OBJECTIVES/GOALS: Innovative educational approaches and training modalities are important for training a diverse workforce in the authentic skills needed to advance all phases of clinical and translational research. Endeavors to study and develop policies that promote the translational science spectrum are steeped in value judgments. Learning how to navigate moral ambiguity and ethical reasoning enlightens our understanding of stakeholder obligations, roles and responsibilities. Ethics education can be challenging if learners are insufficiently engaged in the necessary critical reflection. In this course, decision-making in public health is informed through the analysis of the ethical issues, developing alternative courses of action and providing justification for actions taken in response to real-world dilemmas. The course is provided to students with a variety of backgrounds (science, health, policy) in a Master of Public Health degree program. Course objective were to: 1) Identify ethical issues in public health policy, practice, and research using appropriate concepts and terms; 2) Recognize the full spectrum of determinants of health and related information needed to resolve ethical conflicts in public health policy, practice, and research; 3) Present varied and complex information in written and oral formats; 4) Assess potential solutions to ethical conflicts in public health policy, practice, and research and 5) Decide ethical courses of action for public health policy, practice, and research. We adopted an open pedagogy as a guiding praxis to inform public health ethics discourse amongst our learners. In this way, learner agency was maximized to develop course materials within a generalized framework and shared with each other through the perspectives of each individual. The goal was to not only analyze complex ethical dimensions of public health issues but also gain insights into the disciplinary lenses of one’s peers. METHODS/STUDY POPULATION: Each week was divided into two sessions, a seminar and workshop. Course instructors introduce topics in a one-hour session and then allow students to decide what information is needed for a second session where the ethical issues of the topic will be discussed. Information-gathering tasks are then distributed amongst students in areas that are not their specialty, e.g. social history to be researched by learner with a biology background. The second session then involves the reporting back of background information by each student and a discussion of the ethical issues that arise. Through this process, the ability to communicate with others in different disciplines is supported, while exploring other disciplines and then engaging in ethical discussion and reasoning. Topics were introduced during the seminar session each week over the span of five weeks: 1) global public health, 2) disease prevention & control, 3) environmental & occupational public health, 4) resource allocation & priority setting and 5) research ethics. Learners were tasked with identifying the needed information to address the ethical, policy, and research aspects of the public health question(s) presented in these seminars. Students independently submitted resources they discovered to course instructors prior to the workshop. The following session began with a workshop where learners briefly presented their findings and deliberated on specific facets of the public health issue from that previous seminar while discussing a specific case. Students were assessed on their preparation (submission of identified resources), workshop presentation and participation. Research Preparation: In each seminar, the class decided what key information would be required to support the discussion at the workshop, which revolved around a relevant case study on that week’s topic. Course instructors facilitated the groups identification of material to be researched and the delegation of tasks within the group. Each student submitted a summary document (template provided) to course instructors prior to class for their area of research related to the case. Research Presentation: At the beginning of each workshop, each student was asked to present the research work to the rest of the class so that everyone has the same information for the case study discussion. These short (5-10 minutes) presentations followed the format of the preparation summary. Participation/collaboration: Both the seminar and the workshop asked students to be active learners within the class, participating in discussion, strategizing for information-gathering tasks, presenting researched material and arguments to others, and participating in case study discussion. Participation was assessed in relation to the value of the contributions made by students. RESULTS/ANTICIPATED RESULTS: The open pedagogy allowed the learners to construct the necessary materials to discuss issues with each other and develop not only a deeper understanding of the ethical dimension of public health issues but a shared understanding of each other’s disciplinary lenses. Course feedback was generally very positive, with learners either agreeing (33%) or strongly agreeing (67%) that the course was effective overall. In asking what learners liked best about the course, some indicated the “open pedagogy learning style” and “I liked the discussion format.” The positive comments mostly highlighted the discussion format. Areas for improvement noted by the learners included wanting “a longer course to cover more topics” and that the material was covered in “too short a time frame.” Other comments included that the course “was a bit disorganized” or that “the discussions were not very structured.” While the discussions by their very nature were unstructured, there is opportunity to refine this pedagogy to find right balance of learner agency. DISCUSSION/SIGNIFICANCE OF IMPACT: The goal of this teaching method was to empower the learner with the important critical thinking skills to navigate challenging ethical dilemmas in public health they may encounter in their careers. These skills include the identification of the ethical or moral conflict(s), collecting the necessary information to examine/resolve the dilemma, think creatively about the information that is unavailable and how to discuss/disseminate information to a broad constituency. This an educational model that is easily adaptable for learners working in other areas of the translational research spectrum, e.g. basic, pre-clinical, clinical and implementation sciences.

