OBJECTIVES/GOALS: Clinical trials demonstrate that axillary lymph node dissection (ALND) is unnecessary for most breast cancer patients with 1-3 involved nodes, but whether this is true for those with ILC is unknown. We evaluate the impact of ALND on recurrence-free survival (RFS) in ILC and 1-3 positive nodes. METHODS/STUDY POPULATION: We performed a retrospective cross-sectional analysis of patients with ILC treated between 1992-2019 at our institution. All patients received either sentinel lymph node biopsy (SLNB) or ALND and underwent either breast conservation surgery (BCS) or mastectomy. The primary outcome was RFS, defined as the absence of locoregional or distant recurrence. RESULTS/ANTICIPATED RESULTS: Of 496 cases, 250 (50.4%) underwent BCS, and 246 (49.6%) underwent mastectomy. A total of 93% of patients were hormone receptor positive, and 89% had low or intermediate grade disease. Among patients with 1-3 positive nodes, there was no significant difference in 5- and 10-year RFS based on receipt of ALND for both BCS and mastectomy cohorts. Using a multivariate model, we found no association between ALND and RFS overall (HR = 0.98, 95% CI 0.36-2.7, p>0.20) and among those with 1-3 positive nodes (HR = 0.60, 95% CI 0.12-3.4, p>0.20). DISCUSSION/SIGNIFICANCE OF IMPACT: These findings support the safety of omitting ALND in patients with ILC and 1-3 positive nodes, regardless of whether they receive BCS or mastectomy. Further studies of axillary management in ILC, including imaging tools to predict nodal involvement and response to therapy, are warranted.

OBJECTIVES/GOALS: Military personnel are at significantly greater risk for developing tinnitus, due to increased exposure to acoustic trauma. Many psychiatric disorders are common among individuals with chronic tinnitus, including posttraumatic stress disorder (PTSD). Although tinnitus and PTSD are clearly different, research supports the notion of shared mechanisms between both disorders. First, there are overlapping symptoms between tinnitus-related distress and PTSD, including irritability, distorted cognitions, persistent negative emotional states, diminished interests in activities, exaggerated startle response, sleep disturbance, concentration problems, and hypervigilance. Second, tinnitus and PTSD are highly comorbid with one another, whereas 34% of veterans with tinnitus also carry a PTSD diagnosis. Third, those with both disorders are significantly more emotionally impaired compared to those with tinnitus and any other psychiatric disorder. Lastly, neuroimaging research has shown similar regions within the auditory vigilance network are implicated among those with tinnitus, and separately, among combat PTSD patients, suggesting shared neurobiological mechanisms between both disorders. Though we are aware that tinnitus and comorbid PTSD presents as a significantly greater clinical concern, the relationship between tinnitus-related distress and PTSD symptomotology it is still unknown. Canonical correlation analyses will be conducted to examine the relationship between tinnitus-related distress and PTSD among veterans as a part of a larger clinical trial for posttraumatic headache. Results of the study will shed light on the relationship between tinnitus-related distress and PTSD, and may suggest a different phenotype for those with both disorders. Researchers and clinicians will further understand and conceptualize the relationships among the cognitive, emotional, and behavioral symptoms associated with tinnitus and PTSD, both individually and conjointly. METHODS/STUDY POPULATION: Baseline data (N = 112) from a larger clinical trial examining the effectiveness of two different psychotherapies for the alleviation of posttraumatic headache was examined. The primary aim of this project was to evaluate the relationship between tinnitus-related distress and PTSD based on the eight subscale scores of the Tinnitus Functional Index (TFI) and the four scales of the Clinician Administered PTSD Scale for the DSM-5 (CAPS-5), respectively. To address this aim, canonical correlation analysis was used where the tinnitus-related symptom subscales made up one variable set and PTSD symptom subscales made up the second variable set. First, we evaluated the overall model fit based on Wilks Lambda to determine if the two variable sets were related at the p < .05 level. Next, we evaluated the canonical correlations (comparable to an eigenvalue) for each canonical dimension to determine the required number of significant canonical dimensions (or latent constructs) that were necessary to understand the association between the two variable sets. Finally, the standardized canonical coefficients, which are analogous to regression coefficients, evaluate the magnitude of variate relationships and determine which subscales best describe significant canonical dimensions. RESULTS/ANTICIPATED RESULTS: Prior to the canonical correlation analysis, total score descriptive statistics and subscale score zero-order correlations were carried out. The CAPS-5 total score was 33.24 (SD = 9.39) and the TFI total score was 50.81 (SD = 21.88) in this sample. Interpretation of the zero-order correlations indicated that TFI Relaxation subscale was the only tinnitus-related subscale moderately associated with a PTSD subscale (i.e., Reexperiencing, r = .35). Canonical correlation omnibus model fit analysis via the Wilks Lambda overall multivariate test indicated that the tinnitus variable set was significantly associated with the PTSD variable set, F = 1.55, p = .04. Evaluation of the canonical correlations indicated that one dimension was significant in explaining the relationship between the two variable sets and accounted for 25% of the overall variance, F = 1.55, p < .04, R2 = .249. Standardized canonical coefficients indicated that the PTSD subscales Reexperiencing (b = 0.64) and Negative Alterations in Cognition and Mood (b = 0.55) were the most representative of the identified canonical dimension. In terms of the TFI, the Relaxation (b = 1.28) and Sleep (b = 0.72) subscales appeared to be most related to the canonical dimension. The TFI subscales Auditory Difficulty (b = −0.30) and Quality of Life (b = 0.30) also appeared to be related the canonical dimension to a lesser degree. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings support prior research suggesting particularly deleterious functional outcomes among individuals with comorbid tinnitus and PTSD. Results of this study suggest a latent variable that can explain the unique experience of individuals with both disorders. This latent variable consists of two PTSD constructs: Reexperiencing traumatic events (i.e., flashbacks, nightmares, intrusive memories), and Negative Alterations in Cognition and Mood (i.e., self- and other-blame, strong negative feelings, loss of interest, feeling distant). This latent variable also consists of two tinnitus-related constructs: Sleep (i.e., trouble falling and staying asleep, peaceful sleep) and Relaxation (i.e., ability to relax, enjoyment of peace and quiet). Auditory Difficulty (i.e., hear clearly, understand people) and Quality of Life (i.e., social activities, relationships, difficulty performing tasks) also contributed to the latent variable, but to a lesser degree. It is suggested that the constellation of symptoms related to the latent variable is a Dysphoric Factor, unique to individuals with PTSD, tinnitus, and posttraumatic headache. It may be necessary to incorporate different techniques into existing evidence-based treatments for both tinnitus and PTSD, for optimal symptom improvement.

