ABSTRACT IMPACT: This research will promote understanding the role of the Type-I Interferon signaling pathway during embryo implantation, potentially leading to a new diagnostic or treatment target in early pregnancy failure. OBJECTIVES/GOALS: Studies suggest interferon signaling regulation is tightly balanced between physiologic and pathophysiologic growth in early pregnancy. We propose to determine the impact of interferon-mediated inflammation on embryo implantation and early pregnancy failure in normal conditions and chronic inflammatory diseases in a novel mixed-mouse model. METHODS/STUDY POPULATION: To probe the role of type-I interferons (IFNs) in implantation, we will utilize a mouse model and non-surgically transfer both Ifnar1-/- and Ifnar1-/+ embryos into an immune-competent pseudopregnant wild-type female recipient. This will allow analysis of a litter with distinct genotypes within the same, immune-competent, uterine environment. Type-I IFN stimulation will be systemically induced with Poly-(I:C) at various time points around implantation. A similar approach will be used in mouse models of chronic inflammatory disease states associated with early pregnancy loss (e.g. systemic lupous erythematous). With this model, we will be able to control for deficiencies in maternal immune response to specifically determine the embryonic response to inflammation during implantation and development. RESULTS/ANTICIPATED RESULTS: We anticipate the Ifnar1-/+ embryos - those able to respond to Type-I IFN - and their surrounding implantation sites will exhibit more maternal-fetal barrier dysfunction in the form of impaired trophoblast fusion, improper formation of the microvascular architecture, and increased permeability of the maternal-fetal barrier, compared to embryos unable to respond to IFN. We will also conduct similar analyses in mouse models of chronic inflammatory diseases. We hypothesize these mice to have baseline endometrial inflammation that stimulated the IFN-pathway in IFN-capable embryos, producing breakdown of the maternal-fetal barrier. In these mice, we predict Ifnar1-/- embryos will show improved molecular outcomes when compared to Ifnar1-/+ embryos, and thus improved associated pregnancy outcomes. DISCUSSION/SIGNIFICANCE OF FINDINGS: This work can insight into the immunological mechanisms that govern embryo implantation and early placentation. This could provide more pointed means for management and intervention of early pregnancy failure and/or disease states that are commonly associated with poor reproductive outcomes.

Sense of place describes both affective and cognitive — emotional and intellectual — connections to place. Affective outcomes, tied to arts and humanities education, can facilitate these connections. But little research explores environmental science, arts and humanities (eSAH) curricula on place relationships. Additionally, most research on the sense of place focuses on repeated visits to a place over time, rather than short-term experiences like a field trip. Finally, digital technology is a growing trend across science education, but little research investigates its use in field-based contexts. Our research begins to address these gaps. This article describes an eSAH field trip for middle and high school learners. Using a conventional content analysis, we present pilot data from two high school field trips. Our findings illuminate a framework for understanding active and passive place relationships in the context of short-term interdisciplinary field learning experiences.

Conventional longitudinal behavioral genetic models estimate the relative contribution of genetic and environmental factors to stability and change of traits and behaviors. Longitudinal models rarely explain the processes that generate observed differences between genetically and socially related individuals. We propose that exchanges between individuals and their environments (i.e., phenotype–environment effects) can explain the emergence of observed differences over time. Phenotype–environment models, however, would require violation of the independence assumption of standard behavioral genetic models; that is, uncorrelated genetic and environmental factors. We review how specification of phenotype–environment effects contributes to understanding observed changes in genetic variability over time and longitudinal correlations among nonshared environmental factors. We then provide an example using 30 days of positive and negative affect scores from an all-female sample of twins. Results demonstrate that the phenotype–environment effects explain how heritability estimates fluctuate as well as how nonshared environmental factors persist over time. We discuss possible mechanisms underlying change in gene–environment correlation over time, the advantages and challenges of including gene–environment correlation in longitudinal twin models, and recommendations for future research.

