OBJECTIVES/SPECIFIC AIMS: The aims of this project are to: (1) examine placebo effects on subjective and objective outcome measures, (2) determine if an increase in the placebo is associated with changes in benefit, (3) evaluate if the trauma related insomnia placebo group in our study has different side effect reports compared with insomnia placebo participants in previous suvorexant trials, and (4) (Exploratory) examine associations between the placebo group’s characteristics (e.g., trauma/PTSD severity, demographics) and placebo effects. METHODS/STUDY POPULATION: The parent study is a randomized double-blind placebo-controlled clinical trial (clinicaltrials.gov ID: NCT02704754) of suvorexant for treatment of adults (age 18–55) with insomnia that started or worsened after trauma exposure. Suvorexant is a first in class orexin antagonist and is approved by the FDA for the indication of insomnia. In this 6-week trial, all participants initially take 10 mg of suvorexant/placebo, and the dose will be increased to 20 mg if participants continue to experience clinically significant insomnia symptoms 1 week after starting the medication. Sleep outcomes will be measured by polysomnography, daily sleep diary, and the Insomnia Severity Index. RESULTS/ANTICIPATED RESULTS: We hypothesize that (1) within the placebo group data both subjectively and objectively measured outcomes will similarly show improvement in insomnia symptoms, (2) the increase of the placebo medication dose will result in an increased benefit, (3) the trauma-related insomnia placebo group will have the same type and similar rate of side effects reported in previous suvorexant trials. DISCUSSION/SIGNIFICANCE OF IMPACT: Most previous studies examining placebo effects focused on pain and depression. Information obtained from this project will complement our current understanding of placebo effects by characterizing placebo effects on trauma-related insomnia. This study will inform the development of novel strategies to maximize utility of placebos in future clinical trials.

OBJECTIVES/GOALS: Use the World Trade Center (WTC) Health Program Health Effects Library to identify the breadth and depth of research on the health effects of youth due to exposures from the events of September 11, 2001, to track the research trajectories by study population, and to identify gaps and define needs for future research. METHODS/STUDY POPULATION: We selected references from the WTC Health Effects Library. This curated library includes research publications that measure, report, or discuss health effects of 9/11 at the three disaster sites. Articles included had to evaluate people under 18 years old on 9/11/2001, including those in-utero. Of the 1,813 references considered, 195 were included in our study. Data from each reference was extracted using DistillerSR software and organized in four topics: overview, methods, conditions, and results. Each publication was abstracted independently by a team of two health scientists and conflicts were resolved by the four-person team. All data was then exported from DistillerSR into Microsoft Excel for analysis. RESULTS/ANTICIPATED RESULTS: The 195 articles included were published between 2002 through 2021, of which 29 were funded by the WTC Health Program. The study population represented ranged from in-utero to 18 years old. Research trajectories will be developed by assessing chronological research by outcome groups (physical, mental and behavioral, interventions, and biomarkers), study population categories, as well as exposure location and mechanism. Demographic data extracted will be used to assess whether there are disparities in the research conducted to date for this population and if so, in what areas. Research recommendations and clinical implication extracted from references will be used to assess whether more recent research has addressed research from the early post 9/11 years. DISCUSSION/SIGNIFICANCE: WTC research strengthens our understanding of 9/11 health effects and provides a way to improve healthcare for the people afflicted from 9/11 exposures. The anticipated results from this scoping review can lead us to identify past research challenges and current knowledge gaps that the Program can address in future research grants.

