测量血压、经颅 多普勒超声和神经认知测试评估这些测量的内部和预测有效性 脑血管病的预测(目标2)。因为患有DS的人被证实患有免疫调节失调和 ，我们还将探索全身和血管炎症生物标志物的作用 在CEVD的发展中，目标是确定可能导致 在后续研究中以旨在预防脑血管病的治疗干预措施为目标(目标3)。 职业发展计划：桑托罗博士将完成医疗保健和科学传播方面的课程， 数据分析、流行病学、临床试验设计和生物医学信息学。这一计划也将加强他的 在生物信息学和神经成像方面的能力，并由机构讲习班和 研讨会。这种体验式学习旨在促进知识和技能的发展 两人都执行他的研究，并确保为他过渡到独立研究人员培养技能。 桑托罗博士的职业发展目标将通过经验丰富的 致力于跨学科的团队和授课、体验式和基于团队的学习相结合。这 建议和随后的R01建议旨在改善患有DS的青少年的神经护理。

ABSTRACT: Dr. Jonathan Santoro is a clinician-scientist focused on exploring the interface between vascular disease, cerebrovascular disease (CeVD) and inflammation in persons with Down syndrome (DS). This five-year mentored career development award will provide him with advanced training and skills in population-based data analysis, biostatistics, neuroimaging, and clinical trials development to ensure a successful transition to an independent research career. The outlined proposal builds on previously published work by Dr. Santoro and leverages a mentorship team of experts in DS, neurodevelopment, vascular disease, and cerebrovascular- inflammatory disorders in persons with DS at his home institution and other large academic DS centers. Research Context: Persons with DS have an increased risk of early CeVD, specifically moyamoya syndrome, and the initial presentation is often irreversible neurologic insult secondary to cerebrovascular accident. For persons with DS, there exists no validated means of assessing risk for CeVD. This K23 career development builds on previous work by Dr. Santoro who identified non-invasive ways to screen for CeVD in children with DS. This study will prospectively asses blood pressure (BP) in persons with DS and subsequently use this to predict pre-symptomatic CeVD (Aim 1). Next, this study will compare gold standard CeVD neuroimaging studies to various non-invasive, low-cost, biometric tools such as repeated BP measurements, transcranial Doppler ultrasound and neurocognitive testing to assess internal and predictive validity of these measures in the prediction of CeVD (Aim 2). As persons with DS are established to have immune dysregulation and systemic inflammatory profiles, we will also explore the role of systemic and vascular inflammatory biomarkers in the development of CeVD with the goal of identifying contributory inflammatory cascades that could be targeted with therapeutic interventions geared towards preventing CeVD in subsequent studies (Aim 3). Career Development Plan: Dr. Santoro will complete coursework in healthcare and science communication, data analysis, epidemiology, clinical trial design and biomedical informatics. This plan also will strengthen his competence in both bioinformatics and neuroimaging and be supplemented by institutional workshops and seminars. This experiential learning is designed to promote knowledge and skillset development needed to both execute his research and ensure that skills are developed for his transition to an independent researcher. Dr. Santoro’s career development goals will be supported through close mentorship by an experienced and committed interdisciplinary team and a combination of didactic, experiential, and team-based learning. This proposal and subsequent R01 proposals seek to improve the neurologic care of young persons with DS.