Evaluation of the angiotensin II receptor blocker azilsartan medoxomil in African-American patients with hypertension

The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African-American patients with hypertension in a 6-week, double-blind, randomized, placebo-controlled trial, for which the primary end point was change from baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients, with a mean age of 52years, 57% women, and baseline 24-hour BP of 146/91mmHg. Treatment differences in 24-hour systolic BP between AZL-M 40mg and placebo (-5.0mmHg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80mg and placebo (-7.8mmHg; 95% confidence interval, -10.7 to -4.9) were significant (P.001 vs placebo for both comparisons). Changes in the clinic BPs were similar to the ambulatory BP results. Incidence rates of adverse events were comparable among the treatment groups, including those of a serious nature. In African-American patients with hypertension, AZL-M significantly reduced ambulatory and clinic BPs in a dose-dependent manner and was well tolerated

Modelling the AM CVn and Double Detonation Supernova Progenitor Binary System CD-30∘^{\circ}11223

We present a detailed modelling study of CD-30$^{\circ}$11223 (CD-30), a hot subdwarf (sdB)-white dwarf (WD) binary identified as a double detonation supernova progenitor, using the open-source stellar evolution software MESA. We focus on implementing binary evolution models carefully tuned to match the observed characteristics of the system including $\log g$ and $T_{\rm eff}$. For the first time, we account for the structure of the hydrogen envelope throughout the modelling, and find that the inclusion of element diffusion is important for matching the observed radius and temperature. We investigate the two sdB mass solutions (0.47 and 0.54 $M_{\odot}$) previously proposed for this system, strongly favouring the 0.47 $M_{\odot}$ solution. The WD cooling age is compared against the sdB age using our models, which suggest an sdB likely older than the WD, contrary to the standard assumption for compact sdB-WD binaries. Subsequently, we propose a possible alternate formation channel for CD-30. We also perform binary evolution modelling of the system to study various aspects such as mass transfer, orbital period evolution and luminosity evolution. Our models confirm CD-30 as a double detonation supernova progenitor, expected to explode $\approx55$ Myr from now. The WD accretes a $\approx0.17$ $M_{\odot}$ thick helium shell that causes a detonation, leaving a 0.30 $M_{\odot}$ sdB ejected at $\approx$750 km/s. The final 15 Myr of the system are characterised by helium accretion which dominates the system luminosity, possibly resembling an AM CVn-type system.Comment: 12 pages, 8 figures. Accepted for publication in MNRA

Variability of Red Supergiants in M31 from the Palomar Transient Factory

Most massive stars end their lives as Red Supergiants (RSGs), a short-lived evolution phase when they are known to pulsate with varying amplitudes. The RSG period-luminosity (PL) relation has been measured in the Milky Way, the Magellanic Clouds and M33 for about 120 stars in total. Using over 1500 epochs of R-band monitoring from the Palomar Transient Factory (PTF) survey over a five-year period, we study the variability of 255 spectroscopically cataloged RSGs in M31. We find that all RGSs brighter than M_K~ -10 mag (log(L/L_sun)>4.8) are variable at dm_R>0.05 mag. Our period analysis finds 63 with significant pulsation periods. Using the periods found and the known values of M_K for these stars, we derive the RSG PL relation in M31 and show that it is consistent with those derived earlier in other galaxies of different metallicities. We also detect, for the first time, a sequence of likely first-overtone pulsations. Comparison to stellar evolution models from MESA confirms the first overtone hypothesis and indicates that the variable stars in this sample have 12 M_sun<M<24 M_sun. As these RSGs are the immediate progenitors to Type II-P core-collapse supernovae (SNe), we also explore the implication of their variability in the initial-mass estimates for SN progenitors based on archival images of the progenitors. We find that this effect is small compared to the present measurement errors.Comment: 17 pages, 10 figure

The OmegaWhite Survey for Short-Period Variable Stars IV: Discovery of the warm DQ white dwarf OW J175358.85-310728.9

We present the discovery and follow-up observations of the second known variable warm DQ white dwarf OW J175358.85-310728.9 (OW J1753-3107). OW J1753-3107 is the brightest of any of the currently known warm or hot DQ and was discovered in the OmegaWhite Survey as exhibiting optical variations on a period of 35.5452 (2) mins, with no evidence for other periods in its light curves. This period has remained constant over the last two years and a single-period sinusoidal model provides a good fit for all follow-up light curves. The spectrum consists of a very blue continuum with strong absorption lines of neutral and ionised carbon, a broad He I 4471 A line, and possibly weaker hydrogen lines. The C I lines are Zeeman split, and indicate the presence of a strong magnetic field. Using spectral Paschen-Back model descriptions, we determine that OW J1753-3107 exhibits the following physical parameters: T_eff = 15430 K, log(g) = 9.0, log(N(C)/N(He)) = -1.2, and the mean magnetic field strength is B_z =2.1 MG. This relatively low temperature and carbon abundance (compared to the expected properties of hot DQs) is similar to that seen in the other warm DQ SDSS J1036+6522. Although OW J1753-3107 appears to be a twin of SDSS J1036+6522, it exhibits a modulation on a period slightly longer than the dominant period in SDSS J1036+6522 and has a higher carbon abundance. The source of variations is uncertain, but they are believed to originate from the rotation of the magnetic white dwarf.Comment: 11 pages, 8 figures, 7 tables. Accepted for publication by MNRA