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to measure speech fluency and brain activity before and after 5 days of behavioral speech fluency training alone (sham group) or speech training plus stimulation (active group). A 1-month follow up will also be completed. The first primary outcome measure is changes in brain activation in speech motor control/timing network. The second primary outcome measure is changes in percentage of stuttered syllables during speech sample (speech fluency). The secondary outcome measure is changes from baseline on the Overall Assessment of Speakers Experience of Stuttering (OASES), a detailed subject rating of how stuttering affects their lives. METHODS/STUDY POPULATION: This study is a between subjects, counterbalanced, sham-controlled, double-blind design. Participants will be 40 adults who stutter who will be randomized (using minimization) into either the active or sham stimulation group, with all other study procedures being the same in both groups. Participants will completed 2 days of baseline testing, 5 consecutive days of brain stimulation during speech training, 2 days of post-testing, and a 1-month follow up. All outcome measures will be completed immediately before and after the 5 days of brain stimulation, as well as at follow-up. as of submission, 10 subjects have completed the study. Data collection is ongoing. RESULTS/ANTICIPATED RESULTS: Expected results. Questions this study aims to answer: 1) Does a more intensive training period lead to decreased stuttering? We expect that both groups will show improvements in speech fluency immediately after training. We expect that those in the active group will continue to exhibit improved speech fluency at 1 month follow up. 2) Does a more intensive training period lead to changes in brain activity? We expect that both groups will exhibit increased activity in auditory/motor regions immediately after training. We expect that the active group will continue to exhibit an increase in activity in these regions at 1 month follow up. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first RCT study involving brain stimulation in adults who stutter. We expect to provide preliminary evidence for the effectiveness of tDCS as an augmentative agent for increased speech fluency in adults who stutter during a brief, intensive training paradigm. We also expect to be able to provide information on the effects of tDCS on brain activity in speech and auditory-motor regions of the brain. The findings will add to the growing body of literature suggesting that developmental stuttering is a neurodevelopmental disorder with roots in timing and rhythmic aspects of speech motor control and auditory-motor integration.

Translational science is, by definition, groundbreaking; however, without an emphasis on quality and efficiency, some innovations in healthcare may translate into unnecessary risk, suboptimal solutions, and potentially loss of well-being and even lives. The COVID-19 pandemic and the Clinical and Translational Sciences Award Consortium’s response created an opportunity for quality and efficiency to be better defined, expediently and thoughtfully addressed, and further studied as central foundations in the translational science mission. This paper presents findings of an environmental scan of adaptive capacity and preparedness to illuminate the assets, institutional environment, knowledge, and forward-looking decision-making needed to optimize and sustain research quality and efficiency.

Given the convergence of the long and challenging development path for medical devices with the need for diagnostic capabilities for mild traumatic brain injury (mTBI/concussion), the effective role of public–private partnership (PPP) can be demonstrated to yield Food and Drug Administration (FDA) clearances and innovative product introductions. An overview of the mTBI problem and landscape was performed. A detailed situation analysis of an example of a PPP yielding an innovative product was further demonstrated. The example of PPP has led to multiple FDA clearances and product introductions in the TBI diagnostic product category where there was an urgent military and public need. Important lessons included defining the primary public and military health objective for new product introduction, the importance of the government–academia–industry PPP triad with a “collaboration towards solutions” Quality-by-Design (QbD) mindset to assure clinical validity with regulatory compliance, the development of device comparators and integration of measurements into a robust, evidence-based statistical and FDA pathway, and the utility of top-down, flexible, practical action while operating within governmental guidelines and patient safety.

Institutional Development Awards for Clinical and Translational Research (IDeA-CTR) networks, funded by NIH/NIGMS, aim to advance CTR infrastructure to address historically unmet state and regional health needs. Success depends on the response to actionable feedback to IDeA-CTR leadership from network partners and governance groups through annual surveys, interviews, and governance body recommendations. The Great Plains IDeA-CTR applied internal formative meta-evaluation to evaluate dispositions of 172 governance recommendations from 2017 to 2021. Results provided insights to improve the classification and quality of recommendations, credibility of evaluation processes, responsiveness to recommendations, and communications and governance in a complex CTR network comprising multiple coalitions.