OBJECTIVES/GOALS: 1) Characterize racial differences in congestive heart failure care delivery. 2) Examine the extent to which specific clinical roles were associated with improved care outcomes (i.e., hospitalizations, readmissions, days between readmissions, and charges) of African Americans (AA) with CHF. METHODS/STUDY POPULATION: EMR data was extracted from the Arkansas Clinical Data Repository (AR-CDR) on patients (ages 18-105) who received care between January 1, 2014 and December 31, 2021. Variables included age, sex, race, ethnicity, rurality, clinical diagnosis, morbidities, medical history, medications, heart failure phenotypes, and care delivery team composition. Binomial logistic regression ascertained the effects of these variables on patient’s care outcomes. A Mann Whitney-U test identified racial differences in outcomes. Psychometrically, classical test theory and item response theory assessed items for the risk surveillance tool. RESULTS/ANTICIPATED RESULTS: The study identified 5,962 CHF patients who generated 80,921 care encounters. The results revealed the disproportionate impact of CHF prevalence, hospitalizations, and readmissions on AAs. AAs had a significantly higher number of hospitalizations (i.e., 50% more) than Caucasians. Specific clinical roles (i.e., MDs, RNs, Care Managers) were consistently associated with 30% or greater decrease in odds of hospitalization and readmission, even when stratified by heart failure phenotype. Classical test theory results (e.g., Cronbach’s alpha; 0.88) indicated the set of items on the risk surveillance tool accurately reflect a patient risk for improved outcomes. DISCUSSION/SIGNIFICANCE: The findings stimulate the need for 1) EHR-based tools that manage care delivery equity and 2) investigations of specific clinical roles in risk stratifying and operationalizing the care plans of AAs, advancing formal access-to-care frameworks by ensuring access to clinical roles that are associated with improved outcomes.

ABSTRACT IMPACT: The Hispanic Alliance for Clinical and Translational Research Professional Development Core (PDC) will contribute to the improvement of the health of an increasing US Hispanic population, by supporting and training a new cadre of Hispanic/Latino CTR researchers and community leaders that understand this population’s prevalent health needs. OBJECTIVES/GOALS: To use the Professional Development Core (PDC) of the Hispanic Alliance for Clinical and Translational Research (Alliance) as a hub that coordinates training, mentoring programs, and grant support to address the need for more underrepresented minorities (URM) in clinical and translational research and mentoring. METHODS/STUDY POPULATION: PDC will: (1). Coordinate and offer an effective educational program based for new and mid-career researchers to address the gaps in research competencies on Hispanic/Latino health and healthcare through web-based asynchronous distance training, enhanced with face-to-face interactions. (2). Establish a robust mentoring program to address the mentoring gap for URM faculty by developing mentorship skills of faculty and researchers through a variety of resources, and offering protected time to mentor-mentee teams. (3). Design and implement a tailor-made curriculum to train scientists and community partners jointly, enabling them to carry out multidisciplinary research responsive to the Hispanic/Latino community health’s needs. RESULTS/ANTICIPATED RESULTS: From 2010 to 2019 the PDC supported over 1,000 researchers and faculty and provided 52 activities over the 9 years. PDC-supported researchers submitted 56 proposals and 21 grants (37.5.%) were awarded, for a total of $2, 225,751.00, and to published 94 peer-review papers. We expect that through Alliance PDC will sponsor at least 20 new trainees/mentees in Clinical and Translational Research (CTR), 20 new certified mentors, a continuous support program, and an increase of 30% in the scientific productivity (e.g., grants submission and peer-reviewed publications) of the Hispanic CTRs in Puerto Rico and the establishment of long-term links with the Hispanic community in Puerto Rico and across the United States to address its health needs. DISCUSSION/SIGNIFICANCE OF FINDINGS: The PDC programs are significant in addressing the need for qualified researchers and mentors that understand, have the know-how, and are interested in addressing the health needs of a growing USA Hispanic medically underserved population.

