Cardiovascular safety of antifracture medications in patients with osteoporosis: A narrative review of evidence from randomized studies

Osteoporosis and cardiovascular (CV) disease share common risk factors and pathophysiology. Low bone mineral density (BMD) and fractures appear to increase the risk for multiple CV diseases. Equally, prevalent CV disease appears to predispose to bone loss and increase fracture rates. This relationship has naturally provoked the hypothesis that stopping bone loss may result in some CV benefit. Secondary analyses of safety and adverse event data from many randomized controlled trials (RCTs) have attempted to clarify this putative association. Recently, the discontinuation of odanacatib (anti-cathepsin K monoclonal antibody) over stroke concerns and the imbalance in ischemic events in romosozumab-treated (anti-sclerostin monoclonal antibody) women compared to bisphosphonate-treated women, has provided further justification to better characterize potential CV benefits and harms of osteoporosis medications. This review delves into the seminal, and other major RCTs of osteoporosis medications and, using both published data and additional information provided on trial registration pages, examines the evidence for CV safety and harms of these medications. Accepted and emerging “off-target” effects are explored for validity, biological plausibility, and clinical importance. A brief research agenda is provided to stimulate the next wave of clinical development and CV understanding of osteoporosis medications. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

Circulation, retention, and mixing of waters within the Weddell-Scotia Confluence, Southern Ocean:The role of stratified Taylor columns

The waters of the Weddell-Scotia Confluence (WSC) lie above the rugged topography of the South Scotia Ridge in the Southern Ocean. Meridional exchanges across the WSC transfer water and tracers between the Antarctic Circumpolar Current (ACC) to the north and the subpolar Weddell Gyre to the south. Here, we examine the role of topographic interactions in mediating these exchanges, and in modifying the waters transferred. A case study is presented using data from a free-drifting, intermediate-depth float, which circulated anticyclonically over Discovery Bank on the South Scotia Ridge for close to 4 years. Dimensional analysis indicates that the local conditions are conducive to the formation of Taylor columns. Contemporaneous ship-derived transient tracer data enable estimation of the rate of isopycnal mixing associated with this column, with values of O(1000 m2/s) obtained. Although necessarily coarse, this is of the same order as the rate of isopycnal mixing induced by transient mesoscale eddies within the ACC. A picture emerges of the Taylor column acting as a slow, steady blender, retaining the waters in the vicinity of the WSC for lengthy periods during which they can be subject to significant modification. A full regional float data set, bathymetric data, and a Southern Ocean state estimate are used to identify other potential sites for Taylor column formation. We find that they are likely to be sufficiently widespread to exert a significant influence on water mass modification and meridional fluxes across the southern edge of the ACC in this sector of the Southern Ocean

Phonon-induced quadrupolar ordering of the magnetic superconductor TmNi2_2B2_2C

We present synchrotron x-ray diffraction studies revealing that the lattice of thulium borocarbide is distorted below T_Q = 13.5 K at zero field. T_Q increases and the amplitude of the displacements is drastically enhanced, by a factor of 10 at 60 kOe, when a magnetic field is applied along [100]. The distortion occurs at the same wave vector as the antiferromagnetic ordering induced by the a-axis field. A model is presented that accounts for the properties of the quadrupolar phase and explains the peculiar behavior of the antiferromagnetic ordering previously observed in this compound.Comment: submitted to PR

Training and assessment of non-technical skills in Norwegian helicopter emergency services: a cross-sectional and longitudinal study

Background Deficient non-technical skills (NTS) among providers of critical care in helicopter emergency medical services (HEMS) is a threat to patient and operational safety. Skills can be improved through simulation-based training and assessment. A previous study indicated that physicians underwent less frequent training compared to pilots and HEMS crew members (HCM) and that all professional groups in Norwegian HEMS received limited training in how to cope with fatigue. Since then, training initiatives and a fatigue risk management project has been initiated. Our study aimed to explore if the frequency of simulation-based training and assessment of NTS in Norwegian HEMS has changed since 2011 following these measures. Methods A cross-sectional web-based survey from October through December 2016, of physicians, HCM and pilots from all civilian Norwegian HEMS-bases reporting the overall extent of simulation-based training and assessment of NTS. Results Of 214 invited, 109 responses were eligible for analysis. The frequency of simulation-based training and assessment of NTS has increased significantly for all professional groups in Norwegian HEMS, most prominently for the physicians. For all groups, the frequency of assessment is generally lower than the frequency of training. Conclusions Physicians in Norwegian HEMS seem to have adjusted to the NTS training culture of the other crew member groups. This might be a consequence of improved NTS training programs. The use of behavioural marker systems systematically in HEMS should be emphasized.publishedVersio

Fermi surface and order parameter driven vortex lattice structure transitions in twin-free YBa2Cu3O7

We report on small-angle neutron scattering studies of the intrinsic vortex lattice (VL) structure in detwinned YBa2Cu3O7 at 2 K, and in fields up to 10.8 T. Because of the suppressed pinning to twin-domain boundaries, a new distorted hexagonal VL structure phase is stabilized at intermediate fields. It is separated from a low-field hexagonal phase of different orientation and distortion by a first-order transition at 2.0(2) T that is probably driven by Fermi surface effects. We argue that another first-order transition at 6.7(2) T, into a rhombic structure with a distortion of opposite sign, marks a crossover from a regime where Fermi surface anisotropy is dominant, to one where the VL structure and distortion is controlled by the order-parameter anisotropy.Comment: 4 pages, 3 figures (2 color), minor change

Design Aspects on Winding of an MgB₂ Superconducting Generator Coil

AbstractGenerators based on superconducting rotor coils are considered for future large off-shore wind turbines for their low weight and compact design, and for their possibility to reduce costs. In the 10-20 K temperature range, MgB2 superconductors carry current densities 100 times higher than standard copper conductors at room temperature at one tenth of the wire cost per unit carried current. In the framework of the European project INNWIND.EU, an MgB2 superconducting generator pole will be designed, built and tested. Some of the design aspects of this work with emphasis on the winding process and associated coil insulation are discussed. An overall high current density in the coil is of crucial importance to obtain clear benefits compared to conventional solutions. The wire itself may be the most important parameter in that respect. However, the overall current density of the coil is also influenced by the thickness of the turn-to-turn electrical insulation. Here we discuss the impact of the insulation and suggest the use of a one-step winding process, employing wet-winding, where the applied epoxy also constitutes the insulation layer between turns. In this way the coil is densified by approximately 10% compared to the use of an additional, dedicated, electrical insulation like Kapton for wet-winding or glass-fibre for dry-winding followed by vacuum impregnation. We show the results of a trial winding of 500 m of MgB2 superconducting wire into a double pancake coil using the wet-winding technique. The coil is tested for contacts between the turns to evaluate the suggested one-step wet-winding process

Optimal Design and Tolerancing of Compressor Blades Subject to Manufacturing Variability

This paper presents a computational approach for optimal robust design and tolerancing of turbomachinery compressor blades that are subject to geometric variability. This approach simultaneously determines the optimal blade geometry and manufacturing tolerances to minimize the overall cost of producing and operating the resulting compressor blades. A pathwise sensitivity method is used to compute gradient information that is in turn used to optimize the design and tolerances. Results for a two-dimensional subsonic compressor are presented, demonstrating the significant performance improvements that can be achieved using the proposed approach.Pratt & Whitney Aircraft CompanyBoeing Compan