bluuebunny/crossref_metadata_2025 huggingface dataset:
4556 Gender homophily in translational collaborations; a network analysis study of investigators at one academic medical center
Authors: Nooraie Reza Yousefi , Wayman Elizabeth , Dozier Ann
Published: July 2020

OBJECTIVES/GOALS: Collaborations are at the core of translational science and team science. Differences by gender have been identified in various research contexts from recruitment to retention to promotion. This study assesses the relational associations of translational collaborations, and what role of gender. METHODS/STUDY POPULATION: In 2011 and 2013, clinical and basic sciences investigators at University of Rochester School of Medicine and Dentistry responded to an online survey nominating their research collaborators. Two study years were merged, and name lists were transformed into a collaboration network. Departments were classified into basic sciences (e.g. biochemistry) and clinical (e.g. urology). If respondent and partner were affiliated to different department classes, the collaboration was defined as translational. Multi-level GLM models were developed to assess the associates of the likelihood of translational vs. within discipline collaborations. Partner nominations were nested in respondents. RESULTS/ANTICIPATED RESULTS: 202 respondents were included in the multi-level GLM models. A collaboration was more likely to be translational if the respondent shared more collaborators with the partner (OR:1.13), and respondent was a central actor in collaboration network (OR: 1.2). Translational collaborations were less likely to be reported by clinicians (OR: 0.25). In the model to assess gender match, a collaboration was more likely to be translational if the respondent was male, and nominated a male partner. For both genders, collaboration with a partner of the opposite gender was more likely to be translational if respondent had more shared collaborators with the partner. DISCUSSION/SIGNIFICANCE OF IMPACT: Translational collaborations happen in teams. Gender homophily exits in translational collaborations, and is reduced by shared collaborators; implying the effect of personal connections and community membership. Community-building interventions may increase diversity in translational collaborations.
4499 A look at motivation and income level for families in obesity treatment
Authors: Ramel Melissa , Wilfley Denise , Tabak Rachel
Published: July 2020

OBJECTIVES/GOALS: An evidence-based approach for childhood obesity is family-based treatment (FBT). Research supports that motivation and income level may impact treatment success; however, the relationship between the two is understudied. Therefore, the objective of this study was to examine whether motivation for beginning FBT is associated with income levels. METHODS/STUDY POPULATION: 459 parent and child dyads from the PLAN (Pediatric, Learning, Activity, Nutrition) with Families multisite study were included in this study. PLAN consists of FBT through personalized health coaching over the course of two years, focusing on nutrition, physical activity, and parenting skills. Parent and child also attend height and weight assessments every 6 months in the study. Outcomes of the study include weight change and mastery of behavioral skills. Motivation and income level were provided by self-report at the beginning of the study. Motivation was based on a scale from 1-10 (1 = no motivation, 10 = high motivation). Income levels were grouped into one of three broader categories- low income ($80,000/year). RESULTS/ANTICIPATED RESULTS: The mean level of motivation for the parent was 8.76 and for the child was 7.87. There was a significant difference in the mean level of motivation for the child and parent, t = 7.73, p = < .001. Post-hoc multiple comparisons using Tukey’s HSD test indicated that children in the high-income group had lower levels of motivation (M = 7.29, SD = 2.07) compared to children in the middle (M = 8.18) and low (M = 8.70) income groups. Level of motivation did not differ for children in the middle and low-income groups. Finally, parent motivation level did not differ significantly by income group. While there were significant differences between parent and child motivation levels, the motivation remained high for both groups. DISCUSSION/SIGNIFICANCE OF IMPACT: The data suggests a significant difference in mean child motivation and income level. Child’s high motivation may be from the idea of participating in something new, a rare opportunity for low-income children. To improve the implementation and efficacy of FBT, further study into the relationship between motivation and income level should be done.
4102 Assessment of ivermectin-treated backyard chickens as a novel urban West Nile virus prevention strategy
Authors: Holcomb Karen , Nguyen Chilinh , Foy Brian D. , Barker Christopher M.
Published: July 2020

OBJECTIVES/GOALS: We conducted a randomized field trail to evaluate the efficacy and safety of a novel vector control strategy that involves treating urban backyard chickens with ivermectin (IVM), a widely used antiparasitic and mosquitocial drug. The goal was to reduce vector mosquito populations and West Nile virus (WNV) transmission. METHODS/STUDY POPULATION: We placed eight flocks—four treated and four untreated control—of six Lohmann brown chickens (16 month-old) each in backyard coops across Davis, CA and administered IVM in feed daily at treated coops (200 mg IVM/kg feed) for eleven weeks. We monitored entomological indices weekly (i.e. mosquito abundance, WNV infection prevalence, and parity rate) in Culex mosquito populations near (10 m) and far (150 m) from each coop location for the peak WNV transmission season (Jul-Sep 2019). We also monitored serum IVM levels in treated chickens and tested for WNV antibodies in all chickens throughout the study. RESULTS/ANTICIPATED RESULTS: Since IVM impacts only mosquitoes that live long enough to take a bloodmeal from a treated chicken, we do not expect to find a marked difference in adult Culex abundance between the two treatment arms, but we expect to find a reduction in WNV infection prevalence and a shift in female mosquito age structure towards younger, uninfected individuals at treated coops. We also anticipate seroconversions in treated chickens to occur at lower rates versus untreated control chickens indicating a reduction in WNV transmission intensity at treated coops. We observed no negative health outcomes from the long-term ingestion of IVM by study chickens. A pathological investigation is underway to compare histological findings between treated and untreated chickens. DISCUSSION/SIGNIFICANCE OF IMPACT: IVM provides the potential for targeted mosquito control. Reduced WNV transmission dynamics here is a stepping stone to a commercial WNV control strategy; IVM-treated feed for wild birds for homeowners’ use to combat WNV transmission in their neighborhoods.
4465 Comparing Children’s Physical Activity Accumulation Between a Nature-Based and Traditional Pre-K School Setting
Authors: Tokarek Nathan , Cho Chi C. , Swartz Ann M.
Published: July 2020

