OBJECTIVES/GOALS: The objective of this project was to evaluate the factors that contribute to LGBTQIA2+ patient comfortability. This information was then used to understand how best to create a comfortable space for LGBTQIA2+ patients. METHODS/STUDY POPULATION: This survey was focused on underinsured and uninsured patients seen at the Rainbow Clinic - a free student-run LGBTQIA2+ clinic. Surveys were distributed by undergraduate volunteers on tablets as a qualtrics survey. Surveys collected demographic information in addition to 5 questions that assessed patient comfortability. These questions included evaluating the patient’s comfort with sharing information with the provider and the patient’s comfort of coming into clinical spaces. These surveys were distributed before and after clinic appointments to capture any changes in comfortability that could have occurred as a result of the appointment. RESULTS/ANTICIPATED RESULTS: Up to May of 2023, 49 patients were seen in Rainbow Clinic. 33 patients filled out the intake survey and 31 patients filled out the check-out survey resulting in a 67% and 63% response rate respectively. Questions were asked on a likert scale (1-5) from Strongly Disagree to Strongly Agree. Questions evaluating patient comfort in sharing information with their provider yielded an average score that was statistically significant, suggesting patients felt comfortable at the Rainbow Clinic. Additionally, patients indicated that the LGBTQIA2+ specific labeling of the Rainbow Clinic made them significantly more comfortable coming into the clinic. DISCUSSION/SIGNIFICANCE: This project suggests that patient comfortability can be improved by training and intentional LGBTQIA2+ labeling. Considering the hesitancy of this community towards healthcare, improving comfortability not only benefits clinical care and outcomes but can also bolster the body of research on this community.

OBJECTIVES/GOALS: Atopic dermatitis is one of the most common chronic childhood conditions worldwide and is associated with poor mental health outcomes. Our aim is to determine whether childhood atopic dermatitis is associated with symptoms of depression throughout childhood and adolescence, and whether this association is mediated by serum inflammatory markers. METHODS/STUDY POPULATION: We will perform a longitudinal analysis of over 7000 children from an existing prospective cohort. The primary exposure is atopic dermatitis (AD) annual period prevalence measured by a standardized questionnaire at 12 time points between age 6 months and 16 years. Depression is measured using self-reported responses to the Short Moods and Feelings Questionnaire at 6 time points between 10 and 18 years of age. Cross-sectional regression analyses will be performed to compare depressive signs between children with and without AD and test for dose-response effects with AD and depression. Longitudinal analyses will be conducted using mixed-effects models to estimate the average effect across childhood. We will complete a mediation analysis to determine the extent to which IL-6 and CRP mediate this association. RESULTS/ANTICIPATED RESULTS: We anticipate that atopic dermatitis will be associated with SMFQ scores in a dose response relationship, and that inflammatory markers CRP and IL-6 will partly mediate this association. DISCUSSION/SIGNIFICANCE OF IMPACT: Childhood is a critical time for mental health. Understanding the longitudinal relationship between atopic dermatitis, depression, and inflammatory mediators is crucial as new biologic treatments targeting inflammatory cascades are approved for atopic dermatitis and have the potential to prevent mental health conditions.

OBJECTIVES/GOALS: A workflow management tool is essential in order to help support consistent processes with transparency in next steps of the study process. Prior to this tool, staff has relied upon extensive training and coaching on the study process. While resources and guidelines exist, it requires additional time for staff to identify these resources and allows for confusion and rework. Implementation of a systematic workflow management tool was identified as a critical need in order to support streamlined processes, improve transparency and support business continuity, and to accelerate the study process. METHODS/STUDY POPULATION: This effort was undertaken as part of the Protocol Lifecycle Management effort to implement a comprehensive clinical trial management system for clinical research studies. Mayo Clinic has designed a workflow management tool within the Velos eResearch system. The workflow manager is dynamic and will present specific activities based on the study design and responses to data entered on the ad hoc forms. A Workflow Build group contributed to the design of the workflow in order to reflect appropriate, current operational processes. The workflow was vetted and validated with research teams. In addition to designing activities, planned dates and target timelines were established for relevant workflows to help promote transparency in the study start-up timelines and allow study staff to identify overdue activities. Study status controls were designed in the workflow to protect study staff from inadvertently changing the status until appropriate activities are complete. RESULTS/ANTICIPATED RESULTS: A dynamic workflow has been designed and implemented in the Velos eResearch system to support Mayo Clinic research sites. This system will be implemented February 24, 2020 to all consenting studies. DISCUSSION/SIGNIFICANCE OF IMPACT: The implementation of this workflow management tool is critical to help support research operations in a large, academic medical center. Benefits to implementation are expected to include improved transparency in the study status and next steps, reductions in rework due to confusion in next steps, better understanding from new staff in the appropriate study process, and improved timelines for study start-up. As we prepare for the implementation of the Velos eResearch system at Mayo Clinic, the workflow management tool has been identified in training sessions as a positive benefit.

