Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.

A young adult with late diagnosis of scimitar syndrome underwent infradiaphragmatic baffling of the scimitar vein to left atrium through an intra-atrial tunnel using PhotoFix® bovine pericardium with recurrent extensive fibrovascular granulation of the patch causing pulmonary and systemic venous obstruction leading to eventual explantation of the bovine pericardium.

Background: The Bundled Payment Care Improvement Program is a CMS initiative designed to encourage greater collaboration across settings of care, especially as it relates to an initial set of targeted clinical episodes, which include sepsis and pneumonia. As with many CMS incentive programs, performance evaluation is retrospective in nature, resulting in after-the-fact changes in operational processes to improve both efficiency and quality. Although retrospective performance evaluation is informative, care providers would ideally identify a patient’s potential clinical cohort during the index stay and implement care management procedures as necessary to prevent or reduce the severity of the condition. The primary challenges for real-time identification of a patient’s clinical cohort are CMS-targeted cohorts are based on either MS-DRG (grouping of ICD-10 codes) or HCPCS coding—coding that occurs after discharge by clinical abstractors. Additionally, many informative data elements in the EHR lack standardization and no simple and reliable heuristic rules can be employed to meaningfully identify those cohorts without human review. Objective: To share the results of an ensemble statistical model to predict patient risks of sepsis and pneumonia during their hospital (ie, index) stay. Methods: The predictive model uses a combination of Bernoulli Naïve Bayes natural language processing (NLP) classifiers, to reduce text dimensionality into a single probability value, and an eXtreme Gradient Boosting (XGBoost) algorithm as a meta-model to collectively evaluate both standardized clinical elements alongside the NLP-based text probabilities. Results: Bernoulli Naïve Bayes classifiers have proven to perform well on short text strings and allow for highly explanatory unstructured or semistructured text fields (eg, reason for visit, culture results), to be used in a both comparative and generalizable way within the larger XGBoost model. Conclusions: The choice of XGBoost as the meta-model has the benefits of mitigating concerns of nonlinearity among clinical features, reducing potential of overfitting, while allowing missing values to exist within the data. Both the Bayesian classifier and meta-model were trained using a patient-level integrated dataset extracted from both a patient-billing and EHR data warehouse maintained by Premier. The data set, joined by patient admission-date, medical record number, date of birth, and hospital entity code, allows the presence of both the coded clinical cohort (derived from the MS-DRG) and the explanatory features in the EHR to exist within a single patient encounter record. The resulting model produced F1 performance scores of .65 for the sepsis population and .61 for the pneumonia population.

Funding: None

Disclosures: None

Background: Fluoroquinolones are the perfect target for antimicrobial stewardship programs (ASPs) due to their broad-spectrum nature, poor safety profile, and frequent misuse. In April 2019, the Bureau of Prisons (BOP) created a national antimicrobial stewardship clinical pharmacist consultant program. One of the program’s main initiatives was to screen active fluoroquinolone prescriptions for appropriateness and work with providers to tailor therapy as needed. Since July 2019, pharmacist consultants have utilized a singular system-wide electronic health record (EHR) to conduct fluoroquinolone prospective audit and feedback targeting all BOP sites across the country. The objective was to assess the national impact of prospective audit and feedback on outpatient fluoroquinolone prescriptions utilizing pharmacist consultants and an integrated EHR. Method: Reviews were conducted in a federal correctional setting including 122 BOP sites with an average daily population of 167,308 inmates. The ASP consisted of 7 pharmacists, each assigned a region across the country. Consultant pharmacists were in charge of conducting daily fluoroquinolone reviews within 72 hours of the prescription being written, utilizing a singular system-wide EHR to gain remote access to newly prescribed prescriptions along with all other pertinent information (ie, clinical notes, patient profiles, laboratory, and radiology). Interventions were sent via e-mail. Total fluoroquinolone prescriptions per 1,000 inmates during the preintervention period (July 1, 2018, to September 30, 2018) were compared to the postintervention period (July 1, 2019, to September 30, 2019), after the development of the clinical consultant program. Data were also collected during the 3-month postintervention period to include total fluoroquinolone prescriptions reviewed, total recommendations sent, percentage of recommendations accepted, and intervention types. Results: In total, 833 fluoroquinolone prescriptions of 1, 264 total prescriptions written (66%)were reviewed over the 3-month postintervention period. In total,192 interventions were recommended (23%). Of the interventions recommended, 65 (34%) were accepted. The most common intervention was to stop therapy (41%), followed by changing antibiotic (37%), and shorten therapy duration (8%). Total outpatient fluoroquinolone prescriptions decreased by 1.5 prescriptions per 1,000 patients after the intervention. Conclusions: Pharmacist-driven prospective audit and feedback on a national scale utilizing a singular system-wide EHR resulted in an overall decrease in outpatient fluoroquinolone prescriptions over short period of time.

