ABSTRACT IMPACT: The model of the Clinical Research Support Center at the University of Minnesota of streamlining clinical trial infrastructure can be leveraged by the larger clinical trial community to create valuable efficiencies and facilitate faster initiation of research activities by supporting researchers from concept to dissemination. OBJECTIVES/GOALS: Substantial time, energy, and money are spent bridging disparate resources in research. We describe how the University of Minnesota’s (UMN) Clinical Research Support Center (CRSC) streamlines trial infrastructure, creating valuable efficiencies to support researchers from concept to dissemination. METHODS/STUDY POPULATION: The CRSC, established in 2018 through the Clinical and Translational Science Award (CTSA) program, brings resources together in a single, centralized, and convenient location to help researchers navigate the UMN clinical research startup process and specifically to assist with the development and initiation of a research study from feasibility assessment to project opening. Diverse expertise in components of human subject research is available to support the broad scope of projects at a large institution like the UMN. We present how CRSC services, when coordinated by Clinical Research Specialists, have been used to improve access to clinical research resources during the start up process. RESULTS/ANTICIPATED RESULTS: Since inception in 2018, the CRSC has provided support to over 1700 studies with 437 research projects referred to a Clinical Research Specialist within the CRSC. Of those projects, 97 (22.2%) received comprehensive support from the following expert groups: regulatory guidance (n=74), biostatistics (n=68), clinical (hospital or clinic) partners (n=60), recruitment (n=36), budget development assistance (n=30), and (bio)informatics (n=27). Successful examples of synergies to streamlining study start up include shortening the window between protocol development support from Clinical Research Specialists and IRB submission preparation through to Regulatory Specialists to 3 days. DISCUSSION/SIGNIFICANCE OF FINDINGS: Providing cross-functional support to research teams through the CRSC increases the likelihood of quicker and successful execution and completion of research initiation and subsequently impacts the dissemination of that research to patients and the broader community.

ABSTRACT IMPACT: This study will provide important insight about effective team formation from coming up with an idea to successfully implementing that idea, as well as will highlight the implementation, evolution, and future directions of a team science initiatives. OBJECTIVES/GOALS: The goal of this study is to describe the feasibility of initiating an ideation forum to catalyze team formation, explore the process by which themes and teams are selected to participate in the forum setting, and assess the progress of participating teams post-forum through internal and external funding and other synergistic research activities. METHODS/STUDY POPULATION: Three ideation forums took place between 2018-2019 at Rutgers University, with a defined process and collection of data. The method of intervention to trigger team science, specifically the methodology employed to identify teams and produce new collaborative ideas, will first be described to show the feasibility of such an event to encourage team formation. In post-hoc analysis, we compare various success matrices of participating teams received seed funding versus teams that didn’t receive any funding to assess the progress of teams in the research ideation forum incubation process. RESULTS/ANTICIPATED RESULTS: Triggering team science through ideation forums is feasible and, in fact, quite productive to creating a durable response in formed teams showing continued productivity in publications, fundraising, and other academic metrics. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our case review can illuminate how academic institutions can support team science research through ideation forums. In addition, this study lays an initial foundation for improvements in ideation forum creation and new metrics that can be shared broadly to compare across other institutions.

ABSTRACT IMPACT: As scientific research is trending towards greater interdisciplinary and collaboration in order to meet the challenges of contemporary science, which has led to increased recognition of the importance of Team Science, this study will promote team science research within NJ ACTS Consortium as well as across the country. OBJECTIVES/GOALS: The objective of this study is to assess the feasibility of using the NIH Reporter database for developing and tracking team science metrics within the CTSA-funded NJ ACTS Consortium, which consists of RU, PU, and NJIT. The NIH Reporter database provides detailed information on single-PI and multiple-PI R01 grants funded by NIH. METHODS/STUDY POPULATION: 58 multi-PI projects and 344 single-PI projects are currently funded within the NJ ACTS consortium. We will use information from the database on funding levels, institutional composition of projects (e.g., within-consortium projects vs. projects with PIs both within and outside of the consortium), numbers of publications, impact factors of publications, and funding supplements obtained to quantify and track NIH R01 Team Science activity in the consortium. RESULTS/ANTICIPATED RESULTS: Preliminary analysis suggests that it will be both feasible and efficient to use the NIH reporter database to develop Team Science metrics and to augment information in the database with information on PI characteristics such as department/center/school/university, academic discipline, and rank/tenure status, as well and detailed composition of research teams, such as the mix in terms of senior and junior scholars. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will make an important contribution to this movement by demonstrating the feasibility of using the publicly available NIH Reporter Database to quantify the level and success of Team Science in the form of single-PI and multiple-PI R01 grants funded by NIH, which represent extremely important Team Science activities at universities.

