More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy-Current Data and Future Directions.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.Common to the pathogenesis of acute coronary syndromes (ACS) is the formation of arterial thrombus, which results from platelet activation and triggering of the coagulation cascade.1 To attenuate the risk of future thrombotic events, patients with ACS are treated with dual antiplatelet therapy (DAPT), namely, the combination of aspirin with a P2Y12 inhibitor, such as clopidogrel, ticagrelor, or prasugrel. Despite DAPT, some ≈10% of ACS patients experience recurrent major adverse cardiovascular events over the subsequent 30 days,2 driving the quest for more effective inhibition of thrombotic pathways. In this review, we provide an overview of studies to date and those ongoing that aim to deliver more effective combinations of antithrombotic agents to patients with recent ACS. We have chosen to confine the review to ACS patients without atrial fibrillation because those with atrial fibrillation have a clear indication for combination therapy that includes oral anticoagulation and should, we feel, be treated as a separate cohort. In this article, we discuss the limitations of the currently available clinical trial data and future directions, with suggestions for how practice might change to reduce the risk of coronary thrombosis in those at greatest risk, with minimal impact on bleeding.Peer reviewedFinal Published versio

Magneto-Acoustic Waves of Small Amplitude in Optically Thin Quasi-Isentropic Plasmas

The evolution of quasi-isentropic magnetohydrodynamic waves of small but finite amplitude in an optically thin plasma is analyzed. The plasma is assumed to be initially homogeneous, in thermal equilibrium and with a straight and homogeneous magnetic field frozen in. Depending on the particular form of the heating/cooling function, the plasma may act as a dissipative or active medium for magnetoacoustic waves, while Alfven waves are not directly affected. An evolutionary equation for fast and slow magnetoacoustic waves in the single wave limit, has been derived and solved, allowing us to analyse the wave modification by competition of weakly nonlinear and quasi-isentropic effects. It was shown that the sign of the quasi-isentropic term determines the scenario of the evolution, either dissipative or active. In the dissipative case, when the plasma is first order isentropically stable the magnetoacoustic waves are damped and the time for shock wave formation is delayed. However, in the active case when the plasma is isentropically overstable, the wave amplitude grows, the strength of the shock increases and the breaking time decreases. The magnitude of the above effects depends upon the angle between the wave vector and the magnetic field. For hot (T > 10^4 K) atomic plasmas with solar abundances either in the interstellar medium or in the solar atmosphere, as well as for the cold (T < 10^3 K) ISM molecular gas, the range of temperature where the plasma is isentropically unstable and the corresponding time and length-scale for wave breaking have been found.Comment: 14 pages, 10 figures. To appear in ApJ January 200

Minimal Family Unification

Absract It is proposed that there exist, within a new $SU(2)^{'}$, a gauged discrete group $Q_6$ (the order 12 double dihedral group) acting as a family symmetry. This nonabelian finite group can explain hierarchical features of families, using an assignment for quarks and leptons dictated by the requirements of anomaly cancellation and of no additional quarks.Comment: 10 pages, IFP-701-UNC;VAND-TH-94-

Nucleon decay in gauge unified models with intersecting D6-branes

Baryon number violation is discussed in gauge unified orbifold models of type II string theory with intersecting Dirichlet branes. We consider setups of D6-branes which extend along the flat Minkowski space-time directions and wrap around 3-cycles of the internal 6-d manifold. The discussion is motivated by the enhancement effect of low energy amplitudes anticipated for M-theory and type II string theory models with matter modes localized at points of the internal manifold. The conformal field theory formalism is used to evaluate the open string amplitudes at tree level. We study the single baryon number violating processes of dimension 6 and 5, involving four quarks and leptons and in supersymmetry models, two pairs of matter fermions and superpartner sfermions. The higher order processes associated with the baryon number violating operators of dimension 7 and 9 are also examined, but in a qualitative way. We discuss the low energy representation of string theory amplitudes in terms of infinite series of poles associated to exchange of string Regge resonance and compactification modes. The comparison of string amplitudes with the equivalent field theory amplitudes is first studied in the large compactification radius limit. Proceeding next to the finite compactification radius case, we present a numerical study of the ratio of string to field theory amplitudes based on semi-realistic gauge unified non-supersymmetric and supersymmetric models employing the Z3 and Z2xZ2 orbifolds. We find a moderate enhancement of string amplitudes which becomes manifest in the regime where the gauge symmetry breaking mass parameter exceeds the compactification mass parameter, corresponding to a gauge unification in a seven dimensional space-time.Comment: 63 pages revtex4. 8 postscript figures. 4 tables. Subsection II.B revised. Several new references added. To appear in Physical Review

