bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart Rate Variability as an Index of Resilience
Authors: An Eric , Nolty Anne A T , Amano Stacy S , Rizzo Albert A , Buckwalter J Galen , Rensberger Jared
Published: October 2019

Introduction

Resilience is the ability to maintain or quickly return to a stable physical and psychological equilibrium despite experiencing stressful events. Flexibility of the autonomic nervous system is particularly important for adaptive stress responses and may contribute to individual differences in resilience. Power spectrum analysis of heart rate variability (HRV) allows measurement of sympathovagal balance, which helps to evaluate autonomic flexibility. The present study investigated HRV as a broad index of resilience.

Materials and Methods

Twenty-four male participants from the Army National Guard Special Forces completed psychological measures known to relate to resilience and had HRV measured while undergoing stressful virtual environment scenarios. Pearson product-moment correlations were used to explore the relationships between HRV and resilience factors. All research was conducted with the oversight of the Human Subjects Review Committee of Fuller Theological Seminary.

Results

Trends toward significance were reported in order to provide results that would reasonably be expected in a study of higher power. Trends between resilience factors and HRV were found only during specific stress-inducing simulations (see Tables III).

Conclusion

Greater resilience to stress was associated with HRV during nonstress periods. Higher levels of resilience to traumatic events were associated with HRV during circumstances that were more stressful and emotionally distressing. Post hoc analysis revealed that specific factors including flexibility, emotional control, and spirituality were driving the relationship between general resilience and HRV following emotionally laden stressors. Less stress vulnerability was associated with HRV following intermittent brief stressors. In sum, HRV appears to represent some aspects of an individual’s overall resilience profile. Although resilience remains a complex, multidimensional construct, HRV shows promise as a global psychophysiological index of resilience. This study also offers important perspectives concerning ways to optimize both physical and psychological health.
Numerical modelling of the lobes of radio galaxies in cluster environments – IV. Remnant radio galaxies
Authors: English W , Hardcastle M J , Krause M G H
Published: October 2019

We examine the remnant phase of radio galaxies using three-dimensional hydrodynamical simulations of relativistic jets propagating through cluster environments. By switching the jets off once the lobes have reached a certain length we can study how the energy distribution between the lobes and shocked intracluster medium compares to that of an active source, as well as calculate synchrotron emission properties of the remnant sources. We see that as a result of disturbed cluster gas beginning to settle back into the initial cluster potential, streams of dense gas are pushed along the jet axis behind the remnant lobes, causing them to rise out of the cluster faster than they would due to buoyancy. This leads to increased adiabatic losses and a rapid dimming. The rapid decay of total flux density and surface brightness may explain the small number of remnant sources found in samples with a high flux density limit and may cause analytic models to overestimate the remnant fraction expected in sensitive surveys such as those now being carried out with LOFAR.
Neutrino fluence from gamma-ray bursts: off-axis view of structured jets
Authors: Ahlers Markus , Halser Lea
Published: October 2019

We investigate the expected high-energy neutrino fluence from internal shocks produced in the relativistic outflow of gamma-ray bursts. Previous model predictions have primarily focused on on-axis observations of uniform jets. Here, we present a generalization to account for arbitrary viewing angles and jet structures. Based on this formalism, we provide an improved scaling relation that expresses off-axis neutrino fluences in terms of on-axis model predictions. We also find that the neutrino fluence from structured jets can exhibit a strong angular dependence relative to that of gamma-rays and can be far more extended. We examine this behaviour in detail for the recent short gamma-ray burst GRB 170817A observed in coincidence with the gravitational wave event GW170817.
Study of the Galactic radio sources in the SCORPIO survey resolved by ATCA at 2.1 GHz
Authors: Ingallinera A , Umana G , Trigilio C , Norris R , Franzen T M O , Cavallaro F , Leto P , Buemi C , Schillirò F , Bufano F , Riggi S , Loru S , Agliozzo C
Published: October 2019

We present a catalogue of a large sample of extended radio sources in the SCORPIO field, observed and resolved by the Australia Telescope Compact Array. SCORPIO, a pathfinder project for addressing the early operations of the Australia SKA Pathfinder, is a survey of ∼5 square degrees between 1.4 and 3.1 GHz, centered at l = 343.5○, b = 0.75○ and with an angular resolution of about 10 arcsec. It is aimed at understanding the scientific and technical challenges to be faced by future Galactic surveys. With a mean sensitivity around $100\ \mu \mathrm{Jy\ beam}^{-1}$ and the possibility to recover angular scales at least up to 4 arcmin, we extracted 99 extended sources, 35 of them detected for the first time. Among the 64 known sources 55 had at least a tentative classification in literature. Studying the radio morphology and comparing the radio emission with infrared we propose as candidates 6 new H ii regions, 2 new planetary nebulae, 2 new luminous blue variable or Wolf–Rayet stars and 3 new supernova remnants. This study provides an overview of the potentiality of future radio surveys in terms of Galactic source extraction and characterization and a discussion on the difficulty to reduce and analyze interferometric data on the Galactic plane.
Combining high-z galaxy luminosity functions with Bayesian evidence
Authors: Gillet Nicolas J F , Mesinger Andrei , Park Jaehong
Published: October 2019

