Objectives/Goals: Men and women with opioid use disorder (OUD) show differences in their initiation, use patterns, and outcomes that may have biological underpinnings. Here we present data directly comparing adult male and female rats across heroin-induced behaviors in order to provide insight into the nuances of sex differences in OUD. Methods/Study Population: We first used a 6-hour intermittent access heroin self administration paradigm to quantify six distinct drug-taking and drug-seeking behaviors. Based on the sum of the z-scores for each behavior, we classified rats as having high- or low-severity phenotypes. In a separate group of rats, we adapted this classification system to a 10-minute continuous access self-administration paradigm to better represent the timeframe of use common in people. Finally, we examined locomotor sensitization following daily heroin injections in two groups of rats. The first were given 2 mg/kg/day i.p. heroin for 10 days and the second were given 0.55 mg/kg/day i.v. heroin for 20 days. Results/Anticipated Results: In the 6-hour intermittent access, both sexes showed variability across individuals, but a greater proportion of females were classified as having a high-severity phenotype compared to males. This difference in severity distributions was also found in the 1-hour continuous access experiment. Consistent with the literature, in our sensitization experiments, we found that males had a lower baseline level of locomotion compared to females. Across sex and route of administration, rats treated with heroin initially decreased locomotion, but returned to baseline over the course of treatment. Females given i.v. infusions showed a rapid escalation of locomotion past baseline that was not seen in males or following i.p. injections. Discussion/Significance of Impact: Our results indicate a consistent pattern of females having a greater behavioral response to heroin compared to males. This suggests a sex-based effect on OUD that may interact with gender-based influences. As such, future research needs to consider sex in the development of treatments for OUD and other substance use disorders.

OBJECTIVES/GOALS: Using a community-based participatory research (CBPR) approach, the All of Us (AoU) Wisconsin Froedtert & the Medical College of Wisconsin (MCW) site aimed to improve public understanding of science by creating a Special Interest Group (SIG) of community members and scientists and driving healthcare research relevant to Southeastern Wisconsin. METHODS/STUDY POPULATION: We recruited community members from the AoU advisory boards and scientists from Froedtert & MCW. These SIG participants will converge on a hypothesis that aligns with community priorities and conduct research using the national AoU database, which combines EHR, survey, and whole genome sequencing data. A year of monthly SIG meetings from 2022-2023 will serve as focus group sessions that will be recorded and transcribed. In addition to descriptive statistics on participant demographics and affiliations, we plan to qualitatively characterize transcripts, field notes, and feedback, such as participation satisfaction or reflection on self- and group-driven impact. We will publish alongside all SIG members on both the research outcomes and the SIG-driven process to inform future similar endeavors. RESULTS/ANTICIPATED RESULTS: To date, we held three SIG meetings, which together formed the discover and define stages in the human-centered design framework. We narrowed down SIG membership to 15 consistent participants. Our coalition building conversations emphasized group priorities and future payoffs for independent research and community partnerships. Realizing a crucial need for bioinformaticians to prosecute SIG-driven research questions, we created a data subgroup of trainees and scientists to familiarize themselves with the AoU Researcher Workbench. Through shared decision making during this community engaged process, we are converging on a research direction centering on specific diseases or adverse outcomes with relevance to Southeastern Wisconsin communities and with implications for personalized medicine. DISCUSSION/SIGNIFICANCE: SIG scientists will learn about CBPR and access the AoU database. SIG community members will better understand the research process and share their lessons with local communities. The AoU Wisconsin research team will disseminate findings on the collective research process and empower scientist use of this nationally curated AoU database.