OBJECTIVES/GOALS: The primary aim of this observational study was to explore minute by minute differences in children’s in-school PA accumulation while attending a nature-based compared to a traditional Pre-K program. METHODS/STUDY POPULATION: Participants from a single Pre-K program wore an accelerometer at the waist during school for two consecutive weekdays in the winter, chosen for consistent weather conditions. In this program, one day was spent at a nature-based site, and one day at a traditional classroom location. Accelerometer data was analyzed using Butte (2014) vector magnitude activity thresholds summed by minute across each day. Paired-sample t-tests were applied on a minute-by-minute basis at a significance of p<0.001 to determine the point(s) at which PA accumulation diverged between settings. Direct observation (DO) conducted by a trained researcher also documented activities children engaged in each school day. RESULTS/ANTICIPATED RESULTS: In-school PA differed significantly between settings beginning at minute 37 of classroom time. Based on results obtained through DO, this coincided with the end of unstructured free play time and the start of structured activities across both days. In a traditional classroom setting, structured activities included classroom-based learning, while the nature-based setting incorporated a 10-minute outdoor walk prior to the start of classroom learning. This walking period altered the trajectory of total in-school PA accumulation between program locations, with participants maintaining a significantly greater PA accumulation while in a nature-based setting through the end of the school period. DISCUSSION/SIGNIFICANCE OF IMPACT: Compared to a traditional setting, nature-based programs allow for more active structured periods in school. A 10-minute teacher-led walk can significantly improve the trajectory of children’s PA accumulation throughout the remainder of a school day.
4030 Development of a Falls-Prevention Self-Management Plan for Community Dwelling Older Adults
Authors: Vincenzo Jennifer L. , Lefler Leanne L. , Patton Susan Kane , Wei Jeanne
Published: July 2020

OBJECTIVES/GOALS: 1. To determine older adults’ opinions on content that is valuable for inclusion in a falls-prevention self-management plan. 2. To determine older adults’ recommendations of mode(s) to promote adherence to falls prevention recommendations. METHODS/STUDY POPULATION: On-on-one semi structured interviews with older adults are ongoing to determine their opinions on content for inclusion in a falls-prevention self-management plan and recommendations for mode of delivery. As in our prior investigations, we used the theoretical constructs of the health belief model to develop our questions. Interviews will be recorded and transcribed. Data will be entered into MAXQDA12 and coded. Concurrent data collection and analysis will continue until theoretical saturation of themes are achieved. Through this iterative process, we will identify content and mode of delivery for a falls- prevention self-management plan for implementation with older adults. RESULTS/ANTICIPATED RESULTS: We anticipate we will have conducted enough interviews to achieve data saturation by February, 2020. We expect the results of this qualitative investigation to guide the development of a falls-prevention self-management plan that includes targeted implementation and adherence strategies deemed acceptable and feasible for use among older adults following community-based falls-risk screenings. DISCUSSION/SIGNIFICANCE OF IMPACT: Falls are the leading cause of morbidity and mortality among older adults. Adherence to falls prevention among older adults is poor, even among those that voluntarily seek out recommendations. The results of this study will assist with development and pilot testing of a falls-prevention self-management plan to assist older adults to adhere to recommendations.
4269 Frequent emergency department use among homeless individuals seen in emergent care: High risks of opioid-related diagnoses and adverse health services utilization outcomes
Authors: Yamamoto Ayae , Gelberg Lillian , Tsugawa Yusuke , Kominski Gerald , Needleman Jack
Published: July 2020

OBJECTIVES/GOALS: Using multi-state discharge data, to identify predictors of frequent emergency department (ED) use among the homeless patients seen in emergent care, and to compare frequent versus less frequent homeless ED users for their risk of serious health services utilization outcomes. METHODS/STUDY POPULATION: Based on the State Emergency Department Database and the State Inpatient Database, homeless individuals (n = 88,541) who made at least one ED visit in four states (Florida, Maryland, Massachusetts, and New York) in 2014. In this retrospective cross-sectional analysis, patient-level demographic and clinical factors were assessed as predictors for increased ED use. Risks of opioid overdose, opioid-related hospital admission/ED visit, in-hospital mortality, mechanical ventilation, and number of hospitalizations were compared between individuals with 4 or more vs. 2-3 vs. 1 ED visit(s), adjusting for potential confounders including hospital fixed effects (allowing for within hospital comparisons). RESULTS/ANTICIPATED RESULTS: Higher rates of ED use were associated with Medicare coverage <65; primary diagnosis of alcohol abuse, asthma, or abdominal pain; and co-morbidity of alcohol abuse, psychoses, or chronic pulmonary disease. Individuals with ≥4 visits had significantly higher adjusted risk of opioid overdose (3.7% vs. 1.2% vs. 1.0%), opioid-related hospitalizations/ED visits (17.9% vs. 8.5% vs. 6.6%), mechanical ventilation (9.8% vs. 7.0% vs. 4.7%), and greater # of hospitalizations (3.2 vs. 1.3 vs. 0.8) compared to individuals with 2-3 or 1 ED visit. Individuals with ≥4 and 2-3 ED visits had similar but increased risks of in-hospital mortality compared to individuals with 1 ED visit (2.8% vs. 2.8% vs. 2.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: Homeless patients who were high ED users were more likely to be hospitalized and have other adverse outcomes. These findings encourage targeted interventions (i.e. housing) for the high-utilizer homeless population to reduce the burden of serious outcomes and costs for the patient and society.
4162 Improving Data Capacity and Predictive Capability of NSQIP-P Using Designed Sampling from Databases
Authors: Ingram Martha-Conley , Tian Yao , Mehrotra Sanjay , Apley Dan , Raval Mehul V
Published: July 2020

