bluuebunny/crossref_metadata_2025 huggingface dataset:
401 Creating a Dashboard to Increase Efficiency in Tracking and Reporting on Research Data Requests
Authors: Nerogic Abigail , Lawson Virginia , Rodgers Larisa
Published: April 2023

OBJECTIVES/GOALS: The purpose of the project was to create a Tableau dashboard to track metrics on requests for research data at Atrium Health Wake Forest Baptist. The objectives included: 1) define and identify request fulfillment metrics, 2) build a dashboard to capture metrics, and 3) integrate the dashboard into metrics tracking and reporting activities. METHODS/STUDY POPULATION: Project managers and team leaders in the Office of Informatics collaborated to determine which measures would be most relevant and impactful to report on. Metrics that were collected included: total count of tickets fulfilled over time, number of tickets currently open, sum of outstanding quoted hours, quoted hours vs. actual hours needed to fulfill ticket, and hours billed. Tableau's direct connection feature was used to extract the Trac ticket data from its Postgres database and the dashboard was published to Tableau Server. After the initial draft was created, several rounds of revisions were made as new data insights were discovered through further investigation of the data. RESULTS/ANTICIPATED RESULTS: Each morning, Tableau Server runs an automatic refresh of the data. On the dashboard homepage, users can see a quick view of all available metrics; to minimize noise, only the current statuses, active tickets, and stats for the most recent monitoring periods are displayed. Many of the charts give the user the option to link out to a page with related supplemental information (historic data, ticket status history, etc.). With the help of the dashboard, project managers and team leaders can now monitor how long tickets are in each status, increase quote accuracy using the hours quoted and hours billed charts, and examine ticket complexity over time. DISCUSSION/SIGNIFICANCE: Prior to dashboard creation, metrics were sparse and difficult to assemble. By providing information on the quantity, size, and complexity of data requests, the dashboard enables the Office of Informatics to monitor how the process is functioning overall, make informed decisions about resource allocation, and provide quick interventions.
405 Integrating a Learning Health System Framework Into a Large Academic Medical Center
Authors: Azad Namitas , DiMaria Elisabeth Swift
Published: April 2023

OBJECTIVES/GOALS: The Learning Health System (LHS) framework at Columbia University Irving Medical Center (CUIMC) aims to optimize health system performance through enhancing the patient and care team experience, reducing inequities, costs and improving population health outcomes, through a collaborative, interdisciplinary and data driven approach. METHODS/STUDY POPULATION: In alignment with the Quintuple Aim, the LHS program at CUIMC is composed of five critical components: data integration (particularly using Epic EHR and real-time informatics data), utilization of evidence-based practices, a methodology for continuous improvement, and leadership commitment. Our methodology incorporates an iterative process improvement project cycle into an integrated infrastructure and governance of an academic medical center and its hospital partners to fulfill rapid project design and implementation. The LHS at CUIMC aims to bring a cultural shift through stakeholder engagement, symposia, training, accelerated pilot award opportunities, and building external partnership engagement. RESULTS/ANTICIPATED RESULTS: At CUIMC, our definition of a successful integration of a LHS framework is a cultural shift in thinking, method, and continuous improvement. The LHS program has developed multidisciplinary teams that are involved in defining and sharing data, design, and project management resources. In 2021, the first annual symposium was launched and brought together over 200 stakeholders from across the organization to support continuous education, training, and scaling of the framework. As a result of this foundation, two pilot initiatives have been funded and launched, the innovation accelerator model developed and is supporting over ten unique innovative and transformative clinical and operational programs, and several research grant applications have been submitted citing learning health system methodologies. DISCUSSION/SIGNIFICANCE: Our LHS framework has broken down silos and institutional barriers, creating a network of stakeholder groups. Our interdisciplinary approach has enabled us to create sustainable processes, resources and training on rapid, rigorous design, evaluation and implementation of interventions using real-time informatics data and digital health tools.
406 Living Review of World Trade Center Health Effects
Authors: Katruska Alan , Santiago-Colón Albeliz , Iker Kristen
Published: April 2023

OBJECTIVES/GOALS: The goal of this project is to develop a strategy to collect and extract published evidence in real time and to house and model these data for efficient downstream application to Program activities such as targeted reviews, grant evaluation and partner engagement. METHODS/STUDY POPULATION: We created the World Trade Center Health Effects Library in 2016. Today, this living review is ongoing and is fueled by daily systematic searches of online publication databases. Each day we screen new references for health effects of 9/11. The publication must include measurements, reports, or discussion of 9/11 health effects. If a publication meets these criteria, it is categorized by outcome and funding category. Primary outcome category data, reference metadata, and funding data are then made immediately available for programmatic analysis. All reference data are entered into a data pipeline and modelled for targeted reviews. RESULTS/ANTICIPATED RESULTS: The WTC Health Effects Library curates 1932 references and adds an average of 60 new references each year on a wide range of study populations, exposures, and conditions. The completeness of the library has been verified by comprehensive literature searches for 9/11 health outcomes conducted externally and by CDC Library staff. As a result, the curated library is a proven alternative to a lengthy literature search and allows the Program and stakeholders to explore the data and engage immediately in targeted reviews on curated topics. The data that are collected in the screening and categorization process are merged with publication metadata and funding data to inform a data pipeline that supports outputs such as interactive visuals, charts, reports, and curated bibliographies for structured review. DISCUSSION/SIGNIFICANCE: This living review allows the Program to rapidly conduct focused reviews, to evaluate grants, and to communicate accurate data to partners. By using the curated data, we have reduced the time required to perform mandated evidence reviews by weeks, have conducted two structured reviews, and defined gaps in research maturity and health equity.
428 Development of an Oncolytic Adenovirus to Treat Metastatic Colorectal Cancer
Authors: LaRocca Christopher J. , Wilber Stacey , Jensen Eric , Subramanian Subree , Steer Clifford , Davydova Julia
Published: April 2023