ABSTRACT IMPACT: We compare the cost-effectiveness of treatments for early prostate cancer, and propose how to maximize the value of care within an increasingly cost-constrained healthcare climate. OBJECTIVES/GOALS: Each year 192,000 men in the United States are diagnosed with prostate cancer. With various treatment options available, there is a growing role for cost-effectiveness analyses which may help maximize the value of care to the patient. In this review we compare the cost-effectiveness of primary treatments for clinically localized prostate cancer. METHODS/STUDY POPULATION: In this systematic review we aim to compare the cost-effectiveness or cost-utility of primary treatment strategies for clinically localized prostate cancer. This review, which adheres to 2009 PRISMA guidelines, included studies of men with clinically localized prostate cancer comparing at least two treatment strategies using the incremental cost-effectiveness ratio (ICER). We included analyses only of the United States healthcare system with at least 10 years of follow-up. These studies were published from 2006 to 2019 and generally included men with low or low to intermediate risk prostate cancer. Most studies reported outcomes for men age 65-70. All studies were prospective simulated trials and used a Markov model to simulate patient outcomes. RESULTS/ANTICIPATED RESULTS: Ten articles were included in the analysis. All studies used a Markov model to simulate a randomized trial. Six studies primarily compared radiation modalities, and four compared observation with immediate treatment. There was substantial heterogeneity in treatment protocols and the patients being simulated. Sensitivity analyses showed these models to be influenced by utility values and length of follow-up. A meta-analysis was not possible as no studies reported the variance of the primary outcome. Heterogeneity in study design limited comparisons of treatments across studies. However, these models were sensitive to patient-specific clinical factors, including life expectancy and the utility during and after each treatment. DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies indicate collectively that the cost-effectiveness of prostate cancer treatment for similarly staged men may be heavily impacted by comorbidities and personal preferences. As the US moves towards value-based care, patient preferences may continue to drive the preferred treatment for newly diagnosed prostate cancer.

OBJECTIVES/GOALS: T develop a novel PROTAC to deplete BRK to inhibit tumorigenesis and metastasis, which is unattainable by using tradition kinase inhibitors. METHODS/STUDY POPULATION: We will design, synthesize, and evaluate BRK-specific PROTACs to study both catalytic and scaffolding properties of BRK that contribute to cancer progression. Optimal PRTOAC concentrations will be used to treat MDA-MB-231 cells to determine effects on cell proliferation, cell migration, invasion, metastatic potential, and colony formation. Immunoblotting will be used to determine target protein degradation and to evaluate if PROTAC mediated degradation of BRK allows SMAD4 to form complex with SMAD2 and SMAD3. Finally, a metastatic xenograft mouse model (MDA-MD-231) will be injected subcutaneously or via tail vein into NU/J 002019 mice8, 17 and treated with the BRK PROTAC to evaluate inhibition of tumorigenesis and metastasis. RESULTS/ANTICIPATED RESULTS: We expect that the PROTAC will specifically degrade BRK and restore the anti-tumorigenic and anti-metastatic function of SMAD4 in metastatic breast cancer. In turn, we anticipate that cell proliferation, invasion, and colony formation properties of metastatic breast cancer will be restricted and SMAD4 will form complex with SMAD2 and SMAD3. Additionally, mice treated the BRK targeted PROTAC should experience reduced tumor growth and metastasis compared to placebo. DISCUSSION/SIGNIFICANCE: This substantially new approach will inhibit oncogenic nRTKs to restore the antitumor function of TGFβ/SMAD signaling is expected to bring metastatic cancer under therapeutic control. Thus, the expected outcomes are likely to have a significant impact because it will provide a new targeted therapy to improve metastatic TNBC patient survival.

OBJECTIVES/GOALS: Lupus lesional skin has elevated interferon expression, is highly colonized with Staphylococcus aureus (50%) and has no FDA-approved treatment options. We decided to investigate the effect of topical antibiotics on lupus lesional skin to determine whether it affects inflammatory gene expression. METHODS/STUDY POPULATION: Adult Systemic Lupus Erythematosus (SLE) patients with skin inflammation were recruited for this study from the Michigan Lupus cohort. All patients gave informed consent approved by the University of Michigan IRB. Lesions were swabbed for S. aureus colonization and then skin biopsies were collected from the affected area. Patients were then randomized for either mupirocin treatment or VaselineTM as the control. Product was applied to the lesion thrice daily for 7 days and swab samples and biopsies were collected again. Biopsies were saved at −80 °C. RNA was isolated from the biopsies, checked for quality and RNA-sequencing was performed to determine transcriptomic changes. RESULTS/ANTICIPATED RESULTS: Our preliminary results indicate that a higher number of genes are differentially expressed (DEGs) following treatment with mupirocin (184) than VaselineTM (133). Interestingly the DEGs from the two treatments were almost completely independent with only a few that were DE in both treatments when the data were fitted to a scatter plot. Functional enrichment analysis of the data showed significant downregulation of cytokine and chemokine pathways in the mupirocin but not the VaselineTM treatment group. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary data suggests that inflammatory signaling can be reduced in lesional skin by reducing bacterial load by topical antibiotic treatment in lupus patients. This can be particularly helpful in patients who are recalcitrant to typical treatment protocols for skin inflammation. CONFLICT OF INTEREST DESCRIPTION: J.M.K. received research funding from Celgene and serves on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Eli Lilly and J.E.G. received research funding from AbbVie, SunPharma, Celgene, and Genentech and serves on advisory boards for Novartis, AbbVie, and MiRagen. The other authors have no financial conflicts of interest.