Background: Surgical site infections (SSIs) among cardiothoracic (CT) patients are associated with high rates of morbidity and mortality. Data are limited regarding SSI incidence among pediatric patients undergoing primary reparative procedures for congenital cardiac disease. Published evidence on targeted interventions to prevent pediatric CT-surgery SSI is lacking. We aimed to establish standard metrics for measuring CT-surgery SSI incidence and to implement bundled interventions for SSI prevention. Methods: A dedicated CT-surgery SSI prevention workgroup was established, consisting of hospital leadership, CT surgeons, cardiac critical care unit staff, anesthesia, perfusion, environmental services, instrument sterile processing, risk management, infection prevention and antibiotic stewardship. We created a standard definition for CT-surgery SSI and calculated retrospective SSI rates over a 24-month period (2017–2019). The outcome measured was incidence of CT-surgery SSI per 100 primary cardiac procedures with delayed ( 3 days after primary surgery) or non-delayed chest closure. The difference in proportion of SSI was reported separately for delayed closure and non-delayed closure; statistical significance was tested using a Fisher’s Exact test. We identified many potential improvement opportunities, including gaps in SSI surveillance, poor compliance with daily bathing, inconsistent perioperative antimicrobial prophylaxis, lack of controlled environment for bedside chest closures, and lapses in environmental cleaning. These issues informed the enhanced SSI prevention bundle, which included education on sterility with the operating room (OR) staff. Protocols for care of cardiac patients with delayed chest closures focused on universal daily and preoperative chlorhexidine baths. In addition, the bundle incorporated stringent environmental cleaning interventions including scheduled decluttering of patient rooms and clinical spaces, terminal cleaning of patient rooms prior to returning from the OR, and use of adjunctive ultraviolet light for the daily cleaning of operating rooms and patient rooms at discharge. Results: Surveillance definition of microbiological growth from a clinical sample obtained within 30 days of primary cardiac procedure sufficiently captured all CT-surgery SSIs. Of 551 CT-surgery procedures prior to intervention, 91 (17%) had delayed final operative closures. Prior to the intervention, 16 SSIs were identified from July 2017 – May 2019 for a rate of 2.90 per /100 procedures, and was higher among patients with delayed chest closure 6.59 per /100 procedures (6 SSIs/91 procedures) versus those with primary chest closure 2.17 per /100 procedures (10 SSIs/460 procedures; P = 0.034). Gram-positive organisms, including coagulase coagulase-negative Staphylococci, were most frequently identified as the causative organisms for SSIs. Compliance with bundled intervention, rolled out over a 2-month period, was associated with an immediate decrease in the number of SSIs for primary and delayed chest closures 6SSIs /185 procedures in the initial quarters (August – December 2019) of the post-intervention period. However, this decrease was not reflected in the overall rate (3.24 per /100 procedures) due to fewer procedures performed. Data collection to measure sustainability is ongoing. Conclusions: Bundled interventions targeting skin antisepsis and environmental cleaning may be associated with a decrease in SSIs among pediatric CT-surgery patients. Ongoing surveillance is required to determine sustainability of these interventions.

Funding: None

Disclosures: None

Background: Clinically diagnosed ventilator-associated pneumonia (VAP) is common in the long-term acute-care hospital (LTACH) setting and may contribute to adverse ventilator-associated events (VAEs). Pseudomonas aeruginosa is a common causative organism of VAP. We evaluated the impact of respiratory P. aeruginosa colonization and bacterial community dominance, both diagnosed and undiagnosed, on subsequent P. aeruginosa VAP and VAE events during long-term acute care. Methods: We enrolled 83 patients on LTACH admission for ventilator weaning, performed longitudinal sampling of endotracheal aspirates followed by 16S rRNA gene sequencing (Illumina HiSeq), and bacterial community profiling (QIIME2). Statistical analysis was performed with R and Stan; mixed-effects models were fit to relate the abundance of respiratory Psa on admission to clinically diagnosed VAP and VAE events. Results: Of the 83 patients included, 12 were diagnosed with P. aeruginosa pneumonia during the 14 days prior to LTACH admission (known P. aeruginosa), and 22 additional patients received anti–P. aeruginosa antibiotics within 48 hours of admission (suspected P. aeruginosa); 49 patients had no known or suspected P. aeruginosa (unknown P. aeruginosa). Among the known P. aeruginosa group, all 12 patients had P. aeruginosa detectable by 16S sequencing, with elevated admission P. aeruginosa proportional abundance (median, 0.97; IQR, 0.33–1). Among the suspected P. aeruginosa group, all 22 patients had P. aeruginosa detectable by 16S sequencing, with a wide range of admission P. aeruginosa proportional abundance (median, 0.0088; IQR, 0.00012–0.31). Of the 49 patients in the unknown group, 47 also had detectable respiratory Psa, and many had high P. aeruginosa proportional abundance at admission (median, 0.014; IQR, 0.00025–0.52). Incident P. aeruginosa VAP was observed within 30 days in 4 of the known P. aeruginosa patients (33.3%), 5 of the suspected P. aeruginosa patients (22.7%), and 8 of the unknown P. aeruginosa patients (16.3%). VAE was observed within 30 days in 1 of the known P. aeruginosa patients (8.3%), 2 of the suspected P. aeruginosa patients (9.1%), and 1 of the unknown P. aeruginosa patients (2%). Admission P. aeruginosa abundance was positively associated with VAP and VAE risk in all groups, but the association only achieved statistical significance in the unknown group (type S error <0.002 for 30-day VAP and <0.011 for 30-day VAE). Conclusions: We identified a high prevalence of unrecognized respiratory P. aeruginosa colonization among patients admitted to LTACH for weaning from mechanical ventilation. The admission P. aeruginosa proportional abundance was strongly associated with increased risk of incident P. aeruginosa VAP among these patients.