Galaxy formation during the first billion years of our Universe remains a challenging problem at the forefront of astrophysical cosmology. Although these $z\,\,{\gtrsim}\,\,6$ galaxies are likely responsible for the last major phase change of our Universe, the epoch of reionization (EoR), detailed studies are possible only for relatively rare, bright objects. Characterizing the fainter galaxies which are more representative of the population as a whole is currently done mainly through their non-ionizing UV luminosity function (LF). Observing the faint end of the UV LFs is nevertheless challenging, and current estimates can differ by orders of magnitude. Here we propose a methodology to combine disparate high-z UV LF estimates in a Bayesian framework: Bayesian Data-analysis Averaging (BDA). Using a flexible, physically-motivated galaxy model, we compute the relative evidence of various z = 6 UV LFs within the magnitude range −20 ≤ MUV ≤ −15 which is common to the data sets. Our model, based primarily on power-law scalings of the halo mass function, naturally penalizes systematically jagged points as well as misestimated errors. We then use the relative evidence to weigh the posteriors obtained from disparate LF data sets during the EoR, 6 ≤ z ≤ 10. The resulting LF posteriors suggest that the star formation rate density (SFRD) integrated down to a UV magnitude of -17 represent $60.9^{+11.3}_{-9.6}\%$ / $28.2^{+9.3}_{-10.1}\%$ / $5.7^{+4.5}_{-4.7}\%$ of the total SFRD at redshifts 6 / 10 / 15. The BDA framework we introduce enables galaxy models to leverage multiple, analogous LF estimates when constraining their free parameters.
A systematic study of spiral density waves in the accretion discs of cataclysmic variables
Authors: Ruiz-Carmona R , Groot P J , Steeghs D
Published: October 2019

Spiral density waves are thought to be excited in the accretion discs of accreting compact objects, including cataclysmic variable stars (CVs). Observational evidence has been obtained for a handful of systems in outburst over the last two decades. We present the results of a systematic study searching for spiral density waves in CVs, and report their detection in two of the sixteen observed systems. While most of the systems observed present asymmetric, non-Keplerian accretion discs during outburst, the presence of ordered structures interpreted as spiral density waves is not as ubiquitous as previously anticipated. From a comparison of systems by their system parameters it appears that inclination of the systems may play a major role, favouring the visibility and/or detection of spiral waves in systems seen at high inclination.
Galaxy And Mass Assembly (GAMA): properties and evolution of red spiral galaxies
Authors: Mahajan Smriti , Gupta Kriti Kamal , Rana Rahul , Brown M J I , Phillipps S , Bland-Hawthorn Joss , Bremer M N , Brough S , Holwerda B W , Hopkins A M , Loveday J , Pimbblet Kevin , Wang Lingyu
Published: October 2019

We use multiwavelength data from the Galaxy And Mass Assembly (GAMA) survey to explore the cause of red optical colours in nearby (0.002 < z < 0.06) spiral galaxies. We show that the colours of red spiral galaxies are a direct consequence of some environment-related mechanism(s) that has removed dust and gas, leading to a lower star formation rate. We conclude that this process acts on long time-scales (several Gyr) due to a lack of morphological transformation associated with the transition in optical colour. The specific star formation rate (sSFR) and dust-to-stellar mass ratio of red spiral galaxies is found to be statistically lower than blue spiral galaxies. On the other hand, red spirals are on average 0.9 dex more massive, and reside in environments 2.6 times denser than their blue counterparts. We find no evidence of excessive nuclear activity, or higher inclination angles to support these as the major causes for the red optical colours seen in ≳47 per cent of all spirals in our sample. Furthermore, for a small subsample of our spiral galaxies that are detected in H i, we find that the SFR of gas-rich red spiral galaxies is lower by ∼1 dex than their blue counterparts.
Hydrostatic mass estimates of massive galaxy clusters: a study with varying hydrodynamics flavours and non-thermal pressure support
Authors: Pearce Francesca A , Kay Scott T , Barnes David J , Bower Richard G , Schaller Matthieu
Published: October 2019

We use a set of 45 simulated clusters with a wide mass range (8 × 1013 < M500 [M⊙] < 2 × 1015) to investigate the effect of varying hydrodynamics flavours on cluster mass estimates. The cluster zooms were simulated using the same cosmological models as the BAHAMAS and C-EAGLE projects, leading to differences in both the hydrodynamics solvers and the subgrid physics but still producing clusters that broadly match observations. At the same mass resolution as BAHAMAS, for the most massive clusters (M500 > 1015 M⊙), we find that changes in the smoothed particle hydrodynamics (SPH) method produce the greatest differences in the final halo, while the subgrid models dominate at lower mass. By calculating the mass of all of the clusters using different permutations of the pressure, temperature, and density profiles, created with either the true simulated data or mock spectroscopic data, we find that the spectroscopic temperature causes a bias in the hydrostatic mass estimates that increases with the mass of the cluster, regardless of the SPH flavour used. For the most massive clusters, the estimated mass of the cluster using spectroscopic density and temperature profiles is found to be as low as 50 per cent of the true mass compared to ∼90 per cent for low-mass clusters. When including a correction for non-thermal pressure, the spectroscopic hydrostatic mass estimates are less biased on average and the mass dependence of the bias is reduced, although the scatter in the measurements does increase.
Numerical modelling of medium-speed impacts on a granular surface in a low-gravity environment application to Hayabusa2 sampling mechanism
Authors: Thuillet Florian , Michel Patrick , Tachibana Shogo , Ballouz Ronald-L , Schwartz Stephen R
Published: October 2019

