OBJECTIVES/SPECIFIC AIMS: Compare the short- and long-term effects of 2 treatments, MST and SF, on limitations in function, pain, and movement characteristics. The movement characteristics included the amount of early excursion (1st half of decent) of the knee, hip, and lumbar spine during a functional activity test of picking up an object. METHODS/STUDY POPULATION: 154 participants were randomized to 6, 1-hour treatment sessions (once/week for 6 weeks) of MST or SF. The MST group received individualized training to modify pain-provoking altered movement patterns during functional activities. The SF group received exercises for trunk strength and trunk and limb flexibility. At baseline, post-treatment and 6-month follow-up participants completed the modified Oswestry Disability Questionnaire (MODQ, a functional limitation measure; 0-100%), the Numeric Pain Rating Scale (NRS, average pain prior 7 days; 0-10) and a standardized pick up an object test, where sagittal plane knee, hip and lumbar spine excursion were calculated using 3D motion capture. A mixed model repeated measures ANOVA was used to examine the following effects: Treatment group (Tx), Time and Tx X Time for each self-report and movement variable. When the ANOVA was significant (p < 0.05), a priori planned contrasts were examined. RESULTS/ANTICIPATED RESULTS: There was a significant Tx X Time interaction (p < 0.01) for each outcome. Baseline: MST and SF were similar in MODQ scores [Δ 0.4% (−3.4− 2.9)], NRS [Δ 0.0 (−0.6− 0.6)], knee [Δ 2.2° (−6.7− 2.5)], hip [Δ 0.4° (−2.9− 2.5)], and lumbar spine [Δ 0.1° (−1.4− 1.2)] early excursion. Post-Treatment: Both group’s MODQ and NRS scores decreased (p < 0.01), but MST had a greater reduction in MODQ scores [Δ −7.6% (−3.9− −11.0)] and lower average NRS scores [Δ −0.8 (−0.1− −1.4)] compared to SF. MST changed knee [Δ +18.6° (14.6− 22.1)], hip [Δ +10.8° (8.5− 13.1)], and lumbar spine [Δ −2.0° (−3.0− −1.0)] early excursion, while SF did not change early joint excursion (all p > 0.72). 6-Month Follow-up: The differences between MST and SF were maintained for all outcomes (p > 0.26). DISCUSSION/SIGNIFICANCE OF IMPACT: MST was more effective at reducing functional limitations and pain and improving movement patterns during a functional activity compared to SF. For all variables, the differences identified during treatment between MST and SF were maintained at 6-month follow-up. Therefore compared to SF, MST that targets performance of altered movement patterns during functional activities appears to be superior for attaining and maintaining changes in functional limitations, pain, and movement characteristics in people with CLBP.

OBJECTIVES/SPECIFIC AIMS: Translating conventional and regenerative medicine strategies from the research laboratory into the clinic is a complex process that can delay bringing novel therapies to the patient. Navigating the increasingly complex regulation surrounding cell-based and combination product technologies is a major challenge for the translational biomedical scientist. To this end, Mayo Clinic created a new position, the “Translational Integrator,” as part of the cGMP Biomaterials Facility in the Center for Regenerative Medicine. METHODS/STUDY POPULATION: The Translational Integrator educates investigators about FDA standards and regulatory pathways; determines where the product is on the translational spectrum; works to understand the science behind the product; determines what additional studies may be needed; supports investigators in preparing for FDA communications and submissions; and educates researchers about institutional resources and funding mechanisms needed to move their product into manufacturing and trials. A primary objective is to meet investigators at an early stage in product development to avoid conducting potentially redundant work to meet regulatory requirements. RESULTS/ANTICIPATED RESULTS: Robust training in clinical and translational research methodology enables the integrator to facilitate the collaboration necessary between investigators, clinicians, institutional resources, regulators and funders to move products towards FDA IND/IDE approval and first-in-human trials. It is an iterative process using technology/translational readiness criteria, project management and review by subject matter experts that is highly interactive and customized to each project. Current projects include topics in orthopedic surgery and ENT. In creating and refining this position, several key lessons have been learned. DISCUSSION/SIGNIFICANCE OF IMPACT: First, the Translational Integrator must undergo constant reflection and assessment of investigator needs, which requires flexibility and understanding that their role may change in the context of each product. Second, the support that the Translational Integrator provides can shift the mindset of the investigator from being averse to engaging in the translational process to eager to move their product forward. Finally, for the investigator who does not personally want to move their work into first-in-human trials, establishing connections to intellectual property generation and licensing may support movement of their findings into patients.

