OBJECTIVES/GOALS: Evaluate the impact of COVID-19 on oral clefts services including surgical and dental treatments in Puerto Rico. METHODS/STUDY POPULATION: This Observational retrospective cohort study will consider patients 0-21 y/o with CL/P that visited the UPR school of Dental Medicine, Pediatric University Hospital Dr. Antonio Ortiz and ongoing case-control research project Face-Genes. Records to be used are classified as follow: Pandemic (March 15, 2020 to March 15 2022) Pre-pandemic (March 15, 2015 to March 15, 2017) Power analysis (power=0.80 alpha=0.05) will be calculated. Unavailable and incomplete medical records and those that did not attended study clinic during study period will be excluded. Data extraction instrument will be based on previous published study. Descriptive statistics, Chi-square, Odds Ratios at 95% confidence intervals and multiple logistic regression will be estimated. RESULTS/ANTICIPATED RESULTS: We hypothesize that surgical and dental services in Puerto Rico will be adversely impacted because of COVID-19 pandemic. DISCUSSION/SIGNIFICANCE: CL/P are common congenital diseases that require early interdisciplinary attention. Lack of timely care as well as surgery and treatment delays, could be associated with poorer prognosis, increased morbidity and mortality. If there is high risk of dh services during emergency situations, our findings will help to allocate the available resources

ABSTRACT IMPACT: Our data identify a novel candidate for combination strategy in melanoma treatment, and can inform clinicians in their decision-making process regarding therapeutic intervention for melanoma patients. OBJECTIVES/GOALS: Soluble adenylyl cyclase (sAC) is a novel source of cyclic AMP (cAMP). In melanoma, nuclear sAC localization has an established diagnostic utility and we newly found that nuclear sAC functions as a tumor suppressor by inhibiting Hippo pathway, which affects treatment response. Here, we examine the effect of nuclear sAC on melanoma treatment response. METHODS/STUDY POPULATION: We developed a doxycycline inducible system for increasing sAC activity only in the nucleus. We assessed whether nuclear sAC activity affects treatment response, using BRAFV600 human melanoma cell lines. Using a clonogenic assay, we examined how nuclear sAC activity affects growth inhibition in the presence of a BRAF inhibitor, vemurafenib. Our findings will be confirmed in vivo using tumor xenografts. After tumor formation in NSG mice, mice will be randomized to be fed normal or doxycycline chow for nuclear sAC induction, then subdivided to receive vehicle or vemurafenib to examine the effect of nuclear sAC activity on treatment response in vivo. We will also compare melanoma biopsies collected before and after treatment with BRAF inhibitors to assess how nuclear sAC staining affects tumor morphology in vivo. RESULTS/ANTICIPATED RESULTS: So far, nuclear sAC activity has rendered SkMel178 and M263 cell lines more susceptible to vemurafenib. Cell viability was inversely correlated both with vemurafenib and with doxycycline concentration. Cell viability after vemurafenib treatment was dramatically reduced when nuclear sAC was activated. It appears that nuclear sAC enhances the sensitivity of BRAF mutant melanomas to vemurafenib in vitro. We anticipate that xenografts of these cells in mice will be more susceptible to vemurafenib when nuclear sAC is activated. We also anticipate that positive nuclear sAC staining will correlate with a favorable response to therapy. DISCUSSION/SIGNIFICANCE OF FINDINGS: Targeted therapy with BRAF inhibitors is used in late-stage melanomas, but its use is limited as patients invariably acquire resistance. Here, we identified nuclear sAC activation as a novel candidate for combination strategy. Our data will also inform clinicians how best to integrate this biomarker into their decision-making regarding therapy.

