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

Theory Learning with Symmetry Breaking

This paper investigates the use of a Prolog coded SMT solver in tackling a well known constraints problem, namely packing a given set of consecutive squares into a given rectangle, and details the developments in the solver that this motivates. The packing problem has a natural model in the theory of quantifier-free integer difference logic, a theory supported by many SMT solvers. The solver used in this work exploits a data structure consisting of an incremental Floyd-Warshall matrix paired with a watch matrix that monitors the entailment status of integer difference constraints. It is shown how this structure can be used to build unsatisfiable theory cores on the fly, which in turn allows theory learning to be incorporated into the solver. Further, it is shown that a problem-specific and non-standard approach to learning can be taken where symmetry breaking is incorporated into the learning stage, magnifying the effect of learning. It is argued that the declarative framework allows the solver to be used in this white box manner and is a strength of the solver. The approach is experimentally evaluated

Photosynthetic responses of Amygdalus arabica Olivier and Atriplex canescens (Pursh) Nutt. to drought stress under field conditions

The central Anatolian region of Turkey is exposed to increasing temperatures and severe drought stress. Due to aridity and desertification brought about by global warming, climate change and overutilization, plant species in these regions are under the risk of extinction. Thus, plant species have to adapt to these harsh environmental conditions of extremely high temperatures and low precipitation. In this study, gas exchange and water potentials of the Arabian almond tree Amygdalus arabica Olivier (C3-photosynthesis) and four-winged saltbush Atriplex canescens (Pursh) Nutt. (C4-photosynthesis), two drought-tolerant woody species planted previously in an effort to reduce desertification at Karapınar, Konya, and Central Anatolian Region, were periodically measured from May until September under field conditions. Net photosynthesis and transpiration rates, mid-day water potential and water use efficiency were determined throughout the vegetation period in 2015. Maximum net photosynthetic rates were 12.4 μmol m–2 s–1 in the Arabian almond tree and 29.7 μmol m–2 s–1 in four-winged saltbush, measured in July and September, respectively. Also, the highest transpiration rates were 4.8 mmol m–2 s–1 in the Arabian almond tree and 7.1 mmol m–2 s–1 in four-winged saltbush. Maximum water use efficiency values were measured in June in both species, which made up 5.7 and 7.7 mmol CO2 mol–1 H2O for the Arabian almond tree and four-winged saltbush, respectively. Lowest midday water potentials for both species were recorded in August. The results indicate that both species have the ability to tolerate drought stress in the region, though due to its C4 nature of photosynthesis, the four-winged saltbush might overcome those stresses more efficiently than the Arabian almond tree in arid and barren areas

Does Gender Impact Intensity of Care Provided to Older Medical Intensive Care Unit Patients?

Introduction. Women receive less aggressive critical care than men based on prior studies. No documented studies evaluate whether men and women are treated equally in the medical intensive care unit (MICU). The Therapeutic Intervention Scoring System-28 (TISS-28) has been used to examine gender differences in mixed ICU studies. However, it has not been used to evaluate equivalence of care in older MICU patients. We hypothesize that given nonsignificant, baseline health differences between genders at MICU admission, the level of care provided would be equivalent. Methods. Prospective cohort of 309 patients ≥60 years old in the MICU of an urban university teaching hospital. Explanatory variables were demographic data and baseline measures. Primary outcomes were TISS-28 scores and MICU interventions. We compare TISS-28 scores by gender using a statistical test of equivalence. Results. Women were older and had more chronic respiratory failure at MICU admission. Using equivalence limits of ±15% on gender-based scores of TISS-28, MICU interventions were equivalent. Supplementary analysis showed no statistically significant association between gender and mortality. Conclusions. In contrast with other reports from the cardiac critical care literature, as measured by the TISS-28, gender-based care delivered to older MICU patients in this cohort was equivalent

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

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

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&