Current clinician perspective on non-vitamin K antagonist oral anticoagulant use in challenging clinical cases.

OBJECTIVE: The evolution of non-vitamin K antagonist anticoagulants (NOACs) has changed the horizon of stroke prevention in atrial fibrillation (SPAF). All 4 NOACs have been tested against dose-adjusted warfarin in well-designed, pivotal, phase III, randomized, controlled trials (RCTs) and were approved by regulatory authorities for an SPAF indication. However, as traditional RCTs, these trials have important weaknesses, largely related to their complex structure and patient participation, which was limited by strict inclusion and extensive exclusion criteria. In the real world, however, clinicians are often faced with complex, multimorbid patients who are underrepresented in these RCTs. This article is based on a meeting report authored by 12 scientists studying atrial fibrillation (AF) in diverse ways who discussed the management of challenging AF cases that are underrepresented in pivotal NOAC trials. METHODS: An advisory board panel was convened to confer on management strategies for challenging AF cases. The article is derived from a summary of case presentations and the collaborative discussions at the meeting. CONCLUSION: This expert consensus of cardiologists aimed to define management strategies for challenging cases with patients who underrepresented in pivotal trials using case examples from their routine practice. Although strong evidence is lacking, exploratory subgroup analysis of phase III pivotal trials partially informs the management of these patients. Clinical trials with higher external validity are needed to clarify areas of uncertainty. The lack of clear evidence about complex AF cases has pushed clinicians to manage patients based on clinical experience, including rare situations of off-label prescriptions

GÖKPINAR BARAJI (DENİZLİ) DOLUSAVAK VE EŞİK YAPISI TEMEL ZEMİNİNDE YAPILAN JEOTEKNİK ÇALIŞMALAR

Dams, regulators, irrigation canals etc. have been built to use water resources for economic aims. These types of engineering structures, have to control enormous volume of water, are required to determine all the geological and geotechnical properties of the construction site. The main goal of the study is to mitigate the geological and geotechnical hazards by assessing the pressuremeter test and borehole data performed on the spillway and gate of Gökpınar Dam in Denizli. Geological and geotechnical characteristics of the spillway and gate were also given in the text. Pressuremeter and pull-out tests were carried out on spillway and gate foundations and the obtained results have been correlated to projects data. Some details have also been given about re-enforcement of the weak soil includes cement injection, and bolts.Su kaynaklarının ekonomiye kazandırılması amacıyla baraj, gölet, regülatör ve sulama ana kanalları gibi yapılar inşa edilmektedir. Büyük miktardaki suyun kontrol altında tutulmasını gerektiren bu tür mühendislik yapılarının uzun yıllar kullanılabilmesi; üzerine inşa edileceği jeolojik birimlerin jeoteknik özelliklerinin iyi belirlenerek buna uygun proje tasarımı ve zemin iyileştirmesi yapılmasına bağlıdır. Bu çalışmada, Gökpınar Barajı (Denizli) dolusavak ve eşik yapısı temel zemininde yapılan saha incelemeleri ile temel sondajı ve presiyometre deneylerinin sonuçlarına göre yapılan jeoteknik iyileştirme önlemlerin belirlenmesi amaçlanmaktadır. Baraj alanındaki jeolojik birimlerin jeolojisi ile dolusavak ve eşik yapısının altındaki birimlerin mühendislik özellikleri hakkında bilgiler verilmiştir. Dolusavak ve eşik yapısının oturacağı birimlerin taşıma gücü ve oturma hesaplarına yönelik olarak yerinde (in-situ) presiyometre ve çekme deneyleri yapılmış; bu deneylerin sonuçları yorumlanarak, inşa edilecek yapıdan gelecek yük ile zeminin emniyetli taşıma gücü karşılaştırılmıştır. Zayıf taşıma gücüne sahip birimlerin güçlendirilmesi için alınması gereken önlemler ve güçlendirme işlemleri (zemin sağlamlaştırma enjeksiyonu, ankraj çalışması vb) hakkında bilgiler verilmiştir

Toroidal Magnetic Fields in Type II Superconducting Neutron Stars

We determine constraints on the form of axisymmetric toroidal magnetic fields dictated by hydrostatic balance in a type II superconducting neutron star with a barotropic equation of state. Using Lagrangian perturbation theory, we find the quadrupolar distortions due to such fields for various models of neutron stars with type II superconducting and normal regions. We find that the star becomes prolate and can be sufficiently distorted to display precession with a period of the order of years. We also study the stability of such fields using an energy principle, which allows us to extend the stability criteria established by R. J. Tayler for normal conductors to more general media with magnetic free energy that depends on density and magnetic induction, such as type II superconductors. We also derive the growth rate and instability conditions for a specific instability of type II superconductors, first discussed by P. Muzikar, C. J. Pethick and P. H. Roberts, using a local analysis based on perturbations around a uniform background.Comment: 32 pages, 6 figures; derivations shortened, comments and references added; accepted for publication in MNRA

Risk based facility location by using fault tree analysis in disaster management

Determining the locations of facilities for prepositioning supplies to be used during a disaster is a strategic decision that directly affects the success of disaster response operations. Locating such facilities close to the disaster-prone areas is of utmost importance to minimize response time. However, this is also risky because the facility may be disrupted and hence may not support the demand point(s). In this study, we develop an optimization model that minimizes the risk that a demand point may be exposed to because it is not supported by the located facilities. The purpose is to choose the locations such that a reliable facility network to support the demand points is constructed. The risk for a demand point is calculated as the multiplication of the (probability of the) threat (e.g., earthquake), the vulnerability of the demand point (the probability that it is not supported by the facilities), and consequence (value or possible loss at the demand point due to threat). The vulnerability of a demand point is computed by using fault tree analysis and incorporated into the optimization model innovatively. To our knowledge, this paper is the first to use such an approach. The resulting non-linear integer program is linearized and solved as a linear integer program. The locations produced by the proposed model are compared to those produced by the p-center model with respect to risk value, coverage distance, and covered population by using several test problems. The model is also applied in a real problem. The results indicate that taking the risk into account explicitly may create significant differences in the risk levels. © 2014 Elsevier Ltd