OBJECTIVES/GOALS: Using biomarkers to identify vulnerabilities from cocaine use disorder (CUD) is a focus of recent investigations. Current clinical efforts focus on psychiatric recovery in CUD, however other body systems are missed. Applying blood-based transcriptomics to investigate how clinical conditions relate to CUD can alter current treatment approaches. METHODS/STUDY POPULATION: We conducted a comprehensive longitudinal study of 12 individuals (mean 53 yrs.; M/F ratio 9: 3) with CUD abstinent from cocaine. 44 blood samples collected repeatedly every 3 months for 9 months were bulk RNA sequenced. We began with phenotype harmonization grouping individuals with the following metrics; cocaine withdrawal, cue craving, generalized craving, perceived stress, and days of abstinence. We ran differential gene and transcript expression with time across grouping of metrics using the dream software and used the multivariate test to examine their associations. We used the association of gene-transcripts to determine genetic predispositions with clinical traits using the Multi-marker Analysis of GenoMic Annotation assessing their overlap to a reference GWAS database. RESULTS/ANTICIPATED RESULTS: Individuals were grouped in 2 clusters based on scores of cue craving, generalized craving, cocaine withdrawal, and 3 clusters based on days of abstinence from cocaine use. Gene-transcript(s) associationsrevealed genetic predisposition towards certain clinical conditions and substance use traits. Cannabis use disorder showed significant enrichment between the greater vs. lesser abstinent days, and lesser vs. least abstinent days at 9 months. The “drinks per week” trait showed significant gene enrichment between greater vs. lesser abstinent days at 9 months. Coronary artery disease was also enriched with greater vs. least abstinent days at 3 months. Lastly, significant baseline differences in predisposition to small vessel ischemic stroke were seen in responders with high vs low perceived stress. DISCUSSION/SIGNIFICANCE: These results from a robust and feasible pipeline suggest genetic predisposition in CUD for other substances and cardio-neurovascular diseases. This pilot study may lead to larger studies into whole genome-based blood biomarker approaches for monitoring abstinence and other clinical co-morbidities to be addressed in cocaine addiction recovery.

OBJECTIVES/GOALS: COVID-19 disproportionately affects patients with prior health conditions and those living at a lower socioeconomic status. Persons living with HIV (PLWH) are infected with SARS-CoV-2 at a higher rate than seronegative patients. Risk factors and incidence of post-COVID-19 comorbidities in PLWH, specifically, are still unknown METHODS/STUDY POPULATION: We will study PLWH enrolled in the Emory Centers for AIDS Research (CFAR) Registry who receive care at the Grady Ponce de Leon Center in Atlanta, Georgia to 1) investigate the incidence of, and 2) identify risk factors that predispose PLWH to post-COVID-19 comorbidities. All PLWH with documented COVID-19 (by positive SARS-CoV-2 PCR or antigen test) between March 1, 2020, and September 30, 2021, with a clinic visit within 12 months will be included. We will identify comorbidities using problem list diagnoses and ICD9/10 codes. With a predicted sample size of 395, we will use a Cox proportional hazards model for time-to-detection of comorbidity, and bivariate and multivariate logistic regression models to identify predictors of incident comorbidity within 12 months of COVID-19. RESULTS/ANTICIPATED RESULTS: o Previous work demonstrated that in PLWH, age and non-AIDS comorbidities, but not HIV-related factors, were associated with hospitalization for COVID-19 in a dose dependent fashion.18 We anticipate that rate of incident comorbidities will be significantly higher in PLWH after COVID-19 compared to PLWH without a history of COVID-19. We also expect that pre-existing comorbidities including obesity and cardiovascular disease, male sex, Black race, and older age are associated with higher incidence of post-COVID-19 comorbidities in PLWH. When stratifying by organ system, we also anticipate that prior comorbidities of an organ system will predispose patients to later complications of that same system. DISCUSSION/SIGNIFICANCE: By understanding the incidence and risk factors associated with developing post-COVID-19 comorbiditieswe can improve guidelines for treatment of groups experiencing the disproportionate impact of co-infection with HIV and SARS-CoV-2.

