OBJECTIVES/SPECIFIC AIMS: Identify the impact of the provision of clinical and translational research training awards on investigators’ pursuit of clinical and translational research careers. METHODS/STUDY POPULATION: Propensity score matching and qualitative analysis/investigators receiving MICHR’s KL2 research training awards. RESULTS/ANTICIPATED RESULTS: While the evaluations of the impact of this service have shown participants find them to be valuable it is expected that participation in the workshop may be more beneficial to investigators with certain types of prior research experiences and who utilize more CTSA research support. DISCUSSION/SIGNIFICANCE OF IMPACT: Because this evaluation of a research service incorporate data representing investigator’s receipt of different CTSA resources, the findings can be used to inform the ongoing coordination of these services in ways that optimize their impact on the production of clinical and translational research. There is an enduring need for evaluations of CTSA programs to account for investigators’ use of different constellations of research services in order to identify what combinations of services over time are most effective at fostering successful clinical and translational research careers.

OBJECTIVES/SPECIFIC AIMS: To evaluate the NIH-sponsored Best Practices for Social and Behavioral Research e-learning course. METHODS/STUDY POPULATION: Four universities partnered in a pilot study to evaluate this new course. Outcomes from 294 participants completing the course included efficient progress through the training, perceived relevance of the course to current work, level of engagement with the course material, intent to work differently as a result of the course, and downloading digital resources. RESULTS/ANTICIPATED RESULTS: Participants rated the course as relevant and engaging (6.4 and 5.8 on a 7-point Likert scale) and 96% of respondents said they would recommend the course to colleagues. Qualitative analysis of participant testimonials suggested that most respondents had a readiness to change in the way they worked as a result of the course. Overall, results suggest participants completed the course efficiently, perceived outcomes positively and worked differently after the training. DISCUSSION/SIGNIFICANCE OF IMPACT: These results will inform new guidelines for future participants (e.g., average time to complete, expectations for knowledge checks in the training). Future studies should include larger samples and closer coordination and communication between study sites.

OBJECTIVES/GOALS: To demonstrate how brief online audiovisual presentations, “learning shots”, informed by evaluation, can be used to quickly and effectively provide essential just-in-time research-related education in the complex and evolving world of clinical and translational science. METHODS/STUDY POPULATION: “Learning shots” are an educational tool, originally developed by the University of Virginia IRB for Health Sciences Research, that cover a broad spectrum of methodological, regulatory, and ethical topics in research. They are designed to be responsive to adult learners, a rapidly changing research environment, and the need for flexible offerings. Learning shots target different groups involved in research including clinical research coordinators, investigators, and trainees. A survey was used to assess the role of learning shots in meeting learning needs. Moving forward, continuous evaluation will occur through the addition of tracking and a short evaluation survey to each learning shot. RESULTS/ANTICIPATED RESULTS: The University of Virginia has an online library of over 30 learning shots. Learning shots are used to cover foundational topics (e.g. GCP) as well as more specialized topics (e.g. comparative effectiveness research). They can also be used to quickly respond to breaking issues (e.g. single IRB review). In an initial survey targeting University of Virginia clinical research coordinators, 54 (68%) of 79 respondents reported having viewed a learning shot. Among those who had, 41 (84%) of 49 respondents reported that learning shots were helpful to their learning needs. Continuous evaluation is expected to further inform how learning shots meet clinical and translational science education needs. DISCUSSION/SIGNIFICANCE OF IMPACT: Learning shots are an innovative and versatile educational tool for clinical and translational science that can be used to quickly and effectively convey important research information in response to an increasingly complex research environment and diverse learner needs.

