126 research outputs found
Dose-Dependent Response to Cyclodextrin Infusion in a Rat Model of Verapamil Toxicity
Introduction: Sulfobutylether-b-cyclodextrin (SBE-CD) is a pharmaceutical excipient known to bind verapamil. Following intravenous administration, clearance of SBE-CD approximates glomerular filtration rate. We hypothesized that infusion of SBE-CD would increase time to asystole in a rat model of verapamil toxicity in a dose-dependent manner. The objective was to demonstrate the effect of a range of SBE-CD concentrations in a rat model of verapamil toxicity. Methods: Twenty-five Wistar rats were allocated to control or 1 of 4 intervention groups. All received ketamine and diazepam anesthesia followed by verapamil infusion 32 mg/kg/h. The verapamil infusion for the intervention groups was premixed with SBE-CD in a 1:1, 1:2, 1:4, or 1:8 molar ratio (verapamil to SBE-CD). The control group infusion did not contain SBE-CD. Additional saline or water was added to the infusion so that the total volume infused was the same across groups, and the osmolality was maintained as close to physiologic as possible. Heart rate, respiratory rate, and temperature were monitored. The primary endpoint was time to asystole.Results: Verapamil coinfused with SBE-CD in a molar ratio of 1:4 resulted in prolonged time to asystole compared to control (21.2 minutes vs 17.6 minutes, P , 0.05). There were no differences in time to asystole between control and any other intervention group. There was no significant difference in time to apnea between control and any intervention group. We assessed the effect of a range of SBE-CD concentrations and identified 1 concentration that prolonged time to asystole. Mechanismsthat may explain this effect include optimal volume expansion with a hyperosmolar cyclodextrin containing solution, complexation of verapamil within the hydrophobic cyclodextrin pore, and/or complexation within micelle-like aggregates of cyclodextrin. However, mechanistic explanations for the observed findings are speculative at this point. Conclusion: The 1:4 verapamil to SBE-CD concentration was modestly effective with SBE-CD concentrations above and below this range demonstrating nonstatistically significant improvements in time to asystole. [West J Emerg Med. 2012;13(1):63–67.
Two universal results for Wilson loops at strong coupling
We present results for Wilson loops in strongly coupled gauge theories. The
loops may be taken around an arbitrarily shaped contour and in any field theory
with a dual IIB geometry of the form M x S^5. No assumptions about
supersymmetry are made. The first result uses D5 branes to show how the loop in
any antisymmetric representation is computed in terms of the loop in the
fundamental representation. The second result uses D3 branes to observe that
each loop defines a rich sequence of operators associated with minimal surfaces
in S^5. The action of these configurations are all computable. Both results
have features suggesting a connection with integrability.Comment: 1+12 pages. LaTeX. No figure
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HIV Integrase Inhibitors Block Replication of Alpha-, Beta-, and Gammaherpesviruses
ABSTRACT The catalytic site of the HIV integrase is contained within an RNase H-like fold, and numerous drugs have been developed that bind to this site and inhibit its activity. Herpes simplex virus (HSV) encodes two proteins with potential RNase H-like folds, the infected cell protein 8 (ICP8) DNA-binding protein, which is necessary for viral DNA replication and exhibits recombinase activity in vitro, and the viral terminase, which is essential for viral DNA cleavage and packaging. Therefore, we hypothesized that HIV integrase inhibitors might also inhibit HSV replication by targeting ICP8 and/or the terminase. To test this, we evaluated the effect of 118-D-24, a potent HIV integrase inhibitor, on HSV replication. We found that 118-D-24 inhibited HSV-1 replication in cell culture at submillimolar concentrations. To identify more potent inhibitors of HSV replication, we screened a panel of integrase inhibitors, and one compound with greater anti-HSV-1 activity, XZ45, was chosen for further analysis. XZ45 significantly inhibited HSV-1 and HSV-2 replication in different cell types, with 50% inhibitory concentrations that were approximately 1 µM, but exhibited low cytotoxicity, with a 50% cytotoxic concentration greater than 500 µM. XZ45 blocked HSV viral DNA replication and late gene expression. XZ45 also inhibited viral recombination in infected cells and ICP8 recombinase activity in vitro. Furthermore, XZ45 inhibited human cytomegalovirus replication and induction of Kaposi’s sarcoma herpesvirus from latent infection. Our results argue that inhibitors of enzymes with RNase H-like folds may represent a general antiviral strategy, which is useful not only against HIV but also against herpesviruses
