ABSTRACT IMPACT: This work assesses clinical implementation of a surface guided imaging system to improve the accuracy radiation delivery for treatment of brain lesions using a patient CT derived head phantom. OBJECTIVES/GOALS: Advancements in radiotherapy design have made clinical demand for efficient and accurate methods to deliver stereotactic radiosurgery (SRS) for treatment of intracranial lesions. This study assesses the potential of using surface guided imaging for setup using a 3D patient specific head phantom. METHODS/STUDY POPULATION: A single isocenter, multiple metastases SRS plan was generated on a CT derived RTsafe Prime phantom made of tissue equivalent materials and a polymer gel insert. Five targets of varying diameters were treated with 8Gy of radiation using two different positioning techniques. The first gel insert was irradiated within the phantom according to internal alignment with standard orthogonal x-ray imaging while the second setup used surface guided imaging, based on external anatomy. 42 hours after irradiation, the phantom was scanned in a head coil using a 1.5T MRI. MR images were fused with the patient CT data and structure set to further evaluate calculated and measured dose distributions. RESULTS/ANTICIPATED RESULTS: Discrepancies in phantom setup according to standard orthogonal x-ray imaging compared to surface guided imaging demonstrated to be <1mm in each translational (vertical, longitudinal, and lateral) and angular (rot, roll, pitch) directions. The 3D gel inserts permitted spatial analysis to compare dose distributions of measured values to those calculated in a treatment planning system (TPS). 3D GI (Gamma Index) analysis showed good alignment in high dose regions and resulted in passing rates >94% (5%/2mm) and >87% (3%/2mm). Finally, 3 of 5 targets showed better 3D GI passing rates and less geometric offset for positioning with the surface guided imaging. DISCUSSION/SIGNIFICANCE OF FINDINGS: 3D spatial analysis of human like phantoms demonstrated that patient positioning according to external anatomy performed comparable to standard methods aligning to the internal anatomy, for a multiple met SRS treatment.

OBJECTIVES/GOALS: Nearly 3 million Americans live with arm impairment following stroke. While as many as 20% of patients fully recover, individual differences in recovery make one-size-fits-all rehabilitation approaches suboptimal. The goal of this study was to use our custom rehabilitation platform to identify neuromuscular biomarkers of arm control in stroke. METHODS/STUDY POPULATION: Chronic stroke survivors (N = 10) reached for targets in a virtual reality environment using both hands. They completed 162 reaches divided into 3 blocks. Following baseline, we used our custom exoskeletons to provide 50% arm weight assistance to the impaired limb and 50% arm weight resistance to the non-impaired limb. We removed the exoskeletons during the retention block. We used electromyography to approximate muscle activity in the anterior deltoids. Relative contribution (RC) was calculated as the displacement of the impaired arm divided by the sum of displacements for both arms. Muscle contribution (MC) was calculated as the root mean square of impaired arm muscle activity divided by the sum of activity for both deltoids, normalized to maximum voluntary contraction. RESULTS/ANTICIPATED RESULTS: During baseline, RC of the impaired limb was 43%; patients reached significantly less with their impaired arm compared to their non-impaired arm (p = 0.02). MC of the impaired deltoid was 56% and was similar between arms (p = 0.5). During loading, RC did not change relative to baseline (p = 0.87), but MC tended to decrease by 11% (p = 0.12). These results suggest a tradeoff between kinematic and muscular control of reaching. This new finding closely matches our previous work in 12 healthy controls, where we found a 2% increase in RC and a 11% decrease in MC. Importantly, 4/10 patients exhibited an inverse tradeoff (i.e., decrease in RC and/or increase in MC). We will analyze neuroimaging data to determine the role lesion size and location play in predicting an individual’s response to gravity compensation. DISCUSSION/SIGNIFICANCE: Our tradeoff analysis serves as a potential neuromuscular biomarker of stroke survivors’ responsiveness to gravity compensation. This forms the basis for personalized technologies for stroke rehabilitation. With further development, clinicians can use our platform to fine-tune compensation levels based on the individual needs of the patient.