OBJECTIVES/SPECIFIC AIMS: Current translational research moves beyond bench to bedside and includes translating scientific evidence to clinical practice and into the community settings (T1-T5). This progression is dynamic, involving patient-physician, community, and academic organizational structures and translational strategies. However, basic and clinician scientists are often unprepared and/or ill equipped to successfully conduct community-engaged research which may aid in more efficient translation of their research findings. The recognized need for such training was the impetus for our course which was originally designed and implemented through the innovative and sustainable joint academic-community partnerships of Morehouse School of Medicine and Emory University with the support of Georgia Institute of Technology. Since that time the course has evolved with the recently added partner, University of Georgia. METHODS/STUDY POPULATION: Initially developed and implemented in 2008, the course continues through the Georgia Clinical and Translational Science Alliance, Community Engagement and Research Program (GaCTSA/CERP), a Clinical Translational Science Award (CTSA) (UL1TR002378). The course is an introduction to community-engaged research concepts/methods. This includes behavioral science; community engagement principles; clinical translational research partnerships; and strategies in planning, implementing, evaluating, and disseminating community-engaged research to address health disparities. The course is open to the four GaCTSA academic institutions’ faculty, MD, PhD, MS in Clinical Research, and the Graduate Certificate in Translational Science students. RESULTS/ANTICIPATED RESULTS: Students received scholarly and hands-on training in community engaged research through faculty- and community member-led didactic lectures/interactions, team science activities, and a final assignment involving work with a community-based organization. From 2008-2017 over 230 students have matriculated through this course and many are now involved in community-engaged translational research. Most students in the class were MD/PhD students (33%), however 21% were junior faculty, attending physicians (21%), or fellows/residents/ postdocs (15%). Evaluations over the years indicate that most students were unware of Community-Based Participatory or community-engagement strategies for conducting translational research. DISCUSSION/SIGNIFICANCE OF IMPACT: Effective application of community-engaged translational research requires essential skills training to facilitate the translational research paradigm. Translational researchers, at any stage, will benefit from understanding the entire translational research process and the importance of quickly bringing research advances to patients and the community.

OBJECTIVES/GOALS: Promoting Academics and Community Engagement (PACE) Dissemination grants are funding opportunities via the Michigan Institute for Clinical and Health Research Community Engagement program designed to support the science of clinical and translational research demonstrating community impact. METHODS/STUDY POPULATION: Two statewide funding announcements over a 3-month period were issued to over 2,000 academic and community partners. Proposals were required to meet the following criteria: 1) data collection from an academic and community partnered research project completed; 2) research findings analyzed; and 3) a community-focused dissemination plan developed. Projects were funded up to $5000. RESULTS/ANTICIPATED RESULTS: Six PACE dissemination grants with community-focused plans were funded spanning Southeast, Western, and the Upper Peninsula regions of Michigan, as well as statewide. Examples of funded projects topics areas include the following: firearm safety; housing discrimination; opioid misuse; suicide prevention; and youth mental health. Community dissemination activities include: a) presenting at a community town hall; b) writing a pamphlet for community use; c) creating artwork installation showcase for community display; d) storytelling through community channels; and e) designing and implementing a local social media campaign. DISCUSSION/SIGNIFICANCE: Traditional funding mechanisms often do not provide resources to disseminate research findings with community benefit or impact back to communities. Funding dissemination awards through the PACE mechanism directly supports and accelerates translational science by sharing results directly back to the community in meaningful ways.