OBJECTIVES/GOALS: Older patients with HL have worse outcomes than younger patients, which may reflect treatment selection, including fewer chemotherapy cycles. Immortal time bias exists when patients must survival to initiation, and even completion, of treatment. We described treatment length and death to evaluate the extent of immortal time bias. METHODS/STUDY POPULATION: This retrospective cohort study utilized SEER-Medicare data from 1999-2014. Patients diagnosed with incident advanced stage HL at age ≥65 years and enrolled in Medicare Part A and B fee for service were included. Chemotherapy or radiotherapy treatment initiated within 4 months of diagnosis was determined from inpatient, outpatient, and physician/supplier claims. No treatment was defined by lack of treatment claims. Dates from claims were used to define length of treatment; ≥4 months of treatment indicated complete chemotherapy cycles. Date of death was obtained from Medicare data. Analyses were limited to 1 year post-diagnosis. Summary statistics were used to describe treatment length and subsequent death. RESULTS/ANTICIPATED RESULTS: We included 1492 advanced stage HL patients with a mean age of 76 years (SD = 7). 428 (29%) patients had no documented treatment; 397 (27%) were treated <4 months indicating fewer chemotherapy cycles; and 667 (45%) were treated for ≥4 months indicating complete chemotherapy cycles. Among those with no documented treatment, 15% died within 1 month of diagnosis with 78% dying by 1 year post-diagnosis. Among those treated <4 months, 36% died within 1 month of their last treatment claim with 64% dying by 1 year post-diagnosis. Among those treated ≥4 months, 7% died within 1 month of their last treatment claim with 14% dying by 1 year post-diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Few untreated patients died within 1 month of diagnosis. One-third of patients treated <4 months died soon after completion of treatment, while patients treated longer survived longer, suggesting some patients did not survive to complete treatment. To account for this immortal time bias, landmark analysis will be used to assess the relationship between treatment and survival.