ABSTRACT IMPACT: The implementation of DPYD and UGT1A1 pharmacogenetic testing, a promising tool of precision medicine, translates evidence-based research into clinical oncology practice with personalized dosing to better predict interpatient variability in chemotherapy tolerability. OBJECTIVES/GOALS: Patients with DPYD and UGT1A1 genetic variants are at risk for severe toxicity from fluoropyrimidines and irinotecan, respectively. We propose that providing clinicians with the option to order a pharmacogenetic (PGx) test with relevant dose recommendations will increase test uptake to guide pharmacotherapy decisions and improve safety outcomes. METHODS/STUDY POPULATION: We plan to conduct a non-randomized, pragmatic, open-label study in 600 adult patients with gastrointestinal (GI) cancers initiating a fluoropyrimidine- and/or irinotecan-based regimen at three cancer centers within a health system. Implementation metrics of a new, in-house laboratory developed PGx test will be measured, including feasibility of returning results within one week, fidelity of providers following dose recommendations, and penetrance via test ordering rates. Clinical aims will include assessing severe toxicity during the first six months of chemotherapy. Outcomes will be compared to a historical control of GI cancer patients enrolled in a biobank and treated with standard dose chemotherapy. RESULTS/ANTICIPATED RESULTS: We anticipate that there will be an increase in PGx test uptake given its shorter turnaround time to facilitate clinical decision-making prior to the first dose of chemotherapy. Through integration of test results in the electronic health record (EHR) and clinical decision support tools for patients with actionable genotypes, we also expect that providers will have a high level of agreement to the recommended dose adjustments. We anticipate a decreased incidence of severe (Grade >3) toxicity among prospectively genotyped patients in the first six months of chemotherapy compared to DPYD and UGT1A1 variant carriers in the historical control group. Exploratory clinical utility data on costs of hospitalizations, chemotherapy treatment, PGx test, and medical services will also be reported. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study aims to address barriers identified by key stakeholders to implementing PGx testing to better tailor chemotherapy dosing to the genetic profiles to patients. This may prevent adverse event-related hospitalizations, improve quality of life for patients, and reduce health system resource utilization costs.

OBJECTIVES/GOALS: Contrary to current dogma, prior work has suggested that in humans, SNP-determined endothelial cell reduction in CD39 expression associates with a diminished risk for venous thromboembolism. Our objective was to examine the impact of endothelial cell (EC) CD39 expression on arterial thrombosis that replicates human data. METHODS/STUDY POPULATION: We generated a novel CD39 cell-specific conditional knockout mouse line for endothelial cells (EC-cKO: Tie2-Cre+; cd39flox/flox versus WT: Tie2-Cre-; cd39flox/flox). We validated the knockout of expression of CD39 on EC using FACS analysis and measured EC CD39 activity using the Kinase Glo ATP hydrolysis assay on magnetically sorted EC. We then used a standard FeCl3 carotid injury model to evaluate time to arterial thrombosis in vivo by measuring time to occlusion tracked via a Doppler flow probe on the exposed vessel. RESULTS/ANTICIPATED RESULTS: FACS analysis revealed a specific 97% knockout of CD39 expression on EC (p<0.001) but not on other cells within the vasculature. There was also significant reduction in ATP hydrolysis (81%; p=0.019) in EC-cKO mouse EC versus WT. We next examined the time to arterial thrombosis. EC-specific conditional knockout of CD39 exhibited a significant prolongation in time to thrombosis compared to WT (WT: 8.28 minutes +/- 0.82; EC-cKO: 11.92 minutes +/- 1.34; p=0.024). Analysis of carotid blood-flow revealed that EC-cKO and WT mice had similar baseline blood flow velocity (p=0.51), but after vessel injury with FeCl3, EC-cKO mice exhibited a 16% increase maximal flow velocity relative to baseline compared to WT (p<0.001), as well as a 19% increase at 2-minutes post-injury in comparison to EC-WT mice (p<0.001). DISCUSSION/SIGNIFICANCE: Our findings demonstrate that CD39 activity plays a role in modulating arterial thrombosis and blood-flow regulation within the vasculature. These findings exemplify the therapeutic potential of modulating endothelial CD39 activity, as well as the potential for using SNPs within the gene coding for CD39 as a cardiovascular disease marker.

