Objectives/Goals: We describe the prevalence of individuals with household exposure to SARS-CoV-2, who subsequently report symptoms consistent with COVID-19, while having PCR results persistently negative for SARS-CoV-2 (S[+]/P[-]). We assess whether paired serology can assist in identifying the true infection status of such individuals. Methods/Study Population: In a multicenter household transmission study, index patients with SARS-CoV-2 were identified and enrolled together with their household contacts within 1 week of index’s illness onset. For 10 consecutive days, enrolled individuals provided daily symptom diaries and nasal specimens for polymerase chain reaction (PCR). Contacts were categorized into 4 groups based on presence of symptoms (S[+/-]) and PCR positivity (P[+/-]). Acute and convalescent blood specimens from these individuals (30 days apart) were subjected to quantitative serologic analysis for SARS-CoV-2 anti-nucleocapsid, spike, and receptor-binding domain antibodies. The antibody change in S[+]/P[-] individuals was assessed by thresholds derived from receiver operating characteristic (ROC) analysis of S[+]/P[+] (infected) versusS[-]/P[-] (uninfected). Results/Anticipated Results: Among 1,433 contacts, 67% had ≥1 SARS-CoV-2 PCR[+] result, while 33% remained PCR[-]. Among the latter, 55% (n = 263) reported symptoms for at least 1 day, most commonly congestion (63%), fatigue (63%), headache (62%), cough (59%), and sore throat (50%). A history of both previous infection and vaccination was present in 37% of S[+]/P[-] individuals, 38% of S[-]/P[-], and 21% of S[+]/P[+] (P<0.05). Vaccination alone was present in 37%, 41%, and 52%, respectively. ROC analyses of paired serologic testing of S[+]/P[+] (n = 354) vs. S[-]/P[-] (n = 103) individuals found anti-nucleocapsid data had the highest area under the curve (0.87). Based on the 30-day antibody change, 6.9% of S[+]/P[-] individuals demonstrated an increased convalescent antibody signal, although a similar seroresponse in 7.8% of the S[-]/P[-] group was observed. Discussion/Significance of Impact: Reporting respiratory symptoms was common among household contacts with persistent PCR[-] results. Paired serology analyses found similar seroresponses between S[+]/P[-] and S[-]/P[-] individuals. The symptomatic-but-PCR-negative phenomenon, while frequent, is unlikely attributable to true SARS-CoV-2 infections that go missed by PCR.

Relationship-centred mealtimes can support care home residents, who are at high risk for loneliness. However, care home staff do not consistently promote relationship-centred mealtimes. This secondary analysis examined the impact of factors (selected based on the Theory of Planned Behaviour) upon care home staff interest in making mealtimes more relationship-centred. Data were from a cross-sectional, quantitative survey of 670 care home staff from North America. We used multivariable logistic regression to test hypotheses. The model was statistically significant, and explained 13 per cent of the variance in staff members’ interest in making mealtimes more relationship-centred. Respondents who were more satisfied with current mealtime practices, had used collaborative change strategies in the past, and who perceived organizational support for relationship-centred care were more likely to have interest in making mealtimes more relationship-centred. These are modifiable factors to target in interventions designed to promote care home staff interest in making mealtimes more relationship-centred.

Stieg Larsson's Millennium trilogy is part of a global hypercanon of popular fiction and thus a major commercial enterprise. In the translation of these works, the author and translator are joined by a host of shadowy figures—the source language publisher, scouts, literary agents, target language publishers, editors, and proofreaders—who transform the texts for a particular readership. This essay connects the market-oriented metamorphosis of paratext with substantial alterations to literary content itself. It is based on a computational study of the novels in Swedish and English that singled out major alterations to paragraph meaning and length across the three novels. The study showed that about 6.3% of the paragraphs have been cut or shortened by at least 30%. These extensive changes reveal a process of creative remaking, in which published works become raw content to be reshaped by commercial expectations and the demands of high production speed.

OBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism of toxicity. METHODS/STUDY POPULATION: The epidemiological aim of this study characterizes mitochondrial outcomes in samples of umbilical cord tissue and blood from two Manhattan based birth cohorts. Prenatal PAH exposure is quantified using silicone wristbands worn for 48 hours during the third trimester of pregnancy. Experimentally, we are applying a PAH mixture designed to emulate the exposure profile of the human cohorts to mouse preimplantation embryos on various dosing schedules and quantifying the same mitochondrial outcomes. mtDNAcn is quantified using rtPCR while superoxide production and membrane potential are measured using fluorescence microscopy. The goal of this study design is to leverage the strengths of each approach to draw more robust conclusions than could be derived from either alone. RESULTS/ANTICIPATED RESULTS: Preliminary results of this study have found associations between higher levels of PAH exposure and increased mitochondrial superoxide production and hyperpolarization of the mitochondrial membrane potential in mouse preimplantation embryos. We anticipate these findings to persist across dosing schedules. We furthermore expect a decrease in mtDNAcn in association with higher PAH exposure in umbilical cord tissue samples and decreased mtDNAcn with exposure to the PAH mixture in mouse embryos. DISCUSSION/SIGNIFICANCE: Characterizing the effect of prenatal PAH exposure on the mitochondria is a critical step in understanding the mechanisms that underlie the toxicity of this exposure. By employing a similar exposure mixture and mitochondrial outcomes across epidemiological and experimental approaches, we offer a model of true interdisciplinary research design.

Meltwater drainage beneath ice sheets is a fundamental consideration for understanding ice–bed conditions and bed-modulated ice flow, with potential impacts on terminus behavior and ice-shelf mass balance. While contemporary observations reveal the presence of basal water movement in the subglacial environment and inferred styles of drainage, the geological record of former ice sheets, including sediments and landforms on land and the seafloor, aids in understanding the spatiotemporal evolution of efficient and inefficient drainage systems and their impact on ice-sheet behavior. We highlight the past decade of advances in geological studies that focus on providing process-based information on subglacial hydrology of ice sheets, how these studies inform theory, numerical models and contemporary observations, and address the needs for future research.

Simon Reader's Notework: Victorian Literature and Nonlinear Style, as I discuss below, pushes us to rethink how we understand notes in the nineteenth century and in our own. I will begin with the contemporary implications of Reader's argument by pairing it with Rachel Sagner Buurma and Laura Heffernan's The Teaching Archive: A New History for Literary Study. Both books foreground aspects of the research and writing life that have always supported the publish-or-perish research agenda and yet have seemed instrumental or ephemeral.

The aim of the present study was to assess the seasonal relationship between serum 25(OH)D concentration, lean mass and muscle strength. This was a secondary data analysis of a subgroup of 102 postmenopausal women participating in the 2006–2007 D-FINES (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) study. The cohort was assessed as two age subgroups: <65 years (n=80) and ≥65 years (n=22). Outcome measures included lean mass (DXA), muscle strength (handgrip dynamometry) and serum 25(OH)D concentration (enzymeimmunoassay). Derived outcomes included appendicular skeletal muscle mass (ASM) and relative appendicular skeletal muscle index (RASM). Sarcopenia status was assessed using the European Working Group on Sarcopenia in Older People 2018 criteria. Non-parametric partial correlation using BMI as a covariate was used to evaluate the study aims. There were no statistically significant associations between total lean mass, ASM or RASM and 25(OH)D in any group at any season. There was a trend for handgrip strength to be positively associated with serum 25(OH)D concentration. There was a trend showing a higher prevalence of sarcopenia in women ≥65 years. Sarcopenia status appeared transient for five women. In conclusion, the present study found no significant association between vitamin D status and functional indicators of musculoskeletal health, which were additionally not affected by season.

Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.

This study describes changes in dining practices and provider perspectives on meal-related challenges due to the coronavirus disease (COVID-19) pandemic. An online survey was disseminated between July and September 2020 through stakeholder networks and social media with 1,036 respondents. Altered dining practices included residents eating in rooms (54.3%), spacing residents in common areas for meals (69.3%), and disposable dish use (44.9%). The most common mealtime challenges were reduced socializing opportunities at meals (29.3%), inadequate staffing (22.8%), reduced family/volunteer help (16.7%), and assisting residents to eat (10.5%). Many participants (72.2%) felt conflict balancing safety and relationship-centred care. Geographic region, home size, building age, respondent’s job title, pre-pandemic relationship-centred practices, and mealtime satisfaction, and some pandemic-initiated practices were associated with mealtime challenges and feeling conflicted in binary logistic regression analyses. Considering trade-offs between safety and relational aspects of mealtimes during the pandemic is crucial.

