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

唐氏综合症患者脑血管疾病的无创生物识别筛查。

• 批准号: 10580713
• 负责人: Jonathan Douglas Santoro
• 金额: $ 19.27万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-17 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580713
• 关键词: Acceleration; Accounting; Active Learning; Address; Age; Architecture; Area; Bioinformatics; Biological Markers; Biometry; Blood Pressure; Blood Vessels; Brain; CCL2 gene; Caring; Cerebrovascular Circulation; Cerebrovascular Disorders; Child; Childhood; Chronic; Clinical Trials; Clinical Trials Design; Communication; Competence; Data; Data Analyses; Deposition; Development; Development Plans; Diagnosis; Disease; Disease Pathway; Down Syndrome; Early Diagnosis; Early Intervention; Early identification; Edema; Educational workshop; Ensure; Epidemiology; Etiology; Functional disorder; Funding; Genetic Diseases; Gliosis; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Head and neck structure; Health; Health Sciences; Healthcare; Height; Hemosiderin; Home; Hypertension; Hypotension; Image; Immune; Incidence; Individual; Infant; Inflammation; Inflammatory; Institution; Interferon Type II; Interleukin-6; Investigation; K-Series Research Career Programs; Knowledge; Learning; Link; Location; Los Angeles; Magnetic Resonance Imaging; Measurement; Measures; Mentors; Mentorship; Metabolic dysfunction; Modality; Morbidity - disease rate; Moyamoya Disease; Neck; Neurocognitive; Neurologic; Neurologic Symptoms; PGF gene; Patients; Persons; Physicians; Positioning Attribute; Prevalence; Prevention; Program Development; Prospective Studies; Publishing; Regression Analysis; Reproducibility; Research; Research Personnel; Retrospective Studies; Risk; Risk Assessment; Role; Scientist; Screening procedure; Secondary to; Standardization; Stenosis; Stroke; TNF gene; Techniques; Therapeutic Intervention; Time; Training; Transcranial Doppler Ultrasonography; Ultrasonography; United States; United States National Institutes of Health; Vascular Cell Adhesion Molecule-1; Vascular Diseases; Vascular Endothelial Growth Factors; Weight; Work; aged; biomedical informatics; blood pressure elevation; blood pressure reduction; career; career development; cerebrovascular; chronic inflammatory disease; cohort; comparison control; cost; design; early screening; experience; feasibility research; improved; interleukin-22; mortality; neurocognitive test; neurodevelopment; neuroimaging; population based; predictive marker; prevent; prospective; response; screening; sex; skills; systemic inflammatory response; tool; vascular inflammation

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.

摘要： 博士Jonathan Santoro是一位临床科学家，致力于探索血管疾病， 脑血管疾病（CeVD）和唐氏综合征（DS）患者的炎症。这个五年 辅导职业发展奖将为他提供先进的培训和技能，在人口为基础的 数据分析、生物统计学、神经影像学和临床试验开发，以确保成功过渡到 独立的研究生涯。概述的建议建立在桑托罗博士先前发表的工作基础上， 利用DS、神经发育、血管疾病和脑血管方面的专家组成的导师团队- 在他的家庭机构和其他大型学术DS中心，DS患者的炎症性疾病。 研究背景：DS患者早期CeVD的风险增加，特别是烟雾综合征， 并且最初的表现通常是继发于脑血管意外的不可逆的神经损伤。为 对于DS患者，没有评估CeVD风险的有效方法。K23职业发展 建立在Santoro博士以前的工作基础上，Santoro博士确定了非侵入性的方法来筛查患有CeVD的儿童。 DS.本研究将前瞻性评估DS患者的血压（BP），并随后将其用于 预测症状前CeVD（目标1）。接下来，本研究将比较金标准CeVD神经成像 研究各种非侵入性，低成本，生物识别工具，如重复BP测量，经颅 多普勒超声和神经认知测试，以评估这些措施的内部和预测有效性， CeVD的预测（目标2）。由于患有DS的人被确定为具有免疫失调， 系统性炎症特征，我们还将探讨系统性和血管炎症生物标志物的作用 在CeVD的开发中，目的是确定可能导致 在后续研究中，以预防CeVD的治疗干预为目标（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。该计划也将加强他的 在生物信息学和神经成像方面的能力，并辅之以机构讲习班， 研讨会等这种体验式学习旨在促进知识和技能的发展， 既执行他的研究，并确保技能的发展，他过渡到一个独立的研究人员。 博士桑托罗的职业发展目标将通过一个经验丰富的， 致力于跨学科团队和教学，体验和团队为基础的学习相结合。这 R 01建议及其后的R 01建议旨在改善对患有唐氏症的青少年的神经科护理。