MOTIVATION: Chromatin immunoprecipitation sequencing (ChIP-seq) experiments are inexpensive and time-efficient, and result in massive datasets that introduce significant storage and maintenance challenges. To address the resulting Big Data problems, we propose a lossless and lossy compression framework specifically designed for ChIP-seq Wig data, termed ChIPWig. ChIPWig enables random access, summary statistics lookups and it is based on the asymptotic theory of optimal point density design for nonuniform quantizers. RESULTS: We tested the ChIPWig compressor on 10 ChIP-seq datasets generated by the ENCODE consortium. On average, lossless ChIPWig reduced the file sizes to merely 6% of the original, and offered 6-fold compression rate improvement compared to bigWig. The lossy feature further reduced file sizes 2-fold compared to the lossless mode, with little or no effects on peak calling and motif discovery using specialized NarrowPeaks methods. The compression and decompression speed rates are of the order of 0.2 sec/MB using general purpose computers. AVAILABILITY AND IMPLEMENTATION: The source code and binaries are freely available for download at https://github.com/vidarmehr/ChIPWig-v2, implemented in C ++. CONTACT: milenkov@illinois.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Abstract

Background

Balancing antimicrobial stewardship with sepsis management is a challenge. At our academic medical center, a “Code Sepsis” was implemented as a nursing driven initiative to improve early recognition and management of sepsis. Per protocol, Code Sepsis is activated in patients who meet two or more systemic inflammatory response syndrome (SIRS) criteria due to a suspected infection to allow for early implementation of the sepsis bundle, which includes laboratory testing, fluid resuscitation, and antibiotic administration (Figure 1). We analyzed the impact that Code Sepsis had on antimicrobial use among hospitalized patients over a six month period.

Methods

We reviewed the electronic medical records of hospitalized patients with Code Sepsis activation between January 1, 2018 and June 30, 2018 to determine whether antibiotics were “escalated” or “not escalated.” Among patients who had antibiotic escalation, escalation was classified as “indicated” or “not indicated” (Figure 2). A logistic regression model was used to identify characteristics, SIRS or organ dysfunction criteria predictive of indicated antimicrobial escalation.

Results

Code Sepsis was activated in 529 patients with antibiotics escalated in 247 (47%) and not escalated in 282 (53%) (Table 1). Among patients whose antibiotics were escalated, 64% (152) had an indication. In 36% (89), escalation was not indicated as Code Sepsis was due to a suspected noninfectious source, known infectious source already on appropriate antimicrobials, or a suspected infectious source in which diagnostic results had already shown the absence of the infection (Figure 2). Odds of indicated antibiotic escalation increased with the number of SIRS and organ dysfunction criteria (Table 2).

Conclusion

In our efforts to improve sepsis outcomes, we focused on early recognition (Code Sepsis) and intervention (sepsis bundle). However, our Code Sepsis inadvertently led to antibiotic overutilization. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock, we hope to optimize resource utilization and improve patient outcomes.

Disclosures

All authors: No reported disclosures.

Background

Cigarette lifestyle marketing with psychographic targeting has been well documented, but few studies address non-cigarette tobacco products. This study examined how young adults respond to e-cigarette advertisements featuring diverse peer crowds - peer groups with shared identities and lifestyles - to inform tobacco counter-marketing design.

Methods

Fifty-nine young adult tobacco users in California participated in interviews and viewed four to five e-cigarette advertisements that featured characters from various peer crowd groups. For each participant, half of the advertisements they viewed showed characters from the same peer crowd as their own, and the other half of the advertisements featured characters from a different peer crowd. Advertisements were presented in random order. Questions probed what types of cues are noticed in the advertisements, and whether and how much participants liked or disliked the advertisements.

Results

Results suggest that participants liked and provided richer descriptions of characters and social situations in the advertisements featuring their own peer crowd more than the advertisements featuring a different peer crowd. Mismatching age or device type was also noted: participants reported advertisements showing older adults were not intended for them. Participants who used larger vaporizers tended to dislike cigalike advertisements even if they featured a matching peer crowd.

Conclusion

Peer crowd and lifestyle cues, age and device type are all salient features of e-cigarette advertising for young adults. Similarly, educational campaigns about e-cigarettes should employ peer crowd-based targeting to engage young adults, though messages should be carefully tested to ensure authentic and realistic portrayals.