Background: Contaminated healthcare facility plumbing is increasingly recognized as a source of carbapenemase-producing organisms (CPOs). In August 2019, the Tennessee State Public Health Laboratory identified Tennessee’s twelfth VIM-producing carbapenem-resistant Pseudomonas aeruginosa (VIM-CRPA), from a patient in a long-term acute-care hospital. To determine a potential reservoir, the Tennessee Department of Health (TDH) reviewed healthcare exposures for all cases. Four cases (33%), including the most recent case and earliest from March 2018, had a history of admission to intensive care unit (ICU) room X at acute-care hospital A (ACH A), but the specimens were collected at other facilities. The Public Health Laboratory collaborated with ACH A to assess exposures, perform environmental sampling, and implement control measures. Methods: TDH conducted in-person infection prevention assessments with ACH A, including a review of the water management program. Initial recommendations included placing all patients admitted to room X on contact precautions, screening for CPO on room discharge, daily sink basin and counter cleaning, and other sink hygiene measures. TDH collected environmental and water samples from 5 ICU sinks (ie, the handwashing and bathroom sinks in room X and neighboring room Y [control] and 1 hallway sink) and assessed the presence of VIM-CRPA. Moreover, 5 patients and 4 environmental VIM-CRPA underwent whole-genome sequencing (WGS). Results: From February to June 2020, of 21 patients admitted to room X, 9 (43%) underwent discharge screening and 4 (44%) were colonized with VIM-CRPA. Average room X length of stay was longer for colonized patients (11.3 vs 4.8 days). Drain swabs from room X’s bathroom and handwashing sinks grew VIM-CRPA; VIM-CRPA was not detected in tap water or other swab samples. VIM-CRPA from the environment and patients were sequence type 253 and varied by 0–13 single-nucleotide variants. ACH A replaced room X’s sinks and external plumbing in July. Discharge screening and contact precautions for all patients were discontinued in November, 5 months following the last case and 12 consecutive negative patient discharge screens. Improved sink hygiene and mechanism testing for CRPA from clinical cultures continued, with no new cases identified. Conclusions: An ICU room with a persistently contaminated sink drain was a persistent reservoir of VIM-CRPA. The room X attack rate was high, with VIM-CRPA acquisition occurring in >40% of patients screened. The use of contaminated plumbing fixtures in ACH have the potential to facilitate transmission to patients but may be challenging to identify and remediate. All healthcare facilities should follow sink hygiene best practices.

Funding: No

Disclosures: None

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are a major public health concern because they typically display multidrug resistance and they cause hard-to-treat infections. Organisms harboring metallo-β-lactamases (MBLs) pose a critical challenge in clinical practice because they confer resistance to nearly all β-lactams, including recently approved β-lactam combination agents. A promising new β-lactam-β-lactamase inhibitor combination for treating infections caused by MBL-producing CPE is aztreonam–avibactam. Although clinical trials using aztreonam–avibactam are ongoing, clinicians can administer this combination using 2 US Food and Drug Administration (FDA)–approved drugs: aztreonam and ceftazidime–avibactam. In 2019, the Centers for Disease Control and Prevention (CDC) initiated a pilot program in the Antibiotic Resistance Laboratory Network (AR Lab Network) to address the lack of commercially available antimicrobial susceptibility tests (ASTs) for aztreonam-avibactam by performing broth microdilution (BMD) for this drug combination. We describe the isolates submitted for aztreonam-avibactam AST during the AR Lab Network pilot in 2019. Methods: The AR Lab Network regional laboratories adopted the HP D300e Digital Dispenser to create customized BMD panels for aztreonam–avibactam ASTs. To qualify for aztreonam–avibactam AST, isolates had to be an Enterobacteriaceae displaying nonsusceptibility to all tested β-lactams (including either ceftazidime-avibactam or meropenem-vaborbactam) or confirmed to harbor at least 1 MBL gene (blaVIM, blaNDM, or blaIMP). Regional laboratories confirmed carbapenemase gene(s) using a molecular method. If an MBL gene was confirmed, aztreonam-–avibactam minimum inhibitory concentrations (MICs) were reported back to submitters within 3 working days of receipt. Findings were reported to CDC using a REDCap database. Results: From March through August 2019, aztreonam–avibactam AST was requested for 32 clinical isolates across 16 states. These isolates included 15 Escherichia coli, 12 Klebsiella pneumoniae, 4 Enterobacter cloacae complex, and 1 Proteus mirabilis. Molecular detection identified 27 blaNDM-positive isolates, 2 blaOXA-48-like-positive isolates, and 3 blaOXA-48/blaNDM-positive isolates. Aztreonam-avibactam results were reported for 30 isolates; 5 displayed elevated aztreonam-avibactam MICs of 8/4 µg/mL (n = 4) or 16/4 µg/mL (n = 1). Results for 2 isolates were not reported because the isolates were MBL negative. Aztreonam-avibactam MICs ranged from 0.06/4 µg/mL to 16/4 µg/mL. The MIC50/MIC90 were 0.5/4 µg/mL and 8/4 µg/mL. Conclusions: In the absence of effective FDA-approved treatments and lack of available AST for novel antibiotic combinations, CDC’s provision of AST for aztreonam-avibactam among MBL-producing CPE, offered through the AR Lab Network, helps fill a critical gap to inform patient treatment decisions. To date, our in vitro data suggest that aztreonam–avibactam could be a promising drug combination for use against infections caused by MBL-producing Enterobacteriaceae.

