OBJECTIVES/GOALS: An increasing number of hospitals and provider groups are consolidating into larger health systems, which hold potential to improve access to and quality of surgical cancer care through clinical integration across sites. In order to study clinical integration, we sought to develop: METHODS/STUDY POPULATION: Hospital data from the American Hospital Association were merged with data from the Agency for Healthcare Research and Quality’s Compendium of United States Health Systems. For each health system with more than one acute care hospital, the hospital with the highest surgical volume (inpatient and outpatient) was categorized as the hub hospital while all other hospitals were categorized as spokes. We evaluated the concentration of case volumes at hub versus spoke hospitals and compared characteristics of these hospitals and their surrounding communities using univariate and multivariable logistic regression analyses. RESULTS/ANTICIPATED RESULTS: Within 624 health systems containing 3,554 hospitals, 355 hospitals were characterized as hub hospitals and had 2,645 affiliated spoke hospitals (median 17 spokes per hub, range 2-151). Hub hospitals performed a median of 68% of all surgical cases (25th-75th percentile 44-87%) and were concentrated in metropolitan (88.5%) and urban areas (11.5%) with none in rural areas; spoke hospitals were located in metropolitan (67%), urban (28%) and rural (5%) areas. On multivariable analysis, spoke hospitals were more often located in rural and small urban counties (OR 9.49, CI 4.57-19.70) and took care of a higher percentage of patients with less than high school education (OR 1.06 for each 1% increase, CI 1.03-1.10) but with lower poverty rates (OR 0.90 for each 1% increase in % poverty, CI 0.86-0.95). DISCUSSION/SIGNIFICANCE: For integrated health systems with multiple acute care hospitals, surgical volume is highest at a single hub hospital, supporting use of a hub-spoke taxonomy. Patient populations in counties with hub versus spoke hospitals differ in urban-rural location, poverty rates, and education level, which may impact access to quality care.

OBJECTIVES/GOALS: The objective of this study is to define the molecular mechanisms that control survival of malignant stem cells in acute myeloid leukemia (AML). Leukemia stem cells (LSCs) are not effectively eradicated by standard treatment and lead to resistance and relapse, which contribute to poor survival rates. METHODS/STUDY POPULATION: The recently FDA approved venetoclax, a BCL2 inhibitor, with azacitidine, a hypomethylating agent leads to a 70% response rate in AML patients. Analysis of patients treated with this regimen showed direct targeting of LSCs. BCL2 has a non-canonical function in regulation of intracellular calcium. To determine how BCL2 mediated calcium signaling plays a role in LSC biology, we used LSCs isolated from venetoclax/azacitidine (ven/aza) sensitive and resistant patient samples to measure expression of calcium channels via RNA seq. BIO-ID, siRNA, flow cytometry, seahorse assays, calcium measurements and colony assays were used to determine the effects of calcium channel perturbation on LSC biology. RESULTS/ANTICIPATED RESULTS: BCL2 inhibition leads to decreased OXPHOS activity in primary AML specimens. BIO-ID studies revealed cation/metal ion transporters, ER membrane proteins and ER membrane organization as top enriched pathways interacting with BCL2. RNA-seq data showed increased expression of genes involved in calcium influx into the ER in ven/aza sensitive LSCs and increased expression of genes involved in calcium efflux from the ER in ven/aza resistant samples. Ven/Aza resistant LSCs have increased mitochondrial calcium content, consistent with their increased OXPHOS activity as calcium is required for OXPHOS. Perturbation of these channels leads to decreased OXPHOS activity and decreased viability in LSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: We postulate that a deeper understanding of the mechanisms behind ven/aza targeting of LSCs will lead to the development of novel therapies for patients who do not respond to ven/aza. Our data show targeting intracellular calcium signaling could be a viable therapeutic strategy for AML patients.