Even if craters are very common on Solar System body surfaces, crater formation in granular media such as the ones covering most of visited asteroids still needs to be better understood, above all in low-gravity environments. JAXA’s sample return mission Hayabusa2, currently visiting asteroid (162173) Ryugu, is a perfect opportunity for studying medium-speed impacts into granular matter, since its sampling mechanism partly consists of a 300 m s−1 impact. In this paper, we look at medium-speed impacts, from 50 to 300 m s−1, into a granular material bed, to better understand crater formation and ejecta characteristics. We then consider the sampler horn of Hayabusa2 sampling mechanism and monitor the distribution of particles inside the horn. We find that the cratering process is much longer under low gravity, and that the crater formation mechanism does not seem to depend on the impact speed, in the considered range. The Z-model seems to rightly represent our velocity field for a steady excavation state. From the impact, less than $10{{\ \rm per\ cent}}$ is transmitted into the target, and grains are ejected mostly with angles between 48° and 54°. Concerning the sampling mechanism, we find that for most of the simulations, the science goal of 100 mg is fulfilled, and that a second impact increases the number of ejecta but not necessarily the number of collected particles.
Distinct CoREST complexes act in a cell-type-specific manner
Authors: Mačinković Igor , Theofel Ina , Hundertmark Tim , Kovač Kristina , Awe Stephan , Lenz Jonathan , Forné Ignasi , Lamp Boris , Nist Andrea , Imhof Axel , Stiewe Thorsten , Renkawitz-Pohl Renate , Rathke Christina , Brehm Alexander
Published: October 2019

CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.
96. Human Papilloma Viruses Associated Diseases in a Cohort of Patients with Idiopathic CD4 Lymphopenia
Authors: Mystakelis Harry , Laidlaw Elizabeth , Anderson Megan , Ye Peiying , Manion Maura , Brownell Isaac , Sereti Irini , Lisco Andrea
Published: October 2019

Background

Idiopathic CD4 Lymphocytopenia (ICL) is a rare immunodeficiency characterized by an absolute CD4+ T count of < 300 cells/µL, in absence of HIV-infection or any other known cause. Patients with ICL have an increased risk of opportunistic infections. The prevalence, natural history, and spectrum of Human Papillomaviruses (HPV) associated diseases in ICL patients are unknown.

Methods

ICL patients were enrolled in a prospective observational study (N = 90). Demographic, clinical, and immunologic data were analyzed by nonparametric Methods. Immunophenotyping was performed by flow cytometry.

Results

The median age of ICL patients was 48 years, 47% were women, and 92% were Caucasian. Sixty-five percent of patients had at least one opportunistic infection, with HPV being the most prevalent (34.4%), followed by cryptococcal disease (22%), shingles (15.5%), molluscum contagiosum (8.8%), Histoplasma capsulatum (4.4%), Mycobacterium avium complex (4.4%), and progressive multifocal encephalopathy (2.2%). HPV-related diseases were identified in 18 women and 13 men. ICL patients with HPV disease were younger compared with those without (median age 34 vs. 53.5 years, P < 0.0001). Nine (29%) had anogenital, 9 (29%) had a cutaneous disease (verruca plana, verrucous carcinoma, squamous cell carcinoma) while 13 (42%) had both anogenital and cutaneous disease. Patients with HPV-related disease were also more likely to have history of cryptococcal disease, shingles or molluscum (P = 0.036, P = 0.22 and 0.11, respectively). Thirteen patients had HPV-associated cancers: 7 both mucosal and skin and 3 either skin or mucosal malignancies. Patients with HPV-disease had lower CD4+ T cells (median CD4 70 vs. 114 cells/µL, P = 0.036). No differences were observed in the numbers of CD8+ T cells, B cells, NK cells, and levels of IgG between patients with and without HPV disease.

Conclusion

HPV-related disease represents the most common opportunistic infection in ICL patients. Patients with ICL and HPV disease are younger, have lower CD4s and high prevalence of HPV-associated malignancies. Therefore, for patients presenting early in life with severe HPV disease further immunological workup should be considered and for patients with ICL excessive screening for HPV-related malignancies should be a priority.

Disclosures

All Authors: No reported Disclosures.
902. A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of a Single Immunization of Ad26.RSV.preF against RSV Infection in a Viral Challenge Model in Healthy Adults
Authors: DeVincenzo John , Gymnopoulou Efi , De Paepe Els , Murray Bryan , Rosemary Bastian Arangassery , Haazen Wouter , Noulin Nicolas , Comeaux Christy , Heijnen Esther , Eze Kinglsey , Gilbert Anthony , Lambkin-Williams Rob , Schuitemaker Hanneke , Callendret Benoit , Sadoff Jerald
Published: October 2019

Background

Despite the high disease burden of RSV in older adults and children, there is currently no approved vaccine. Ad26.RSV.preF, an experimental RSV vaccine, has demonstrated immunogenicity and tolerability in first-in-human clinical studies. The aim of this study was to assess the potential of the Ad26.RSV.preF vaccine to protect against RSV infection and disease in an established RSV human challenge model, used for the first time to evaluate a vaccine.

Methods

We conducted a randomized, double-blind, placebo-controlled, human challenge study (NCT03334695). Healthy adults received 1 × 1011 vp Ad26.RSV.preF vaccine (active) or placebo (pbo) intramuscularly. After 28 days, volunteers were challenged intranasally with a low-passage clinical strain of RSV-A (0.8 mL of Memphis 37b) and then quarantined for 12 days. Nasal washes were collected twice daily throughout quarantine, starting 2 days post-challenge (viral load [VL] by qRT-PCR and quantitative cultures). Disease severity was recorded thrice daily using symptom diary cards.