OBJECTIVES/SPECIFIC AIMS: The objective of this exploratory study is to evaluate the relationship between the individual genetic variants in COMTrs4680 and DRDrs1076560 and relevant alcohol use behaviors (i.e. alcohol consumption and reward processing behaviors) in non-dependent drinkers within experimentally controlled IV-ASA CAIS sessions. The overall goal of this study is to begin gathering data on the influence of individual genetic variants on alcohol consumption and other drinking-related behaviors. This will aid in the creation of a polygenic model of risk for AUD which will provide more insight into how the mesolimbic pathway is affected by alcohol use. METHODS/STUDY POPULATION: Study population: The sample included male and female non-dependent drinkers (N=149). Genotypes for functional polymorphisms in COMT (rs4680) and DRD2 (rs1076560) genes were determined for all subjects from blood samples obtained during screening. Alcohol consumption was assessed using the 90-day Timeline Followback Interviews (TLFB). Study population demographics: Self-reported gender (53.5% identified as male); Self-reported race (61.2% identified as white); Age ranged from 21-46 years old, with 22 years being the mode. Experiment: Free access (open-bar) intravenous alcohol self-administration (IV-ASA) using the computer-assisted alcohol infusion system (CAIS) paradigm; Subjects had the choice of pressing a button ad libitum for IV alcohol infusions during the session, neurobehavioral questionnaires were collected throughout the 2.5-hr alcohol infusion session. Primary outcome measures included: Total Rewards, Peak breath alcohol concentration (BrAC) achieved, and Total Ethanol consumed. Statistical Analyses: Conducted using SPSS IBM Statistics Versions 1.0.0-2482; non-dependent drinkers were organized into two groups based on their genotypes, minor allele carriers and major allele homozygotes. Outcome measures were compared between genotype groups using analysis of variance or non-parametric Mann-Whitney U-test as appropriate. RESULTS/ANTICIPATED RESULTS: -We expect the genetic makeup of the sample to be reflective of larger genome samples that are publically available (e.g. e!Ensembl) - Initial analysis for COMTrs4680 did not reveal significant effects on IV-ASA measures. Specifically, the majo DISCUSSION/SIGNIFICANCE OF IMPACT: Alcohol Use Disorder (AUD) affects millions of men and women globally. The heterogeneity within AUD individuals has made it difficult to identify biological and/or psychological factors that could be targeted for the development of treatments. By using the human laboratory model of free access IV-ASA, this study evaluated the relationship between dopaminergic genetic variants, COMTrs4680 and DRDrs1076560, and alcohol consumption in non-dependent drinkers within a controlled experimental environment. This study will begin to evaluate genetic and behavioral data that can be used to create a polygenic model of risk for AUD, which will provide more insight as to how the mesolimbic reward pathway is affected by alcohol use and contributes to risk for AUD.

OBJECTIVES/GOALS: Leveraging Patient’s Experience to improve Diagnosis (LEAPED) is our proposed method of measuring diagnostic error through seeking patient feedback on their understanding of their diagnosis and health status following emergency department discharge. To pilot test LEAPED’s feasibility, we deployed and determined patient uptake of LEAPED. METHODS/STUDY POPULATION: To test LEAPED, we employed a longitudinal cohort study design at emergency departments across one academic health system in the Mid-Atlantic region. Patients consented to complete questionnaires regarding their understanding of their diagnosis and/or follow-up steps and their health status at 2 weeks, 1 month, and 3 months following emergency department discharge. People aged 18 and older who were seen at the emergency department within the past 7 days with at least one chronic condition (hypertension, diabetes, history of stroke, arthritis, cancer, heart disease, osteoporosis, depression, and/or chronic obstructive lung disease) and one or more of the following common chief complaints: chest pain, upper back pain, abdominal pain, shortness of breath/cough, dizziness, and headache were eligible to join the study. RESULTS/ANTICIPATED RESULTS: Of those enrolled (n = 59), 95% (n = 53) responded to the two week post-ED discharge questionnaire (1 and 3-month ongoing). Of the 6 non-responders, 1 had died and 3 were hospitalized at two weeks. The average age was 50 years (SD 16) and 64% were female. Over half of participants (53%) were white and 41% were black. Almost one-third (27%) reported they were not given an explanation of their health problem on leaving the ED, and of those, a third did not have an understanding of what steps to take after leaving the ED. Participants reported a new health problem was identified after ED discharge (19%), worsening health status (12%), and health status stayed the same (16%). DISCUSSION/SIGNIFICANCE OF IMPACT: Patient uptake of LEAPED was high, which suggests that patient-report is a feasible method of evaluating diagnostic decision making and delivery to patients and yields insightful information beyond administrative data. The next steps are to validate the accuracy of patient-reported diagnostic error by comparing with administrative data.