OBJECTIVES/SPECIFIC AIMS: Suggestibility, defined as the inclination to accept and internalize messages, has not been assessed much in relation to alcohol use. Prior research has shown that suggestibility to social cues and peer influence may play a role in driving alcohol consumption. Our previous work has shown associations between suggestibility and alcohol consumption in social drinkers. This study aims to examine how suggestibility and social susceptibility are related to ideas alcohol consumption and consequences across the spectrum of alcohol use and misuse. We hypothesize that those with higher suggestibility and social susceptibility reports will also have higher alcohol consumption and consequences, and that the impact of susceptibility is lower in dependent compared to non-dependent drinkers. METHODS/STUDY POPULATION: Study participants enrolled in the NIAAA screening and assessment protocol (N=157) completed questionnaires on suggestibility and alcohol consumption, The Multidimensional Iowa Suggestibility Scale (MISS) is a 95-question self-report assessment of suggestibility which draws from subcategories of consumer suggestibility, perceivability, physiological suggestibility, physiological reactivity, and peer conformity. Alcohol measures included 90-day Timeline Followback interviews and the Alcohol Use Disorder Identification Test (AUDIT). Participants also underwent the Structured Clinical Interviews for DSM-IV or DSM-5 disorders, and were stratified into two groups: alcohol dependent (N = 86) and non-dependent (N=71). Median split by age was additionally used to explore age’s relationship with suggestibility and alcohol with the under 36 (N = 45) and over 36 (N = 26) non-dependent groups. RESULTS/ANTICIPATED RESULTS: Initial analyses showed marked differences between the dependent and non-dependent groups in the relationship between the MISS total score and AUDIT total score. The non-dependent group showed significant positive correlations between MISS and AUDIT scores (r = 0.460, p < 0.001), while the dependent group did not show any correlation between MISS and AUDIT scores. Further examination of these relationships in the nondependent group revealed that MISS scores were also significantly positively correlated with AUDIT subscores of consumption, harm, and dependence. Age was found to have a significant negative correlation with MISS score (r = −0.354, p < 0.01). To better understand the role of age, the sample was split based on the median age (36 yrs), and analyzed separately. Results indicated robust relationships between MISS score and AUDIT (r = 0.457, p < 0.01) in the younger age group. In addition, the younger age group also showed significant relationships between MISS score and 90-day TLFB measures of total drinks, days drinking, and heavy drinking days. DISCUSSION/SIGNIFICANCE OF IMPACT: In non-dependent individuals, there was a significant positive relationship between suggestibility and alcohol measures, and these effects were amplified in younger individuals. No relationship was found between suggestibility and alcohol measures in the alcohol dependent individuals. This may be related to a greater impact of social and external contextual cues in younger social drinkers compared to dependent drinkers where tolerance and craving may have greater impact on alcohol consumption. These findings have important implications for traits that may put individuals at risk for developing harmful patterns of alcohol use and misuse. Future analyses will aim to examine biobehavioral underpinnings of the relationship between suggestibility and alcohol consumption.