Funding: None

Disclosures: None

Background: In the United States, carbapenemases are rarely the cause of carbapenem resistance in Pseudomonas aeruginosa. Detection of carbapenemase production (CP) in carbapenem-resistant P. aeruginosa (CRPA) is critical for preventing its spread, but testing of many isolates is required to detect a single CP-CRPA. The CDC evaluates CRPA for CP through (1) the Antibiotic Resistance Laboratory Network (ARLN), in which CRPA are submitted from participating clinical laboratories to public health laboratories for carbapenemase testing and antimicrobial susceptibility testing (AST) and (2) laboratory and population-based surveillance for CRPA in 8 sites through the Emerging Infection Program (EIP). Objective: We used data from ARLN and EIP to identify AST phenotypes that can help detect CP-CRPA. Methods: We defined CRPA as P. aeruginosa resistant to meropenem, imipenem, or doripenem, and we defined CP-CRPA as CRPA with molecular identification of carbapenemase genes (blaKPC, blaIMP, blaNDM, or blaVIM). We applied CLSI break points to 2018 ARLN CRPA AST data to categorize isolates as resistant, intermediate, or susceptible, and we evaluated the sensitivity and specificity of AST phenotypes to detect CP among CRPA; isolates that were intermediate or resistant were called nonsusceptible. Using EIP data, we assessed the proportion of isolates tested for a given drug in clinical laboratories, and we applied definitions to evaluate performance and number needed to test to identify a CP-CRPA. Results: Only 203 of 6,444 of CRPA isolates (3%) tested through AR Lab Network were CP-CRPA harboring blaVIM (n = 123), blaKPC (n = 53), blaIMP (n = 16), or blaNDM (n = 13) genes. Definitions with the best performance were resistant to ≥1 carbapenem AND were (1) nonsusceptible to ceftazidime (sensitivity, 93%; specificity, 61%) (Table 1) or (2) nonsusceptible to cefepime (sensitivity, 83%; specificity, 53%). Most isolates not identified by definition 2 were sequence type 111 from a single-state blaVIM CP-CRPA outbreak. Among 4,209 CRPA isolates identified through EIP, 80% had clinical laboratory AST data for ceftazidime and 96% had clinical laboratory AST data for cefepime. Of 967 CRPA isolates that underwent molecular testing at the CDC, 7 were CP-CRPA; both definitions would have detected all 7. Based on EIP data, the number needed to test to identify 1 CP-CRPA would decrease from 135 to 42 for definition 1 and to 50 using definition 2. Conclusions: AST-based definitions using carbapenem resistance combined with ceftazidime or cefepime nonsusceptibility would rarely miss a CP-CRPA and would reduce the number needed to test to identify CP-CRPA by >60%. These definitions could be considered for use in laboratories to decrease the testing burden to detect CP-CRPA.

Funding: None

Disclosures: In the presentation we will discuss the drug combination aztreonam-avibactam and acknowledge that this drug combination is not currently FDA approved.

Self-reported measures for body mass index (BMI) are considered a limitation in research design, especially when they are a primary outcome. Studies have found some populations to be quite accurate when self-reporting BMI; however, there is mixed research on the accuracy of self-reported measurements in adolescents. The aim of this study is to examine the accuracy of self-reported BMI by comparing it with measured BMI in a sample of U.S. adolescents and to understand gender differences. This cross-sectional study collected self-reported height and weight measurements of students from five high schools in four states (Tennessee, South Dakota, Kansas and Florida). Trained researchers took height and weight of students for an objective measurement. BMI was calculated from both sources and categorized (underweight, normal, overweight and obese) using the Centers for Disease Control and Prevention's BMI-for-age percentiles. Participants (n 425; 51⋅0 % female) had a mean age of 16⋅3 years old, and the majority were White (47⋅5 %). Limits of agreement (LOA) analysis revealed that BMI and weight were underreported, and height was overreported in the overall sample, in females, and in males. LOA analysis was fair for BMI in all three groups. Overall agreement in BMI categorisation was considered substantial (Κ 0⋅71, P < 0⋅001). As BMI increased, more height and weight inaccuracies led to decreased accuracy in BMI categorisation, and the specificity of obese participants was low (50⋅0 %). This study's findings suggest that using self-reported values to categorize BMI is more accurate than using continuous BMI values when self-reported measures are used in health-related interventions.