OBJECTIVES/GOALS: The goal of this study was to examine the attitudes of central Pennsylvania rural residents toward data sharing in the setting of the COVID-19 pandemic. We determined their willingness to provide cell phone data and personal information to public health staff investigating COVID-19 cases, as well as their concerns about sharing this information. METHODS/STUDY POPULATION: We used the electronic medical records of an academic healthcare institution in central Pennsylvania to obtain names and addresses of patients who had visited an outpatient clinic or been an inpatient within the prior three years, were 18 years or older, and who resided in a community defined as rural by the Commonwealth of Pennsylvania. The survey included four statements about contact tracing, three statements about intent to receive the COVID-19 vaccine, and validated scales for general trust and for distrust in healthcare organizations. All study variables were summarized to determine their distributions, and bivariate binomial logistic regression was conducted. A multivariable model including all of the independent variables was then fit for each outcome variable. RESULTS/ANTICIPATED RESULTS: The response rate was 19.5%. 95 % of respondents were white, 56% were female, and nearly two-thirds were older than 60 years. Binomial logistic regression showed that both distrust in healthcare organizations and political values influenced respondents willingness to share information with contact tracers as well as their concerns about sharing. In multivariate analysis, political values were a consistent predicator of willingness to share and concerns about sharing. Respondents who indicated that they wanted to get vaccinated as soon as possible were significantly more likely than those who did not want to be vaccinated to be willing to share their cell phone location data and personal data. Conversely, they were less likely to be concerned with these data being shared without their permission. DISCUSSION/SIGNIFICANCE: Understanding rural residents concerns about sharing personal information is critical if we are to develop successful strategies for lessening the impact of COVID-19 and managing future pandemics. This study is a first step in eliciting such concerns in the context of COVID-19and has implications for directing a successful pandemic response.

OBJECTIVES/GOALS: Implementation science evaluations are often too time-intensive to provide actionable feedback during implementation, suggesting the need for more agile methods. We present an evaluation of the World Health Organization’s Emergency Care Toolkit implementation in Zambia using rapid qualitative methods to provide timely feedback. METHODS/STUDY POPULATION: We evaluated the implementation of the Emergency Care Toolkit in eight general and referral hospitals in Zambia in 2023 using a rapid-cycle, qualitative template analysis approach grounded in the Consolidated Framework for Implementation Research (CFIR). We gathered qualitative data from operational field notes, focus groups, and key informant interviews of administrators, clinicians, nurses, and support staff in all eight hospitals in Zambia. We parsimoniously applied CFIR constructs and tool-specific codes, focused on barriers and facilitators, to allow for rapid but comprehensive cross-case analysis. The results were used to generate a matrix of stakeholder-relevant, plain-language barriers and facilitators for each tool. RESULTS/ANTICIPATED RESULTS: We completed eight site visits with focus groups and interviews following initial implementation in September 2023 to gather firsthand knowledge related to implementation of the Toolkit. The CFIR-focused coding accelerated analysis by centering on barriers and facilitators for each tool while maintaining a comprehensive evaluation framework. Summary tables of barriers and facilitators were easily interpreted by lay stakeholders. Visualization in tables allowed for identification of common themes across tools and hospitals, making comprehensive recommendations to the implementation and dissemination process quickly possible. We anticipate the study findings will empower implementing partners to make timely, actionable improvements. DISCUSSION/SIGNIFICANCE: Rapid-cycle qualitative implementation evaluations allow for rigorous yet timely feedback on the implementation process compared to traditional methods. This efficient strategy is particularly important in resource-constrained environments where inefficient implementation wastes limited resources and create delays that cost lives.

