Mexiletine-quinidine combination: Electrophysiologic correlates of a favorable antiarrhythmic interaction in humans

Combination therapy with mexiletine and quinidine has been shown to be more effective than either agent alone. The ability of mexiletine monotherapy, quinidine monotherapy and mexiletine-quinidine combination therapy to suppress inducible sustained ventricular tachycardia was related to drug-induced changes in ventricular refractoriness, conduction times and monophasic action potential duration recorded from both ventricles. Ventricular tachycardia could no longer be induced in 7 (35%) of the 20 patients studied with combination therapy. This was a significantly higher proportion of patients than that of the groups responding to either monotherapy (quinidine, 10%; mexiletine, 5%).Ventricular effective and functional refractory periods were measured when applying single (S2), double (S3) and triple (S4) extrastimuli. Quinidine monotherapy increased functional and effective refractory periods of both single and multiple extrastimuli. However, when comparing measurements made during mexiletine treatment with those at baseline, mexiletine monotherapy increased only the refractory periods of S4. The effective refractory period of S4 during mexiletine monotherapy (200 ± 20 ins) was significantly longer than at baseline (160 ± 21 ms). Similarly, when comparing measurements made during combination therapy with those during quinidine monotherapy, combination therapy significantly increased the refractory periods only of multiple extrastimuli. The effective refractory period of S4 during combination therapy (253 ± 26 ms) was significantly longer than that of quinidine monotherapy (223 ± 27 ms). The only other significant difference between combination therapy and monotherapy with either agent was a greater prolongation of conduction time to the left ventricular dyskinetic zone with combination therapy.Therefore, mexiletine-quinidine combination therapy is associated with additional prolongation of the refractory periods of multiple extrastimuli and with further prolongation of conduction into the dyskinetic zone of the left ventricle. These electrophysiologic effects may be markers of enhanced antiarrhythmic activity

Potential Use of Perennial Sunflower to Reduce Blackbird Damage to Sunflower

Wildlife Conservation Sunflower Plots (WCSP) have shown potential to reduce blackbird (Icteridae) damage in commercial sunflower. Also known as lure, decoy, or trap crops, WCSP are strategically placed food plots that provide an easily available and proximate food source that entices blackbirds away from valuable commercial crops. By providing an alternative food source, WCSP reduce direct damage to commercial fields, while also lowering indirect costs that producers incur attempting to prevent blackbird damage. However, cost inefficiencies have deterred widespread use of WCSP. Cost-benefit ratios of using WCSP would be greatly improved if a perennial sunflower were used instead of the annual types currently available. Perennial sunflower would reduce seed cost and planting cost, and perhaps lower opportunity costs, if able to thrive on poorer quality soils. In the near-term, scientists are focused on producing a perennial sunflower sufficiently productive to replace annualWCSP plantings. In 2013, scientists from the University of Minnesota, USDA-Agricultural Research Service, and USDAWildlife Services National Wildlife Research Center evaluated a test plot of an open-pollinated variety of perennial sunflower resulting from genetic crossing of a domesticated annual species (Helianthus annuus) and a perennial wild species (H. tuberosus). Here, we report on results from the 2013 field test and discuss the outlook for development of perennial sunflower, which would help lessen damage to commercial sunflower when used in WCSP; provide a pesticide-free food source for beneficial insects, such as honey bees; help stabilize highly erodible lands near wetlands; and provide year-round habitat for wildlife. Lastly, we provide an initial strategy for using perennial sunflower to reduce blackbird damage in commercial sunflower

Potential Use of Perennial Sunflower to Reduce Blackbird Damage to Sunflower

Wildlife Conservation Sunflower Plots (WCSP) have shown potential to reduce blackbird (Icteridae) damage in commercial sunflower. Also known as lure, decoy, or trap crops, WCSP are strategically placed food plots that provide an easily available and proximate food source that entices blackbirds away from valuable commercial crops. By providing an alternative food source, WCSP reduce direct damage to commercial fields, while also lowering indirect costs that producers incur attempting to prevent blackbird damage. However, cost inefficiencies have deterred widespread use of WCSP. Cost-benefit ratios of using WCSP would be greatly improved if a perennial sunflower were used instead of the annual types currently available. Perennial sunflower would reduce seed cost and planting cost, and perhaps lower opportunity costs, if able to thrive on poorer quality soils. In the near-term, scientists are focused on producing a perennial sunflower sufficiently productive to replace annualWCSP plantings. In 2013, scientists from the University of Minnesota, USDA-Agricultural Research Service, and USDAWildlife Services National Wildlife Research Center evaluated a test plot of an open-pollinated variety of perennial sunflower resulting from genetic crossing of a domesticated annual species (Helianthus annuus) and a perennial wild species (H. tuberosus). Here, we report on results from the 2013 field test and discuss the outlook for development of perennial sunflower, which would help lessen damage to commercial sunflower when used in WCSP; provide a pesticide-free food source for beneficial insects, such as honey bees; help stabilize highly erodible lands near wetlands; and provide year-round habitat for wildlife. Lastly, we provide an initial strategy for using perennial sunflower to reduce blackbird damage in commercial sunflower