OBJECTIVES/SPECIFIC AIMS: The central aim of the study is to examine the effect of a Dietary Approaches to Stop Hypertension (DASH) diet on hemodynamic, cardiometabolic, and inflammatory markers in advanced heart failure patients with implanted hemodynamic monitoring devices. METHODS/STUDY POPULATION: This pilot study will employ a clinical feeding trial using a 1-group pre-post test design with an anticipated sample size of n=36 (n=20 plus 44% expected attrition). Heart failure patients 18+ years of age with English language literacy, classified as NYHA functional stage III, regardless of ventricular ejection fraction, who have undergone CardioMEMS™ hemodynamic monitoring device (St. Jude Medical, Atlanta, GA, USA) implantation and have received optimized heart failure therapy for 3+ months will be recruited at Piedmont Athens Regional Hospital in Athens, GA. The study is divided in (a) a calibration (self-selected diet) and (b) a DASH feeding intervention phase (each 21 days in length). The DASH meals will strictly follow meal planning guidelines published by the National Heart, Lung, and Blood Institute of the National Institutes of Health, and be prepared under the supervision of a registered dietitian at the University Health Center in Athens, GA. The DASH diet is a heart-healthy eating pattern that is focused on adequate consumption of fruits, vegetables, whole grains, low-fat dairy, fish, poultry, beans, nuts, and vegetables oils while emphasizing limited intake of foods containing saturated fat, such as fatty red meats, full-fat dairy products, and tropical oils, such as coconut, palm kernel, and palm oils, as well as sugar-sweetened beverages and sweets. Participants will visit the University of Georgia Clinical and Translational Research Unit on 3 occasions at baseline, upon completion of the calibration phase, and following completion of the intervention phase for repeated collection of anthropometric (height, weight, waist and hip circumference, percent body fatness), cardiometabolic (blood pressure, blood glucose, HbA1C, lipid panel, basic metabolic panel, BNP, NT-proBNP, troponin 1, MR-proADM, sST2), functional status (6-min walk test), inflammatory (IL-1a, IL-1b, IL-6, TNF-a), and self-reported measures (demographic and economic characteristics, health, chronic diseases, perceived stress, heart failure-related quality of life, social support, sleep quality, food insecurity, tobacco smoking status, healthcare utilization, medication adherence). Hemodynamic marker (pulmonary artery pressure, heart rate) and pharmacotherapy information (medication count, type, strength, and dosing) will be obtained from through retrospective assessment of EHR data. Descriptive statistics [percentage, mean (SD), median (IQR), mode, range] will be used to describe sample characteristics at each of the study visits, as well as characteristics of participants’ self-selected diets during the calibration phase. To measure changes in hemodynamic, cardiometabolic, and inflammatory markers pre-post DASH diet intervention, we will use paired Student t-tests (normal distribution) or Wilcoxon rank-sum tests (non-normal distribution), as appropriate. Data collection will be carried out between February and November 2018. RESULTS/ANTICIPATED RESULTS: The study builds upon previous studies showing improvement of ventricular function, arterial stiffness, oxidative stress, and blood pressure after short-term consumption of a sodium-restricted DASH diet in heart failure patients with preserved ejection fraction, and will provide new information on the cumulative effect of short-term adherence with a DASH diet on indicators of heart failure complications, including hemodynamic, cardiometabolic, and inflammatory markers. In addition, it will give better insight on heart failure patients’ habitual dietary intake in the context of other sociodemographic, economic, health, and social factors. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings from the proposed study will provide key knowledge of dietary influences on ventricular function in order to define evidence-based diet therapy needed for the early prevention of HF complications in advanced heart failure patients.