Funding: None

Disclosures: None

Background: Contaminated surfaces within patient rooms and on shared equipment is a major driver of healthcare-acquired infections (HAIs). The emergence of Candida auris in the New York City metropolitan area, a multidrug-resistant fungus with extended environmental viability, has made a standardized assessment of cleaning protocols even more urgent for our multihospital academic health system. We therefore sought to create an environmental surveillance protocol to detect C. auris and to assess patient room contamination after discharge cleaning by different chemicals and methods, including touch-free application using an electrostatic sprayer. Surfaces disinfected using touch-free methods may not appear disinfected when assessed by fluorescent tracer dye or ATP bioluminescent assay. Methods: We focused on surfaces within the patient zone which are touched by the patient or healthcare personnel prior to contact with the patient. Our protocol sampled the over-bed table, call button, oxygen meter, privacy curtain, and bed frame using nylon-flocked swabs dipped in nonbacteriostatic sterile saline. We swabbed a 36-cm2 surface area on each sample location shortly after the room was disinfected, immediately inoculated the swab on a blood agar 5% TSA plate, and then incubated the plate for 24 hours at 36°C. The contamination with common environmental bacteria was calculated as CFU per plate over swabbed surface area and a cutoff of 2.5 CFU/cm2 was used to determine whether a surface passed inspection. Limited data exist on acceptable microbial limits for healthcare settings, but the aforementioned cutoff has been used in food preparation. Results: Over a year-long period, terminal cleaning had an overall fail rate of 6.5% for 413 surfaces swabbed. We used the protocol to compare the normal application of either peracetic acid/hydrogen peroxide or bleach using microfiber cloths to a new method using sodium dichloroisocyanurate (NaDCC) applied with microfiber cloths and electrostatic sprayers. The normal protocol had a fail rate of 9%, and NaDCC had a failure rate of 2.5%. The oxygen meter had the highest normal method failure rate (18.2%), whereas the curtain had the highest NaDCC method failure rate (11%). In addition, we swabbed 7 rooms previously occupied by C. auris–colonized patients for C. auris contamination of environmental surfaces, including the mobile medical equipment of the 4 patient care units that contained these rooms. We did not find any C. auris, and we continue data collection. Conclusions: A systematic environmental surveillance system is critical for healthcare systems to assess touch-free disinfection and identify MDRO contamination of surfaces.

Funding: None

Disclosures: None

Background: Central-line–associated bloodstream infection (CLABSI) rates have steadily decreased as evidence-based prevention bundles were implemented. Bone marrow transplant (BMT) patients are at increased risk for CLABSI due to immunosuppression, prolonged central-line utilization, and frequent central-line accesses. We assessed the impact of an enhanced prevention bundle on BMT nonmucosal barrier injury CLABSI rates. Methods: The University of Iowa Hospitals & Clinics is an 811-bed academic medical center that houses the only BMT program in Iowa. During October 2018, we added 3 interventions to the ongoing CLABSI prevention bundle in our BMT inpatient unit: (1) a standardized 2-person dressing change team, (2) enhanced quality daily chlorhexidine treatments, and (3) staff and patient line-care stewardship. The bundle included training of nurse champions to execute a team approach to changing central-line dressings. Standard process description and supplies are contained in a cart. In addition, 2 sets of sterile hands and a second person to monitor for breaches in sterile procedure are available. Site disinfection with chlorhexidine scrub and dry time are monitored. Training on quality chlorhexidine bathing includes evaluation of preferred product, application per product instructions for use and protection of the central-line site with a waterproof shoulder length glove. In addition to routine BMT education, staff and patients are instructed on device stewardship during dressing changes. CLABSIs are monitored using NHSN definitions. We performed an interrupted time-series analysis to determine the impact of our enhanced prevention bundle on CLABSI rates in the BMT unit. We used monthly CLABSI rates since January 2017 until the intervention (October 2018) as baseline. Because the BMT changed locations in December 2018, we included both time points in our analysis. For a sensitivity analysis, we assessed the impact of the enhanced prevention bundle in a hematology-oncology unit (March 2019) that did not change locations. Results: During the period preceding bundle implementation, the CLABSI rate was 2.2 per 1,000 central-line days. After the intervention, the rate decreased to 0.6 CLABSI per 1,000 central-line days (P = .03). The move in unit location did not have a significant impact on CLABSI rates (P = .85). CLABSI rates also decreased from 1.6 per 1,000 central-line days to 0 per 1,000 central-line days (P < .01) in the hematology-oncology unit. Conclusions: An enhanced CLABSI prevention bundle was associated with significant decreases in CLABSI rates in 2 high-risk units. Novel infection prevention bundle elements should be considered for special populations when all other evidence-based recommendations have been implemented.

