bluuebunny/crossref_metadata_2025 huggingface dataset:
Unicorns—what drives multibillion-dollar valuations?
Authors: Bock Carolin , Hackober Christian
Published: July 2020

The number of ventures with a market value of one billion USD or more has considerably increased during the last decade. Driven by new technologies and business models, these ventures became an integral part of our daily life. Particularly, the number of unicorns based in China and other regions outside the US raised during recent years whereas the phenomenon was initially limited to the US region. Existing research has mainly focused on descriptive approaches to examine the rise of these ventures but lacks knowledge on the drivers of this phenomenon. We address these research gaps and investigate the underlying factors that foster the emergence of such high-valued ventures. Our results present several economic environmental as well as investor-related factors that impact the likelihood for a venture to achieve a market valuation of more than one billion USD. Subsequently, we derive theoretical and practical implications that may foster the future emergence of new high-valued ventures, covering regulatory, investor- and venture-specific aspects.
Female Genital Self-Image in Women With and Without Female Genital Mutilation/Cutting in Jeddah, Saudi Arabia
Authors: Rouzi Abdulrahim A. , Berg Rigmor C. , Alamoudi Rana , Alzaban Faten , Sehlo Mohammad
Published: July 2020

Introduction

The consequences of female genital mutilation/cutting (FGM/C) on female genital self-image are not known.

Aim

To assess whether women with and without FGM/C differed with regard to female genital self-image.

Methods

A survey was administered to a group of women attending the King Abdulaziz University Hospital obstetrics and gynecology clinic from December 2016 to August 2017. 963 consecutive adult women seen at the clinic completed the survey.

Main outcome measures

The main outcome measure of this study was female genital self-image being assessed with the female genital self-image scale (FGSIS).

Results

One-fifth (18.2%) of the women self-reported having undergone FGM/C as young girls. Women with FGM/C had a similar FGSIS score as women with no FGM/C (21.3 ± 4.6, n = 175 vs 21.6 ± 4.8, n = 756, analysis of variance, P = .37). In multivariate regression analysis, only level of education remained independently associated with the FGSIS score. Women with some university education had a greater mean FGSIS score than women with no university education (22.1 ± 4.49, n = 564 vs 20.8 ± 5.03, n = 399, P < .0001).

Conclusions

Women with and without FGM/C in a Saudi Arabian clinic generally had a similarly positive genital self-image. Only level of education was independently associated with the FGSIS score.

Rouzi AA, Berg RC, Alamoudi R, et al. Female Genital Self-Image in Women With and Without Female Genital Mutilation/Cutting in Jeddah, Saudi Arabia. Sex Med 2020;8:752–756.
4125 Plan for a Retrospective Evaluation of a Multi-Modal Weight-centric Prediabetes Intervention.
Authors: Manalac Raoul J , Stewart Tiffany , Ryan Donna
Published: July 2020

OBJECTIVES/GOALS: To determine if a multi-modal, interdisciplinary intervention delivered to a group of prediabetic patients will result in reduced rates of diabetes progression. This project is a retrospective evaluation that will exam the feasibility and possibly efficacy of this intervention. METHODS/STUDY POPULATION: We will evaluate outcomes of 50 participants for the clinic, aged 21-60 inclusive. Patients will have a Body Mass Index >25kg/m2 with a diagnosis of prediabetes. Patients must be non-pregnant, using approved contraception, and agree to not become pregnant for 1 year after enrollment. After enrollment, the initial treatment period is for 1 year and includes a 12 week low calorie diet plan, a 6-month intensive behavioral and lifestyle modification plan followed by a 6 month behavior reinforcement extension. Weight management medications may be used if appropriate for the patient from a clinical perspective during the 6-month intensive behavioral/lifestyle modification. RESULTS/ANTICIPATED RESULTS: It is anticipated that there will be decreased weight with a mean weight loss goal of approximately >10%. Furthermore, it is expect that there will be improvement of other markers of metabolic disease. These include improvement of lipid values (LDL-C, HDL-C, Triglycerides, Total Cholesterol) as well as blood pressure with expected blood pressures of below 130/80 in greater than 50% of participants. Finally, It is expected that 50% or greater participants will have improvement of glycemic control. It is anticipated that greater than 50% of participants will have improvement of glycemic control and achieve normoglycemia. These values will be determined based upon fasting glucose or A1c. DISCUSSION/SIGNIFICANCE OF IMPACT: The significance of this intervention is enormous. By demonstrating feasibility in this trial, we can work toward both assessing efficacy and possibly dissemination of this model program. If these interventions provide durable changes at scale, this could help slow the epidemic of obesity and obesity related comorbid conditions.
4084 Predictors of mortality among non-severe hemophilia A patients in the United States
Authors: Lim Ming Y , Cheng Dunlei , Key Nigel
Published: July 2020

