During their northward migration, Red Knots Calidris canutus rufa stop at the Lagoa do Peixe National Park in the extreme south of Brazil to build up fat reserves for their journey to their Canadian breeding grounds. We tracked five Red Knots with PinPoint Argos-75 GPS transmitters to investigate differences in migration strategies from this stopover. Tracked birds used two different routes: the Central Brazil route and the Brazilian Atlantic Coast route. One bird flew 8,300 km straight from Lagoa do Peixe to the Delaware Bay (USA). Another bird stopped in Maranhão (north-east Brazil) and a third one used a yet unknown environment for the species, the mouth of the Amazon River at Baía Santa Rosa, Brazil. These two birds made short flights, covering stretches of 1,600 km to 3,600 km between stop-overs, where they stayed from 4 to 18 days. Our study highlights the occurrence of intrapopulation variation in migratory strategies and reveals the connectivity of environments that are essential for the viability of rufa Red Knot populations.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

Background: Data regarding the effects of the SARS-COV-2 (COVID-19) pandemic on healthcare-associated infections (HAIs) in Canadian acute-care hospitals are limited. We examined the impact of the COVID-19 pandemic on HAIs and antimicrobial resistant organisms in hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Methods: We analyzed 13,406 HAIs including adult mixed intensive care unit (ICU) central-line–associated bloodstream infections (CLABSIs), and healthcare-associated (HA) Clostridioides difficile infection (CDI), methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), vancomycin-resistant Enterococcus (VRE) BSI, and carbapenemase-producing Enterobacterales (CPE) infections collected using standardized case definitions and questionnaires from 29–64 hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) from January 2018 to December 2021. We used a generalized linear mixed model with quasi-Poisson distribution to assess step and slope changes in monthly HAI rates between the pre–COVID-19 pandemic period (January 1, 2018–February 29, 2020; 26 time points) and the COVID-19 pandemic period (March 1, 2020–December 31, 2021; 22 time points). Results were reported as incidence rate ratios (IRRs) with 95% confidence intervals (CIs) and adjusted for seasonality, hospital clustering, and hospital characteristics of interest. Results: In the CNISP network, 7,352 (55%) HAIs were reported in the prepandemic period and 6,054 (45%) in the pandemic period. Median age was significantly younger during the pandemic period compared to the prepandemic period among patients with HA-CDI, HA-MRSA BSI, and adult mixed ICU CLABSIs, and more than half of cases among all reported HAIs were male (range, 52%–65%). The 30-day all-cause in-hospital mortality rate did not significantly change between the prepandemic and pandemic periods for all reported HAIs and was highest among HA-VRE BSIs (34%). Modeling results indicated that the COVID-19 pandemic was associated with an immediate increase in HA-CDI and adult mixed ICU CLABSI rates whereas HA-MRSA BSI, HA-CPE and HA-VRE BSI rates immediately decreased. However, pandemic status did not have a statistically significant lasting impact on monthly rate trends for all reported HAIs after adjusting for seasonality, clustering, and hospital covariates (Fig. 1 and 2). Adjusted IRRs for all HAIs ranged from 1.00 to 1.01 (95% CI, 0.94–0.99 to 1.01–1.05).

Conclusions: Although the COVID-19 pandemic placed a significant burden on the Canadian healthcare system, the immediate impact on monthly rates of HAIs in Canadian acute-care hospitals was not sustained over time. Understanding the epidemiological effects of the COVID-19 pandemic in the context of changing patient populations, and clinical and infection control practices, are essential to inform the continued management and prevention of HAIs in Canadian acute-care settings.

Disclosures: None

Background: The Canadian Nosocomial Infection Surveillance Program (CNISP) observed increased mortality among neonatal intensive care unit (NICU) patients with central-line–associated bloodstream infection (CLABSI) starting in 2017. In this study, we compared NICU patients with CLABSIs before and after 2017, and quantified the impact of epidemiological factors on 30-day survival. Methods: We included 1,276 NICU patients from 8–16 participating CNISP hospitals from the pre-2017 period (2009–2016) and the post-2017 period (2017–2022) using standardized definitions and questionnaires. We used Cox regression modeling to assess the impact of age at date of positive culture, sex, birthweight, CLABSI microorganism, region of the country, and surveillance period (before 2017 vs after 2017) on time to 30-day all-cause mortality from date of positive culture. Gestational age was not available for this analysis. We reported model outputs as hazard ratios with 95% CIs. Results: In total, 769 (60%) NICU CLABSIs were reported in the pre-2017 period and 507 (40%) in the post-2017 period. The 30-day all-cause mortality rate was 8% (n = 100 of 1,276) overall, and significantly higher after 2017 (12%, n = 61 of 507) than before 2017 (5%, n = 39 of 769) (P < .001).

During the post-2017 period, cases were significantly younger: 16 days (IQR, 9–33) versus 21 days (IQR, 11–49) (P = .002). Median days from ICU admission to infection were shorter: 14 (IQR, 8–31) versus 19 (IQR, 10–41) (P < .001). More gram-negative CLABSIs were identified (29% vs 24%; P = .040) and fewer gram-positive CLABSIs were identified (64% vs 72%; P = .006) compared to the pre-2017 period. Mortality was higher in CLABSIs caused by gram-negative bacteria (15%, n = 50 of 328) than gram-positive bacteria (4.4%, n = 39 of 877) (P < .001), and mortality was higher in neonates with birthweight <1,000 g (11%, n = 71 of 673) compared to those weighing ≥1,000 g (5%, n = 28 of 560) (P < .001).