Funding: None

Disclosures: None

A 53-year-old male presents with cough, fever, and myalgias for 7 days. Vitals include temperature, 38.0°C; heart rate, 110; blood pressure, 118/70 mm Hg; respiration rate, 28; and oxygen saturation 83% on room air. His only past medical history is hypertension. Your community is in the midst of the coronavirus disease 2019 (COVID-19) pandemic. The patient is hypoxic but responds to oxygen supplementation with nasal cannula and a face mask. His chest x-ray demonstrates multifocal infiltrates. Are there any therapeutic agents currently available for COVID-19?

A 37-year-old female presents with cough, fever, dyspnea, and myalgias for five days after recent contact with a family member with confirmed 2019 coronavirus disease (COVID-19). Her vital signs include T 38.3° C, HR 108, BP 118/70 mm Hg, RR 26 breaths per minute, and oxygen saturation 67% on room air. She is not in respiratory distress currently and is protecting her airway. Her chest X-ray reveals bilateral airspace opacities. You plan to immediately intervene and address her hypoxia.

There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.

Recent technological advances have led to unprecedented amounts of generated data that originate from the Web, sensor networks, and social media. Analytics in terms of defeasible reasoning – for example, for decision making – could provide richer knowledge of the underlying domain. Traditionally, defeasible reasoning has focused on complex knowledge structures over small to medium amounts of data, but recent research efforts have attempted to parallelize the reasoning process over theories with large numbers of facts. Such work has shown that traditional defeasible logics come with overheads that limit scalability. In this work, we design a new logic for defeasible reasoning, thus ensuring scalability by design. We establish several properties of the logic, including its relation to existing defeasible logics. Our experimental results indicate that our approach is indeed scalable and defeasible reasoning can be applied to billions of facts.

Discussions of optimal types of spoken and written input for language learning have traditionally focused on the relative merits of authentic and linguistically simplified spoken and written texts. I will argue that elaborated input and, in particular, modified elaborated input, constitute better options, with tasks, not just texts, functioning as important input sources. Modified elaborated input, potentially coupled with bimodal presentation, has many positive features, especially, but not only, for programs seeking to increase students' opportunities for enhanced incidental learning.

A piezoelectric biomedical microelectromechanical system (bioMEMS) cantilever device was designed and fabricated to act as either a sensing element for muscle tissue contraction or as an actuator to apply mechanical force to cells. The sensing ability of the piezoelectric cantilevers was shown by monitoring the electrical signal generated from the piezoelectric aluminum nitride in response to the contraction of iPSC-derived cardiomyocytes cultured on the piezoelectric cantilevers. Actuation was demonstrated by applying electrical pulses to the piezoelectric cantilever and observing bending via an optical detection method. This piezoelectric cantilever device was designed to be incorporated into body-on-a-chip systems.

OBJECTIVES/SPECIFIC AIMS: 1. Identify the extent of CD implementation for trained childcare teachers. 2. Explore teacher perspectives on the impact of CD. 3. Explore teacher perspectives on barriers and facilitators to full implementation of CD. METHODS/STUDY POPULATION: We conducted a survey with 267 childcare teachers who had been trained in CD across the state, representing early childhood educational environments in urban and rural settings. Specific questions were asked related to level of CD implementation, perceived benefit, and facilitators/barriers to full implementation. A random subset of the sample (8 teachers) participated in a subsequent focus group to explore survey themes in greater depth. Focus group members were asked about their rationale for attending CD training, CD implementation (including barriers/facilitators to full implementation), and perceived impact on their classrooms. The focus group was recorded and transcribed to capture questions and comments. RESULTS/ANTICIPATED RESULTS: Objective 1: 1. 30% of teachers reported full implementation of CD. 2. 50% of teachers reported partial implementation of CD. Objective 2: 1. The vast majority of teachers (95%) agreed that CD had a positive impact on their classroom, including better structure and enhanced relationships with the children. 2. The vast majority of teachers (85%) agreed that CD had a positive impact on the children in their classroom, including increases in problem-solving abilities and self-control. Objective 3: 1. Most teachers (71%) reported experiencing barriers to CD implementation, with the majority of those surveyed (93%) stating that additional implementation support would be helpful. 2. The top three barriers to implementation elicited in survey and focus groups included uncertainty regarding how to begin implementing CD in the classroom, lacking materials for CD implementation, and lacking time to focus on applying knowledge from training into the classroom. 3. The top three facilitators for implementation elicited in survey and focus groups included coaching support for teachers, training agency leadership in CD, and greater perceived impact of CD. DISCUSSION/SIGNIFICANCE OF IMPACT: Childhood disruptive behaviors are among the most frequent reasons for referral to specialized services in and out of the classroom (Sukhodolsky, Smith, McCauley, Ibrahim, & Piasecka, 2016). Disruptive and aggressive behaviors are problematic, not only for victims of children who are aggressive but also for aggressive children as they age. Although effective treatments exist, the level of effective implementation of these interventions are understudied. These results demonstrate that 2/3 of teachers trained in CD are not fully implementing the model and provides concrete barriers and facilitators to current implementation. These data will provide the initial foundation for the development of a targeted implementation strategy that supports full implementation of CD within early childhood education settings.

Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman’s rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3β), catenin β1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.

OBJECTIVES/SPECIFIC AIMS: (1) Identify current barriers to coordinated care between behavior consultation and PCIT services. (2) Identify current facilitators to coordinated care between behavior consultation and PCIT services. (3) Utilize this knowledge to create and pilot a coordinated care model that will enhance PCIT and behavior consultation service outcomes. METHODS/STUDY POPULATION: Objectives 1 and 2: Two focus groups consisting of 8–10 behavior consultants will be conducted to gather initial information on barriers and facilitators to coordinated care. Participants will be recruited from the state-funded behavior consultation team, to represent consultation occurring in rural and urban settings. All focus groups will be recorded and transcribed to capture questions and comments. Focus groups will be provided with an initial 10-minute overview of PCIT, including theory, prescribed strategies, and mode of intervention. A grand tour question will then be asked to elicit consultant perceptions of PCIT (e.g., “What are your thoughts on the compatibility between PCIT and behavior consultation services”), followed by probe questions deigned to elicit more detailed information about any perceived differences based on philosophical approach; differences in what is recommended in childcare settings Versus at home, etc.; and perceived barriers to coordinated care between school and outpatient services (e.g., “What factors make coordinating care with outpatient providers challenging?). Participants will be asked about their willingness to participate in a second focus group to review materials created to enhance coordinated care, based on their feedback. Objective 3. Based on feedback from the focus groups and quantitative data regarding factors associated with PCIT outcomes, we will develop an enhanced childcare component(s) for eventual implementation. To confirm our approach, we will invite the members of both focus groups back for a second session, in which we provide them with the created materials and elicit their feedback. We will start with a grand tour question (e.g., “How do you think parents and teachers would react to these materials?”) and then follow-up with probe questions related to feasibility (e.g., “How do you anticipate using these tools?”), appropriateness (e.g., “How adequately do you feel these materials address concerns with coordinated care?”), and acceptability (e.g., “How likely are you to begin using these tools within your consultation?”). Both focus groups will be recorded and transcribed to capture questions and comments. RESULTS/ANTICIPATED RESULTS: (1) Barriers and facilitators to coordinated care will include individual (e.g., acceptability of PCIT framework) and system-level factors (e.g., ease of communication between providers). (2) There will be significant overlap in coordination between the first phase of PCIT (which focuses on positive parenting strategies) and what is prescribed by behavior consultants. (3) There will be less compatibility between the second phase of PCIT (which focuses on disciplinary strategies) and what is prescribed by behavior consultants. (4) A coordinated are model will be rated as more feasible, appropriate, and acceptable to behavior consultants than PCIT services as currently prescribed. DISCUSSION/SIGNIFICANCE OF IMPACT: Childhood disruptive behaviors are among the most frequent reasons for referral to outpatient child/adolescent mental health clinics (Sukhodolsky et al., 2016). Disruptive and aggressive behaviors are problematic, not only for victims of children who are aggressive but also for aggressive children as they age. Although effective treatments exist, families are often provided with conflicting strategies for behavior management by outpatient clinicians and behavior consultants in the daycare setting, thus providing children inconsistent feedback which will delay their attainment of new skills. These data will provide the initial foundation for the development of a coordinated care model that promotes treatment efficacy by improving the compatibility between clinic-based PCIT and daycare-based behavior consultation services.