bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cosmic acceleration in an extended Brans–Dicke–Higgs theory
Authors: Chakrabarti Soumya 
Published: January 2021

ABSTRACT
We consider an extended scalar–tensor theory of gravity where the action has two interacting scalar fields, a Brans–Dicke field that makes the effective Newtonian constant a function of coordinates and a Higgs field that has derivative and non-derivative interaction with the lagrangian. There is a non-trivial interaction between the two scalar fields that dictates the dominance of different scalar fields in different era. We investigate if this set-up can describe a late-time cosmic acceleration preceded by a smooth transition from deceleration in recent past. From a cosmological reconstruction technique, we find the scalar profiles as a function of redshift. We find the constraints on the model parameters from a Markov chain Monte Carlo analysis using observational data. Evolution of an effective equation of state, matter density contrast, and thermodynamic equilibrium of our Universe are studied and their significance in comparison with a ΛCDM cosmology is discussed.
A numerical jet model for the prompt emission of gamma–ray bursts
Authors: Farinelli Ruben , Basak Rupal , Amati Lorenzo , Guidorzi Cristiano , Frontera Filippo 
Published: January 2021

Abstract
Gamma-ray bursts (GRBs) are known to be highly collimated events, and are mostly detectable when they are seen on-axis or very nearly on-axis. However, GRBs can be seen from off-axis angles, and the recent detection of a short GRB associated to a gravitational wave event has conclusively shown such a scenario. The observer viewing angle plays an important role in the observable spectral shape and the energetic of such events. We present a numerical model which is based on the single-pulse approximation with emission from a top-hat jet and has been developed to investigate the effects of the observer viewing angle. We assume a conical jet parametrized by a radius Rjet, half-opening angle θjet, a comoving-frame emissivity law and an observer viewing angle θobs, and then study the effects for the conditions θobs &lt; θjet and θobs &gt; θjet. We present results considering a smoothly broken power-law emissivity law in jet comoving frame, albeit the model implementation easily allows to consider other emissivity laws. We find that the relation $E^{\rm i}_{\rm p}\propto E_{\rm iso}^{0.5}$ (Amati relation) is naturally obtained from pure relativistic kinematic when $\Gamma \gtrsim 10$ and θobs &lt; θjet; on the contrary, when θobs &gt; θjet it results $E^{\rm i}_{\rm p}\propto E_{\rm iso}^{0.25}$. Using data from literature for a class of well-know sub-energetic GRBs, we show that their position in the $E^{\rm i}_{\rm p}-E_{\rm iso}$ plane is consistent with event observed off-axis. The presented model is developed as a module to be integrated in spectral fitting software package XSPEC and can be used by the scientific community.
The COMBS Survey - II. Distinguishing the metal-poor bulge from the halo interlopers
Authors: Lucey Madeline , Hawkins Keith , Ness Melissa , Debattista Victor P , Luna Alice , Asplund Martin , Bensby Thomas , Casagrande Luca , Feltzing Sofia , Freeman Kenneth C , Kobayashi Chiaki , Marino Anna F 
Published: January 2021

ABSTRACT
The metal-poor stars in the bulge are important relics of the Milky Way’s formation history, as simulations predict that they are some of the oldest stars in the Galaxy. In order to determine if they are truly ancient stars, we must understand their origins. Currently, it is unclear if the metal-poor stars in the bulge ([Fe/H] &lt; −1 dex) are merely halo interlopers, a unique accreted population, part of the boxy/peanut-shaped bulge, or a classical bulge population. In this work, we use spectra from the VLT/FLAMES spectrograph to obtain metallicity estimates using the Ca-II triplet of 473 bulge stars (187 of which have [Fe/H] &lt; −1 dex), targeted using SkyMapper photometry. We also use Gaia DR2 data to infer the Galactic positions and velocities along with orbital properties for 523 stars. We employ a probabilistic orbit analysis and find that about half of our sample has a &gt;50 per cent probability of being bound to the bulge, and half are halo interlopers. We also see that the occurrence rate of halo interlopers increases steadily with decreasing metallicity across the full range of our sample (−3 &lt; [Fe/H] &lt; 0.5). Our examination of the kinematics of the confined compared to the unbound stars indicates the metal-poor bulge comprises at least two populations; those confined to the boxy/peanut bulge and halo stars passing through the inner galaxy. We conclude that an orbital analysis approach, as we have employed, is important to understand the composite nature of the metal-poor stars in the inner region.
3. Phase 3 Pivotal Evaluation of 20-valent Pneumococcal Conjugate Vaccine (PCV20) Safety, Tolerability, and Immunologic Noninferiority in Participants 18 Years and Older
Authors: Essink Brandon , Sabharwal Charu , Xu Xia , Sundaraiyer Vani , Peng Yahong , Moyer Lisa , Pride Michael W , Scully Ingrid L , Jansen Kathrin U , Gruber William C , Scott Daniel , Watson Wendy 
Published: January 2021

