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Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.

Abstract Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer that affects primarily adolescents and young adults. It is associated with a poor overall prognosis. There is a need to better define risk factors, but small sample size has limited such studies. An FLC patient registry now provides data sufficient for statistically robust inferences. We leveraged a unique patient community–based FLC registry to analyze the prognostic impact of demographic and clinical characteristics evident at diagnosis. Variables were analyzed using Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariable models of 149 patients (88 females and 61 males), female gender was associated with statistically significant improved survival with HR of 0.52 (95% CI 0.29–0.93). Factors evident at diagnosis that are associated with worse survival included the presence of 10 or more tumors within the liver (HR 7.1; 95% CI 2.4–21.04), and metastases at diagnosis (HR 2.17; 95% CI 1.19–3.94). Positive lymph nodes at diagnosis, despite being found significantly associated with worse survival in a univariate analysis, did not remain significant when adjusted for covariates in a multivariable analysis. We found no statistically significant effect of age at diagnosis nor tumor size at diagnosis on survival. Female gender may confer a favorable prognosis in FLC. Established high‐risk prognostic factors that we confirmed in this Registry included the diagnostic presence of numerous intrahepatic tumors, and metastases. This is the first study derived from a FLC patient community–based registry, and highlights how registries of rare tumors can empower patients to meaningfully advance clinical and scientific discoveries.

Abstract Background Risk prediction models are useful tools in clinical decision-making which help with risk stratification and resource allocations and may lead to a better health care for patients. AutoScore is a machine learning–based automatic clinical score generator for binary outcomes. This study aims to expand the AutoScore framework to provide a tool for interpretable risk prediction for ordinal outcomes. Methods The AutoScore-Ordinal framework is generated using the same 6 modules of the original AutoScore algorithm including variable ranking, variable transformation, score derivation (from proportional odds models), model selection, score fine-tuning, and model evaluation. To illustrate the AutoScore-Ordinal performance, the method was conducted on electronic health records data from the emergency department at Singapore General Hospital over 2008 to 2017. The model was trained on 70% of the data, validated on 10% and tested on the remaining 20%. Results This study included 445,989 inpatient cases, where the distribution of the ordinal outcome was 80.7% alive without 30-day readmission, 12.5% alive with 30-day readmission, and 6.8% died inpatient or by day 30 post discharge. Two point-based risk prediction models were developed using two sets of 8 predictor variables identified by the flexible variable selection procedure. The two models indicated reasonably good performance measured by mean area under the receiver operating characteristic curve (0.758 and 0.793) and generalized c-index (0.737 and 0.760), which were comparable to alternative models. Conclusion AutoScore-Ordinal provides an automated and easy-to-use framework for development and validation of risk prediction models for ordinal outcomes, which can systematically identify potential predictors from high-dimensional data.

Summary: The AutoScore framework can automatically generate data-driven clinical scores in various clinical applications. Here, we present a protocol for developing clinical scoring systems for binary, survival, and ordinal outcomes using the open-source AutoScore package. We describe steps for package installation, detailed data processing and checking, and variable ranking. We then explain how to iterate through steps for variable selection, score generation, fine-tuning, and evaluation to generate understandable and explainable scoring systems using data-driven evidence and clinical knowledge.For complete details on the use and execution of this protocol, please refer to Xie et al. (2020),1 Xie et al. (2022)2, Saffari et al. (2022)3 and the online tutorial https://nliulab.github.io/AutoScore/. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