OBJECTIVES/GOALS: Designed sampling from databases (DSD) methods have been used to cross-check electronic medical records for errors, structure study design, and, we hypothesize, can be used to make data collection for surgical quality metrics more efficient, particularly within national databases. We plan to apply statistical and DSD methods to accomplish the following aims:

1.

Identify the most important elements in managing post-operative pain

2.

Identify the most informative procedure or population-based targets to focus collection of additional, labor-intense detail surrounding adequacy of pain control (i.e., Patient Reported Outcome Measures (PROMs)).

METHODS/STUDY POPULATION: Our study population includes all children, ages 1-18 years, captured in the National Surgical Quality Improvement Project-Pediatric (NSQIP-P) from 2019 to 2021. We plan to apply statistical (regression modeling) and DSD methods to accomplish the aims listed above. RESULTS/ANTICIPATED RESULTS: For Aim 1, we expect to identify patient, procedure, and perioperative pain management practices that influence postoperative pain. For Aim 2, we will focus on outcomes such as PROMs that are challenging to obtain. By applying DSD methods, we will identify specific procedure and/or population-based cohorts to capture PROMs and decrease data collection burdens, while maintaining power, as the project is scaled nationally to all of NSQIP-P. DISCUSSION/SIGNIFICANCE OF IMPACT: Data from this study will inform expansion of NSQIP-P to collect novel outcomes of clinical and societal importance without prohibitively increasing data collection burden.
4239 Racial/ethnic difference in the relationship between periodontitis and cardiovascular disease among adult populations
Authors: Shaheen Magda , Khona Neeraj Harish , Schrode Katrina
Published: July 2020

OBJECTIVES/GOALS: Several lines of studies have supported the existence of periodontitis (inflammation of the gums) as a risk factor for cardiovascular disease (CVD). The goal of this study is to evaluate the relationship between periodontitis and CVD among Hispanic, African American, and Caucasian populations. METHODS/STUDY POPULATION: We analyzed data from the National Health and Nutrition Examination Survey, 1999-2004 (NHANES). The population was all adults with a periodontal exam. Periodontal Disease was defined as mild, moderate, and severe (2 loss of attachments of at least 3mm, 2 sites with probing depth of at least 4mm, or one site with probing depth of at least 5mm). Cardiovascular disease was defined by a questionnaire regarding prevalence of any of 5 diagnosis (congestive heart failure [CHF], coronary artery disease [CAD], angina, heart attack or stroke). Data were analyzed using multinomial regression in SAS version 9.3 taking into consideration the design and weight. RESULTS/ANTICIPATED RESULTS: The study included 3375 adults; 13% were Hispanic and 10% were Blacks, 58% had > high school education, 81% were insured, 11% were heavy alcohol drinkers, 27% were smokers, 13% were physically inactive, 14% had periodontitis, 62% visited dentist last year, 2% had CHD, and 1.5% had CHF or stroke. In the multiple multinomial regression, overall, people with periodontitis were more likely to have both CHD (AOR = 2.0, 95% CI = 1.1-3.8, p<0.05) and CHF or stroke (AOR = 1.8, 95% CI = 1.01, 3.0, p<0.05) than to have no heart condition. There was a racial/ethnic difference in the relationship between periodontitis and cardiovascular disease but it was not statistically significant (p>0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, people with periodontitis were more likely to have CHD, CHF or stroke than to have no heart condition, but with no significant effect of racial/ethnic group. This study provides a foundation to future studies on the connection of periodontitis and CVD in relation to ethnic/racial groups.
4432 Transportation Barriers and Preferences Among Drivers with Developmental Disabilities in Southeast
Authors: Svancara Austin , Kana Rajesh , McManus Benjamin , Bednarz Haley , Sherrod Gabriela , Stavrinos Despina
Published: July 2020