OBJECTIVES/SPECIFIC AIMS: The promise and potential of connected personal health records (PHRs) has not come to fruition. This may be, in part, due to the lack of user-centered design and of a patient-centric approach to curating personal health data for use by patients. Co-design with end-users could help mitigate these issues by ensuring the software meets user’s needs, and also engages patients in informatics research. Our team partnered with patients with multiple chronic conditions to co-design a patient-centric PHR. This abstract will describe our experience with the co-design process, highlight functionalities desired by patients, and showcase the final prototype. METHODS/STUDY POPULATION: We conducted 3 design sessions (90 min per session) with patients as co-designers and employed an iterative process for software development. Patients were recruited from Chapel Hill and surrounding areas. The initial design session laid the foundation for future sessions, and began with brainstorming about what patients thought their ideal version of an engaging connected PHR would look like in terms of features and functionalities. After each software iteration, our entire design team, including our patient co-designers, was shown the prototype during a subsequent design session. Once the final prototype was developed, usability testing was conducted with patient participants. Our team then conducted a final design session to debrief about the final prototype. RESULTS/ANTICIPATED RESULTS: We started with an initial group of 12 patients (6 males) who all had diabetes and an additional comorbidity such as hypertension and hyperlipidemia. Age of participants ranged from 30 to 77 years with an average age of 56. The majority of participants were Caucasian with 1 Asian and 2 African Americans. Hemoglobin A1c values ranged from 6.0% to 9.2% with approximately half having A1c values less than the goal of 7.0%. Half the patients were aware of PHRs, majority had smartphones, and all participants had access to the Internet and used email. Two of the patients were retired engineers who had prior experience with software design. The other sessions had between 7 and 8 participants at each session, and 7 patients completed the 90-minute usability testing session. There was a core group of 7 patients who were engaged in the design and testing sessions throughout the entire 9-month study. Key features of the PHR that emerged from design sessions included the following: (1) allow for annotation of data by patients (particularly important for lab values like glucose or for physical activity); (2) calendars, to do list, and reminder functions should be linked so that an entry in one of these allows for auto-population of this data within the other sections; (3) notifications whenever new data from the electronic health record or other sources are pushed to the PHR account; (4) allow for drag and drop of photos of pills/medications taken via smartphone or from other sources so that medication list has photo of actual pills or pill bottle; (5) allow for patients to customize the order of sections in the PHR dashboard so that the sections most important to the individual patient can be displayed more prominently; (6) allow for notifications from pharmacies to be pushed to the PHR (eg, confirmation of receipt of prescription requests or alert that prescription is ready to pick up); and (7) graphical display of trends over time (patients would like to select the measures and time frames to plot for display). Patients cited the importance of data provenance so that patient-entered data Versus provider or electronic health record data could be easily differentiated. Patients also highlighted the importance of having this PHR be a “one-stop shop for all their health data” and to have meaningful data dashboards for the different types of information needed to comprehensively manage their health. Patients wished for a single PHR that could easily bring together data from multiple patient portal accounts to avoid having to manage multiple accounts and passwords. They felt that heat map displays such as those used on popular fitness tracking websites were not intuitive and that the color-coding made interpretation challenging. Participants noted that engagement in the design process made them feel that they contributed towards developing software that could not only positively impact them individually but others as well. Every patient indicated the desire to participate on future design projects. Of the 19 tasks evaluated during usability testing, only 5 tasks could not be completed (eg, adding exercise to the calendar, opening the heat map, etc.). Patients felt that the overall PHR design was clean and aesthetically pleasing. Most patients felt that the site was “pretty easy to use” (6 out of 7). The majority of participants would like to use this PHR in the future (5) and would recommend this PHR to their friends/family to use (6). DISCUSSION/SIGNIFICANCE OF IMPACT: Involving patients directly in the design process for creating a patient-centric connected PHR was essential to sustaining engagement throughout the software life cycle and to informing the design of features and functionalities desired by patients with chronic conditions.

OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.

OBJECTIVES/GOALS: There is universal recognition of the importance of team science and team leadership. We have developed a semi-quantitative translational science specific team leadership competency assessment tool and have begun implementation studies to assess the impact of personalized feedback on the team science leadership skills of KL2 Clinical Scholars. METHODS/STUDY POPULATION: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to concretize the relevant constructs, then used these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively create domain-specific survey items. Further discussion helped refined the number, grouping, and wording. Scholars also contributed feedback in item development. We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars, and having each Scholar rate themselves. Each item was answered using a six-point Likert scale where a low score indicated poor expression and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Incorporation into a REDCap data base made consenting and rating process by TSE’s and the Scholars straightforward. The a priori domains (Foundational Leadership Competencies, Professionalism, Team Building and Team Sustainability, Appropriate Resource Use and Study Execution, and Regulatory Accountability) had high internal validity and good internal factor structure. The congruence between TSE and Scholar self-ratings were uniformly high, and discordance was often a function of “confidence” and “modesty” on the part of the scholar, rather than deficiency. Supporting comments were informative about performance barriers and mechanisms for improvement. Return of results allowed for the exploration of training gaps. Scholars were surveyed to gauge their reaction to the formal feedback. DISCUSSION/SIGNIFICANCE OF IMPACT: This quantification of team science leadership constructs has allowed for A)- the articulation of constructs essential for successful Translational Scientists to acquire during their training, B)- identification of gaps in that training and skill set, and C)- mechanisms for bolstering any identified gaps in these essential leadership constructs. CONFLICT OF INTEREST DESCRIPTION: None