OBJECTIVES/GOALS: Colorectal cancer (CRC) is a leading cause of cancer mortality, and many patients will develop metastatic disease at some point during their treatment course. Conventional therapies such as surgery, chemotherapy, and radiation are often of limited effectiveness in these advanced stages, which necessitates the development of novel therapies. METHODS/STUDY POPULATION: Our group has designed an oncolytic adenovirus backbone structure expressing the sodium iodide symporter (NIS) which can be used in conjunction with radioiodine to facilitate cancer imaging and therapy. Using multiple CRC cell lines, oncolytic adenoviruses with different fibers were tested in vitro to determine which of these modifications yielded the highest binding to the cancer cells. Additionally, multiple promoter structures are being tested to determine the impact on the replication and oncolytic effect of the virus. Furthermore, the potential of adenovirus-mediated NIS expression to facilitate PET/CT imaging and therapy with I-131 will be explored. RESULTS/ANTICIPATED RESULTS: The Ad5/3 chimeric fiber modification demonstrated the best binding in CRC cell lines. Additionally, tissue specific promoters are employed in oncolytic viruses to confer selective replication in cancer cells, while minimizing off target effects in nearby normal tissues. We have employed a Cox2 promoter, which has demonstrated an excellent oncolytic effect. In vitro NIS expression was shown in multiple CRC cell lines through immunostaining. Small animal PET/CT imaging demonstrated signal uptake in mice with subcutaneous CRC tumors after virus and radioiodine (I-124) administration. We anticipate that future studies employing radioactive iodine (I-131) in combination with our oncolytic virus will yield an augmented antitumor effect. DISCUSSION/SIGNIFICANCE: The NIS-expressing adenovirus has the ability to support radionuclide-based imaging and therapy for CRC. With additional pre-clinical testing, our adenovirus construct has the potential to bring NIS-based therapeutics to the bedside to positively impact CRC patient care outcomes.
436 Novel approach for tracking interdisciplinary research productivity using institutional databases
Authors: Bengert Elizabeth , Noyes Katia , Towle-Miller Lorin , Boccardo Joseph , Mercene Geoffrey , Ohtake Patricia J. , Balkundi Prasad , Elkin Peter L. , Balthasar Joseph , Murphy Timothy F.
Published: April 2023

OBJECTIVES/GOALS: This study proposes a pragmatic approach for tracking institutional changes in research teamwork and productivity in real time using common institutional electronic databases such as eCV and grant management systems. Dissemination of this approach could provide a standard metric for comparing teamwork productivity across different programs. METHODS/STUDY POPULATION: This study tracks research teamwork and productivity using commonly available institutional electronic databases such as eCV and grant management systems. We tested several definitions of interdisciplinary collaborations based on number of collaborations and their fields of discipline. Publication characteristics were compared by faculty seniority and appointment type using non-parametric Wilcoxon Rank Sum Test (p RESULTS/ANTICIPATED RESULTS: Interdisciplinary grants constitute 24% of all grants but the trend has significantly increased over the last five years. Tenure track faculty collaborated with more organizations (3.5, SD 2.5 vs 2.3, SD 1.1, p DISCUSSION/SIGNIFICANCE: This study provides empirical evidence of the benefits of interdisciplinary collaboration in research and identifies an important role that senior faculty may be playing in creating the culture of interdisciplinary teamwork. More research is needed to improve efficiency of interdisciplinary collaborations.
444 Team Science Competencies for Clinical Research Professionals: Determining Skills and Leveling Through a Modified Delphi Approach
Authors: Mendell Angela , Fritter Jessica , Summerside Nicole , Capili Bernadette 'Candi' , Exe Nicole , Hildreth Laura , Kopras Elizabeth J. , Colagreco Joe , Ronning Andrea , Johnson Kathryn , Varnadoe-Rothman Christa , Helm Shirley , Kolb Bob , Jones Thomas
Published: April 2023