OBJECTIVES/GOALS: Compiling information about characteristics and progress of scholars is required for career development applications and progress reports. The range of information is substantial, and preparation is onerous. We sought to create a tool to facilitate gathering key data about trainees and mentors who participate in programs like NIH K- and T-awards. METHODS/STUDY POPULATION: Using the REDCap platform, we developed forms and surveys to support intake of applicants, updates from scholars, and information about their participation in activities and use of resources. We deployed application programming interfaces (APIs) to automate capture of publicly available data about publications, impact metrics, and federal grant funding. Similar tools capture descriptions of mentor expertise including grant funding, prior trainees, and publications with mentees We also built modules to 1) allow connection to institutional grant and contract data to capture foundation and other funding; 2) pre-populate follow-up surveys to update information about career trajectories with minimal scholar effort; and 3) support mentee-mentor agreements as living documents. RESULTS/ANTICIPATED RESULTS: After a pilot period at our institution, we disseminated Flight Tracker to more than 50 academic institutions, most of whom are CTSA hubs. They track scholars in TL1/T32s, KL2/K12s, MSTP programs, and academic groups. Beyond federal reporting, uses now include publication impact factors (relative citation ratios, Altmetrics scores), grant funding of groups, maps of network relationships among investigators, scholar receipt of internal pilot awards, and statistics about transition to independence and time-to-promotion. Scholars can be separated into smaller cohorts by demographics, training dates, and funding dates. Over 34,000 scholars are tracked nationally among over 260 programs. Having structured data supports program evaluation, continuous improvements, and documents program strengths. DISCUSSION/SIGNIFICANCE: We informally estimate Flight Tracker reduces staff and leadership effort in preparation of program data by 75%, preserving time to focus on service to scholars. Ready access to data over time and within and across institutions creates new opportunities for collaborative data analysis to support evidence-based career development.

OBJECTIVES/SPECIFIC AIMS: To date, only 1 documented case of an individual cured of HIV has been reported. He received an allogeneic bone marrow transplant with cells harboring an HIV-resistant genotype. To mimic this result, we have initiated a Phase I to evaluate the safety of an autologous stem cell gene therapy bone marrow transplant in HIV-related lymphoma patients. METHODS/STUDY POPULATION: The first cohort of patients will receive a 1:1 ratio of unmanipulated CD34 hematopoietic stem cells (HSC) and lentivector modified CD34 HSC expressing a combination of HIV-resistant genes and a selectable marker for cell sorting prior to transplantation. Safety of the HIV-resistant stem cells will be assessed by evaluating engraftment, expression of the anti-HIV genes, and the stability and sequence of the vector. RESULTS/ANTICIPATED RESULTS: One patient has been enrolled and transplanted with the HIV-resistant stem cells. After 1 and 2 months post-transplant, patient blood samples were received, processed for genomic DNA, analyzed by quantitative PCR (qPCR), and displayed successful engraftment of 16 and 12 vector copies per 100 cells, respectively. Expression of all anti-HIV genes was confirmed by qPCR. PCR on genomic DNA confirmed the correct sizes and sequences of the integrated vector and confirmed the successful engraftment of our gene modified cells. Currently, we are enrolling more patients into the trial. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, this therapy has the potential to change HIV treatment.

OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.