(1) Background: With increasing international travel and mass population displacement due to war, famine, climate change, and immigration, pathogens, such as Staphylococcus aureus (S. aureus), can also spread across borders. Methicillin-resistant S. aureus (MRSA) most commonly causes skin and soft tissue infections (SSTIs), as well as more invasive infections. One clonal strain, S. aureus USA300, originating in the United States, has spread worldwide. We hypothesized that S. aureus USA300 would still be the leading clonal strain among US-born compared to non-US-born residents, even though risk factors for SSTIs may be similar in these two populations (2) Methods: In this study, 421 participants presenting with SSTIs were enrolled from six community health centers (CHCs) in New York City. The prevalence, risk factors, and molecular characteristics for MRSA and specifically clonal strain USA300 were examined in relation to the patients’ self-identified country of birth. (3) Results: Patients born in the US were more likely to have S. aureus SSTIs identified as MRSA USA300. While being male and sharing hygiene products with others were also significant risks for MRSA SSTI, we found exposure to animals, such as owning a pet or working at an animal facility, was specifically associated with risk for SSTIs caused by MRSA USA300. Latin American USA300 variant (LV USA300) was most common in participants born in Latin America. Spatial analysis showed that MRSA USA300 SSTI cases were more clustered together compared to other clonal types either from MRSA or methicillin-sensitive S. aureus (MSSA) SSTI cases. (4) Conclusions: Immigrants with S. aureus infections have unique risk factors and S. aureus molecular characteristics that may differ from US-born patients. Hence, it is important to identify birthplace in MRSA surveillance and monitoring. Spatial analysis may also capture additional information for surveillance that other methods do not.

Abstract Introduction: Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of “informativeness,” highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise. Methods and Results: Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies. Conclusions: We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal liver cancer with no proven effective systemic therapy. Inhibition of the antiapoptotic protein BCL-XL was found to synergize with a variety of systemic therapies in vitro using cells dissociated from patient-derived xenografts (PDX) of FLC or cells dissociated directly from surgical patient resections. As BCL-XL is physiologically expressed in platelets, prior efforts to leverage this vulnerability in other cancers have been hampered by severe thrombocytopenia. To overcome this toxicity, we treated FLC models with DT2216, a proteolysis targeting chimera (PROTAC) that directs BCL-XL for degradation via the von Hippel-Lindau (VHL) E3 ligase, which is minimally expressed in platelets. The combination of irinotecan and DT2216 in vitro on cells directly acquired from patients or in vivo using several xenografts derived from patients with FLC demonstrated remarkable synergy and at clinically achievable doses not associated with significant thrombocytopenia.

OBJECTIVES/GOALS: Low-dose aspirin is an established treatment to prevent preeclampsia, a leading cause of maternal and perinatal complications. Nevertheless, aspirin failure is not uncommon. We are investigating whether a gain-of-function genetic polymorphism in a platelet thrombin receptor is associated with aspirin failure in the prevention of preeclampsia. METHODS/STUDY POPULATION: Women who had preeclampsia in an initial pregnancy who then received low-dose aspirin in a subsequent pregnancy will be evaluated. We will compare between women who developed preeclampsia despite aspirin (aspirin non-responders) to women who did not develop preeclampsia with aspirin treatment (aspirin responders). Specifically, we will evaluate the allelic frequency of a single nucleotide variant (rs773902) in PAR4 thrombin receptor on platelets. This variant is associated with increased platelet function and potentially aspirin resistance. In addition, we will analyze the platelet response to PAR4 activation before and 1 hour after administering a single 81 mg enteric-coated aspirin tablet. RESULTS/ANTICIPATED RESULTS: We hypothesize that the prevalence of the PAR4 variant will be significantly higher among women who had recurrence of preeclampsia despite aspirin therapy. We also postulate that women who developed preeclampsia despite aspirin prophylaxis and have the polymorphism will have increased platelet aggregation in response to activation of PAR4, either by thrombin or peptides that activate the receptor, both at baseline and 1 hour after aspirin administration. DISCUSSION/SIGNIFICANCE: If our hypothesis that aspirin failure in preeclampsia prevention is associated with the gain-of-function polymorphism in the platelet PAR4 thrombin receptor, there may be justification for additional experimental studies to assess whether better pregnancy outcomes can be obtained by targeting thrombin itself using low molecular weight heparin.

Background: Hidradenitis suppurativa (HS) demonstrates high placebo response rates in clinical trials, possibly due to the natural variability of the disease. No quantification of variability in lesion counts of untreated disease has been undertaken. Objective: To quantify the variability of untreated HS. Methods: Deidentified individual patient data from the placebo arms of PIONEER studies were analyzed, and measurements of within-subject coefficients of variation were examined. Variability was stratified by disease-associated variables (Hurley stage, BMI, sex, smoking, family history) and body site. Results: Analysis of within-subject coefficients of variation demonstrated that half of the participants had a middle spread [difference between 75th and 25th percentiles of the subject's abscess and nodule counts] greater than 33% and 40% of their median abscess and nodule counts, and 25% of the subjects had a middle spread greater than 70% and 78% of their median abscess and nodule counts in PIONEER I and II, respectively. Hurley stage 2 participants had significantly greater within-subject variation than Hurley stage 3 patients. Variation was greater in the axillary and groin regions than in other anatomical locations. Limitations: Limitations include the use of precollected clinical trial data. Conclusion: The within-subject variability of the lesion counts in untreated HS was greater than previously appreciated. This has profound effects on outcome measures and the conduct of future clinical trials of HS.