OBJECTIVES/GOALS: Community-based residency programs often lack formal training in research scholarship required by ACGME. To address this need, UCSF’s CTSI collaborated with residency leaders to implement a self-paced online curriculum for residents called Training in Practice Based Research (TIPR). We describe characteristics of the initial trainee cohort. METHODS/STUDY POPULATION: In the 2022-23 academic year, TIPR was offered to 10 UCSF-affiliated family medicine residency programs across Northern California and the Central Valley, and 8 chose to participate. An additional community-based psychiatry residency independently contacted our team and was also granted permission to participate. We conducted baseline surveys with participants to understand their prior research experience and motivation to join TIPR. Descriptive data for demographics of trainees and their prior research experience were collected using Qualtrics. Thematic analyses were conducted on qualitative responses. RESULTS/ANTICIPATED RESULTS: Of 32 participants, 29 completed the survey (91%). Learners identified as 40% non-Hispanic White, 28% Asian, 16% Hispanic, 9% non-Hispanic Black, and 15% non-Hispanic other. 28% were motivated to participate in the program because it was a residency requirement, 31% wanted to improve their scholarly skills and confidence, 16% were interested in career development, and 6% were interested in networking. 19% reported no research experience. Participants are currently working on scholarly projects designed during the first year of TIPR. In 2023-2024, with the addition of two new family medicine residency programs, an additional 40 residents have enrolled in TIPR. In April 2024, we will present data on projects completed, and demographics of the full cohort. DISCUSSION/SIGNIFICANCE: With CTSI support, TIPR has reached a large cohort of ethnically diverse physician trainees in community-based settings. Future evaluation will focus on whether TIPR increases the quantity and quality of practice-based research within residency training programs served by this program.

OBJECTIVES/SPECIFIC AIMS: Therapeutic hypothermia (TH) is a neuroprotective therapy regularly used in newborn infants following traumatic births. The infant’s temperature is maintained at 33.5°C for 72 hours by a cooling blanket upon which the infant is placed. Parents are not permitted to hold their infant while TH is ongoing due to concerns for unintentional rewarming or accidental dislodging of catheters or other monitoring equipment. Our prior qualitative research with nurse and parent interviews described the inability to hold an infant during TH as a significant source of stress. We assessed the feasibility of a 30-minute period of maternal holding for infants being actively treated with TH and assessed both the maternal experience of holding and the nurse experience of supporting holding. METHODS/STUDY POPULATION: This was a feasibility study employing a mixed-methods approach. Inclusion criteria were gestational age at birth of 35 weeks or greater, absence of clinical or electrographic seizures during the first 24 hours of TH, and designation as “clinically stable” by the attending neonatologist with the infant on room air, nasal cannula, or continuous positive airway pressure. Quantitative data were obtained from vital sign monitoring every 2 minutes before, during and after holding and from maternal and nurse research surveys. Qualitative data were obtained from nurse surveys. Infant rewarming was prevented through use of a thin foam insulating barrier placed between mother and infant during holding. Adverse events were defined as a change in infant temperature greater than 0.5°C above or below 33.5°C, accidental dislodging of central lines/disruption of EEG leads or early termination of holding due vital sign instability present for greater than 2 recorded measurements including infant bradycardia defined as heart rate less than 80 beats per minute, hypotension defined as mean arterial pressure less than 40 mmHg or oxygen saturation of less than 93%. RESULTS/ANTICIPATED RESULTS: There were 10 newborn infants undergoing TH for neonatal encephalopathy (median gestational age 39.4 weeks) and their mothers (median age=31 years) were recruited. Infants remained on the hypothermia blanket during holding and were transferred safely to their mother’s arms without medical equipment malfunction/dislodgement. Holding occurred at a median of 47 hours of life. The mean temperature prior to holding was 33.4°C and at completion of holding the mean temperature was 33.5°C (p=0.18). There were no significant bradycardia, hypotension or oxygen desaturation events. In total, 80% of mothers reported difficulty bonding with their baby prior to holding and 90% reported a high level of stress before holding. After holding, all mothers felt their bond was “stronger” or “much stronger” and all felt “less stressed” or “much less stressed.” After holding, 75% of nurses reported that they felt a more positive emotional response to the infant. One nurse stated, “being a part of this emotional experience made me feel closer and more connected to this family and gave me a different perspective on just what they had been dealing with and feeling since giving birth to their child.” In free text responses, on 5 separate occasions, nurses commented on the relaxed, calmed or less irritable appearance of the infant while being held during TH. DISCUSSION/SIGNIFICANCE OF IMPACT: In this sample of term infants treated with TH, a 30-minute period of maternal holding was not associated with increased temperature or other adverse events. Holding during TH was associated with extremely positive feedback from mothers and nurses. Future larger studies could consider assessing the impact of holding on endocrinological markers of stress and bonding, on infant glycemic control, on breastfeeding success rates, and the impact of earlier and improved bonding on the developmental outcomes of children held during their treatment with TH. Increasing the duration of holding and allowing both parents to hold on more than one occasion during the 72 hours of TH may increase the proposed benefits of this intervention.

