The Stanford Population Health Sciences Data Ecosystem was created to facilitate the use of large datasets containing health records from hundreds of millions of individuals. This necessitated technical solutions optimized for an academic medical center to manage and share high-risk data at scale. Through collaboration with internal and external partners, we have built a Data Ecosystem to host, curate, and share data with hundreds of users in a secure and compliant manner. This platform has enabled us to host unique data assets and serve the needs of researchers across Stanford University, and the technology and approach were designed to be replicable and portable to other institutions. We have found, however, that though these technological advances are necessary, they are not sufficient. Challenges around making data Findable, Accessible, Interoperable, and Reusable remain. Our experience has demonstrated that there is a high demand for access to real-world data, and that if the appropriate tools and structures are in place, translational research can be advanced considerably. Together, technological solutions, management structures, and education to support researcher, data science, and community collaborations offer more impactful processes over the long-term for supporting translational research with real-world data.

OBJECTIVES/GOALS: The Appalachian Translational Research Network (ATRN) Newsletter provides a unique platform that facilitates communication among Appalachian-serving CTSAs/CTSIs and partnering academic and community organizations that strengthens research efforts and advances translational science across the region. METHODS/STUDY POPULATION: Published biannually, each ATRN Newsletter features content submitted by ATRN member universities and organizations. Members of the Communications Committee, who represent both CTSA- or non-CTSA- affiliated ATRN member institutions, provide as well as review and edit content for the Newsletter. Regular features include researcher and community member spotlights; funding opportunity announcements; information on upcoming seminars, trainings, and special events; and opportunities for collaborations among partnering ATRN institutions. Complementing regularly scheduled Newsletters, special editions are released as warranted, such as a special COVID-19 focused edition published in 2020. RESULTS/ANTICIPATED RESULTS: First published in 2012, the ATRN Newsletter initially represented founding ATRN institutions, the University of Kentucky and the Ohio State University CTSAs, and a readership of 50. Reflecting ATRN growth that now represents 9 academic centers including NCATS- and IDeA-funded hubs, affiliated universities and partnering organizations, readership has grown to include 500 subscribers from across the U.S. and 3 other countries. With the establishment of the official ATRN website in 2019, the ATRN Newsletter became a prominent addition, providing ATRN members’ access to both new and archived editions, thereby expanding reach and further strengthening critical communication across the Network. DISCUSSION/SIGNIFICANCE: Providing a vehicle for communication that supports ATRN collaborations and networking, the Newsletter is foundational to the success of the ATRN mission to improve health outcomes across Appalachia by fostering collaborative inter-institutional and community-academic research partnerships.

Researchers have begun to examine the psychological toll of the ongoing global COVID-19 pandemic. Data are now emerging indicating that there may be long-term adverse effects of the pandemic on new mothers and on children born during this period. In a longitudinal study of maternal mental health and child emotional development during the pandemic, we conducted online assessments of a cohort of women at two time points: when they were pregnant at the beginning of the surge of the pandemic in the United States (baseline, N = 725), and approximately 1 year postpartum (follow-up, N = 296), examining prenatal and postnatal maternal mental health, prenatal pandemic-related stress, and infant temperament. Pandemic-related stress at baseline was associated with concurrent depressive symptoms and infant negative affect at follow-up. Baseline maternal depressive symptoms were associated with follow-up depressive symptoms, which in turn were also associated with infant negative affect. Pandemic-related stress during pregnancy may have enduring effects on infant temperament. These findings have important implications for our understanding of the emotional development of children who were in utero during the COVID-19 pandemic.

Little is known about the early history of the chicken (Gallus gallus domesticus), including the timing and circumstances of its introduction into new cultural environments. To evaluate its spatio-temporal spread across Eurasia and north-west Africa, the authors radiocarbon dated 23 chicken bones from presumed early contexts. Three-quarters returned dates later than those suggested by stratigraphy, indicating the importance of direct dating. The results indicate that chickens did not arrive in Europe until the first millennium BC. Moreover, a consistent time-lag between the introduction of chickens and their consumption by humans suggests that these animals were initially regarded as exotica and only several centuries later recognised as a source of ‘food’.

From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.

Different dimensions of adversity may affect mental health through distinct neurobiological mechanisms, though current supporting evidence consists largely of cross-sectional associations between threat or deprivation and fronto-limbic circuitry. In this exploratory three-wave longitudinal study spanning ages 9–19 years, we examined the associations between experiences of unpredictability, threat, and deprivation with the development of functional connectivity within and between three brain networks implicated in psychopathology: the salience (SAL), default mode (DMN), and fronto-parietal (FPN) networks, and tested whether network trajectories moderated associations between adversity and changes in internalizing symptoms. Connectivity decreased with age on average; these changes differed by dimension of adversity. Whereas family-level deprivation was associated with lower initial levels and more stability across most networks, unpredictability was associated with stability only in SAL connectivity, and threat was associated with stability in FPN and DMN-SAL connectivity. In youth exposed to higher levels of any adversity, lower initial levels and more stability in connectivity were related to smaller increases in internalizing symptoms. Our findings suggest that whereas deprivation is associated with widespread neurodevelopmental differences in cognitive and emotion processing networks, unpredictability is related selectively to salience detection circuitry. Studies with wider developmental windows should examine whether these neurodevelopmental alterations are adaptive or serve to maintain internalizing symptoms.