Objectives/Goals: Metallothioneins (MT) are cysteine-rich proteins that bind metals and regulate oxidative stress. MT2A, the most expressed MT gene, is lost in ~70% of High Grade Serous Ovarian Cancer cases. We hypothesize that MT2A loss disrupts mitochondrial function and metabolism, promoting tumor progression. Methods/Study Population: To explore this, MT2A was knocked down (KD) in CAOV3 HGSOC cells via lentiviral shRNA. KD was confirmed transcriptionally via RT-qPCR and functionally using a nuclei-counting assay, which assesses sensitivity to cadmium chloride (CdCl₂), a cytotoxic heavy metal. Mitochondrial membrane potential (MMP) was assessed via flow cytometry, and oxygen consumption rate (OCR) was measured with Resipher. Clonogenic potential was evaluated by soft-agar colony formation assays. Results/Anticipated Results: MT2A KD cells showed a significant decrease in nuclei count in response to CdCl₂. MMP was reduced in MT2A KD cells, indicating compromised mitochondrial integrity. OCR was significantly decreased in MT2A KD cells, suggesting impaired oxidative phosphorylation. These phenotypes are characteristic features of the Warburg effect, which is a hallmark of aggressive cancers. Soft agar assays revealed that MT2A loss significantly enhanced the cell’s ability to multiply adhesion free from a single cell, a phenotype associated with aggressive oncogenic transformation. Discussion/Significance of Impact: In summary, MT2A loss disrupts mitochondrial dynamics and oxidative metabolism while promoting tumor aggressiveness. These findings support our hypothesis that MT2A plays a key role in regulating mitochondrial homeostasis and may influence metabolic adaptation in HGSOC.

OBJECTIVES/GOALS: Face transplant can offer functional and aesthetic restoration to patients who have exhausted reconstructive options. Ethical issues in face transplant still abound, including that of patient selection. The goal of this study was to assess ethicists’ viewpoints on face transplant. METHODS/STUDY POPULATION: A large-scale online survey of attendees of the International Conference on Clinical Ethics Consultation (N = 401) was performed to assess ethicists’ opinions on issues in face transplant. Questions were asked regarding the risk-benefit ratio of immunosuppression, permissibility of face transplant for more recipient subpopulations (including children and blind patients), donor-recipient age, gender, and ethnicity mismatches, and ethics committee make-up. RESULTS/ANTICIPATED RESULTS: Among 84 respondents, 84% agreed it is permissible to perform a face transplant on an adult with no medical contraindications. The majority of respondents agreed that it is permissible to perform a face transplant on a child or blind recipient. An issue of continued concern was risk of immunosuppression. Respondents had a high threshold of permissibility for ethnic mismatches between donor and recipient, and 43% reported it is permissible to have a gender mismatch. A 10 year age difference between donor and recipient was the most commonly accepted. Questions regarding the ideal composition of a face transplant ethics committee demonstrated consensus on the roles that should be represented. DISCUSSION/SIGNIFICANCE OF IMPACT: This study provides insight into ethicists’ viewpoints on face transplant, which demonstrates a high level of permissibility towards the procedure. This may be due to the early success of face transplants and the shifting ethical issues in the field to practical aspects of the procedure. This research also provides guidance to programs regarding questions of donor and recipient selection, ethics committee composition, and offers insight into strengthening the ethical framework of the field.