OBJECTIVES/GOALS: The purpose of this report is to describe the role of Periodontal Disease (PD) in Coronary Artery Disease (CAD) in a Hispanic country. METHODS/STUDY POPULATION: Literature and Puerto Rican experience was reviewed and will be discussed. RESULTS/ANTICIPATED RESULTS: PD produces inflammatory disease by bacterial infection in the gingiva. This factor PD activates an inflammatory process affecting the CAD cascade inducing myocites, endothelial cells activation and cytokines. The incidence of gingival disease in the Puerto Rican population (P) is around 50%; of this group 80% will develop periodontal disease. Including this factor and diabetes mellitus Type 2, still the incidence of CAD is 20-30% less than the U.S.A. DISCUSSION/SIGNIFICANCE OF IMPACT : CAD is a systemic disease related to genetic factors and inflammation. PD is related to an inflammatory process, which will activate the CAD process, producing tissue infarcts. The daily use of resolving or liquid Omega 3 in the gingival tissue is useful in the prevention of gingival and periodontal disease. CONFLICT OF INTEREST DESCRIPTION: All authors have no relationship with any industry or financial associations in connection with the submitted abstract.

OBJECTIVES/GOALS: Severe malarial anemia due to Plasmodium falciparum is often accompanied by thrombocytopenia. Treatment includes transfusion of whole blood, which contains erythrocytes, platelets, and other blood components. The objective of the study was to assess the effect of whole blood transfusion on survival in children with severe falciparum malaria and to examine the potential interaction of thrombocytopenia with malaria mortality and transfusion response. METHODS/STUDY POPULATION: We analyzed a retrospective cohort of 842 hospitalized children in Zambia with severe malarial anemia (703 transfused, 139 not transfused due to stock-out or other reason). Severe malarial anemia was defined as a positive rapid diagnostic test or blood smear in combination with an admission hemoglobin concentration ≤5 g/dL. RESULTS/ANTICIPATED RESULTS: Mortality was 13% (94/703) in the transfused group and 24% (34/139) in the non-transfused group. Kaplan-Meier survival estimates stratified by transfusion status and thrombocytopenia (150,000/μL threshold) showed increased mortality in children with thrombocytopenia who did not undergo transfusion, with no differences in mortality among the other transfused and non-transfused groups (log-rank test P = 0.0001). Effect modification analysis by Cox proportional hazards regression adjusted for age, sex, hemoglobin concentration, blood group type, and eosinophilia showed a significant interaction between platelet count and transfusion status (P = 0.028). Children with thrombocytopenia who were transfused and died had little or no post-transfusion increase in platelets, in contrast to those who survived. Freshness of transfused whole blood, construed from expiration dates, correlated with greater platelet recovery and improved survival. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of platelets in malaria pathophysiology is complex and incompletely understood; prior studies describe preferential binding of platelets to parasitized erythrocytes and direct parasitocidal activity, whereas others detailed deleterious effects in malaria involving the central nervous system vasculature. These findings point to a potential clinical role for platelet-directed transfusion strategies to improve survival in children with severe falciparum malaria, which should be further assessed in randomized interventional studies.

OBJECTIVES/GOALS: Obsessive compulsive disorder (OCD) is a serious and impairing disorder. The peripartum is associated with changes in pre-existing OCD, including exacerbation and improvement of the disorder. This meta-analysis seeks to understand the proportion of women reporting a change in OCD during this time. METHODS/STUDY POPULATION: Nine studies with independent samples examining change in obsessive-compulsive symptomology (OCS) in the peripartum were included in the meta-analysis. Studies were included if the sample examined with women with a clinical diagnosis of OCD that pre-existed pregnancy onset. The meta-analysis was conducted using R Studio with Meta, Metafor and Weightr packages. A moderation analysis was conducted to examine the impact of gestational period on OCD symptoms. Gestational periods were defined as pregnancy, postpartum, or the peripartum. Peripartum refers to a collapsed postpartum/pregnant period such that the period was not identified or specified during data collection. RESULTS/ANTICIPATED RESULTS: The summary proportion of women who experienced no change in symptoms was 46.7% (CI: 42.0-51.4%). No change by period was: pregnancy 49.6% (CI: 36.3-62.9%); postpartum 45.6% (CI: 41.4-49.9%); peripartum 52.4% (CI: 42.4-50.3%). The summary proportion of women who experienced exacerbation was 39.2% (CI: 33.5-45.5%). Exacerbation by period: pregnancy 35.5% (CI: 24.8-47.9%); postpartum 42.9% (CI: 34.8-51.4%); peripartum 34.6% (CI: 23.7-47.4%). The summary proportion of women who experienced improvement was 11.5% (CI: 9.3-14.4%). Improvement by period: pregnancy 42.9% (CI: 14.7-77.0%); postpartum 7.8% (CI: 5.7-10.4%); peripartum 19.6% (CI: 13.7-27.3%). Gestational period had a moderating effect. DISCUSSION/SIGNIFICANCE OF IMPACT: During the peripartum 46% report no change, 40% a worsening and 12% an improvement. Improvement typically occurs during pregnancy and may be followed by a postpartum worsening. This may reflect a hormonally-sensitive subsection of women impacted by the acute changes that occur during this time.