Objectives/Goals: Micro-credentials (MCs) or digital badges are short programs designed to allow learners to gain knowledge and skills at their own pace to tailor their professional development. This study aims to examine the characteristics of learners completing MCs and explore their motivation for pursuing MCs through the University at Buffalo Clinical and Translational Science Institute (CTSI) program. Methods/Study Population: Currently, the CTSI offers five MCs in Effective Teaching, Good Clinical Practice, Responsible Research, Scientific Communication, and Translational Teamwork. Individuals who completed an MC (2019–2024) were identified by the UB Office of Micro-credentials. An invitation email and two reminders were sent to all individuals who received MCs asking them to complete a short online survey in July-August 2024. The survey included three questions about the type(s) of MCs completed, learners’ motivation for pursuing MCs, and perceived or actual benefits of completing an MC. The questions included multiple choice, select all that apply, and open-ended format, respectively. The survey was sent using Google Forms; data were analyzed using descriptive statistics. We received 25 completed surveys (29% response rate). Results/Anticipated Results: Since 2019, 85 individuals completed MCs at Buffalo CTSI including 21 faculty, 18 trainees, 26 students, and 20 staff. The most popular MC, Responsible Research (65% of completers), is based on the Responsible Conduct of Research series, which consists of modules on authorship ethics, ethical use of animals (IACUC) and human subjects (IRB), conflicts of interest/commitment, and responsible data acquisition and management. We found that 33% of responders were motivated to obtain the MC to advance their career and for professional development, 30% for lifelong learning, and 23% intended to use the badges to showcase their proficiency to potential employers. The greatest benefits reported were to obtain knowledge/skills for their professional career (46%) and improve their ability to receive research funding (14%). Discussion/Significance of Impact: Micro-credentials are valuable learning tools to stay current on changing research requirements, with ability to engage asynchronously. Badges also provide unique professional development opportunities for students and research workforce (staff and community stakeholders) who have limited resources (time and money).

OBJECTIVES/GOALS: Almost 8 million Americans live with disability caused by stroke. However, recent advances in stroke rehabilitation are costly and lack resemblance to activities of daily living. The goal of this study was to develop a rehabilitation platform to increase stroke patients paretic limb use using inexpensive virtual reality and exoskeleton devices. METHODS/STUDY POPULATION: We conducted a feasibility study with 2 hemiplegic stroke participants. They reached for targets in a virtual reality environment using both hands. They completed 162 reaches divided into 3 blocks. Following baseline, we used an exoskeleton to provide 50% arm weight compensation to the paretic limb and used wrist weights to provide 50% arm weight resistance to the non-paretic limb. We removed the exoskeleton and wrist weights during the retention block. We used electromyography to approximate muscle activity in the biceps brachii. Relative contribution (RC) was calculated as the displacement of the paretic arm divided by the sum of displacements for both arms. Muscle contribution (MC) was calculated as the root mean square of paretic arm muscle activity divided by the sum of activity for both arms. RESULTS/ANTICIPATED RESULTS: During baseline, RC of the impaired limb was 44% and 48%, and MC of the impaired bicep was 43% and 35% in two mild to moderately impaired patients (Fugl-Meyer Upper Extremity scores of 43 and 37, respectively). During loading, RC increased by 5.6% and 1.1% and MC decreased by 8.3% and 11.8%. These data suggest hemiplegic stroke participants alter limb coordination when our device normalizes muscular output asymmetries between limbs. Importantly, these results closely match data from our previous work in 12 healthy controls, where we found a 2% increase in RC is significantly predicted by a 11% decrease in MC. By collecting more data on stroke patients, we will quantify this tradeoff between coordination and muscle activity modulation, allowing us to optimize the exoskeleton mechanics to maximize paretic limb use. DISCUSSION/SIGNIFICANCE: We demonstrate our platform is well tolerated by mild to moderately impaired stroke patients; this feasibility study forms the basis for low cost at-home technologies for stroke rehabilitation. With further development, clinicians can use our platform to fine-tune the level of limb constraint based on the individual needs of the patient.