OBJECTIVES/GOALS: Vaginal ring delivery of antiretroviral drugs may provide protection against acquisition of HIV-1 when used as pre-exposure prophylaxis. As part of a randomized placebo-controlled safety trial of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR), we assessed product acceptability through surveys of 17 women after continuous ring use. METHODS/STUDY POPULATION: Sexually active, HIV negative women between the ages of 18 and 45 were enrolled to investigate the safety and pharmacokinetics of three months of continuous TDF IVR use. The study was designed to include 40 US participants randomly assigned (3:1) to a TDF or placebo IVR. Twelve were randomized to TDF and five were assigned to the placebo group before the study was electively discontinued due to development of vaginal ulcerations in eight women in the TDF group. Acceptability data regarding TDF and placebo ring use was gathered via self-administered, computer-based questionnaires at the one- and three-month study visits. Participants were asked about overall attitudes and feelings regarding the TDF and placebo IVR, vaginal changes associated with ring use, and their experiences with ring use during menses and with sex. RESULTS/ANTICIPATED RESULTS: The mean age of participants was 30 years (range 18 - 42). Sixteen of 17 (94%) participants completed all study questions at both visits. When asked about ring likeability at one-month, 12 of 16 (75%) women reported overall liking the ring, including 5 of 8 (63%) who developed ulcerations. Vaginal changes described during ring use included 8 participants who indicated that the “vagina was wetter” and 2 who reported that the “vagina was drier.” Additionally, 10 of 12 (83%) who had their period during the first month of the study were not bothered by ring use during menses, and 11 of 16 (69%) stated that the ring was not bothersome with use during sex. When asked at the three-month visit, most reported that they would prefer to wear the ring rather than use a condom during sex, however, condom use was low at baseline in this population. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite unanticipated ulcers, the IVRs were acceptable, especially when used with menses and during sex. Regardless of the group assigned or vaginal changes experienced, and even amongst those who developed ulcerations, the women had positive attitudes towards the ring, which is promising for future use of vaginal rings as a method for HIV prevention.

OBJECTIVES/SPECIFIC AIMS: Autism spectrum disorder (ASD) affects 1 in 68 people and includes restricted, repetitive behavior, and social communication deficits. Aspects of face processing (i.e., identity, emotion perception) are impaired in some with ASD. Neuroimaging studies have shown aberrant patterns of brain activation and connectivity of face processing regions. However, small sample sizes and inconsistent results have hindered clinical utility of these findings. The study aims to establish consistent patterns of brain responses to faces in ASD and provide directions for future research. METHODS/STUDY POPULATION: Neuroimaging studies were identified through a multi-database search according to PRISMA guidelines. In total, 23 studies were retained for a sample size of 383 healthy controls and 345 ASD. Peak coordinates were extracted for activation likelihood estimation (ALE) in GingerALE v2.3.6. Follow-up ALE analyses investigated directed Versus undirected gaze, static Versus dynamic, emotional Versus neutral, and familiar Versus unfamiliar faces. RESULTS/ANTICIPATED RESULTS: Faces produced bilateral activation of the fusiform gyrus (FG) in healthy controls (−42 −52 −20; 22 −74 −12, p<0.05, FDR) and left FG activation in ASD (−42 −54 −16, p<0.05, FDR). Activation in both groups was lateral to the mid-fusiform sulcus. Follow-up results pending. DISCUSSION/SIGNIFICANCE OF IMPACT: Reduced right FG activation to faces may inform biomarker or response to intervention studies. Mid-fusiform sulcus proved a reliable predictor of functional divides should be investigated on a subject-specific level.

OBJECTIVES/GOALS: Disparities in pediatric kidney transplantation (KT) result in reduced access and worse outcomes for minority children. We aimed to assess the impact of recent systemic changes on these disparities. METHODS/STUDY POPULATION: Retrospective cohort study of pediatric patients utilizing data from the United States Renal Data System (USRDS) and Scientific Registry of Transplant Recipients (SRTR). We compared access to transplantation, time to deceased donor kidney transplant (DDKT), and allograft failure (ACGF) using Cox proportional hazards in the 4 years preceding KAS to the 4 years post-KAS implementation. RESULTS/ANTICIPATED RESULTS: Compared to the pre-KAS era, patients post-KAS were more likely to be pre-emptively listed (26.8% vs 38.1%, p<0.001) and pre-emptively transplanted (23.8% vs 28.0%, p<0.001), however these benefits were not uniform across racial groups. Only 12.7% and 15.7% of Black and Hispanic children received a pre-emptive transplant compared to 29.6%, 49.8% and 54.4% of White, Asian and Other race children respectively. Compared to White children, Black and Hispanic children had a lower likelihood of transplant listing within 2 years of first dialysis service aHR 0.67 (0.59-0.76) and 0.82 (0.73-0.92), in the post-KAS era. Time to DDKT after listing was comparable across all racial groups in both eras. Black children have disproportionally worse 5-yr ACGF, aHR 1.50 (1.08-2.09), p=0.02. DISCUSSION/SIGNIFICANCE: After KAS implementation there remains equity in time to DDKT, however disparities persist in transplant listing and ACGF among Black children. Further studies are needed to identify granular SES factors impacting delayed referral and systemic barriers to transplant, as well as risk factors for poor allograft outcomes among minority children.