OBJECTIVES/GOALS: Transportation may be a barrier for individuals with Autism Spectrum Disorder (ASD). More individuals with ASD utilize public transportation compared to typically developing (TD) individuals. This study seeks to elucidate the transportation needs of individuals with ASD in the Southeast. METHODS/STUDY POPULATION: Sixty-one licensed drivers with a diagnosis of ASD (n = 21), Attention-Deficit/Hyperactivity Disorder (ADHD; n = 19), or no diagnosis (TD; n = 21) were recruited and were matched across diagnosis groups by age (16-30 years old), gender, and IQ. Participants completed an adapted version of the Barriers to Care Scale and a survey assessing transportation preferences and quality of life. Means and frequencies were obtained. Chi-square analyses were conducted to estimate associations between diagnosis and transportation preferences. RESULTS/ANTICIPATED RESULTS: Nearly all of the sample had access to a car (98.4%). Yet, only 71.4% of drivers ASD preferred to use their own car compared to 89.5% and 90.5% of the ADHD and TD groups respectively. The use of public transportation (6.6%) and ride-hailing services (18%) for general transportation needs was very low across the groups. There was a significant association between group type and the reliance on others for transportation (χ2(2,61) = 9.9, p < .01). Only 21.1% of those with ADHD relying on others for transportation needs, compared to 61.9% of TD and 66.7% of individuals with ASD. 23.8% of ASD drivers, 10.5% of ADHD drivers, and 9.5% of TD drivers believe transportation proved as an obstacle. DISCUSSION/SIGNIFICANCE OF IMPACT: The proportion of ASD drivers who believed transportation to be a barrier appeared slightly higher than other groups. Public transportation use may be low due to lower accessibility to such services in the Southeast. The travel patterns of individuals with ASD and ADHD merits further exploration.
4151 Understanding barriers and solutions towards access to mental health among rural adolescents
Authors: Davis Brandy , Garza Kimberly B. , Westrick Salisa , Chou Edward , Jackson Cherry
Published: July 2020

OBJECTIVES/GOALS: There are two objectives: 1) To identify healthcare providers’ (HCP) barriers and potential solutions towards rural adolescents’ access to mental healthcare. Healthcare providers include pharmacists, physicians, and mental healthcare providers (MHPs). 2) To identify rural high schoolers’ barriers and potential solutions towards access to mental healthcare. METHODS/STUDY POPULATION: Fifteen HCPs will be recruited via email listserv and the snowball method. Perceived barriers of rural adolescents, personal barriers, current practices to address mental health in adolescents, and preferred solutions will be discussed. Twenty student and parent dyads will be recruited using fliers in school systems and will be interviewed individually outside of class time on school grounds or over the phone. Barriers to care and preferred solutions will be discussed. All interviews will be semi-structured, recorded, conducted in person or over the phone, and last for 30 minutes to an hour. Compensation will be $25 for students and parents each, $50 for pharmacists and mental health providers and $100 for physicians. Thematic qualitative data analysis will be performed using Atlas.ti software. RESULTS/ANTICIPATED RESULTS: Data collection is ongoing. Anticipated results for barriers include absence of mental healthcare providers in rural areas, inability to access mental healthcare providers further away, stigma towards mental healthcare, and lack of knowledge of mental health conditions and treatment. Anticipated results for potential solutions may include promoting mobile applications to assist with telehealth and self-care. Other solutions may be collaboration among rural healthcare providers for adolescents with mental health conditions. Preferred solutions may also include pharmacists disseminating knowledge to rural adolescents and their parents or referrals to mental healthcare providers. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will identify barriers and solutions to access to mental healthcare among rural adolescents. These solutions can then be applied towards the creation of programs that address salient issues within rural communities with a greater chance of uptake and use so that rates of depression and suicide will decrease. CONFLICT OF INTEREST DESCRIPTION: Funding through UAB TL1 award.
4512 Allopregnanolone Dose Finding for Status Epilepticus Treatment by Pharmacokinetic-Pharmacodynamic Modeling using Quantitative EEG in Dogs
Authors: Patterson Edward “Ned” , Vuu Irene , Zolkowska Dorota , Wu Chun-Yi , Leppik Ilo , Worrell Greg , Kremen Vaclav , Cloyd James
Published: July 2020

OBJECTIVES/GOALS: Allopregnanolone (ALLO), a modulator of GABAA receptors, may be useful as a treatment for human and canine benzodiazepine-refractory status epilepticus (SE). Our objective was to develop a phamacokinetic-pharmacodynamic (PKPD) model relating ALLO plasma concentrations to electroencephalographic (EEG) effects in dogs. METHODS/STUDY POPULATION: Four healthy dogs and one dog with epilepsy that had implanted intracranial electrodes were utilized. ALLO doses ranging from 1-6 mg/kg were administered IV over 5 min. EEG data were collected during four IM doses (1-2 mg/kg). Blood samples were collected up to 6 hr following dosing. ALLO concentrations were measured using HPLC-MS/MS. Power density was determined in EEG bands using a custom algorithm. A two-compartment link PKPD model was developed to describe the relation between ALLO plasma concentration and change in EEG power in the alpha, beta, delta and theta bands. RESULTS/ANTICIPATED RESULTS: ALLO caused a rapid increase in absolute power density in all EEG bands measured (1-4, >4 – 8, >8 – 12, >12 – 25, and >25 – 100 Hz). The onset of effect was rapid (1-3 min) and demonstrated by frequency band and dose analysis. Concentration-EEG data were best fit by a two-compartment PK model and sigmoidal Emax PD indirect link model. The beta frequency band was most sensitive, showing increases in power at the lowest ALLO concentrations. The EC50 concentration for the beta frequency was ~270 ng/mL. The EC50 values for effects on the other frequency bands were ~500-700 ng /mL. In conclusion, IV ALLO causes a rapid effect on EEG that can be used to determine minimal plasma concentrations associated with target engagement. DISCUSSION/SIGNIFICANCE OF IMPACT: Dose selection for future clinical trials will use the effective concentrations determined here in conjunction with studies in animal status epilepticus models. Studies are planned in client owned dogs with epilepsy to evaluate clinical efficacy in dogs and as nonclinical proof-of-concept evidence supporting translational studies in people. CONFLICT OF INTEREST DESCRIPTION: Michael Rogawski and Dorota Zolkowska are named as inventors on patent applications claiming use of neuroactive steroids including allopregnanolone and ganaxolone in the treatment of status epilepticus.
4395 alpha-Synuclein Induced Reactive Gliosis
Authors: Carey Sean David , Alshawi Sarah , McCann Mondona , Maguire-Zeiss Kathleen
Published: July 2020