The fastest unbound star in our Galaxy ejected by a thermonuclear supernova

Hypervelocity stars (HVS) travel with velocities so high, that they exceed the escape velocity of the Galaxy. Several acceleration mechanisms have been discussed. Only one HVS (US 708, HVS 2) is a compact helium star. Here we present a spectroscopic and kinematic analysis of US\,708. Travelling with a velocity of $\sim1200\,{\rm km\,s^{-1}}$, it is the fastest unbound star in our Galaxy. In reconstructing its trajectory, the Galactic center becomes very unlikely as an origin, which is hardly consistent with the most favored ejection mechanism for the other HVS. Furthermore, we discovered US\,708 to be a fast rotator. According to our binary evolution model it was spun-up by tidal interaction in a close binary and is likely to be the ejected donor remnant of a thermonuclear supernova.Comment: 16 pages report, 20 pages supplementary material

Deterministic mechanical model of T-killer cell polarization reproduces the wandering of aim between simultaneously engaged targets

T-killer cells of the immune system eliminate virus-infected and tumorous cells through direct cell-cell interactions. Reorientation of the killing apparatus inside the T cell to the T-cell interface with the target cell ensures specificity of the immune response. The killing apparatus can also oscillate next to the cell-cell interface. When two target cells are engaged by the T cell simultaneously, the killing apparatus can oscillate between the two interface areas. This oscillation is one of the most striking examples of cell movements that give the microscopist an unmechanistic impression of the cell's fidgety indecision. We have constructed a three-dimensional, numerical biomechanical model of the molecular-motor-driven microtubule cytoskeleton that positions the killing apparatus. The model demonstrates that the cortical pulling mechanism is indeed capable of orienting the killing apparatus into the functional position under a range of conditions. The model also predicts experimentally testable limitations of this commonly hypothesized mechanism of T-cell polarization. After the reorientation, the numerical solution exhibits complex, multidirectional, multiperiodic, and sustained oscillations in the absence of any external guidance or stochasticity. These computational results demonstrate that the strikingly animate wandering of aim in T-killer cells has a purely mechanical and deterministic explanation. © 2009 Kim, Maly

Sifting for Sapphires: Systematic Selection of Tidal Disruption Events in iPTF

We present results from a systematic selection of tidal disruption events (TDEs) in a wide-area (4800~deg$^2$), $g+R$ band, Intermediate Palomar Transient Factory (iPTF) experiment. Our selection targets typical optically-selected TDEs: bright ($>$60\% flux increase) and blue transients residing in the center of red galaxies. Using photometric selection criteria to down-select from a total of 493 nuclear transients to a sample of 26 sources, we then use follow-up UV imaging with the Neil Gehrels Swift Telescope, ground-based optical spectroscopy, and light curve fitting to classify them as 14 Type Ia supernovae (SNe Ia), 9 highly variable active galactic nuclei (AGNs), 2 confirmed TDEs, and 1 potential core-collapse supernova. We find it possible to filter AGNs by employing a more stringent transient color cut ($g-r <$ $-$0.2 mag); further, UV imaging is the best discriminator for filtering SNe, since SNe Ia can appear as blue, optically, as TDEs in their early phases. However, when UV-optical color is unavailable, higher precision astrometry can also effectively reduce SNe contamination in the optical. Our most stringent optical photometric selection criteria yields a 4.5:1 contamination rate, allowing for a manageable number of TDE candidates for complete spectroscopic follow-up and real-time classification in the ZTF era. We measure a TDE per galaxy rate of 1.7$^{+2.9}_{-1.3}$ $\times$10$^{-4}$ gal$^{-1}$ yr$^{-1}$ (90\% CL in Poisson statistics). This does not account for TDEs outside our selection criteria, thus may not reflect the total TDE population, which is yet to be fully mapped.Comment: 24 pages, 21 figures. Accepted for publication in the Astrophysical Journal Supplement Serie

Transmission of Human Immunodeficiency Virus I Drug Resistance - a Case Report. What are the Clinical Implications?

The success of first-line antiretroviral therapy can be challenged by the acquisition of primary drug resistance. Here we report a case where baseline genotypic resistance testing detected resistance conferring nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-associated mutations, but no primary mutations for protease inhibitor (PI). Subsequent PI-based HAART with boosted saquinavir led to virological treatment success with persistently undetectable viral load. After treatment simplification from saquinavir to an atazanavir based PI-therapy and no change in backbone therapy rapid virological breakthrough occurred. Retrospective analysis displayed preexisting gag cleavage site mutations which may have reduced the genetic barrier in a clinical relevant manner in combination with the already existing NRTI resistance mutations. Alternatively, this effect could be explained with a different antiviral potency for the respective PIs used