OBJECTIVES/GOALS: Research ethics services are critical to the clinical, research, and educational missions of an academic health science center. Our ethics program aims to develop a culture where investigators are as intellectually engaged in ethical issues of scientific integrity as they are in study design, data collection, and implementation. METHODS/STUDY POPULATION: This descriptive analysis depicts the historical development, from 2010 to 2022, of our research ethics program as an exemplar of ethics integration into the research enterprise of an academic health science center that engages in translational research. In this culture, clinicians, translational researchers and their scientific peers, research participants, and community members become involved in ethics investigation, deliberation, and innovation. RESULTS/ANTICIPATED RESULTS: There are four pillars to our research ethics program: 1) research ethics consultation service, which fosters the development of ethical best practices and standards for the practice of translational research; 2) education, which provides customized training and educational opportunities in research ethics to diverse stakeholders; 3) leadership, through collaboration and partnerships; 4) scholarly engagement, in the pursuit of innovative ethics research and professional development. Through these initiatives we can engage a broad constituency of stakeholders, become an integral component of research oversight, engage as active participants in the research enterprise, and have a critical role in guiding institutional culture. DISCUSSION/SIGNIFICANCE: The integration of our ethics program mirrors the translational science continuum which promotes the multidirectional flow of ideas among ethics consultants, laboratory/clinical scientists, implementation researchers and the community.

ABSTRACT IMPACT: Findings from this study will better characterize the role of hearing loss in falls risk among patients with vestibulopathy and identify groups that are most at risk for falls. OBJECTIVES/GOALS: Vestibular dysfunction and hearing loss are independent risk factors for experiencing falls. The purpose of this study is to determine the extent, if any, to which hearing loss contributes to falls in patients with concomitant vestibular dysfunction presenting to a specialty vestibular clinic. METHODS/STUDY POPULATION: A retrospective chart review of patients ≥18 years who underwent vestibular evaluation at our institution from June 1, 2015 to October 7, 2020 will be conducted. Patients who underwent vestibular evaluation also received audiologic evaluation and degree of hearing loss will be characterized by the 4-frequency pure-tone average (0.5, 1, 2, and 4 kHz) of the better hearing ear. Falls status will be determined by the response to the following question administered at clinic-check in, ‘Have you fallen in the last 90 days?’ Demographics, comorbidities, and falls-associated medications will also be collected. RESULTS/ANTICIPATED RESULTS: A total of 3,265 unique patients who underwent vestibular evaluation in the study time period were identified. Patients will be categorized into discrete groups (benign paroxysmal positional vertigo, unilateral hypofunction, bilateral hypofunction, central dysfunction, and normal) based on laboratory results. Regression models will be developed to evaluate the potential association between degree of hearing loss and falls in patients with different types of vestibular dysfunction, while adjusting for demographics, comorbidities, and falls-associated medications. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will better characterize the role of hearing loss in falls risk among patients with vestibulopathy and identify groups that are most at risk for falls. This study may potentially indicate the importance of hearing evaluation in the work-up of patients with vestibulopathy.

OBJECTIVES/GOALS: Breast cancer survivors have a high risk for chronic disease and early mortality, especially if their psychological and physical symptoms persist beyond treatment. We compared survivors’and noncancer patient controls’health trajectories. We also examined how their relationship satisfaction—a key health determinant—impacted their health. METHODS/STUDY POPULATION: In this longitudinal study, participants were women who were married/domestic partners with an initial suggestive test of cancer identified at cancer clinics. After follow-up testing, women received either a malignant diagnosis (cancer survivors; n=139, stages 0–IIIC) or benign diagnosis (noncancer patient controls; n=69). Breast cancer survivors completed a baseline visit prior to beginning cancer treatment and two follow-up visits 6 and 18 months after treatment ended (surgery, radiation, or chemotherapy, whichever came last); noncancer patient controls completed visits within a comparable timeframe. At each visit, all women completed self-report questionnaires assessing their relationship satisfaction, insomnia, and depressive symptoms. RESULTS/ANTICIPATED RESULTS: We used mixed models and adjusted for participant age, comorbidities, cancer treatment and stage, BMI, and menopause status. At the pre-treatment visit, cancer survivors reported greater depressive symptoms than noncancer patient controls. Cancer survivors’depressive symptoms also decreased over time and were higher before treatment than at the 6- and 18-month post-treatment visits. Insomnia in cancer survivors, but not noncancer patient controls, decreased over time: insomnia was higher at the pre-treatment and 6-months post-treatment visits relative to the 18-month post-treatment visit. Survivors, but not noncancer patient controls, had lower depressive symptoms and insomnia at visits when they reported higher satisfaction than at visits when they reported lower satisfaction. DISCUSSION/SIGNIFICANCE: Cancer survivors had poorer psychological health than those without cancer before treatment, but survivors’psychological and physical health improved after finishing treatment. Survivors’satisfying relationships predicted better psychological and physical health, demonstrating the notable health benefits of survivors’relationships.