OBJECTIVES/GOALS: Reactive gliosis is a hallmark of neurodegenerative disease and is characterized by the release of pro-inflammatory cytokines and physiologic changes to glial cells. Our work identifies a novel inflammatory glial-glial cell interaction and role for mGluR5 that has the potential to provide novel insight into the mechanisms of neurodegeneration. METHODS/STUDY POPULATION: Cell Culture: Mouse primary astrocytes and microglia were isolated from P0-P3 C57BL/6 or Cx3cr1GFP/+ mice.1Treatment: Glia were treated with oligomeric α-synuclein 1μg/mL or mGluR5 agonist CHPG 100 μM.2,3ELISA: Glia culture media was collected and analyzed according to the manufacturer. qRT-PCR: TaqMan™ probes were used according to manufacturer on extracted glia mRNA. ICC: Microglia were labeled with 1:750 Rb x Iba1 (Wako) and 1:500 Alexa Fluor 488 Gt x Rb. Phagocytosis Assay: Primary glia were treated with α-synuclein or astrocyte-conditioned culture media for 24-48hrs. For treatment of microglia with conditioned media, astrocytes were washed with PBS and fresh media was added to prevent carry over of α-synuclein to microglia. The number of fluorescent microbeads per microglia was quantified. RESULTS/ANTICIPATED RESULTS: Mouse primary cortical astrocytes simulated with α-synuclein aggregates adopt a reactive A1 phenotype independent of microglial stimulation. This A1 phenotype is characterized by release of pro-inflammatory cytokines including Complement Component 3 and the monocyte chemoattractant CCL2. Reactive astrocyte media induces a phagocytic phenotype in primary mouse microglia. Along with this, α-synuclein-directed microglial phagocytosis was attenuated with the addition of the mGluR5 agonist CHPG. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that oligomeric α-synuclein is capable of inducing a reactive phenotype in astrocytes independent of microglia and implicate crosstalk between glia as an important mediator of inflammation and microglial phagocytosis in synucleinopathies.
4425 Anibiotic-Resistant Organism Acquisition in Nursing Facility Patients
Authors: Wang Joyce , Cassone Marco , Gibson Kristen , Lansing Bonnie , Mody Lona , Snitkin Evan , Rao Krishna
Published: July 2020

OBJECTIVES/GOALS: We investigated the association between gut microbiota features in newly admitted nursing facility (NF) patients and the acquisition of vancomycin-resistant Enterococcus (VRE) and/or resistant Gram-negative bacteria (rGNB) within 14 days. METHODS/STUDY POPULATION: Patients were recruited at 6 Michigan NFs from 09/16-08/18. VRE or rGNB colonization status was determined by culture swabs collected from multiple body sites at enrolment, day 7, and day 14. Our analysis focused on patients with no colonization at baseline, a perirectal swab collected at baseline, and at least one follow-up visit. The V4 hypervariable region of the 16S rRNA gene from bacterial DNA in each sample was PCR-amplified and sequenced on the MiSeq platform. Sequencing results were then processed with the mothur bioinformatics pipeline to classify bacterial taxa present in each sample. Taxa typically associated with the skin microbiota were removed. The primary outcome was acquisition of VRE and/or rGNB within 14 days. Exposures of interest included patient and microbiota characteristics. RESULTS/ANTICIPATED RESULTS: Among 61 patients, 18 (30%) acquired AROs within 14 days of enrolment (3 VRE, 13 rGNB, 2 both) (Table 1). The baseline microbiota features differed significantly in those who acquired a new ARO. Of the major 8 phyla found across samples, patients who acquired an ARO were depleted in the number of phyla present (5.74 ± 1.20 vs 5.06 ± 1.43; p = 0.037) (Fig. 1). The log10-transformed relative abundance of Enterococcus was enriched in patients who acquired an ARO (−0.32 ± 1.47) compared to those who did not (−1.68 ± 1.76; p = 0.021) (Fig. 2). Patients who did not acquire an ARO tended to harbour more butyrate-producing bacterial taxa and strict anaerobes, although the differences were not statistically significant (relative abundance of butyrate producer: 29.49 ± 22.09 vs 22.05 ± 17.76; anaerobes: 64.78 ± 23.54 vs 53.68 ± 27.61). DISCUSSION/SIGNIFICANCE OF IMPACT: Microbiota metrics calculated from perirectal samples are predictive of ARO acquisition. The clinical utility of perirectal samples thus warrants further assessment.
4259 Application of Design Sprint Methodology to Prototype a Proactive Outreach Tool for COPD Patients
Authors: Cui Michael , Zimmerman Lindsay , Chokshi Shashin
Published: July 2020