OBJECTIVES/SPECIFIC AIMS: Translational Science 101 aims to: (1) Orient the public to the field of clinical and translational science; (2) Provide a brief overview of each phase of translation (T0-T4); (3) Provide real-world examples of clinical and translational researchers and research projects that have directly impacted patients; (4) Provide learners with information on how they can become involved in clinical and translational science through many different avenues (study volunteer, student, faculty member, or study coordinator). METHODS/STUDY POPULATION: The primary audience for Translational Science 101 is the general public and media outlets who are interested in learning more about clinical and translational science and how this research is improving population health. The University of Rochester Clinical and Translational Science Institute created the course in order inform the public about the field of clinical and translational science, orient the public to the types of research that fall under the translational science umbrella, and demonstrate how translational research impacts populations. The Coursera Massive Open Online Course (MOOC) platform was selected to host the course in order promote the greatest level of exposure and also to expand the educational reach of the UR-CTSI to new external audiences. The course was constructed from scratch utilizing the Community of Inquiry (CoI) framework, an approach that is often utilized to guide the design and construction of asynchronous online coursework. CoI highlights the elements of social presence, cognitive presence and teaching presence as key factors impacting the educational experience learners have when enrolled in an online course. Discussion boards, embedded quizzes, and end of module quizzes were integrated in to the course design to promote learner engagement, collaborative learning, and interactions among learners. The “storytelling” instructional strategy is the backbone of the Introduction to Clinical Science modules, with various researchers from the University of Rochester Medical Center explaining their lines of research and how the research impacts patients and communities. Educational research has shown that there are many benefits to including storytelling in instruction (Green, 2004; Geanellos, 1996), including: (1) Stories create interest: The narrative structure increases learner interest and engagement as they are drawn in to a good story. (2) Stories create a more personal link between the learner and the content: Storytelling allows exploration of shared lived experiences without the demands of practice and allows students to make connections between the shared experiences and their own previous experiences and knowledge. (3) Stories provide a structure for remembering course materials: The inclusion of stories facilitates remembering because it is easier to remember a story rather than a list of disparate facts, and stories evoke vivid mental images which are an excellent cue for recall. (4) Stories are a familiar and accessible form of sharing information: Storytelling aids in overall learner understanding as it is a nonthreatening way of sharing information. Storytelling can also enhance course discussions as students feel more at ease discussing a story than discussing abstract or new concepts that they are still in the process of mastering. RESULTS/ANTICIPATED RESULTS: Introduction to Translational Science was launched on October 16, 2017, and is automatically scheduled to begin a new session every 3 weeks. To date the course has reported the following analytics: (1) 2308 learners have visited the course page, (a)476 learners have enrolled in the course; (b) 244 learners are currently active in the course; (c) 11 learners have completed all of the requirements of the course. (2)Learners by Continent, (a) North America 31%; (b) Asia 30%; (c) Europe 23%; (d) Africa 9%;(e) South America 5%; (f) Oceania 2%. (2) Learners by Country: Learners have come from 84 different countries from around the world. The 15 highest enrollment numbers are: (a) USA 25%, (b) India 11%, (c) Egypt 3.7%, (d) United Kingdom 3.4%, (e) Mexico 3.2%, (f) Brazil 2.8%, (g) China 2.8%, (h) Saudi Arabia 2.2%, (i) Spain 2.2%, (j) Germany 1.7%, (k) Russian Federation 1.7%, (l) Malaysia 1.5%, (m) Turkey 1.5%, (n) Italy 1.5%, and (o) Canada 1.5%. (3) Gender: 48% women and 50% men. (4) Age: (a) 13–17: 0.72%, (b) 18–24: 19.6%, (c) 25–34: 44%, (d) 35–44: 14.4%, (e) 45–54: 8.6%, (f) 55–64: 7.2%, (g) 65+: 3.6%. (5)Highest Education Level o Doctorate Degree: 17%; (a) Professional School Degree: 14%; (b) Master’s Degree: 31%; (c) Bachelor’s Degree: 27%; (d) Associate’s Degree: 2.3%; (e) Some College But No Degree: 4.5%; (f) High School Diploma: 3.8%; (g) Some High School: 0.75%. DISCUSSION/SIGNIFICANCE OF IMPACT: The Massive Open Online Course (MOOC) platform offers new, exciting opportunities for CTSA institutions to create courses and trainings that are accessible by learners all over the world. This greatly expands the educational reach that the CTSA education programs can have, moving beyond hub-focused or consortium-focused education to a much broader audience. The expansion of educational reach can promote increased visibility of the CTSA program, encourage collaborations amongst researchers at different institutions, and also inform the public about clinical and translational science, potentially fostering advancement opportunities.

OBJECTIVES/GOALS: The objective of this initiative was to promote MICHR staff’s production of Clinical and Translational Science publications. MICHR leadership approved this initiative, including an evaluation plan with measurable outcomes goals, and contracted with an experienced scientific writing coach with over 20 years of experience working with CTSAs. METHODS/STUDY POPULATION: A sequential mixed methods program evaluation designs was used. Pre- and post-surveys were used to measure participating staff’s gain in skill, understanding & satisfaction. An interview with the instructor was then conducted to characterize staff performance, and identify possible areas of programmatic improvement. This initial phase of the program evaluation was conducted in the Summer of 2023. The results were used to inform an expansion of the program to include more staff in the the Fall of 2023. Pre- and post-program surveys of the participants were conducted and interviews with each program participant were conducted. Finally, interviews with non-participating staff were conducted to assess their need for writing support and the challenges and facilitators of their scientific writing. RESULTS/ANTICIPATED RESULTS: Preliminary evaluation results obtained in the summer of 2023 were positive. All participants completed the course, and spent an average of 3.3 hours working between sessions. Six manuscripts were developed, five of which are being readied for submission and one submitted as of August 2023. Analysis of the pre-and post-program surveys indicated that all participants gained writing skill and authorship knowledge. Specifically, they gained confidence in 7 writing skills and 6 first-author roles evaluated during the course. All participants were satisfied with their experience and recommended the course to their colleagues, and the course instructor was also satisfied with the course. However, the participants noted that competing work demands and variable preparation hindered their work in the course. DISCUSSION/SIGNIFICANCE: With the increasing focus on Clinical and Translational Science taking place across the CTSA Consortium it is important to involve research staff in paper writing teams, including in first-author roles. Professional development in scientific writing can support Clinical and Translational Research staff contributing to this emerging science.