OBJECTIVES/GOALS: Sodium (Na) intake can elevate blood pressure and is a factor in developing chronic kidney disease (CKD). Twenty-four-hour urinary Na (24hUNa) is the gold standard for assessing Na intake but is burdensome. Validated equations estimate 24hUNa (e24hUNa) from a spot urine sample, but these estimations are not validated against a known Na intake in CKD. METHODS/STUDY POPULATION: The current study is a secondary analysis of a 9-day controlled feeding study in moderate CKD patients matched to healthy adults. Only CKD patients were used for the current analyses (n = 8). Participants consumed a controlled diet for 9 days, providing ~2400 mg Na/d as determined by inductively coupled plasma optical emission spectroscopy (ICP). On days 7 and 8, participants collected all urine in an inpatient setting, beginning with a fasting sample on day 7. Urine sample mineral analyses were performed by ICP and urinary creatinine by the Jaffe reaction. The day 7 fasting urine sample was used to calculate e24hUNa using 6 published equations. Log-transformed Na intake, measured 24hUNa, and e24hUNa were compared by repeated-measures ANOVA with planned contrasts using SAS. RESULTS/ANTICIPATED RESULTS: Fifty percent of the CKD patients (n = 4) were female; 63% (n = 5) were white, and 37% (n = 3) were black. On average, participants were aged 56.6 ± 13.8 y with a BMI of 31.7 ± 9.4 kg/m2 and eGFR of 40.7 ± 7.9 mL/min. Based on actual food intake, average Na intake on day 7 was 2024 ± 388 mg. Average measured 24hUNa was 2529 ± 1334 mg. The main ANOVA was significant (p = 0.02). Results from the planned contrasts found that e24hUNa from the SALTED cohort, an equation developed specifically for CKD patients, was significantly higher than both Na intake (p<0.001) and measured 24hUNa (p = 0.007). For the remaining 5 equations, e24hUNa was not significantly different from measured 24hUNa nor dietary Na intake. DISCUSSION/SIGNIFICANCE OF IMPACT : Our results suggest that e24hUNa calculated using most published equations may provide a reliable and low-burden method of assessing dietary Na intake in moderate CKD patients. These findings should be confirmed in larger samples. Additional studies are needed to validate or dispute the use of the SALTED equation for estimating Na intake.

OBJECTIVES/GOALS: The rib construct is a novel device for treating childhood hyperkyphosis and kyphoscoliosis. The purpose of this study was to investigate the biomechanics, mechanism, and clinical outcomes of this device. The overarching hypothesis was that the rib construct is safe and effective for correcting hyperkyphotic spinal deformity. METHODS/STUDY POPULATION: Biomechanical evaluation: An ex vivo porcine spine biomechanical study compared traditional pedicle screw proximal fixation to the rib construct in terms of proximal fixation strength and construct stiffness. Porcine model hyperkyphosis correction with rib construct: An in vivo hyperkyphotic porcine model was used to study the ability of the rib construct to correct hyperkyphosis in the developing porcine spine. Human hyperkyphotic correction with rib construct: A retrospective study was conducted to examine the radiographic outcomes, complication rates, procedure times, and blood losses experienced by human patients that received rib construct surgery. RESULTS/ANTICIPATED RESULTS: Biomechanical evaluation: The rib construct was significantly less prone to proximal fixation failure and less stiff compared to pedicle screws. Porcine model hyperkyphosis correction with rib construct: The average T6-T14 thoracic kyphosis was 35.8 ± 3.2° at the time of hyperkyphosis creation surgery. In response to corrective surgery with the rib-hook construct, T6-T14 thoracic hyperkyphosis decreased immediately post-op to 11.3 ± 7.8° and continued to decrease to 7.8 ± 7.6° until final follow-up 8 weeks post-op (n = 3). Human hyperkyphosis correction with rib construct: Pre-op sagittal Cobb angle was 81 ± 31° and fell to 43 ± 24° post-op and to 38 ± 24° at final follow-up; indicating ~100% correction (normal thoracic kyphosis is 40°). DISCUSSION/SIGNIFICANCE OF IMPACT: The results suggest that the rib construct is a highly effective technique and superior to existing methods.