OBJECTIVES/GOALS: Racial discrimination and its associated stress are well-documented contributors to health disparities among African Americans (AA).This feasibility study aimed to acquire methodological insights and build the infrastructure for a subsequent mindfulness interventional study to reduce the effects of racism-based stress. METHODS/STUDY POPULATION: 20 AA participants ( female 12, male 8 )ages 18-50 were enrolled, and clinical data (blood pressure, waist/hip, BMI, lipids, HbA1c, creatinine) for Allostatic Index were collected. Racism-based stress was measured using RBTSSS and the Everyday Discrimination Scale (EDS). Psychometric measures (Coping, resilience, mindfulness, social connection) and sleep (PSQI) were included. Bivariate analysis explored associations between psychological measures and stress biomarkers, supported by Spearman’s correlation analysis. RESULTS/ANTICIPATED RESULTS: Low discrimination (EDS) was associated with a lower Total cholesterol/HDL ratio (2.99 vs. 4.20, p=0.009) and higher HDL (62 vs. 52, p=0.001). Low EDS participants also had better sleep (mean=3, SD=1.33, vs. mean=5.8, SD=3.99, p=0.05*) but reported less coping through drugs and alcohol (p=0.022*) and higher resilience (p=0.047*). Mindfulness negatively correlated to sleep disturbance (r=-0.477 to r=-0.62), coping and resilience. . EDS correlated with overall life stress and drug and alcohol use. Sleep disturbance was negatively associated with social connection (r=-0.569**) and mindfulness. Sleep disturbance and discrimination correlated positively with drug and alcohol use and overall life stress (r=0.52 and r=0.0.59, respectively), while resilience was negatively correlated with sleep (r=-0.45). DISCUSSION/SIGNIFICANCE: Discrimination was associated with increased stress and unfavorable coping, while mindfulness may offer potential benefits for sleep, coping, and resilience. These preliminary findings provide a foundation for further exploring the potential of mindfulness interventions to address the biopsychological impacts of racism-induced stress.

OBJECTIVES/SPECIFIC AIMS: The specific objectives of this project are (1) identify, test, and validate the parameters for a simplified NLOM imaging probe that will provide specific research and point-of-care information on biofilm presence, therapeutic need and response of individual wounds to treatment. (2) Identify specific proteomic and metabolomic biomarkers of (i) wound susceptibility to infection, (ii) wound response to the most commonly used antibacterial measures in wounds, and (iii) establish criteria for more effective interventions. METHODS/STUDY POPULATION: First, optimal use parameters for NLOM including illumination, field of view, focal length, linear Versus concentric image acquisition, detection and filter wavelengths were identified. Parameters for evaluation included ease and speed of imaging, ability to map diagnostic criteria. Next, using the optimised NLOM imaging modality in bacterial biofilm isolates and subsequently a rabbit ear model of biofilm wound infection, proteomic and metabolomic biomarkers of susceptibility to infection were identified. The effects of 2 standard debridement and anti-infective treatments, polyvidone-iodine solution or cetrimide 15%+ chlorhexidine gluconate 1.5% were mapped in situ for up to 10 days using the NLOM probe. RESULTS/ANTICIPATED RESULTS: Using the novel custom NLOM probe, high resolution mapping of wound biofilm infection, as well as the underlying tissue was performed throughout the onset, development, treatment, and resolution of wound biofilm infection. Specific microbiological, microstructural, oxygenation, and pH parameters were mapped at defined surface and subsurface locations and time-points. Findings included the determination that some standard antimicrobial formulations provide a supportive environment for wound infection, and that micro-channels within the biofilm and their interface with the tissues serve as an important predictor and indicator of wound infection establishment, progression, and response. DISCUSSION/SIGNIFICANCE OF IMPACT: The novel multimodality in vivo NLOM imaging approach establishes an important tool for earlier and more specific diagnosis of wound infection risk, virulence, and invasiveness along with markers of successful treatment, and a simple clinical imaging tool for improving wound infection prevention and treatment.

OBJECTIVES/GOALS: To develop a loop-mediated isothermal amplification (LAMP) assay for the detection of cytomegalovirus (CMV) infection and drug resistance. METHODS/STUDY POPULATION: We designed core and loop primers sets utilizing the NEB LAMP Primer Design Tool. Each set contained four or six primers targeting major-immediate early genes – essential for viral entry/replication – or regions known to confer resistance to the antiviral drug ganciclovir. Optimization of reactions conditions was achieved employing DNA reference materials. Reactions were visualized through a change in color as amplification reactions accumulated. Successful reaction conditions were selected based on specific amplification products in less than 60 minutes. Limits of detection were evaluated as the main performance outcome. RESULTS/ANTICIPATED RESULTS: Genomic data were extracted and used to design a series of LAMP primers (48 total) that aimed to detect specific genomic regions of CMV. Using this strategy, we successfully designed and identified eight primer sets that showed high 100% sensitivity and 100 % specificity, when detecting > 1.00 x 10^5 copies/mL of CMV gDNA. We are in the process of characterizing a new set of primers to determine the diagnostic utility of a LAMP assay in detecting selected single-nucleotide mutations at the UL97 loci. The expected outcomes at completion include: (1) the identification of LAMP primers to detect drug-resistance mutants, (2) defining optimal conditions for successful reactions, and (3) determining limits of detection for subsequent validation with clinical specimens. DISCUSSION/SIGNIFICANCE: CMV infection remains one of the most dangerous infectious agents for immunocompromised hosts, newborns, and unborn children. This study will describe a proof-of-concept LAMP assay for the genotypic detection of drug resistance in CMV-infected individuals and hence, create new avenues for selection of effective therapies to treat CMV disease.