OBJECTIVES/GOALS: The aim of this study was to design and implement the Pharos application to map the cellular network support structure around Lake Victoria in Western Kenya. Additionally, the Pharos app was used to collect images of disease-relevant vector and plant life surrounding the study sites to train a computer vision algorithm to map disease-relevant areas. METHODS/STUDY POPULATION: Pharos was provided to a 4-person team of healthcare workers. The app was pre-loaded on both iOS and Android devices to be used during the course of normal field activity. Pharos ambiently collects network data and the team was asked to capture images of landmarks relevant to their work in schistosomiasis control. The field team traveled to 4 counties of differing schistosomiasis risk surrounding Kisumu, Kenya in autumn 2022 and will return to these areas in early spring 2023. Cell signal indicators (upload and download speed) were collected and asynchronously uploaded to a database for further analysis. Additionally, all landmark images (cell network towers, landmarks (e.g. schools, churches, public centers), plant life, vectors, and water bodies) were recorded and tagged with GPS coordinates and time stamps. RESULTS/ANTICIPATED RESULTS: Iterative development powered by small, informal, user-centered focus group discussions with the field team led to several key adaptations to the Pharos software. On the first deployment, 1,297 unique upload and download events were recorded across 3 Kenyan cell providers and 1 American provider. 1,197 data points were collected in Kenya using both Android and iOS devices using several versions of the Pharos application. 154 unique landmarks were photographed, but a distinct difference in landmark recording was observed between devices, prompting a transition to iOS-only data collection. Of the landmarks recorded, the majority (120, 77.9%) were landmarks or cell network towers, while 22.1% were water bodies, plant life, or schistosomiasis vectors. DISCUSSION/SIGNIFICANCE: For the first time, high-detail maps of cellular signal and critical schistosomiasis-related landmarks were generated. Future work on this project is focused on training computer vision algorithms using the captured images of environmental and ecological factors to isolate possible areas of human disease transmission.

OBJECTIVES/SPECIFIC AIMS: This research project envisions the integration of Homeless Management Information System (HMIS) and UI Health Cerner electronic medical record (EMR) system with the following goals: (1) enable sharing of data about the status of the housing insecure and homeless. (2) Identify and match patient record accurately. (3) Record housing insecurity or homelessness information with structured data elements in the EMR. METHODS/STUDY POPULATION: We created a Master Person Index (MPI) of the homeless individuals from HMSI using OpenEMPI software package, which is an open source implementation of an Enterprise Master Patient Index (EMPI). An entity model was generated based on the selective data elements from HMIS database, which were relevant for the patient identity management and healthcare service management. An automated script was implemented to extract data from HMIS and load it into OpenEMPI to build the MPI. Once the MPI is setup, the Emergency Department users were able to perform patient identity matching and confirm housing insecure or homeless status of their patients by querying the index using the web-based tool. We developed structured data elements to record homelessness information, which will allow us to measure the prevalence of this risk among patients. We are also exploring the possibility to integrate the systems the using the IHE PIX/PDQ profile, which provides ways for healthcare applications to query a patient information server for a patient based on user-defined search criteria, and retrieve a patient’s information directly into the application. RESULTS/ANTICIPATED RESULTS: We implemented a MPI of homeless individuals, which would allow the emergency department users to perform patient identity matching of housing insecure or homeless patients, without undue privacy intrusions. We are confident that IHE PIX/PDQ profile is able to support the integration of healthcare and housing and homeless services systems and enable the data sharing in an efficient way. DISCUSSION/SIGNIFICANCE OF IMPACT: The project addressed the gap in the sharing of data about housing insecure or homeless persons between healthcare and housing and social services that will result in improvements in coordination of care, reduce the cycle time from recognition of risk to the referral to housing and services and improve health outcomes and residential stability. Successful completion of this integration project will give us a model that we can scale to many other communities.