OBJECTIVES/GOALS: Pilot grants are small financial investments given out by CTSA hubs to facilitate new clinical and translational research projects. The New Jersey Alliance of Clinical and Translational Science (NJ ACTS) is one of 65 CTSA hubs. The goal of this project was to evaluate and improve the NJ ACTS program by learning from pilot programs across the consortium. METHODS/STUDY POPULATION: The initial research on pilot programs was conducted using the CTSA Search Solutions tool, a tool developed at NJ ACTS which provides links to individual pages by topic in all the hub websites. Using the tool, public information was accessed, including common award amounts, significant dates, and preferred categories of research. Then, a survey created in REDCap was distributed to colleagues at all CTSA hubs to gather additional information and thoughts on pilot programs. The data were compiled in an excel database to observe and analyze trends. These trends were graphically presented in figures developed from the data to see how NJ ACTS compares to other CTSA hubs in how they focus and operate their pilot programs. RESULTS/ANTICIPATED RESULTS: There are both similarities and differences between NJ ACTS and other hubs. NJ ACTS utilizes a REDCap form for its application, as do 14 other CTSA hubs. Surveys also show that NJ ACTS follows similar processes for: letter of intent and application due dates; having a standing review committee; and the categories of awards. Award categories for Clinical/Translational Innovation, Methodology/Infrastructure, and Partnership/Collaboration are shared with 47, 25, and 41 institutions, respectively. NJ ACTS requires collaboration between its multiple institutions, as do 28 other hubs. It does not, however, have a public notification of award date, and notifications tend to go out relatively late. NJ ACTS funded multiple proposals pertaining to COVID-19, something 11 other CTSA hubs did as well. DISCUSSION/SIGNIFICANCE: Although a new CTSA hub, NJ ACTSs Pilot Program operates comparably to more mature CTSA hubs. Using the survey data, NJ ACTS can implement modest changes, better serving its scientific community. CTSA Search Solutions has proven an excellent tool and can be used by any hub to understand how they compare and implement changes to improve their programs.

OBJECTIVES/SPECIFIC AIMS: Alzheimer’s disease (AD) is the leading cause of dementia, and a rapidly growing public health crisis as life expectancy increases. Two hallmark symptoms of the disease are memory impairment and the pathological accumulation of amyloid beta protein. The hippocampus is a brain region critical for the consolidation of new memories, and one of the first regions in which amyloid accumulation is observed. Our lab and others have observed a disruption to hippocampal network activity that is critical for memory consolidation in amyloid-accumulating mice. However, the mechanisms and neuronal micro-circuitry underlying this disruption are under-explored, a critical gap that warrants exploration if we are to understand memory disruption in the disease. In this study we have investigated the hypothesis that a preferential disruption to inhibitory PV neurons and the extracellular matrix that surrounds this cell type underlies downstream network alterations. METHODS/STUDY POPULATION: We have employed the 5xFAD mouse model of familial Alzheimer’s disease crossed with transgenic lines that selectively fluoresce in different neuronal sub-types. In a multi-modal approach, we have investigated behavioral, electrophysiological, and biochemical alterations between 3-month-old amyloid-accumulating 5xFAD mice and littermate controls. RESULTS/ANTICIPATED RESULTS: We observe a 35% increase in the incidence of synchronous hippocampal oscillations known as sharp wave ripples (SWRs) in amyloid-accumulating mice versus littermate controls (n = 28, p = 0.01), as well as a 95% increase in the power of slow gamma oscillations (p = 0.002). This hyperexcitability of the hippocampal network is correlated with an impairment in hippocampal-dependent memory, assayed with the Barnes Maze, a behavioral test of spatial memory (172% increase in latency to find escape hole, n = 8, p = 0.01). To elucidate the micro-circuitry that underlies this network disruption, we have investigated the integrity of peri-neuronal nets (PNNs), part of the extracellular matrix of proteins that preferentially ensheathe inhibitory PV neurons and support their function. We observe a 60% decrease in intensity of PNNs (n = 5, p = 0.005), suggesting PNN integrity is impaired in amyloid-accumulating mice. Ongoing experiments into the activity and synaptic input to both inhibitory PV and excitatory pyramidal neurons seek to determine the effects of this PNN disruption on downstream micro-circuitry. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that a preferential impairment to PNNs and inhibitory PV cells underlie hippocampal hyperexcitability in a mouse model of AD. As hippocampal network activity is critical for memory consolidation, these effects contribute to our understanding of memory disruption during early disease progression, which has been poorly understood to date. These findings provide a foundation for future in vivo studies employing optogenetic stimulation to this neuronal sub-type, to determine if restoring physiological network balance can ameliorate memory decline.

