The Common Metrics Initiative aims to develop and field metrics to improve research processes within the national Clinical and Translational Science Award (CTSA) Consortium. A Median Accrual Ratio (MAR) common metric was developed to assess the results of efforts to increase subject accrual into a set of clinical trials within the expected time period. A pilot test of the MAR was undertaken at Tufts Clinical and Translational Science Institute (CTSI) with eight CTSA Consortium hubs. Post-pilot interviews were conducted with 9 CTSA Principal Investigators (PIs) and 23 pilot team members. Over three-quarters (78%) of respondents reported that the MAR could be useful for performance improvement, but also described limitations or concerns. The most commonly cited barrier to MAR use for performance improvement was difficulty in interpreting the single value that is produced. Most respondents were interested in using the MAR to assess recruitment at an individual trial level. Majority of respondents (63%) had mixed opinions about aggregating metric results across the CTSA Consortium for comparison or benchmarking. Collecting data about additional contextual factors, and comparing accrual between subgroups, were cited as potentially helping address concerns about aggregation. Significant challenges remain in ensuring that the MAR can be sufficiently useful for collaborative process improvement. We offer recommendations to potentially improve metric usefulness.

OBJECTIVES/SPECIFIC AIMS: Our objective is to study the role of soluble adenylyl cyclase in the melanocyte regulation of pigment in response to ultraviolet radiation. Melanocytes are specialized cells that produce melanin in organelles called melanosomes, and melanin determines the pigmentation of hair and skin. cAMP is a master regulator of pigmentation and transmembrane class of adenylyl cyclases are essential for expression of important enzymes involved in melanogenesis. However, pigmentation is also controlled by melanosomal pH, which regulates melanogenesis, tyrosinase activity, and melanosome maturation. The relationship between melanosomal pH and cAMP has been elusive. Soluble adenylyl cyclase is a noncanonical source of cAMP that is not responsive to G proteins but rather functions as a pH sensor. We recently demonstrated that loss of soluble adenylyl cyclase (sAC) activity leads to increased melanosomal pH as well as increased pigmentation in cells and hair. We expanded our research to investigate the role of sAC in the intrinsic response of melanocytes to ultraviolet radiation. METHODS/STUDY POPULATION: We utilized sACfl/fl (wild type) and sACKO mouse melanocytes and compared their change in pigmentation in response to ultraviolet radiation. Melanin was used as a measure of pigmentation. We irradiated these cells at differing doses of UVB (0, 1, 2, or 3 mJ/cm2) daily for 3 days. After UVB treatment, cells were observed and the surviving cell numbers were determined. Cells were then analyzed for melanin content using spectroscopy. RESULTS/ANTICIPATED RESULTS: We found that while both sACfl/fl and sACKO cells had increased melanin content in response to UVB, the melanin content of sACKO cells increased more compared with sACfl/fl cells (p=0.001 at daily dose of 3 mJ/cm2). In addition, sACKO cells required less UVB dose to induce a response. We also observed that sACKO cells show increased cell death compared with sACfl/fl cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Although both sACfl/fl and sACKO cells can induce melanin production in response to UV, our results suggest that sACKO cells are more sensitive. We believe that this increased response in sACKO cells is due to increased melanosomal pH. In addition, sACKO cells show increased cell death, suggesting that sAC is important in the damage response secondary to UV exposure. UV plays a wide range of roles in skin biology such as contributing to cancer risk and pigmentation. Since pigmentation is essential for the protection of the skin from UV insult, further investigation of possible mechanisms in which sAC can influence pigmentation in response to UV is warranted.