Clinical research professionals (CRPs) are essential contributors to clinical and translational research endeavors, encompassing roles such as research nurses, research coordinators, data managers, and regulatory affairs specialists. This paper reports on the implementation of a novel training program for the CRPs, the Co-mentoring Circles Program, developed by the University of Florida Health Clinical Research Professionals Consortium, and proposes an initial logic model of CRP workforce development informed by the observations, participant feedback, and the established Translational Workforce Logic Model. The co-mentoring program was delivered through an online didactic curriculum and bi-monthly meetings over nine months, from January to September 2022. The formative evaluation identified the factors that support CRP workforce development through knowledge acquisition and professional relationship building. Finally, this paper proposes a logic model of CRP workforce development, including financial and human inputs, didactic and co-mentoring activities, workforce outputs, outputs related to workforce and clinical research study progress, and resulting impacts of increased national capacity for translational research and increased rate of research translation.

Machine learning (ML) provides the ability to examine massive datasets and uncover patterns within data without relying on a priori assumptions such as specific variable associations, linearity in relationships, or prespecified statistical interactions. However, the application of ML to healthcare data has been met with mixed results, especially when using administrative datasets such as the electronic health record. The black box nature of many ML algorithms contributes to an erroneous assumption that these algorithms can overcome major data issues inherent in large administrative healthcare data. As with other research endeavors, good data and analytic design is crucial to ML-based studies. In this paper, we will provide an overview of common misconceptions for ML, the corresponding truths, and suggestions for incorporating these methods into healthcare research while maintaining a sound study design.

The Students Participating as Ambassadors for Research in Kentucky (SPARK) program provides novel health equity research training and targeted mentorship for undergraduates, particularly those from groups underrepresented in the biomedical and behavioral research and workforce. SPARK aims to address inadequate diversity in the medical and scientific research fields by providing comprehensive research mentorship and skill-building. Unlike most existing research training programs that are brief, focus on laboratory research, or are limited to graduate students and junior faculty, SPARK delivers a 16-month intensive behavioral and population health science training, equipping students with needed tools to conceptualize, plan, execute, and analyze their own health equity research study. Trainees complete didactic coursework on health equity, study design and proposal development, data analysis, and ethics. Students receive a stipend and research expenses, and multiple mentors guide them in creating original research projects for which they serve as Principal Investigator. Students disseminate their findings annually at an academic research conference as a capstone. Evaluation data from the first three cohorts suggest SPARK has been pivotal in preparing students for graduate studies and research careers in health equity and behavioral and population health sciences, providing strong support for further investments in similar undergraduate research training models.

The COVID-19 global pandemic required the rapid development of vaccines with a quick start up of phase 1–3 studies with large enrollment targets. The University of California San Diego was identified as a site for the phase 3 trial of the mRNA-1273-SARS-CoV-2 vaccine. There were many challenges with scaling up a large-scale clinical trial in such a short time. This report describes the processes and procedures that were implemented to successfully complete the enrollment target in under 10 weeks. This required the team to identify existing tools that could rapidly be accessed to develop a database, scheduling system, effective communication, document management, staff time tracking/efficiency, subject scheduling/tracking, project management, and accrual/study performance. The outcome of these efforts resulted in rapid enrollment and study completion in a short time. The lessons learned from this experience can be used by other clinical trial sites faced with similar challenges.

OBJECTIVES/SPECIFIC AIMS: To understand the role of PGF2a and to characterize a novel cyclooxyrgenase (COX)-independent prostaglandin synthesis pathway in epithelial ovarian cancer. METHODS/STUDY POPULATION: We used high grade epithelial ovarian cancer cell line (OVCAR3) as a model to study our pathway. Our main mode of PGF2a detection is through mass spectrometry. RESULTS/ANTICIPATED RESULTS: Our current results suggest the OVCAR3 cells may synthesize PGF2a independently of COX enzymes. We anticipate this novel pathway may be dependent on the TGFb pathway. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding the role and synthesis pathway of PGF2a may allow us to uncover a novel therapeutic pathway for high grade ovarian cancer.