OBJECTIVES/GOALS: The CDC estimates that Influenza infections account for an average of 420,000 hospitalizations and 34,700 deaths in the U.S. each year. This project explores the underlying mechanisms of the infectious process of Influenza A in human lung organoids by examining the differential transcriptomic expression compared to uninfected controls. METHODS/STUDY POPULATION: Lung organoids were cultured from differentiated human bronchial epithelial cells from lung transplant donors on an air-liquid interface until they were confirmed to contain both mucous producing and ciliated cells. Lung organoids are ideal models in translational science due to their structural and functional characteristics which closely mimic those of in vivo human epithelial tissue. Half the organoids were exposed to Influenza A pH1N1 for 72h; the other half served as uninfected controls. RNA was isolated from both groups and sequenced using the Oxford Nanopore MinION which generates full length reads. Reads were aligned to the human reference genome (GRCh38.p14) using Minimap2. RESULTS/ANTICIPATED RESULTS: The MinION sequenced an average of 3.24m reads per sample and a total of 13,128 genes were relevantly expressed (defined as greater than 1 read per million in at least half the samples). ANOVA with a 5% false discovery rate (Benjamini and Hochberg correction) revealed 5,417 differentially expressed genes between infected and control groups. Within this subset, we identified downregulation of mucociliary clearance, mitochondrial and ß-oxidation, peroxisome, and glutathione replenishment genes. We further identified upregulation in inflammatory markers, lactate dehydrogenase enzymes, and several s100 proteins. The downregulation of mitochondrial and β-oxidation markers and the upregulation of lactate dehydrogenase enzymes revealed a Warburg-like phenotype which has not previously been reported. DISCUSSION/SIGNIFICANCE: This study reveals a novel Warburg-like phenotype in Influenza A infection alongside downregulated mucociliary clearance and upregulated inflammatory processes. These findings improve our understanding of Influenza A infection and point to potential therapeutic targets to advance precision medicine approaches to treatment.

Objectives/Goals: Develop a precision hydrogel-organoid model to determine how extracellular matrix (ECM) biomechanics drive the malignant transformation of oral epithelial dysplasia (OED) to oral squamous cell carcinoma (OSCC) and identify mechanoresponsive pathways. Methods/Study Population: Patient-derived oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) organoids will be encapsulated in an interpenetrating network hydrogel engineered with tunable stiffness and viscosity to mimic healthy, dysplastic, and cancerous tissue. Organoid growth, morphology, and expression of mechanosensitive markers will be analyzed by imaging and immunostaining. Single-cell RNA sequencing will identify mechanoresponsive markers across genetically diverse patient lines. Targeted inhibitors of EGFR, YAP, and p53 pathways will text whether blocking these signals can prevent mechanics-driven malignant transformation. Results/Anticipated Results: We anticipate that OED organoids in stiffer matrices similar to OSCC tumor stroma will exhibit increased proliferation, altered morphology, and activation of tumorigenic markers similar to OSCC. scRNA-seq is expected to reveal conserved and patient-specific mechanosensitive pathways. Targeted inhibition of these pathways should mitigate mechanics-driven malignant transformation. These outcomes will define molecular mechanisms linking ECM biomechanics to tumor progression and reveal new therapeutic opportunities for early intervention. Discussion/Significance of Impact: This hydrogel-organoid model links patient-specific genetics and ECM biomechanics to tumor progression, enabling controlled studies of how mechanical cues drive malignancy and therapeutic response in a clinically relevant, precision medicine context.