ABSTRACT IMPACT: Improved radiation treatment will yield higher doses at the tumor site, while reducing damage to healthy tissue, which will improve clinical outcomes. OBJECTIVES/GOALS: Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized and the mechanism uncovered. The efficacy of these particles will be tested in a murine system. METHODS/STUDY POPULATION: Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol then covalently conjugated to chlorin e6, a known, FDA approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species following X-irradiation was measured. Enhanced cell killing was measured clonogenically and in vivo efficacy and tumor pathology was assessed in a murine system. Further studies will determine the optimum combination of particle shape, photosensitizer structure, and ratio of components, as well as the optimal dosing schedule. RESULTS/ANTICIPATED RESULTS: Conjugation of the particle to the photosensitizer was successfully achieved, and the molecule was detectable by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates significantly increased cell killing during radiation treatment, while neither the particle alone or the photosensitizer significantly affected clonogenic survival at the same concentrations. Pathology of breast tumors grown in immunocompetent mice showed a significant increase in necrotic tissue following a single 20 gy treatment when the conjugate was present. DISCUSSION/SIGNIFICANCE OF FINDINGS: Radiation therapy is widely used clinically and it is a highly localized form of treatment. However, the total dose of radiation is limited largely to prevent injury to adjacent normal tissue. This conjugate has the potential to increase the effective dose in the tumor thereby reducing damage to healthy tissue and providing a more effective therapy.

OBJECTIVES/GOALS: Micronutrient deficiencies contribute to poor health and childhood development outcomes. The objective of this study was to examine the independent and combined effects of responsive parenting and multiple micronutrient supplementation interventions on preschooler hemoglobin and ferritin concentrations in southwestern Guatemala. METHODS/STUDY POPULATION: We enrolled 387 preschoolers (36-52 months) at nutritional risk (height-for-age z-score < -1) (51% male; 17% indigenous ethnicity) in a double blind, 2 x 2, cluster randomized controlled trial. Participants in the parenting intervention received culturally tailored responsive parenting or nutrition education (control) curriculum, delivered over 6 home visits. Participants in the nutrition supplementation group received daily supplementation with a maize-soy product fortified with 21 micronutrients for 6 months or a control product fortified with vitamin B2 only. Linear mixed models were used to estimate changes in hemoglobin and ferritin from baseline (2015) to endline (2017) in a subsample with blood specimens (n = 218). RESULTS/ANTICIPATED RESULTS: At baseline, 14% of preschoolers were iron deficient and 11% were anemic. Preschooler ferritin significantly increased over time in most arms, with the largest increase in the combined responsive parenting + multiple micronutrient supplementation arm (ferritin = 95.6 (95% CI 46.4, 144.74); rates of change did not differ between study arms (p = 0.16). Preschooler hemoglobin did not change over time. Further analysis will examine the moderation of intervention effects by pre-specified child and household factors. DISCUSSION/SIGNIFICANCE: Increases in preschooler ferritin did not differ between intervention and control arms. There was no effect of the intervention on hemoglobin. Future analyses will examine intervention effects on pre-specified subgroups including baseline micronutrient deficiencies.

OBJECTIVES/GOALS: To comprehensively understand the training needs of clinical research professionals (CRPs) employed across various roles in team science. The purpose is to identify areas for competency development and determine the modality of training desired to enhance their skills further. METHODS/STUDY POPULATION: This study targets Clinical Research Professionals (CRPs) across various roles in Academic Health Centers via an online survey. From novices to experts, participants are often trained on the job covering some clinical research competencies, but team science aspects like communication and leadership are usually overlooked. The survey will assess current skills, identify training gaps, and explore preferred learning methods and topics. Participants will be recruited through the CTSA hub research network. Additionally, they'll share experiences of team cohesion, dynamics, conflict, and their contributions to the team through participation in focus group sessions.The focus groups will be held via Zoom with volunteer participants from the survey (6 per session, 3 sessions, N=18). RESULTS/ANTICIPATED RESULTS: The recently developed leveled CRP team science competencies based on Lotrechianno (2022) will be the basis of the survey items. Demographic characteristics of the participants by role will be presented. Moreover, perceptions of team science applications, learning needs and training preferences will be described. Results will be compared across CRP roles. Finally, three recorded and transcribed focus groups (n=18) will contribute to knowledge gained through this research allowing for a deeper understanding of training needs. Qualitative analyzes of recorded focus-group discussions will present key themes. Qualitative data will be coded by more than two people for interrater reliability. DISCUSSION/SIGNIFICANCE: This study offers the first needs assessment on academic medical center CRP team science learning requirements, utilizing newly established CRP individual and team competencies. Findings will guide the creation of tailored training and research initiatives.