OBJECTIVES/GOALS: The goal of this study is to evaluate and optimize the characterization of cystoid macular edema (CME) using an investigational swept source (SS)-OCT system. Our knowledge of CME in preterm infants is limited; optimizing its characterization is a critical step in understanding its impact on vision. METHODS/STUDY POPULATION: In this IRB-approved protocol, 118 preterm infants were imaged in the Duke intensive care nursery (ICN) with a novel lightweight, hand-held, high-speed, SS-OCT system following routine clinical eye exams. SS-OCT images were deidentified, automatically segmented using custom software (DOCTRAP), measured for several retinal layer thicknesses, and reviewed by masked expert graders for the presence and severity of CME. Reliability of SS-OCT measures will be assessed, and the association between CME status and retinal layer thicknesses will be calculated using logistic regression modeling. RESULTS/ANTICIPATED RESULTS: The prevalence of CME overall and by severity will be calculated. The distribution of several retinal layer thicknesses will be reported and compared by infant CME status and, when edema is present, by CME severity. Reproducibility and repeatability will be reported for objective variables, and intra-grader and inter-grader agreement will be reported for subjective variables. Multivariate logistic regression coefficients and odds ratios will be calculated for each retinal layer thickness variable. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will use a novel SS-OCT system to identify retinal thickness measures that may be objective markers of CME status. This will refine the characterization of CME and provide a framework for correlating CME with functional outcomes like visual acuity. CONFLICT OF INTEREST DESCRIPTION: SC and CT have unlicensed patents on relevant technologies. CT receives royalties from Alcon and Hemosonics and consultation fees from EMMES.

OBJECTIVES/GOALS: The purpose of this pilot study is to evaluate the clinical utility and patient/provider acceptability of a buprenorphine (bup) precision dosing approach for opioid use disorder (OUD) in Puerto Rico (PR) to in estimate the most adequate bup dosing regimen based on the unique pharmacological and clinical characteristics of these patients. METHODS/STUDY POPULATION: The goal of this pilot study is to evaluate the extent to which people delivering (providers) or receiving (patients) opioid use disorder care in PR consider our 'bup precision dosing approach' to be appropriate, based on anticipated or experienced cognitive and emotional responses. We will use the Theoretical Framework of Acceptability (TFA) to conduct this evaluation. We expect to generate a baseline understanding of the acceptability of our bup precision dosing approach in terms of clinical utility and attitudes by OUD patients and providers in clinics in PR, We will conduct focus groups and surveys to document patients and providers perceptions, beliefs, attitudes and reception of our bup evidence-based dosing approach. RESULTS/ANTICIPATED RESULTS: We seek to answer the following questions: How do OUD providers and patients in PR view, and how will they engage with our buprenorphine precision dosing approach? Will our intervention based in science be accepted be these individuals? What are their attitudes towards this? How they perceive the efficacy of this intervention to be? What are the barriers and facilitators of this evidence based intervention? This knowledge is crucial before clinical implementation is pursued, we expect to comprehend the unique attitudes and perceptions of these population that supports the successful implementation in the nearby future and enhance the innovation uptake of our bup dosing model for OUD in PR. DISCUSSION/SIGNIFICANCE: It is important that adequate assessments that assess acceptability and feasibility prior to implementation and while still in developmental phases are conducted to plan ahead for the implementation of interventions since innovation uptake depends largely on contextual factors, not just innovation effectiveness.