ABSTRACT IMPACT: A robust and collaborative network of expertise and services is essential for successful research commercialization, including timely and scalable educational support for CTSA institutions and individual faculty investigators with biomedical innovations. OBJECTIVES/GOALS: Leverage expertise at the University of Michigan (UM) by creating collaborative and scalable interactive online courses to instruct and prepare internal and external faculty to navigate critical stages of life science academic research commercialization. METHODS/STUDY POPULATION: UM’s Fast Forward Medical Innovation created two online courses with the UM Office of Technology Transfer and the Michigan Institute for Clinical & Health Research (MICHR). Collaborative planning committees, with content and educational experts, set course goals and learning objectives based on audience needs (e.g. preparation for consultations, commercialization concepts, etc.). Draft content was developed, peer reviewed, and revised before Articulate Storyline was used to convert didactic content to active learning content (e.g. interactive slides, scenarios, quizzes, and forms). Pilot testing was conducted prior to the launch to faculty investigators throughout the UM network. RESULTS/ANTICIPATED RESULTS: Intellectual Property in the Academic Setting launched via the FFMI website and newsletter in July 2020 and has had 66 learners to date. Medical Device Regulations launched in October 2020 and has 22 learners. OTT and MICHR have successfully integrated the courses into their consultation process by requesting review from faculty investigators. We suspect that this will lead to more in-depth and meaningful conversation. Additionally, these courses have been integrated into an FFMI commercialization course to instruct on critical concepts. Evaluation and refinement for both use cases will ensue, as well as inform future collaborative courses. DISCUSSION/SIGNIFICANCE OF FINDINGS: Early results suggest that the courses are advantageous and can serve as a model for future collaborations. The opportunity to disseminate the courses across the CTSA network, as well as collaborate with other institutions, to scale localized expertise to a broader network is promising.

OBJECTIVES/SPECIFIC AIMS: Our objective is to create a Resistant Hypertension (RHTN) computable phenotype from electronic health record (EHR)-based data, and to determine the characteristics associated with RHTN within a large, diverse, EHR-based database. METHODS/STUDY POPULATION: The OneFlorida Clinical Research Consortium includes 10 unique health care systems providing care for approximately half of the state (48%, ~10 million). OneFlorida houses a Data Trust which contains longitudinal EHR data and claims data from these providers in a common format, the PCORnet common data model v3.0. For the current project, data from 5 health care systems were considered. All of the adult hypertension (HTN) patients with a HTN diagnosis from an outpatient encounter were extracted from the OneFlorida Data Trust. Additional data such as demographics, prescribing, and vitals information were also extracted. The RHTN computable phenotype was created by constructing a drug exposure variable that took into consideration the number of antihypertensive medications an individual was prescribed at any point in time over the course of the OneFlorida dataset. RHTN was defined as any blood pressure requiring four or more antihypertensive drugs, or uncontrolled blood pressure (≥140/90) on 3 antihypertensive drugs. RHTN cases had to meet the definition criteria twice during the data period, at least 30 days apart. All data extraction, computation phenotype coding, and statistical analyses were conducted using SQL or SAS. RESULTS/ANTICIPATED RESULTS: Our preliminary results show that there were n=342,026 adults with a HTN diagnosis from an outpatient visit in the data set. After the RHTN computable phenotype was constructed, n=11,670 RHTN cases were identified from the n=130,901 HTN individuals with all of the required variables in the data set (8.9% RHTN prevalence). In all, 55% of RHTN cases were Black or African American, compared with the total HTN population (25% Black/African American). RHTN cases also had more prescriptions for loop diuretics, centrally acting agents, α-blockers, and vasodilators compared with the total HTN population. Not surprisingly, the RHTN cases had 26% of the antihypertensive prescriptions in the data set, and the RHTN cases had fewer blood pressure readings that were in control (only 49.4% of readings <140/90). DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, our preliminary data shows that it is possible to create the very complicated computable phenotype of RHTN within the OneFlorida Data Trust. We found that the RHTN prevalence in OneFlorida is 8.9% which is consistent with previous studies from NHANES. Although promising, these results require further validation of the computable phenotype and replication in other similar data sets in order to ascertain their true meaning. Once validated, the experience gained from this computable phenotype can be applied to many other phenotypes.

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.