OBJECTIVES/GOALS: To determine predictors of mortality in non-severe hemophilia A (NSHA) patients. METHODS/STUDY POPULATION: The ATHNdataset was used to identify NSHA patients who have authorized the sharing of their demographic and clinical information for research. Factors examined included race, ethnicity, hemophilia severity, Hepatitis B, Hepatitis C and HIV infections. A mortality rate was calculated for each factors examined. The relative risk of death between patients in different categories of the factors was assessed by using the ratio of these mortality rates. To adjust for the effects of all of the studied factors with mortality, a multivariate analysis was performed using logistic regression. All hypothesis testing was two-tailed, with a significance level of .05. RESULTS/ANTICIPATED RESULTS: A total of 6,606 NSHA patients were followed for an average of 8.5 years. During 56,064 person years of observation, 136 (2.1%) NSHA patients died; 20% of deaths were malignancy-related. Mortality rates were similar across racial group. Hispanic patients were 60% less likely to die than non-Hispanic patients (p = 0.006). Patients with Hepatitis C infection and HIV infection were 7 times as likely to die compared to those without infections (p<0.001). After adjusting for the effects of all examined factors in a multivariate analysis, patients with hepatitis C and HIV infection remain significantly associated with increased mortality at 6.1 times and 3.6 times the risk, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite significant improvement in the therapeutic approaches for infectious diseases, Hepatitis C and HIV infections remain strong predictors of mortality in this NSHA cohort. CONFLICT OF INTEREST DESCRIPTION: N/A.
4314 The Impact of Axillary Surgery on Recurrence-Free Survival in Invasive Lobular Carcinoma (ILC) of the Breast
Authors: Abel Mary Kathryn Reed , Wong Jasmine , Alvarado Michael , Ewing Cheryl , Esserman Laura J. , Park Catherine , Mukhtar Rita A.
Published: July 2020

OBJECTIVES/GOALS: Clinical trials demonstrate that axillary lymph node dissection (ALND) is unnecessary for most breast cancer patients with 1-3 involved nodes, but whether this is true for those with ILC is unknown. We evaluate the impact of ALND on recurrence-free survival (RFS) in ILC and 1-3 positive nodes. METHODS/STUDY POPULATION: We performed a retrospective cross-sectional analysis of patients with ILC treated between 1992-2019 at our institution. All patients received either sentinel lymph node biopsy (SLNB) or ALND and underwent either breast conservation surgery (BCS) or mastectomy. The primary outcome was RFS, defined as the absence of locoregional or distant recurrence. RESULTS/ANTICIPATED RESULTS: Of 496 cases, 250 (50.4%) underwent BCS, and 246 (49.6%) underwent mastectomy. A total of 93% of patients were hormone receptor positive, and 89% had low or intermediate grade disease. Among patients with 1-3 positive nodes, there was no significant difference in 5- and 10-year RFS based on receipt of ALND for both BCS and mastectomy cohorts. Using a multivariate model, we found no association between ALND and RFS overall (HR = 0.98, 95% CI 0.36-2.7, p>0.20) and among those with 1-3 positive nodes (HR = 0.60, 95% CI 0.12-3.4, p>0.20). DISCUSSION/SIGNIFICANCE OF IMPACT: These findings support the safety of omitting ALND in patients with ILC and 1-3 positive nodes, regardless of whether they receive BCS or mastectomy. Further studies of axillary management in ILC, including imaging tools to predict nodal involvement and response to therapy, are warranted.
4486 Assessing the Validity of an ICD-9 and ICD-10 Coding Algorithm for Identifying Cervical Premalignant Lesions Using Administrative Claims Data
Authors: Shing Jaimie Zhi , Griffin Marie , Slaughter James C , Pemmaraju Manideepthi , Mitchel Edward F , Chang Rachel S , Hull Pamela C
Published: July 2020

OBJECTIVES/GOALS: We compared the validity of an International Classification of Diseases, Clinical Modification (ICD) algorithm for identifying high-grade cervical intraepithelial neoplasia and adenocarcinoma in situ (together referred to as CIN2+) from ICD 9th revision (ICD-9) and 10th revision (ICD-10) codes. METHODS/STUDY POPULATION: Using Tennessee Medicaid data, we identified cervical diagnostic procedures in 2008-2017 among females aged 18-39 years in Davidson County, TN. Gold-standard cases were pathology-confirmed CIN2+ diagnoses validated by HPV-IMPACT, a population-based surveillance project in catchment areas of five US states. Procedures in the ICD transition year (2015) were excluded to account for implementation lag. We pre-grouped diagnosis and procedure codes by theme. We performed feature selection using least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation and validated models by ICD-9 era (2008-2014, N = 6594) and ICD-10 era (2016-2017, N = 1270). RESULTS/ANTICIPATED RESULTS: Of 7864 cervical diagnostic procedures, 880 (11%) were true CIN2+ cases. LASSO logistic regression selected the strongest features of case status: Having codes for a CIN2+ tissue diagnosis, non-specific CIN tissue diagnosis, high-grade squamous intraepithelial lesion, receiving a cervical treatment procedure, and receiving a cervical/vaginal biopsy. Features of non-case status were codes for a CIN1 tissue diagnosis, Pap test, and HPV DNA test. The ICD-9 vs ICD-10 algorithms predicted case status with 68% vs 63% sensitivity, 95% vs 94% specificity, 63% vs 64% positive predictive value, 96% vs 94% negative predictive value, 92% vs 89% accuracy, and C-indices of 0.95 vs 0.92, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, the algorithm’s validity for identifying CIN2+ case status was similar between coding versions. ICD-9 had slightly better discriminative ability. Results support a prior study concluding that ICD-10 implementation has not substantially improved the quality of administrative data from ICD-9.
4525 Estimates of Dose Response using the Dixon Up-and-Down Method and BOIN study designs
Authors: Minard Charles Gene
Published: July 2020