OBJECTIVES/GOALS: Team science competencies are not well-defined for nonfaculty staff of Clinical Research Professionals (CRPs) who conduct research. Using an existing framework, our work has determined skills associated with team science competencies as related to CRPs. Our team also outlined examples of those skills on a fundamental, skilled, and advanced level. METHODS/STUDY POPULATION: The team consists of both CRPs and those working in the Team Science space. This team used a modified Delphi approach to determine the skills and leveling examples of each team science competency. The team broke into four groups and was assigned 3-4 competencies each. Each group determined skills needed to support (exhibit, promote) each competency and then described an example of this skill at the fundamental, skilled, and advanced levels. Once each group was finished with their assigned competencies, they were re-assigned to a different group for review and changes. Finally, team science and CRP experts reviewed the skills and levels. RESULTS/ANTICIPATED RESULTS: Our results are a rubric that defines 3-5 practical skills per described competency. These skills are needed to support and promote each competency as a CRP. An additional outcome from this work includes examples of each skill at the fundamental, skilled, and advanced levels in a CRP’s career. Each leveled example is described in a concise, actionable way using Bloom’s taxonomy. This rubric is meant to be easily understood, very useable and able to be used in conjunction with existing CRP competency frameworks. By using Bloom’s taxonomy, we set the stage for future educational programming in Team Science skill-building for clinical research professionals. DISCUSSION/SIGNIFICANCE: Team science concepts and competencies have been increasingly integrated into translational science teams. However, team science competencies related to CRPs have remained largely undefined. Our work helps to define these competencies for CRPs in a practical way. Our rubric fills gaps in, and builds on, existing CRP competency frameworks.
447 Characterization of the human iridocorneal angle in vivo using a custom design goniolens with OCT gonioscopy
Authors: Carmichael-Martins Alessandra , Gast Thomas J. , Burns Stephen A. , Walker Brittany R. , King Brett J.
Published: April 2023

OBJECTIVES/GOALS: The trabecular meshwork (TM) and Schlemm’s canal (SC), located within the iridocorneal angle (ICA), form the main outflow pathway and a major target for glaucoma treatments. We characterized the human ICA in vivo with Optical Coherence Tomography (OCT) imaging using a customized goniolens and a commercial OCT device (Heidelberg Spectralis). METHODS/STUDY POPULATION: Imaging these structures is difficult due to the optical limitations of imaging through the cornea at high angles. Therefore, a clinical gonioscopy lens was modified with a 12mm plano-convex lens placed on its anterior surface to focus light on the ICA structures, and capture returning light. Each subjects’ eye was anesthetized with 1 drop of Proparacaine 0.5%. The goniolens was coupled to the eye with gonio-gel and it was held by a 3D adjustable mount. OCT volume scans were acquired on 10 healthy subjects. The linear polarization of the OCT was rotated with a half-waveplate to measure dependence of the ICA landmarks on polarization orientation. RESULTS/ANTICIPATED RESULTS: The TM was seen in 9 of 10 subjects. Polarization rotation modified the brightness of the band of extracanalicular limbal lamina (BELL) and corneoscleral bands due to the birefringent nature of the collagenous structures, increasing the contrast of SC. SC width was 99 ± 20Âµm varying in size over space, including a subject with SC narrowing in the inferior-temporal quadrant. DISCUSSION/SIGNIFICANCE: This clinically suitable gonioscopic OCT approach has successfully been used to image the human ICA in 3D in vivo, providing detailed characterization of the TM and SC as well as enhancing their contrast against their birefringent backgrounds by rotating the polarization of the imaging beam.
448 Establishing the efficacy of naturally occurring endocannabinoid-like substance in an in vitro model of Fragile X Tremor/Ataxia Syndrome (FXT/AS)
Authors: Brown Collis , Sobrian Sonya , Hudson Tamaro
Published: April 2023

OBJECTIVES/GOALS: FXT/AS is a devastating, rare neurological syndrome that negatively impacts movement and cognition and is suspected to induce mitochondria dysfunction. Currently, no effective pharmacological treatments for FXTAS exist. The goal is to restore mitochondrial viability using endocannabinoid-like compounds in a cell culture model of FXTAS. METHODS/STUDY POPULATION: To establish a cell model of mitochondrial dysfunction, fibroblast baby hamster kidney (BHK-21) cell lines were treated with glucose oxidase (GluOx) at varying concentrations and times. Mitochondrial viability was assessed by the colorimetric Janus B Green Assay, which stains the mitochondria and enables assessment of cell numbers and the presence of oxygen in anchorage-dependent cell culture. Upon establishing this model of mitochondrial dysfunction, we next investigated the ability of three novel mitochondrial antioxidants (e.g., macamides) to protect mitochondrial viability. RESULTS/ANTICIPATED RESULTS: GluOx treatment of BHK-21 cells caused a dose- and time-dependent increase in oxidative stress. The data demonstrated significant disruption in the morphology of BHK-21 cells at a high glucose concentration, i.e., 40 nM, between 2 and 24 hours post-exposure. The morphology data were confirmed by the Janus B Green colorimetric assay. In examining the effects of glucose on mitochondrial viability, we demonstrated that at 15, 30, 35, and 40 nM, glucose significantly decreased mitochondria viability compared to the untreated, with 40 nM having the greatest effect. Under these conditions of mitochondrial dysfunction, co-incubation of the cells with the 0.5 uM MAM69 macamide attenuated the GluOx-induced increase in oxidative stress, with 0.5 uM MAM69 alone showing no effect on mitochondria viability. DISCUSSION/SIGNIFICANCE: This study illustrates the efficacy of macamides, natural occurring endocannabinoid like-compound, as novel prognostic and therapeutic candidates in the treatment of mitochondrial dysfunction that is associated with FXTAS. The use of BHK-21 fibroblast cells provides a rapid screening model to test for pharmacological therapeutic efficacy.
451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation
Authors: Asher Amber M. , Morilak David A.
Published: April 2023