The present study uses event-related potentials (ERPs) to examine nonlocal agreement processing between native (L1) English speakers and Chinese–English second language (L2) learners, whose L1 lacks number agreement. We manipulated number marking with determiners (the vs. that/these) to see how determiner-specification influences both native and nonnative processing downstream for verbal number agreement. Behavioral and ERP results suggest both groups detected nonlocal agreement violations, indexed by a P600 effect. Moreover, the manipulation of determiner-number specification revealed a facilitation effect across the board in both grammaticality judgment and ERP responses for both groups: increased judgment accuracy and a larger P600 effect amplitude for sentences containing violations with demonstratives rather than bare determiners. Contrary to some claims regarding the potential for nonnative processing, the present data suggest that L1 and L2 speakers show similar ERP responses when processing agreement, even when the L1 lacks the relevant distinction.

The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents’ mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13–19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who previously exhibited higher resting HRV or higher HRV reactivity. For adolescents who exhibited lower resting HRV or HRV augmentation, COVID-19 stress was not associated with emotional problems. Conversely, lower resting HRV indicated vulnerability to the effect of COVID-19 family adversity on emotional problems. Different patterns of parasympathetic functioning may reflect differential susceptibility to the effects of COVID-19 stress versus vulnerability to the effects of COVID-19 family adversity on mental health during the pandemic.

Social anxiety disorder (SAD) is commonly diagnosed during adolescence and is associated with psychological stress reactivity and heightened physiological arousal. No study, however, has systematically examined which aspects of autonomic nervous system function mediate likely links between stress sensitivity and social anxiety symptoms in adolescents. Here, we assessed 163 adolescents (90 females; 12.29 ± 1.39 years) with respect to life stress and social anxiety symptoms, and measured respiratory sinus arrhythmia (RSA) and skin conductance levels (SCL) during a psychosocial stress paradigm. We operationalized stress sensitivity as the residual variance in subjective stress severity after accounting for objective severity and changes in autonomic regulation using standardized change scores in RSA and SCL. In females only, stress sensitivity and social anxiety symptoms were significantly correlated with each other (p < .001) and with autonomic regulation during both reactivity and recovery (all ps < 0.04). Further, sympathetic nervous system dominance during recovery specifically mediated associations between stress sensitivity and social anxiety symptoms (B = 1.06, 95% CI: 0.02–2.64). In contrast, in males, stress sensitivity, autonomic regulation during reactivity or recovery, and social anxiety symptoms were not significantly associated (all ps > 0.1). We interpret these results in the context of psychobiological models of SAD and discuss implications for interventions targeting autonomic processes.

The warm, equable, and ice-free early Eocene Epoch permits investigation of ecosystem function and macro-ecological patterns during a very different climate regime than exists today. It also provides insight into what the future may entail, as anthropogenic CO2 release drives Earth toward a comparable hothouse condition. Studying plant–insect herbivore food webs during hothouse intervals is warranted, because these account for the majority of nonmicrobial terrestrial biodiversity. Here, we report new plant and insect herbivore damage census data from two floodplain sites in the Wind River Basin of central Wyoming, one in the Aycross Formation (50–48.25 Ma) at the basin edge (WRE) and the second in the Wind River Formation in the interior of the basin (WRI). The WRI site is in stratigraphic proximity to a volcanic ash that is newly dated to 52.416 ± 0.016/0.028/0.063 (2σ). We compare the Wind River Basin assemblages to published data from a 52.65 Ma floodplain flora in the neighboring Bighorn (BH) Basin and find that only 5.6% of plant taxa occur at all three sites and approximately 10% occur in both basins. The dissimilar floras support distinct suites of insect herbivores, as recorded by leaf damage. The relatively low-diversity BH flora has the highest diversity of insect damage, contrary to hypotheses that insect herbivore diversity tracks floral diversity. The distinctiveness of the WRE flora is likely due to its younger age and cooler reconstructed paleotemperature, but these factors are nearly identical for the WRI and BH floras. Site-specific microenvironmental factors that cannot be measured easily in deep time may account for these differences. Alternatively, the Owl Creek Mountains between the two basins may have provided a formidable barrier to the thermophilic organisms that inhabited the basin interiors, supporting Janzen's hypothesis that mountain passes appear higher in tropical environments.

OBJECTIVES/SPECIFIC AIMS: Hepatitis C viral (HCV) infections are rising significantly both in young adults and as newly diagnosed cases in “baby boomers.” New HCV therapeutics cure over 95% of cases, and a call has been made for elimination of the epidemic by 2030; yet major HCV cascade of care (CoC) barriers exist. We secured CTSA pilot funding to obtain preliminary data for an innovative clinical trial utilizing big data modeling toward HCV elimination. METHODS/STUDY POPULATION: Our pilot work has developed a coordinated, real-time clinical data management process across 3 major CTSA affiliated hospital systems (MedStar Health, Emory-Grady, and UT-Southwestern), and additional data will be obtained from a pragmatic clinical trial. Electronic medical records data will be mapped to the OHDSI model, securely transmitted to Oak Ridge National Laboratory, Knoxville, TN and exposed to integrated data, analytics, modeling and simulation (IDAMS). RESULTS/ANTICIPATED RESULTS: Our U01 CTSA application proposes that HCV-IDAMS will model modifications to the established HCV CoC at community and population levels and thus simulate future outcomes. As data volume increases, system knowledge will expand and recursive applications of IDAMS will increase the accuracy of our models. This will reveal real-world reactions contingent upon population dynamics and composition, geographies, and local applications of the HCV CoC. DISCUSSION/SIGNIFICANCE OF IMPACT: Only an innovative, integrated approach harnessing pragmatic clinical data, big data and supercomputing power can create a realistic model toward HCV elimination.