OBJECTIVES/GOALS: To describe team science training that can be tailored to specific audiences, in this case, Clinical Research Professionals (CRP) using discipline-specific vignettes, and to highlight the benefits of audience-specific training in team science. METHODS/STUDY POPULATION: Translational science teams are comprised of members from various disciplines. All members can benefit from team science training. Our education team has incorporated discipline-specific training into educational offerings. This project focuses on education tailored to CRPs and their role in clinical research. Historically, team science training has been focused on faculty and trainees. The exclusion of CRPs can limit the impact of this training. We’ve created workshops specifically geared toward CRPs. This presentation demonstrates how we tailor team science training to CRPs by using relevant examples and real-world vignettes to highlight concepts. RESULTS/ANTICIPATED RESULTS: The team science workshops conducted specifically for CRPs have been well received. CRPs have been eager to engage with team science-related material. The number of team science workshops requested by CRP groups is continuing to increase. We will share both quantitative and qualitative evaluation results from several team science workshops conducted to-date. The inclusion of scenarios that relate to common situations encountered by CRPs has been especially helpful in demonstrating team science concepts they have personally experienced. DISCUSSION/SIGNIFICANCE: Helping CRPs directly apply team science concepts to their work is very valuable for improving high-functioning team behavior. CRPs can use new knowledge and skills to enhance efficiency and reduce stress and burnout. The impact of team science is maximized when all members of the team are trained.

OBJECTIVES/GOALS: Autologous periodontal ligament cells (PDLCs) are a promising tool for rebuilding tooth-supporting (periodontal) tissues but require scaffolds that enable delivery while maintaining PDLC bioactivity. The goal of this study was to design a synthetic hydrogel that fulfilled these criteria to support clinical translation of PDLC delivery. METHODS/STUDY POPULATION: Hydrogels were formed using poly(ethylene glycol) (PEG) polymers and synthetic peptides. PDLCs were isolated from human 3rd molars following informed consent and were cultured using established techniques. Integrin-binding peptides were utilized to promote specific PDLC behaviors, testing PDLCs from 3 human donors in a design of experiments (DOE) approach. Two promising hydrogel designs, identified in the DOE, were selected for validation testing using PDLCs from 3 additional donors. Finally, a small animal model for hydrogel-mediated PDLC delivery was used to determine if benchtop outcomes could predict in vivo tissue regeneration. RESULTS/ANTICIPATED RESULTS: Hydrogel scaffolds maintained high PDLC viability and controlled differentiation of each donor’s PDLCs based on differential presentation of integrin-binding peptides RGD and GFOGER. Two hydrogel designs were selected that optimized either PDLC alkaline phosphatase (ALP) activity or matrix mineralization, outcomes typically associated with cementum and bone formation. ALP activity-optimized hydrogels displayed enhanced PDLC pyrophosphate regulation while mineralization-optimized hydrogels promoted PDLC osteogenic differentiation. When used to deliver PDLCs to periodontal defects, both ALP activity-optimized and mineralization-optimized hydrogels stimulated new cementum formation with inserting PDL fibers, while mineralization-optimized hydrogels promoted enhanced bone formation. DISCUSSION/SIGNIFICANCE: Numerous challenges remain for translating PDLC regenerative potential to clinical practice. This study demonstrates that a synthetic hydrogel scaffold could overcome certain barriers, including controlling PDLC bioactivity with a simplified fabrication and delivery scheme, and may be a promising scaffold for periodontal tissue regeneration.