ABSTRACT IMPACT: Implement and evaluate a fellowship program to foster a new generation of entrepreneurial and collaboratively-minded team scientists, equipped with the knowledge and skills to innovate technology-based solutions for COVID-19 to advance human health OBJECTIVES/GOALS: Mount Sinai Targeted Healthcare Innovation Fellowship (THRIVE) is a 9-month program for participants from diverse professional backgrounds to develop HealthTech innovations related to COVID-19. The program is designed to provide an experiential team science platform for fellows to take an idea from concept to commercially viable innovation. METHODS/STUDY POPULATION: Following a competitive application process, 16 THRIVE fellows comprise four teams working collaboratively in an online forum with input from experts in the field. Success of the program will be evaluated by:

assessing pre- and post- collaborative research orientation among THRIVE fellows using the ROI scale1

using social network analysis (SNA) to investigate the social networks of THRIVE fellows to capture patterns of communication and collaboration related to innovation development

exploring participant experiences of group formation, teamwork and collaboration related to innovation development using one-to-one semi-structured interview

determining team success in innovation development, measured by number of publications, funding awarded, provisional patents and viable products. RESULTS/ANTICIPATED RESULTS: Paired t-tests will determine whether collaborative orientation of THRIVE fellows changes pre- vs. post- program participation, indicating changes in attitude toward multidisciplinary team work. SNA will be used to describe structural patterns of communication that occur at individual and group levels. Network-level indices will provide insight into patterns of communication that exist in innovation development: degree centrality (number of connections per individual), betweenness centrality (number of bridges to others in a network), closeness centrality (closeness to others in a network). We will also test for associations between network characteristics and team success. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding patterns of formal and informal relationships, interactions, and perceptions of the collaborative process among individuals in THRIVE teams will elucidate whether such a program can provide an effective forum for team science and innovation development related to COVID-19.

ABSTRACT IMPACT: Recognizing Interdisciplinary Collaborative Research in Promotion and Tenure Processes OBJECTIVES/GOALS: Academic institutions have traditionally focused on individual achievements for promotion. We present our effort on identifying and measuring attitudes on promotion and tenure (PT) criteria that values and rewards interdisciplinary research (IR). We have developed a toolkit to facilitate the recognition of IR in PT processes. METHODS/STUDY POPULATION: Our group reviewed appointment, promotion and tenure (APT) policies from each of the six Health Science Schools and the College of Engineering at the University of Washington (UW) to assess language of objective criteria and attributes of IR to guide APT committees in the evaluation of interdisciplinary researchers. We surveyed faculty about their attitudes relating to IR within the context of promotion and tenure. Interviews of department chairs and administrators about institutional policies and infrastructure that supports or inhibits IR, and current best practices, were conducted. We have developed toolkits for junior faculty, department chairs, external reviewers, and APT committees to facilitate rewarding IR at promotion. RESULTS/ANTICIPATED RESULTS: Review of APT policies found criteria that recognizes IR for APT in three schools. 118 faculty responded to the survey (44% Professor, 26% Associate, and 37% eligible for APT committees). The majority of faculty reported they were currently conducting IR (95%), considered IR important (98%), and believed the UW faculty code should encourage IR (85%). Although a vast majority considered their units supportive of IR (>80%), less than half (43%) reported that their APT criteria provided examples that included participation in IR. Our survey also found that APT committees were challenged about best practices to reward IR, APT external reviewers struggle to evaluate individual vs team contributions, and individual faculty are challenged to describe contributions for APT within context of an interdisciplinary team. DISCUSSION/SIGNIFICANCE OF FINDINGS: IR is conducted and valued by UW faculty; however, current structures, policies, and APT code do not facilitate IR for promotion and tenure. We have developed a toolkit for promotion-eligible faculty, chairs, external reviewers, and APT committees to facilitate IR. Our goal is to modify UW faculty code and unit APT criteria to recognize and reward IR.