Abstract

Background
PCV20 contains the 13-valent pneumococcal conjugate vaccine (PCV13) components, and 7 additional conjugates (for serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F), extending pneumococcal serotype coverage. Key data from the pivotal Phase 3 evaluation of PCV20 in adults are presented.

Methods
Adults naïve to pneumococcal vaccination were enrolled into 3 age cohorts (≥60, 50–59, and 18–49 years of age). Participants ≥60 years received either PCV20 and saline 1 month later, or PCV13 and 23-valent pneumococcal polysaccharide (PPSV23) 1 month later (1:1 randomization, double blind). Participants 50–59 and 18–49 years received either a dose of PCV20 or PCV13 (3:1 randomization, double blind). Tolerability, safety and immunogenicity (opsonophagocytic activity [OPA] responses) were assessed.

Results
3889 participants received vaccine. 1507 and 1490 participants ≥60 years received PCV20 or control respectively. All 20 vaccine serotypes induced robust responses and OPA geometric mean titers (GMTs) to all 13 matched serotypes were noninferior to PCV13. In addition, the OPA GMTs to 6 of the 7 additional serotypes 1 month after PCV20 were noninferior compared to the same serotypes in PPSV23. The OPA GMT of serotype 8 missed noninferiority by a very narrow margin (2-sided 95% lower bound of GMT ratio [20vPnC/PPSV23] was 0.49, with noninferiority criterion of &gt;0.5); this is unlikely to be clinically significant given the high geometric mean fold rise of OPA titers after PCV20 (22-fold above baseline). GMTs after PCV20 in each of the younger age cohorts (18–49 years, 50–59 years) were noninferior to adults 60–64 years. The tolerability and safety profile of PCV20 was similar to PCV13.

Conclusion
Based on the robust immune responses and comparability to licensed pneumococcal vaccines, as well as bridging to the younger age group, these data support that PCV20 will be protective against pneumococcal disease due to the 20 serotypes in adults.

Disclosures
Charu Sabharwal, MD, MPH, Pfizer (Employee, Shareholder) Xia Xu, PhD, Pfizer (Employee, Shareholder) Vani Sundaraiyer, PhD, MS, Pfizer (Independent Contractor) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Lisa Moyer, BS, Pfizer (Employee, Shareholder) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Ingrid L. Scully, PhD, Pfizer Inc (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Daniel Scott, MD, Pfizer (Employee, Shareholder) Wendy Watson, MD, Pfizer (Employee, Shareholder)
12. Evaluation of Rapid Phenotypic Testing for KPC Carbapenemase Producing klebsiella Pneumoniae Directly from Positive Blood Cultures by Use of “Hot Chocolate” Plates
Authors: Lawandi Alexander , Leite Gleice C , Lefebvre Brigitte , Longtin Jean , Lee Todd C 
Published: January 2021

Abstract

Background
Invasive infections with Carbapenemase Producing Enterobacterales are associated with considerable morbidity and mortality, in part due to the risk of inappropriate empiric therapy. Consequently, the rapid identification of carbapenem resistance is crucial to the management of these infections. We sought to evaluate possible reductions in turnaround time to identification of this resistance in blood cultures growing these organisms by applying rapid phenotypic test kits to growth from “hot chocolate” plates.

Methods
30 blood cultures, spiked with carbapenem resistant Klebsiella pneumoniae isolates or susceptible controls, were inoculated onto chocolate agars that had pre-warmed at 37°C. These plates were incubated at 37ºC for 3.5 hours. The resulting minimal growth was then identified using MALDI-TOF and underwent rapid phenotypic testing using three commercially available products (β-lacta and β-carba, from Bio-Rad, Marnes-la-Coquette, France, and Carba-NP, from bioMérieux, Durham, NC). The time to identification of carbapenem resistance using this method was then compared to that of the conventional laboratory workup.