Abstract Introduction: Recognition of faces of family members, friends, and colleagues is an important skill essential for everyday life. Individuals affected by prosopagnosia (face blindness) have difficulty recognizing familiar individuals. The prevalence of prosopagnosia has been estimated to be as high as 3%. Prosopagnosia can severely impact the quality of life of those affected, and it has been suggested to co-occur with conditions such as depression and anxiety. Methods: To determine real-world diagnostic frequency of prosopagnosia and the spectrum of its comorbidities, we utilized a large database of more than 7.5 million de-identified electronic health records (EHRs) from patients who received care at major academic health centers and Federally Qualified Health Centers in New York City. We designed a computable phenotype to search the database for diagnosed cases of prosopagnosia, revealing a total of n = 902 cases. In addition, data from a randomly sampled matched control population (n = 100,973) were drawn from the database for comparative analyses to study the condition’s comorbidity landscape. Diagnostic frequency of prosopagnosia, epidemiological characteristics, and comorbidity landscape were assessed. Results: We observed prosopagnosia diagnoses at a rate of 0.012% (12 per 100,000 individuals). We discovered elevated frequency of prosopagnosia diagnosis for individuals who carried certain comorbid conditions, such as personality disorder, depression, epilepsy, and anxiety. Moreover, prosopagnosia diagnoses increased with the number of comorbid conditions. Conclusions: Results from this study show a wide range of comorbidities and suggest that prosopagnosia is vastly underdiagnosed. Findings imply important clinical consequences for the diagnosis and management of prosopagnosia as well as its comorbid conditions.

The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar’s primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development.

Abstract Introduction: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD in part due to a consequence of impaired hepatic fructose metabolism. Preclinical data emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to determine if two weeks of excess fructose consumption significantly alters gut microbiota or permeability in humans. Methods: We performed a pilot double-blind, cross-over, metabolic unit study in 10 subjects with obesity (body mass index [BMI] 30–40 mg/kg/m2). Each arm provided 75 grams of either fructose or glucose added to subjects’ individual diets for 14 days, substituted isocalorically for complex carbohydrates, with a 19-day wash-out period between arms. Total fructose intake provided in the fructose arm of the study totaled a mean of 20.1% of calories. Outcome measures included fecal microbiota distribution, fecal metabolites, intestinal permeability, markers of endotoxemia, and plasma metabolites. Results: Routine blood, uric acid, liver function, and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (including Akkermansia muciniphilia), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation, and plasma metabolites were essentially unchanged by either intervention. Conclusions: In contrast to rodent preclinical findings, excess fructose did not cause changes in the gut microbiome, metabolome, and permeability as well as endotoxemia in humans with obesity fed fructose for 14 days in amounts known to enhance NAFLD.

Recurrent skin and soft tissue infections (SSTI) caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) or Methicillin-Sensitive Staphylococcus aureus (CA-MSSA) present treatment challenges. This community-based trial examined the effectiveness of an evidence-based intervention (CDC Guidelines, topical decolonization, surface decontamination) to reduce SSTI recurrence, mitigate household contamination/transmission, and improve patient-reported outcomes. Participants (n = 186) were individuals with confirmed MRSA(+)/MSSA(+) SSTIs and their household members. During home visits; Community Health Workers/Promotoras provided hygiene instructions; a five-day supply of nasal mupirocin; chlorhexidine for body cleansing; and household disinfecting wipes (Experimental; EXP) or Usual Care Control (UC CON) pamphlets. Primary outcome was six-month SSTI recurrence from electronic health records (EHR). Home visits (months 0; 3) and telephone assessments (months 0; 1; 6) collected self-report data. Index patients and participating household members provided surveillance culture swabs. Secondary outcomes included household surface contamination; household member colonization and transmission; quality of life; and satisfaction with care. There were no significant differences in SSTI recurrence between EXP and UC in the intent-to-treat cohort (n = 186) or the enrolled cohort (n = 119). EXP participants showed reduced but non-significant colonization rates. EXP and UC did not differ in household member transmission, contaminated surfaces, or patient-reported outcomes. This intervention did not reduce clinician-reported MRSA/MSSA SSTI recurrence. Taken together with other recent studies that employed more intensive decolonization protocols, it is possible that a promotora-delivered intervention instructing treatment for a longer or repetitive duration may be effective and should be examined by future studies.