Funding: None

Disclosures: None

Background: Healthcare exposure results in significant microbiome disruption, particularly in the setting of critical illness, which may contribute to risk for healthcare-associated infections (HAIs). Patients admitted to long-term acute-care hospitals (LTACHs) have extensive prior healthcare exposure and critical illness; significant microbiome disruption has been previously documented among LTACH patients. We compared the predictive value of 3 respiratory tract microbiome disruption indices—bacterial community diversity, dominance, and absolute abundance—as they relate to risk for ventilator-associated pneumonia (VAP) and adverse ventilator-associated events (VAE), which commonly complicate LTACH care. Methods: We enrolled 83 subjects on admission to an academic LTACH for ventilator weaning and performed longitudinal sampling of endotracheal aspirates, followed by 16S rRNA gene sequencing (Illumina HiSeq), bacterial community profiling (QIIME2) for diversity, and 16S rRNA quantitative PCR (qPCR) for total bacterial abundance. Statistical analyses were performed with R and Stan software. Mixed-effects models were fit to relate the admission MDIs to subsequent clinically diagnosed VAP and VAE. Results: Of the 83 patients, 19 had been diagnosed with pneumonia during the 14 days prior to LTACH admission (ie, “recent past VAP”); 23 additional patients were receiving antibiotics consistent with empiric VAP therapy within 48 hours of admission (ie, “empiric VAP therapy”); and 41 patients had no evidence of VAP at admission (ie, “no suspected VAP”). We detected no statistically significant differences in admission Shannon diversity, maximum amplicon sequence variant (ASV)–level proportional abundance, or 16S qPCR across the variables of interest. In isolation, all 3 admission microbiome disruption indices showed poor predictive performance, though Shannon diversity performed better than maximum ASV abundance. Predictive models that combined (1) bacterial diversity or abundance with (2) recent prior VAP diagnosis and (3) concurrent antibiotic exposure best predicted 14-day VAP (type S error < 0.05) and 30-day VAP (type S error < 0.003). In this cohort, VAE risk was paradoxically associated with higher admission Shannon diversity and lower admission maximum ASV abundance. Conclusions: In isolation, respiratory tract microbiome disruption indices obtained at LTACH admission showed poor predictive performance for subsequent VAP and VAE. But diversity and abundance models incorporating recent VAP history and admission antibiotic exposure performed well predicting 14-day and 30-day VAP.

Disclosures: None

Funding: None

This paper describes a collaborative approach to professional learning that has provided an opportunity for refreshed practices and growth in capacity in schools supporting students with various learning needs in several schools that are part of the Association of Independent Schools in the Australian Capital Territory. An action research approach to professional learning for school staff was facilitated with the participating schools in 2018/2019, centred on the Nationally Consistent Collection of Data on School Students with Disability.

The coronavirus disease 2019 (COVID-19) pandemic introduced challenges to the use of simulation, including limited personal protective equipment and restricted time and personnel. Our use of video for in situ simulation aimed to circumvent these challenges and assist in the development of a protocol for protected intubation and simultaneously educate emergency department (ED) staff. We video-recorded a COVID-19 respiratory failure in situ simulation event, which was shared by a facilitator both virtually and in the ED. The facilitator led discussions and debriefs. We followed this with in situ run-throughs in which staff walked through the steps of the simulation in the ED, handling medications and equipment and becoming comfortable with use of isolation rooms. This application of in situ simulation allowed one simulation event to reach a wide audience, while allowing participants to respect social distancing, and resulted in the education of this audience and successful crowdsourcing for a protocol amidst a pandemic.