ABSTRACT IMPACT: This study aims to advance the understanding of the biological mechanisms associated with feeding disturbances in infants born to diabetic mothers through non-invasive salivary gene expression analyses and body composition measurements at birth. OBJECTIVES/GOALS: To determine if non-invasive salivary gene expression analyses and body composition measurements at birth could elucidate biological mechanisms associated with aberrant feeding behaviors and disrupted metabolic profiles commonly seen in infants born to diabetic mothers. METHODS/STUDY POPULATION: This prospective cohort study enrolls subjects born at ≥35 weeks’ gestation without a history of intrauterine growth restriction or major congenital anomalies. The diabetic cohort is defined as infants born to mothers with gestational diabetes or type 2 diabetes. The primary outcome is salivary expression of the hunger signaling genes, AMPK and NPY2R. Secondary outcomes include infant body composition measurements, obtained by skinfold measurement and/or air displacement plethysmography, and salivary expression of the adipokines, leptin, ghrelin, and adiponectin. Multiple logistic regression will be used to determine which factors are associated with AMPK and NPY2R expression. RESULTS/ANTICIPATED RESULTS: We propose that poor oral intake seen in infants of diabetic mothers may be due to alterations in the expression of hunger signaling genes (decreased expression of AMPK; increased expression of NPY2R) resulting in a diminished feeding drive in these large for gestational age infants. In addition, infant adiposity and the expression of genes involved in the adipoinsular axis will be inversely proportional to feeding volume intake. Namely, increased neonatal fat mass will be associated with increased expression of leptin and decreased expression of ghrelin and adiponectin. DISCUSSION/SIGNIFICANCE OF FINDINGS: Infants of diabetic mothers are at higher risk of poor oral feeding in the newborn period. This study aims to elucidate the link between neonatal body composition, adipoinsular axis, and hunger signaling to explain this unique feeding phenotype.

OBJECTIVES/GOALS: Inexpensive, accurate home monitoring is the standard-of-care in many diseases like hypertension or diabetes; however, it has yet to be widely used in neurodegenerative diseases. We used wearable activity monitors and computer-vision evaluated assessments to estimate Parkinson’s disease (PD)-related disease burden. METHODS/STUDY POPULATION: We recruited 22 people from the University of Iowa Movement Disorders Clinic. Each person completed a standardized set of 3 fine motor tasks using their hands. We recorded a video of this activity, which was evaluated using MediaPipe - an open-source pose classification program from Alphabet - as well as had an nurse-practitioner evaluate the performance on a validated scale (UPDRS). Participants wore a Fitbit Inspire 3 activity tracker at home for the next two weeks. We quantified disease burden using the Parkinson’s Disease Questionnaire 39 - a validated 39-item survey about the intensity of PD-related impairment. Using data from the videos and activity trackers, we estimated 1) the standardized UPDRS assessment of motor impairment and 2) the total PDQ-39 score. RESULTS/ANTICIPATED RESULTS: We found observationally recorded fastest sustained (at least 5 minutes) walking speed was a strong predictor of PDQ-39, explaining over one third of the variability in the measure. Range of motion in the videos was a significant predictor of UPDRS scores; however, was only weakly related to the overall PDQ-39 score. Further processing of the signals from the video, including wavelets and frequency domain analysis, may provide better predictive capabilities. PDQ-39 subscores (e.g., cognition, social support, mobility) will be the subject of further analysis. DISCUSSION/SIGNIFICANCE: Home monitoring has become the standard in other fields because of the better generalizability of home measurements. Improving the detection and evaluation of PD using home monitoring will lead to more timely and accurately changes in medication and less need for clinic visits - especially off levodopa.