OBJECTIVES/GOALS: There is universal recognition of the importance of team science and team leadership. We have developed a semi-quantitative translational science specific team leadership competency assessment tool and have begun implementation studies to assess the impact of personalized feedback on the team science leadership skills of KL2 Clinical Scholars. METHODS/STUDY POPULATION: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to concretize the relevant constructs, then used these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively create domain-specific survey items. Further discussion helped refined the number, grouping, and wording. Scholars also contributed feedback in item development. We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars, and having each Scholar rate themselves. Each item was answered using a six-point Likert scale where a low score indicated poor expression and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Incorporation into a REDCap data base made consenting and rating process by TSE’s and the Scholars straightforward. The a priori domains (Foundational Leadership Competencies, Professionalism, Team Building and Team Sustainability, Appropriate Resource Use and Study Execution, and Regulatory Accountability) had high internal validity and good internal factor structure. The congruence between TSE and Scholar self-ratings were uniformly high, and discordance was often a function of “confidence” and “modesty” on the part of the scholar, rather than deficiency. Supporting comments were informative about performance barriers and mechanisms for improvement. Return of results allowed for the exploration of training gaps. Scholars were surveyed to gauge their reaction to the formal feedback. DISCUSSION/SIGNIFICANCE OF IMPACT: This quantification of team science leadership constructs has allowed for A)- the articulation of constructs essential for successful Translational Scientists to acquire during their training, B)- identification of gaps in that training and skill set, and C)- mechanisms for bolstering any identified gaps in these essential leadership constructs. CONFLICT OF INTEREST DESCRIPTION: None

OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.

OBJECTIVES/GOALS: To describe principles, best practices, and techniques recommended to instill deep understanding of the application and interpretation of statistical techniques and statistical inference among translational scientists and trainees, that best support the concepts of scientific Rigor, Reproducibility and Reporting. METHODS/STUDY POPULATION: Each of the six New York City Area Biostatistics, Epidemiology and Research Design (BERD) resources have strong educational programs, novel curricular components, and creative strategies, implemented by award winning educators. To capitalize on shared knowledge, innovation, and resources, the six teams formed the New York City Area BERD Collaborative (NYC-ABC) comprised of BERD resources from Mt. Sinai, Cornell, Einstein, Columbia, Rockefeller, and NYU. The collaborative suggests principles, concepts, tools and approaches to support the concepts of scientific Rigor, Reproducibility and Reporting in translational science. RESULTS/ANTICIPATED RESULTS: Principles: Value of team science approach and including biostatisticians early and often.Carefully designing experiments to reduce bias and increase precision.Trainees’ focus is often on “statistical significance” and the p-value. Consequences of data dredging/p-hacking, and the impact of sample size and other factors on statistical significance.Emphasizing the effect size and answering the scientific hypothesis when reporting results.Statistical code used to produce results should be well annotated and raw data posted online to enhance reproducibility. Approaches: Incorporate effective multiple modalities (i.e. didactic, demonstrative, hands on workshops, applications, and tools).Approach from “the drivers’ seat” perspective, rather than strictly mathematical.Endorse flipped classroom approach

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 possibleQualifying and monitoring suppliers, testing laboratories, in-house departments, and Contract Drug Manufacturing Organizations (CDMO)Bringing together the deliverables for the IND CMC sectionWhere and how to leverage available products and science to simplify safe and reliable production