OBJECTIVES/SPECIFIC AIMS: Women with GDM have a 7-fold higher risk of developing T2DM, and rates of GDM are higher among racial and ethnic minorities and women of lower socio-economic status. There are no data on postpartum diabetes screening after the first postpartum year or among women receiving care in FQHCs. We aim to address this gap in the literature by (1) defining the rates of follow-up screening for T2DM at 6–12 weeks and 1–3 years postpartum and (2) characterizing patient, provider, and healthcare system attributes that are associated with lack of follow-up screening for T2DM in a population of low-income women with GDM. METHODS/STUDY POPULATION: This is a retrospective cohort study of women with GDM during pregnancy receiving care in Missouri FQHCs from 2010 to 2015. Electronic health records (EHR) data from 26 FQHCs is housed in a central repository through the Missouri Primary Care Association (MPCA). This includes patient demographic, lab, and medication information as well as encounter level patient and provider data for the prenatal and postpartum period. EHR data does not include accurate delivery information, however. Pregnancies during the study time frame were identified using CPT and ICD9/10 codes. Deidentified data on individuals with a pregnancy was utilized to identify a subpopulation of “GDM candidates,” using a broad definition of glucose abnormalities as follows: ICD-9/ICD-10 codes for diabetes, medications and testing supplies used for diabetes, infant birth weight ≥4000 g or 8 lb or 13 oz, or abnormal glucose labs [defined as fasting glucose≥95, gestational glucose screen≥130, 1 h test≥130 (or ≥180 if 2 h test and 3 h test recorded on same day), 2 h test≥155, 3 h test≥140, A1C≥6, any glucose≥130, or any positive urine glucose]. This subpopulation was then linked to Medicaid administrative claims data [housed at the University of Missouri Office of Social and Economic Development Analysis (OSEDA)], providing detailed information on delivery, to further characterize patients with GDM in the time frame and provide all dates necessary to classify pregnancy and postpartum periods. RESULTS/ANTICIPATED RESULTS: From the de-identified pregnancy data set including 45,810 individuals, we identified 8008 “GDM candidates.” EHR data were linked to Medicaid claims data for these individuals from 2010 to 2015. Utilizing the enhanced data set, we are defining a pregnancy for each individual by the delivery date in the Medicaid record and an algorithm using lab and ultrasound record dates to define gestational age at delivery. This will result in a pregnancy level data set linked with individual encrypted identifiers with each record representing 1 pregnancy and postpartum period. GDM in pregnancy will be defined as having a baby with birth weight≥4000 g or 8 lb or 13 oz, ICD-9 or ICD-10 code for GDM during pregnancy or at delivery, or an oral glucose tolerance test (oGTT) 12–16 weeks before delivery with 2 or more abnormal results by Carpenter and Coustan criteria. We anticipate that our final GDM data set will include 2000–3000 individuals. We will then calculate the percentage of individuals receiving recommended screening tests at 6–12 weeks (fasting glucose or 2 h oGTT) and 1–3 years postpartum (fasting glucose, 2 h oGTT, HbA1C). We will use multivariable regression techniques to identify risk factors for lack of screening. We will be able to incorporate predictors not previously evaluated including distance from home to health center, access to public transport, specialty and training of the patient’s providers, pregnancy weight gain, postpartum appointment time of day, and number of various types of office visits. DISCUSSION/SIGNIFICANCE OF IMPACT: The creation of a linked data set of pregnancies complicated by GDM in women receiving care in FQHCs in Missouri is the first step toward better characterizing follow-up diabetes screening rates in this population and understanding patient, provider, and healthcare system variables that affect postpartum screening. The ultimate goal is to translate evidence-based patient-centered sustainable interventions into practice for low-income women with a history of GDM and improve population outcomes with the ability to track progress prospectively over time.

Acknowledgements: The authors thank Susan Wilson (MPCA), Jill Lucht, and Bhawani Mishra (OSEDA).

ABSTRACT IMPACT: This research takes a transcriptomic approach to parse genes and molecular pathways that underlie the fear memory circuitry and, in doing so, identifies therapeutic targets that can further be developed into treatments for fear disorders, such as post-traumatic stress disorder. OBJECTIVES/GOALS: Normal fear learning produces avoidance behavior that promotes survival, but excessive and persistent fear after trauma can lead to development of phobias and post-traumatic stress disorder (PTSD). Our goal is to understand the mechanism and identify novel genetic targets underlying fear responses. METHODS/STUDY POPULATION: Involvement of the basolateral amygdala (BLA) in fear acquisition is well established and requires activation of N-methyl-D-aspartic acid receptors (NMDARs). At a cellular level, NMDAR activation leads to production of nitric oxide (NO) by a process mediated by interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS). To elucidate mechanisms underlying the role of the PSD95-nNOS-NO pathway in conditioned fear, here we use rodent behavioral paradigms, pharmacological treatment with a small molecule PSD95-nNOS inhibitor, RNA-sequencing, and an AAV-mediated knockdown of the nNOS gene in the BLA. RESULTS/ANTICIPATED RESULTS: We show that treatment with ZL006 attenuates rodent cued-fear consolidation. Additionally, with RNA-sequencing, expression of 516 genes was altered in the BLA following fear expression; of these genes, 83 were restored with systemic ZL006 treatment. Network data and gene ontology enrichment analyses further revealed that cGMP effects, insulin-like growth factor binding, and cognition-related pathways were significantly altered. Finally, we show that a BLA-specific knockdown of nNOS attenuates cued fear consolidation, without adverse effects on other memory and motor behaviors. DISCUSSION/SIGNIFICANCE OF FINDINGS: Via a model of NMDAR-mediated fear consolidation, our results reveal novel pathways and genetic targets that underlie plasticity of fear memory circuitry. Importantly, these results will inform future therapeutic strategies for targeting fear related disorders like PTSD.