Objectives/Goals: Cervical cancer is preventable through HPV vaccination and the detection/removal of precancerous lesions. Incidence and mortality rates have only decreased by 3–4% in the past decade. Despite having the tools to prevent all cervical cancers, they are not being fully utilized. Our goal is to identify barriers and design strategies to overcome them. Methods/Study Population: Women in urban (750) and rural (750) settings will be screened for the presence of high-oncogenic risk HPV (hrHPV) by self-vaginal swab, complete the Monitoring Blunting Style Scale, a validation scale to determine attentional style, and a structural barrier to care survey. A subset (Results/Anticipated Results: The study, launched in September 2024 at the Medicine Primary Care Clinic at UMC in New Orleans, has enrolled 16 women. Sample adequacy was high (82%), with 5 women having hrHPV present. Participants expressed high satisfaction and acceptance of the self-administered vaginal swab, with most samples demonstrating high quality. Surveys have been collected, and hrHPV-positive women have been referred for gynecological follow-up. Shreveport site will recruit women across over 20 rural clinical sites using a Mobile Health Unit to increase access in rural and underserved communities. Discussion/Significance of Impact: The baseline study will take 12–18 months. We will identify and address key barriers to follow-up gynecological care, including logistical issues (improving access and navigation), educational needs (developing culturally sensitive materials), and emotional support. We will create a care delivery model to eliminate cervical cancer in Louisiana.

OBJECTIVES/SPECIFIC AIMS: Cesarean delivery is typically performed in the extremely preterm period (23 to 28 weeks) when the fetus is in breech presentation to avoid the potential risk of head entrapment by an insufficiently dilated cervix during a vaginal delivery. Assessment of the prevalence of extremely preterm breech cesarean delivery would help to appropriately guide future clinical interventions designed to increase the feasibility of vaginal delivery for this sub-group of patients. METHODS/STUDY POPULATION: We performed a cross-sectional study of the 2106 U.S. National Vital Statistics birth certificate database to estimate the prevalence of cesarean deliveries performed during the period of gestation from 23 to 28 weeks with a fetus in breech presentation. RESULTS/ANTICIPATED RESULTS: An analysis of the total births in the 2016 registry (3,945,875) was performed. The gestational age was limited to the target range of 23 0/7 to 27 6/7 weeks. Multiple gestation deliveries were excluded. This yielded 16,092 births of which 4,849 were noted to have breech presentation. The proportion of cesarean deliveries performed for singleton breech fetuses at this gestational range was 87% (4,203/4,849). DISCUSSION/SIGNIFICANCE OF IMPACT: The probability of undergoing a cesarean delivery for an extremely preterm fetus in breech presentation is notably higher (87%) when compared to an overall cesarean delivery rate of 31.9%. Specific interventions to allow for vaginal delivery in this particular sub-group of the obstetric population would be useful to reduce maternal morbidity by increasing vaginal deliveries. Future work will attempt to address innovative solutions to prevent head entrapment by the cervix in this particular population and ultimately avoid cesarean delivery.

OBJECTIVES/SPECIFIC AIMS: Skillful research staff members are critical to productive translational research teams and yet their ongoing professional development is rarely formally addressed. Through the Strategic Teamwork for Effective Practice-Mentor Development Program (STEP-MDP), we aimed to both create a community of practice (COP) for research staff and build the skills needed to enhance research team performance. METHODS/STUDY POPULATION: We selected 16 participants of 32 staff-level applicants from among the NYU Schools of Medicine, Social Work and Nursing for the first STEP-MDP cohort. Participants included research assistants, coordinators, managers, and directors. We delivered 3, two-hour workshops, scheduled 3 weeks apart, focused on team communication, identifying team areas for improvement, and mentorship/coaching skills. Peer-Coaching Teams (PCTs) were created by pairing participants at the same position level, and PCTs worked together at each session to explore and practice learned skills. Sessions featured brief didactics, group-based learning and exercises based on participants’ real issues. A variety of active learning techniques such as brainstorming, role-playing, problem solving, and peer coaching were used. Practical core readings, worksheets, and summary cards were provided. PCTs met between sessions to practice coaching skills, and troubleshoot problems. RESULTS/ANTICIPATED RESULTS: Participants (n=16) completed a 37-item retrospective pre/post self-assessment of team behaviors and skills, and a STEP-MDP evaluation survey at the end. We saw pre-post improvements in each of 5 self-assessment domains: Communication (4 items, pre-mean 2.66, post mean 3.36, p≤0.001), Leadership (8 items, pre-mean 2.76, post mean 3.55, p≤0.001), Empowerment and Motivation (12 items, pre-mean 2.86, post mean 3.51, p≤0.001), Coaching (6 items, pre-mean 2.40, post mean 3.58, p≤0.001), and Community (3 items, pre-mean 2.33, post mean 3.76, p≤0.001). On average, PCTs met twice (range 2–4 times) between workshop sessions. Learners valued the PCTs, and 1 commented on the value of working with peers in PCTs, having no one in a similar position within his immediate work environment. Participants’ written comments strongly endorsed the value of the workshops for their work, with the coaching skills session seen as the most valuable. Some participants worry that skills will decrease over time without continued reinforcement. All but 1 participant reported that they planned to continue with the PCT. DISCUSSION/SIGNIFICANCE OF IMPACT: The number of applicants to our program suggests a need and motivation for staff to participate in the STEP-MDP. Participants’ reported improved skills and sense of community. To maintain the COP and address worry about degradation of skills we are planning to remind PCTs to meet once a month and will follow-up with them 3 and 6 months post intervention to evaluate their continued development. This spring a second cohort will receive the training. We believe developing these core teamwork skills will lead to more collaborative, efficient, and innovative research. We have implemented a successful program targeting critical members of research teams with potential to facilitate expansion of institutional capacity for translational research. It will be important to understand the long-term impact of the program on individuals, on team science, on research, and ultimately on the health of the public.