Results

Fifty-three volunteers (active, n = 27; pbo, n = 26) were challenged with RSV-A. Quantitative viral assessments were consistently lower in active than pbo. The primary endpoint of the study was met: the area under the curve (AUC) for RSV VL over time (via qRT-PCR) was significantly lower in active pbo (P = 0.012). Median peak VL was lower for active (0 log10 copies/mL) than pbo (5.4 log10 copies/mL). Median AUC for RSV VL over time (quantitative culture) was lower for active than pbo (0 vs. 109, P = 0.002). Disease severity was lower for active than pbo, with a median AUC total symptom score of 35 (active) vs. 167 (pbo) (P = 0.002). Overall, RSV infection (defined by qRT-PCR alone or combined with symptoms) and disease severity over time were lower in active vs. pbo.

Conclusion

RSV infections, VL, and RSV disease severity were consistently lower in healthy adults receiving Ad26.RSV.preF vs. placebo, demonstrating promising protection from RSV infection and disease. This was the first time that antiviral prevention was observed against RSV after active immunization. Ad26.RSV.preF warrants further evaluation in field trials for efficacy against natural RSV infections in populations considered at risk of severe RSV disease.

Disclosures

All Authors: No reported Disclosures.
978. Changes in BMI Associated with Antiretroviral Regimens in Treatment-Experienced, Virologically Suppressed Individuals Living with HIV
Authors: Mounzer Karam , Brunet Laurence , Hsu Ricky , Fatukasi Terra , Fusco Jennifer S , Vannappagari Vani , Henegar Cassidy , van Wyk Jean A , Crawford Melissa , Lo Janet , Fusco Gregory
Published: October 2019

Background

A potential association between integrase inhibitor (INSTI) use and weight gain has been reported in people living with HIV (PLWH). We examined body mass index (BMI) increases after a switch to dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV) among virologically suppressed ART-experienced PLWH.

Methods

ART-experienced, suppressed (ART-ES; baseline viral load < 200 copies/mL) PLWH ≥ 18 years of age initiating DTG, EVG/c, RAL, RPV, or bDRV for the first time were identified in the OPERA® cohort. The association between core agents and mean increases in BMI at 6, 12, and 24 months was estimated with multivariable linear regression. Inverse probability-of-censoring weights (IPCW) were used to account for censoring (regimen discontinuation, loss to follow-up, death, pregnancy, or no BMI measured). Analyses were stratified by baseline BMI categories (underweight: <18.5, normal weight: ≥18.5 to <25, overweight: ≥25 to <30, obese: ≥30).

Results

At baseline, endocrine disorders were reported in >40% of PLWH receiving DTG and RAL; >60% were overweight/obese in all groups (Figure 1). Mean BMI (unadjusted) increased for all ARVs over time, with changes at 24 months ranging from 0.30 (DRV) to 0.83 (RPV, Figure 2). At 6 months, the adjusted mean BMI increase was statistically smaller with EVG/c, RAL, and bDRV (range –0.15 to –0.30) than with DTG (Figure 3); these differences only remained significantly different for bDRV at 12 (–0.29) and 24 months (–0.29, Figure 3). Among those with a normal baseline BMI, the adjusted mean change in BMI at 12 months was smaller with EVG/c, bDRV, and RAL than DTG (range –0.26 to –0.27). Among overweight PLWH, the adjusted mean BMI increase was statistically smaller with bDRV than DTG (–0.32, Figure 4). Results were consistent in IPCW estimates.

Conclusion

The majority of PLWH on stable ART in this US-based cohort were overweight/obese at the time of switch to the regimens of interest. Small mean increases in BMI for all regimens were noted over time, for which the clinical significance is not yet known. Apparent differences in BMI changes favoring EVG/c, RAL, and bDRV vs. DTG over the short term were largely attenuated with longer follow-up, with significant differences mainly observed in those with a normal BMI at baseline.

Disclosures

All Authors: No reported Disclosures.
1832. Development of an Ultrasensitive Field-Applicable Plasmodium falciparum Assay for Malaria Diagnosis and Eradication
Authors: Lee Rose , De Puig Guixe Helena , Dvorin Jeffrey , Collins James
Published: October 2019

Background

Malaria control and eradication have been hampered by asymptomatic carriage which serves as a parasite reservoir. Low-density infections (< 100 parasites/microliter) frequently fall below the limit of detection (LOD) of microscopy and rapid diagnostic tests (RDT) which are antigen-based tests. Molecular methods such as polymerase chain reaction are capable of higher sensitivity yet remain impractical for resource-limited settings. We describe development of an isothermal assay using the nucleic acid detection platform SHERLOCK (Specific High-Sensitivity Enzymatic Reporter UnLOCKing), which may also be increasingly important as there has been rising detection of histidine-rich protein 2 (HRP2) gene deletions in Plasmodium spp. HRP2 is the most commonly used antigen in RDTs and deletion of this gene would render many RDTs obsolete.

Methods

SHERLOCK leverages the endonucleases of CRISPR-associated microbial adaptive immunity. Cas12a is an RNA-guided, DNA-cleaving enzyme, which can be programmed with guide RNAs to cleave nontarget reporter ssDNA. We exploit the nonspecific degradation of labeled ssDNA to detect the presence of the dsDNA target that activated Cas12a (Figure 1). Recombinase polymerase amplification (RPA) coupled with Cas12a detection enables a lower LOD. Plasmodium falciparum whole genomic DNA was compared with parasites cultured in red blood cells (RBCs) with known parasitemia and boiled at 95°C for 5 minutes for lysis of RBCs/parasites then diluted 1:2.5 to prevent solidification.