OBJECTIVES/GOALS: Racial identity, one’s perception of that identity, and their perception of how others view their racial identity influences mental health. We aimed to assess the relationship between childhood trauma exposure, post-traumatic stress disorder (PTSD), and postpartum depression symptoms with individual Black identity in adulthood. METHODS/STUDY POPULATION: We examined whether racial identity, as measured by the regard subsection of the Multidimensional Inventory of Black Identity (MIBI), was impacted by childhood trauma exposure and related to PTSD and depressive symptoms in a sample of pregnant persons (N= 215, Mage=27.5, SDage=5.3) who identified within the Black diaspora, seeking prenatal care at Grady Hospital in Atlanta, GA. The regard subsection of the MIBI determines extent to which individuals feel positively about membership within the Black group (private regard) and the extent to which they think others feel positively about the Black group (public regard). We assessed childhood trauma using Childhood Trauma Questionnaire (CTQ) and depression and PTSD symptoms with Edinburgh Postnatal Depression Scale, and PTSD Checklist for DSM-5, respectively. RESULTS/ANTICIPATED RESULTS: Public regard (pubR) and private regard (privR) were significantly negatively correlated with childhood emotional abuse, emotional neglect, and overall childhood trauma exposure (all p’s.05). PrivR was significantly negatively correlated with both postpartum depression and PTSD symptoms (p DISCUSSION/SIGNIFICANCE: Ethnic-racial identity formation is a critical aspect of our psychological well-being, beginning in childhood and continuing across one’s lifespan. Our findings suggest that childhood trauma impacts racial identity in persons of the Black diaspora, which may contribute to negative mental health outcomes, including PTSD and depression.

OBJECTIVES/SPECIFIC AIMS: Leadership is an essential and recognized team science competency. To support the development of leadership skills at Mount Sinai, the LEAD (Leadership Emerging in Academic Departments) program, launched in 2016, delivers a structured 12-month blended learning program for junior faculty. The program aims to promote personal and professional leadership capacity, skills and behaviors. Following a competitive application process, 24 participants each year are selected to participate. In its second year, the challenge for the LEAD program leadership is to support alumni in fostering a culture of leadership that extends beyond the 12-month program. In order to promote a leadership community of practice and offer continued support to junior faculty, the LEAD Alumni program aims to bring former LEAD participants together to maintain motivation, share challenges and successes, meet with mentors and role models, and foster an ongoing community of practice that seeks to embed evidenced-based leadership culture at Mount Sinai. METHODS/STUDY POPULATION: The previous two cohorts of LEAD participants were approached to volunteer for the LEAD Alumni Forum working group. Four LEAD alumni came forward to form a self-selected working group. With input from the program leadership, the alumni working group is tasked with organizing regular events that bring the 48 previous LEAD participants together. The events provide the opportunity for individuals with expertise and a passion for leadership to create a supportive environment. This ultimately seeks to increase the transfer and utilization of leadership skills in practice, and promotes a culture of leadership. These alumni events also provide the opportunity for alumni to interact with senior leaders at Mount Sinai, thereby learning from role models within the organization. RESULTS/ANTICIPATED RESULTS: Evaluating learning transfer and culture change is challenging, so a number of proxy measures will provide insight into the success of the Alumni Forum. Firstly, the number of LEAD Capstone projects implemented in practice, and the success of these initiatives, will provide insight into transfer of leadership learning to practice. Secondly, participants will complete a validated survey tool, Leadership Programs Outcome Measure (LPOM), which explores self-reported leadership change at a personal, organizational and community level. Finally, participants will be followed up in the long-term to track promotion, awards, and other formal or informal leadership positions assumed following engagement in the LEAD program and the subsequent LEAD Alumni Forum. DISCUSSION/SIGNIFICANCE OF IMPACT: It is hoped the LEAD Alumni program will enhance the ability of participants to implement leadership knowledge and skills to practice, which may subsequently advance organization and culture change. Fostering a community of practice will further the reach of the LEAD program and as the number of LEAD alumni grows, and the Alumni Forum may provide the supportive environment that allows these individuals to have real impact.