OBJECTIVES/GOALS: We will use a novel syngeneic model of prostate cancer to examine impairments and uncover potential changes in inflammatory signaling in the brains of animals with and without tumors. We will then investigate the interaction between peripheral tumor, age, and chemotherapy on cognitive impairments and any accompanying neuroinflammation METHODS/STUDY POPULATION: Male Copenhagen rats (aged 3 or 10 months) were subjected to tumor fragment implantation (Dunning R2237G cells) or sham surgery. Once tumors were palpable, animals received either docetaxel (4.5mg/kg, intraperitoneal) or it’s vehicle once every other day for 5 days (3 injections total) followed by a two-week recovery period. During this time, TNFa and IL-6 was quantified in plasma samples obtained once per week for two weeks. Hippocampal-mediated visuospatial and working memories were assessed using the novel object task and percent alternation in a y-maze, respectively. Afterwards, trunk blood and hippocampal tissue were isolated. TNFa and IL-6 protein was quantified in plasma. Hippocampal tissue was probed for markers of neuroinflammation, including increases in TNFa, IL-6, and reactive microglia RESULTS/ANTICIPATED RESULTS: The presence of a tumor alone produces deficits in hippocampal-mediated visuospatial memory and working memory regardless of treatment and persistent elevations in TNFa and IL-6 in plasma. Docetaxel administration also produces impairments in hippocampal-mediated visuospatial memory, but not in working memory. We anticipate these cognitive impairments will be accompanied by hippocampal neuroinflammation. We expect age and docetaxel chemotherapy to exacerbate working memory deficits and markers in hippocampal neuroinflammation, including increases in TNFa, IL-6 and reactive microglia DISCUSSION/SIGNIFICANCE: This study will provide insight into the interaction between tumor, age, and chemotherapy in impairments in visuospatial memories. This model provides a substrate upon which interventions can be tested to ensure the efficacy of the cancer treatment is maintained when treating these cognitive impairments.
457 Assessment of Mental Health Needs of Transgender Adults Seen at a Midwest Transgender Center
Authors: Cortez Samuel
Published: April 2023

OBJECTIVES/GOALS: Prior studies suggest that transgender individuals are at greater risk of mental health problems. This study aims to determine the mental health care needs of the adult transgender population seen at a tertiary referral hospital in the Midwest region of the United States and assess necessary resources to provide optimal care. METHODS/STUDY POPULATION: This descriptive, retrospective, cross-sectional study included all new transgender patients > 18 years old, seen at the Washington University Transgender Center since December 2019 through May 2022. Electronic medical record data obtained from their initial and subsequent follow-up visits include 1) Demographics: date of birth, age, race, ethnicity, sex assigned at birth, gender identity, zip code of residency 2) Mental health diagnosis: Previous mental health diagnosis, mental health history 3) Mental health care access: mental health providers, mental health treatment, previous mental health admission, resources provided in clinic. RESULTS/ANTICIPATED RESULTS: 487 patient records were reviewed. Median age at initial visit was 24 years (18 - 75 yr), with 46% identify as woman, 37% as man. Predominantly white (84%), 11% were black. 93% had primary health insurance At the first visit, 81% reported having some mental health diagnosis: depression (88%), anxiety (71%), attention deficit disorder (21%). Prior suicide attempt reported on 12% and 5% with self-harm behavior. Only 48% had a therapist and 22% had an established psychiatrist First follow up occurred with a median of 4 months (1-22 months). 4 patients reported new suicide attempt, 3 reported new self-harm behavior. 9 patients required a hospital admission due to a psychiatric condition. 4% reported a new mental health diagnosis (most common: depression and anxiety). No changes noted on access to therapist or psychiatrist DISCUSSION/SIGNIFICANCE: Our study shows that adult transgender individuals have high rates of depression, anxiety, and overall psychological distress which is exacerbated by poor access to mental healthcare. This indicates a critical need to include mental healthcare professionals during the evaluation of adult transgender individuals
466 Development of a novel tocotrienol analogue, tocoflexol, as a radiomitigator
Authors: Shrimali Shivangi , Singh Awantika , Manian Rajeshkumar , Thakkar Shraddha , Jones Darin E. , Aykin-Burns Nukhet , Breen Philip , Compadre Cesar M.
Published: April 2023

