Modified Project Summary / Abstract: Prior research has documented substantial differences in levels of physiological stress among adolescents, a period of particular importance from a developmental perspective with the potential to influence chronic disease risk in adulthood. The proposed project seeks to explore the role of exposure to multiple dimensions of everyday activity space locations – including area-level violence and perceptions of belonging – in contributing to everyday (real-time) perceptions of both physical and psychological unsafety and their contribution to explaining differences in physiological stress during adolescence (Aim 1). We will also consider the impact of activity space exposures, unsafety perceptions, and physiological stress as predictors of substance use and mental health outcomes (Aim 2). The project will collect aim-relevant data on a cohort of adolescents residing in the Columbus, OH metropolitan area employing an innovative two-stage design: The first phase will produce rich cross-sectional data (N=700) including standard survey items for youth and their caregivers; estimates of youth activity space exposures from self-reported routine activity locations combined with extensive contextual ratings and administrative data, physiological stress markers (cortisol and inflammatory), and health outcomes. The second phase will involve a supplemental intensive longitudinal data collection period taking place over a six-month period for a subsample of Phase 1 youth (N=300) selected using a novel exposure-based sampling strategy. Data collected during this supplemental phase will include an unprecedented combination of continuous high-resolution GPS tracking; ecological momentary assessments of perceived psychological and physical safety; continuously-sensed heart rate variability; and hair cortisol concentration and C-reactive protein measured at three additional time points. In addition to analyses of the novel data sources produced by the project, by drawing on data from the Adolescent Health and Development in Context Study (2014-2016) previously conducted by our study team, we will also examine recent changes in activity space exposures, safety and physiological stress, and their health consequences (Aim 3).