ABSTRACT IMPACT: This analysis helps disentangle various paths to translational collaboration, with implications for departmental capacity building and support. OBJECTIVES/GOALS: Studies that bridge research collaboration networks are cross-disciplinary and translational. We explored the characteristics of researchers and their collaboration patterns in bridging research grants at University of Rochester School of Medicine and Dentistry. METHODS/STUDY POPULATION: the database of sponsored research grants from 2011 to 2018, obtained from an internal University database was transformed into a two-mode network of grant-to-investigator. Grants at 90th percentile and above of normalized two-mode betweenness centrality were defined as ‘bridging grants’. For each grant we extracted the gender, academic rank, academic degree, affiliating department, and centrality-status (being at 75th percentile of degree centrality in one-mode collaboration network) of the Principal Investigator (PI), as well as the number of co-investigators (CI) and the existence of central actor(s) in the research team. RESULTS/ANTICIPATED RESULTS: Out of 2491 sponsored grants, 250 were ‘bridging grants’. The significant predictors of bridging were centrality of PI, existence of central CI(s), PI holding PhD, and larger number of CIs. The PI’s academic rank (being full professor) and gender were not significant predictors. Among bridging grants 79 included both central PI and CIs (central actors group) and 60 included no central actor on the team. In the latter group, more PIs were clinical faculty and fewer were full professors. Network analysis of affiliating departments showed that Medicine was the prominent actor in the central actors group, while the network of no-central actor group was more fragmented with Neurology as central. DISCUSSION/SIGNIFICANCE OF FINDINGS: Widely recognized researchers are more likely to collaborate with each other in bridging studies possibly marginalizing less experienced peers. Bridging grants led by less central researchers, often clinician-scientists, may thrive where supportive culture and departmental facilities exist.

ABSTRACT IMPACT: Our research identifies key opportunities for increased cross-CTSA collaboration, as a means to improve community-research cooperation and better CBPR practices. OBJECTIVES/GOALS: Currently, team science training prioritizes developing the collaborative competencies of interdisciplinary scientists to work with each other and, more recently, with communities. Community-facing team science resources are scarce but present among some CTSAs, suggesting that capacity gaps might be remedied through cross-hub collaboration. METHODS/STUDY POPULATION: We reviewed online information provided by the 62 current CTSAs to identify: (1) which hubs engage in community research, and (2) what resources the hubs utilize to orient, train, and support community stakeholders as research partners. We then examined the capacities of the collectively available CTSA resources to address needed knowledge, skills, and attitudes that community-engaged researchers have identified as essential for community-based stakeholders to partner equally in research. Finally, we explored practical challenges in team-based dynamics (e.g., interpersonal difficulties, expertise gaps, resource management) that may facilitate or hinder communities’ research endeavors, and suggest resources that CTSAs might implement to facilitate team science dynamics. RESULTS/ANTICIPATED RESULTS: Hubs (n=59) have community engagement programs, 12 of which provide community-based participatory research toolkits. Toolkits vary from basic checklists to fully developed modules. Some hubs also offer consultation services and partner match-making. Learning objectives include: outcome definition, logic models, and goal-setting. Learning resources remain underdeveloped to help communities appreciate the benefits of research engagement and convince academic partners of the value of real-world knowledge and community improvement relative to scientific advancement. Also lacking is easily accessible support to understand the research process, build verifiable trust, maintain bidirectional knowledge and assets, and implement consistent, best practice methodological and reporting protocols. DISCUSSION/SIGNIFICANCE OF FINDINGS: Gaps between current hub offerings and community needs suggest prioritizing creation of resources whose learning objectives highlight the benefits of research engagement for community partners; foster mutual values affirmation between partners; and offer tools that build warranted community-researcher rapport.

ABSTRACT IMPACT: This study will provide valuable insight regarding the effectiveness of a top-down approach for team formation. OBJECTIVES/GOALS: Rutgers’ Big Ideas is a philanthropic initiative designed to gather team science ideas and present them to donors. We intend to evaluate this Team Science intervention and determine its feasibility in catalyzing the inception of team formation. We will explore the composition of teams that are formed using this particular method and team outcomes. METHODS/STUDY POPULATION: Our group will first evaluate the themes that were covered by the initial 210 submissions as well as the 40 ideas chosen to be presented at the Big Ideas Symposium. We will also be taking a look at the donor population that these ideas were presented to. Then, we will evaluate the 8-12 winning teams that were chosen to move forward. We will compare various success metrics of the 8-12 teams that were chosen compared to the 40 ideas that had not been chosen. RESULTS/ANTICIPATED RESULTS: Encouraging team science through an initiative such as the Big Ideas forum is not only feasible, but also highly effective in creating resilient teams that show prolonged productivity in fundraising, publications, and other academic metrics. DISCUSSION/SIGNIFICANCE OF FINDINGS: Team Science is an exciting movement with immense potential. To that extent, this study seeks to discuss ways that academic leadership can inspire and foster effective team science collaboration. Concurrently, our case review lays the groundwork for further improvements to Team Science initiatives.