OBJECTIVES/GOALS: This study evaluates the utility of self-reported quality of life measure in children with hearing loss. We will compare self-reported HEAR-QL scores with parent-reported HEAR-QL scores. We will then test the relationship between HEAR-QL scores and scores on a standardized assessment of cognition, the NIH Cognition Battery. METHODS/STUDY POPULATION: We will administer the HEAR-QL questionnaire to children with hearing loss and their parents. We will then administer the NIH Cognition Battery to the child. We will include in our population children ages 7 to 14 with hearing loss of any severity or side. We will exclude those with intellectual disability, disorders of speech or language, or those who would be unable to complete the questionnaires for any reason. Children will be recruited from Otolaryngology clinics at St. Louis Children’s Hospital based on ICD diagnosis of sensorineural hearing loss between 01/2015 – 03/2020. RESULTS/ANTICIPATED RESULTS: We will aim to recruit 44 patients in total, which is the sample size needed to detect a moderate correlation (r = 0.4) with a 1-sided α = 0.05 and 1-β = 0.8. HEAR-QL scores and NIH Cognition Battery scores will be reported using descriptive statistics. Linear regression as well as correlation analysis between HEAR-QL scores and cognitive testing scores will be performed using a 1-sided α = 0.05, with 1-β = 0.8. If recruitment is sufficient, we will adjust for demographics that are significantly correlated with the outcome on multivariate analysis. Finally, we will test for agreement between parent report and child report by calculating a Kappa statistic. DISCUSSION/SIGNIFICANCE OF IMPACT: There is little clarity on the necessity of amplification in children with hearing loss, yet the child’s perspective is not routinely assessed in clinical practice. This study employs self-report in a pediatric population with hearing loss to find out if children provide new and reliable information.

OBJECTIVES/GOALS: This study was performed to explore the capabilities of simultaneous [89 Zr]trastuzumab-PET/MRI acquisition in a cohort of metastatic HER2+ breast cancer. The insights derived provide additional noninvasive characterization and precise intratumoral analysis tools for healthcare providers. METHODS/STUDY POPULATION: A total of 13 patients, aged between 40 and 70, diagnosed with HER2-positive breast cancer, were selected to participate in this study. Whole-body [89 Zr]trastuzumab-PET/MR imaging was performed 5 ± 1 days post-injection of the radiopharmaceutical during ongoing HER2-directed therapy. Concurrently acquired T1-weighted MRI facilitated the identification of normal organ and tumor regions of interest, which were further analyzed for mean ADC and mean standardized uptake value. Multiparametric intratumoral habitat analysis was performed. Utilizing the median metric values, tumors were evaluated for heterogeneity, specifically assessing high and low HER2 expression through an image processing framework in conjunction with ADC metrics. Long-term treatment response evaluation is ongoing. RESULTS/ANTICIPATED RESULTS: Initial analysis indicate all tumors exhibited higher overall uptake of [89 Zr]trastuzumab across various sites including the bone (p=0.019), brain (p=0.014), and breast (p=0.069), when compared to corresponding normal organs. Additionally, increased ADCmean values were observed in all regions besides brain tumors (bone: p=0.002, brain: p=0.5, breast: p=0.03, juxtapulmonary: p=0.037), indicating distinct patterns of cellularity. Notably, one of five patients with a breast lesion, who exhibited a complete response to HER2-targeted therapy, exhibited the highest breast lesion SUVmean. Brain and lymph node lesions demonstrated intratumoral heterogeneity of HER2 expression. Qualification of multi parametric maps is anticipated to inform on intratumoral heterogeneity DISCUSSION/SIGNIFICANCE: Despite limitation in clinical applications of quantitative approaches due to lack of standardization of processing, initial investigations, in combining molecular imaging of HER2 and quantitative MRI demonstrate potential in characterizing metastatic HER2+ breast cancer for intratumoral classification and therapeutic stratification.