Rotating membranes on G_2 manifolds, logarithmic anomalous dimensions and N=1 duality
We show that the behaviour found for long strings rotating
on may be reproduced by membranes rotating on and on a warped M-theory solution. We go on to obtain rotating
membrane configurations with the same relation on
holonomy backgrounds that are dual to gauge theories in four
dimensions. We study membrane configurations on holonomy backgrounds
systematically, finding various other Energy-Charge relations. We end with some
comments about strings rotating on warped backgrounds.Comment: 1+44 pages. Latex. No figures. Minor corrections to make all membrane
configurations consistent. One configuration is now noncompac
Scintillation-limited photometry with the 20-cm NGTS telescopes at Paranal Observatory
Ground-based photometry of bright stars is expected to be limited by atmospheric scintillation, although in practice observations are often limited by other sources of systematic noise. We analyse 122 nights of bright star (Gmag ≲ 11.5) photometry using the 20-cm telescopes of the Next-Generation Transit Survey (NGTS) at the Paranal Observatory in Chile. We compare the noise properties to theoretical noise models and we demonstrate that NGTS photometry of bright stars is indeed limited by atmospheric scintillation. We determine a median scintillation coefficient at the Paranal Observatory of CY=1.54, which is in good agreement with previous results derived from turbulence profiling measurements at the observatory. We find that separate NGTS telescopes make consistent measurements of scintillation when simultaneously monitoring the same field. Using contemporaneous meteorological data, we find that higher wind speeds at the tropopause correlate with a decrease in long-exposure (t = 10 s) scintillation. Hence, the winter months between June and August provide the best conditions for high-precision photometry of bright stars at the Paranal Observatory. This work demonstrates that NGTS photometric data, collected for searching for exoplanets, contains within it a record of the scintillation conditions at Paranal
Curriculum Guidelines for Undergraduate Programs in Data Science
The Park City Math Institute 2016 Summer Undergraduate Faculty Program met for the purpose of composing guidelines for undergraduate programs in data science. The group consisted of 25 undergraduate faculty from a variety of institutions in the United States, primarily from the disciplines of mathematics, statistics, and computer science. These guidelines are meant to provide some structure for institutions planning for or revising a major in data science
Planet Hunters NGTS: New Planet Candidates from a Citizen Science Search of the Next Generation Transit Survey Public Data
We present the results from the first two years of the Planet Hunters Next Generation Transit Survey (NGTS) citizen science project, which searches for transiting planet candidates in data from the NGTS by enlisting the help of members of the general public. Over 8000 registered volunteers reviewed 138,198 light curves from the NGTS Public Data Releases 1 and 2. We utilize a user weighting scheme to combine the classifications of multiple users to identify the most promising planet candidates not initially discovered by the NGTS team. We highlight the five most interesting planet candidates detected through this search, which are all candidate short-period giant planets. This includes the TIC-165227846 system that, if confirmed, would be the lowest-mass star to host a close-in giant planet. We assess the detection efficiency of the project by determining the number of confirmed planets from the NASA Exoplanet Archive and TESS Objects of Interest (TOIs) successfully recovered by this search and find that 74% of confirmed planets and 63% of TOIs detected by NGTS are recovered by the Planet Hunters NGTS project. The identification of new planet candidates shows that the citizen science approach can provide a complementary method to the detection of exoplanets with ground-based surveys such as NGTS
Introduction to A Compendium of Strategies to Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates.
Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients, leading to substantial morbidity, mortality, and excess healthcare expenditures, and persistent gaps remain between what is recommended and what is practiced.The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others
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