OBJECTIVES/GOALS:

1. 1. analyze urinary protein exosome content pattern before and during DASH diet.

2. 2. characterize urine electrolyte changes associated with changes in protein profiles, and hormonal changes before/after DASH diet.

3. 3. analyze the association of these changes to the DASH-related BP response.

METHODS/STUDY POPULATION: In this proof of concept study, hypertension stage 1 volunteers will receive a DASH based menu during 14 consecutive days of elective admission to the RU research hospital. Participants will complete a food frequency questionnaire (VioScreen) with a bionutritionist. Throughout the intervention period, participants will be assessed for blood pressure, plasma renin and aldosterone, and 24 hour urines for electrolytes, creatinine, protein, albumin and first morning urine collected for exosomes. Exosome analysis will be performed by a commercial lab. Proteome analysis will be conducted in the RU Mass-spectrometry service. RESULTS/ANTICIPATED RESULTS: The causal pathway we will elucidate hypothesizes that: 1) changes in diet affect blood electrolytes, and through these, aldosterone. 2) Aldosterone alters the expression of specific transporter proteins in the renal tubule; protein expression will be reflected in the urine exosome. 3) These transporters affect the excretion of electrolytes, as reflected by urinary ratio of sodium (Na) to Potassium (K). During consumption of the Western diet, the Na/K ratio is approximately 2-2.5, whereas we expect the urinary sodium/potassium ratio to be <1, when the participant is eating a DASH based diet. DISCUSSION/SIGNIFICANCE OF IMPACT: This assay provides a clinical tool to assess dietary adherence, and the project will provide insights into the mechanism whereby DASH reduces blood pressure.

OBJECTIVES/GOALS: Precisely, the goal of the device is to initiate a friction force between the delivery system and the arterial vessel wall to both assure immediate stent deployment and prevent axial advancement of the stent-anchoring wire. METHODS/STUDY POPULATION: A prototype was constructed and its effectiveness of applying a friction force to a vessel wall was tested ex vivo using an LRX Plus Materials Testing Machine. Afterwards, the experimental performance of the device was compared to that of a finite element simulated model. RESULTS/ANTICIPATED RESULTS: The device demonstrated the ability to apply a friction force to the vessel wall to meet its objective. However, experimental values were consistently greater than those gathered from the simulation. Since the force prescribed by the device is minimal, future work includes increasing the force capabilities of the device and defining force requirements. DISCUSSION/SIGNIFICANCE OF IMPACT: Upon further development and testing, this device can be implemented into endovascular neurosurgery to improve occlusion rates of intracranial aneurysms and reduce patient risk during these operations. CONFLICT OF INTEREST DESCRIPTION: I am pursuing intellectual property on this invention. I was careful not to describe the invention in too much detail in my abstract submission for this reason. This research is my thesis work, and I placed on one year embargo on it before it is published to give us time to sort out IP. I would like to be considered for inclusion in Translational Science 2020 if I am able to get IP on this work before publishing, which I expect will be the case. I have every intention of obtaining IP before the conference in April 2020.

OBJECTIVES/GOALS: Rapid and accurate identification of primary malaria vector species from collected specimens is the most critical aspect of effective vector surveillance and control. This interdisciplinary team of engineers aims to automate identification using a deep learning computer vision algorithm. METHODS/STUDY POPULATION: The team spent August of 2019 observing and participating in control and surveillance activities in Zambia and Uganda. They conducted >65 interviews with key stakeholders across 9 malaria control and surveillance sites, ranging from field and community health workers, to malaria researchers and Ministry of Health employees. Stakeholder feedback validated the need for a more accurate and efficient method of vector identification in order to more effectively deploy targeted malaria interventions. The team set forth in designing and prototyping a portable, automated field tool that could speciate mosquito vectors to the complex level using artificial intelligence. RESULTS/ANTICIPATED RESULTS: The team’s research demonstrated that accuracy, cost effectiveness, and ease of use would be critical to the successful adoption of the tool. Results of initial prototyping, usability studies, and stakeholder surveys were used to determine the tool’s minimal user specifications: 1) the ability to distinguish between Anopheles Gambiae and Anopheles Funestus, the two principal malaria vectors in the countries visited, 2) achieving an identification accuracy of ≥90% to the complex level, and 3) accessibility to the speciation data 3-7 days following vector collection. Next steps include optimizing the tool to deploy a minimal viable product for testing in Kenya by the summer of 2020. DISCUSSION/SIGNIFICANCE OF IMPACT: The accurate, high-quality surveillance enabled by this device would allow malaria control programs to scale surveillance to remote regions where an entomologist may not be available, allowing malaria programs to deploy effective interventions, monitor results, and prevent disease.