OBJECTIVES/SPECIFIC AIMS: As pediatric care becomes more concentrated in large urban hospitals, smaller rural hospitals with reduced pediatric care capacity may opt to transfer pediatric patients to higher levels of care even if the patient has a condition that is manageable in a general ED. Up to 20-40% of pediatric transfers are considered avoidable, placing a burden on the patient, their family and the health care system. The aim of this study is to determine the association between pediatric readiness (as measured by the National Pediatric Readiness Project score) and risk of interfacility transfer. We hypothesized that emergency departments with higher measures of pediatric readiness would be less likely to transfer pediatric patients to another facility. METHODS/STUDY POPULATION: The most recent and complete National Pediatric Readiness Project data were from 300 California hospitals in 2012. These data include the overall pediatric readiness score, presence of inter-facility guidelines (written protocols on patients needing care not available at the hospital), presence of interfacility agreements (written agreements with other hospitals regarding transfer patients), and other variables on the facility’s capacity to care for pediatric patients. We linked these hospital data with patient encounter data from the California Office of Statewide Health Planning and Development Emergency Department (ED) Database (OSHPD) using hospital name and zip code. To be eligible for the study, the patient must have a documented ED encounter and be less than 18 years old during the encounter. A patient was considered a transfer patient if they were transferred to a separate general hospital, children’s hospital, federal health care facility, rehabilitation facility, Critical Access Hospital or psychiatric hospital. Chi-square tests and t-tests were used for descriptive statistics. For non-normal data, we used the non-parametric Kruskall-Wallis test. We also used logistic regression to compare the odds of transfer between comparison groups. Statistical analyses were conducted in the R environment version 3.4.4. RESULTS/ANTICIPATED RESULTS: In 2012, there were 2,604,723 pediatric ED encounters, of which 10,966 resulted in a transfer (0.4%). Transferred patients on average were older (15 vs. 5 years, p < 0.001) and more likely to be female (58.6% vs 46.6%, p < 0.001). The transfer group originated from hospitals with a lower median pediatric readiness score (76.0 vs 78.3, p < 0.001). Patients were less likely to be transferred if they were seen at a hospital with written guidelines with transfer protocols (OR 0.89, 95% CI 0.83—0.95, p < 0.001). Patients were more likely to be transferred if they were seen at a hospital with written interfacility agreements with other hospitals (OR 1.17, 95%CI 1.10—1.25, p < 0.001). We anticipate, that even with more sophisticated multilevel statistical models, pediatric readiness scores will remain associated with odds of transfer. DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary data suggest that hospitals with higher levels of pediatric readiness and written guidelines with transfer protocols are less likely to transfer pediatric patients. There may be actionable policy and procedural items that a hospital could enact to lower the rate of transfer patients. Future analyses will include more complex statistical modeling to adjust for confounders, will include inpatient data, and will compare the risk of potentially avoidable transfers between hospitals with varying levels of pediatric readiness.