Results

This SHERLOCK assay detected simulated Plasmodium falciparum infection at attomolar LODs when applied to whole genomic DNA and simulated samples of infected RBCs spiked into whole blood. The genomic assay detected down to 0.2 parasites/microliter and the simulated sample detected to 10 parasites/microliter in the final reaction volume. In comparison, LODs from the initial input volume was 5aM and 250aM, respectively (Figure 2).

Conclusion

We demonstrate an isothermal nucleic acid detection platform capable of diagnosis in 60 minutes in a one-pot assay requiring minimal sample preparation and reaching an LOD recommended by the WHO for malaria eradication. In summary, we illustrate the utility of the SHERLOCK platform in application to malaria and global health.

Disclosures

All Authors: No reported Disclosures.
1873. Pregnancy and Birth Outcomes Among Colombian Women with Zika Virus Disease in 3 Surveillance Sites, Proyecto Vigilancia de Embarazadas con Zika
Authors: Honein Margaret (Peggy) , Mercado Marcela , Gilboa Suzanne , Valencia Diana , Daza Marcela , Galang Romeo , Winfield Christina , Godfred-Cato Shana , Benavides Mónica , Villanueva Julie , Daniels Jonathan , Bhatnagar Julu , Schiffer Jarad , Corchuelo Sheryll , Tinker Sarah , Anderson Kayla , Osorio Johana , Burkel Veronica , Hojnacki Jacob , Tong Van , Gonzalez Maritza , Moore Cynthia , Lucia Ospina Martha
Published: October 2019

Background

Proyecto Vigilancia de Embarazadas con Zika (VEZ) was an intensified surveillance system built upon existing national surveillance of pregnant women with symptoms of Zika virus (ZIKV) disease and conducted in three Colombian cities with a high prevalence of Zika. This analysis of data from VEZ estimates the risk of Zika-associated birth defects among pregnant women with symptoms of ZIKV disease, and among a subset with laboratory evidence of possible ZIKV infection during pregnancy.

Methods

During April–November 2016, pregnant women were enrolled if they were reported to the surveillance system (Sivigila) or visited participating clinics with symptoms of ZIKV disease. Maternal and pediatric data were abstracted from prenatal care, ultrasound, and delivery records, as well as from pediatric or specialist visit records. Available maternal and infant specimens were tested for the presence of ZIKV RNA and/or anti-ZIKV immunoglobulin (IgM) antibodies.

Results

Of 1,223 women enrolled, 47.8% and 34.3% reported first or second trimester symptom onset, respectively. Of 381 pregnancies with maternal and/or infant specimens tested, 108 (29%) had laboratory evidence of possible ZIKV infection during pregnancy; half of these (53.3%) were positive for ZIKV RNA only, 37.4% for IgM antibodies only, and 9.3% for both. Of 1,190 of pregnancies with known outcome, 63 (5%) had Zika-associated brain or eye defects; among the subset with any laboratory evidence, 12 (11%) had Zika-associated brain or eye defects. The prevalence of Zika-associated brain or eye defects was 5.9% (35/593) and 4.5% (19/423) among pregnancies with symptom onset in the first and second trimester, respectively.

Conclusion

Among pregnant women with symptoms of ZIKV disease enrolled during the height of the ZIKV epidemic in Colombia, prevalence of any Zika-associated brain or eye defect was 5%, with a higher prevalence among those with laboratory evidence of possible ZIKV infection. Rapid enhancements to Colombia’s national surveillance enabled the estimation of the risk of birth defects associated with ZIKV disease in pregnancy.

Disclosures

All Authors: No reported Disclosures.
1875. La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Review and Evaluation for Predictors of Disease Severity
Authors: Boutzoukas Angelique Eleni , Freedman Daniel , Garrett Hunt W , Mack Kathleen A , Yildiz Vedat , Chung Melissa , Twanow Jamie , de los Reyes Emily , Ouellette Christopher
Published: October 2019

Background

La Crosse Virus (LACV) is the most common neuroinvasive arboviral disease in children. Contemporary data on clinical presentation, management, outcomes, and predictors of disease severity are lacking.

Methods

A retrospective analysis was performed of children (0–18 years) admitted to Nationwide Children’s Hospital from January 2009 to December 2018 diagnosed with LACV neuroinvasive disease (LACV-ND). LACV-ND diagnosis was defined as a compatible clinical illness and serum serologic detection of LACV in the absence of other infectious etiologies. Demographic, clinical, laboratory, electroencephalography (EEG), radiologic, and outcome data were recorded. Severe disease was defined as the presence of clinical or electroencephalographic status epilepticus, SIADH, PICU admission, mechanical ventilation (MV), parenteral/tube feeding, inpatient rehab, or intracranial pressure monitoring. Single variable and multivariate analyses were performed to determine factors predictive of disease severity.

Results

Of the 140 patients, 76 (54%) males with a median age of 8 years [10 months-16 years], were identified with LACV-ND. Symptoms at presentation, laboratory abnormalities, EEG, radiography, and outcomes are shown in Table 1. Fifty-seven (41%) patients met criteria for severe disease, notably for PICU admission (n = 41), status epilepticus (n = 35), MV (n = 13), and inpatient rehab (11). No in-patient deaths were observed. Exploratory analysis revealed that patients with severe disease were often younger at presentation, had higher rates of altered mental status (AMS), and seizures. Elevated serum white blood cell counts (WBC) and polymorphonuclear cell (PMN) predominance in serum and cerebrospinal fluid (CSF) were observed more frequently in severe disease. Multivariate analysis revealed presentation with seizures (OR 4.7 [95% CI 1.7–12.6], P = 0.001), elevated serum WBC (OR 1.7 [95% CI 1.2–2.5], P = 0.004), and a higher CSF PMN% (OR 1.03 [95% CI 1.01–1.06, P = 0.003) to be independent predictors of severe disease.