OBJECTIVES/GOALS: Ebolavirus disease survivors report persistent, debilitating health concerns dubbed Post-Ebola Syndrome (PES). Attention to PES in young survivors is lacking, we describe PES in pediatric EVD survivors in Eastern Sierra Leone. Additionally, we introduce our proposal investigating differential presentations of PES in pediatric survivors. METHODS/STUDY POPULATION: EVD survivors were enrolled a median of 2.5 years after resolution of disease. Survivors were eligible if listed in a national register maintained by the Sierra Leone Association of Ebola Survivors. Household contacts (HCs) were identified by survivors. Participants were assigned into three comparison groups: pediatric (7-11), adolescent (12-17) and young adult (18-25). A self-reported symptom questionnaire, and a physical exam were conducted. Variables were clustered within organ system and compared across groups. RESULTS/ANTICIPATED RESULTS: Pediatric survivors had lower levels of long-term sequelae compared to adolescents and young adults. Symptoms and abnormal physical exam signs increase with age. Musculoskeletal, psychiatric, ophthalmologic, and GI signs and symptoms were significantly different between groups. Pediatric survivors had significantly more persistent sequelae than age-matched HCs with no history of EVD; particularly within the cardiac/GI (p=.006) and psychiatric/neurological (p=.025) clusters. PES is heterogeneous with respect to age, calling for a deeper understanding of age-based differences. Even the youngest group of survivors experienced significantly more sequelae than HCs, highlighting the elevated symptom burden in these children over their peers. DISCUSSION/SIGNIFICANCE: Understanding mechanistic drivers will ultimately improve targeted treatments for PES. We will characterize symptom groups defining PES in children, determine the relationship between accelerated aging and PES in this population, and test how immune profiles associated with accelerated aging relate to the development of PES in children.

OBJECTIVES/SPECIFIC AIMS: Our primary objective is to determine whether the bacteria exerts its effect intra- or extra-cellularly. We have genomic and microscopy preliminary evidence indicating that the bacteria is capable of invading endometrial cells. Our secondary objective is to identify what type of impact the bacteria have on the host cells and whether they are capable of transforming the host cells from a benign into a malignant phenotype. We are currently testing a putative mechanism by which the bacteria may cause the overexpression of the hypoxia inducible factor (HIF), a hallmark of endometrial cancer. METHODS/STUDY POPULATION: We are utilizing our custom built optofluidics platform (microfluidics platform incorporated into an advanced microscope with optical laser tweezers) to isolate single cells from the endometrial tissues of 150 patients with and without endometrial cancer. We are utilizing single cell whole genome amplification followed by qPCR to identify if the bacteria is present intracellularly. We are coupling this procedure with standard microbiological invasion assays with endometrial cell line cultures and P.somerae. We are also utilizing our optofluidics platform to perform single cell transcriptomic amplification, followed by sequencing of cells invaded or in the presence of the bacteria to determine the impact in the transcriptome of the host cell. We are coupling this with western blots of factors hypothesized to be impacted by the bacteria in the overexpression of HIF. RESULTS/ANTICIPATED RESULTS: Based on our preliminary data we anticipate to find evidence that P.somerae is invading the host cells, in particular the cells in tumor tissues. We also expect to find that the intracellular presence of the bacteria is causing the overexpression of the HIF pathway, hence resulting in a cancerous phenotype. DISCUSSION/SIGNIFICANCE OF IMPACT: Our long-term goal is to develop primary prevention strategies that will reduce endometrial cancer incidence rates. A confirmation of our hypothesis could suggest that it is sufficient for endometrial cancer prevention efforts to eliminate P.somerae, in line with gastric and cervical cancer efforts. It could also mean that targeting P.somerae in cancer treatment is necessary to contain the disease and prevent recurrence.