OBJECTIVES/GOALS: The development of early university technologies for commercialization is largely inefficient and exhibits a high rate of failure, often due to a lack of researcher time and commercialization experience. We have created the Translational Fellow role to address these needs and increase the throughput of university technology transfer. METHODS/STUDY POPULATION: Translational Fellows will first build their initial competencies to identify, evaluate, and develop new technologies through internships with intake organizations within the university ecosystem, including the Office of Technology Management, the LEAP gap-funding mechanism, and local venture capital firms. Following this training, Fellows will provide tailored support to validated projects by establishing development milestones, liaising with industry experts, navigating regulatory requirements, and drafting marketing materials such as executive summaries and financial projections. Lastly, Fellows will partner with a highly developed project to facilitate the commercialization of the technology, whether through a SBIR/STTR grant, direct licensing event, or startup creation. RESULTS/ANTICIPATED RESULTS: We anticipate that implementation of this mechanism will increase the proportion of university-generated inventions that undergo successful commercialization events, as well as increase the rate at which these projects develop after initial validation. Furthermore, we expect that the skills acquired through this program will allow Fellows to successfully transition to a variety of roles in the biotech space. We also expect that Fellows will be capable of training other scientific teams in the preparation of SBIR/STTR grants, further expanding opportunities for commercialization in the research space. DISCUSSION/SIGNIFICANCE OF IMPACT: Translational Fellows fill a unique interdisciplinary niche, allowing them to address common barriers faced by academic inventors. Improving commercialization throughput further capitalizes on the wealth of ideas generated in universities, thereby driving innovation in the biomedical space and directly contributing to improved human health. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest.

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

ABSTRACT IMPACT: This work aims to identify best practices for university-based asset development programs to improve commercialization throughput, which in turn will drive innovation in the biomedical space and directly contribute to improved human health. OBJECTIVES/GOALS: University technology transfer exhibits a high rate of failure, often due to a lack of researcher experience or early-stage financial capital. The LEAP program at Washington University (WUSTL) was created to address these needs. The goal of this study is to assess the performance of LEAP against similar gap funds and further improve program operations. METHODS/STUDY POPULATION: The goals of LEAP are achieved by providing university inventors with individualized consulting and feedback from industry experts, as well as awarding funding to the most promising projects. To determine whether these activities are impactful, we distributed an awardee report form to collect data on all funded LEAP projects, and then combined the results with project registration information. We also collected records Office of Technology Management, including invention disclosures, licenses, and startup creations. The resulting dataset was used to calculate program metrics and then evaluated against comparable gap funds. Sentiment data from participant surveys were also analyzed to assess perceived program value and knowledge transfer. RESULTS/ANTICIPATED RESULTS: As of the Sp2020 cycle, LEAP has funded 76 projects. Resubmitted projects had a funding rate of 52%, vs. 34% for new projects. Of the startups founded off of WUSTL intellectual property since 2016, nearly two-thirds had previously participated in LEAP. Funded LEAP projects also had a 29% licensing rate, which is comparable to similar gap funds. Lastly, participants self-reported an increase in knowledge across a range of commercialization areas. DISCUSSION/SIGNIFICANCE OF FINDINGS: The increased repeat funding rate and self-reported knowledge suggest that LEAP is impactful in building commercialization proficiency. The licensing rate and prevalence of LEAP projects in WUSTL startups also indicate that LEAP is indeed promoting tech transfer. Together, these results suggest that LEAP could be a model for other institutions.