OBJECTIVES/GOALS: To determine the relationship among serum concentration of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and mortality in community-acquired pneumonia (CAP) patients. METHODS/STUDY POPULATION: This is a multicenter 2-year cohort study in Spain, designed to better understand the role of sTWEAK concentrations in CAP patients. CAP patients were prospectively enrolled in two University hospitals and sTWEAK was measured within the first 24 hours of ICU admission. Samples were collected and stored for laboratory analyses. To detect sTWEAK in human samples, we used a commercially available ELISA kit following manufacturer’s instructions. Demographic patients’ characteristics and ICU mortality were prospectively collected. Descriptive statistics and logistical regressions were used to assess the proposed aims. RESULTS/ANTICIPATED RESULTS: A total of forty-three patients were included in the study (10 healthy users, 10 uninfected controls and 23 CAP patients). In comparison to healthy volunteers, patients admitted to the hospital (both, infected and non-infected) had lower level of sTWEAK. During hospital admission, 7 (17%) patients died. Patients whom died during ICU stay due to CAP, had significantly lower levels of sTWEAK when comparing with patients whom survived (Median [IQR]; 509.35 [357.49, 953.92] Vs 1103.03 [716.93, 1663.16]; p = 0.015). In contrast, patients that developed shock did not have different concentrations of sTWEAK (Median [IQR]; 1008.04 [531.87, 1390.80] Vs 1062.29 [575.24, 1598.83], p = 0.84). DISCUSSION/SIGNIFICANCE OF IMPACT: Community-acquired pneumonia (CAP) is the first cause of death in underdeveloped countries. CAP is a pulmonary infection that creates a proinflammatory environment not just locally but also systemically, secondary to upregulation of molecular cascades with a wide variety of proteins being released perpetuating this inflammation and tissue damage. Several of these molecules have been described and linked to a greater risk of inhospital complications, longer length of hospital stay and mortality. TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF-alpha superfamily, involved in immune response, cell growth, angiogenesis, NF-kB activation and apoptosis induction in tumor cells. It is known that serum-TWEAK plays a role in inflammatory processes, however, its behavior is unknown in patients with CAP. Therefore, this study aims to identify whether there is a relationship between serum concentration of TWEAK and prognosis in CAP patients. To our knowledge, this is the first study to shown that concentration of sTWEAK within the first 24 hours of ICU admission is lower in patients with CAP. Moreover, patients whom died during ICU admission due to CAP, have lower sTWEAK levels. This biomarker may identify patients at higher risk of dying due to CAP and may represent severe CAP. However, further studies are needed to confirm these findings.

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to investigate the associations of systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) with knee articular cartilage composition using magnetic resonance imaging (MRI)-based T2 relaxation time measurements in study participants from the Osteoarthritis Initiative (OAI). METHODS/STUDY POPULATION: In this longitudinal study, 1,139 participants from the OAI, a multi-center, observational study of the evolution of knee OA, were selected using the following inclusion criteria: right knee Kellgren Lawrence (KL) score (radiographic classification of OA severity) 0-2 indicating no to mild radiographic OA at baseline, no history of rheumatoid arthritis at baseline, available blood pressure measurements at baseline, available T2 measurements in at least three knee compartments at baseline and 48-month follow-up. Linear regression models were performed using standardized values for SBP, DBP and PP as primary predictors and change in cartilage T2 over 48 months, a measure of cartilage matrix quality and degeneration, as the primary outcome. PP was defined as SBP minus DBP. Change in superficial layer and deep layer cartilage T2, which reflect differences in the laminar organization of knee cartilage T2, were also included as outcomes. Statistical models were adjusted for common risk factors for knee OA (baseline age, sex, BMI, KL score) as well as number of currently used anti-hypertensive medications (AHM) reported at baseline. We included AHMs whose primary indication was the treatment of hypertension including beta blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), thiazides, chlorthalidone, dihydropyridine calcium channel blockers (CCB) and aliskiren. All predictors, outcomes and covariates (except sex) were analyzed as continuous variables. We included interaction terms in the models to evaluate whether the covariates (age, sex, BMI, KL score, number of AHMs) modified the association of SBP, DBP and PP with cartilage T2. RESULTS/ANTICIPATED RESULTS: The average age of all study participants was 58.8 years (SD ± 8.6) with a higher proportion of men (59.4%), average body mass index (BMI) was 28.3 (SD ± 4.5), average SBP was 122.4 (SD ± 15.4) mmHg, average DBP was 75.5 (SD ± 9.6) mmHg and 469 (38.1%) study participants were taking at least one AHM. Higher baseline DBP was significantly associated with a faster increase in global T2 (0.22 [0.10,0.35], P < 0.001), global deep layer T2 (0.20 [0.03,0.36], P < 0.022) and global superficial layer T2 (0.39 [0.20,0.58], P < 0.001). These associations were significant in both unadjusted and the models adjusted for age, sex, BMI and KL score. No significant associations were found between SBP or PP and cartilage T2 and no significant interactions were found between SBP, DBP, PP and the covariates. DISCUSSION/SIGNIFICANCE OF IMPACT: Higher baseline DBP was associated with a faster increase in knee cartilage T2, suggesting accelerated cartilage degeneration. This association was stronger for the superficial layer of knee cartilage T2 compared to the deep layer. Although further basic mechanistic studies are needed to elucidate the underlying pathophysiology of this relationship, these results suggest lowering DBP may influence knee OA.