OBJECTIVES/GOALS: We have designed an analogue of the Vitamin E tocotrienols called tocoflexol, which improves their pharmacokinetic limitations to make it an effective radiation medical countermeasure. Our goal is to demonstrate that tocoflexol is an effective radiomitigator in vivo when administered after exposure to lethal doses of total body irradiation. METHODS/STUDY POPULATION: Tocoflexol was designed using computational techniques to improve binding to ATTP, the key transporter that reduces the rate of elimination of tocols. In vitro studies compared the antioxidant and cell uptake properties to conventional tocotrienols. Next, we used a mouse model of lethal total body irradiation to evaluate its radioprotection efficacy (treating before radiation). To determine the optimal administration route for radiomitigation (treating after radiation), we will test oral and subcutaneous dosing. Mouse survival will be monitored for 30 days after irradiation. Sample tissues will be taken to evaluate the ability of tocoflexol to protect key organs from acute radiation syndrome. The bioavailability of tocoflexol will be evaluated in a rodent model. RESULTS/ANTICIPATED RESULTS: Known Results: Results show that tocoflexol has potent antioxidant properties and high cell uptake. When tocoflexol was administered 24 hours before exposure to lethal doses of radiation, tocoflexol-treated mice showed 100% survival. Anticipated Results: Because of its improved bioavailability and pharmacokinetic properties, we expect that tocoflexol will show radiomitigation efficacy when administered 24 hours after radiation, improving survival and protecting key organ systems from acute radiation syndrome. DISCUSSION/SIGNIFICANCE: There is an unmet need for safe and effective radiomitigators that can offer multi-organ protection and be rapidly administered in the event of nuclear emergencies. Demonstration of radiomitigation efficacy will position tocoflexol as a prime candidate to be developed into a nuclear medical countermeasure and stockpiled for emergencies.
475 Financial Toxicity in Dementia Caregiving
Authors: Hart Danielle M. , Leggins Brandon , Sanches Clara , Chiong Winston
Published: April 2023

OBJECTIVES/GOALS: Financial toxicity describes the adverse effects of medical expenses on financial security and health related quality of life. Though dementia caregiving carries serious costs, financial toxicity has not been studied in this context. Here we assess the prevalence of financial toxicity in dementia caregiving and its sociodemographic correlates. METHODS/STUDY POPULATION: We utilized the COmprehensive Score for financial Toxicity (COST)â€” 12-item questionnaire validated to quantify financial toxicity in patients and their caregiversâ€” to conduct a nationally representative survey of 317 US dementia caregivers, oversampling non-Hispanic Black (n = 75) and Hispanic (n = 61) caregivers. Participants were required to be currently providing unpaid care to someone 50 years or older with dementia. Financial toxicity was defined as COST 0 & RESULTS/ANTICIPATED RESULTS: COST scores ranged between 0 and 44, with a survey-weighted mean of 24.57 and standard deviation of 9.8. Weighted analysis revealed 52.7% of American dementia caregivers experience some degree of financial toxicity. Of those who experience financial toxicity, 73.1% are classified as mild, 25.7% as moderate, and 1.2% as severe. Financial toxicity was identified in 69.5% of non-Hispanic Black, 54.1% of Hispanic, and 42.3% of non-Hispanic White caregivers, with non-Hispanic Black caregivers significantly more likely to experience financial toxicity compared to their non-Hispanic White counterparts (p = 0.017). DISCUSSION/SIGNIFICANCE: Most US dementia caregivers experience financial toxicity, though prevalence varies significantly by caregiver race. Discerning the pervasiveness of financial toxicity in this population and significant correlates will inform the development and expedient delivery of resources for patients and families.
493 Prevalence and Clinical Presentation of Chronic Neck Pain in Individuals with Generalized Joint Hypermobility
Authors: Abbott Rebecca , Ludewig Paula , Ellingson Arin M
Published: April 2023

OBJECTIVES/GOALS: Evidence suggests that individuals with generalized joint hypermobility (GJH), or excessive joint range of motion, are at higher risk of developing chronic neck pain. The objective of this study is to determine the prevalence and clinical presentation of chronic neck pain in GJH and investigate its associations with other measures of spine health. METHODS/STUDY POPULATION: Data was collected at the Driven to Discover Research Facility at the 2022 Minnesota State Fair. Individuals 18 years and older were invited to participate. All enrolled participants completed Phase 1, which included: the Beighton Score (measure of GJH), the 5-Point-Questionnaire (self-report survey for current or historical GJH), and a custom self-report survey for demographics and musculoskeletal pain. A subset of participants was also asked to complete Phase 2 of the study. Phase 2 consisted of additional self-report surveys (Neck Disability Index (NDI) and PROMIS-10 Global) and the following physical measures: neck range of motion in all planes, neck strength in flexion-extension and lateral bending, and grip strength. RESULTS/ANTICIPATED RESULTS: A total of 559 participants were enrolled in the study. All participants completed Phase 1, and 285 of those individuals completed Phase 2. Those with a Beighton Score≥4 were categorized as having GJH. The overall prevalence of GJH was 23.8% for females and 9.1% for males. Consistent with previous studies, multiple linear regression analysis (R2=0.20, F(2,552) = 69.37, p DISCUSSION/SIGNIFICANCE: This is one of the largest studies investigating GJH, pain, and physical measures of neck function in the general population. The results highlight the higher prevalence of chronic neck pain in those with GJH and will form the basis for a subsequent study to identify mechanisms and potential therapeutic targets for individuals with GJH and chronic pain.
495 Radon and Fracking Exposures and Lymphoma Risk in a Canine Model of non-Hodgkin Lymphoma
Authors: Tindle Ashleigh , Trepanier Lauren
Published: April 2023