Adjusting for all other factors, survival modeling indicated that NICU CLABSIs identified in the post-2017 period had 2.12 (95% CI, 1.23–3.66) times the hazard ratio of 30-day all-cause mortality compared to those before 2017 (P < .006). Those identified with a gram-positive bacterium had a 0.28 hazard ratio (95% CI, 0.12–0.65) of 30-day mortality compared to those with a gram-negative bacterium or fungus (P = .003). In the fully adjusted model, age, sex, and birthweight were not significantly associated with NICU CLABSI survival. Conclusions: NICU patients with CLABSIs had significantly higher all-cause mortality between 2017–2022 compared to 2009–2016, and those who acquired gram-positive–associated CLABSIs had improved survival compared to other organisms. Further work is needed to identify and understand factors driving the increased mortality among NICU CLABSI patients from 2017–2022.

Disclosures: None

Of 731 restricted antimicrobial prescriptions subject to antimicrobial stewardship program (ASP) prospective audit and feedback (PAF) over a 3-year period, 598 PAF recommendations (82%) were fully accepted. Physician auditors had an increased odds of PAF recommendation acceptance, reinforcing the complementary role of the ASP physician in the multidisciplinary ASP team.

OBJECTIVES/GOALS: Microtubule poisons, like Taxol, are used to treat triple negative breast cancer (TNBC) and may induce lethal aneuploidy in cancer cells. Patients initially respond, but often develop drug resistance. New targeted drugs that cause aneuploidy may be a valuable approach to therapy. One potential target is the Kinesin 13 MCAK, which limits aneuploidy. METHODS/STUDY POPULATION: TCGA and GSE47561 databases were probed for MCAK expression, and data was stratified by subtype and survival statistics. Knockdown studies were performed to test whether MCAK knockdown sensitizes cells to taxanes for cell proliferation and for induction of aneuploidy. FRET and image-based screens were used to identify MCAK inhibitors from small molecule inhibitor libraries. Inhibitors were then tested for functional effects in multiple cell-based assays and for clonal growth in colony formation assays. RESULTS/ANTICIPATED RESULTS: MCAK expression is upregulated in TNBC and associated with reduced overall survival. Knockdown of MCAK caused a two-to-five-fold reduction of the IC50 for Taxol in cancer cell lines, with no change in normal cell lines. Taxol treatment or MCAK knockdown increased aneuploidy induction, with no additive effect between the two. Our small molecule screen identified three putative MCAK inhibitors, which induced aneuploidy in both taxane-sensitive and taxane-resistant cells. These inhibitors also reduced clonogenic growth, and the most potent inhibitor, C4, caused an approximate five-fold reduction in the IC50 for Taxol in cell proliferation assays. DISCUSSION/SIGNIFICANCE: MCAK can serve as a biomarker of breast cancer prognosis. MCAK knockdown or inhibition sensitizes cancer cells to Taxol without affecting normal cells, making it a potential target in combination therapy. MCAK inhibitors also reduce growth as single agents in taxane resistant lines, giving them potential use as therapies in resistant disease.

Historically, natural and manmade disasters create many victims and impose pressures on health-care infrastructure and staff; potentially hampering the provision of patient care and overloading clinician capacity. Throughout the course of history, clinicians have performed heroics to work well above their required duty, despite limitations, even putting their own health and safety at risk. In times when clinicians needed to either physically abandon patients or consider abandoning active treatment, we have seen extreme hesitancy to do so, fearing that they may be giving up too soon, that undue harm may come to patients, or even feeling unsure of legal or moral burdens that may ensue. In times when clinicians are placed in this unimaginable position, feeling isolated and overwhelmed, it is essential that they be supported and provided with resources to standardize decision-making.

Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, “Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease,” includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.

This paper proposes a framework for comprehensive, collaborative, and community-based care (C4) for accessible mental health services in low-resource settings. Because mental health conditions have many causes, this framework includes social, public health, wellness and clinical services. It accommodates integration of stand-alone mental health programs with health and non-health community-based services. It addresses gaps in previous models including lack of community-based psychotherapeutic and social services, difficulty in addressing comorbidity of mental and physical conditions, and how workers interact with respect to referral and coordination of care. The framework is based on task-shifting of services to non-specialized workers. While the framework draws on the World Health Organization’s Mental Health Gap Action Program and other global mental health models, there are important differences. The C4 Framework delineates types of workers based on their skills. Separate workers focus on: basic psychoeducation and information sharing; community-level, evidence-based psychotherapeutic counseling; and primary medical care and more advanced, specialized mental health services for more severe or complex cases. This paper is intended for individuals, organizations and governments interested in implementing mental health services. The primary aim is to provide a framework for the provision of widely accessible mental health care and services.

A clinical decision tree was developed using point-of-care characteristics to identify patients with culture-proven sepsis due to extended-spectrum β-lactamase–producing Enterobacterales (ESBL-PE). We compared its performance with the clinical gestalt of emergency department (ED) clinicians and hospital-based clinicians. The developed tree outperformed ED-based clinicians but was comparable to inpatient-based clinicians.