Objectives/Goals: The objective of this project is to develop a tool for evaluating clinical trial (CT) eligibility criteria for demonstrated “gender literacy,” defined as the recognition that biologically assigned “sex” is distinct from personally defined “gender identity,” as a way to quantify the inclusion of gender minority populations. Methods/Study Population: The study is validating an assessment scale that evaluates gender literacy based on CT eligibility criteria (EC). Two health professionals will serve as “coders,” tasked with grading 15 CTs. EC for all CTs will be exported from clinicaltrials.gov. Once trained with using the scale, each coder will give a score for each trial. After this first scoring period, coders will share their scores and experiences using the scale. Coders will be tasked again with grading 15 new CTs. This second scoring period will yield final scores to calculate the inter-rater reliability (IRR), or the extent to which qualitative measurements are consistent and not due to random chance. IRR will be quantified by Cohen’s kappa to validate the scale. Results/Anticipated Results: Cohen’s kappa is on a continuous interval from 0 to 1, where 0 means no agreement and 1 means perfect agreement. It is expected that the Cohen’s kappa for this assessment scale will exceed 0.80. Such validation is necessary to ensure the scale is robust and dynamic for multiple use-cases and consistent across any coder. By having a discussion after the initial scoring period, we can identify confusions or challenges with the scale early on and correct them before the secondary scoring period. In comparing these two coders’ performance, it is expected that the second scores will be more similar, thus a kappa closer to 1. However, if the kappa is low, this may be because gender literacy is a learned skill, through the internalized recognition that gender is truly different from sex. Discussion/Significance of Impact: Systemic barriers and exclusionary language have excluded gender minorities from CT spaces for too long. Tools such as these, paired with standardized language for sex and gender eligibility criteria, will greatly bolster the representation of this population and spark change for a more inclusive future.

OBJECTIVES/GOALS: The purpose of this study was to assess if the Mentoring Competency Assessment (MCA) could be used to capture mentee gains in mentorship skills and how the mentorship competencies may vary structurally for mentees compared to mentors, while the original MCA was shown to be a validated measure to assess mentor skills. METHODS/STUDY POPULATION: The mentee training survey data were collected nationally from 2015 to 2022. The survey data set included 401 respondents who consented to participate after 59 mentee training events hosted by 34 institutions/organizations who participated in face-to-face and online training as well as completed the Mentoring Competency Assessment (MCA) in their surveys. We conducted principal component analysis (PCA) with varimax rotation to investigate the internal structure of the MCA and Hatcher’s criteria were applied. After a team of mentoring experts independently interpreted the PCA results and reached a consensus on the interpretations of the components, factor analysis and internal consistency reliability analysis were applied to assess the construct validity and the reliability. RESULTS/ANTICIPATED RESULTS: There were significant component loadings of the eight components with varimax rotation and 22 of the total 26 items were loaded into components. Four items, (5) pursuing strategies to improve communication, (6) coordinating with other mentors, (11) developing strategies to meet goals, and (23) setting career goals, were excluded from the factor analysis and Cronbach’s alpha analysis since these items were not significantly loaded into any components. The eight-component structure was validated (χ2=313.209, p<.001, RMSEA=.083, CFI=.907, TLI=.881, SRMR=.073) and the hypothesized model of the eight components resulted in an acceptable fit to the data with standardized factor loadings ranging from 0.58 to 0.93. The alpha coefficient is from 0.58 to 0.90, suggesting the items have high internal consistency. DISCUSSION/SIGNIFICANCE: Based upon the findings we recommend that the full revised MCA for mentees is used to capture mentees’ mentorship skill gains even if not all of the competency modules are used in the training. The development and validation of measures such as the MCA are important as we move toward the use of common measures across programs such as the CTSAs.