OBJECTIVES/GOALS: Early pediatric intensive care unit (PICU) mobilization is safe and associated with improved outcomes. Nursing-specific mobility training is desired and improves mobilization compliance. Thus, our aim is to implement a nurse-targeted, simulation-based early mobility curriculum to determine if it increases the frequency of PICU mobilizations. METHODS/STUDY POPULATION: We will conduct a single center pre-post interventional study of an in situ nurse-targeted, simulation-based early mobility curriculum. We will prospectively evaluate mobilization events in 100 patients admitted during the pre-intervention phase (n=50) and the post-intervention phase (n=50). Inclusion criteria are children ages 1 day to 17 years old admitted to the PICU for ≥3 days. Exclusion criteria include specific mobility contraindications. PICU-wide deployment will be complete when >80% of nurses have participated in the curriculum. Demographic and clinical information will be obtained. Mobility data obtained will include number of nursing-led mobilizations, highest level of mobility achieved, and potential safety events. Data will be collected from the EMR and the nurse caring for the patient. RESULTS/ANTICIPATED RESULTS: The primary endpoint will be the change in the number of nursing-led mobilization events per patient day. The secondary effectiveness outcome is the highest level of mobility achieved by patients during mobilization events in a day. A final secondary end point will be safety events defined as unplanned extubations, medical device dislodgement, falls, and cardiac arrests. Descriptive statistics for continuous variables will be presented as the median and interquartile range and categorical variables will be expressed as percentages. The effect of the simulation curriculum on the clinical outcomes will be assessed using mixed-effects models. Due to the lack of normality in number of nurse-led mobilizations and highest level of mobility achieved, the analysis will be performed using log-normal models. DISCUSSION/SIGNIFICANCE: We hypothesize that we will demonstrate the crucial importance of hands-on nursing education to improve and increase early mobility of critically ill children

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/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

OBJECTIVES/GOALS: Our goal is to determine the structure of the CACHE domain of the Vibrio cholerae quorum sensing receptor CqsR as well as its autoinducer (AI). We are performing X-ray crystallography on the protein in its apo form, with the fractions containing the AI, and with known ligand ethanolamine (ETA). METHODS/STUDY POPULATION: We have transformed BL21(DE3) E. coli cells with a pTB146 vector to contain the gene for the CqsR CACHE domain. We grow these cells to high optical density and induce protein expression, at which point we harvest them and purify the protein. This entails lysing the cells, separating the protein with Ni-NTA resin, cleaving our protein tag, and column chromatography. With purified protein, high-throughput screens are set up to find crystallization conditions of apo CqsR, CqsR-ETA, and CqsR-AI. We then determine conditions that best lead to crystal formation and optimize them. Crystals are then diffracted with X-rays, process the data, and determine the structure of protein and AI. RESULTS/ANTICIPATED RESULTS: We anticipate finding the structure of the CqsR CACHE domain to a high resolution in addition to the identity of its autoinducer. Previous results found that the structure is homologous to another V. cholerae chemoreceptor, Mlp37, and we expect the results from this project to confirm this. In addition, we know that the autoinducer weighs approximately 62 daltons, the same as the known ligand, ethanolamine. Given that CACHE domains bind specifically to their ligands, we anticipate that the autoinducer will be structurally similar to ethanolamine. DISCUSSION/SIGNIFICANCE: The results will reveal the structure of the CqsR CACHE domain and its autoinducer. This knowledge will better allow researchers to treat cholera, as both autoinducer identity and receptor conformational changes will be uncovered, allowing for drug development to inhibit cell growth.

The Translational Science TS22 conference in Chicago in April 2022 was the first time post-pandemic that members of the Association of Clinical and Translational Science were able to meet up in person to share scientific advances. Given the remaining level of risk due to COVID-19, the meeting was designed as hybrid allowing virtual participation to some of the presentations. Prior to the meeting, JCTS Junior Editors were invited to report on the plenary sessions of the meeting. The present perspective constitutes a summary of three plenary sessions.