OBJECTIVES/GOALS: Patients with multiple myeloma (MM) experience significant disease- and treatment-related symptom burden, especially with higher lines of therapy (LOT). We used a remote symptom monitoring app to characterize overall symptom profile, symptom bother, and quality of life (QOL) among patients with MM across LOT and longitudinally. METHODS/STUDY POPULATION: We used Carevive PROmpt, a symptom monitoring app for cancer patients. From 11/10/22 to 9/27/23, we enrolled 84 adult patients with MM of any stage and anywhere in the treatment continuum from Duke Health MM clinics. Participants received weekly symptom surveys while on active treatment. Per prior studies, we defined heavily pretreated patients as those on current LOT ≥4. Our sample had a mean (SD) age of 63.7 (10.8) years and was 56.0% male; 73.8% had a prior bone marrow transplant, 40.5% were on LOT ≥4 (53.6% on LOT <4, 6.0% missing), 58.3% were on triplet therapy or higher. For 14 symptoms, we described the prevalence of moderate to very severe (MOD-VS) symptoms based on LOT overall and over time. We also described responses to “How bothersome are treatment side effects?” and “Overall QOL over the past week” based on LOT. RESULTS/ANTICIPATED RESULTS: Surveys continued for a mean (SD) of 14.9 (9.6) weeks (range: 44). The top 5 MOD-VS symptoms ever experienced were fatigue (66.7% of patients), neuropathy (48.8%), muscle pain (44.0%), insomnia (39.3%), and general pain (38.1%). Patients on LOT ≥4 had most of these symptoms more often than LOT <4 (fatigue: 70.6% of patients vs. 60.0%, neuropathy: 71.8% vs. 40.0%, muscle pain: 47.1% vs. 42.2%, insomnia: 35.3% vs. 40.0%, general pain: 47.1% vs. 33.3%). For those on LOT ≥4, 42.9% of survey responses endorsed “somewhat”, “quite a bit”, or “very much” symptom bother compared to 32.7% for LOT <4. QOL was similar between groups. Over many months, patients on LOT ≥4 had several persistent symptoms (neuropathy, sadness, insomnia), but even those on LOT <4 had unmet symptom needs (fatigue, general pain, constipation). DISCUSSION/SIGNIFICANCE: Evidence shows that treatment selection at higher LOT in MM often underrates the impact of cumulative symptom burden. Our study reveals significant longitudinal unmet needs regarding symptom and distress management in MM; understanding this can help guide treatment decisions and palliative care for MM patients with escalating treatment demands.

ABSTRACT IMPACT: This research shows that physical intimate partner violence was associated with never testing for HIV while verbal intimate partner violence was associated with increased testing for HIV suggesting that HIV testing interventions should consider intimate partner violence prevention. OBJECTIVES/GOALS: HIV incidence is higher among women who experience intimate partner violence (IPV). However, few studies have assessed the association between HIV testing (regardless of the result) and the experience of IPV. Our objective was to assess the relationship between IPV and HIV testing among women from rural southwestern Uganda. METHODS/STUDY POPULATION: We conducted a whole-population, cross-sectional study including women ?18 years of age who were permanent residents in 8 villages of Rwampara District, southwestern Uganda from 2011-2012 who reported having a primary partner in the past 12 months. We surveyed participants to assess their exposure to 12 different forms of verbal, physical, and/or sexual IPV, and whether they had ever been tested for HIV. We used three separate modified Poisson regression models, clustering by village, to estimate the association between each type of IPV and ever testing for HIV, adjusting for categorical age, completion of more than primary education, and any food insecurity measured by the nine-item Household Food Insecurity Access Scale. RESULTS/ANTICIPATED RESULTS: Among 496 women with a primary partner (>95% response rate), 64 (13%) had never tested for HIV, 297 (60%) reported verbal IPV, 81 (16%) reported physical IPV, and 131 (26%) reported sexual IPV. Further, among these women, 208 (42%) were aged <30 years, 378 (76%) had a primary or no education, and 390 (79%) experienced food insecurity. Never having been tested for HIV was positively associated with physical IPV (adjusted risk ratio (ARR): 1.61, 95% confidence interval (CI): 1.02-2.56) and negatively associated with verbal IPV (ARR: 0.67, 95% CI: 0.44-0.99), but not sexual IPV (ARR: 1.05, 95% CI: 0.51-2.12). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among this population of adult women with partners in Uganda, physical IPV was associated with never testing for HIV while verbal IPV was associated with increased testing for HIV. Evidence suggests that HIV testing interventions should consider IPV prevention, and future studies should focus on why certain IPV types impact HIV testing rates.