OBJECTIVES/GOALS: Academic research centers often struggle to recruit and retain a diverse and competent clinical and translational science (CTS) workforce. Specifically, the clinical research professional (CRP) career pathway is not well known to undergraduate students and other individuals outside of academic medicine despite various potential career routes. METHODS/STUDY POPULATION: To address these workforce challenges, the CRP Task Force at the University of Cincinnati (UC) aims to train a competent and diverse CRP workforce through targeted educational programming in the UC undergraduate population. Using a six-step curriculum development process that included: 1) performing a needs assessment, 2) determining content, 3) writing goals and objectives, 4) selecting the educational strategies, 5) implementing the curriculum, and 6) evaluating the curriculum, we designed an undergraduate certificate program in CTS. RESULTS/ANTICIPATED RESULTS: The needs assessment included both internal and external data gathering to inform curriculum development and program decisions. Content was determined using the CRP Competency Framework 2.0, and program learning outcomes were written with both the competency framework and local workforce needs in mind. Educational strategies were selected based upon optimization of available resources and local expertise with an emphasis on interactive didactics complemented by experiential learning. Implementation is underway and evaluation will follow once students begin enrolling. DISCUSSION/SIGNIFICANCE: We anticipate an increase in numbers of well-qualified, diverse applicants who pursue CRP careers locally and regionally. In addition, we expect that the certificate program will build competency earlier in CRP staff, improving job satisfaction and retention as a result of a stronger foundation from which to build their professional skills.

OBJECTIVES/SPECIFIC AIMS: Lead (Pb) exposure can seriously affect nervous system and kidney. Young children are vulnerable to Pb exposure. However, the role of low-level Pb exposure in asthma in children and the age and racial disparity is not well studied. The objectives are to examine the relation between Pb level and asthma status and to determine the age and racial/ethnic differences in this relation. METHODS/STUDY POPULATION: We analyzed data from National Health and Nutrition Examination Survey 1999-2016 for 22,885 children 1-15 years old. Asthma information was collected by questionnaire. Blood lead level was measured using mass spectrometry. The association between blood Pb level and asthma status was assessed by logistic regression after adjusting for children’ age, gender, race/ethnicity, insurance status, and source of care; household poverty, mother’s age and smoking status. Data were analyzed using Stata 14 considering design and sample weight and p<0.05 is statistically significant. RESULTS/ANTICIPATED RESULTS: Pb level was associated with asthma status (Adjusted Odds Ratio (AOR)=1.4, 95% Confidence Interval (CI) = 1.2-1.7, p < 0.001). Stratified analysis by age showed that blood Pb level is related to asthma only in children 1-5 years old (AOR = 1.3, 95% CI = 1.1-1.5, p = 0.004). There was no racial/ethnic difference in this association. DISCUSSION/SIGNIFICANCE OF IMPACT: Pb level is associated with asthma status in children especially young children. Health risk of low Pb is a concern. Preventive measures by reducing potential sources of Pb should be introduced early.

OBJECTIVES/GOALS: Young and middle-aged adults with a myocardial infarction (MI) represent an understudied group potentially with unique risk indicators such as emotional stress. We sought to investigate if mental stress-induced myocardial ischemia (MSIMI), a marker of cardiovascular vulnerability to psychological stress, is associated with poor outcomes among this population. METHODS/STUDY POPULATION: We studied 306 patients (150 women and 156 men) ≤61 years of age who were hospitalized for MI in the previous 8 months. Clinical, behavioral and psychosocial factors were assessed with standardized measures. Patients underwent myocardial perfusion imaging with mental stress (public speaking) and conventional stress (exercise or pharmacological testing). MSIMI and conventional stress-induced ischemia were defined as a new or worsening perfusion defect. Patients were followed for 3 years for adverse events, which were independently adjudicated. Cox proportional hazard models were used to estimate the association of MSIMI and CSIMI with a composite endpoint of recurrent MI or cardiovascular (CV) death with adjustment for demographic, clinical and psychosocial risk factors. RESULTS/ANTICIPATED RESULTS: The mean age of the sample was 50 years (range, 22-61). MSIMI occurred in 16% of the patients, and conventional ischemia in 35%. Over a 3-year follow-up, 28 individuals had a recurrent MI and 2 died due to cardiovascular causes. The incidence of the composite endpoint of MI or CV death was more than doubled in patients with MSIMI (20%) than those without MSIMI (8%), HR 2.6, 95%CI, 1.2-5.6. Further adjustment for demographic and clinical risk factors and depressive symptoms did not substantially change the relationship. In contrast, conventional stress ischemia was not significantly related to the outcome (HR 1.4, 95%CI, 0.6-3.0). DISCUSSION/SIGNIFICANCE OF IMPACT: Young and middle-aged individuals with MSIMI after MI have a >2-fold higher likelihood of recurrent MI and CV mortality compared with those without MSIMI. In this patient group, MSIMI is a better risk indicator than ischemia with a conventional stress. These findings point to psychological stress as an important determinant of risk in this patient population. Ischemia induced by mental stress is a potent risk indicator in young post-MI patients. Stress-reduction interventions may be especially beneficial in patients who show this abnormal response.