OBJECTIVES/GOALS: Although there is ample evidence that environmental contaminants impact reproductive health, the exact mechanisms of action, for the most part, remains unclear. We sought to determine whether known contaminants in Puerto Rico can contribute to the selection of a bioassay to add granularity to geospatial contamination data at the cellular level. METHODS/STUDY POPULATION: A PubMed literature search was conducted: Puerto Rico AND Vieques AND Environmental Contaminants AND Heavy Metals OR Phthalates OR Metals OR PCB OR Air Pollution OR CVOC . Additional inclusion criteria were free full text, English language and year of publication between 2000 to 2022 (n = 244 studies). References that were not related to Puerto Rico and environmental contaminants in air, soil, water, or vegetation were excluded. A second PubMed literature search was conducted to determine whether a clinical link has been established between contaminant exposure and the male reproductive system. Search terms were: heavy metals AND hypospadias OR cryptorchidism NOT female NOT animal NOT review , heavy metals AND male infertility NOT female NOT animal NOT review . The same strategy was used for phthalates. RESULTS/ANTICIPATED RESULTS: We found that 12 out of 15 studies that were conducted in the Archipelago of Puerto Rico between 2000-2022 reported heavy metals- and/or phthalates- contamination in soil and water. We also found that there is a paucity of clinical studies that consider plausible relationships between a given contaminant and congenital conditions or male reproductive function. Specifically, we found that heavy metal exposure has been linked to hypospadias (n=1 study), comorbidity of hypospadias plus cryptorchidism (n= 1 study) or male infertility (n=14 studies). Phthalates exposure has been linked to comorbidity of hypospadias and cryptorchidism (n=1 study) or male infertility (n=1 study). Male subfertility has been overlooked so far. We noted that Sertoli cell dysfunction has been linked to all of these conditions. DISCUSSION/SIGNIFICANCE: The geography of Puerto Rico provides an opportunity to close the gap in knowledge between environmental contamination and male reproductive health. Based on our findings, we propose that the use of a bioassay with an immortalized Sertoli cell line can uncover the cellular processes that may be affected in male reproduction upon contaminant exposure.

OBJECTIVES/GOALS: The present study investigated contextual factors linking rural Black American mens experiences of racial discrimination to their COVID vaccine hesitancy. Specifically, we investigated two potential mediators of the link between racial discrimination and COVID vaccine hesitancy: (1) medical mistrust, and (2) COVID conspiratorial beliefs. METHODS/STUDY POPULATION: Hypotheses were tested using structural equation modeling with 7 waves of data from 504 Black American men participating in a longitudinal study of risk behavior and substance use during young adulthood. At baseline, mens mean age was ~20. Data were collected before and during the COVID pandemic. The COVID pandemic began after Wave 4 data had been collected. A series of 3 online surveys, at 3-month intervals, were conducted to examine acute COVID-related stressors and impacts. RESULTS/ANTICIPATED RESULTS: The dual mediation model fit the data as follows: χ2(7) = 19.00, p < .008; χ2/ df = 2.71; RMSEA = 0.06; CFI = 0.95; SRMR= 0.04. Results indicated that racial discrimination was directly associated with increases in COVID conspiratorial beliefs (B = .14, p<.05) and medical mistrust (B = .22, p<.001). COVID conspiratorial beliefs was directly associated with increases in COVID vaccine hesitancy (B = .11, p<.05). Indirect effects were detected whereby racial discrimination was associated with increases COVID vaccine hesitancy indirectly via increases in COVID conspiratorial beliefs (B = 0.016; 95% CI [0.001, 0.048]). DISCUSSION/SIGNIFICANCE: Investigating race-related factors in the context of vaccine hesitancy is a novel area of inquiry that could facilitate the development of targeted interventions for Black Americans to increase their vaccine uptake. Future research is needed to more thoroughly examine the relationship between racial discrimination and conspiratorial beliefs.