ABSTRACT IMPACT: The implementation of nasal nitric oxide (nNO) as a diagnostic tool to understand the phenotypic/genotypic profiles of Primary Ciliary Dyskinesia (PCD) in Puerto Rico (PR) will be translated in early disease diagnosis, avoidance of comorbidities, and increase survival in our population. OBJECTIVES/GOALS: This study aims to evaluate the role of nNO levels in PCD diagnosis in the Puerto Rican population. Also, we aim to describe the clinical, genetic, and physiological characteristics of PCD in Puerto Ricans to develop a better understanding of the disease. METHODS/STUDY POPULATION: We plan to conduct a cross-sectional study on participants recruited from patients of the Pediatric Rare Lung and Asthma Institute in PR. We will compare nNO levels among genetically confirmed PCD patients, suspected PCD patients with variant of unknown significance (VUS) mutations, suspected PCD patients without genetic mutations, and age-matched healthy subjects. We plan to analyze clinical data and genetic variants to understand the natural history of the disease. The nNO measurements will be completed following previous published protocols. We will also assess the accuracy of the nNO measurements by repeating the measurements two weeks after the initial measurement. RESULTS/ANTICIPATED RESULTS: We hypothesize that many of the VUS present in our population may represent potential new founder mutations not previously reported in the literature. Our expectation is to identify new atypical PCD phenotypes contemplating the heterogenous genetic Puerto Rican pool. We anticipate that nNO levels will help to screen, identify, and confirm diagnosis of patients with clinical PCD in PR. Our findings will be translated in avoidance of further comorbidities and mortality due to earlier disease PCD diagnosis and will expand our genetic understanding about PCD in PR and other diverse populations with heterogenous genetic admixture. DISCUSSION/SIGNIFICANCE OF FINDINGS: We present a significant and novel research proposal that plan to impact the quality of life of patients living with PCD in PR. The implementation of state-of-the-art diagnostic tools like nNO measurement will positively impact and expand our current capabilities to diagnose rare lung diseases like PCD on the island.

OBJECTIVES/SPECIFIC AIMS: (1) Assess if the total duration of EEG suppression during a protocolized exposure to general anesthesia predicts cognitive performance in multiple cognitive domains immediately following emergence from anesthesia. (2) Assess if the total duration of EEG suppression in the same individuals predicts the rate of cognitive recovery in a three-hour period following emergence from anesthesia. METHODS/STUDY POPULATION: This was a non-specified substudy of NCT01911195, a multicenter investigation taking place at the University of Michigan, University of Pennsylvania, and Washington University in St. Louis. 30 healthy volunteers aged 20-40 years were recruited to receive general anesthesia. Participants in the anesthesia arm were anesthetized for three hours at isoflurane levels compatible with surgery (1.3 MAC). Multichannel sensor nets were used for EEG acquisition during the anesthetic exposure. EEG suppression was detected through automated voltage-thresholded classification of 2-second signal epochs, with concordance assessed across sensors. Following return of responsiveness to verbal commands, participants completed up to three hours of serial cognitive tests assessing executive function, reaction time, cognitive throughput, and working memory. Non-linear mixed effects models will be used to estimate the initial cognitive deficit and the rate of cognitive recovery following anesthetic exposure; these measures of cognitive function will be assessed in relation to total duration of suppression during anesthesia. RESULTS/ANTICIPATED RESULTS: Participants displayed wide variability in the total amount of suppression during anesthesia, with a median of 31.2 minutes and range from 0 minutes to 115.2 minutes. Initial analyses suggest that greater duration of burst suppression had a weak relationship with participants’ initial cognitive deficits upon return of responsiveness from anesthesia. Model generation of rate of recovery following anesthetic exposure is pending, but we anticipate this will also have a weak relationship with burst suppression. DISCUSSION/SIGNIFICANCE OF IMPACT: In healthy adults receiving a standardized exposure to anesthesia without surgery, burst suppression appears to be a poor predictor of post-anesthesia cognitive task performance. This suggests that burst suppression may have limited utility as a predictive marker of post-operative cognitive functioning, particularly in young adults without significant illness.