Given the emerging tobacco landscape, dual use of cigarettes and e-cigarettes has increased among young adults, but little is known about its associated factors. Peer crowds, defined as macro-level connections between individuals with similar core values (e.g., "Hip Hop" describing a group that prefers hip hop music and values strength, honor, and respect), are a promising way to understand tobacco use patterns. We examined associations between peer crowds and tobacco use patterns by using data from a cross sectional survey of 1340 young adults in the San Francisco Bay Area in 2014. Outcomes were the past 30-day use of: neither cigarettes nor e-cigarettes; cigarettes but not e-cigarettes; e-cigarettes but not cigarettes; and both cigarettes and e-cigarettes. Peer crowds included Hipster, Hip Hop, Country, Partier, Homebody, and Young Professional. Multinomial regression analysis indicated that peer crowds were significantly associated with different tobacco use patterns. Compared to Young Professionals, Hip Hop and Hipster crowds were more likely to dual use; Hipsters were more likely to use e-cigarettes only, and Country participants were more likely to smoke cigarettes only. These findings suggest that tobacco control campaigns and cessation interventions should be tailored to different young adult peer crowds and address poly-tobacco use.

Motivation:Chromatin immunoprecipitation sequencing (ChIP-seq) experiments are inexpensive and time-efficient, and result in massive datasets that introduce significant storage and maintenance challenges. To address the resulting Big Data problems, we propose a lossless and lossy compression framework specifically designed for ChIP-seq Wig data, termed ChIPWig. ChIPWig enables random access, summary statistics lookups and it is based on the asymptotic theory of optimal point density design for nonuniform quantizers. Results:We tested the ChIPWig compressor on 10 ChIP-seq datasets generated by the ENCODE consortium. On average, lossless ChIPWig reduced the file sizes to merely 6% of the original, and offered 6-fold compression rate improvement compared to bigWig. The lossy feature further reduced file sizes 2-fold compared to the lossless mode, with little or no effects on peak calling and motif discovery using specialized NarrowPeaks methods. The compression and decompression speed rates are of the order of 0.2 sec/MB using general purpose computers. Availability and implementation:The source code and binaries are freely available for download at https://github.com/vidarmehr/ChIPWig-v2, implemented in C ++. Contact:milenkov@illinois.edu. Supplementary information:Supplementary data are available at Bioinformatics online.

This study examined the effect of exposure to "cigalike" (products resembling cigarettes) e-cigarette advertisements on adolescents' perceptions of cigarettes. A nationally representative sample of 802 adolescents (13-17 years old) was randomly assigned to watch three e-cigarette or three control advertisements. Never-smokers who saw the e-cigarette advertisements (n = 352) reported significantly lower perceived risks of smoking than those in the control condition (n = 320). Ever-smokers (n = 130) did not show significant differences across the conditions. In subgroup analyses, current smokers (reported smoking in the past 30 days, n = 31) in the e-cigarette condition reported significantly lower perceived benefits of smoking than those in the control condition. E-cigarette advertisements can affect adolescents' perceptions of cigarettes. Many advertisements, especially the ones promoting "cigalikes," depict e-cigarettes as being similar to cigarettes (e.g., look, flavor) but also as a solution for cigarettes' shortcomings (e.g., bad smell). While the advertisements include messages about problems posed by cigarettes, proposing e-cigarettes as a solution may decrease the perceived risks of smoking among never-smokers. It may also not be clear to adolescents whether advertisements are for cigarettes or e-cigarettes. Regulating e-cigarette advertisements to minimize adolescents' exposure may prevent potential harmful effects on never-smokers' perception of smoking.

Abstract

Background

Early reports have indicated widespread empiric antimicrobial usage in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As data regarding bacterial complications in patients with Coronavirus Disease 2019 (COVID-19) are limited and emerging, it is important to delineate the burden of complications with bacterial pneumonia in patients with COVID-19 and its implication on antimicrobial usage.

Methods

We conducted a retrospective cohort study of all hospitalized patients diagnosed with COVID-19 based on detection of SARS-CoV-2 on RT-PCR from March 1, 2020 to May 10, 2020. Data were collected retrospectively to determine the presence of bacterial pneumonia among patients hospitalized with COVID-19 and to identify demographics, comorbidities, or laboratory values that may help to distinguish patients with bacterial pneumonia. Fisher’s exact test was used to analyze categorical data and Student’s t test was used to analyze differences between means.