ABSTRACT IMPACT: A comparative evaluation of the mechanical properties of commonly used posterior spinal fusion assemblies will allow surgeons to choose an assembly based on desired properties. The results will better inform surgical decision making and may lead to improved patient outcomes. OBJECTIVES/GOALS: The objective of this study is to evaluate and compare the mechanical properties of three posterior spinal fusion assemblies commonly used to cross the cervicothoracic junction. Fusion success depends on immobilization of vertebrae. The results will better inform surgical decision making and may improve patient outcomes. METHODS/STUDY POPULATION: Three titanium alloy posterior spinal fusion assemblies intended to cross the cervicothoracic junction underwent static compressive bending, tensile bending, and torsion as described in ASTM F1717 to a torque of 2.5 Nm: 3.5mm rods (Assembly A), 3.5mm to 5.5mm dilating rods (Assembly B), and two 3.5mm rods connected to two 5.5mm rods (Assembly C). Five samples of each assembly were attached to ultrahigh molecular weight polyethylene blocks via multiaxial screws for testing. The distance from the axis of rotation to the point of attachment of the rod and cervical screw was used as the lever arm to calculate the force required to create the desired torque for each test: lever arm of 37mm, requiring 67.6N of force to generate 2.5Nm of torque. Force and displacement were recorded, and stiffness of each construct calculated. RESULTS/ANTICIPATED RESULTS: An ANOVA was performed and resulted in p-values all p<0.005, indicating the test groups were significantly different. Therefore, pairwise t-tests with Bonferroni corrections (p<0.017) were used to determine pairs that were significantly different. Assembly A (3.5mm rods only) was found to be significantly less stiff than Assembly B (dilating rods) and Assembly C (3.5mm-connector-5.5mm rods) in each mode of bending: compression bending, tension bending, and torsion. Assembly A had a significantly greater range of motion in compression bending and torsion, but not tension bending, when compared to Assembly B and Assembly C. The only significant difference between Assembly B and Assembly C was found in the stiffness value of compression bending. DISCUSSION/SIGNIFICANCE OF FINDINGS: The results of this study indicate that incorporating a 5.5mm rod in a fusion assembly adds significant stiffness to the posterior spinal fusion construct. When stability of a fusion is of heightened concern, as demonstrated by the ASTM F1717 vertebectomy (worst case scenario) model, including 5.5mm rods increases the likelihood of fusion success.

OBJECTIVES/GOALS: The objective for this study was to evaluate the associations between weight stigma and symptoms of depression, anxiety, and binge eating following bariatric surgery. METHODS/STUDY POPULATION: Bariatric surgery is the leading evidence-based treatment for severe obesity; however, mental health challenges can compromise long-term improvements in quality of life. Weight stigma is a major contributor to mental health challenges for individuals with obesity generally; however, the role of weight stigma post-operatively after significant weight loss is poorly understood.148 patients underwent pre-bariatric surgery psychological evaluation and completed a follow-up study approximately 2 years after. Measures included the Stigmatizing Situations Inventory-Brief, Patient Health Questionnaire, Generalized Anxiety Questionnaire, and Binge Eating Scale. RESULTS/ANTICIPATED RESULTS: In regression models controlling for demographic covariates (sex, age, education, race), body mass index, and baseline measure of each outcome (e.g., depressive symptoms pre-surgery in models predicting depression post-surgery), weight stigma was independently associated with depression (p=.023), anxiety (p <.001), and binge eating (p=.008) symptoms post-surgery.Above and beyond weight, demographics, and pre-surgery measurements of mental health, weight stigma continues to influence mental health outcomes in the years following bariatric surgery. Despite weight loss after bariatric surgery, this data suggests the cumulative experiences of stigma and discrimination continue to negatively impact mental health. DISCUSSION/SIGNIFICANCE: Interventions for bariatric surgery patients must consider the effects of weight stigma, at both the societal and individual levels. Interventions countering stigma could optimize long-term quality of life and associated outcomes.