ABSTRACT IMPACT: Understanding how spinal cord stimulation works and who it works best for will improve clinical trial efficacy and prevent unnecessary surgeries. OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for chronic low back pain where standard interventions fail to provide relief. However, estimates suggest only 58% of patients achieve at least 50% reduction in their pain. There is no non-invasive method for predicting relief provided by SCS. We hypothesize neural activity in the brain can fill this gap. METHODS/STUDY POPULATION: We tested SCS patients at 3 times points: baseline (pre-surgery), at day 7 during the trial period (post-trial), and 6 months after a permanent system had been implanted. At each time point participants completed 10 minutes of eyes closed, resting electroencephalography (EEG) and self-reported their pain. EEG was collected with the ActiveTwo system and a 128-electrode cap. Patients were grouped based on the percentage change of their pain from baseline to the final visit using a median split (super responders > average responders). Spectral density powerbands were extracted from resting EEG to use as input features for machine learning analyses. We used support vector machines to predict response to SCS. RESULTS/ANTICIPATED RESULTS: Baseline and post-trial EEG data predicted SCS response at 6-months with 95.56% and 100% accuracy, respectively. The gamma band had the highest performance in differentiating responders. Post-trial EEG data best differentiated the groups with feature weighted dipoles being more highly localized in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding how SCS works and who it works best for is the long-term objective of our collaborative research program. These data provide an important first step towards this goal.

ABSTRACT IMPACT: Implementing a team science approach with broad engagement from academic researchers, healthcare payers, providers, patients, and community-based organizations is complex, yet critical to implementing evidence into real world settings. OBJECTIVES/GOALS: 1. Participants will be able to deploy novel strategies for creating and training a regional multi-stakeholder consortium to improve the quality and value of healthcare.

2. Participants will be to examine ways in which team science provides holistic sustainable strategies to improve care and outcomes in real-world settings. METHODS/STUDY POPULATION: The Quality & Value Innovation Consortium (QVIC) has created a network of hospitals and other stakeholders (providers, payers, purchasers, patients, community-based organizations, and researchers) to collaborate and innovate on healthcare delivery. This initiative began with a team of a physician researcher, a health services researcher, and a nurse researcher first identifying healthcare systems’ priorities through individual meetings with leadership from 14 regional hospitals. Concurrently, meetings were held with other stakeholders. These interviews identified 32 key quality improvement topics.

Focus groups and surveys reduced these to 11 topics that were then selected for community forums. Through a mixed methods approach, two priority topics were selected for regional implementation. RESULTS/ANTICIPATED RESULTS: The QVIC meetings have prioritized two topics and highlighted novel information sharing across entities, and strategies to address the social determinants of health. The QVIC efforts have been recognized as a community asset for helping build collaboration and partnerships among diverse stakeholders. Ultimately, two regional initiatives, opioid management, and transitions in heart failure care were selected for implementation. Both of these initiatives aim to reduce readmissions by addressing social determinants of health. Implementation strategies and evaluation metrics are being customized for pragmatic integration within each system, utilizing a collaborative team science approach. DISCUSSION/SIGNIFICANCE OF FINDINGS: While the entire country is grappling with the challenge of improving the quality of care, while lowering its costs, Kansas City has modeled a unique culture and strategy for achieving this goal, important for learning health systems and communities.