Conclusion

At presentation, patients with severe disease tended to be younger, have greater rates of neurologic symptoms, and leukocytosis with PMN predominance in blood and CSF. These clinical and laboratory findings may serve as useful biomarkers to predict disease severity.

Disclosures

All Authors: No reported Disclosures.
1890. Missed Clinical Opportunities to Prevent Infections and Treat Substance Use Disorder (SUD) in People Who Inject Drugs (PWID)
Authors: Bardossy Ana C , Gokhale Runa H , Hartnett Kathleen , Hatfield Kelly M , Jackson Kelly A , Felsen Christina B , McDonald Robert , Kracalik Ian , Lucas Todd , McGovern Olivia L , Van Beneden Chris , Vallabhaneni Snigdha , Williams Sabrina R , Mendoza Michael , Bohm Michele K , Brooks John , Asher Alice K , Magill Shelley S , Fiore Anthony , Blog Debra , Dufort Elizabeth , See Isaac , Dumyati Ghinwa
Published: October 2019

Background

The age-adjusted rate of drug overdose deaths in the United States tripled from 1999 to 2016. Public health surveillance data indicate that an increasing proportion of infections due to bacterial and fungal pathogens is associated with injection drug use (IDU). We describe healthcare encounters (HCEs) of PWID as potential opportunities to prevent infections related to IDU by identifying risks and treating SUD, including with medication-assisted treatment (MAT) for opioid use disorder.

Methods

At six hospitals in western New York, we abstracted medical records from hospital admissions and emergency department (ED) visits for PWID (i.e., IDU in the preceding year) who had positive cultures for Staphylococcus aureus (any clinical specimen, April–July 2017), group A Streptococcus (invasive specimens, all of 2017) or Candida spp. (blood specimens, all of 2017). We reviewed hospital admission and ED records for 1 year preceding the positive culture to identify visits during which opportunities to prevent infection and treat SUD by addressing SUD and IDU were missed.

Results

We identified 99 PWID with positive cultures. The median age was 33 years (range 19–68) and 61 were female. Sixty-nine had a skin and soft-tissue infection, 44 had a bloodstream infection, and 20 had both. Thirty-one PWID left against medical advice during a hospital admission or an ED visit. Seventy-nine PWID were hospitalized, of whom 4 died. Ninety-five used opioids and 71 used cocaine in the preceding year. Seventy-five PWID had an HCE in the 12 months prior to the index visit, with a median of two HCE per person (interquartile range 1–4); 53 of PWID had a previous HCE for infection and 28 for opioid overdose. SUD was documented during a prior HCE at the same hospital for 61 PWID, but only 10 (16%) were offered MAT during any prior HCE and for 24 (39%) there was no documentation that any form of treatment for SUD was offered.

Conclusion

In this cohort, PWID frequently had one or more healthcare encounters documented at the same hospital in the year prior to a serious bacterial or fungal infection. These prior HCEs were often for infections or overdose that signaled the need for MAT, demonstrating that there are critical missed opportunities to identify risks, prevent infection, and treat SUD.

Disclosures

All Authors: No reported Disclosures.
1960. Lost in Translation: Comparing Rates of Outpatient Antibiotic Use in Three Metrics
Authors: Prestel Christopher , King Laura M , Bartoces Monina , Neuhauser Melinda M , Hicks Lauri , Fleming-Dutra Katherine E
Published: October 2019

Background

The Centers for Disease Control and Prevention (CDC) tracks US outpatient antibiotic use in prescriptions per 1000 persons (Rx/1000), while the World Health Organization uses defined daily doses per 1000 persons (DDD/1000), which are based on average adult dose, for global surveillance. A third metric, days of therapy (DOT)/1,000 persons, has not been previously evaluated at the national level. We aim to compare time trends in outpatient oral antibiotic use as Rx/1000, DDD/1000, and DOT/1,000 in the same data to inform ongoing CDC surveillance and facilitate international comparison.

Methods

We identified dispensed outpatient oral antibiotics using pharmacy claims in 2011–2016 IBM® MarketScan® Commercial Databases for individuals <65 years old. Using enrollment data, we calculated mean annual membership with drug coverage. Annual rates of outpatient oral antibiotic use were calculated for Rx/1000, DDD/1000, and DOT/1000 persons. Prescriptions written with a ratio of DDD to days supplied >10 were considered biologically implausible and excluded from DDD calculations. We examined trends for each metric from 2011 to 2016 using negative binomial regression.

Results

Annual numbers of outpatient oral antibiotic prescriptions ranged from 18.6 million to 30.0 million (mean 24.3 million). Overall, Rx/1000 decreased by 7% from 892 in 2011 to 829 in 2016 (Figure 1). From 2011 to 2016, DDD/1000 increased 2% from 23.8 to 24.2 while DOT/1000 decreased 9% from 25.4 to 23.1. Significant per-year decreases were found from 2011 to 2016 for Rx/1000 (−1.1%) and for DOT/1000 (−1.6%), while no significant per-year change was seen with DDD/1000 (table). DDD/1000 underestimate use in pediatrics under the age of 10 (Figure 2). Prolonged duration is seen in adolescents and reflected by DOT/1000.

