The Electric and Magnetic Field Instrument and Integrated Science (EMFISIS) investigation on the NASA Radiation Belt Storm Probes (now named the Van Allen Probes) mission provides key wave and very ...low frequency magnetic field measurements to understand radiation belt acceleration, loss, and transport. The key science objectives and the contribution that EMFISIS makes to providing measurements as well as theory and modeling are described. The key components of the instruments suite, both electronics and sensors, including key functional parameters, calibration, and performance, demonstrate that EMFISIS provides the needed measurements for the science of the RBSP mission. The EMFISIS operational modes and data products, along with online availability and data tools provide the radiation belt science community with one the most complete sets of data ever collected.
Cholesterol reduction from statin therapy has been one of the greatest public health successes in modern medicine. Simvastatin is among the most commonly used prescription medications. A ...non‐synonymous coding single‐nucleotide polymorphism (SNP), rs4149056, in SLCO1B1 markedly increases systemic exposure to simvastatin and the risk of muscle toxicity. This guideline explores the relationship between rs4149056 (c.521T>C, p.V174A) and clinical outcome for all statins. The strength of the evidence is high for myopathy with simvastatin. We limit our recommendations accordingly.
Clinical Pharmacology & Therapeutics (2012); 92 1, 112–117. doi:10.1038/clpt.2012.57
We present constraints on extensions of the minimal cosmological models dominated by dark matter and dark energy, ΛCDM and wCDM, by using a combined analysis of galaxy clustering and weak ...gravitational lensing from the first-year data of the Dark Energy Survey (DES Y1) in combination with external data. We consider four extensions of the minimal dark energy-dominated scenarios: (1) nonzero curvature Ωk, (2) number of relativistic species Neff different from the standard value of 3.046, (3) time-varying equation-of-state of dark energy described by the parameters w0 and wa (alternatively quoted by the values at the pivot redshift, wp, and wa), and (4) modified gravity described by the parameters μ0 and Σ0 that modify the metric potentials. We also consider external information from Planck cosmic microwave background measurements; baryon acoustic oscillation measurements from SDSS, 6dF, and BOSS; redshift-space distortion measurements from BOSS; and type Ia supernova information from the Pantheon compilation of datasets. Constraints on curvature and the number of relativistic species are dominated by the external data; when these are combined with DES Y1, we find Ωk=0.0020−0.0032+0.0037 at the 68% confidence level, and the upper limit Neff<3.28(3.55) at 68% (95%) confidence, assuming a hard prior Neff>3.0. For the time-varying equation-of-state, we find the pivot value (wp,wa)=(−0.91−0.23+0.19,−0.57−1.11+0.93) at pivot redshift zp=0.27 from DES alone, and (wp,wa)=(−1.01−0.04+0.04,−0.28−0.48+0.37) at zp=0.20 from DES Y1 combined with external data; in either case we find no evidence for the temporal variation of the equation of state. For modified gravity, we find the present-day value of the relevant parameters to be Σ0=0.43−0.29+0.28 from DES Y1 alone, and (Σ0,μ0)=(0.06−0.07+0.08,−0.11−0.46+0.42) from DES Y1 combined with external data. These modified-gravity constraints are consistent with predictions from general relativity.
Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics ...Program (TPP) of the National Institutes of Health (NIH) Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real‐world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene–drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams. TPP participant institutions developed diverse solutions to overcome many barriers, but the use of Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provided some consistency among the institutions. The TPP also collected some pharmacogenetic implementation outcomes (scientific, educational, financial, and informatics), which may inform healthcare systems seeking to implement their own pharmacogenetic testing programs.
Most human extraintestinal Escherichia coli infections, including those involving antimicrobial resistant strains, are caused by the members of a limited number of distinctive E. coli lineages, ...termed extraintestinal pathogenic E. coli (ExPEC), that have a special ability to cause disease at extraintestinal sites when they exit their usual reservoir in the host's intestinal tract. Multiple lines of evidence suggest that many of the ExPEC strains encountered in humans with urinary tract infection, sepsis, and other extraintestinal infections, especially the most extensively antimicrobial-resistant strains, may have a food animal source, and may be transmitted to humans via the food supply. This review summarizes the evidence that food-borne organisms are a significant cause of extraintestinal E. coli infections in humans.
CYP2C19 is one of the principal enzymes involved in the bioactivation of the antiplatelet prodrug clopidogrel. A common loss‐of‐function allele, CYP2C19*2 (c.681G>A; rs4244285), is associated with ...increased risk for serious adverse cardiovascular events in both heterozygous and homozygous patients (~25–50% of the population) with acute coronary syndromes (ACSs) who are receiving clopidogrel, particularly among those undergoing percutaneous coronary intervention (PCI). We provide evidence from published literature and guidelines for CYPC19 genotype–directed antiplatelet therapy (periodically updated at http://www.pharmgkb.org).
Clinical Pharmacology & Therapeutics (2011) 90 2, 328–332. doi:10.1038/clpt.2011.132
ABSTRACT We report a new ultra-faint stellar system found in Dark Energy Camera data from the first observing run of the Magellanic Satellites Survey (MagLiteS). MagLiteS J0644−5953 (Pictor II or Pic ...II) is a low surface brightness ( within its half-light radius) resolved overdensity of old and metal-poor stars located at a heliocentric distance of . The physical size ( ) and low luminosity ( ) of this satellite are consistent with the locus of spectroscopically confirmed ultra-faint galaxies. MagLiteS J0644−5953 (Pic II) is located from the Large Magellanic Cloud (LMC), and comparisons with simulation results in the literature suggest that this satellite was likely accreted with the LMC. The close proximity of MagLiteS J0644−5953 (Pic II) to the LMC also makes it the most likely ultra-faint galaxy candidate to still be gravitationally bound to the LMC.
We present the first detailed elemental abundances in the ultra-faint Magellanic satellite galaxies Carina II (Car II) and Carina III (Car III). With high-resolution Magellan/MIKE spectroscopy, we ...determined the abundances of nine stars in Car II, including the first abundances of an RR Lyrae star in an ultra-faint dwarf galaxy (UFD), and two stars in Car III. The chemical abundances demonstrate that both systems are clearly galaxies and not globular clusters. The stars in these galaxies mostly display abundance trends matching those of other similarly faint dwarf galaxies: enhanced but declining /Fe ratios, iron-peak elements matching the stellar halo, and unusually low neutron-capture element abundances. One star displays a low outlying Sc/Fe = −1.0. We detect a large Ba scatter in Car II, likely due to inhomogeneous enrichment by low-mass asymptotic giant branch star winds. The most striking abundance trend is for Mg/Ca in Car II, which decreases from +0.4 to −0.4 and indicates clear variation in the initial progenitor masses of enriching core-collapse supernovae. So far, the only UFDs displaying a similar Mg/Ca trend are likely satellites of the Large Magellanic Cloud. We find two stars with Fe/H ≤ −3.5 whose abundances likely trace the first generation of metal-free Population III stars and are well fit by Population III core-collapse supernova yields. An appendix describes our new abundance uncertainty analysis that propagates line-by-line stellar parameter uncertainties.
The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics-pharmacodynamics has ...resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents.
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