OBJECTIVES/GOALS: The primary objective of this study was to apply design sprint methodology to develop a proactive outreach tool prototype for patients with chronic obstructive pulmonary disease (COPD). METHODS/STUDY POPULATION: We utilized a 3-day process to align our team and key stakeholders behind answering the following question: “how might we empower COPD patients to understand their healthcare information, make decisions in partnership with their providers, and more easily manage their daily health?” On Day 1, we focused on understanding and defining the problem, and mapping the patient experience. On Day 2, we quickly brainstormed potential solutions, sketched our top ideas, and listed the solutions’ inherent assumptions. On Day 3, we created a prototype of our top solution and storyboarded each step of the prototype experience to review its potential usability and comprehensibility with patients. RESULTS/ANTICIPATED RESULTS: At the end of the design sprint, our team developed a prototype centered around personalized communication between COPD patients and providers. The prototype focuses on augmenting the current transitional care management (TCM) workflow in the post-discharge period. We are working to further develop the prototype prior to formal testing with care coordinators and patients. We anticipate that our prototype will assist in automating the current TCM workflow and facilitate contact with more patients post-discharge. DISCUSSION/SIGNIFICANCE OF IMPACT: Contact with patients is currently challenging due limited resources and the time sensitive nature of the TCM requirements. Automated patient outreach may be especially effective in engaging patients on a large scale, while also minimizing time and resources needed from healthcare staff.
4323 Inflammation partially mediates fatigue-like behavior in mice
Authors: Alshawi Sarah , Wolff Brian , Saligan Leorey
Published: July 2020

OBJECTIVES/GOALS: Fatigue is a distressing side effect of cancer and its treatment. It is a subjective symptom that can include mental, physical, emotional, and motivational components. We sought to determine whether preventing inflammation affects fatigue-like behavior in a mouse model of radiation therapy. METHODS/STUDY POPULATION: C57BL/6 mice received three consecutive 8 gray doses of daily peripheral irradiation. We used voluntary wheel running activity to measure fatigue-like behavior before and after this period. Minocycline, an antibiotic with anti-inflammatory effects, was administered beginning a week before irradiation and continued throughout the experiment. We also tested mice lacking the toll-like receptor adaptor protein, MyD88. Cognitive abilities were tested using spontaneous alternation in a Y-maze. RESULTS/ANTICIPATED RESULTS: We found that minocycline reduces fatigue-like behavior exhibited after irradiation, but had no effect on pre-irradiation activity levels. Similarly, fatigue-like behavior after radiation was partially reversed by genetic loss of MyD88. Y-maze spontaneous alternation performance remained similar in all groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Both pharmacological and genetic anti-inflammatory manipulations increased voluntary activity levels after irradiation. Our results suggest that inflammation is an important factor in the development of fatigue-like behavior. Modulators of inflammatory processes hold potential for alleviating fatigue.
4335 Role of PSD95 and nNOS interaction in gene regulation following fear conditioning and implications for molecular mechanisms underlying PTSD
Authors: Patel Jheel , Dustrude Erik , Haulcomb Melissa , Li Liangping , Jiang Guanglong , Liu Yunlong , Lai Yvonne , Molosh Andrei , Shekhar Anantha
Published: July 2020

OBJECTIVES/GOALS: Normal fear learning produces avoidance behavior that promotes survival, but excessive and persistent fear after trauma can lead to development of phobias and post-traumatic stress disorder (PTSD). Our goal is to understand the mechanism and identify novel genetic targets underlying fear responses. METHODS/STUDY POPULATION: Involvement of the amygdala in fear acquisition is well established and requires activation of N-methyl-D-aspartic acid receptors (NMDARs). At a cellular level, NMDAR activation leads to production of nitric oxide (NO) by a process mediated by interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS). To elucidate mechanisms underlying the role of the PSD95-nNOS-NO pathway in conditioned fear, here we use rodent behavioral paradigms, pharmacological treatment with a small molecular PSD95-nNOS inhibitor, co-immunoprecipitation, Western blotting, and RNA-sequencing. RESULTS/ANTICIPATED RESULTS: We show that fear conditioning enhances the PSD95-nNOS interaction and that the small-molecule ZL006 inhibits this interaction. Treatment with ZL006 also attenuates rodent cued-fear consolidation and prevents fear-mediated shifts in glutamatergic receptor and current densities in the basolateral amygdala (BLA). With RNA-sequencing, expression of 516 genes was altered in the BLA following fear expression; of these genes, 83 were restored by systemic ZL006 treatment. Network data and gene ontology enrichment analysis with Ingenuity Pathway Analysis and DAVID software found that cell-cell interaction, cognition-related pathways, and insulin-like growth factor binding were significantly altered. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results reveal novel genetic targets that underlie plasticity of fear-memory circuitry via their contribution of NMDAR-mediated fear consolidation and can inform future strategies for targeting fear related disorders like PTSD. CONFLICT OF INTEREST DESCRIPTION: Anantha Shekhar and Yvonne Lai are co-founders of Anagin, Inc., which is developing some of the related molecules for the treatment of PTSD.
4322 Structure-guided design of the TIL1383I T cell receptor
Authors: Alonso Jesus , Singh Nishant , Devlin Jason , Davancaze Lauren , Baker Brian
Published: July 2020