Massive Neutrinos and (Heterotic) String Theory

String theories in principle address the origin and values of the quark and lepton masses. Perhaps the small values of neutrino masses could be explained generically in string theory even if it is more difficult to calculate individual values, or perhaps some string constructions could be favored by generating small neutrino masses. We examine this issue in the context of the well-known three-family standard-like Z_3 heterotic orbifolds, where the theory is well enough known to construct the corresponding operators allowed by string selection rules, and analyze the D- and F-flatness conditions. Surprisingly, we find that a simple see-saw mechanism does not arise. It is not clear whether this is a property of this construction, or of orbifolds more generally, or of string theory itself. Extended see-saw mechanisms may be allowed; more analysis will be needed to settle that issue. We briefly speculate on their form if allowed and on the possibility of alternatives, such as small Dirac masses and triplet see-saws. The smallness of neutrino masses may be a powerful probe of string constructions in general. We also find further evidence that there are only 20 inequivalent models in this class, which affects the counting of string vacua.Comment: 18 pages in RevTeX format. Single-column postscript version available at http://sage.hep.upenn.edu/~bnelson/singpre.p

Strategies Employed by Community-Based Service Providers to Address HIV-Associated Neurocognitive Challenges: A Qualitative Study

Background: HIV-associated neurocognitive disorders and other causes of neurocognitive challenges experienced by people living with HIV (PLWH) persist as public health concerns in developed countries. Consequently, PLWH who experience neurocognitive challenges increasingly require social support and mental health services from community-based providers in the HIV sector. Methods: Thirty-three providers from 22 AIDS service organizations across Ontario, Canada, were interviewed to determine the strategies they used to support PLWH experiencing neurocognitive difficulties. Thematic analysis was conducted to determine key themes from the interview data. Results: Three types of strategies were identified: (a) intrapersonal, (b) interpersonal, and (c) organizational. Intrapersonal strategies involved learning and staying informed about causes of neurocognitive challenges. Interpersonal strategies included providing practical assistance, information, counseling, and/or referrals to PLWH. Organizational strategies included creating dedicated support groups for PLWH experiencing neurocognitive challenges, partnering with other organizations with services not available within their own organization, and advocating for greater access to services with expertise and experience working with PLWH. Conclusion: Through concerted efforts in the future, it is likely that empirically investigating, developing, and customizing these strategies specifically to address HIV-associated neurocognitive challenges will yield improved social support and mental health outcomes for PLWH

Of CP and other Gauge Symmetries in String Theory

We argue that \CP is a gauge symmetry in string theory. As a consequence, \CP cannot be explicitly broken either perturbatively or non-pertubatively; there can be no non-perturbative \CP-violating parameters. String theory is thus an example of a theory where all $\theta$ angles arise due to spontaneous \CP violation, and are in principle calculable.Comment: 8 page

Primordial Magnetic Fields, Right Electrons, and the Abelian Anomaly

In the standard model there are charges with abelian anomaly only (e.g. right-handed electron number) which are effectively conserved in the early universe until some time shortly before the electroweak scale. A state at finite chemical potential of such a charge, possibly arising due to asymmetries produced at the GUT scale, is unstable to the generation of hypercharge magnetic field. Quite large magnetic fields ($\sim 10^{22}$ gauss at $T\sim 100$ GeV with typical inhomogeneity scale $\sim \frac{ 10^6}{T}$) can be generated. These fields may be of cosmological interest, potentially acting as seeds for amplification to larger scale magnetic fields through non-linear mechanisms. Previously derived bounds on exotic $B-L$ violating operators may also be evaded.Comment: Revised version, to appear in Phys. Rev. Lett.. Analysis has been extended to larger chemical potentials, for which large magnetic fields survive at the electroweak scale. Previous bounds on $B-L$ violating operators are also evaded in this cas

Bianchi Type I Cosmologies in Arbitrary Dimensional Dilaton Gravities

We study the low energy string effective action with an exponential type dilaton potential and vanishing torsion in a Bianchi type I space-time geometry. In the Einstein and string frames the general solution of the gravitational field equations can be expressed in an exact parametric form. Depending on the values of some parameters the obtained cosmological models can be generically divided into three classes, leading to both singular and nonsingular behaviors. The effect of the potential on the time evolution of the mean anisotropy parameter is also considered in detail, and it is shown that a Bianchi type I Universe isotropizes only in the presence of a dilaton field potential or a central deficit charge.Comment: REVTEX, 10 pages, 8 figure