OBJECTIVES/SPECIFIC AIMS: To establish an effective team of researchers working towards developing and validating prognostic models employing use of image analyses and other numerical metadata to better understand pediatric undernutrition, and to learn how different approaches can be brought together collaboratively and efficiently. METHODS/STUDY POPULATION: Over the past 18 months we have established a transdisciplinary team spanning three countries and the Schools of Medicine, Engineering, Data Science and Global Health. We first identified two team leaders specifically a pediatric physician scientist (SS) and a data scientist/engineer (DB). The leaders worked together to recruit team members, with the understanding that different ideas are encouraged and will be used collaboratively to tackle the problem of pediatric undernutrition. The final data analytic and interpretative core team consisted of four data science students, two PhD students, an undergraduate biology major, a recent medical graduate, and a PhD research scientist. Additional collaborative members included faculty from Biomedical Engineering, the School of Medicine (Pediatrics and Pathology) along with international Global Health faculty from Pakistan and Zambia. We learned early on that it was important to understand what each of the member’s motivation for contributing to the project was along with aligning that motivation with the overall goals of the team. This made us help prioritize team member tasks and streamline ideas. We also incorporated a mechanism of weekly (monthly/bimonthly for global partners) meetings with informal oral presentations which consisted of each member’s current progress, thoughts and concerns, and next experimental goals. This method enabled team leaders to have a 3600 mechanism of feedback. Overall, we assessed the effectiveness of our team by two mechanisms: 1) ongoing team member feedback, including team leaders, and 2) progress of the research project. RESULTS/ANTICIPATED RESULTS: Our feedback has shown that on initial development of the team there was hesitance in communication due to the background diversity of our various member along with different cultural/social expectations. We used ice-breaking methods such as dedicated time for brief introductions, career directions, and life goals for each team member. We subsequently found that with the exception of one, all other team members noted our working environment professional and conducive to productivity. We also learnt from our method of ongoing constant feedback that at times, due to the complexity of different disciplines, some information was lost due to the difference in educational backgrounds. We have now employed new methods to relay information more effectively, with the use of not just sharing literature but also by explaining the content. The progress of our research project has varied over the past 4-6 months. There was a steep learning curve for almost every member, for example all the data science students had never studied anything related to medicine during their education, including minimal if none exposure to the ethics of medical research. Conversely, team members with medical/biology backgrounds had minimal prior exposure to computational modeling, computer engineering and the verbage of communicating mathematical algorithms. While this may have slowed our progress we learned that by asking questions and engaging every member it was easier to delegate tasks effectively. Once our team reached an overall understanding of each member’s goals there was a steady progress in the project, with new results and new methods of analysis being tested every week. DISCUSSION/SIGNIFICANCE OF IMPACT: We expect that our on-going collaboration will result in the development of new and novel modalities to understand and diagnose pediatric undernutrition, and can be used as a model to tackle several other problems. As with many team science projects, credit and authorship are challenges that we are outlining creative strategies for as suggested by International Committee of Medical Journal Editors (ICMJE) and other literature.