New distances to RAVE stars

Probability density functions are determined from new stellar parameters for the distance moduli of stars for which the RAdial Velocity Experiment (RAVE) has obtained spectra with S/N>=10. Single-Gaussian fits to the pdf in distance modulus suffice for roughly half the stars, with most of the other half having satisfactory two-Gaussian representations. As expected, early-type stars rarely require more than one Gaussian. The expectation value of distance is larger than the distance implied by the expectation of distance modulus; the latter is itself larger than the distance implied by the expectation value of the parallax. Our parallaxes of Hipparcos stars agree well with the values measured by Hipparcos, so the expectation of parallax is the most reliable distance indicator. The latter are improved by taking extinction into account. The effective temperature absolute-magnitude diagram of our stars is significantly improved when these pdfs are used to make the diagram. We use the method of kinematic corrections devised by Schoenrich, Binney & Asplund to check for systematic errors for general stars and confirm that the most reliable distance indicator is the expectation of parallax. For cool dwarfs and low-gravity giants tends to be larger than the true distance by up to 30 percent. The most satisfactory distances are for dwarfs hotter than 5500 K. We compare our distances to stars in 13 open clusters with cluster distances from the literature and find excellent agreement for the dwarfs and indications that we are over-estimating distances to giants, especially in young clusters.Comment: 20 pages accepted by MNRAS. Minor changes to the submitted versio

Quinidine pharmacodynamics in patients with arrhythmia: Effects of left ventricular function

Objectives.This study was undertaken to determine whether quinidine pharmacodynamics are altered in the presence of left ventricular dysfunction.Background.Left ventricular function is an independent predictor of antiarrhythmic drug efficacy. However, the effects of left ventricular dysfunction on the pharmacodynamics of antiarrhythmic drugs have not been studied extensively.Methods.Signal-averaged electrocardiograms were obtained and quinidine plasma concentrations measured during 24-h quinidine washout in 22 patients.Results.Linear quinidine concentration-effect relations were observed for QRS and QT intervals corrected for heart rate. The slopes of the concentration-effect relation describing changes in the corrected QT (QTc) interval were significantly higher in the group with left ventricular ejection fraction ≥0.35 ([mean ±SD] 29.5 ± 11.2 ms/μg per ml) than in the group with a low left ventricular ejection fraction (15.7 ± 9.7 ms/μg per ml, p = 0.001). The QRS concentration-effect relations were not different in the two groups. A significant linear correlation was observed between the slopes of the concentration-effect relations describing changes in QTc intervals and left ventricular ejection fraction (r = 0.7, p < 0.001). Nineteen patients with inducible ventricular tachycardia underwent serial electrophysiologic studies for evaluation of quinidine efficacy. Ventricular tachycardia could not be induced during quinidine therapy in eight patients. The slopes of the quinidine concentration-effect relations for QTc intervals were significantly higher in quinidine responders than in nonresponders (p < 0.05).Conclusions.The effects of quinidine on ventricular repolarization are linearly related to left ventricular ejection fraction. Quinidine concentration-effect relations describing ventricular repolarization are associated with antiarrhythmic efficacy in patients with ventricular tachycardia

The R-Process Alliance: Discovery of a Low-α, r-process-enhanced Metal-poor Star in the Galactic Halo

A new moderately r-process-enhanced metal-poor star, RAVE J093730.5−062655, has been identified in the Milky Way halo as part of an ongoing survey by the R-Process Alliance. The temperature and surface gravity indicate that J0937−0626 is likely a horizontal branch star. At [Fe/H] = −1.86, J0937−0626 is found to have subsolar [X/Fe] ratios for nearly every light, α, and Fe-peak element. The low [α/Fe] ratios can be explained by an ~0.6 dex excess of Fe; J0937−0626 is therefore similar to the subclass of "iron-enhanced" metal-poor stars. A comparison with Milky Way field stars at [Fe/H] = −2.5 suggests that J0937−0626 was enriched in material from an event, possibly a Type Ia supernova, that created a significant amount of Cr, Mn, Fe, and Ni and smaller amounts of Ca, Sc, Ti, and Zn. The r-process enhancement of J0937−0626 is likely due to a separate event, which suggests that its birth environment was highly enriched in r-process elements. The kinematics of J0937−0626, based on Gaia DR2 data, indicate a retrograde orbit in the Milky Way halo; J0937−0626 was therefore likely accreted from a dwarf galaxy that had significant r-process enrichment