OBJECTIVES/GOALS: Murine and clinical data suggest that antibody-dependent cellular cytotoxicity (ADCC) is associated with greater protection against disseminated neonatal HSV disease. To quantify the relative transfer of Abs with different functions and targets, we conducted a prospective study of mother-infant term and preterm dyads pre and during COVID-19 METHODS/STUDY POPULATION: Total and HSV lysate, glycoprotein D (gD) and glycoprotein B (gB)-specific IgG, IgG1 and IgG3 as well as HSV neutralizing Abs (nAbs) and ADCC were quantified in paired 3rd-trimester pregnant women and their newborns (cord) blood. Transfer ratios (TR) were defined as cord:maternal Ab levels. IgG1 and IgG3 subclass and gD or gB-specific Abs were isolated by column purification and glycan profiles were assessed by mass spectrometry. The study population included 21 term and 15 preterm dyads who were HSV-1 (+/- HSV-2) seropositive enrolled between 2018-2019 (pre-COVID) and 25 additional HSV-1 (+/- HSV-2) seropositive term dyads whose mothers were SARS-CoV-2 PCR and COVID Ab+ at delivery; 14 were asymptomatic and 11 had mild-moderate COVID disease. None of the mothers had active genital HSV lesions during delivery RESULTS/ANTICIPATED RESULTS: Anti-HSV IgG, IgG1 and IgG3 TR were higher in term vs. preterm dyads (p<0.05). The nAb TR was 2.4 in term vs. 0.8 in preterm (p<0.001) but the ADCC TR was < 1.0 for both. To determine if the latter reflected antigenic target, subclass or glycans, we enriched for gD and gB specific and IgG1 and IgG3 Abs. The gD Abs were IgG1 and had only neutralizing activity. In contrast, gB Abs were polyfunctional and included IgG1 and IgG3 but only the IgG1 Abs had ADCC activity. The gD Abs were enriched for glycans associated with an affinity for the neonatal Fc receptor (FcRn); gB Abs expressed glycans associated with both FcRn and FcγRIIIa binding. There was no significant difference in total HSV-specific IgG TR in pre-COVID vs post-COVID dyads but the nAb TR was lower (p=0.018) and ADCC TR higher (p<0.001) in the COVID compared to pre-COVID cohort DISCUSSION/SIGNIFICANCE: HSV ADCC Abs, which may provide greater protection than nAbs against neonatal disease, transfer poorly particularly to preterm newborns. However, in the setting of SARS-CoV-2, the TR of HSV ADCC is significantly higher. This may reflect alterations in the placental architecture and/or glycan composition which is currently being investigated.

OBJECTIVES/SPECIFIC AIMS: Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and multiple visceral organs. Effective therapies for SSc are needed. Lysyl oxidase (LOX) is a copper-dependent amide oxidase that plays a critical role in the crosslinking of the extracellular matrix (ECM). In this study, we investigated the role of LOX in the pathophysiology of SSc. METHODS/STUDY POPULATION: LOX expression and protein levels were measured in lung tissues and primary fibroblasts from patients with SSc and healthy controls. The effects of recombinant LOX (rLOX) were measured in vitro in primary fibroblasts, ex vivo in human lung tissues and in vivo in mice given bleomycin in combination with rLOX. LOX levels and activity were evaluated in lung fibroblasts treated with an endostatin-derived peptide that ameliorates fibrosis and in mice treated with bleomycin in combination with the peptide. Further, to differentiate the crosslinking activity of LOX from other potential effects, primary human fibroblasts were cultured with rLOX in the presence of the inhibitor, beta-aminopropionitrile. The expression levels of ECM (collagen and fibronectin), pro-fibrotic factors (IL-6 and TGF-beta), and transcription factor (c-Fos) were examined by real-time PCR, ELISA, immunoblotting, or hydroxyproline assay. RESULTS/ANTICIPATED RESULTS: LOX mRNA was increased in lung tissues and matching fibroblasts of SSc patients. rLOX-induced ECM production in vitro and ex vivo in lung fibroblasts and in human lung tissues maintained in organ culture, respectively. Additionally, TGF-beta and bleomycin induced ECM production, LOX mRNA expression and activity. Endostatin peptide abrogated these effects. In vivo, rLOX synergistically exacerbated pulmonary fibrosis in bleomycin-treated mice. The inhibition of LOX catalytic activity by beta-aminopropionitrile failed to abrogate LOX-induced ECM production. LOX increased the production of IL-6. IL-6 neutralization blocked the effects of LOX. Further, LOX induced c-Fos expression and its nuclear localization. DISCUSSION/SIGNIFICANCE OF IMPACT: LOX expression and activity were increased with fibrosis in vitro, ex vivo, and in vivo. LOX induced fibrosis via increasing ECM, IL-6 and c-Fos translocation to the nucleus. These effects were independent of the crosslinking activity of LOX and mediated by IL-6. Our findings suggest that inhibition of LOX may be a viable option for the treatment of lung fibrosis. Further, the use of human lung in organ culture establishes the relevance of our findings to human disease.