OBJECTIVES/GOALS: Our goal is to employ a structure-guided design approach to engineering a safer and more effective variant of the TIL1383I T cell receptor (TCR) currently under study in clinical trials for malignant melanoma METHODS/STUDY POPULATION: Using our unpublished structure of TIL1383I we are in process of designing a panel of TCR variants with the goal of identifying candidates that improve “focus” towards the tyrosinase antigen presented on the MHC class I molecule HLA-A2. RESULTS/ANTICIPATED RESULTS: Structural analysis of TIL1383I revealed key residues, particularly beta-chain residues E97, G101, L102, responsible for engaging the tyrosinase peptide bound to HLA-A2. The crystal structure of TIL1383I in complex with tyrosinase-HLA-A2 also highlighted its uncharacteristic binding geometry and we therefore hypothesize that this binding orientation is associated with the observed CD8 co-receptor independence of TIL1383I. Indeed, functional analysis with TIL1383I-transduced CD8-positive and CD8-negative T cells, transduced T cells expressing a truncated CD8 lacking the intracellular LCK signaling domain, and tyrosinase peptide variants presented by HLA-A2 mutants outline this co-receptor independence. Combined with our interrogation of tyrosinase peptide cross-reactivity via a peptide positional scanning library approach, structure-guided design resulted in the identification of TIL1383I variants with improved binding affinities to the tyrosinase peptide as well as an understanding of structural characteristics that may contribute to TIL1383I’s co-receptor independence.
4296 Targeting ERG Through Toll-Like Receptor 4 in Prostate Cancer
Authors: Greulich Ben , Plotnik Josh , Hollenhorst Peter
Published: July 2020

OBJECTIVES/GOALS: The objective of this research was to learn how the oncogenic transcription factor, ERG, is regulated in prostate cancer. If we could learn how ERG is regulated and which genes are important for its oncogenic phenotype in prostate cells, we could design new therapeutic strategies against ERG, which has proven to be difficult to target. METHODS/STUDY POPULATION: We conducted an shRNA screen in prostate cells to determine candidate genes and pathways that are important for ERG function. To validate the findings of the screen, we performed a variety of cell-based functional assays, including trans-well migration, wound healing, and clonogenic survival assays. To further investigate the mechanism between ERG and the genes revealed by the screen, we performed biochemical and molecular biology experiments such as Western blotting and qRT-PCR for protein and mRNA expression, co-immunoprecipitation assays to determine protein-protein interactions, and chromatin immunoprecipitation (ChIP-qPCR) to determine transcription factor binding to DNA sites. RESULTS/ANTICIPATED RESULTS: The screen revealed that genes involved in the toll-like receptor 4 (TLR4) pathway are important for ERG-mediated migration. We tested the effect of a TLR4 inhibitor on ERG function and observed decreased migration and clonogenic survival exclusively in ERG-positive cells. Expression of pMEK and pERG was reduced when TLR4 was inhibited, which suggests a mechanism in which TLR4 upregulates pMEK, leading to the phosphorylation and activation of ERG. This is supported by functional assays in which cells expressing a phosphomimetic ERG are resistant to the TLR4 inhibitor. We demonstrated that ERG drives the transcription of TLR4 and its endogenous ligands HSPA8 and BGN. Therefore, ERG can sensitize the cell to TLR4 activation by increasing the number of receptors as well as providing the ligands needed for stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: This research provides a new therapeutic pathway for treating ERG-positive patients through TLR4 inhibition. This can be beneficial because many patients become resistant to the standard therapy, leaving very few treatment options. TLR4-based therapies could provide an alternative for patients who have developed resistance.
4371 The Role of B Cells in Keloid Formation
Authors: Anderson Jaclyn B , Harrant Alexander B , Navarro-Alvarez Nalu , Wang Zhaohui , van Bokhoven Adrie , High Whitney , Chong Tae W , Huang Christene A.
Published: July 2020

OBJECTIVES/GOALS: Recent studies indicate B cells are involved in dermal fibroblast activation and collagen deposition in the skin. However, B cell distribution in epidermal and dermal layers is unknown. Here, We aim to characterize the distribution of B cells residing in normal skin and keloidal scars. METHODS/STUDY POPULATION: One abdominal normal skin sample and two keloid samples (ear and shoulder) were obtained from the University of Colorado Biorepository Core Facility and from the Plastic Surgery Clinics. Five micron sections from formalin-fixed paraffin-embedded samples were prepared for multiplex fluorescence immunohistochemistry by the Human Immunology & Immunotherapy Initiative. We stained for CD20+, CD19+, and DAPI. Slides were imaged using Vectra®3 scanning system from PerkinElmer. Images were analyzed in InForm®Tissue Finder, phenotpr, phenoptrReports by Akoya biosciences. RESULTS/ANTICIPATED RESULTS: We found a significant increase in the percentage of CD20+ and CD19+ B cells in keloid skin compared to normal skin tissue (14.50% and 14.20% vs 6.47% and 7.56% of the total cells), respectively. Interestingly, we found that in the epidermis of keloid skin CD20+ cell were more abundant (14.46%) whereas in the epidermis normal skin CD20+ cells were less predominant (5.14%). In the dermis of keloid skin, CD20+ and CD19+ were in equal proportions (13%) whereas in normal skin CD19+ cells were more predominant (10.44%) compared to CD20+ cells (7.04%). Dual positive B cells, CD19+/CD20+ cells, were more abundant in keloid dermis (11.06%) compared to normal skin dermis (1.24%). DISCUSSION/SIGNIFICANCE OF IMPACT: B cells are involved in fibroblast activation in diseases such as scleroderma and rheumatoid arthritis. With the increase of CD19+/CD20+ B cells in keloids, the role of B cells in keloid pathogenesis warrants further study. CD27 staining may determine if these are activated or follicular B cells.
4353 The Role of BCL2 Mediated Calcium Signaling on Leukemia Stem Cell Metabolism
Authors: Inguva Anagha , Pei Shanshan , Amaya Maria , Stevens Brett , Jones Courtney , Pollyea Daniel , Jordan Craig
Published: July 2020