Results
The identification was 100% accurate to the species level using MALDI-TOF paired to the 3.5 hour growth on the “hot choocolate” plates. The β-lacta kit identified resistance to 3rd generation cephalosporins for all ESBL and carbapenemase producing Klebsiella pneumoniae isolates, while the β-carba and Carba-NP kits identified carbapenem resistance only in the carbapenemase producers. The sensitivity of all assays was 100% (95% CI 0.87–1.0) and the specificity of carbapenemase detection was 100% (97.5% one-sided CI 0.4–1.0). The corresponding sensitivities and specificities of direct disc diffusion for ertapenem resistance detection were 88.5% (95% CI 0.70–0.98) and 100% (95%CI 0.40–1.0) respectively. The turnaround time for the rapid kits coupled to the “hot chocolate” plates was 4.25 to 5.1 hours as compared to 16 hours for the conventional workup.

Conclusion
Rapid phenotypic tests performed after inoculation of “hot chocolate” plates are highly sensitive for the presence of carbapenemase production and can be incorporated into the laboratory workflow for Klebisella pneumoniae with important reductions in turnaround time.

Disclosures
All Authors: No reported disclosures
22. Patient Satisfaction Remains Unchanged Following Implementation of an Antibiotic Stewardship Intervention in Primary Care
Authors: Hostetler Zachary , Hamilton Keith W , Cressman Leigh , Todman McWelling H , Lautenbach Ebbing , Dutcher Lauren 
Published: January 2021

Abstract

Background
Inappropriate prescription of antibiotics for respiratory tract infections (RTIs) in ambulatory care settings is common, increasing the risk of adverse health outcomes. Behavioral and educational interventions targeting primary care providers (PCPs) have shown promise in reducing inappropriate antibiotic prescribing for RTIs. While one perceived barrier to such interventions is the concern that these adversely impact patient satisfaction, few data exist in this area. Here, we examine whether a recent PCP-targeted intervention that significantly reduced antibiotic prescribing for RTIs was associated with a change in patient satisfaction.

Methods
The PCP-targeted intervention involved monthly education sessions and peer benchmarking reports delivered to 31 clinics within an academic health system, and was previously shown to reduce antibiotic prescribing. Here, we performed a retrospective, secondary analysis of Press Ganey (PG) surveys associated with the outpatient encounters in the pre- and post-intervention periods. We evaluated the impact on patient perceptions of PCPs based on provider exposure to the intervention using a mixed effects logistic regression model.

Results
There were 17,416 out of 197,744 encounters (8.8%) with associated PG surveys for the study time period (July 2016 to September 2018). In the multivariate model, patient satisfaction with PCPs was most strongly associated with patient-level characteristics (age, race, health status, education status) and survey-level characteristics (survey response time, patient’s usual provider) (Figure 1). Satisfaction with PCPs did not change following delivery of the provider-based intervention even after adjusting for patient- and survey-level characteristics [adjusted odds ratio (95% CI): 1.005 (0.928, 1.087)]. However, a small increase in satisfaction associated with receiving antibiotics during the entire study period was seen [adjusted odds ratio (95% CI): 1.146 (1.06, 1.244)].
Figure 1: Association of a provider-targeted intervention as well as patient, provider, and practice characteristics with patient satisfaction in a multivariable mixed effects logistic regression model

Conclusion
Patient perceptions of PCPs remain unchanged following the delivery of a behavioral and educational intervention to primary care providers that resulted in observable decreases in antibiotic prescribing practices for RTIs.

Disclosures
All Authors: No reported disclosures
29. Rapid Restoration of Bile Acid Compositions After Treatment with Investigational Microbiota-based Therapeutic RBX2660 for Recurrent clostrioides Difficile Infection
Authors: Ferdyan Nicky , Papazyan Romeo , Walsh Dana , Klein Sarah , Qi Steve , Blount Ken , Srinivasan Karthik , Fuchs Bryan 
Published: January 2021

Abstract

Background
Recurrent Clostrioides difficile infection (rCDI) is a public health threat associated with intestinal microbiome disruption (dysbiosis), which is postulated to increase CDI recurrence risk via disruption of bile acid(BA)-mediated resistance to C. difficile colonization. RBX2660 is an investigational microbiota-based therapeutic in clinical development for reducing rCDI recurrence. Herein, we assessed BA composition among participants in a Phase 2 trial of RBX2660 for rCDI.