ABSTRACT IMPACT: Our implementation model translates two evidence-based nutritional and behavioral interventions to lower blood pressure, into a community-based intervention program for seniors receiving congregate meals. OBJECTIVES/GOALS: The Rockefeller University, Clinical Directors Network, and Carter Burden Network received an Administration for Community Living Nutrition Innovation grant to test whether implementation of DASH-concordant meals and health education programs together lower blood pressure among seniors aging in place. METHODS/STUDY POPULATION: n=200, >60 yr, >4 meals/week at CBN; engagement of seniors/stakeholders in planning and conduct; Advisory Committee to facilitate dissemination; menus aligned with Dietary Approaches to Stop Hypertension (DASH) and NYC Department for the Aging nutritional guidelines; interactive sessions for education in nutrition, BP management, medication adherence. Training in use of automated daily home BP monitors (Omron 20). Validated surveys at M0, M1, M3, M6. Taste preference and cost assessed through Meal Satisfaction (Likert scale) and Plate Waste measures. Primary Outcome: Change in Systolic BP (SBP) at Month 1; change in %BP controlled. Secondary: validated cognitive, behavioral, nutritional measures (SF-12, PQH-2), economics; staff/client satisfaction, trends and significant associations. RESULTS/ANTICIPATED RESULTS: n=94, x2 age =73 +/- 8 years, 65% female, 50% White, 32% Black/African American, 4% Asian, 1% American Indian, Alaskan Native, 13% Other, 32% Latino/a, 43% with income

OBJECTIVES/GOALS: We have developed a comprehensive Translational Research Navigation Program to guide investigators all the way from protocol development through study closure. As the program evolved, we initially developed organizational tools and then restructured them into a series of checklists to ensure that critical elements were not excluded or duplicated. METHODS/STUDY POPULATION: A series of checklists to assure that all research elements, including regulatory, scientific, and institutional, are addressed from protocol inception through study closure were developed by clinical research coordinators/navigators. The checklists are periodically updated and modified to reflect changing local and national regulations and policies. The first tool became the “Protocol Development Checklist” and then additional tools were developed and modified into a suite of navigation checklists that include “Protocol Implementation Checklist,” “Protocol Conduct Checklist,” and “Protocol Completion Checklist.” RESULTS/ANTICIPATED RESULTS: The checklists have been incorporated into the Translational Research Navigation Program and have enhanced the organization and quality of protocols throughout their lifespan. For example, implementation of the Protocol Development Checklist resulted in a reduction in time to IRB approval (currently 10 days), and implementation of the Protocol Implementation Checklist has impacted the time from IRB approval to study start-up. The Protocol Conduct Checklist has aided investigators in being better prepared and more organized for study conduct activities and the Protocol Closure Checklist has assured timely protocol closure and regulatory compliance, including reporting to ClinicalTrials.gov. DISCUSSION/SIGNIFICANCE OF IMPACT: Protocol checklists are powerful tools to enhance thoroughness, organization, and quality of the clinical research process. The Rockefeller University protocol checklists are available to the CTSA and Scientific Communities. CONFLICT OF INTEREST DESCRIPTION: NA.

OBJECTIVES/GOALS: Irreproducible and incompletely reported research lead to misallocated resources, wasted effort in pursing inappropriate avenues of investigation, and loss of public trust. To address this challenge, we employed a Team Science approach to create a multi-modal program to support Rigor, Reproducibility, and Reporting in Translational Science. METHODS/STUDY POPULATION: We conducted literature searches to reveal sources of irreproducibility and recommended corrective actions, invited leaders in the field to give lectures on opportunities to support reproducible science, and worked with the Rockefeller team science leadership group to instill an overarching rigor approach, infused into all training efforts. This multifaceted program was labeled R3 (R-cubed) for Enhancing Scientific Rigor, Reproducibility, and Reporting. RESULTS/ANTICIPATED RESULTS: Didactic Courses: Introduction to Biostatistics and Critical Thinking – focus on pitfalls in inferential statistics, consequences of poor research, and errors in published research.Scientific Writing – teaches methods and procedures in writing to ensure reproducibility. Lecture SeriesEstablished nine lectures on topics related to R3, including Data Management, Statistical Methods, Genomic Analyses, Data Repositories, Data Sharing, Pharmacy Formulation, and e-lab notebooks. WebsiteCreating a comprehensive website as repository for research, methods, programs, updates, and improvements related to R3. KL2 Clinical Scholars Seminars and NavigationScholars participate in seminars and tutorials to discuss opportunities to improve R3 across the research life-course.