OBJECTIVES/SPECIFIC AIMS: This study considered how threat appraisal and religious social support associate with subjective well-being and subjective experience of pain. Appraisal in this study refers to the individual’s perception and interpretation of the significance of learning of his/her HIV status. The study incorporated the stress-buffering model to propose that the beneficial effects of religious social support will modify the association between threat appraisal and well-being for PLHIV in a palliative care setting. Well-being was assessed both as the participant’s subjective report of their well-being, and their subjective report of their experience with bodily pain. Participants’ subjective report of well-being was hypothesized to be inversely associated with threat appraisal, and positively associated with religious social support. Subjective experience with bodily pain was hypothesized to be directly associated with threat appraisal, and inversely associated with religious social support. It was further also hypothesized that religious social support modifies the impact of threat-appraisal on well-being such that higher levels of religious social support reduce the observed effect of threat appraisal. METHODS/STUDY POPULATION: This was a cross-sectional study using baseline data from a randomized clinical trial–the FACE palliative care study in Washington, DC (FACE: FAmily CEntered Advance Care Planning). Participants were PLHIV who received their HIV care from 5 Washington, DC hospital-based HIV-specialty clinics. The FACE 3000 study paired participants into dyads of patient and surrogate decision-maker. The patient is a PLHIV for whom the advanced care planning care study is geared. The surrogate decision-maker is considered the patient’s healthcare proxy who agrees to honor and advocate for the patient’s treatment preferences, if the patient were unable to communicate with the health care team directly. Some surrogates are HIV positive, however due to their role as the patient’s healthcare proxy, some of their surveys contain different content from those of the patient’s. Potentially eligible participants in the FACE study received a secondary screening to determine eligibility to ensure competency to participate in end-of-life decision making. For this analysis, only the patient data was used. RESULTS/ANTICIPATED RESULTS: Subjective well-being showed significant associations with total threat appraisal, and four threat appraisal sub-constructs. Those with lower threat appraisals reported higher values of well-being compared to those with higher threat appraisals. Results from the regression analysis indicated that only one of the threat appraisal sub-constructs was significantly associated with a participant’s subjective experience of pain. Overall, religious social support did not seem to buffer the effect of threat appraisal on well-being or subjective experience of pain. Findings from this study suggest that subjective well-being is associated with cognitive threat appraisal and this finding could assist PLHIV and their caregivers in understanding the coping processes of HIV-infected people. DISCUSSION/SIGNIFICANCE OF IMPACT: Due to stigmatization, an HIV diagnosis can influence a person’s physical, behavioral, psychological, and even spiritual health (McIntosh & Rosselli, 2012). As a stressor, it can compromise immune function to worsen the effects of the infection, while mentally depressing an individual and contributing to adverse coping mechanisms (e.g. alcohol consumption, drug use) (McIntosh & Rosselli, 2012). How someone copes with stress (threat appraisal) may contribute to health-promoting or health-damaging behaviors (Fife, Scott, Fineberg, & Zwickl, 2008). Hence, the quality of life of those managing HIV/AIDS remains a pressing concern. Findings from this study suggest that Lazarus and Folkman’s theoretical framework on the cognitive appraisal of threat could assist PLHIV and their caregivers in understanding the coping processes in PLHIV. For service providers, recognizing early threat appraisals and damaging coping mechanisms can be useful, especially for patients receiving an initial HIV diagnosis. For example, an understanding of the patient’s HIV appraisal can provide insight into the barriers to optimal care and adherence to ART and, potentially, help to reduce these barriers (Anderson, 1995). Furthermore, with the advancements of HIV medication, living with HIV has become a chronic condition, though as a stressor, it also poses long-term effects on the psychopathology of an individual living with HIV(McIntosh & Rosselli, 2012). Studies such as this study can help illuminate interventions aimed at reducing the psychological impact of HIV on a person’s life. For example, support groups have been developed and structured to provide social support and have been demonstrated to increase the perceived well-being among PLHIV (Hyde, Appleby, Weiss, Bailey, & Morgan, 2005). This has further expanded into the consideration of online-based support groups for PLHIV (Blackstock, Shah, Haughton, & Horvath, 2015). In another light, but still within psychosocial interventions for managing HIV infection, mindfulness meditation has been used pervasively in studies assessing its use as an intervention to reduce depression and perceived stress in people living with HIV in order to increase both physical and psychological health (Moskowitz etal., 2015). Interventions, such as mindful meditation, have risen as we understand more about appraisal pathways and coping strategies (such as seeking social support), and how they influence both physiological and psychological responses (Moskowitz etal., 2015) to affect the health of a person. Therefore, longitudinal research aimed toward management of the psychological and social consequences of HIV is central to promoting an accurate understanding of the quality of life for PLWH (Anderson, 1995).