ABSTRACT IMPACT: This work will standardize necessary image pre-processing for diagnostic and prognostic clinical workflows dependent on quantitative analysis of conventional magnetic resonance imaging. OBJECTIVES/GOALS: Conventional magnetic resonance imaging (MRI) poses challenges for quantitative analysis due to a lack of uniform inter-scanner voxel intensity values. Head and neck cancer (HNC) applications in particular have not been well investigated. This project aims to systematically evaluate voxel intensity standardization (VIS) methods for HNC MRI. METHODS/STUDY POPULATION: We utilize two separate cohorts of HNC patients, where T2-weighted (T2-w) MRI sequences were acquired before beginning radiotherapy for five patients in each cohort. The first cohort corresponds to patients with images taken at various institutions with a variety of non-uniform acquisition scanners and parameters. The second cohort corresponds to patients from a prospective clinical trial with uniformity in both scanner and acquisition parameters. Regions of interest from a variety of healthy tissues assumed to have minimal interpatient variation were manually contoured for each image and used to compare differences between a variety of VIS methods for each cohort. Towards this end, we implement a new metric for cohort intensity distributional overlap to compare region of interest similarity in a given cohort. RESULTS/ANTICIPATED RESULTS: Using a simple and interpretable metric, we have systematically investigated the effects of various commonly implementable VIS methods on T2-w sequences for two independent cohorts of HNC patients based on region of interest intensity similarity. We demonstrate VIS has a substantial effect on T2-w images where non-uniform acquisition parameters and scanners are utilized. Oppositely, it has a modest to minimal impact on T2-w images generated from the same scanner with the same acquisition parameters. Moreover, with a few notable exceptions, there does not seem to be a clear advantage or disadvantage to using one VIS method over another for T2-w images with non-uniform acquisition parameters. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results inform which VIS methods should be favored in HNC MRI and may indicate VIS is not a critical factor to consider in circumstances where similar acquisition parameters can be utilized. Moreover, our results can help guide downstream quantitative imaging tasks that may one day be implemented in clinical workflows.

OBJECTIVES/GOALS: (1) Assess challenges with our current continuous improvement processes via stakeholders. (2) Implement a revised continuous improvement process. (3) Evaluate the revised processes to assess implementation and use for strategic improvement. (4) Implement analysis mechanisms for new process to assess trends across the CTSI. METHODS/STUDY POPULATION: We used a mixed-methods, multi-phased, stakeholder-engaged approach with different processes per objective. Obj. 1: We implemented focus groups, surveys, and listening sessions incorporating two populations: both teams required to participate in reporting process, and CTSI leadership. Obj. 2: We utilized data from Obj. 1 processes to develop a revised continuous improvement process. Obj. 3: We integrated qualitative feedback processes onto the structure of continuous improvement processes, and we implemented a survey to assess use and value for the new process. Obj. 4: We developed a qualitative coding schema to assess key trends across teams and over time. RESULTS/ANTICIPATED RESULTS: Obj. 1: Numerous challenges in metrics format and process, including significant limitations in data use to inform decision-making and appropriately assess impact. Obj. 2: Resultant changes to continuous improvement processes, including a restructured reporting format and use-oriented approach that enhanced organizational integration; changes included added focus on facilitators of success, challenge, and key opportunities to better inform decision-making. Obj. 3: The majority of teams experienced the new quarterly process as a better tool for program monitoring and communicating program needs to leadership, but that fuller integration into vertical communication is needed. Obj. 4: Implementation of new analysis process enabling examination of trends and themes across diverse teams within the CTSI. DISCUSSION/SIGNIFICANCE: This work has particular relevance within ACTS given our focus on a clinical and translational research enterprise, the complexity in evaluating the diverse work of translation research entities, and limitations in a commonly-used metrics-monitoring approach. Our focus on improving translational processes advances translational science.