ABSTRACT IMPACT: This work reveals the influence of a season of American football-related head impact exposure on two functional outcome measures in a cohort of adolescent boys, shedding light on the chronic effects of 'subconcussive head impacts.' OBJECTIVES/GOALS: To examine the influence of a season of exposure to head impacts in American football on changes in neurocognitive and oculomotor function in adolescent male athletes. METHODS/STUDY POPULATION: Participants were recruited from a local high school: the football group (FB; n = 26) was instrumented with sensor-installed mouthguards to track impact exposure during games and practices, and members of the men’s cross-country team were recruited to the control group (CON; n = 9). All participants were administered Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) and were assessed for near point of convergence (NPC) at pre- and post-season. Linear models will be fit for changes in the five ImPACT composite scores and NPC values, with group and one of the head impact variables as predictors for each model. In a secondary within-group analysis, correlation coefficients will be calculated for the relationships between the head impact variables and the functional change scores for the FB group. RESULTS/ANTICIPATED RESULTS: The two groups did not differ significantly on age or number of previous concussions; the CON group had significantly lower BMI. Group assignment was significantly associated with change in NPC (p < 0.05 for all three models); no significant associations were observed for any of the head impact variables with change in NPC. Group and each of the head impact variables (total impacts, sum of peak linear acceleration [PLA], and sum of peak rotational acceleration [PRA]) were not significantly associated with change in any of the five ImPACT composite scores. Change in visual memory composite score was negatively correlated with total impacts (r = -0.37, p = 0.034) and sum of PRA (r = -0.36, p = 0.040). DISCUSSION/SIGNIFICANCE OF FINDINGS: Significant, albeit relatively weak, correlations between change in visual memory composite score and two head impact kinematic variables, coupled with significant increases in NPC in the FB group compared to the CON group, suggest that a season of exposure to football-related head impacts has the potential to elicit minor functional impairments.

ABSTRACT IMPACT: This study assesses patient and volumetric risk factors for distant recurrence within 6 months of completion of curative chemoradiation with brachytherapy in locally advanced cervical cancer. OBJECTIVES/GOALS: Initial tumor volume and tumor shrinkage velocity are prognostic of cure and survival after curative chemoradiation (CRT) for cervical cancer. We explored whether local tumor volumetric changes influence time to distant recurrences outside the radiation field. METHODS/STUDY POPULATION: We performed a retrospective cohort study of patients with FIGO Stage IB-IVA cervical cancer treated with curative CRT and brachytherapy at a tertiary academic center with minimum 3 months follow up and standard post-treatment FDG-PET. Patients received 6 weekly fractions of brachytherapy interdigitated with external beam radiation and cisplatin. Tumor volumes were assessed by MRI at brachytherapy planning. Patients who developed distant metastasis were classified as earliest (3-6 months), early (6-24 months) or late (>24 months) following completion of CRT. Absolute and percent decrease in tumor volume for each fraction were calculated with respect to first brachytherapy volume. Fisher’s exact and Mann Whitney-U tests were used for comparison of categorical and continuous variables. RESULTS/ANTICIPATED RESULTS: 143 of 574 (25%) patients developed distant metastasis. Distribution of age, histology, FIGO 2018 stage, primary tumor SUVmax, treatment length, and pre/post treatment squamous cell carcinoma antigen levels were not associated in each group. Para-aortic lymph metastases were more common in patients with earliest distant recurrence (33% earliest, 26% early, 12% late, p=0.03). Median initial tumor volume in the earliest (n=24), early (n =29) and late (n=9) groups was 57, 28 and 40 mL, respectively (p=0.08); 57 (earliest) vs 30mL (early+late groups), p=0.04. Average mid treatment (fraction 4) and end of treatment (fraction 6) percent shrinkage was 80 (earliest) vs 73 (early+late), p=0.84 and 94 vs 92, p=0.95, respectively. Neither absolute nor percent tumor shrinkage differed between early vs. late groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: Tumor volumetric changes during definitive chemoradiation were not associated with the timing of developing distant metastasis, which is linked to presence of lymph node metastasis and tumor volume at diagnosis.