ABSTRACT IMPACT: This study provides insights on how to replicate a successful initiative for preventing unintended teen pregnancy. OBJECTIVES/GOALS: Reducing unintended teen pregnancy is a national health priority, and a recommended strategy is to increase awareness and availability of long-acting reversible contraception (LARC). The Rochester LARC Initiative did this, and teen LARC use rose from 4% to 24%. The goal of this study is to determine key elements for replicating the intervention. METHODS/STUDY POPULATION: Our initiative used an innovative approach we call ‘community detailing’ to deliver education about LARC to adults working with teens. We analyzed the intervention goals, design components, implementation strategies, and public health outcomes. Our analysis was informed by the CDC model for Promoting Science-Based Approaches to Teen Pregnancy Prevention Using Getting to Outcomes (PSBA-GTO), Diffusion of Innovations, and RE-AIM framework for implementation outcomes. We compared our model with characteristics of LARC-promotion efforts, as well as successful health education campaigns. We tabulated the components of our intervention across theoretical domains, aiming to determine essential elements of effective design, adaptation, and dissemination & implementation. RESULTS/ANTICIPATED RESULTS: The initiative incorporated multiple components common to successful health education programs: measurable behavior-change outcomes; formative research before roll-out; tailored communications for different audiences; speakers who were credible, knowledgeable and skilled communicators; content that was new to recipients and essential for decreasing barriers to desired behaviors. It included elements of successful LARC promotion/teen pregnancy prevention programs, such as organizing information by effectiveness of methods and using youth-empowering messaging. It differed from other successful programs by offering discussions to adults who work with teens in both medical and community settings. This analysis also highlights unintended positive ripple effects. DISCUSSION/SIGNIFICANCE OF FINDINGS: These results establish how community detailing is effective for disseminating actionable information about the safety, efficacy and availability of LARC. These insights could inform other prevention initiatives. An anticipated practical product of this study will be a user-friendly manual for replicating the LARC Initiative in other locations.