OBJECTIVES/GOALS: The Dixon up-and-down method (U/D), original developed for testing explosives, is especially common in anesthesia research studies. The objective of this research is to compare the performance of the U/D method for obtaining and analyzing sensitivity data with that of the Bayesian Optimal Interval (BOIN) method. METHODS/STUDY POPULATION: A simulation study will compare the performance of the U/D method with the BOIN design. The two study designs offer alternative decision-making algorithms with respect to the dose at which the next experimental unit is treated. These alternative decisions may impact the precision of point estimates of the mean and standard deviation of the effective dose to elicit a response. Transition probability matrices are developed, and maximum likelihood estimates of the unknown parameters assessed for accuracy. For simulation, the effective dose is assumed to be randomly distributed with a known mean and standard deviation. Fixed dose levels are defined, and decisions for what level the next experimental unit should be treated at are defined by the Dixon up-and-down method and the BOIN design. For the U/D method, the stimulus is increased by one level in the absence of a response or decreased if a response occurs from an initial stimulus. A target toxicity probability of 0.50 is used to define the dose escalation or de-escalation rules for the application of the BOIN design. RESULTS/ANTICIPATED RESULTS: A feature of both methods is that the consecutive observations are concentrated about the mean value of the effective dose. However, the BOIN design tends to be more concentrated between these two dose levels. In the presence of severe adverse events, the BOIN design can choose to eliminate doses that are too toxic whereas the U/D design cannot eliminate any dose levels. Transition probability matrices are defined and parameters for the distribution of the effective dose are estimated using maximum likelihood estimation. Mean squared errors for the estimated mean and standard deviations compare the two study designs. DISCUSSION/SIGNIFICANCE OF IMPACT: The BOIN design offers an alternative method for decision-making compared with the U/D method. The BOIN design tends to concentrate dose levels about the mean more than the U/D. This may provide better estimates of the mean and standard deviation of the effective dose for eliciting a response in some circumstances.
4179 Use of tobacco products and their association with wheezing among adult current tobacco users in the US – Findings from The Population Assessment of Tobacco and Health Study (2015-2016)
Authors: Schneller Liane M , Quiñones-Tavárez Zahíra , Goniewicz Maciej , Xie Zidian , McIntosh Scott , O’Connor Richard , Ossip Deborah J. , Rahman Irfan , Li Dongmei
Published: July 2020

OBJECTIVES/GOALS: Wheezing has been shown to be associated with use of cigarettes, and more recently, electronic nicotine delivery systems (ENDS). This study assessed the association of poly use of tobacco products with wheezing among a national representative sample of US adult current tobacco users. METHODS/STUDY POPULATION: Data from the Population Assessment of Tobacco and Health (PATH) Study Wave 3 (W3) were used. Weighted prevalences of self-reported wheezing and related respiratory symptoms for non-users compared to users of cigarettes, ENDS, cigars, and any combination of these products (poly use of tobacco products) were presented for 28,082 adults. The cross-sectional association of tobacco use with self-reported wheezing and other related respiratory symptoms was assessed using weighted multivariable and ordinal logistic regression with consideration of complex sampling design. RESULTS/ANTICIPATED RESULTS: Most adults who reported on wheezing symptoms did not currently use cigarettes, ENDS or cigars (79%), 15% used cigarettes, 3% used a combination of cigarettes, ENDS and cigars, 1% used ENDS, and 1% used cigars. Significantly higher odds of ever had wheezing or whistling in chest at any time in the past was observed among current cigarette (adjusted OR: 2.62, 95%CI: 2.35, 2.91), ENDS (1.49, 95%CI: 1.14, 1.95), and poly users (2.67, 95%CI: 2.26, 3.16) compared to non-users. No differences were seen for cigar use. Polytobacco use was associated with a higher odds of ever wheezing when compared to ENDS (1.61, 95%CI: 1.19, 2.17) and cigar use (2.87, 95%CI: 1.93, 4.26), but not cigarettes. DISCUSSION/SIGNIFICANCE OF IMPACT: Wheezing is associated with the use of cigarettes, ENDS, or any combination of cigarette, ENDS and cigars likely due to the inhalation of noxious chemicals and gases found in the smoke of cigarettes and ENDS that are likely to increase the odds of experiencing wheezing. CONFLICT OF INTEREST DESCRIPTION: MLG serves as a paid consultant for Johnson & Johnson and has received research grant from Pfizer, manufacturers of smoking cessation medications. The other authors have no conflicts to declare.
4581 Autonomic Dysfunction as a Marker of Depression and Coronary Artery Disease
Authors: Shah Anish Sanjay
Published: July 2020