OBJECTIVES/GOALS: We report an automated manufacturing system, and a series of cylindrical multi-layer microfluidic artificial lungs manufactured with the system and tested for fluidic fidelity and function. METHODS/STUDY POPULATION: A Roll-to-Roll (R2R) system to engrave multiple-layer devices was assembled. A 100 um-thick silicone sheet passes through an embedded CO2 laser engraver, which creates patterns of any geometry on the surface. The sheet is plasma-activated to create an irreversible bond, and rerolled into a processed device. Unlike typical applications of R2R, this process is synchronized to achieve consistent radial positioning. This allows the fluidics in the device to be accessed without being unwrapped. The result is a cylindrical core surrounded by many layers of microfluidic channels that can be accessed through the side of the device or through fluidic vias. This core is cut to expose the microfluidic layers, and then installed into a housing which routes the fluids into their respective microfluidic flow paths. RESULTS/ANTICIPATED RESULTS: To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer microfluidic artificial lungs (µALs). Gas and blood flow channels are engraved in alternating layers and routed orthogonally. The close proximity of gas and blood separated by gas-permeable PDMS permits CO2 and O2 exchange. Three µALs were successfully manufactured. Their flow paths were visualized using dyed water and checked for leaks. Then they were evaluated using water for pressure drop and CO2 gas-exchange. The top performing device had 15 alternating blood and gas layers. Test with whole blood demonstrated oxygenation from venous (70%) saturation levels to arterial (95%) saturation levels at a flow rate of 3 ml/min. DISCUSSION/SIGNIFICANCE: The ability to cost-effectively produce high surface area microfluidic devices would bring many small-scale technologies from the realm of research to clinical and commercial applications. In particular, most microfluidic artificial lungs only have small rated flows due to a lack of manufacturing processes able to create high surface area devices.

OBJECTIVES/SPECIFIC AIMS: Traditional hospice focuses on symptoms and quality of life (QOL) at the very end of life. Clinical symptoms and QOL in the last 1–2 years of life are also important and may be affected by dementia. Our objective was to characterize how symptoms differ between people with and without dementia in the last years before death and whether symptoms impact social dimensions of QOL. METHODS/STUDY POPULATION: We studied 1270 community-dwelling participants who died between 2011 and 2015 in the National Health and Aging Trends Study, a nationally representative cohort of older adults. From the last interview before death, we examined sensory (vision; hearing), physical (pain; problems with breathing, chewing/swallowing, speaking, upper or lower extremity strength/movement, and balance/coordination), and psychiatric (depression; anxiety; insomnia) symptoms by dementia status. We examined associations between symptoms and participation restrictions (visiting family/friends, attending religious services, participating in clubs/activities, going out for enjoyment, and engaging in favorite activity). RESULTS/ANTICIPATED RESULTS: Low energy (69%), pain (59%), and lower extremity strength/movement problems (56%) were most common. People with dementia (37.3% of decedents) had higher prevalence of all symptoms (p≤0.01), except pain, breathing problems, and insomnia. Dementia and greater symptom burden were independently associated with greater odds of participation restrictions (p<0.05). Problems speaking were significantly associated with limitations in all activities except for attending religious services. Balance/coordination, energy, and strength/movement problems were associated with limitations in 3 activities. DISCUSSION/SIGNIFICANCE OF IMPACT: Sensory, physical, and psychiatric symptoms are common in the year before death, with greater symptom prevalence in people with dementia. Both dementia and symptoms are associated with restrictions in participation. Older patients may benefit not only from earlier emphasis on palliative care but also programs and assistive devices that accommodate physical impairments.