OBJECTIVES/GOALS: To describe how the UCLA Clinical and Translational Science Institute (CTSI) assembled and deployed a science team in support of a local jurisdictions effort to manage and control COVID-19 outbreaks in one of the nations largest metropolitan regions, Los Angeles County (LAC). METHODS/STUDY POPULATION: During the COVID-19 pandemic (2020-21), building an efficient data infrastructure to support outbreak management became a priority for the local health department. In response, the UCLA CTSI assembled a science team with expertise across the translational continuum: epidemiology, laboratory and microbiology, machine learning, health policy, medicine and clinical care, and community engagement. The team partnered with a new LAC Data Science Team to foster a collaborative learning environment for scientists and public health personnel, employing improvement and implementation science to help mitigate COVID-19 outbreaks in sectors including healthcare, skilled nursing facilities, and K-12 education. The goal was a public health workforce that is prepared to problem-solve complex, evolving outbreaks. RESULTS/ANTICIPATED RESULTS: The science team created a learning environment with data modeling and visualization, problem-based learning, and active knowledge and skills acquisition. First, control charts and time series methods were used to visualize COVID-19 data and find signals for action. Second, a series of 16 Grand Rounds offered interactive sessions on problem-solving of outbreak challenges in different sectors. Third, a biweekly Public Health Digest provided fieldworkers with the latest scientific studies on COVID-19. All three elements guided and empowered the workforce to implement timelier, efficient outbreak mitigation strategies in the field. The partnered team also identified barriers to adoption of selected new data and management techniques, revealing areas for further skill-building and data-driven leadership. DISCUSSION/SIGNIFICANCE: The UCLA CTSI science team offered a backbone science infrastructure for helping public health and other sector agencies manage COVID-19 outbreaks and mitigation. It showed promise in bringing and translating science into public health practice. It revealed future priorities for CTSI innovation and scientific support of public agencies.

OBJECTIVES/SPECIFIC AIMS: The current study examined hangover following IV alcohol self-administration (IV-ASA) using the Computer-Assisted Infusion System. The goal of the study was to identify predictors of hangover, including drinking history, alcohol sensitivity, family history, expectancies, and sex differences in nondependent drinkers. METHODS/STUDY POPULATION: The study sample included 89 healthy, nondependent drinkers aged 21–45 years. After a screening to exclude any medical illness or psychiatric disorders, participants completed an IV-ASA session. Each session consisted of a 25-minute priming phase, during which participants were prompted to press a button to receive individually standardized alcohol infusions, followed by a 2-hour “open bar” phase, during which they were instructed to recreate a typical drinking experience. Results from the IV-ASA included peak and average BrAC. Drinking patterns were assessed using the Alcohol Use Disorders Identification Test, which provided 3 subscales: consumption (AUDIT-C), dependence (AUDIT-D), and harmful drinking (AUDIT-H). Subjective response to alcohol was measured using the Drug Effects Questionnaire (DEQ). The Alcohol Hangover Scale (AHS) was used to assess hangover for the period between participants’ departure from the study unit and 10 am the next morning. The Alcohol Effects Questionnaire (AEFQ) is a measure which includes 40 true/false statements about how alcohol typically makes respondents feel, and was used to measure alcohol expectancies. RESULTS/ANTICIPATED RESULTS: Results showed that 78% of participants endorsed having at least 1 hangover symptom following IV-ASA. The most commonly reported items were tired, thirsty, headache, and hangover. There was no association between hangover scores and the AUDIT-C or IV-ASA. Because alcohol consumption was not related to hangover symptoms, risky drinking behavior was examined. Results indicated that participants endorsing 4 or more items on the AUDIT-D plus AUDIT-H subscales showed significantly higher average hangover scores. Linear regression analyses indicated that alcohol hangover scores were associated with DEQ items feel, high, and intoxicated. Ongoing analyses are examining additional predictors of hangover including family history, alcohol expectancies, sex differences, and other alcohol sensitivity measures. DISCUSSION/SIGNIFICANCE OF IMPACT: The results indicated that risky drinking patterns and alcohol response measures were positively associated with hangover symptoms in non-dependent drinks, while no correlation between consumption and hangover symptoms were found. Since previous research has shown than greater subjective response is associated with heavy drinking and predictive of alcohol use disorder, it is possible that hangover symptoms is a marker of this relationship. Since the role of hangover in the transition from heavy drinking to disorder still remains unclear, it will be important to characterize this relationship between alcohol sensitivity and hangover as a function of drinking patterns. This understanding may help to prevent this transition from at-risk drinking to alcohol dependent drinking.