OBJECTIVES/GOALS: Dysfunction of the autonomic nervous system (ANS) may be important in both depression and coronary artery disease (CAD). A novel heart rate variability (HRV) metric, Dyx, may be a be a potentially useful tool to study ANS dysfunction in these diseases. We propose that ANS dysfunction, measured by decreased Dyx, will associate with both depression and obstructive CAD. METHODS/STUDY POPULATION: We included participants undergoing coronary angiography for suspected CAD. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9). HRV data were collected continuously on participants before catheterization using a new ECG patch (VivaLNK). We assessed HRV by Dyx (primary) and high and low frequency power, multiscale entropy, and deceleration capacity. Two-sample t-tests and logistic regressions (with adjustment for age and sex) were used to study the difference in HRV (before cardiac catheterization) between those with high versus low depressive burden (PHQ-9 ≥ 10), and in those with versus without obstructive CAD (>70% stenosis). RESULTS/ANTICIPATED RESULTS: We assessed 30 individuals with mean (SD) age 62.4 (13.2); 7.1% were female and 15.4% were black. Mean Dyx in high depressive symptoms (N = 21, 70%) was 1.8 (0.2) and in none-low depressive symptoms (N = 7, 23%) was 2.2 (0.2). Differences were also observed for high frequency (HF) (4.4 (1.1) vs. 6.0 (1.4)) and deceleration capacity (−4.2 (2.1) vs. −10.7 (8.5)). Mean Dyx in obstructive CAD (N = 17, 57%) and non-obstructive CAD (N = 10, 33%) was 1.7 (0.6) and 2.6 (1.2) respectively. Differences were seen with sample entropy (1.2 (0.2) vs. 1.5 (0.2)). Every 1 unit of log(HF) had an odds ratio = 0.14 (95% CI 0.06 – 0.36) for depression. DISCUSSION/SIGNIFICANCE OF IMPACT: ANS dysfunction, measured by HRV, associates with both depression and obstructive CAD. Autonomic ECG markers may play an important role in assessing brain-heart pathology, and may be useful to study the interaction between depression and CAD.
4329 Investigating the role of Klotho in neurocognitive outcomes, brain volumes, and white matter changes in pediatric brain tumor survivors
Authors: Edwards Caleb Simpeh , Stoller Schuyler , Savchuk Sol , Ugaz Valencia Christian Rodrigo , Tong Liz , Rauschecker Andreas , Dubal Dena , Kline Cassie , Mueller Sabine
Published: July 2020

OBJECTIVES/GOALS: Klotho is a protein linked to improved cognition in aging adults. A specific KLOTHO gene variant, KL-VS, increases circulating levels of Klotho. The current study aims to identify if the KL-VS haplotype and Klotho levels are associated with improved neurocognition in pediatric brain tumor survivors. METHODS/STUDY POPULATION: We are actively accruing pediatric brain tumor patients at UCSF alongside an existing multi-institutional cohort study investigating radiation-induced vasculopathies and cognitive outcomes in this population. Normal controls are being enrolled in parallel. Each patient undergoes: 1) single nucleotide polymorphism genotyping to identify KL-VS haplotype status, 2) enzyme-linked immunosorbent assays to measure circulating Klotho, 3) neurocognitive assessments with a computer-based, validated Cogstate battery, and 4) brain volume and white matter lesion segmentation analyses using MRI sequences obtained as part of routine care. RESULTS/ANTICIPATED RESULTS: Genotyping has been performed on 99 enrolled patients. KL-VS heterozygosity was seen in 22.7% of patients. To date, KL-VS status is not associated with neurocognitive outcomes at baseline or Year 1 testing. Association between KL-VS status, circulating Klotho levels, neurocognitive outcomes, brain volume and white matter lesion segmentation analyses is ongoing. We hypothesize that elevated Klotho levels will be associated with improved neurocognition, increased brain volumes in regions of interest and decreased white matter lesion volumes. DISCUSSION/SIGNIFICANCE OF IMPACT: If circulating Klotho leads to improved neurocognition in pediatric brain tumor survivors, Klotho levels might serve as a prognostic biomarker. Furthermore, as Klotho is being investigated for therapeutic indications, it may represent an intervention to prevent cognitive deficits in these patients.
4564 Nilotinib alters microRNAs that regulate specific autophagy and ubiquitination genes in the cerebrospinal fluid of Parkinson’s patients
Authors: Fowler Alan , Torres-Yhagi Yasar , Pagan Fernando , Hebron Michaeline , Willmarth Barbara , Arellano Joy , Howard Helen , Matar Sara , Chiu Timothy , Ahn Jaeil , Moussa Charbel
Published: July 2020

OBJECTIVES/GOALS: Our preclinical data demonstrate that the principal effects of nilotinib, a multi-tyrosine kinase inhibitor, in models of neurodegeneration is clearance of misfolded proteins via autophagy. Here we aimed to evaluate the effects of nilotinib on microRNAs in the cerebrospinal fluid of Parkinson’s disease patients. METHODS/STUDY POPULATION: Cerebrospinal fluid (CSF) was collected as part of an open label phase I (NCT02281474) (n = 12, 300 mg nilotinib taken orally once daily for 6 months), and a phase II randomized, double-blind, placebo-controlled study (NCT02954978) (n = 75, randomized 1:1:1 into placebo, 150 mg or 300 mg nilotinib taken orally once daily for 12 months). RNA was isolated from CSF and Indexed sequencing libraries were prepared from total RNA plus miRNA. Next generation whole-genome sequencing (single-end 1x75 bp, 25 million raw reads per sample) was performed to identify miRNAs significantly differentially expressed (fold-change ≥ 2, Benjamini-Hochberg FDR p-value ≤ 0.05 or Empirical Bayes FDR ≤ 0.05) with treatment compared to baseline. RESULTS/ANTICIPATED RESULTS: Next generation whole-genome sequencing of microRNAs in the CSF demonstrated that nilotinib significantly increases microRNAs that specifically regulate expression of autophagy and ubiquitination genes in individuals with Parkinson’s disease. In the open label phase I, samples, 28 microRNAs found to regulate autophagy and ubiquitination genes, were significantly altered with treatment (Benjamini-Hochberg FDR p-value ≤ 0.05). In the phase II randomized, double-blind, placebo-controlled study samples, we verified several of those 28 candidate microRNAs had been significantly deferentially expressed with treatment (Empirical Bayes FDR p-value ≤ 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data provide robust evidence that nilotinib’s effects on misfolded protein clearance is via autophagy and CSF miRNA sequencing is a valid biomarker of nilotinib’s effects in a definitive phase III study to investigate nilotinib in Parkinson’s and other neurodegenerative diseases. CONFLICT OF INTEREST DESCRIPTION: Charbel Moussa is listed as an inventor on several Georgetown University patents for the use of tyrosine kinase inhibitors as a treatment for neurodegenerative diseases
4482 Horizontal ridge augmentation in maxilla using bone expansion vs bone splitting techniques in adult patients: a prospective cohort
Authors: Acevedo Amanda Figueroa , Pedroza José E. , Elias-Boneta Augusto , Orsini Elizabeth , Guerrero Lidia M. , Rivas-Tumanyan Sona
Published: July 2020