Results

Among 99 patients hospitalized with COVID-19 during the study period, complication with bacterial pneumonia was seen in 17 (17%) based on sputum, tracheal aspirate or lower respiratory tract cultures performed 8.9 ± 7.8 (mean ± SD) days from the detection of SARS-CoV-2 on RT-PCR. Staphylococcus aureus was the causative organism in 8 (47%) cases while Enterobacteriaceae were isolated in 7 (41%) cases, Burkholderia cepacia in one (6%) and Rahnella aqualitis in one (6%) case. There were no significant differences in demographics, comorbidities, or laboratory findings between patients with or without complication with bacterial pneumonia. However, those with complication with bacterial pneumonia were more likely to be intubated (24% vs. 88%, p< 0.01), on vasopressors (23% vs. 82%, p < 0.01), and require intensive care unit admission (37% vs. 94%, p< 0.01).

Conclusion

Nosocomial and ventilator-associated pneumonia were commonly seen among hospitalized patients with COVID-19 requiring intubation and intensive care use admission. With complications of bacterial pneumonia common among critically-ill patients infected with SARS-CoV-2, widespread antimicrobial usage may increase the selective pressure for antibiotic resistance in this patient population.

Disclosures

All Authors: No reported disclosures

Abstract Background As of June 2, 2020, 67,113 cases and 321 deaths due to Coronavirus Disease 19 (COVID-19) have been reported in healthcare personnel (HCP) in the United States. Given the close contact of HCP with individuals with COVID-19, it is important to quantify the risk of acquiring COVID-19 in the healthcare setting. Methods We conducted a retrospective cohort study of HCP exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at our academic medical center from March 15, 2020 to May 16, 2020. Exposure during the study period was defined as having contact with patients or other HCP with COVID-19 within 6 feet of distance for at least 90 seconds when HCP’s eyes, nose, or mouth were not covered. HCP with exposures were monitored for symptoms consistent with COVID-19 for 14 days from last exposure and those who developed symptoms were tested for SARS-CoV-2 using RT-PCR. Results We identified 33 exposure events; 19 of which were patient-to-HCP exposures and 14 of which were HCP-to-HCP exposures. These 33 events resulted in 959 exposed HCP among whom 238 (25%) developed one or more symptoms of COVID-19 and required SARS-CoV-2 RT-PCR testing. Testing was performed at 7.1 ± 5.0 (mean ± SD) days from exposure. Of the 238 HCP who were tested, 82% were female and 49% were registered nurses (Table 1). Five HCP tested positive for SARS-CoV-2 by RT-PCR, but one was presumed to have acquired the disease from a household member with confirmed COVID-19. Among the four HCP who were infected due to occupational exposure, three were nurses while one was an environmental service worker (Table 1). Conclusion Despite exposures among HCP, the risk of acquiring symptomatic COVID-19 in the healthcare setting was low with less than 1% of HCP with occupational exposure subsequently diagnosed with COVID-19. With the definition of exposure now changed to at least 15 minutes of close contact without personal protective equipment, we anticipate fewer exposures at our healthcare facility and that much of COVID-19 transmission affecting HCP are due to community exposures. Disclosures All Authors: No reported disclosures

Cancer cells condition macrophages and other inflammatory cells in the tumor microenvironment so that these cells are more permissive for cancer growth and metastasis. Conditioning of inflammatory cells reflects, at least in part, soluble mediators (such as transforming growth factor β and IL-4) that are released by cancer cells and alter the phenotype of cells of the innate immune system. Signaling pathways in cancer cells that potentiate this activity are incompletely understood. The urokinase receptor (uPAR) is a cell-signaling receptor known to promote cancer cell survival, proliferation, metastasis, and cancer stem cell-like properties. The present findings show that uPAR expression in diverse cancer cells, including breast cancer, pancreatic cancer, and glioblastoma cells, promotes the ability of these cells to condition co-cultured bone marrow-derived macrophages so that the macrophages express significantly increased levels of arginase 1, a biomarker of the alternatively activated M2 macrophage phenotype. Expression of transforming growth factor β was substantially increased in uPAR-expressing cancer cells via a mechanism that requires uPA-initiated cell signaling. uPAR also controlled expression of IL-4 in cancer cells via a mechanism that involves activation of ERK1/2. The ability of uPAR to induce expression of factors that condition macrophages in the tumor microenvironment may constitute an important mechanism by which uPAR promotes cancer progression.