ABSTRACT IMPACT: Evaluate the accuracy of applying a predictive algorithm using clinical measures only in persons with stroke in the US. OBJECTIVES/GOALS: PREP2 is an algorithm, that predicts UL functional capacity at 3 months post stroke from measures taken within the first week.(1, 2) Despite its accuracy and ease of use, challenges arise of applying PREP2 in the US. The objective of this study was to evaluate the accuracy of PREP2 using only clinical measures in persons with stroke in the US. METHODS/STUDY POPULATION: Individuals with first-ever stroke were recruited from a local hospital and followed longitudinally, as part of an ongoing observational cohort. Variables captured within two weeks of stroke and entered into the algorithm were: age, SAFE score(1-3) and NIH Stroke Scale(4) total score. The algorithm classifies individuals into one of four expected categories: excellent, good, limited, or poor. The dependent variable was the predicted category of UL functional capacity as defined by ranges of the 3-month Action Research Arm Test score.(5) Accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the algorithm, were calculated using a 4x4 contingency table. Other statistics analyzed include demographic characteristics and a weighted kappa for the algorithm. RESULTS/ANTICIPATED RESULTS: Data from 49 individuals were analyzed (57% male, 88% ischemic stroke, age = 65±8.56 years). Expected categorization matched observed categorization in 29/49 subjects, with the overall accuracy of the algorithm of 59% (95% CI = 0.44-0.73). The sensitivity of the algorithm was low except for the excellent category (0.95). Specificity was moderate to high for good (0.81), limited (0.98), and poor (0.95) categories. PPV was low for all categories and NPV was high for all categories except the good category. Additional results including weighted kappa and inaccuracy of predictions to be presented. DISCUSSION/SIGNIFICANCE OF FINDINGS: PREP2 algorithm, with clinical measures only, is better than chance (chance = 25% for each of the 4 categories) alone at predicting a category of UL capacity at 3 months post stroke. PREP2 is a simple tool that facilitates evaluation of eventual UL outcome from measures routinely captured after a stroke within most healthcare settings in the US.

ABSTRACT IMPACT: Urine tumor DNA non-invasively detects minimal residual disease and infers tumor mutational burden in locally advanced bladder cancer prior to radical cystectomy, which may potentially enable the selection of patients for bladder-sparing treatment or facilitate personalized adjuvant immunotherapy. OBJECTIVES/GOALS: Standard-of-care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. The inability to assess minimal residual disease (MRD) non-invasively limits our ability to offer bladder-sparing treatment. We sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS/STUDY POPULATION: We applied uCAPP-Seq, a targeted sequencing method for detecting utDNA, to urine cell-free DNA samples acquired on the day of radical cystectomy from 42 patients with bladder cancer. utDNA variant-calling was performed non-invasively without prior tumor mutational knowledge. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. Tumor mutational burden (TMB) was inferred from the number of non-silent mutations detected in urine cell-free DNA by applying a linear relationship derived from TCGA whole exome sequencing of 409 MIBC tumors. RESULTS/ANTICIPATED RESULTS: utDNA levels were significantly higher in patients with residual disease detected in their surgical pathology compared to those who achieved a pathologic complete response (P = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD significantly predicted the absence of pathologic complete response with a sensitivity of 81% and specificity of 81%. Positive utDNA MRD also portended significantly worse progression-free survival (HR = 7.4; P = 0.03) compared to negative utDNA MRD. Furthermore, we applied a linear relationship (Pearson r = 0.84; P < 0.0001) to identify patients with high inferred TMB who may have been candidates for early immune checkpoint blockade. DISCUSSION/SIGNIFICANCE OF FINDINGS: utDNA MRD analysis prior to surgery correlated significantly with pathologic response and progression-free survival, which may help select patients for bladder-sparing treatment. utDNA can also non-invasively infer TMB, which could facilitate personalized adjuvant therapy for patients in the future.

ABSTRACT IMPACT: The results of this research may influence NCCN guidelines on PET/CT surveillance for this population of patients for whom the guidelines are currently vague. OBJECTIVES/GOALS: We aim to quantify and describe the yield of surveillance PET/CT for detecting asymptomatic recurrence of melanoma after primary surgical treatment for stages IIB, IIC, and IIIA. Our goal is to provide evidence to inform appropriate guidelines for scheduling surveillance PET/CT for this population. METHODS/STUDY POPULATION: This is a retrospective study of patients who have undergone a PET/CT at Barnes-Jewish Hospital. Data will be collected in our Research Electronic Data Capture (REDCap) database. The sample size is 158. Data analysis will be explanatory for the yield of imaging and description of false positives and additional unnecessary workup. Survival endpoints will be reported and multivariate analysis with subgroups will be performed for predictors of PET/CT results. Cost-efficiency analysis will be conducted in collaboration with the Center for Health Economics and Policy (CHEP), with emphasis on a patient-oriented perspective. RESULTS/ANTICIPATED RESULTS: To date, we have collected data for 158 patients, with approximately equal numbers of each stage (56 IIB, 54 IIC, 48 IIIA). Due to lack of clear guidelines for this population, there is significant variation of imaging schedules and results between similar patients or groups of patients. This makes it difficult to anticipate results. Based on clinical experience, literature review, and preliminary data, we may anticipate lower yield of routine PET/CT for the detection of asymptomatic recurrence, with frequent false negatives and occasional false positives, in addition to detection and further workup of benign processes. DISCUSSION/SIGNIFICANCE OF FINDINGS: The high-risk stages IIB, IIC, and IIIA currently occupy a gray area where surveillance PET/CT remains controversial. For this group of patients, it is important to weigh the benefits of early detection and risks of false positives, unnecessary workup and anxiety, and cost.