OBJECTIVES/GOALS: The objective of the study is to compare two horizontal bone augmentation techniques (bone expansion and bone splitting) that are currently used for horizontally deficient maxillary ridges. Bone expanded in millimeters (mm), implant stability, and patient satisfaction will be compared with each technique. METHODS/STUDY POPULATION: This pilot (prospective cohort) study will be divided in two sites, a private practice and the Oral and Maxillofacial Surgery (OMS) Clinic at the University of Puerto Rico, School of Dental Medicine. A total of 20 patients will be selected, 10 patients in each site. In both sites, pre-operative and post-operative Cone Beam CT radiographs will be taken to measure bone width. Implant stability will be measured using an Osstell. 2 weeks post-surgery, a patient satisfaction questionnaire will be given to patients. A two-sample T test will be used to compare techniques statistically. RESULTS/ANTICIPATED RESULTS: We anticipate that bone expansion will be as good as (non-inferiority) bone splitting in terms of bone expanded in millimeters to desire width, and implant diameter will not be compromised. We also expect that implants placed with the bone manipulation technique will have a higher implant stability at baseline and less pain, discomfort and swelling in terms of patient satisfaction. DISCUSSION/SIGNIFICANCE OF IMPACT: Our contributions here are expected to illustrate clinical and radiographic bone expansion techniques that will enhance implant placement treatment for implantologists and patient’s experience.
4138 Development of an Antibiofilm Resorbable Membrane for Treating Peri-implantitis
Authors: Ye Zhou , Rahimi Joseph R. , Fischer Nicholas G. , Chew Hooi Pin , Aparicio Conrado
Published: July 2020

OBJECTIVES/GOALS: Peri-implantitis is the inflammation of peri-implant mucosa and subsequent loss of supporting bone. Its treatment is only <40% successful mainly due to persistent bacterial infection. The goal of this project is to increase success rates by developing a robust antibiofilm multi-biomolecular membrane that can be placed around implant surfaces. METHODS/STUDY POPULATION: A collagen membrane was soaked in the antimicrobial peptide GL13K solution overnight to form an interpenetrating fibrillary network. The nanostructure of the membrane was imaged with scanning electron microscope (SEM). The hydrophobicity of the membrane was analyzed by water contact angle (WCA) measurements. The biodegradability was tested in a 0.01 mg/mL Type I collagenase solution for up to 5 weeks. The antimicrobial activity of the membrane was assessed with Gram-positive oral bacteria Streptococcus gordonii. The cytotoxicity was evaluated by culturing human gingival fibroblasts (HGF), and the osteogenesis was assessed using preosteoblasts MC3T3. Pure collagen membrane was used as the control. Statistical significance (p<0.05) was determined by one-way ANOVA with Tukey’s HSD test. RESULTS/ANTICIPATED RESULTS: The antimicrobial peptide GL13K self-assembled to short fibrils (< 1 µm long), which entangled with the larger collagen fibers (around 200 nm in diameter). The collagen fibers presented characteristic periodic banding structures, which provided biomimetic cues for cell behavior as extracellular matrix. The interpenetrated GL13K fibrils turned the highly hydrophilic collagen membrane to a hydrophobic membrane (WCA = 135 °) and significantly reduced the rate of degradation by collagenases. The developed membrane was efficient in preventing the attachment of S. gordonii. A large portion of the attached bacteria was killed on the surface of the membrane. The incorporation of GL13K did not affect the cytocompatibility of the membrane for HGF. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed an antibiofilm membrane with interpenetrating collagen and antimicrobial peptide fibrils. The strong antimicrobial activity and low cytotoxicity support its further translational evaluation as scaffolds for increasing success rate in treating peri-implantitis.
4123 Characterization of Physical Restraint and Sedative Use for Treatment of Agitation in the Emergency Department
Authors: Wong Ambrose H , Crispino Lauren , Parker John , McVaney Caitlin , Rosenberg Alana , Ray Jessica , Whitfill Travis , Iennaco Joanne , Bernstein Steven
Published: July 2020