OBJECTIVES/GOALS: Errors in patient matching could result in serious adverse safety events. Unlike publicized mix-ups by healthcare providers these errors are insidious and with increased data sharing, this is a growing concern in healthcare. The following project will examine patient matching errors and quantify their association with safety. METHODS/STUDY POPULATION: EHR systems perform matching out-of-the-box with unknown quality. Using matching processes outside the EMR, the rate at which matching errors are present was quantified and the erroneous records were flagged providing both comparative measures and data necessary to evaluate patient safety. To understand the relationship between matching and safety we will establish a percent of voluntarily reported safety events in our institution where a matching error existed during an encounter. Any safety events occurring for a flagged patient will be reviewed to determine if matching errors contributed to the safety problem. Not all safety events are reported so we will perform full chart review of a filtered list of medical records that have a higher likelihood of safety events. RESULTS/ANTICIPATED RESULTS: We were able to quantify matching errors, and the preliminary matching error rate is approximately 1%, representing over 700 patients. The work is in progress and we are beginning to determine the association between safety events and incorrect matching. Together these results will provide an incentive to identify errors, make corrections, and develop methods to achieve these objectives. The number of matching errors impacts patient care as well as business operations and is likely to have a negative financial impact on institutions with high error rates regardless of its relationship to safety. DISCUSSION/SIGNIFICANCE OF IMPACT: Patient matching is bundled with EHR software and institutions have little control over error rates, yet bear the liability for resulting clinical error. Institutions need to be able to identify undetected matching errors and any associated safety events and this project will provide that solution.

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.

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

OBJECTIVES/GOALS:

1. 1. Examine the associations among BMI and markers of cardiometabolic risk, including blood pressure, lipids and blood glucose.

2. 2. Assess prevalence of kidney function deterioration, identified as hyperfiltration and moderately increased albuminuria (MIA), in obese compared to normal weight adolescents.

METHODS/STUDY POPULATION: De-identified electronic health records (EHR) data were extracted for female adolescents, aged 12-21 years, and their offspring through 24 months, who received health care services (Jan 2012 to Dec 2016) in NYC from 12 academic health centers and community health centers that are part of PCORnet NYC Clinical Data Research Network (NYC-CDRN). Data were analyzed using SAS (version 3.2.5). Patient characteristics overall and for study subgroups were examined using standard summary statistics. Trends in cardio-renal variables were examined by BMI groups coded according to NHANES as underweight, normal weight, overweight or obese. Multiple linear regression analyses will control for covariates. RESULTS/ANTICIPATED RESULTS: Data from 651,066 adolescent females ages 12-21 were retrieved. Analysis was performed on a subset of 202,214 unique patients (26% white, 15% black, 12.9% Latina) for whom there was complete data for BMI and blood pressure. Distribution of BMI was 6% underweight, 59% normal weight, 19% overweight, and 17% obese. There were significant differences in mean systolic (SBP, mean±SD mmHg: 102±12, 108±11, 112±12, 116±12) and diastolic blood pressure (DBP, mean±SD mmHg: 62±10, 66±8, 68±8.9, 70±9) across the four BMI groups with an increasing trend (p-values<0.0001). We will examine renal function trends, and whether these cardio-renal differences persist when controlling for age, race and ethnicity. DISCUSSION/SIGNIFICANCE OF IMPACT: Although SBP/DBP means were within normal limits across BMI groups, significant increasing trends suggest that women in higher BMI groups may be at increased risk for hypertension and potentially for renal dysfunction. We will examine contributions of race/ ethnicity and age to these associations.

