357 research outputs found
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 and ellipticity 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 T) to emit detectable gravitational radiation, the
neutron star must have a strong toroidal field component, with maximum internal
toroidal field strength T; for gravitational
waves to be detected from the Cas A CCO at 300 Hz, T, whereas detection at 100 Hz would require 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 ) 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
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
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
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
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