Methods
In a double-blinded trial (PUNCH CD2), rCDI participants were randomized to receive RBX2660 or placebo. Primary efficacy was defined as absence of CDI recurrence at 8 weeks after the last study treatment. Participants were asked to provide stool samples before (baseline) and up to 24 months after treatment. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 36 BAs from a total of 167 participant stool samples from 47 participants. Participant-matched samples at baseline and 1, 4, and 8 weeks were compared with a linear mixed effects model.

Results
Primary BAs predominated at baseline but were significantly reduced (p&lt; .02) as early as 1 week after treatment and remained so to 24 months. Concurrently, secondary BAs, most notably deoxycholic acid (DCA) and lithocholic acid (LCA), were significantly increased (p&lt; .01) after treatment and remained so throughout. Moreover, increases in DCA and LCA were associated with treatment response (p=.05 and p&lt; .01, respectively), recognizing the limited sample size of treatment failures. Observed BA changes coincided with changes in taxonomic compositions—a shift from Gammaproteobacteria and Bacilli predominance before treatment to Clostridia and Bacteroidia predominance after treatment.
Figure 1: BA restoration of successfully-treated participants

Conclusion
In a trial of RBX2660 for rCDI, participant BA compositions significantly changed from before to after treatment, remained so for at least two years, and correlated with treatment outcome. The resulting predominance of secondary BAs coincided with microbiome compositional changes. Because secondary BA are thought to repress C. difficile colonization, these changes may partly explain how RBX2660 reduced CDI recurrence. Continued evaluation of RBX2660 for rCDI is underway.

Disclosures
Romeo Papazyan, PhD, Ferring Pharmaceuticals (Employee) Dana Walsh, PhD, Rebiotix Inc. (Employee) Steve Qi, PhD, Ferring Pharmaceuticals (Employee) Ken Blount, PhD, Rebiotix Inc. (Employee) Karthik Srinivasan, PhD, Ferring Pharmaceuticals (Employee) Bryan Fuchs, PhD, Ferring Pharmaceuticals (Employee)
30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection
Authors: Walsh Dana , Gonzalez Carlos , Shannon Bill , Blount Ken 
Published: January 2021

Abstract

Background
Antimicrobial resistance (AMR) is a challenge in individuals at risk for recurrent Clostrioides difficile infection (rCDI). Recognizing that AMR bacteria colonize the intestinal microbiota, therapeutic approaches that decolonize the gut of AMR bacteria would be valuable. Herein, we assessed the microbial resistome before and after treatment with RBX7455—a room temperature-stable, orally-administered investigational microbiota-based therapeutic—in a Phase 1 trial for reducing CDI recurrence.

Methods
This investigator-sponsored trial enrolled 30 rCDI patients in 3 open-label treatment groups (n=10 per group): 1) Four RBX7455 capsules BID for 4 days, 2) Four RBX7455 capsules BID for 2 days, 3) Two RBX7455 capsules BID for 2 days. RBX7455 administration began 48 hours after finishing CDI antibiotics. Participants were asked to submit stool samples at baseline, 1, 7, 28 and 56 days after treatment. These were extracted and sequenced using a shallow shotgun method. Relative taxonomic abundances at the class level and the presence of AMR genes were determined for 148 participant samples and 11 product samples using 90% K-mer sequence coverage based on the MEGARes database.

Results
Ninety percent of participants met the primary endpoint of no CDI recurrence through 8 weeks after treatment, and participant microbiome compositions became more similar to RBX7455 after treatment. The total AMR counts per participant decreased from before to after treatment (p&lt; .05, mixed effects model), with the pattern of AMRs identified (resistome) becoming more like the RBX7455 resistome (Figure 1). Most notably, AMRs associated with multi-drug, fluoroquinolone, and betalactam resistance decreased from before to after treatment. There was no significant difference among the groups with respect to clinical response or changes in microbiome composition and AMR content.
Figure 1 Average total and per-class AMR gene counts in participant samples before and after RBX7455 treatment.

Conclusion
In a Phase 1 trial of RBX7455 for rCDI, AMR gene content decreased after treatment. This underscores the potential of microbiota-based therapies for decolonizing AMR bacteria from the gut microbiota. Continued clinical evaluation of RBX7455 is underway.