OBJECTIVES/GOALS: Agitation has high prevalence in the emergency department (ED), but limited evidence exists regarding clinical decisions to use sedatives and physical restraint. We examined clinical factors and agitation attributes impacting thresholds for sedative and restraint use in the emergency setting. METHODS/STUDY POPULATION: We conducted a prospective cohort study of adult patients (318 yo) with acute or escalating agitation during their ED visit at an urban tertiary care referral center. Consecutive patients requiring security presence or scoring >1 on an agitation scale were enrolled during randomized 8-h blocks. We recorded patient characteristics, staff/team factors, and environmental/systems data as well as scores on 3 validated agitation scales: Agitated Behavior Scale, Overt Aggression Scale, and Severity Scale. We performed descriptive analyses, bivariable analyses, and logistic regression modeling of factors with relation to sedative/restraint use. We observed 95 agitation events on unique patients over 2 months. RESULTS/ANTICIPATED RESULTS: Median age was 42, and 62.1% were male. Most frequent chief complaints were alcohol/drug use (37.9%) and psychiatric (23.2%). Majority of events (73.7%) were associated with sedative/restraint use. Factors related to treatment course or staff interactions were the primary reasons for agitation in 56.8% of events. A logistic regression model found no association between demographics and odds of sedative/restraint use. Overt Aggression Scale scores were associated with significantly higher odds of sedative use (AOR 1.62 [1.13–2.32]), while Severity Scale scores had significantly higher odds of restraint use (AOR 1.39 [1.12–1.73]) but significantly lower odds of sedative use (AOR 0.79 [0.64–0.98]). DISCUSSION/SIGNIFICANCE OF IMPACT: External factors may be important targets for behavioral techniques in ED agitation management. Further study of the Severity Scale may allow for earlier detection of agitation and identify causal links between agitation severity and use of sedatives and restraints.
4110 Frequency and patterns of polysubstance use among adults: Findings from a Focus Group that guide development of rodent models for translational research
Authors: Varma Deepthi S , Liu Yiyang , Striley Catherine , Setlow Barry , Knackstedt Lori , Cottler Linda B.
Published: July 2020

OBJECTIVES/GOALS: To explore the patterns, sequence, quantity, frequency and duration of poly substance use among adults for back translation of information to rodent models. METHODS/STUDY POPULATION: From May –December 2019, we conducted 13 focus group discussions with adults 19 to 63 years of age who reported concurrent use of cocaine with alcohol and/or marijuana in the past 30 days. All participants were recruited from the community through community outreach activities. Written informed consent was obtained and all focus group discussions were audio recorded, transcribed and analyzed using the qualitative data analysis software Atlas Ti™. RESULTS/ANTICIPATED RESULTS: A total of 34 cocaine users, (68% male, and 59% minority) participated. The majority reported cocaine as the drug of preference, while marijuana and alcohol were used to extend or control the ‘highs’, or ‘to take the edge off’ after cocaine use. All participants reported when they used alcohol with cocaine, they could keep drinking a large amount of alcohol without feeling its effect. Participants also reported using marijuana throughout the day while driving, at work, or in class. Frequent patterns noted for the study included using two drugs at the same time or right before or after each other with alcohol used throughout the day. Participants also gave feedback on our Poly Substance Use (PSU) assessment that captures exact patterns so that the most common can be translated for the rodent models. DISCUSSION/SIGNIFICANCE OF IMPACT: Our focus group discussions provided detailed information on patterns, sequence, quantity, and types of poly substance use that could be useful for developing a poly substance use assessment in the collection of data for rodent models to understand effects of poly substance use.
4345 Two-step Algorithm for Clostridioides difficile is Inadequate for Differentiating Infection from Colonization in Children
Authors: Nicholson Maribeth R , Parnell Jacob M , Fazili Irtiqa , Bloch Sarah C. , Lacy D. Borden , Skaar Eric , Edwards Kathryn M
Published: July 2020

OBJECTIVES/GOALS: In 2017, new guidelines recommended multi-step algorithms for CDI diagnosis, and clinical centers rapidly implemented changes despite limited pediatric data. We assessed a multi-step algorithm using NAAT followed by EIA for ability to differentiate symptomatic CDI from colonization in children. METHODS/STUDY POPULATION: We prospectively enrolled pediatric patients with cancer, cystic fibrosis, or inflammatory bowel disease who were not being tested or treated for CDI and obtained a stool sample for NAAT. If positive by NAAT (colonized), EIA was performed. Children with symptomatic CDI who tested positive by NAAT via the clinical laboratory were also enrolled and EIA performed on residual stool. A functional cell cytotoxicity neutralization assay (CCNA) was performed in addition. RESULTS/ANTICIPATED RESULTS: Of the 138 asymptomatic children enrolled, 24 (17%) were colonized. An additional 37 children with symptomatic CDI were enrolled. Neither EIA positivity (41% versus 21%, P = 0.11) or CCNA positivity (49% versus 46%, P = 0.84) were significantly different between symptomatic versus colonized children. When both EIA and CCNA were positive, children were more commonly symptomatic than colonized (33% versus 13%, P = 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: A multi-step testing algorithm with NAAT and EIA failed to differentiate symptomatic CDI from colonization in our pediatric cohort. As multi-step algorithms are moved into clinical care, pediatric providers will need to be aware of the continued limitations in diagnostic testing.
4071 Dynamic Control of Tumor Vessels Augments Antitumor Responses
Authors: Gabriel Emmanuel M , Bahr Deborah , Bagaria Sanjay , Muhkopadhyay Debrabata , Knutson Keith
Published: July 2020