Conclusion

Trends in DDD/1000 for population aged <65 years do not mirror trends in Rx/1000 and DOT/1000. These differences may reflect that Rx/1000 and DOT/1000 more accurately capture antibiotic prescriptions in children than DDD/1000. As DDD/1000 underestimate antibiotic use in children, DDD/1000 underestimates reduction in antibiotic use over time and may not accurately reflect changes in use over time.

Disclosures

All Authors: No reported Disclosures.
1961. Grindr™ on Screen Activity on iPhones Correlates with HIV Risk and Substance Use in Men Who Have Sex with Men, San Diego
Authors: Hoenigl Martin , Little Susan J , Stockman Jamila K , Skaathun Britt , Grelotti David , Weibel Nadir , Smith Davey M
Published: October 2019

Background

Technology has changed the way men-who-have-sex-with-men (MSM) seek sex; ≥60% of MSM in the United States use the internet to find sex partners, primarily via Grindr™ which is the most used dating app among MSM. Studies to date have mostly evaluated Grindr™ use as a dichotomous variable and found inconsistent results regarding associations with increased HIV risk behavior. Importantly, Grindr™ “on-screen” activity is monitored by phones and can provide an objective measure of app usage. Here we aimed to assess Grindr™ “on-screen” activity in MSM undergoing community-based HIV and sexually transmitted infection (STI) screening in San Diego, and to correlate activity with sexual risk behavior and substance use.

Methods

This nested cohort study was conducted between December 2018 and April 2019 and leveraged our “Good to Go” (AI106039) screening program for participant recruitment. During their testing encounter participants not on HIV PrEP were provided with surveys on demographics, substance use and risk behavior during previous 3 months, and Grindr™ usage. Participants with iPhones were instructed on how to assess Grindr™ on-screen activity (i.e., time on-screen during last 7 days) on their phones (Figure 1). Risk behavior was classified using the validated San Diego Early Test (SDET) Score (Figure 2).

Results

Overall 378/784 (48%) MSM participants indicated that they had opened Grindr™ during the previous 7 days. Grindr™ users had higher SDET scores than those not using Grindr™ (median SDET 2, IQR 0–5; mean 2.29) while there was no difference in proportion of substance users (alcohol and marijuana excluded, 21% vs. 17%; P = 0.14). Of 231 MSM who indicated recent Grindr™ use (61%) had iPhones; median on-screen activity during the previous 7 days was 144 minutes (range 1–2,640 minutes). Participants with high Grindr™ utilization (>80th percentile of time on screen corresponding to >480 minutes), had significantly higher SDET scores (median 5 vs. 2; mean 4.02 vs. 3.26; P < 0.001) and a tendency toward a higher proportion of substance users (29% vs. 20%) than those with lower Grindr™ utilization.

Conclusion

This study introduces Grindr™ on-screen activity as an objective measure that can help identify MSM at high risk for HIV.

Disclosures

All Authors: No reported Disclosures.
2839. Efficacy, Pharmacokinetics (PK), and Safety Profile of Suvratoxumab (MEDI4893), a Staphylococcus aureus Alpha Toxin (AT)-Neutralizing Human Monoclonal Antibody in Mechanically Ventilated Patients in Intensive Care Units; Results of the Phase 2 SAATELLITE Study Conducted by the Public-Private COMBACTE Consortium
Authors: Francois Bruno , Sánchez Garcia Miguel , Eggimann Philippe , Dequin Pierre-Francois , Laterre Pierre-François , Huberlant Vincent , Viña Soria Lucia , Boulain Thierry , Bretonnière Cédric , Pugin Jerome , Trenado Álvarez José , Catalina Hernandez Padilla Ana , Coenjaerts Frank , Ali Omar , Shoemaker Kathryn , Ruzin Alexey , Pierre Vadryn , Wu Yuling , Colbert Susan , McCarthy Michael , Dubovsky Filip , S. Jafri Hasan
Published: October 2019

Background

Staphylococcus aureus (SA) pneumonia imposes significant morbidity and mortality in mechanically ventilated, intensive care unit (MV ICU) patients despite best clinical care. We assessed efficacy, PK, AT-neutralizing antibodies (AT NAbs), and safety of suvratoxumab (suvra) in MV ICU subjects in the placebo-controlled, randomized Phase 2 SAATELLITE study (NCT02296320; EudraCT 2014-001097-34).

Methods

Subjects with PCR-confirmed SA colonization of the lower respiratory tract were randomized to either a single intravenous infusion of 5,000 mg suvra (n = 96) or placebo (n = 100) and followed for 190 days post dose. Efficacy endpoints were Endpoint Adjudication Committee-determined relative risk reduction (RRR) of SA pneumonia incidence in suvra vs. placebo recipients within 30 days post dose (primary endpoint, tested at 2-sided α = 0.1), incidence of all-cause pneumonia, and all-cause pneumonia or death. Serum suvra PK and levels of AT NAbs were measured through 90 days post dose and analyzed for statistical correlation. Treatment-emergent adverse events (TEAEs) and serious AEs (SAEs) were assessed through 190 days post dose.