Although mentoring is critical for career advancement, underrepresented minority (URM) faculty often lack access to mentoring opportunities. We sought to evaluate the impact of peer mentoring on career development success of URM early career faculty in the National Heart Lung and Blood Institute-sponsored, Programs to Increase Diversity Among Individuals Engaged in Health-Related Research-Functional and Translational Genomics of Blood Disorders (PRIDE-FTG). The outcome of peer mentoring was evaluated using the Mentoring Competency Assessment (MCA), a brief open-ended qualitative survey, and a semi-structured exit interview. Surveys were completed at baseline (Time 1), 6 months, and at the end of PRIDE-FTG participation (Time 2). The following results were obtained. Between Time 1 and Time 2, mentees’ self-assessment scores increased for the MCA (p < 0.01) with significant increases in effective communication (p < 0.001), aligning expectations (p < 0.05), assessing understanding (p < 0.01), and addressing diversity (p < 0.002). Mentees rated their peer mentors higher in the MCA with significant differences noted for promoting development (p < 0.027). These data suggest that PRIDE-FTG peer mentoring approaches successfully improved MCA competencies among URM junior faculty participants with faculty ranking peer mentors higher than themselves. Among URM faculty, peer mentoring initiatives should be investigated as a key strategy to support early career scholar development.

OBJECTIVES/GOALS: The purpose of the project was to create a Tableau dashboard to track metrics on requests for research data at Atrium Health Wake Forest Baptist. The objectives included: 1) define and identify request fulfillment metrics, 2) build a dashboard to capture metrics, and 3) integrate the dashboard into metrics tracking and reporting activities. METHODS/STUDY POPULATION: Project managers and team leaders in the Office of Informatics collaborated to determine which measures would be most relevant and impactful to report on. Metrics that were collected included: total count of tickets fulfilled over time, number of tickets currently open, sum of outstanding quoted hours, quoted hours vs. actual hours needed to fulfill ticket, and hours billed. Tableau's direct connection feature was used to extract the Trac ticket data from its Postgres database and the dashboard was published to Tableau Server. After the initial draft was created, several rounds of revisions were made as new data insights were discovered through further investigation of the data. RESULTS/ANTICIPATED RESULTS: Each morning, Tableau Server runs an automatic refresh of the data. On the dashboard homepage, users can see a quick view of all available metrics; to minimize noise, only the current statuses, active tickets, and stats for the most recent monitoring periods are displayed. Many of the charts give the user the option to link out to a page with related supplemental information (historic data, ticket status history, etc.). With the help of the dashboard, project managers and team leaders can now monitor how long tickets are in each status, increase quote accuracy using the hours quoted and hours billed charts, and examine ticket complexity over time. DISCUSSION/SIGNIFICANCE: Prior to dashboard creation, metrics were sparse and difficult to assemble. By providing information on the quantity, size, and complexity of data requests, the dashboard enables the Office of Informatics to monitor how the process is functioning overall, make informed decisions about resource allocation, and provide quick interventions.