Objectives/Goals: This study aims to uncover immuno-endotypes in sepsis-associated pediatric acute respiratory distress syndrome (SA-PARDS) by using single-cell RNA sequencing (scRNA seq) to analyze the immune cell populations of the lower respiratory tract of intubated pediatric subjects with SA-PARDS. Methods/Study Population: Inclusion criteria are age less than 18 years, admission to the PICU, diagnosis of SA-PARDS, and intubation. Both sepsis and PARDS will be defined using the most recent consensus definitions. Exclusion criteria include an order of limited resuscitation and clinician discretion. After informed consent is obtained, a tracheal aspirate and blood sample will be obtained on days 1, 3, and 7. Both samples will be processed for single-cell RNA seq via the HIVE platform per manufacturer protocol. cDNA libraries will then be sent for 150 base pair paired-end sequencing. Sequences will be aligned to a reference genome, and count matrices will be generated. The Seurat package in R will be used for cell-type annotation and analysis of differential gene expression. Clinical variables, labs, and outcomes will be recorded in REDCap. Results/Anticipated Results: We expect to find that subjects with nonresolving SA-PARDS, defined as intubation and mechanical ventilation, will have a monocyte/macrophage transcriptome characterized by continued hyper-inflammation (M1-like phenotype) that does not transition over time to an anti-inflammatory and pro-repair phenotype (M2-like). Additionally, we expect to see that subjects with non-resolving SA-PARDS will have evidence of continued inflammation driven by hyper-inflammatory neutrophils. Finally, we expect that subjects with non-resolving SA-PARDS will have epithelial cells characterized by continued upregulation of canonical pathways of innate immunity including interferon signaling and the damage associated molecular pattern recognition pathway. Discussion/Significance of Impact: The discovery of immuno-endotypes in SA-PARDS would represent a major step toward developing precision medicine therapies for this group of patients. It would simultaneously provide a strategy to reduce biological heterogeneity and identify novel pathways and targets for therapy.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Implementation assessment plans are crucial for clinical trials to achieve their full potential. Without a proactive plan to implement trial results, it can take decades for one-fifth of effective interventions to be adopted into routine care settings. The Veterans Health Administration Office of Research and Development is undergoing a systematic transformation to embed implementation planning in research protocols through the Cooperative Studies Program, its flagship clinical research program. This manuscript has two objectives: 1) to introduce an Implementation Planning Assessment (IPA) Tool that any clinical trialist may use to facilitate post-trial implementation of interventions found to be effective and 2) to provide a case study demonstrating the IPA Tool’s use. The IPA Tool encourages study designers to initially consider rigorous data collection to maximize acceptability of the intervention by end-users. It also helps identify and prepare potential interested parties at local and national leadership levels to ensure, upon trial completion, interventions can be integrated into programs, technologies, and policies in a sustainable way. The IPA Tool can alleviate some of the overwhelming nature of implementation science by providing a practical guide based on implementation science principles for researchers desiring to scale up and spread effective, clinical trial-tested interventions to benefit patients.

Rural and low-socioeconomic status women face social determinants of health barriers leading to disproportionately low rates of breast cancer screening and markedly reduced participation in clinical trials. To address this gap, we developed the WeCARE (Women’s Engagement for Cancer Awareness, Resources, and Education) intervention using a community-engaged approach. This paper describes how Community Advisory Board feedback informed the development of Mayo Clinic Health System’s WeCARE intervention components. Their input was systematically analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0) to identify determinants of acceptability, appropriateness, and feasibility and to guide actionable refinements to intervention content and delivery.

OBJECTIVES/GOALS:

• To describe trends in fall risk screening and referrals to community-based programs among physical therapy professionals.

• To compare fall risk screening practices to clinical practice guidelines among

• To identify gaps in fall risk screening and referrals to community-based programs among physical therapy professionals.

METHODS/STUDY POPULATION: A panel of experts between the American Physical Therapy Association (APTA) - Geriatrics, and the National Council on Aging (NCOA) developed a web-based survey to identify practices among physical therapy professionals (PTs) for fall risk screenings and community-based referrals for older adults. The web-based survey was disseminated to PTs via email, e-blasts, and social media. The survey focused on questions related to knowledge of fall risk screening tools, fall risk management for older adults, and knowledge of and referrals to community-based interventions. RESULTS/ANTICIPATED RESULTS: To date, 453 PTs representing 50 states completed the survey. The majority of PTs (50.9%) had over 20 years of experience in various settings. Eighty-three percent regularly screen older adults for fall risk. Approximately 40% conduct community-based screenings. The majority (81.3%) were somewhat to very familiar with the CDC-recommended STEADI (Stopping Elderly Accidents, Deaths, and Injuries) screening toolkit. Despite familiarity, only 32% responded to the question if they used STEADI for screening. Of those, 83.4% used the tool. The majority (73.4%) of PTs were aware that NCOA recommends evidence-based programs to address health needs of aging adults and 59.6% refer. PTs did not refer due to lack of knowledge that programs existed (21.3%) or lack of knowledge of availability (33.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: Although PTs are have some familiarity with the STEADI for fall risk screening, the tool is not common in practice. PTs are lacking awareness of local evidence-based community programs to address health needs of aging adults. Educational efforts should target these knowledge gaps and provide additional resources to improve referrals.