OBJECTIVES/GOALS: The objective of this study was to determine whether residential radon and proximity to horizontal oil and drilling (fracking) are risk factors for the development of multicentric lymphoma in pet dogs, a spontaneous, immunocompetent model for non-occupational risk for NHL in humans. METHODS/STUDY POPULATION: Two case-control populations of dogs with multicentric lymphoma were utilized, with a focus on two dog breeds at high risk for lymphoma. Control dogs were matched for age, breed, and sex. Home addresses were collected for 54 Golden retrievers with lymphoma and 108 Golden retriever controls, and for 56 boxer dogs with lymphoma and 84 unaffected boxer controls. Counties of residence were matched to radon zones and percentage of home radon tests that exceeded the actionable level of 4 pCi/L, available by county through the EPA and the CDC National Environmental Public Health Tracking Network from 2008 to 2017. Locations of horizontal oil and gas wells were obtained from the Enverus Database, and distances from dog homes to the closest well, and well density by county, were calculated for each case and control. RESULTS/ANTICIPATED RESULTS: We found no significant differences in radon zones, county level radon measurements, or residential proximity to active fracking wells between dogs with lymphoma and unaffected controls in either the Golden Retriever or boxer populations. DISCUSSION/SIGNIFICANCE: Canine multicentric lymphoma resembles human NHL and is a valuable model of non-occupational environmental risk for NHL in people. Although we did not find geographic associations between radon and fracking wells, follow-up studies will measure household radon, as well as household air, water, and dog urine for potentially genotoxic chemicals.
500 The Aging Exposome: Characterizing Bidirectional Effects of Exposures and Aging
Authors: Gouripeddi Ram , Stewart Caden , Facelli Julio
Published: April 2023

OBJECTIVES/GOALS: The objective of this study is to synthetically generate and use records of exposure, and so that we can understand the effects of exposure on aging and vice-versa. METHODS/STUDY POPULATION: Quantifying bidirectional effects of environment and aging requires time series of data from all contributing exposures which can span endogenous processes within the body, biological responses of adaptation to environment, and socio-behavioral factors. Gaps in measured data may need to be filled with computationally modeled data. Essentially, the challenge in generating aging exposome is the absence of readily available records for individuals over the course of their life. Instead, these would need to be assimilated from historic person reported data (e.g. residential location, durations, behaviors) along with publically available data. This could lead to potential gaps and uncertainties that would need inform on how the exposomic records can be used for aging research. RESULTS/ANTICIPATED RESULTS: We present a pragmatic approach to generation of longitudinal exposomic and aging records as required for different study archetypes. Such records can then be used to understand the bidirectional effects of exposures and aging. DISCUSSION/SIGNIFICANCE: Effects of a lifetime of environmental and lifestyle exposures on aging or age-associated diseases are not well understood. Characterizing differential, additive and intense sporadic multi-agent exposures require advanced big data and artificial intelligence methods.
504 Topical adenosine treatment inhibits inflammation and mucus production in viral acute rhinosinusitis
Authors: Hua Xiaoyang , Waldstein Kody A. , Ganama Maria , Varga Steven M. , Tilley Stephen , Hua Xiaoyang
Published: April 2023

OBJECTIVES/GOALS: Viral acute rhinosinusitis (ARS), a.k.a, the common cold, affects millions every year. The symptoms caused by viral ARS dramatically affect the general well-being and functional levels of patients, causing work and school absence, and antibiotic abuse. In this study, we examined the therapeutic potential of topical adenosine in viral ARS METHODS/STUDY POPULATION: Rhinosinusitis was induced in WT and adenosine receptor (AR) knockout mice by respiratory syncytial virus (RSV) infection in the upper airways. Mice were subjected to adenosine or vehicle control within the sinuses. Adenosine receptor expression, inflammatory cytokine expression, and histologic mucus and inflammation score was assessed. The effect of endogenous adenosine accumulation within the sino-nasal tract was assessed in adenosine deaminase knockout (ADA-/-) mice. RESULTS/ANTICIPATED RESULTS: Topical administration of adenosine significantly inhibited the expression of pro-inflammatory cytokines, mucus production, and cell damage in the nose of mice with viral ARS, without prolonging virus clearance. This inhibitory effect was primarily mediated by the A2A adenosine receptor (AR). We also examined and compared the expression of ARs in the nasal tissue, trachea, and lungs. The nasal tissue exhibited the lowest baseline expression of ARs as compared to the lung and trachea which was further downregulated following adenosine treatment. Additionally, accumulation of endogenous adenosine in ADA-/- mice showed no signs of inflammation within the nasal tissue. Together, we demonstrated that topical adenosine effectively decreased inflammation and mucus production in a mouse model of viral ARS. DISCUSSION/SIGNIFICANCE: Previously, we found that topical adenosine dramatically enhances mucociliary clearance in the nose and sinuses. In this study, we found that nasal topical adenosine effectively decreased inflammation and mucus production in viral ARS. Our data suggest that nasal topical adenosine is an effective topical therapeutic option for viral ARS.
505 Use of Implementation Science to Identify Implementation Determinants of Chronic Obstructive Pulmonary Disease Practice Guidelines
Authors: Raghavan Deepa , Kirchner JoAnn
Published: April 2023