OBJECTIVES/GOALS: Writing self-efficacy & self-regulation are tied to publication & grant submission” writers high in these traits are more productive. We investigated if participating in Shut Up & Write! would produce statistically significant gains in self-efficacy & self-regulation when comparing pre/post surveys. METHODS/STUDY POPULATION: 47 US med students, TL1/KL2, & early-career faculty expressed interest in participating. We conducted a 12-week, 1 hr/week Shut Up & Write!-style (SUAW) activity, held on Zoom, and measured the effect using a pre-post survey adapted from the Writer Self-Perception Scale. Matched pairs t-tests (I2=0.05) to test for significant differences between pre- and post-test means were conducted on 3 subscales. The 3 subscales reflected writing attitudes (self-efficacy), writing strategies (self-regulation), and avoiding writing distractions (self-regulation). Subscales showed acceptable internal consistency with Cronbach’s alphas of 0.80, 0.71, and 0.72. RESULTS/ANTICIPATED RESULTS: 24/37 (65%) completed pre-post surveys. 81% presented as female. 60% were NIH-defined URB and/or were from MSIs. 60% previously participated in an activity similar to SUAW. Sum scale statistics for those who previously participated were significant for the self-efficacy subscale (p=0.020) and writing strategies subscale (p=0.041). Sum scale statistics for those who had not previously participated were significant for the writing strategies subscale (p=0.002). We saw no difference in the avoiding writing distractions subscale. 80% were very satisfied/satisfied with SUAW (I really loved these sessions” they helped me to identify a writing goal that could actually be accomplished in an hour.) DISCUSSION/SIGNIFICANCE: We found significant differences in self-efficacy & self-regulation, building upon findings from a 2021 pilot, and providing evidence that regular participation in an activity like SUAW produces increased self-efficacy and self-regulation and may increase manuscript and grant-writing productivity

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.

OBJECTIVES/GOALS: 1. Standardize pathways, training and evaluations 2. Expose apprentices to a variety of research experiences 3. Remove barriers to hiring early talent 4. Expand opportunities for underrepresented minority applicants to obtain clinical research professional positions METHODS/STUDY POPULATION: Collaborators connected by the Clinical Research Professional Taskforce ACTS SIG conducted a landscape analysis survey to identify aspects of CRP Apprentice models and formed a Subgroup. Members will share plans for multiple apprenticeship programs, including specific training modalities and skill sets used to prepare apprentices for a successful clinical research professional career. Methods across institutions include: • Increasing awareness of the profession • Facilitating talent identification for managers • Making the business case for funding and staffing • Implementing work-based learning for fundamental competency development Survey results from CRP institutions demonstrated apprenticeships are value added to teaching how to conduct research. RESULTS/ANTICIPATED RESULTS: The landscape survey of Apprentice programs revealed multiple models in use. The newly formed Apprentice subgroup is engaging in analysis and actively working to build a standardized repository of competency-aligned, research courses and experiences for apprentices. Results will help make the business case for starting or growing programs. Subgroup members have focused on a shared goal of expanding opportunities for underrepresented minority applicants, with current outreach efforts that are extending awareness of the CRP profession. We anticipate a continuous strengthening of connections between institutions to share a variety of models to implement, develop shared tools (e.g., proficiency tests), and share existing tools to standardize pathways and training for CRP apprenticeships. #_msoanchor_1 DISCUSSION/SIGNIFICANCE: Academic Medical Centers (AMCs) need novel strategies to support clinical research portfolios.Innovative Apprenticeship Models improve efficiency and sustainability of the clinical research professional (CRP) workforce to train the next generation of CRPs in an effective and timely way.