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: Severe malarial anemia due to Plasmodium falciparum is often accompanied by thrombocytopenia. Treatment includes transfusion of whole blood, which contains erythrocytes, platelets, and other blood components. The objective of the study was to assess the effect of whole blood transfusion on survival in children with severe falciparum malaria and to examine the potential interaction of thrombocytopenia with malaria mortality and transfusion response. METHODS/STUDY POPULATION: We analyzed a retrospective cohort of 842 hospitalized children in Zambia with severe malarial anemia (703 transfused, 139 not transfused due to stock-out or other reason). Severe malarial anemia was defined as a positive rapid diagnostic test or blood smear in combination with an admission hemoglobin concentration ≤5 g/dL. RESULTS/ANTICIPATED RESULTS: Mortality was 13% (94/703) in the transfused group and 24% (34/139) in the non-transfused group. Kaplan-Meier survival estimates stratified by transfusion status and thrombocytopenia (150,000/μL threshold) showed increased mortality in children with thrombocytopenia who did not undergo transfusion, with no differences in mortality among the other transfused and non-transfused groups (log-rank test P = 0.0001). Effect modification analysis by Cox proportional hazards regression adjusted for age, sex, hemoglobin concentration, blood group type, and eosinophilia showed a significant interaction between platelet count and transfusion status (P = 0.028). Children with thrombocytopenia who were transfused and died had little or no post-transfusion increase in platelets, in contrast to those who survived. Freshness of transfused whole blood, construed from expiration dates, correlated with greater platelet recovery and improved survival. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of platelets in malaria pathophysiology is complex and incompletely understood; prior studies describe preferential binding of platelets to parasitized erythrocytes and direct parasitocidal activity, whereas others detailed deleterious effects in malaria involving the central nervous system vasculature. These findings point to a potential clinical role for platelet-directed transfusion strategies to improve survival in children with severe falciparum malaria, which should be further assessed in randomized interventional studies.

ABSTRACT IMPACT: We present a minimally-invasive approach to monitoring heavy metal exposures in geographically disperse populations; this framework may encourage and facilitate greater participation in a broad range of related clinical studies that require biosampling. OBJECTIVES/GOALS: We hypothesize that microneedle array (MA) extraction of interstitial fluid (ISF) will enable minimally-invasive quantitation of heavy metal (HM) exposure. We establish analytical parameters for ICP-MS analysis of HMs in ISF, quantify baseline HM content in ISF vs other fluids, and characterize a mixed HM exposure model. METHODS/STUDY POPULATION: Recent advances in ISF extraction and analysis suggest a minimally-invasive to monitor HM exposure longitudinally in both urban and dispersed communities. ISF can be collected with MAs and is a rich source of disease and exposure biomarkers. To refine analytical methods, Human subjects with no underlying skin disease were recruited into the IRB-approved study. Each subject had blood and urine collected. ISF was also collected using 3D-printed MA-holders. The fluids were analyzed, using ICP-MS, to quantify the levels of uranium (U), cadmium (Cd), vanadium (V), and arsenic (As). Additionally, we analyzed 2,770 subjects from the public NHANES dataset from 2018-2019. Python and Scikit-learn were used to analyze the demographics, survey responses, and metal concentrations for these individuals. RESULTS/ANTICIPATED RESULTS: While several studies have described the surface water and sediment content of toxic metals, determining biological loads remains challenging due to the need to collect blood or urine from a dispersed rural population over time. Our preliminary results suggest similar HM concentrations in ISF, compared with blood in a small unexposed population. Analysis of subjects from the NHANES public datasets suggest similar baseline blood HM concentrations in diverse subject populations with some differences in Cd depending on smoking and e-cigarette usage. Correlation maps also suggest possible synergy between different metals with cobalt and chromium showing the highest correlation. The initial results from this study have been applied to develop a mixed HM exposure model in rats for further translational testing. DISCUSSION/SIGNIFICANCE OF FINDINGS: We present a minimally-invasive HM monitoring approach. Exposure to multiple HMs is suspected to have additive or synergistic harmful health effects. We ultimately envision a wearable microneedle patch that could be mailed to individuals or distributed through community centers, worn for a few hours, and returned to a central laboratory.