ABSTRACT IMPACT: This proof-of-concept study demonstrates that systematically altering limb dynamics with two exoskeleton devices alters ingrained, bilateral upper-limb coordination with the potential to rehabilitate functional reaching in chronic stroke survivors OBJECTIVES/GOALS: Advances in virtual reality and exoskeleton technologies have allowed researchers to alter upper limb coordination with more precision than ever before. The goal of this study was to systematically enhance the use of the nondominant limb during a bimanual reaching task, with an eye towards improving rehabilitative strategies post stroke. METHODS/STUDY POPULATION: Healthy, right-handed volunteers performed a bimanual reaching task in virtual reality (VR) space while simultaneously moving under the influence of two exoskeleton devices. The VR task had participants move a shared cursor, displayed at the midpoint between the hands, to targets arranged at shoulder and eye levels and located at 70% of full arm extension. Two exoskeleton devices applied either resistive torque to the dominant limb or assistive torque to the non-dominant limb. Three-dimensional hand position data were recorded at 50 Hz and analyzed offline. The primary outcome measure was relative contribution, calculated as the ratio of dominant/non-dominant displacement. RESULTS/ANTICIPATED RESULTS: Preliminary results from 3 participants showed that during baseline trials, when no torque was applied by the exoskeletons, relative contribution was 50.6% in favor of the dominant hand, with the dominant hand reaching on average 1.1cm farther than the left. When the exoskeletons resisted movement in the dominant limb while simultaneously assisting movement in the non-dominant limb, relative contribution was 49.7% indicating an increase in non-dominant limb usage. Further analysis showed that this effect was driven by one participant who reached 3.7cm farther with her non-dominant hand compared to baseline. DISCUSSION/SIGNIFICANCE OF FINDINGS: These pilot data suggest our testing platform is capable of altering normal coordination patterns and is likely the result of participants adopting an optimal control strategy imposed by the shared cursor. These findings will form the basis for a rehabilitation intervention to promote the use of the paretic limb in chronic stroke survivors.

OBJECTIVES/SPECIFIC AIMS: Background: Children with autism spectrum disorder (ASD) show a broad range of unusual responses to sensory stimuli and experiences. It has been hypothesized that early differences in sensory responsiveness arise from atypical neural function and produce “cascading effects” on development across a number of domains, impacting social and communication skill, as well as broader development in children affected by ASD. A primary challenge to confirming these hypotheses is that ASD cannot be definitely diagnosed in the earliest stages of development (i.e., infancy). A potential solution is to prospectively follow infants at heightened risk for ASD based on their status as infant siblings of children who are diagnosed. We examined the developmental sequelae and possible neurophysiological substrates of three different patterns of sensory responsiveness—hyporesponsiveness (reduced or absent responding to sensory stimuli) and hyperresponsiveness (exaggerated responding to sensory stimuli), as well as sensory seeking (craving of or fascination with certain sensory experiences). Infants at high risk (HR) for ASD were compared with a control group of infants at relatively lower risk for ASD (LR; siblings of children with typical developmental histories). Objectives: Research questions included: (a) Do HR infants differ from LR infants in early sensory responsiveness?, (b) Does sensory responsiveness predict future ASD and related symptomatology? and (c) Is sensory responsiveness predicted by resting brain states? METHODS/STUDY POPULATION: Methods: To answer these questions, we carried out a longitudinal correlational investigation in which 20 HR infants and 20 LR controls matched on sex and chronological age were followed over 18 months. At entry to the study, when infants were 18 months old, sensory responsiveness was measured using the Sensory Processing Assessment and the Sensory Experiences Questionnaire, and a number of putative neural signatures of early sensory differences were measured via resting state EEG. When infants were 24 and 36 months of age, ASD and related symptomatology was evaluated in a comprehensive diagnostic evaluation. RESULTS/ANTICIPATED RESULTS: Results: HR infants trended towards increased hyporesponsiveness and hyperresponsiveness and showed significantly elevated levels of sensory seeking relative to LR controls at 18 months of age. Both groups, furthermore, displayed a high degree of heterogeneity in sensory responsiveness. Atypical sensory responsiveness (increased hyperresponsiveness and/or hyporesponsiveness, as well as sensory seeking behavior) predicted several aspects of ASD and related symptomatology, including social, communication, and play skill, and was associated with differences in resting brain state, including metrics of oscillatory power, complexity, and connectivity, as well as hemispheric asymmetry. Moderation analyses revealed that several relations varied according to risk group, such that associations were stronger in magnitude in the HR Versus LR group. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion: Findings provide empirical support for the notion that early sensory responsiveness may produce cascading effects on development in infants at heightened risk for ASD. Differences in resting brain states may underlie atypical behavioral patterns of sensory responsiveness. From a clinical standpoint, results suggest that early sensory differences may be useful for predicting developmental trajectories, and be potentially important targets for early preventive intervention, in infants at risk for autism.