OBJECTIVES/GOALS: To facilitate the development of innovative injection products by providing translational researchers with a regulatory and manufacturing road map for producing small batch sterile products for Phase 1 research use. To leverage recent AMC investments in facility improvements and pharmacy training in the areas of sterile product production, testing, and environmental controls, that can be used to support production of phase 1 clinical trial supplies METHODS/STUDY POPULATION: Searching and organizing relevant data and information from web portals and databases in the following: areas: FDA, EMA, USP regulations, regulatory science, pharmaceutical formulation and analytics, supply vendors, analytical testing laboratories, and product testing laboratories. Present the information using a user friendly format including flow charts and development timelines, taking the perspective of the translational investigator. RESULTS/ANTICIPATED RESULTS:

• Choosing AMC resources vs outside consultants and vendors, leveraging local resources where possible

• Qualifying and monitoring suppliers, testing laboratories, in-house departments, and Contract Drug Manufacturing Organizations (CDMO)

• Bringing together the deliverables for the IND CMC section

• Where and how to leverage available products and science to simplify safe and reliable production

DISCUSSION/SIGNIFICANCE OF IMPACT: Use and utility of injectable drug products, both small molecule and biologics, is growing rapidly, and is projected to continue to escalate well into the next decade. This is due not only to advances in medicine, but also to improvements in AMC-based sterile product production, and a better understanding of small batch manufacturing methods. All three trends align in academic medical centers (AMC) and can be utilized by translational researchers, if they can understand the potential and regulatory requirements.

ABSTRACT IMPACT: The purpose of the T1-T4 in 3 Minutes program is to improve trainees’ capacity for communication of complex to a non-scientific audience as well as to ensure that our community stakeholders have access to, and understanding of, ongoing clinical and translation research OBJECTIVES/GOALS: The T1-T4 in 3 Program: ο Increases knowledge of research across institution; ο Increases capacity of trainees to convey complex science to lay audiences, funders, colleagues, and the media; ο Increases health and scientific literacy; ο Bridges gaps between trainees and potential entrepreneurial mentors METHODS/STUDY POPULATION: T1-T4 in 3 (Minutes) is an adaptation of the University of Queensland’s Three Minute Thesis competition in which PhD students present their thesis in 3 minutes or less to a lay audience. The competition enables them to cogently communicate their ideas and research findings to a non-specialist audience. Our adapted version, T1-T4 in 3, requires a presentation in three minutes or less to a lay audience, but rather than a thesis, the topics are on trainees’ research, and in this particular case, an idea for a commercial venture. The competition provides awards for the first- and second-best projects as determined by a panel of judges, and a ‘people’s choice’ award determined by a lay audience. RESULTS/ANTICIPATED RESULTS: This exercise is anticipated to improve trainees’ capacity for communications as well as ensure that community stakeholders and research and business community partners have access to, and understanding of, ongoing clinical and translation research with potential commercial applications. Further, the increased ability of our faculty and trainees to effectively communicate complex science to the public and other audiences’‘ including potential funders’‘ supports additional stakeholder dissemination mechanisms by increasing their confidence in their abilities to converse with non-specialists about their research, thus increasing the likelihood of participation in other community-based activities. DISCUSSION/SIGNIFICANCE OF FINDINGS: To increase ITS commercialization efforts, we envision involving numerous external partners to educate, fund, and support new ventures. T1-T4 in 3 judges will include commercialization scholars from regional and national institutions as well as pharmaceutical entities and regional angel investors.