OBJECTIVES/SPECIFIC AIMS: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to help concretize the relevant constructs, and then usied these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively creating domain-specific survey items, and then further discussed and refining the number, grouping, and wording of the items. METHODS/STUDY POPULATION: We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars. Each item was answered using a six-point Likert scale where a low score indicated poor expression of the specific leadership attribute and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Means, medians, standard deviations, and ranges of each item were calculated and tabulated. A complete (Pearson) correlation matrix was computed so that the raw inter-item relationships can be observed. For each a priori Domain an equal weighted summary scale was created and tabulated for review. The internal consistency of each a priori scale was assessed by calculating Cronbach’s Alpha (α). Items with low Item to Construct coefficients were candidates for elimination or modification, and overall scales with low’s will undergo further discussion. To challenge our assumptions of the construction and integrity of each domain, we employed exploratory Principal Components Analysis (PCA), followed by orthogonally rotated Factor Analysis (FA). We also forced the PCA / FA analysis to extract the a priori dimensions that allowed us to compare if the empirical and a priori structures match. DISCUSSION/SIGNIFICANCE OF IMPACT: We are partnering with the CTSA programs at Penn and Yale to assess issues of generalizability and scalability. We are working with Vanderbilt to install survey onto REDCap for ease of dissemination. Will continue to assess psychometric properties and refine as we receive more input.

OBJECTIVES/SPECIFIC AIMS: To develop a KL2 curriculum on the science and art of drug formulation. METHODS/STUDY POPULATION: Develop training materials for KL2 scholars that outline the art of formulation development. Materials will include syllabi, reading materials, and course work. RESULTS/ANTICIPATED RESULTS: This will enhance the training of KL2 scholars by incorporating formulation development concepts into their human health enhancing research projects. DISCUSSION/SIGNIFICANCE OF IMPACT: For new chemical entities, formulation goals must be realistic and move along in a step-wise manner from the laboratory bench, through toxicology studies, and on to Phase 1 studies. By training scholars in phase-specific formulation goals, their interactions with funding agencies, formulation scientists, and regulators will be more efficient, productive, and successful. For those scholars who are working to improve existing treatments, introducing the concept of formulation improvements that can create new indications, or improve efficacy, safety and patient compliance will open up more possibilities for creative product development.

Agriculture/horticulture has traditionally been an important sector in the economy of Bulgaria. The paper outlines the structural changes in Bulgarian agriculture since 1989 and discusses the product and market orientation of the horticultural farms in the Plovdiv region of Bulgaria. This paper analyses how farm owners / managers with different sized farms evaluated 5 product/market strategic options: ‘doing what you currently do but better’, ‘developing new horticultural products’, ‘developing new markets’, ‘developing new agricultural activities’ and ‘developing new nonagricultural activities’. The owners / managers identifi ed; whether they perceived these options as feasible for their future development, the encouraging/discouraging factors and the outcomes they expected from their implementation. The small-scale farms (less than 2 ha) were mainly subsistence farms that were relying upon the farmer’s experience to survive during the transition period. The second type of farm (2-10 ha) was ‘transitional’ farms and were working under pressure either for survival or expansion under the new EU related conditions. The third type of farm (over 10 ha) was more business orientated, aiming at business viability and trying to respond to the rapidly changing business environment in Bulgaria as they recognised that the EU accession would present new challenges and opportunities for the successful future development of their farm businesses.

This paper reports on the development process of an Electronic Social Care Record (ESCR), which used an adapted approach to Participatory Design (PD). PD is an established range of methodologies and principles for involving users in the design and implementation of systems or products. University researchers worked as part of a wider team including corporate social service stakeholders, a multidisciplinary children's social service team, and a technology provider, to develop a system that supports the integration of information of various teams/disciplines which need to work together to intervene with children who are in need. Using action research and ethnographic techniques, the researchers sought to understand and address the challenges faced by the various stakeholders when designing a system to deliver an ESCR.