OBJECTIVES/SPECIFIC AIMS: In the context of skeletal muscle, IL-6 plays a major role in muscle quality. The goal of this project was to study the influence of systemic IL-6 on skeletal muscle mitochondrial physiology, most notably mitochondrial function (respiration and ROS production) and mitochondrial content. METHODS/STUDY POPULATION: To determine the influence of interleukin-6 (IL-6) on skeletal muscle mitochondria, high-resolution respirometry was performed to simultaneously measure oxygen consumption (JO2) and ROS production in differentiated myotubes incubated with increasing IL-6 (0, 10, 50, 100 ng/mL) for 18 hours in serum free conditions. To evaluate the impact of IL-6 on mitochondrial content we performed western blots on cell lysates from treated cells, measuring proteins of the mitochondrial electron transport chain (ETC) using a cocktail antibody and PGC-1α/PGC-1ß for mitochondrial biogenesis. To determine the role of mitochondrial ROS production on JO2 and mitochondrial content, we co-treated differentiated myotubes for 18 hours with 50 and 100ng/mL IL-6 and the mitochondrial specific antioxidant, MitoQ and performed respirometry for mitochondrial functional measurements and western blots for mitochondrial content.Statistical significance was evaluated by using a 2-tailed Student’s t-test and two-way ANOVA. Post hoc all-group analyses were conducted to determine which groups were different when the model was significant. RESULTS/ANTICIPATED RESULTS: Mitochondrial functional measurements show increased JO2 and increased ROS production in an IL-6 dose-dependent manner. Targeting mitochondrial ROS production with 0.5µm MitoQ attenuated IL-6 induced increases in JO2 and ROS production. Complexes I and II (CI, CII) of the ETC increased significantly in an IL-6 dose-wise fashion, and co-treatment with MitoQ normalized increases at 100ng/mL Il-6. 100ng/mL IL-6 significantly increased protein expression of PGC-1α and PGC-1ß. Co-treatment with MitoQ normalized IL-6 induced increase in PGC-1α. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest that when treated chronically at a high dose, IL-6 increases mitochondrial respiration, ROS production, and content. Targeting mitochondrial ROS production normalizes these mitochondrial adaptations. The present study provides new insights into mitochondrial physiology in the context of inflammation. Therapeutically targeting mitochondrial ROS production may impact skeletal muscle quality in certain populations.

ABSTRACT IMPACT: Implementation of digital and mobile applications in clinical research crisis response protocols can mitigate their impact on clinical research. OBJECTIVES/GOALS: Crisis management is fundamental to ensuring the protection of human subjects during a clinical trial. Mobile apps have the capacity to allow for quick access to crisis response plans and can serve to mitigate their impact on clinical research. Electronic data capture tools can be used to create digital applications for such a response. METHODS/STUDY POPULATION: The Clinical Research Center at Rutgers University transferred a paper-based crisis management response plan to a digital mobile application format using Vanderbuilt’s Research Electronic Data Capture Tool (REDCap). REDCap’s branching logic allowed for programming a decision support functionality to guide users through 3 specific crises. (1) threatening or aggressive study subject behavior; (2) clinical research center break in or theft; and (3) adverse event observed for ongoing or closed clinical research study. Applicable U.S. Code of Federal Regulations, IRB guidelines, institutional policies and procedures were also used as a component of the mobile development. RESULTS/ANTICIPATED RESULTS: The Crisis Management Decision-Support Portal within the Clinical Research Center has an interactive structure. The use of branching logic demonstrates the ability for users to answer each question and be guided to appropriate responses specific to selected criteria related to each event. The tool contains a self-correct function by providing a reset option after answering each section. The portal itself can be accessed using any computer or cellphone with an internet connection. It provides the users with appropriate criteria to determine to exact communication and management protocols for reporting for the crisis event they are witnessing. As users access the portal, usage data can be collected, tracked, and stored. DISCUSSION/SIGNIFICANCE OF FINDINGS: The REDCap platform offers the opportunity to digitize crisis management protocols that ensure professionals have easy access to appropriate responses to crises at the center. The use a digital application rather than paper allows for a CTSA sponsored hub to mitigate damage, simply build new protocols, modify existing protocols, and track usage.