OBJECTIVES/SPECIFIC AIMS: The goal of this project is to determine the role of ETV6 in early B-cell development and define how germline ETV6 mutations result in predisposition to leukemia. METHODS/STUDY POPULATION: Gene expression commons were queried for expression levels of Etv6 and Pax5 at different stages of hematopoiesis. Mouse bone marrow was isolated and fractioned into cells committed to the B cell lineage via B220+ and CD43+ staining by flow cytometry and then separated into the following fractions: Fraction A (CD24low, CD19−), Fraction B (CD19+, CD24+, BP1−), and Fraction C (CD19+ CD24+ BP1+). Wild-type or germline mutant P214L ETV6 were cloned in an MiG vector and expressed in Ba/F3 cells. ChIP-PCR was performed by cross-linking proteins to DNA with 1% formaldehyde for 10 minute at room temperature, followed by cell lysis with RIPA buffer. Lysates were sonicated to shear DNA to a length of 200–1000 base pairs, then Protein A agarose beads were used to clean and immunoprecipitate chromatin. RESULTS/ANTICIPATED RESULTS: We observed that Etv6 is highly expressed in hematopoietic stem and lymphoid progenitor cells through the pre-pro-B stage (FrA), but its expression is significantly reduced in fraction B and thereafter (p<0.0001). Etv6 expression decreases as B cells develop and is negatively correlated with Pax5 expression (r2=0.9993; p=0.0167). We next confirmed the expression patterns of ETV6 and PAX5 during B cell development in human samples. We found that ETV6 expression was higher in the early B cell fraction (CD10+, CD34+, CD19−, and CD20−) compared to the pre-B cell fraction (CD10+, CD34−, CD19+, CD20−). Conversely, we observed that PAX5 expression was higher in the preB cell fraction compared with the early B cell fraction. In Ba/F3 cells expressing ETV6 constructs, ETV6, but not ETV6 P214L overexpression significantly decreased Pax5 expression (p≤0.05). ETV6 is associated with the proximal GGAA site 72 base pairs upstream of the Pax5 TSS, but not GGAA sites further from the TSS. In addition, the transcriptional repressors SIN3A and HDAC3 were detected on the same regions of the Pax5 locus. We detected association of ETV6, SIN3A, and HDAC3 with the proximal GGAA site upon expression of WT ETV6, but not ETV6 P214L. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results provide a mechanism of interaction for ETV6 and PAX5, 2 genes often disrupted in B-cell leukemia. These findings are significant because PAX5 misregulation results in a B cell development halt, lineage infidelity, and leukemogenesis. In continuing our studies, we have generated a transgenic mouse endogenously expressing the ETV6 P214L mutation by CRISPR/Cas9 editing, and these mice appear to have a thrombocytopenic phenotype similar to that observed in patients carrying the ETV6 P214L mutation. These animals will be the focus of our continued investigation of the mechanism by which ETV6 germline mutation results in a predisposition to leukemia. Our ultimate goal is a comprehensive understanding of how this process may be targeted more efficiently in patients with both heritable and sporadic forms of leukemia involving ETV6.

OBJECTIVES/SPECIFIC AIMS: As the sole Clinical and Translational Science Award (CTSA) site in Michigan, the Michigan Institute for Clinical & Health Research (MICHR) at the University of Michigan (UM) is working to develop community networks that drive clinical and translational research on community-identified health priorities. METHODS/STUDY POPULATION: These CBRNs will be modeled from successful work that has been accomplished in Jackson, MI where stakeholders from the local healthcare community, County Health Department, Health Improvement Organization, and grassroots community members created a Community of Solution to address the unmet behavioral health and social needs of community members. The CBRN’s will focus on identifying community health priorities by receiving input from community members in underserved communities using deliberative software called Choosing All Together (CHAT). RESULTS/ANTICIPATED RESULTS: In the fall of 2017, 3 focus groups were held in Northern Michigan to identify community health priorities. The top 5 community health priorities include; (1) mental wellness, (2) long-term illness, (3) alcohol and drugs, (4) air, water, and land, and (5) affording care. Additional focus groups are scheduled for the winter in 2 additional geographic areas. DISCUSSION/SIGNIFICANCE OF IMPACT: Future work for the creation of CBRNs includes building leadership groups comprised of clinicians, community leaders, public health leaders, health system leaders and researchers to inform the leadership groups of community-identified health priorities. In addition, the team is working to identify a platform to connect academic investigators across UM and community partners on shared research priorities in real time. In order to measure and map relationships within the networks, we are planning to utilize Social Network Analysis as an evaluation tool.