Results

Baseline characteristics were similar between groups. Suvra provided 31.9% RRR in incidence of SA pneumonia vs. placebo (17.7% vs. 26%; P = 0.166), 30% RRR (P = 0.146) in incidence of all-cause pneumonia, and 23% RRR (P = 0.164) in incidence of all-cause pneumonia or death. Suvra reduced mean hospital stay and ICU duration by 3.0 and 2.4 days, resp. vs. placebo. Mean serum ± SD suvra level was 296 ± 131 µg/mL at 30 days post dose. Serum AT Nab ± SD levels reached 156.03 ± 72.48 IU/mL at 2 days post dose, declining slowly to 33.74 ± 16.04 IU/mL by 90 days post dose. AT NAbs correlated with PK (r2 = 0.7), thereby confirming functional activity of suvra over time. Proportion of subjects with TEAEs or SAEs was similar between groups: ≥1 TEAE (93.8% suvra; 93.0% placebo); ≥1 serious; and/or ≥grade 3 severity SAE (66.7% suvra; 58.0% placebo).

Conclusion

A single intravenous dose of suvra produced a trend toward reduced incidence of SA pneumonia, health resource savings, sustained functional exposure in serum, and an acceptable safety profile. These results support continued development of suvra in MV ICU patients.

Disclosures

All Authors: No reported Disclosures.
2848. Spatial Distribution of Community-Acquired Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Infections and its Association with Sewer Overflows in Middle Georgia
Authors: Omatsone Margaret , Ponce-Terashima Rafael , Cole Baker Thomas
Published: October 2019

Background

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) were described first in relation to hospital-acquired infections. However, infections by these organisms acquired in the community have become a public health problem. There are no well-known risk factors for acquisition of these bacteria in the community. Surface waters and sanitation conditions may serve as reservoir and transmission.

Methods

We conducted a retrospective study over 12 months of patients who had positive cultures with ESBL-PE in our laboratory. We excluded patients with hospitalization in the previous 3 months, those in skilled nursing facilities, and those whose culture was taken 3 or more days after hospitalization. Geographic Information System analysis was performed based on patient’s residence, population, and sewer overflow public data.

Results

Among 485 patients with cultures positive for ESBL-PE in 2018, 64 were included in the study. Mean age was 54, and 68.7% were females. Organisms isolated were E. coli (78.2%) and K. pneumoniae ESBL (21.8%). These were isolated from urine 47 (73.4%), blood 5 (7.8%), abscess 6 (9.3%), ulcers 5 (7.8%), and sputum 1 (1.5%). Antibiotic exposure in the preceding 3 months was noted in 12 patients (18.7%). Spatial distribution of patients in the community was not random based on nearest neighbor analysis (Z score = −2.6). Kernel density estimation showed clustering of cases. Infection rates were calculated per census tracts. There was poor correlation between infection rate and mean family income (R2 = 0.18, P = 0.017). Analysis of Kernel density estimations showed that sewer overflow distribution explained over 50% of the variance of distribution of cases with ESBL-PE (R2 = 0.51, P < 0.001).

Conclusion

Patients presenting with infections due to ESBL-PE acquired in the community did not have a random spatial distribution. Other factors besides prior antibiotic use and financial status should be investigated. Proximity to sanitary sewer overflows may be a contributing factor. Location of residence within a community may aid in identifying patients at risk for acquisition of ESBL-PE.

Disclosures

All Authors: No reported Disclosures.
2894. Metrics of Antimicrobial Use Within Inpatient Settings: Impacts of Statistical Methods and Case-Mix Adjustments
Authors: Goto Michihiko , Nair Rajeshwari , Alexander Bruce , Beck Brice , Richards Christopher , Perencevich Eli N , Livorsi Daniel J
Published: October 2019

Background

The necessary data elements and optimal statistical methods for benchmarking hospital-level antimicrobial use are still being debated. We aimed to describe the relative influence of case-mix adjustment and different statistical methods when ranking hospitals on antimicrobial use (AU) within inpatient settings.

Methods

Using administrative data from the Veterans Health Administration (VHA) system in October 2016, we calculated total antimicrobial days of therapy (DOT) and days present according to the National Healthcare Safety Network (NHSN) protocol. Patient-level demographics, comorbidities, and recent procedures were used for case-mix adjustments. We compared hospital rankings across 4 different methods: (A) crude antimicrobial DOT per 1,000 days present, aggregated at the hospital-level; (B) observed/expected (O/E) AU ratio with risk adjustment for ward-level variables (analogous to NHSN’s Standardized Antimicrobial Administration Ratio); (C) O/E AU ratio with risk adjustment for ward-/patient-level variables; (D) predicted/expected (P/E) AU ratio with risk adjustment for ward-/patient-level variables, based on a multilevel model accounting for clustering effects at hospital- and ward-levels.

Results

The cohort included 165,949 DOTs and 318,321 days present at 122 acute care hospitals within VHA. Crude DOTs per 1,000 days present ranged from 153.6 to 900.8 (Figure A), and ward-level risk adjustment only modestly changed rankings (Figure B). When adjusted for ward- and patient-level variables (including demographics, 14 comorbidities and 22 procedures), rankings changed substantially (Figure C). Risk-adjustment by a multilevel model changed rankings even further, while shrinking variabilities (Figure D). Ten hospitals in the lowest and 11 hospitals in the highest quartiles by O/E risk adjustment for only ward-level variables were classified to different quartiles on P/E risk adjustment.

Conclusion

We observed that the selection of variables and statistical methods for case-mix adjustment had a substantial impact on hospital rankings for antimicrobial use within inpatient settings. Careful consideration of methodologies is warranted when providing benchmarking metrics for hospitals.

Disclosures

All Authors: No reported Disclosures.