OBJECTIVES/GOALS: Our overall objective is to develop a directly observable and reproducible method of enhanced blood flow through tumor vessels (i.e. dynamic control) at the time of systemic treatment delivery. Our central hypothesis is that the dynamic control of tumor vessels will improve (1) systemic drug delivery and (2) effector cell trafficking to target tumor. METHODS/STUDY POPULATION: B16 melanoma cells were inoculated into C57BL/6 (B6) mice (male and female) in both regional (hind leg) and systemic (flank) models. Dynamic control consisted of an IV saline bolus (500 ul) and phenylephrine (10 ug). Tumor vessel response was observed in real-time through window chambers using intravital microscopy (IVM). Dynamic control was combined with melphalan (20 mg/ml) either regionally (isolated limb perfusion) or systemically. Outcomes included tumor growth, survival, IHC, and toxicity. Dynamic control will be combined with adoptive transfer of effector T cells. B6 mice will be inoculated with B16/OVA (flank with window chamber) and treated with fluorescently labeled (calcein), OVA-specific CD8+ T cells from OT-1 transgenic mice. IVM, IHC, and flow cytometry will be used to measure T cell trafficking. RESULTS/ANTICIPATED RESULTS: Dynamic control (1) restored blood flow in non-functional tumor vessels and (2) increased and then transiently reversed blood flow in functional vessels. Vessel diameters did not change, suggesting that shunting of systemic blood to the tumor vasculature accounted for the observed changes. Dynamic control augmented tumor responses in our regional therapy model of melanoma. Increases in DNA adduct formation (melphalan mechanism of action) detected by IHC, decreased tumor growth, and increased survival were observed with dynamic control. There was no increased limb toxicity. Similarly, dynamic control augmented responses in our systemic therapy model (decreased tumor growth and improved survival). We anticipate that dynamic control will improve trafficking of effector T cells in the next set of experiments. DISCUSSION/SIGNIFICANCE OF IMPACT: Heterogeneous responses to systemic therapies represent a major gap in current cancer treatment. An essential requirement for any effective therapy is its ability to reach tumor via the tumor-associated vasculature. We have therefore developed an approach to enhance drug delivery (dynamic control), which we also plan to test in clinical trials.
4009 Magneto-electric nanoparticles (MENs) cobalt ferrite-barrium titanate (CoFe2O4–BaTiO3) for non-invasive neuromodulation
Authors: Nguyen Tyler , Vriesman Zoe , Andrews Peter , Masood Sehban , Stewart M , Khizroev Sakhrat , Jin Xiaoming
Published: July 2020

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.
4303 Optimization of primary septal-hippocampal co-cultures to study central cholinergic synapse formation and dysfunction
Authors: Djemil Sarra , Ressel Claire R. , Pak Daniel T.S.
Published: July 2020

OBJECTIVES/GOALS: Septal cholinergic innervation to the hippocampus is critical for normal learning and memory and is severely degenerated in Alzheimer’s disease. To understand the molecular events underlying this loss, we optimized a primary septal-hippocampal co-culture system that facilitates study of central cholinergic synapses. METHODS/STUDY POPULATION: We developed an optimized in vitro septal-hippocampal co-culture system modified from previous published protocols. Briefly, hippocampal and septal tissue were harvested from embryonic day 19 (E19) Sprague-Dawley rats, digested with 0.1% trypsin, and an equal number of cells from each region plated onto coverslips coated with poly-D-lysine and laminin at a final density of 300 cells/mm2. We use immunostaining with validated primary antibodies and a fluorescent binding assay, together with confocal microscopy, to determine the structure of cholinergic synapses that are 1) native, 2) mammalian, 3) CNS derived, 4) comprised of physiological synaptic partners, and 5) developmentally mature. RESULTS/ANTICIPATED RESULTS: After DIV21, co-cultures maintained a healthy morphology. A subpopulation of neurons strongly expressed the cholinergic markers vesicular ACh transporter (vAChT), choline acetyltransferase (ChAT), and the high-affinity choline transporter (ChT1), whereas most neurons lacked vAChT expression and were presumably glutamatergic or GABAergic. The percentage of cholinergic neurons in the co-culture attained up to ~5-7%, depending on conditions such as embryo age at dissection or ratio of septal to hippocampal cells. We also report on cholinergic synapse structure by examining postsynaptic markers (excitatory and inhibitory) and staining for nicotinic acetylcholine receptor subunits. DISCUSSION/SIGNIFICANCE OF IMPACT: Primary septal-hippocampal co-cultured neurons have not been exploited extensively in the field, perhaps due to the difficulty in maintaining such cultures for extended periods. Here, we optimized an in vitro septal-hippocampal co-culture system, a powerful tool to comprehensively analyze central cholinergic synapse formation and dysfunction.
4072 Optimizing ex-vivo perfusion in Vascularized Composite Allotransplantation using Hyperosmolar solution and Electric Stimulation: Preliminary Results
Authors: Jonczyk Michael , Tratnig-Frankl Philipp
Published: July 2020