OBJECTIVES/SPECIFIC AIMS: To characterize the CD4+ T-cell response during CTLA-4 blockade immunotherapy with ipilimumab in patients with metastatic melanoma by correlating cytokine profiles with phenotypic changes in the intratumoral lymphocyte compartment of tumor biopsies obtained before and after treatment. METHODS/STUDY POPULATION: Peripheral blood mononuclear cell samples were obtained from patients with metastatic melanoma undergoing monotherapy with ipilimumab via the Interdisciplinary Melanoma Cooperative Group at New York University Langone Medical Center. We isolated CD4+ T-cells and used a cytometric bead array assay following in vitro activation with anti-CD3, anti-CD28 antibodies to characterize cytokine expression profiles by quantifying IFN gamma, IL-2, IL-4, IL-6, IL-10, IL-17, and TNF-α at 5 time points during therapy. In total, 53 peripheral blood samples were included from 12 patients. To correlate cytokine profiles with CD4+ T-cell phenotypes in the intratumoral lymphocyte compartment, multiplex immunofluorescence was performed using CD4, CD8, CCR7, CD45RO, and FOXP3 antibodies on tumors before and after treatment with ipilimumab. RESULTS/ANTICIPATED RESULTS: Patients with evidence of clinical benefit (CB), as defined by having achieved partial response or stable disease, were compared with nonresponders (NR). All patients had an increase in IFN-γ, IL-2, and IL-10 secretion by CD4+ T-cells during ipilimumab therapy. NR had a statistically higher increase in all 3 cytokines. Mean IL-10 secretion was 22.3-fold higher compared with patients with CB (p value 0.0458; 95% CI=0.6676–43.89). Mean IFN-γ secretion was 12.4-fold higher from baseline levels in NR compared with CB (p value 0.046; 95% CI=0.3589–24.35). Mean IL-2 secretion was 6.9-fold higher in NR compared with CB (p value 0.032; 95% CI=0.9688–12.75). There were no statistically significant differences seen in the secretion of IL-4, IL-6, IL-17, or TNF-α. Multiplex immunofluorescence for immune profiling of 20 pre and post treatment tumor biopsies is ongoing. We expect to see distinct intratumoral lymphocyte compartment changes which correlate with clinical response and the above described differential cytokine profiles. Specifically, we anticipate CB patients will have increased intratumoral effector T-cells and decreased regulatory T-cells when compared with their NR counterparts. DISCUSSION/SIGNIFICANCE OF IMPACT: Cytokine expression profiles of peripheral blood CD4+ T-cells have not been previously correlated with patient response in patients undergoing treatment with ipilimumab. We describe distinct secretion profiles for IFN-γ, IL-2, and IL-10 for CB Versus NR patients. NR had a statistically higher increase in IL-10, an inhibitory cytokine which typically indicates upregulation of regulatory T-cells and consequent immune escape. Increased secretion of IL-2 and IFN-γ suggests skewing towards a Th1 type, anti-tumor effector T-cell response; these cytokines increased with ipilimumab treatment in both patient groups. However, the mean increase was several fold higher in NR. Recent evidence suggests loss of the interferon gamma pathway in tumor cells confers resistance to anti-CTLA4 therapy. Chronic IFN-γ secretion is associated with an exhausted T-cell phenotype and impaired tumor rejection. Therefore, higher increases in IFN-γ secretion by CD4+ T-cells in NR suggest impaired IFN-γ dependent tumor rejection in these patients. Our findings suggest IFN-γ, IL-2, and IL-10 cytokine expression profiles can be useful as biomarkers for response to ipilimumab treatment.

Composite endpoints can encode multiple pieces of information and are increasingly adopted in clinical trials. Advocacy for using composite endpoints began decades ago in cardiovascular trials, leading to incorporation of patient-oriented outcomes and consideration of a hierarchical ranking system. The use of composite endpoints in coronavirus disease (COVID-19) trials has evolved similarly. We conducted a literature review to investigate the use of composite endpoints in acute heart failure and COVID-19 clinical trials. The results showed more frequent use of patient-oriented outcomes and ordinal composite endpoints in COVID-19 trials, which might be driven by global consensus on a set of common outcome measures.

Older adults are often underrepresented in clinical research, even though older adults are major consumers of novel therapies. We present major themes and recommendations from the 2021 "Inclusion of Older Adults in Clinical Research" Workshop, convened by the Clinical and Translational Science Award (CTSA) Inclusion of Older Adults as a Model for Special Populations Workgroup and the Research Centers Collaborative Network (RCCN). The goal of this workshop was to develop strategies to assist the research community in increasing the inclusion of older adults in clinical research. Major identified barriers include historical lack of federal guidelines, ageist biases and stereotypes, and lack of recruitment and retention techniques or infrastructure focused on older adults. Three key recommendations emerged: 1) engaging with the policymaking process to further promote inclusion; 2) using the CTSA Workgroup Presentation Materials Library and other resources to overcome ageism, and 3) building institutional capacity to support age inclusion.