Gravitational wave emission from a magnetically deformed non-barotropic neutron star

A strong candidate for a source of gravitational waves is a highly magnetised, rapidly rotating neutron star (magnetar) deformed by internal magnetic stresses. We calculate the mass quadrupole moment by perturbing a zeroth-order hydrostatic equilibrium by an axisymmetric magnetic field with a \emph{linked poloidal-toroidal structure}. In this work, we do \emph{not} require the model star to obey a barotropic equation of state (as a realistic neutron star is not barotropic), allowing us to explore the hydromagnetic equilibria with fewer constraints. We derive the relation between the ratio of poloidal-to-total field energy $\Lambda$ and ellipticity $\epsilon$ and briefly compare our results to those obtained using the barotropic assumption. Then, we present some examples of how our results can be applied to astrophysical contexts. First, we show how our formulae, in conjunction with current gravitational wave (non-)detections of the Crab pulsar and the Cassiopeia A central compact object (Cas A CCO), can be used to constrain the strength of the internal toroidal fields of those objects. We find that, for the Crab pulsar (whose canonical equatorial dipole field strength, inferred from spin down, is $4\times 10^8$ T) to emit detectable gravitational radiation, the neutron star must have a strong toroidal field component, with maximum internal toroidal field strength $B_{\mathrm{tm}}=7\times 10^{12}$ T; for gravitational waves to be detected from the Cas A CCO at 300 Hz, $B_{\mathrm{tm}}\sim 10^{13}$ T, whereas detection at 100 Hz would require $B_{\mathrm{tm}}\sim 10^{14}$ T. Using our results, we also show how the gravitational wave signal emitted by a magnetar immediately after its birth (assuming it is born rapidly rotating, with $\Lambda\lesssim 0.2$) makes such a newborn magnetar a stronger candidate for gravitational wave detection than, for example, an SGR giant flare.Comment: 15 pages, 8 figures, 2 table

Structure, Deformations and Gravitational Wave Emission of Magnetars

Neutron stars can have, in some phases of their life, extremely strong magnetic fields, up to 10^15-10^16 G. These objects, named magnetars, could be powerful sources of gravitational waves, since their magnetic field could determine large deformations. We discuss the structure of the magnetic field of magnetars, and the deformation induced by this field. Finally, we discuss the perspective of detection of the gravitational waves emitted by these stars.Comment: 11 pages, 2 figures, prepared for 19th International Conference on General Relativity and Gravitation (GR19), Mexico City, Mexico, July 5-9, 201

Lattice dynamics and structural stability of ordered Fe3Ni, Fe3Pd and Fe3Pt alloys

We investigate the binding surface along the Bain path and phonon dispersion relations for the cubic phase of the ferromagnetic binary alloys Fe3X (X = Ni, Pd, Pt) for L12 and DO22 ordered phases from first principles by means of density functional theory. The phonon dispersion relations exhibit a softening of the transverse acoustic mode at the M-point in the L12-phase in accordance with experiments for ordered Fe3Pt. This instability can be associated with a rotational movement of the Fe-atoms around the Ni-group element in the neighboring layers and is accompanied by an extensive reconstruction of the Fermi surface. In addition, we find an incomplete softening in [111] direction which is strongest for Fe3 Ni. We conclude that besides the valence electron density also the specific Fe-content and the masses of the alloying partners should be considered as parameters for the design of Fe-based functional magnetic materials.Comment: Revised version, accepted for publication in Physical Review

Targeting lyn kinase in chorea-acanthocytosis: A translational treatment approach in a rare disease

Background: Chorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms in this disease, and therefore represents a promising drug target. Methods: We evaluated an individual off-label treatment with the tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8–50.4 weeks) of three ChAc patients. Alongside thorough safety monitoring, we assessed motor and non-motor scales (e.g., MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g., serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells). Results: Dasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels, and acanthocyte count did not reveal consistent effects. However, a reduction of initially elevated Lyn kinase activity and accumulated autophagy markers, as well as a partial restoration of the actin cytoskeleton, was found in red blood cells. Conclusions: We report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for “clinical trial readiness”. We suggest a panel of outcome parameters for future clinical trials in ChA

CP and related phenomena in the context of Stellar Evolution

We review the interaction in intermediate and high mass stars between their evolution and magnetic and chemical properties. We describe the theory of Ap-star `fossil' fields, before touching on the expected secular diffusive processes which give rise to evolution of the field. We then present recent results from a spectropolarimetric survey of Herbig Ae/Be stars, showing that magnetic fields of the kind seen on the main-sequence already exist during the pre-main sequence phase, in agreement with fossil field theory, and that the origin of the slow rotation of Ap/Bp stars also lies early in the pre-main sequence evolution; we also present results confirming a lack of stars with fields below a few hundred gauss. We then seek which macroscopic motions compete with atomic diffusion in determining the surface abundances of AmFm stars. While turbulent transport and mass loss, in competition with atomic diffusion, are both able to explain observed surface abundances, the interior abundance distribution is different enough to potentially lead to a test using asterosismology. Finally we review progress on the turbulence-driving and mixing processes in stellar radiative zones.Comment: Proceedings of IAU GA in Rio, JD4 on Ap stars; 10 pages, 7 figure