Improved distances and ages for stars common to TGAS and RAVE

ABSTRACT We combine parallaxes from the first Gaia data release with the spectrophotometric distance estimation framework for stars in the fifth RAVE survey data release. The combined distance estimates are more accurate than either determination in isolation – uncertainties are on average two times smaller than for RAVE-only distances (three times smaller for dwarfs), and 1.4 times smaller than TGAS parallax uncertainties (two times smaller for giants). We are also able to compare the estimates from spectrophotometry to those from Gaia, and use this to assess the reliability of both catalogues and improve our distance estimates.We find that the distances to the lowest log g stars are, on average, overestimated and caution that they may not be reliable. We also find that it is likely that the Gaia random uncertainties are smaller than the reported values. As a byproduct we derive ages for the RAVE stars, many with relative uncertainties less than 20 percent. These results for 219 566 RAVE sources have been made publicly available, and we encourage their use for studies that combine the radial velocities provided by RAVE with the proper motions provided by Gaia. A sample that we believe to be reliable can be found by taking only the stars with the flag notification ‘flag_any=0’. Key words: Galaxy: fundamental parameters – methods: statistical –Funding for the research in this study came from the Swedish National Space Board, the Royal Physiographic Society in Lund, and some of the computations were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at Lunarc under project SNIC 2016/4-17. Funding for RAVE has been provided by: the Australian Astronomical Observatory; the Leibniz-Institut fuer Astrophysik Potsdam (AIP); the Australian National University; the Australian Research Council; the French National Research Agency; the German Research Foundation (SPP 1177 and SFB 881); the European Research Council (ERC-StG 240271 Galactica); the Istituto Nazionale di Astrofisica at Padova; The Johns Hopkins University; the National Science Foundation of the USA (AST-0908326); the W. M. Keck foundation; the Macquarie University; the Netherlands Research School for Astronomy; the Natural Sciences and Engineering Research Council of Canada; the Slovenian Research Agency (research core funding No. P1-0188); the Swiss National Science Foundation; the Science & Technology Facilities Council of the UK; Opticon; Strasbourg Observatory; and the Universities of Groningen, Heidelberg and Sydney. The RAVE web site is https://www.rave-survey.org. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC; https://www.cosmos.esa.int/web/gaia/dpac/consortium). Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement

Correlations between age, kinematics, and chemistry as seen by the RAVE survey

We explore the connections between stellar age, chemistry, and kinematics across a Galactocentric distance of 7.5 < R(kpc) < 9.0, using a sample of ∼12 000 intermediate-mass (FGK) turn-off stars observed with the RAdial Velocity Experiment (RAVE) survey. The kinematics of this sample are determined using radial velocity measurements from RAVE, and parallax and proper motion measurements from the Tycho–Gaia Astrometric Solution (TGAS). In addition, ages for RAVE stars are determined using a Bayesian method, taking TGAS parallaxes as a prior. We divide our sample into young (0 < τ < 3 Gyr) and old (8 < τ < 13 Gyr) populations, and then consider different metallicity bins for each of these age groups. We find significant differences in kinematic trends of young and old, metal-poor and metal-rich, stellar populations. In particular, we find a strong metallicity dependence in the mean Galactocentric radial velocity as a function of radius (∂VR/∂R) for young stars, with metal-rich stars having a much steeper gradient than metal-poor stars. For ∂Vϕ/∂R, young, metal-rich stars significantly lag the LSR with a slightly positive gradient, while metal-poor stars show a negative gradient above the LSR. We interpret these findings as correlations between metallicity and the relative contributions of the non-axisymmetries in the Galactic gravitational potential (the spiral arms and the bar) to perturb stellar orbits.∂Vϕ/∂R, young, metal-rich stars significantly lag the LSR with a slightly positive gradient, while metal-poor stars show a negative gradient above the LSR. We interpret these findings as correlations between metallicity and the relative contributions of the non-axisymmetries in the Galactic gravitational potential (the spiral arms and the bar) to perturb stellar orbits