OBJECTIVES/GOALS: Adolescent and young adult (AYA) patients, diagnosed with cancer between 15 and 39 years of age, often have worse outcomes compared to younger children and older adults. We will characterize age differences in acuity and severity of illness at initial presentation, as a measure for health outcomes, in patients with new diagnoses of leukemia or lymphoma. METHODS/STUDY POPULATION: We will perform a single institution-based, retrospective analysis of a cohort of pediatric oncology patients at Children’s Healthcare of Atlanta (CHOA) who were diagnosed with leukemia or lymphoma from 2010 to 2018. Data will be abstracted from the CHOA medical record and cancer registry. We will construct a severity score, with one point for 1) admission to the Intensive Care Unit (ICU), 2) ICU-level requirements at admission, 3) stage IV or metastatic disease, and 4) white blood cell count over 100,000/microliter. We will associate this score with age at presentation using logistic regression models among patients overall and stratified by disease type. All regression models will adjust for confounders (e.g., health insurance, race and ethnicity, and local-area social vulnerability level). RESULTS/ANTICIPATED RESULTS: Previous literature has shown increased cancer incidence and mortality in AYAs compared to younger children. Therefore, we hypothesize that AYA patients with a new diagnosis of leukemia or lymphoma will have a higher acuity and severity of illness at presentation than younger patients. We conducted a pilot study analyzing acuity and severity of illness by age, race, ethnicity, and insurance status. Bivariate comparisons suggested patients aged 10 and older were as likely as those younger to have a severity score of more than 0 at diagnosis (OR=0.661 , 95% CI 0.43-1.01). However, this result was collapsed across all hematologic malignancies, did not encompass the entire cohort, and did not address possible confounders; we anticipate our estimates will be different taking these factors into account. DISCUSSION/SIGNIFICANCE: Our work will be the first steps in creating a validated tool to understand disease acuity and severity. By using this tool to characterize presentation by disease type and age, we will identify unmet needs prior to an initial diagnosis of cancer. Our findings inform strategies toward narrowing age disparities in outcomes for AYA hematologic cancers.

ABSTRACT IMPACT: Framework is designed to aid selection of implementation strategies to promote adoption and sustainability of EBP to improve health care quality, safety and value. OBJECTIVES/GOALS: An application-oriented implementation framework based on Diffusion of Innovation theory, identified 81 strategies for clinician-use within four implementation phases. The goal of this research was to further specify strategies based on emerging implementation science and establish external validity. METHODS/STUDY POPULATION: An iterative mixed-methods process guided framework revisions. First, individuals (n=1,578) requesting use of the framework over the last seven years were sent an electronic questionnaire. Evaluation captured usability, generalizability, accuracy of phases, and implementation phases for each of 81 strategies. Second, nurses who use the framework pile sorted strategies for multidimensional scaling and hierarchical analysis using Anthropac software. Third, a panel of five EBP/implementation experts used data and a consensus process to add clarity with the naming, and further specify strategies. RESULTS/ANTICIPATED RESULTS: Survey respondents (n = 127, 8% response) were nurses (94%), at least Master’s educated (94%), from health systems (52%) or academia (31%), in the U.S. (84%). The framework, rated on a four-point scale (1 = not/strongly disagree to 4 = very/strongly agree; reported are ratings 3 and 4) was deemed useful (92%), generalizable (100%), and with accurate timing (96%). 51 participants linked strategy timing to a single phase (54 strategies, 66.7%, p<0.05, Cochran’s Q); most strategies (30) matched the original model. Pile sorting (n=23) generated a concept map and hierarchical clusters of groups. Experts used these data and implementation science to specify each strategy and revise the framework. DISCUSSION/SIGNIFICANCE OF FINDINGS: The Iowa Implementation for Sustainability Framework (IISF) offers a typology to guide implementation for healthcare improvements. This study specifies 77 implementation strategies, confirms four phases, identified 10 domains, and begins to establish external validity for the framework.

OBJECTIVES/SPECIFIC AIMS: Platelets govern signal-dependent inflammatory responses by leukocytes. Although dysregulated inflammation is common in older adults, platelet-leukocyte signaling events and downstream inflammatory gene synthesis in aging is not known. METHODS/STUDY POPULATION: Highly-purified platelets and monocytes were isolated from healthy older (age>60, n=27) and younger (age<45, n=36) adults and incubated together in autologous and nonautologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of activated platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in older and younger adults. Differentially expressed candidates in aged platelets were validated and recombinant granzyme A (in the presence and absence of TLR4 and Caspase-1 inhibition) identified putative ligands controlling inflammatory gene synthesis. RESULTS/ANTICIPATED RESULTS: In unstimulated or activated conditions, monocyte chemoattractant protein 1 (MCP-1) and interleukin-8 (IL-8) synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous activated platelets, monocytes from older adults synthesized significantly greater MCP-1 (867.150 vs. 216.36 ng/mL, p<0.0001) and IL-8 (41.5 vs. 9.2 ng/mL, p<0.0001) than younger adults. Nonautologous, or switch experiments, demonstrated that aged platelets were sufficient for upregulating MCP-1 and IL-8 synthesis by monocytes. Surprisingly, classic platelet proteins known to signal to monocytes and induce MCP-1 synthesis (p-selectin, RANTES, and PF4) were not increased in platelets from older adults. Using RNA-seq followed by validation via RT-PCR and immunoblot, we identified candidate platelet molecules increased in aging that mediate platelet-monocyte signaling and pro-inflammatory gene synthesis. We confirmed that granzyme A (GrmA), a serine protease not previously identified in platelets, is present in human platelets at the mRNA and protein level. GrmA is secreted by activated platelets in signal-dependent fashion. Moreover, GrmA in platelets is significantly increased in aging (~9-fold vs. younger adults). Blocking GrmA inhibited MCP-1 and IL-8 synthesis in older adults. Finally, we uncovered that platelet GrmA signaling to monocytes is regulated through TLR4 and Caspase-1. DISCUSSION/SIGNIFICANCE OF IMPACT: Human aging is associated with reprogramming of the platelet transcriptome. A previously unrecognized protein in platelets, GrmA, is increased in aging and causes increased MCP-1 and IL-8 gene synthesis by target monocytes in a TLR4 and Caspase-1 dependent mechanism. Increased platelet GrmA in aging may contribute to injurious inflammatory responses common in older adults.