OBJECTIVES/GOALS: COPD is a progressive airways disease that results in death or disability. There is poor uptake of clinical guidelines (CPG) to manage COPD and studies to bridge this implementation gap have shown inconsistent results. Using implementation science principles we aim to understand COPD-CPG implementation determinants from providers’perspective. METHODS/STUDY POPULATION: The study is being conducted in ten VA Primary Care Clinics. Guided by the Consolidated Framework for Implementation Research (CFIR), a conceptual framework developed to guide systematic assessment of multilevel implementation contexts, we are using semi-structured guides to conduct key informant qualitative interviews (physicians, physician extenders and nurses), to support a formative evaluation. CFIR domains relevant to the study were determined by a multidisciplinary team. Informants are identified through online outreach and voluntary participation. Sampling adequacy will be assessed by achievement of code saturation. A qualitative template analysis will be used to summarize the barriers and facilitators of each component of COPD-CPG organized by CFIR-domain. RESULTS/ANTICIPATED RESULTS: We anticipate a list of modifiable and non-modifiable contextual, recipient (provider and patient), and COPD CPG content (innovation) barriers to implementation. Many settings do not have critical elements of these CPG, such as a standardized inhaler education/assessment pathway, patient education material, or pulmonary rehabilitation referral pathway. Existing literature indicate reasons behind the insufficient uptake of COPD CPG include low familiarity with guidelines, perception of minimal value of guidelines by physicians, and time constraints; we will present contextual, recipient and innovation determinants specific to our setting. DISCUSSION/SIGNIFICANCE: This comprehensive assessment of barriers and facilitators to COPD-CPG will inform tool development and implementation strategies identification to improve COPD CPG uptake. COPD is the most common veteran lung disease. Improvement in COPD care has enormous potential for benefit for local veterans, as well as potential for wider dissemination.
Peer mentoring to support career advancement among underrepresented minority faculty in the programs to increase diversity among individuals engaged in health-related research (PRIDE)
Authors: Coleman Taylor M. , Starlard-Davenport Athena , Onwuemene Oluwatoyosi A. , Stepleman Lara M. , Pace Betty S.
Published: April 2023

Although mentoring is critical for career advancement, underrepresented minority (URM) faculty often lack access to mentoring opportunities. We sought to evaluate the impact of peer mentoring on career development success of URM early career faculty in the National Heart Lung and Blood Institute-sponsored, Programs to Increase Diversity Among Individuals Engaged in Health-Related Research-Functional and Translational Genomics of Blood Disorders (PRIDE-FTG). The outcome of peer mentoring was evaluated using the Mentoring Competency Assessment (MCA), a brief open-ended qualitative survey, and a semi-structured exit interview. Surveys were completed at baseline (Time 1), 6 months, and at the end of PRIDE-FTG participation (Time 2). The following results were obtained. Between Time 1 and Time 2, mentees’ self-assessment scores increased for the MCA (p < 0.01) with significant increases in effective communication (p < 0.001), aligning expectations (p < 0.05), assessing understanding (p < 0.01), and addressing diversity (p < 0.002). Mentees rated their peer mentors higher in the MCA with significant differences noted for promoting development (p < 0.027). These data suggest that PRIDE-FTG peer mentoring approaches successfully improved MCA competencies among URM junior faculty participants with faculty ranking peer mentors higher than themselves. Among URM faculty, peer mentoring initiatives should be investigated as a key strategy to support early career scholar development.
Idea evaluation as a design process: understanding how experts develop ideas and manage fixations
Authors: Boudier Justine , Sukhov Alexandre , Netz Johan , Le Masson Pascal , Weil Benoit
Published: April 2023

Idea evaluation is used to identify and select ideas for development as future innovations. However, approaching idea evaluation as a decision gate can limit the role of the person evaluating ideas, create fixation bias, and underutilise the person’s creative potential. Although studies show that during evaluation experts are able to engage in design activities, it is still not clear how they design and develop ideas. The aim of this study was to understand how experts develop ideas during evaluation. Using the think-aloud technique, we identify different ways in which experts develop ideas. Specifically, we show how experts transform initial idea concepts using iterative steps of elaboration and transformation of different idea components. Then, relying on concept-knowledge theory (C-K theory), we identify six types of reasoning that the experts use during idea evaluation. This helps us to distinguish between three different roles that experts can move between during evaluation: gatekeeper, designer managing fixation, and designer managing defixation. These findings suggest that there is value in viewing idea evaluation as a design process because it allows us to identify and leverage the experts’ knowledge and creativity to a fuller extent.
On the connectedness principle and dual complexes for generalized pairs
Authors: Filipazzi Stefano , Svaldi Roberto
Published: April 2023

Let

$(X,B)$

be a pair, and let

$f \colon X \rightarrow S$

be a contraction with

$-({K_{X}} + B)$

nef over S. A conjecture, known as the Shokurov–Kollár connectedness principle, predicts that

$f^{-1} (s) \cap \operatorname {\mathrm {Nklt}}(X,B)$

has at most two connected components, where

$s \in S$

is an arbitrary schematic point and

$\operatorname {\mathrm {Nklt}}(X,B)$

denotes the non-klt locus of

$(X,B)$

. In this work, we prove this conjecture, characterizing those cases in which

$\operatorname {\mathrm {Nklt}}(X,B)$

fails to be connected, and we extend these same results also to the category of generalized pairs. Finally, we apply these results and the techniques to the study of the dual complex for generalized log Calabi–Yau pairs, generalizing results of Kollár–Xu [Invent. Math. 205 (2016), 527–557] and Nakamura [Int. Math. Res. Not. IMRN13 (2021), 9802–9833].
A generalized theory of flow forcing by rough topography
Authors: Radko Timour
Published: April 2023