ABSTRACT IMPACT: Examining lipid immunity for Mycobacterium tuberculosis in a translatable Guinea pig model may serve as a critical foundation for the creation of an efficacious human lipid based vaccine against tuberculosis. OBJECTIVES/GOALS: CD1 is a group of glycoproteins on antigen-presenting cells (APCs) that present lipid antigens to T cells. Mycobacterium tuberculosis (Mtb) has a lipid-rich cell wall which is essential for the pathogenesis of tuberculosis. Our goal is to determine the frequency, phenotypes, and functionality of CD1 T cells against Mtb using the guinea pig model. METHODS/STUDY POPULATION: Guinea pigs serve as the best translational model for CD1 immunology as they have both group 1 and group 2 CD1 complexes, comparable to human CD1. We performed ex-vivo and in-vivo experiments to analyze lipid antigen-specific CD1 T cell responses with Mtb infection. Assays to detect lipid-specific CD1 T cell activation include cellular proliferation, cytotoxicity assays, and interferon-gamma (IFNγ) release assay (Elispot) using both synthetic and Mtb-derived lipids. We isolated and characterized CD1 T cells using tetramerized CD1 complexes loaded with specific Mtb lipids. Spatial interaction between lipid loaded CD1 APCs with CD1 T cells were demonstrated by immunohistochemistry (IHC). Lastly, we will investigate the impact of lipid-based immunology via knockdown and overexpression of CD1 complexes. RESULTS/ANTICIPATED RESULTS: The cytotoxicity assay demonstrated that the CD1b1 and CD1b3 complexes play roles in the presentation of Mtb lipids, specifically glucose monomycolate, and mycolic acid, as noted by T cell killing of fibroblasts that express specific CD1 complexes that can present Mtb lipids. Similarly, cellular proliferation exhibited lipid specific T cell proliferation. IFNγ production by the stimulated CD1-restricted T cells (Elispot) was weak indicating CD1 T cells may not produce IFNγ. IHC successfully showed CD1 APCs in lungs and spleens of infected guinea pigs. It is anticipated that knocking out CD1 expression will lead to impaired immunity, and increase severity of disease as noted by pathologic lesions/bacterial burden, and systemic spread; in contrast, CD1 enhancement will limit the severity of tuberculosis. DISCUSSION/SIGNIFICANCE OF FINDINGS: We characterized CD1 T cells in infected guinea pigs at the tissue level, demonstrating Mtb lipid immunology. As a result, we laid the groundwork for investigating whether augmenting lipid immunity in the guinea pig model will enhance immunity against tuberculosis. Fruition of such work may lead to the development of effective tuberculosis vaccines.

ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.