OBJECTIVES/GOALS: The purpose of this study is to understand how hemodynamics during dialysis in End-Stage Renal Disease (ESRD) patients on hemodialysis (HD) affect white matter health and how those effects cause cognitive impairments. METHODS/STUDY POPULATION: We collected demographic data, comorbidities, intradialytic measurements of blood pressure and cerebral oximetry, cognitive measures in several domains using NIH Toolbox Cognition Battery, diffusion-weighted and anatomical MRIs for 20 participants on HD. Specific tracts were identified using tractography and were used to calculate the average DTI measurements in each tract. Regression analysis was used to examine the relationship between mean DTI measurements of white matter integrity and cognitive performance scores. In addition, we compared diffusion MRI and T1 anatomical images of 16 healthy age-matched controls from a previous study. RESULTS/ANTICIPATED RESULTS: In our cohort 18 participants had imaging data that could be used in the analysis. We found widespread decreases in DTI white matter integrity compared to healthy age-matched controls, mean whole-brain fractional anisotropy was .3218 in the HD cohort and .3472 in controls p = .0018. Decreased integrity was found in most of the tracts identified but more decreased in tracts implicated in cognition. Partial regression analysis identified significant relationships between the white matter integrity of the left superior longitudinal fasciculus and overall fluid cognitive performance, R = .5525, p = .0174 before multiple comparisons correction when controlling for differences due to age. DISCUSSION/SIGNIFICANCE OF IMPACT: We found a widespread decrease in white matter integrity and significant correlations between cognitive performance and specific tract integrity in our HD cohort using regions identified by tractography imaging analysis. This analysis shows that HD patients have decreased white matter health and identifies several tracts that are important for cognitive performance in HD patients.

OBJECTIVES/GOALS: The objective of this study is to examine the independent and combined effectiveness of a multiple micronutrient supplementation and responsive caregiving intervention on early child development in southwestern Guatemala. METHODS/STUDY POPULATION: We conducted a double blind, 2 x 2, cluster randomized controlled trial combining micronutrient supplementation and responsive caregiving treatments. We enrolled 309 infants (6-18 months) and 387 preschoolers (36-52 months) at nutritional risk (height-for-age z-score < -1) (51% male; 17% indigenous ethnicity; 76% of caregivers completed ≤ primary school). The supplementation arm received a maize-soy product fortified with 21 micronutrients for 6 months; the control was fortified with B2. The responsive caregiving intervention was adapted from the UNICEF Care for Child Development program and delivered over 6 home visits. We examined changes in early child development from baseline (2015) to endline (2017) using the Bayley Scales of Infant and Toddler Development III and Bracken Scales of School Readiness. RESULTS/ANTICIPATED RESULTS: Among infants, age standardized Bayley cognitive development scores declined over time in each treatment arm. Infant Bayley motor development scores significantly increased in the combined multiple micronutrient supplementation + responsive caregiving arm (â^† = 3.67 [95% CI: 0.17, 7.17], p = 0.04). Among preschoolers, school readiness decreased over time in each treatment arm. The rates of change in infant development and preschooler school readiness did not differ between treatment arms. Further analysis will explore effect modification of the intervention by pre-specified child and household factors. DISCUSSION/SIGNIFICANCE: Combined multiple micronutrient supplementation and responsive caregiving supported motor development while cognitive and school readiness were not impacted by the intervention. These findings will inform the effectiveness and beneficiaries of multisectoral interventions to promote early child development in adverse environments.