OBJECTIVES/GOALS: The objective of this study is to define the molecular mechanisms that control survival of malignant stem cells in acute myeloid leukemia (AML). Leukemia stem cells (LSCs) are not effectively eradicated by standard treatment and lead to resistance and relapse, which contribute to poor survival rates. METHODS/STUDY POPULATION: The recently FDA approved venetoclax, a BCL2 inhibitor, with azacitidine, a hypomethylating agent leads to a 70% response rate in AML patients. Analysis of patients treated with this regimen showed direct targeting of LSCs. BCL2 has a non-canonical function in regulation of intracellular calcium. To determine how BCL2 mediated calcium signaling plays a role in LSC biology, we used LSCs isolated from venetoclax/azacitidine (ven/aza) sensitive and resistant patient samples to measure expression of calcium channels via RNA seq. BIO-ID, siRNA, flow cytometry, seahorse assays, calcium measurements and colony assays were used to determine the effects of calcium channel perturbation on LSC biology. RESULTS/ANTICIPATED RESULTS: BCL2 inhibition leads to decreased OXPHOS activity in primary AML specimens. BIO-ID studies revealed cation/metal ion transporters, ER membrane proteins and ER membrane organization as top enriched pathways interacting with BCL2. RNA-seq data showed increased expression of genes involved in calcium influx into the ER in ven/aza sensitive LSCs and increased expression of genes involved in calcium efflux from the ER in ven/aza resistant samples. Ven/Aza resistant LSCs have increased mitochondrial calcium content, consistent with their increased OXPHOS activity as calcium is required for OXPHOS. Perturbation of these channels leads to decreased OXPHOS activity and decreased viability in LSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: We postulate that a deeper understanding of the mechanisms behind ven/aza targeting of LSCs will lead to the development of novel therapies for patients who do not respond to ven/aza. Our data show targeting intracellular calcium signaling could be a viable therapeutic strategy for AML patients.
High levels of endemism and local differentiation in the fungal and algal symbionts of saxicolous lecideoid lichens along a latitudinal gradient in southern South America
Authors: Ruprecht Ulrike , Fernández-Mendoza Fernando , Türk Roman , Fryday Alan M.
Published: July 2020

Saxicolous, lecideoid lichenized fungi have a cosmopolitan distribution but, being mostly cold adapted, are especially abundant in polar and high-mountain regions. To date, little is known of their origin or the extent of their trans-equatorial dispersal. Several mycobiont genera and species are thought to be restricted to either the Northern or the Southern Hemisphere, whereas others are thought to be widely distributed and occur in both hemispheres. However, these assumptions often rely on morphological analyses and lack supporting molecular genetic data. Also unknown is the extent of regional differentiation in the southern polar regions. An extensive set of lecideoid lichens (185 samples) was collected along a latitudinal gradient at the southern end of South America. Subantarctic climate conditions were maintained by increasing the elevation of the collecting sites with decreasing latitude. The investigated specimens were placed in a global context by including Antarctic and cosmopolitan sequences from other studies. For each symbiont three markers were used to identify intraspecific variation (mycobiont: ITS, mtSSU,RPB1; photobiont: ITS, psbJ-L, COX2). For the mycobiont, the saxicolous generaLecidea,Porpidia,PoeltideaandLecidellawere phylogenetically re-evaluated, along with their photobiontsAsterochlorisandTrebouxia. For several globally distributed species groups, the results show geographically highly differentiated subclades, classified as operational taxonomical units (OTUs), which were assigned to the different regions of southern South America (sSA). Furthermore, several small endemic and well-supported clades apparently restricted to sSA were detected at the species level for both symbionts.
Why do interest groups prioritise some policy issues over others? Explaining variation in the drivers of policy agendas
Authors: Fraussen Bert , Halpin Darren R. , Nownes Anthony J.
Published: July 2020

Interest groups cannot advocate on every issue they might consider relevant. They must decide what issues to prioritise and which ones to leave to one side. In this article, we examine how groups seek to balance different internal and external considerations when prioritizing issues, and which factors might explain variation in the relative strength of these drivers. We integrate data of a survey of national interest groups in Australia with findings from interviews with a cross section of high-profile groups. While the literature often suggests a clash between external political considerations and internal membership demands, we find that groups view these drivers as largely compatible. Our explanatory analysis points to the policy orientation and insider status of the group, its democratic character, and the extent to which it faces competition for membership contributions, as important factors shaping the relative strength of distinct drivers of internal agenda setting.