OBJECTIVES/SPECIFIC AIMS: To improve the quality of evidence synthesis projects, including systematic reviews and other comparative effectiveness reviews, at the University of Utah. METHODS/STUDY POPULATION: Systematic reviews and other types of evidence syntheses are best when collaborative teams with expertise in multiple disciplines participate, including content experts, librarians and information specialists, systematic review methodologists, and statisticians. The Center for Clinical & Translational Science (CCTS), due to its interdisciplinary nature, connectivity to clinical experts, and existing Cores of methodologists, presented an opportune location for a Systematic Review Core. We designed the Systematic Review Core to focus on 2 primary aspects of evidence synthesis support: overall systematic review methodology guidance and in-depth information retrieval planning and execution. After establishing a conceptual partnership, a new position, Evidence Retrieval and Synthesis Librarian, was created to build capacity within the Core. RESULTS/ANTICIPATED RESULTS: Close connections with the CCTS’s Population Health Research Foundation have led to better interdisciplinary coverage of systematic reviews and other evidence syntheses produced by the University of Utah. We are able to partner with statisticians and clinical experts from formulating the question to completing the final manuscript. Hourly rates charged through a cost recovery model have enabled us to grow our staff able to work on the Core, as well as offset costs for major databases and resources these bibliographic data-heavy research methods require. After 1 year of existence, the Core is already at maximum capacity, with no sign of slowing. Projects have ranged from brief consultations to highly intense interactions for the duration of the research spectrum. We have also been added as key personnel to grants with systematic review components. DISCUSSION/SIGNIFICANCE OF IMPACT: Systematic reviews and other evidence syntheses are a labor-intense, interdisciplinary team effort that fit well within the scope of CTSA’s. They are a key component of the translation of science to practice, and can be used at all stages of the translational science spectrum. Quality of systematic reviews remains poor, particularly surrounding protocol development, sensitive search strategy design and reporting, and overall reporting. Librarians and information specialist involvement has been shown to positively correlate to the search strategy design and reporting aspects of systematic reviews, and librarians and information specialists increasingly act as systematic review methodologists. By including librarians and information specialists as part of the CTSA’s official Core structure, these systematic review methodologists are able to connect with statisticians, other methodologists, and clinical experts in a nexus of interdisciplinarity. At the University of Utah, the visibility and structure provided by the CCTS helps the Systematic Review Core with promotion, creating connections and opportunities for collaboration across the campus. This partnership has already led to increased uptake in services, and over time, we believe it will increase the quality of the science produced. CTSA’s have a natural partner with their health science library colleagues in translational science, as shown by this model.

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: Community-based primary care autism diagnostic models are one promising solution to delays in autism diagnosis. Our objective is to describe the development and report on outcomes related to primary care professional (PCP) training and sustained engagement in a longitudinal learning collaborative across a statewide network for autism diagnosis. METHODS/STUDY POPULATION: We developed ADAPT (i.e., Accelerating the Diagnosis of Autism with Primary care Training), a training program to prepare PCPs to develop independent competency in evaluation of autism in children ages 14-48 months. ADAPT includes didactic and case-based modules and expert practice-based coaching delivered by a diagnostic specialist; following training PCPs participate in a longitudinal learning collaborative. Aligned with competency-based medical education standards, measures of autism evaluation knowledge and diagnostic competency are collected. RESULTS/ANTICIPATED RESULTS: To date, 13 PCPs have completed ADAPT didactic and practicum training reaching competency in independent autism evaluation. Clinicians demonstrated significant improvement in total autism knowledge following didactic training (p=.02). There was an overall trend toward increased scoring agreement on an autism observational assessment over case observations and practicum evaluations. Similarly, PCPs demonstrated improved evaluation competence, moving on average from Advanced Beginner to Competent Performer as rated by expert trainers. Following training, PCPs attended 57% of monthly learning collaborative sessions. DISCUSSION/SIGNIFICANCE: Training PCPs to deliver autism evaluations as part of community-based models of care is a promising solution to address access and waitlist challenges. ADAPT is an intensive, standard PCP training model which results in achievement of independent competency and sustained engagement in in autism evaluation.

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.