North Carolina Central University (NCCU) and Duke Cancer Institute implemented an NCI-funded Translational Cancer Disparities Research Partnership to enhance translational cancer research, increase the pool of underrepresented racial and ethnic group (UREG) researchers in the translational and clinical research workforce, and equip UREG trainees with skills to increase diversity in clinical trials. The Cancer Research Education Program (C-REP) provided training for UREG graduate students and postdoctoral fellows at Duke and NCCU. An innovative component of C-REP is the Translational Immersion Experience (TIE), which enabled Scholars to gain knowledge across eight domains of clinical and translational research (clinical trials operations, data monitoring, regulatory affairs, UREG accrual, biobanking, community engagement, community outreach, and high-throughput drug screening). Program-specific evaluative metrics were created for three broad domains (clinical operations, basic science/lab research, and population-based science) and eight TIE domains. Two cohorts (n = 13) completed pre- and post-surveys to determine program impact and identify recommendations for program improvement. Scholars reported statistically significant gains in knowledge across three broad domains of biomedical research and seven distinct areas within TIE. Training in translational research incorporating immersions in clinical trials operation, biobanking, drug development, and community engagement adds value to career development of UREG researchers.

OBJECTIVES/SPECIFIC AIMS: The purposes of this study are to examine the relationships among sleep characteristics (duration, efficiency), stress biomarkers, and child behavior problems among toddlers living in socioeconomically disadvantaged homes and how these characteristics change over time from age of 12 months to 24 months. Aim 1: examine changes in subjective and objective sleep characteristics from 12 to 24 months of age. Aim 2: examine changes in stress biomarkers from 12 to 24 months of age. Aim 3: examine the cross sectional and longitudinal relationships between sleep characteristics and stress response. Aim 4: examine the cross sectional and longitudinal relationships between sleep characteristics and toddlers’ child behavior problems. METHODS/STUDY POPULATION: In this cross-sectional study we are recruiting parents with healthy toddlers from early head start programs and a community clinic to prospectively examine the relationships among sleep characteristics, stress biomarkers, and children’s health. Data on sleep characteristics will include subjective and objective measures of sleep duration and efficiency and parental interactive bedtime behaviors to assist their toddlers’ sleep initiation. Multisystemic biomarkers of stress including cortisol, CRP, IL-6, and BMI, will be measured individually. The associations between sleep characteristics and the biomarkers, considered as a latent variable of the stress response, will be explored. Health measures will include secretory IgA and parent-reported behavioral problems. Generalized linear models will be used in the data analysis. RESULTS/ANTICIPATED RESULTS: To date we have obtained objective (9 days/nights of actigraphy) measures of 33 toddlers’ sleep and subjective measures of parenting interactive behaviors. Using the Parental Interactive Bedtime Behavior (PIBB) Survey and subscales [active physical comforting, encourage autonomy, settle by movement, passive physical comforting (PPC), social comforting], we are currently reporting on the associations between PIBB and toddler’s sleep characteristics. The sample included 33 toddlers (mean age=1.33 years, SD=0.54). The toddlers’ sleep duration averaged 8.22 hours (SD=0.86). There were statistically significant moderate associations between sleep duration and parents’ PPC (r=−0.41, p=0.02). Intra-individual variability in the amount of wake after sleep onset was also significantly associated with total PIBB and PPC (r=0.37, p=0.05; r=0.52, p=0.002, respectively). Intra-individual variability in the amount of sleep fragmentation within toddlers was significantly associated with total PIBB (r=0.36, p=0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Although active physical comforting (eg, rocking to sleep, patting or rubbing child’s back) is most commonly associated with sleep patterns in infancy and toddlerhood among samples of higher socio-economic status, findings from this study suggest a stronger association between PPC (eg, presence of the parent in the room to fall asleep) and less sleep duration and more individual variability in night wakings. The biomarker data are currently being analyzed and results will be presented within the year. Taken together, these preliminary results and pending results will inform future intervention development that may address the role of parenting behavior in promoting health sleep early in life.