An analytical model is developed which explores the impact of irregular sea-floor roughness on large-scale oceanic flows. The previously reported asymptotic ‘sandpaper’ theory of flow-topography interaction represents relatively swift currents and exhibits singular behaviour in the weak flow limit. The present investigation systematically spans a wider parameter space and identifies the principal dissimilarities in the topographic regulation of slow and fast currents. The fast flows are controlled by the Reynolds stresses produced by topographically generated eddies. In contrast, relatively weak flows are more affected by the eddy-induced bottom form drag. The asymptotic models for fast and slow currents are then combined to arrive at a concise description of flow forcing by small-scale topography in homogeneous and multilayer models. The proposed closure is validated by comparing corresponding topography-resolving and parametric simulations.
Electromagnetically driven anticyclonic rotation in spherical Couette flow
Authors: Proal D. , Domínguez-Lozoya D.R. , Figueroa A. , Rivero M. , Piedra S. , Núñez J.
Published: April 2023

The electromagnetically driven anticyclonic flow in the wide gap of a rotating concentric spheres system is studied experimentally and numerically in the laminar regime. The working fluid is an electrolyte contained in the spherical gap. The outer sphere rotates at constant angular speed, and the inner sphere is at rest. The electromagnetic stirring is generated due to the interaction of a direct current, which is injected radially through ring-shaped electrodes located at the equatorial zone of each sphere, and a dipolar magnetic field produced by a permanent magnet located inside the inner sphere. Experimental velocity fields in the equatorial plane were obtained with particle image velocimetry. Additionally, full three-dimensional numerical simulations were performed. The high shearing at the equatorial region promotes an instability that can be perceived as a triggering mechanism of four tornado-like vortical structures tilted and entangled in the polar direction. The instability structure rotates in either the cyclonic or the anticyclonic direction, depending on the flow parameters, namely, the angular velocity of the outer sphere and the applied electric current. To the best knowledge of the authors, this is the first time the phenomenon under study is reported with electromagnetic forcing. The numerical results agree quantitatively with the experimental observations.
The internal structure of forced fountains
Authors: Huang Jingzi , Burridge Henry C. , van Reeuwijk Maarten
Published: April 2023

We study the mixing processes inside a forced fountain using data from direct numerical simulation. The outer boundary of the fountain with the ambient is a turbulent/non-turbulent interface. Inside the fountain, two internal boundaries, both turbulent/turbulent interfaces, are identified: (i) the classical boundary between upflow and downflow which is composed of the loci of points of zero mean vertical velocity; and (ii) the streamline that separates the mean flow emitted by the source from the entrained fluid from the ambient (the separatrix). We show that entrainment due to turbulent fluxes across the internal boundary is at least as important as that by the mean flow. However, entrainment by the turbulence behaves substantively differently from that by the mean flow and cannot be modelled using the same assumptions. This presents a challenge for existing models of turbulent fountains and other environmental flows that evolve inside turbulent environments.
Post-shock turbulence recovery in oblique-shock/turbulent boundary layer interaction flows
Authors: Yu Ming , Dong SiWei , Liu PengXin , Tang ZhiGong , Yuan XianXu , Xu ChunXiao
Published: April 2023

The oblique shock impinging on the supersonic turbulent boundary layer leads to a mixing layer and the emergence of large-scale coherent structures within the interaction zone which leave significant velocity defect and turbulence amplification downstream. In the present study, we investigate the turbulence recovery in the post-shock region by exploiting direct numerical simulation data of the oblique-shock/turbulent boundary layer interaction flow at the incoming Mach number of

$2.28$

and the shock angle of

$33.2^\circ$

, with special attention paid to the contribution of the mixing layer and large-scale structures to flow dynamics. For that purpose, we propose to split the mean velocity, Reynolds stresses and spanwise spectra into a canonical portion that is constructed according to the statistics of canonical turbulent boundary layers, and a mixing-layer-induced portion. We found that the hidden mixing layer grows with the boundary layer thickness and that the induced mean shear and Reynolds stresses decay at different rates. The mean velocity recovers to the canonical profiles at a distance of 13 boundary layer thicknesses downstream where the mixing-layer-induced mean shear ceases to have strong impacts. The recovery of Reynolds stresses requires 10 boundary layer thicknesses in the near-wall region but a much longer streamwise extent in the outer region due to the slow decay of large-scale motions. These large-scale motions superpose on the near-wall turbulence, intensifying the turbulent fluctuations, yet having a trivial impact on the skin friction, for the contribution of the mixing-layer-induced mean shear and Reynolds shear stress are balanced by the advection term. We further establish a simple physical model capable of approximately predicting the streamwise evolution of mixing-layer-induced mean shear and turbulent kinetic energy. This model suggests that the complete recovery of turbulence in the outer region requires a streamwise extent of approximately 50 boundary layer thicknesses.