OBJECTIVES/GOALS: To improve the implementation of FDRs in translation research. Current statistical packages are hard to use and fail to adequately convey strong assumptions. We developed a software package that allows the user to decide on assumptions and choose the hey desire. We encourage wider reporting of FDRs for observed findings. METHODS/STUDY POPULATION: We developed a user-friendly R function for computing FDRs from observed p-values. A variety of methods for FDR estimation and for FDR control are included so the user can select the approach most appropriate for their setting. Options include Efron’s Empirical Bayes FDR, Benjamini-Hochberg FDR control for multiple testing, Lindsey’s method for smoothing empirical distributions, estimation of the mixing proportion, and central matching. We illustrate the important difference between estimating the FDR for a particular finding and adjusting a hypothesis test to control the false discovery propensity. RESULTS/ANTICIPATED RESULTS: We performed a comparison of the capabilities of our new p.fdr function to the popular p.adjust function from the base stats-package. Specifically, we examined multiple examples of data coming from different unknown mixture distributions to highlight the null estimation methods p.fdr includes. The base package does not provide the optimal FDR usage nor sufficient estimation options. We also compared the step-up/step-down procedure used in adjusted p-value hypothesis test and discuss when this is inappropriate. The p.adjust function is not able to report raw-adjusted values and this will be shown in the graphical results. DISCUSSION/SIGNIFICANCE OF IMPACT: FDRs reveal the propensity for an observed result to be incorrect. FDRs should accompany observed results to help contextualize the relevance and potential impact of research findings. Our results show that previous methods are not sufficient rich or precise in their calculations. Our new package allows the user to be in control of the null estimation and step-up implementation when reporting FDRs.

OBJECTIVES/GOALS: Composition of demographics or image types in publicly available datasets may detract from deep learning (DL) diagnosis performance of underrepresented melanoma subtypes. We evaluate a DL model’s performance on melanoma subtypes (acral; head and neck) that have known association with poor prognosis. METHODS/STUDY POPULATION: We trained a CNN using a single InceptionV3 model for 30 epochs on dermoscopic images of pigmented lesions from the International Skin Imaging Collaboration (ISIC). The ISIC 2018 challenge training set had 10008 total images, with 1113 total nevi, 6705 total melanomas, 97 acral nevi, 10 acral melanomas, 256 head and neck (H&N) nevi, and 164 H&N melanomas. The non-acral test set had 117 melanomas and 200 nevi. The acral test set had 201 melanomas and 161 nevi. The H&N test set had 199 melanomas and 128 nevi. Area under the receiver operating curve (AUC) was calculated. The model was retrained with acral lesion oversampling (10x) and performance on the acral test set was re-evaluated. RESULTS/ANTICIPATED RESULTS: The model performed on the non-acral test with an AUC of 80.5%, on the acral test with an AUC of 76.3%, and on the head and neck test with an AUC of 83.8% After oversampling acral lesions within the training set, the model showed nearly the same performance as without oversampling on acral lesions: AUC of 75.6%. DISCUSSION/SIGNIFICANCE OF IMPACT: Diagnosis of high-risk melanoma subsets (acral; H&N) remains reliable despite underrepresentation during training, increasing validity for broad implementation of DL technology. Datasets for individual subtypes may not be warranted as findings suggest features may be learned from other skin lesions.

OBJECTIVES/GOALS: To evaluate whether the default mode network experiences age-related changes in functional connectivity and to identify these patterns of progression across seven decades of life. The overall goal is to evaluate whether quantifying these functional changes can serve as potential neurobiomarkers of aging for further quantitative genetic analyses. METHODS/STUDY POPULATION: Scans were performed at the RII on a 3T Siemens Trio scanner with an 8-channel head coil. Whole-brain, rsfMR imaging was performed using a gradient-echo EPI sequence sensitive to the BOLD effect (TE/TR = 30/3000 ms; flip angle = 90°; isotropic 1.72 mm2). Subjects were instructed to lie in dimmed light with their eyes open and try not to fall asleep. Image analysis was performed with FMRIB’s Software Library tools (www.fmrib.ox.ac.uk/fsl). Preprocessing of resting state data includes motion correction, brain extraction, spatial smoothing, and high-pass temporal filtering. Time series data was extracted from 9 DMN ROIs using FSL’s Featquery tool with 6mm radius spherical ROI masks created in Mango. After extraction, DMN connectivity was assess using structural equation modeling implemented in Amos 22.0 (IBM, Inc.). RESULTS/ANTICIPATED RESULTS: The exploratory SEM (eSEM) default mode network (DMN) model used consists of 9 regions of interest and 13 functional connectivity paths. The eSEM DMN model exhibited exceptional model fit to a primary resting state data set of 1169 subjects from the Genetics of Brain Structure project (1R01MH078111-01, David Glahn PI) with an RMSEA of 0.037. This model also had excellent model fit in 7 cohorts that were grouped by decade age (10s – RMSEA: 0.058, 20s – 0.051, 30s – 0.045, 40s – 0.048, 50s – 0.043, 60s – 0.035, 70s – 0.037). Analysis of the decade group-wise path coefficients identified 7 of the 13 paths (pC -> LMTG, pC -> PCC, PCC -> MPFG, PCC -> vACC, MPFG -> vACC, LIPL -> RIPL, LMTG -> RMTG) significantly negatively correlated with age-related changes. As early as the 1st decade of life, the functional connectivity within the DMN decreases. DISCUSSION/SIGNIFICANCE OF IMPACT: The DMN experiences progressive age-related decreases in connectivity, beginning in the first decade of life. Our results suggest that DMN path coefficients can serve as biomarkers of cognitive aging, which can then be used as quantitative traits for genetic analyses to identify genes associated with normal aging and age-related cognitive diseases.