OBJECTIVES/GOALS: There is a need for high-quality and efficient translation of health technologies in the Ontario healthcare system. The goal of this project is to understand the decision-making processes of government expert groups developing recommendations for the system-level implementation of pharmacogenomic testing. METHODS/STUDY POPULATION: This prospective observational case study includes the Ontario Health Pharmacogenomics (PGx) Working Group focused on developing recommendations for a PGx testing implementation strategy in the province. Ontario Health is the government agency that oversees provincial healthcare planning and service delivery. Using qualitative ethnographic methods, we will observe and document the working group’s activities over a 10-month period. Data collection involves meeting recordings, correspondences, researcher field notes, decision-making processes, and group characteristics. Using descriptive statistics and inductive qualitative analyses, the data will be examined to build theory and frameworks for knowledge translation. RESULTS/ANTICIPATED RESULTS: The results will be presented through a case report, process maps, decision milestones, visualizations, and procedural recommendations for future expert groups. This study will contribute to the body of foundational knowledge about translational sciences and support the National Center for Advancing Translational Sciences’guiding principles. To enhance translational processes and train the future translational workforce, this research can be used for educational initiatives. In addition, the observed processes will inform a theory about how expert recommendations are developed in public healthcare systems. DISCUSSION/SIGNIFICANCE: This research addresses a current gap in understanding around translational processes, government decision-making, and the development of recommendations for the adoption, implementation, and dissemination of the novel health technologies transforming public healthcare in Canada.

OBJECTIVES/GOALS: The overall objective of this study is to determine if medial arterial calcification (MAC) is an independent predictor of diabetes and to evaluate the relationship between MAC, periodontitis and Type II diabetes mellitus. METHODS/STUDY POPULATION: A retrospective case-control model analyzing radiographs for periodontitis and MAC to identify potential biomarkers for underlying systemic conditions, such as diabetes. Charts of patients attending UPENN School of Dental Medicine clinics between 2015 and 2022 were reviewed. Demographics, medical and dental history, diabetic status (identified by POC blood glucose level, fasting blood glucose and/or A1C), and medication history were documented amongst other variables. Patients aged 18 years or older with diabetes and having full mouth intraoral radiographs (FMX), panoramic radiographs and CBCTs were included. Patients with radiographs of poor quality were excluded. Multivariate analysis was used to determine possible associations between diabetes and periodontitis among persons with or without MAC. RESULTS/ANTICIPATED RESULTS: In our pilot study involving 28 participants, 53% of the population with moderate or severe periodontitis had MAC. By the Fisher’s Exact Test, there was an association, meaning those with more periodontal disease are more likely to have MAC (p=0.014). Sixty-three percent of patients with diabetes had MAC, while 19% of patients without evidence of diabetes also had MAC, (p=0.067). There was not enough evidence of association between diabetes and presence of MAC at this time, due to a small sample size, however there was a high prevalence of MAC among the diabetics. We hypothesized that periodontitis, a condition that shares many risk factors with diabetes would also be associated with incident MAC. Findings from this study will be key for the implementation of preventive screening protocols and referral systems. DISCUSSION/SIGNIFICANCE: Diabetes is on the rise and about half of diabetics are undiagnosed. CBCT imaging frequently used in dentistry can detect incidental findings such as MAC. This study has the potential of detecting statistically significant links between MAC, periodontitis and diabetes, hence serving as a sensitive radiographic biomarker for diabetes.