Disclosures
Dana Walsh, PhD, Rebiotix Inc. (Employee) Carlos Gonzalez, MS, BioRankings, LLC (Employee) Bill Shannon, PhD MBA, BioRankings, LLC (Employee) Ken Blount, PhD, Rebiotix Inc. (Employee)
43. The Capsule and Beyond: Genetic Determinants of Pediatric streptococcus Pneumoniae empyema
Authors: Pershing Nicole L , Kapusta Aurelie , Nielsen Shannon , Crandall Hillary , Korgenski Kent , Byington Carrie L , Ampofo Krow , Blascke Anne 
Published: January 2021

Abstract

Background
Streptococcus pneumoniae is the most common cause of pneumonia in children, including empyema, a severe complication with increasing incidence in the post-pneumococcal vaccine era. Only a subset of &gt; 90 serotypes cause empyema. Virulence determinants of empyema remain largely unknown.

Methods
We performed Illumina sequencing of invasive Pneumococcal isolates from pediatric patients at Primary Children’s Hospital (Salt Lake City, UT) isolated between 1996–2018, de novo genome assembly (SPADES), annotation (PROKKA), serotyping (Quelling and SeroBA), and pan-genome assembly (ROARY). SCOARY and pyseer were used for microbial GWAS. Maximum likelihood phylogeny was calculated using RAxML/Gubbins.

Results
366 pneumococcal isolates were analyzed from 39 serotypes and multiple phenotypes including pneumonia (n=76), empyema (n=63), CNS infection (n=54), and isolated bacteremia (n=79). Serotypes and empyema phenotype clustered roughly by phylogeny. Most analyzed empyema isolates after 2010 were serotype 3 (19/25); prior to PCV-13 introduction serotypes 1 (8/38), 7F (7/38), and 19A (11/38) were more highly represented. Genes implicated in capsule synthesis, transposases, and metabolism were statistically correlated with the empyema phenotype.

Conclusion
Specific capsular or metabolic genes may confer optimal fitness for pleural disease. Further characterization of these genetic associations is needed and will inform future treatment and prevention.

Disclosures
Carrie L. Byington, MD, BioFire (Other Financial or Material Support, Royalties for Intellectual Property)IDbyDNA (Advisor or Review Panel member) Krow Ampofo, MBChB, Merck (Grant/Research Support)
13. Uncommon rash and neurological symptoms related to Shingrix
Authors: Yadava sanjay K , Mahapatra Rahul 
Published: January 2021

Abstract

Background
Shingrix is a non-live recombinant vaccine approved by the Food and Drug Administration (FDA) in 2017 to prevent shingles and postherpetic neuralgia in immunocompetent adults age 50 years and older. A myriads of local and systemic reactions due to the vaccine have been reported, but diffuse erythematous maculopapular rash and neurological symptoms have not yet been reported in English literature.

Methods
Using Google and PubMed, we searched for relevant case reports and journal articles describing adverse effects related to shingrix vaccination.

Results
A 54-year female without significant past medical history presented with diffuse erythematous maculopapular rash, itching and a feeling of weakness in both legs. Her symptoms started with itching and erythematous macular rash at the site of shingles shot followed by headache, myalgia, and malaise which did not improved much with Benadryl. Next day, she felt numbness and weakness in both legs. On the third day, she awoke with diffuse red rash on the face, trunk, lower extremities, fewer lesions on upper extremities. Her review of systems was negative except as mentioned. on examination, she was found to have diffuse erythematous maculopapular itchy rash as shown in Fig 1, but no sensory, motor, cranial never or cerebellar signs. Infectious disease was consulted who recommended IV acyclovir considering early varicella with given morphology. The morphology of lesions did not change over a period of times and VZV PCR of lesions came negative hence acyclovir was discontinued after three days. Her symptoms and rash improved over the hospital stay with supportive treatment and was discharged home on day fifth of admission.
Fig. 1A, Rash over face

Fig. 1B, Rash over right thigh

Conclusion
The safety of shingrix was evaluated by the pool data from eight clinical trials of more than 10,000 participants. Among the study population, 9.4% had local injection-site reactions including pain, redness, and swelling and 10.8% had systemic events including myalgia, fatigue, headache, shivering, fever, and gastrointestinal symptoms. The nature and duration of rash described in our patient has not been reported in english literature including these clinical trials. Noticing new reactions with broad use of new vaccine is conceivable.

Disclosures
All Authors: No reported disclosures