ABSTRACT IMPACT: I hope that our work will improve surveillance endoscopy experiences, by engaging both patients and providers. OBJECTIVES/GOALS: A large proportion of colonoscopies are performed for post-polypectomy surveillance. Data show that there is overuse of surveillance for low-risk adenomas (LRAs), which can be attributed to patient and provider factors. The objective is to understand patient and provider perspectives for decision-making for LRA surveillance colonoscopy. METHODS/STUDY POPULATION: Semi-structured, one-on-one virtual interviews of patients and providers are currently being conducted at Richard L. Roudebush VA Medical Center and Eskenazi Health. Using a criterion sampling approach, we identified patients 50-75 years of age who had a screening colonoscopy with finding of LRAs, and providers in primary care and gastroenterology, at each site. We plan to recruit at least 8 patients and 8 providers from each site until thematic saturation. Domains that will be covered include: perceived involvement with surveillance decision-making; experiences with, and preferences for, communication about test results; and barriers and facilitators to undergoing colonoscopy. A 3-phase approach, comprising immersion, reduction, and interpretation, is being used to collect and analyze data. RESULTS/ANTICIPATED RESULTS: This study is currently in the recruitment phase and results will be forthcoming. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding decision-making for LRA surveillance colonoscopy will inform future interventions to improve endoscopic resource use and efficiency while improving patient and provider experiences with endoscopic care coordination.

OBJECTIVES/SPECIFIC AIMS: We previously developed a translationally relevant model of temporal lobe epilepsy (TLE) in which glutamine synthetase is irreversibility inhibited by methionine sulfoximine (MSO), resulting in spontaneous seizures and dentate hilar neuron loss. The objective of this study was to determine the effects of chronic BCAA ingestion on neuronal viability in the dentate hilus in the MSO model of TLE. METHODS/STUDY POPULATION: Sixteen rats were randomly divided into 2 groups: 8 rats drank a 4% aqueous solution of all 3 BCAAs (BCAA group) ad libitum for 31 days, and the other 8 rats drank regular water (control group) for the same period. After 10 days of drinking, a microinfusion cannula (Alzet osmotic pump, model 2004) was surgically implanted in the right dentate gyrus to continuously infuse MSO at a rate of 0.625 g/hour for 28 days. After 31 days of drinking, rats were perfused transcardially with 0.9% NaCl followed by 4% paraformaldehyde in phosphate buffer. The brains were removed and fixed, sectioned on a Vibratome at 50-μm thickness, and were mounted on a gelatin-coated slides and stained with NeuN. Neuron counts in the hilar region were performed ipsilateral and contralateral to the infusion site using a stereological technique. RESULTS/ANTICIPATED RESULTS: Rats in the BCAA group had 37% fewer neurons in the ipsilateral dentate hilus than the control group (5.8×10−4±6.8×10−5 vs. 8.9×10−4±5.6×10−5 cells, respectively, p<0.01). Similarly, rats in the BCAA group had 39% fewer neurons in the contralateral dentate hilus than the control group (5.0×10−4±5.8×10−5 vs. 7.0×10−4±3.4×10−5 cells, respectively, p=0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that chronic ingestion of BCAAs aggravates hilar neuronal loss in a translationally relevant rodent model of MTLE. This study gives important insight into how BCAAs may affect neuronal viability. Although the role of BCAAs on seizure activity is poorly understood, these results suggest that BCAAs may play an important role in neurochemical modulation and neurotoxicity.