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

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

Evaluation of a surgical interface for robotic cryoablation task using an eye-tracking system

Computer-assisted navigation systems coupled with surgical interfaces (SIs) are providing doctors with tools that are safer for patients compared to traditional methods. Usability analysis of the SIs that guides their development is hence important. In this study, we record the eye movements of doctors and other people with no medical expertise during interaction with an SI that directs a simulated cryoablation task. There are two different arrangements for the layout of the same SI, and the goal is to evaluate whether one of these arrangements is ergonomically better than the other. We use several gaze related statistics some of which are employed in an SI design context for the first time. Even though the performance and gaze related analysis reveals that the two arrangements are comparable in many respects, there are also differences. Specifically, one arrangement leads to more saccades along the vertical and horizontal directions, lower saccade amplitudes in the crucial phase of the task, more locally clustered and yet globally spread viewing. Accordingly, that arrangement is selected for future use. The present study provides a proof of concept for the integration of novel gaze analysis tools developed for scene perception studies into the interface development process.European Commissionpost-prin

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

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

The long helical jet of the Lighthouse nebula, IGR J11014-6103

Jets from rotation-powered pulsars have so far only been observed in systems moving subsonically trough their ambient medium and/or embedded in their progenitor supernova remnant (SNR). Supersonic runaway pulsars are also expected to produce jets, but they have not been confirmed so far. We investigated the nature of the jet-like structure associated to the INTEGRAL source IGR J11014-6103 (the "Lighthouse nebula"). The source is a neutron star escaping its parent SNR MSH 11-61A supersonically at a velocity exceeding 1000 km/s. We observed the Lighthouse nebula and its jet-like X-ray structure through dedicated high spatial resolution observations in X-rays (Chandra) and radio band (ATCA). Our results show that the feature is a true pulsar's jet. It extends highly collimated over >11pc, displays a clear precession-like modulation, and propagates nearly perpendicular to the system direction of motion, implying that the neutron star's spin axis in IGR J11014-6103 is almost perpendicular to the direction of the kick received during the supernova explosion. Our findings suggest that jets are common to rotation-powered pulsars, and demonstrate that supernovae can impart high kick velocities to misaligned spinning neutron stars, possibly through distinct, exotic, core-collapse mechanisms.Comment: 8 pages, 6 figures, 1 table. Discussion (sec.3) expanded and typos fixed; results unchanged. Published on A&

Linking Scottish vital event records using family groups

Funding: This work was supported by ESRC Grants ES/K00574X/2 “Digitising Scotland” and ES/L007487/1 “Administrative Data Research Centre – Scotland.”The reconstitution of populations through linkage of historical records is a powerful approach to generate longitudinal historical microdata resources of interest to researchers in various fields. Here we consider automated linking of the vital events recorded in the civil registers of birth, death and marriage compiled in Scotland, to bring together the various records associated with the demographic events in the life course of each individual in the population. From the histories, the genealogical structure of the population can then be built up. Rather than apply standard linkage techniques to link the individuals on the available certificates, we explore an alternative approach, inspired by the family reconstitution techniques adopted by historical demographers, in which the births of siblings are first linked to form family groups, after which intergenerational links between families can be established. We report a small-scale evaluation of this approach, using two district-level data sets from Scotland in the late nineteenth century, for which sibling links have already been created by demographers. We show that quality measures of up to 83% can be achieved on these data sets (using F-Measure, a combination of precision and recall). In the future, we intend to compare the results with a standard linkage approach and to investigate how these various methods may be used in a project which aims to link the entire Scottish population from 1856 to 1973.PostprintPeer reviewe

Magnetic Field Generation in Stars

Enormous progress has been made on observing stellar magnetism in stars from the main sequence through to compact objects. Recent data have thrown into sharper relief the vexed question of the origin of stellar magnetic fields, which remains one of the main unanswered questions in astrophysics. In this chapter we review recent work in this area of research. In particular, we look at the fossil field hypothesis which links magnetism in compact stars to magnetism in main sequence and pre-main sequence stars and we consider why its feasibility has now been questioned particularly in the context of highly magnetic white dwarfs. We also review the fossil versus dynamo debate in the context of neutron stars and the roles played by key physical processes such as buoyancy, helicity, and superfluid turbulence,in the generation and stability of neutron star fields. Independent information on the internal magnetic field of neutron stars will come from future gravitational wave detections. Thus we maybe at the dawn of a new era of exciting discoveries in compact star magnetism driven by the opening of a new, non-electromagnetic observational window. We also review recent advances in the theory and computation of magnetohydrodynamic turbulence as it applies to stellar magnetism and dynamo theory. These advances offer insight into the action of stellar dynamos as well as processes whichcontrol the diffusive magnetic flux transport in stars.Comment: 41 pages, 7 figures. Invited review chapter on on magnetic field generation in stars to appear in Space Science Reviews, Springe

Strongly magnetized pulsars: explosive events and evolution

Well before the radio discovery of pulsars offered the first observational confirmation for their existence (Hewish et al., 1968), it had been suggested that neutron stars might be endowed with very strong magnetic fields of $10^{10}$-$10^{14}$G (Hoyle et al., 1964; Pacini, 1967). It is because of their magnetic fields that these otherwise small ed inert, cooling dead stars emit radio pulses and shine in various part of the electromagnetic spectrum. But the presence of a strong magnetic field has more subtle and sometimes dramatic consequences: In the last decades of observations indeed, evidence mounted that it is likely the magnetic field that makes of an isolated neutron star what it is among the different observational manifestations in which they come. The contribution of the magnetic field to the energy budget of the neutron star can be comparable or even exceed the available kinetic energy. The most magnetised neutron stars in particular, the magnetars, exhibit an amazing assortment of explosive events, underlining the importance of their magnetic field in their lives. In this chapter we review the recent observational and theoretical achievements, which not only confirmed the importance of the magnetic field in the evolution of neutron stars, but also provide a promising unification scheme for the different observational manifestations in which they appear. We focus on the role of their magnetic field as an energy source behind their persistent emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of "NewCompStar" European COST Action MP1304, 43 pages, 8 figure