ABSTRACT IMPACT: Chronic kidney disease (CKD) affects ˜15% of the US population and the majority of patients are diagnosed too late to benefit from early intervention. We are developing a new diagnostic imaging tool (RadioCF-PET) for the kidney to enable early detection of diseases and to monitor overall kidney health. OBJECTIVES/GOALS: Nephron mass, or the number of functioning nephrons, is a measure of the functional capacity of the kidney. RadioCF-PET may enable early detection of nephron loss in patients with or at risk of CKD before changes are clinically detectable, facilitating early interventions to improve outcomes in these patients. METHODS/STUDY POPULATION: RadioCF-PET, labeled with Cu-64, has the advantage of using sub pharmacological doses for imaging, carrying low risk and can be used with the FDA’s exploratory IND (eIND) mechanism for early in human testing. We are developing the technology to be used in pre-eIND toxicology and pharmacology studies. We are also developing other aspects of translational science to propel this technology toward translation, including: market analysis, critical path to market, customer discovery, and commercialization strategy. RESULTS/ANTICIPATED RESULTS: Milestone 1: Apply technology in mouse model study and in human kidneys rejected for transplant. Anticipated Result 1: PET signal from RadioCF-PET correlates with glomerular density in healthy and diseased model male mice (R2 = 0.98). RadioCF-PET signal correlates with glomerular number in a donated human kidney (R2= 0.78). Milestone 2: Application to federal funding (STTR) and gap funding mechanisms to enable pre-eIND studies. Anticipated Result 1: Application for funding will aid to clarify and validate our market analysis and commercialization strategy. Milestone 3: Continued research and development with the technology in new studies. Other Anticipated Results: Future work with RadioCF-PET will enhance technology performance in preparation for pre-eIND studies. DISCUSSION/SIGNIFICANCE OF FINDINGS: We foresee a large clinical and commercial potential for RadioCF-PET to provide precise, early monitoring in patients at risk for or with CKD. The two biggest hurdles for clinical translation are validating safety and proving efficacy. This work targets both issues to facilitate RadioCF-PET toward clinical translation.

ABSTRACT IMPACT: Quantifying the types of dental procedures patients with healthcare needs receive can help understand and improve modalities of dental care to improve healthcare outcomes. OBJECTIVES/GOALS: 1. Quantify how medical complexity based on special needs diagnosis impacts dental treatment rendered

2. Comprehend how medical diagnosis of a special need can affect rate of treatment and type of treatment METHODS/STUDY POPULATION: This study consists of a chart review of all active patients in a dental school setting who have one of the following diagnoses of a special need: autism, developmental disorder, epilepsy, cerebral palsy, neuromuscular disorder, and hydrocephaly. Medical diagnoses were used to extract records and quantify the types of dental treatment rendered for these patients (preventative, restorative, and surgical), as well as the rates of appointments for this patient population. RESULTS/ANTICIPATED RESULTS: The medical complexity of patients of this population, as defined by the number medical diagnoses, impacts the type of treatment rendered as well as how frequently these patients are seen for dental care (rate of appointments). DISCUSSION/SIGNIFICANCE OF FINDINGS: Over- or under-utilization of dental treatment modalities can impact the oral health status and outcomes for patients with special needs. The differences in types and frequency/ rate of dental treatment rendered for patients of different medical complexity can further impede their oral health and systemic health status and health outcomes.

ABSTRACT IMPACT: Genomic data can be used by policy and decision makers to guide, and assess the impact of, public health responses to the COVID-19 pandemic. OBJECTIVES/GOALS: Our objective is to investigate the transmission and population dynamics of SARS-CoV-2 in New Mexico and other Mountain West states using whole genome sequencing. Understanding how the virus is spreading within and between communities is vital for the design of rational, evidence-based control measures. METHODS/STUDY POPULATION: We obtained an aliquot of 500ul - 1 ml of inactivated viral transport media (VTM) from positive SARS-CoV-2 nasopharyngeal swabs as determined by qPCR from the New Mexico Department of Health, TriCore Reference Laboratory, Idaho Bureau of Laboratories, and Wyoming Public Health Laboratory. We extracted viral RNA from the VTM, and sequenced the genomes using the methodology as described by the widely adopted ARTIC amplicon tiling protocol for SARS-CoV-2. Viral genomes were then sequenced on either an Illumina MiSeq or an Oxford Nanopore Technologies (ONT) GridION. We placed these samples within the context of globally representative sequences made available via the GISAID database. Consensus sequences were aligned and added into this global dataset using the Nextstrain augur pipeline. RESULTS/ANTICIPATED RESULTS: We sequenced over 1,000 SARS-CoV-2 genomes thus far from New Mexico (n=861), Wyoming (n=213) and Idaho (n=44). We used this sequence data to infer the transmission dynamics and spread of the virus, both within states and in context of regional and international spread. We inferred at least 128 separate introductions of the virus into New Mexico and at least 29 introductions into Wyoming. The origins of these introductions are diverse, spread across multiple regions in the US and abroad. We also sequenced samples from an individual who had multiple positive tests over time. Our results suggest that this individual was re-infected with a different strain than that of the initial infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our data show that New Mexico and other Mountain West states have continually experienced many introductions of the virus that then seed local outbreaks. By understanding the number of introductions over time, we can assess the impact of travel restrictions on transmission. Our data also supports that some individuals can be re-infected.