OBJECTIVES/GOALS: Vascularized composite allotransplantation (VCA) restores devastating soft tissue injuries. However, graft viability may be compromised during ischemia time, thus preservation techniques continue to evolve. Here we summarize our preliminary findings from preservation techniques utilizing hyperosmolar extracellular solution (HES) and electric stimulation in a 6 hour ex-vivo perfusion model. METHODS/STUDY POPULATION: A published, MGH rodent hindlimb ex-vivo perfusion model was utilized for this project. Three baseline control elements were taken to compare our results including: a baseline muscle biopsy, harvested hindlimb preserved on ice(4°C) in static cold storage (SCS), and 6 hour perfusion (SNMP) were used to compare results of our four aims. The four aims are shown in Table 1. HES was composed of muscle media and the addition of mannitol until 3 concentrations were made: 300, 500, and 800 mOsm concentrations. In aim 4, the perfusate composition was changed to test a hyper-oncotic purfusate. After 6 hours a muscle biopsy was taken to analyze energy cofactors via liquid chromatography-mass spectrometry, referred to as energy charge. Weight gain (edema), lactate levels, oxygen consumption and energy charge (EC) were used as markers for muscle tissue viability. RESULTS/ANTICIPATED RESULTS: In Aim 1, the higher osmolarity of HES indirectly reduced weight gain but consequentially reduced the EC below 5% when compared to SCS control group. We next incorporate HES into the perfusion model, Aim 2, and noticed a diminution in weight gain. The 500 mOsm group had substantial improvement in EC, lactate production and improved oxygen exchange when compared to a controls: fresh muscle biopsy and SNMP. In Aim 3, after a 6 hour perfusion with the addition of electric stimulation, graft edema improved by 10%, EC improved by 23% and O2 dissociation was highest of all 4 aims. Consequentially, due to muscular contraction the lactate levels were highest. In Aim 4, using a hyper-oncotic perfusate, edema reduced the most during the 6 hour perfusion but revealed lower EC and similar lactate/O2 results. However when left on for 24 hours, edema was significantly higher with lactate build up, EC improved with time as well as O2 dissociation. DISCUSSION/SIGNIFICANCE OF IMPACT: Here we have shown our preliminary results comparing our known ex-vivo perfusion model to multiple hypothesis to improve VCA graft viability. These preservation techniques demonstrate promising results but further studies are ongoing to confirm this encouraging outcome.
Expressions of psychological distress in Sierra Leone: implications for community-based prevention and response
Authors: Horn Rebecca , Sesay Simeon S. , Jalloh Mamadu , Bayoh Amjata , Lavally Joan B. , Ager Alastair
Published: July 2020

Background

Over recent decades there has been considerable mental health research in Sierra Leone but little on local conceptualisations of mental health conditions. Understanding these is crucial both for identifying the experienced needs of the population and utilising relevant community-based resources to address them. This study took a grounded approach to identify the ways in which adults in Sierra Leone express psychological distress.

Methods

Rapid ethnographic methods deployed included 75 case study interviews with community members, 12 key informant (KI) pile sorts and 55 KI interviews. Thematic analysis of data was supported by frequency analysis and multi-dimensional scaling.

Results

Thirty signs of distress were identified. The only consistent ‘syndrome’ identified with respect to these was a general concept of crase, which referred to psychosis-related presentation but also a wide range of other signs of distress. We did not find consensus on locally defined concepts for mild-moderate forms of mental disorder: people use multiple overlapping signs and terms indicating psychological distress.

Conclusions

Analysis supports calls to view mental health problems as a ‘continuum of distress’ rather than as discrete categories. This framing is coherent with opportunities for prevention and response in Sierra Leone which do not focus primarily on formal healthcare service providers but rather involve a range of community-based actors. It also enables attention to be paid to the identification of milder signs of distress with a view to early response and prevention of more severe mental health problems.
UNDERSTANDING REGIONAL ECONOMIC PERFORMANCE AND RESILIENCE IN THE UK: TRENDS SINCE THE GLOBAL FINANCIAL CRISIS
Authors: Sensier Marianne , Devine Fiona
Published: July 2020

We investigate economic resilience of UK regions before, during and after the 2007/8 global financial crisis. We date business cycle turning points in real output, employment and productivity to assess the resilience dimensions of resistance, recovery and renewal and rank the economic resilience of regions in a resilience scorecard. Our empirical results reveal that the business cycle in productivity has not returned to its pre-recession peak level for Yorkshire and the Humber and the employment level has not recovered in Scotland. The resilience scorecard ranks the South East as the most resilient region with Northern Ireland the least resilient.
The effects of dietary lipids and roughage level on dairy goat performance, milk physicochemical composition, apparent transfer efficiency and biohydrogenation rate of milk fatty acids
Authors: Büyükkılıç Beyzi S. , Gorgulu M. , Kutlu H. R. , Konca Y.
Published: July 2020

The study was conducted to investigate the effects of fish or palm oil diets with different roughage levels on dairy performance, milk physicochemical composition and apparent transfer efficiency of fatty acids (FA) in goat milk. The experiment was conducted with 40 Aleppo goats with a mean parity of 2.53 ± 0.8 (multiparous), mean initial body weight of 47.23 kg and 25 ± 5 days in milk which were allocated to four (2 × 2) experimental diets with two oil sources (fish or palm oil) at 25.6 g/kg of dietary dry matter and forage levels (400 or 600 g/kg). The experimental data were analysed by repeated measures analysis, using the MIXED procedure. The concentrations of saturated FA decreased with high forage level and fish oil diets; however, the fish oil diets caused an increase in C14 saturated FA. Fish oil diets with high roughage levels more efficiently increased conjugated linoleic acid, n-6 (18 : 2), and n-3 (20 : 5). The apparent transfer efficiency of 18 : 1, 18 : 2, 18 : 3 and 20 : 5 decreased and the transfer efficiency of 22 : 6 increased with the use of fish oil in the diet. The roughage level did not affect the apparent transfer efficiency of 18 : 1 and 18 : 2, but the low roughage level increased the apparent transfer efficiency of 20 : 5. High roughage diets improved milk quality parameters through increasing eicosapentaenoic acid, polyunsaturated fatty acids (PUFA), PUFA/saturated FA and atherogenicity index, thus it was concluded that dietary roughage level could be considered as an important designator of milk quality when a supplement of fish oil and palm oil was supplied to goats.