OBJECTIVES/GOALS: We compared the validity of an International Classification of Diseases, Clinical Modification (ICD) algorithm for identifying high-grade cervical intraepithelial neoplasia and adenocarcinoma in situ (together referred to as CIN2+) from ICD 9th revision (ICD-9) and 10th revision (ICD-10) codes. METHODS/STUDY POPULATION: Using Tennessee Medicaid data, we identified cervical diagnostic procedures in 2008-2017 among females aged 18-39 years in Davidson County, TN. Gold-standard cases were pathology-confirmed CIN2+ diagnoses validated by HPV-IMPACT, a population-based surveillance project in catchment areas of five US states. Procedures in the ICD transition year (2015) were excluded to account for implementation lag. We pre-grouped diagnosis and procedure codes by theme. We performed feature selection using least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation and validated models by ICD-9 era (2008-2014, N = 6594) and ICD-10 era (2016-2017, N = 1270). RESULTS/ANTICIPATED RESULTS: Of 7864 cervical diagnostic procedures, 880 (11%) were true CIN2+ cases. LASSO logistic regression selected the strongest features of case status: Having codes for a CIN2+ tissue diagnosis, non-specific CIN tissue diagnosis, high-grade squamous intraepithelial lesion, receiving a cervical treatment procedure, and receiving a cervical/vaginal biopsy. Features of non-case status were codes for a CIN1 tissue diagnosis, Pap test, and HPV DNA test. The ICD-9 vs ICD-10 algorithms predicted case status with 68% vs 63% sensitivity, 95% vs 94% specificity, 63% vs 64% positive predictive value, 96% vs 94% negative predictive value, 92% vs 89% accuracy, and C-indices of 0.95 vs 0.92, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, the algorithm’s validity for identifying CIN2+ case status was similar between coding versions. ICD-9 had slightly better discriminative ability. Results support a prior study concluding that ICD-10 implementation has not substantially improved the quality of administrative data from ICD-9.

OBJECTIVES/GOALS: Recent studies have assessed the association between surgery with general anesthesia and cognitive decline in longitudinal cohorts of older adults. Patients diagnosed with dementia more frequently drop out of these longitudinal studies or are unable to complete the test battery. We revisit this aim with focus on methods for informative dropout. METHODS/STUDY POPULATION: We use data from the Mayo Clinic Study of Aging (MCSA), a longitudinal epidemiological study of the prevalence, incidence, and risk factors for mild cognitive impairment (MCI) and dementia. Our primary outcome of interest was global cognitive z-score, assessed at study visits every 15 months. We implement linear mixed effects models to assess the association between post-enrollment exposure to surgery/anesthesia and subsequent cognitive decline trajectories. Demented patients more frequently drop out of MCSA, so, subjects with the worst cognitive outcomes are unobserved and missing data may be informative. Since this missingness may be missing not at random, we use shared parameter models to analyze continuous cognitive outcomes while jointly modeling time to dementia. RESULTS/ANTICIPATED RESULTS: A total 1948 subjects, non-demented at baseline, from the MCSA were included. Median age was 79, 51% of subjects were male, and 16% had MCI at enrollment. Among median follow-up of 4 study visits over median 5.4 years, 172 patients developed dementia and dropped out from further assessments of cognitive function. In adjusted linear mixed effects models, our data suggest post-enrollment exposure to surgery/anesthesia is associated with a decline in cognitive function over time (change in slope = −0.07 standard deviations of cognitive z-score per year, 95%CI = −0.08, −0.05, p<.001). After adjusting for informative dropout using shared parameter models, surgery/anesthesia is associated with greater cognitive decline (change in slope = −0.14 per year, 95%CI = −0.16, −0.12, p<.001). DISCUSSION/SIGNIFICANCE OF IMPACT: We revisited a prior analysis by our group with consideration of informative dropout. Subjects who dropout due to dementia may have different trajectories of cognitive decline compared to non-demented subjects. Shared parameter models estimate the association between surgery/anesthesia and cognitive decline accounting for informative dropout.