Global Prospective Safety Analysis of Rivaroxaban.

BACKGROUND: The efficacy of direct oral anticoagulants (DOACs) for stroke prevention in patients with atrial fibrillation (AF) has been established in clinical trials. However, well-conducted, prospective, real-world observational studies of the safety and effectiveness of DOACs are needed. OBJECTIVES: This study sought to assess the real-world safety profile of rivaroxaban through a pooled analysis of patients with AF enrolled in the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) program worldwide. METHODS: A pre-planned pooled analysis of the XANTUS, XANAP (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Asia), and XANTUS-EL (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Latin America and EMEA Region) registries was performed. Patients with AF newly starting rivaroxaban for stroke prevention were followed for 1 year. Primary outcomes were treatment-emergent major bleeding, adverse events (AEs)/serious AEs, and all-cause death. Secondary outcomes included treatment-emergent thromboembolic events and nonmajor bleeding. Major outcomes were centrally adjudicated. RESULTS: Overall, 11,121 patients were included (mean age 70.5 ± 10.5 years; female 42.9%). Comorbidities included heart failure (21.2%), hypertension (76.2%), and diabetes (22.3%). Event rates were: events/100 patient-years: major bleeding 1.7 (95% confidence interval [CI]: 1.5 to 2.0; lowest: Latin America 0.7; highest: Western Europe, Canada, and Israel 2.3); all-cause death 1.9 (95% CI: 1.6 to 2.2; lowest: Eastern Europe 1.5; highest: Latin America, Middle East, and Africa 2.7); and stroke or systemic embolism 1.0 (95% CI: 0.8 to 1.2; lowest: Latin America 0; highest: East Asia 1.8). One-year treatment persistence was 77.4% (lowest: East Asia 66.4%; highest: Eastern Europe 84.4%). CONCLUSIONS: This large, prospective, real-world analysis in 11,121 patients from 47 countries showed low bleeding and stroke rates in rivaroxaban-treated patients with AF, with low treatment discontinuation in different regions of the world. Results were broadly consistent across regions. (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation [XANTUS]; NCT01606995; Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Latin America and EMEA Region [XANTUS-EL]; NCT01800006; and Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Asia [XANAP]; NCT01750788)

A Short-Term Forecasting Model of the Swiss Economy

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Biogeochemical Cycling of Cadmium Isotopes along a High-Resolution Section through the North Atlantic Ocean

Cadmium (Cd) is a bioactive trace element in the oceans, with a nutrient-like distribution that closely matches dissolved phosphate. Seawater-dissolved stable Cd isotope ratios (δ114Cd) are a relatively new parameter, which show much promise for furthering our understanding of the biogeochemical cycling of Cd in the oceans. Here we present a high-resolution paired section of dissolved Cd concentrations and dissolved δ114Cd from 21 open-ocean stations along the US GEOTRACES GA03 transect through the North Atlantic Ocean. Dissolved Cd concentrations along the section are strongly influenced by water-mass distribution and the cycling of Cd. The highest dissolved Cd concentrations (400–540 pmol kg−1) are associated with Antarctic-sourced water masses, whilst biological uptake in the surface ocean results in a strong vertical gradient in dissolved Cd towards the surface, reaching as low as 0.03 pmol kg−1 in western surface waters. Dissolved δ114Cd is also characterized by a vertical gradient from ∼+0.2‰ in the deep ocean to +2‰ to +5‰ in the Cd-depleted surface ocean (relative to NIST SRM 3108). This variability in δ114Cd can be ascribed to mixing of Antarctic and North Atlantic water masses, together with fractionation due to in situ biological uptake of light Cd in the very surface ocean. Subtle deviations from this overall pattern of dissolved Cd concentration and dissolved δ114Cd are observed within low-oxygen waters off North Africa, where a dissolved Cd deficit relative to phosphate is associated with higher dissolved δ114Cd values. Together with elevated particulate Cd and Ba, this suggests that Cd sulfide precipitation is occurring within the water column of the North Atlantic, constituting a potentially important sink for isotopically light Cd. Additionally, the first measurements of dissolved δ114Cd within a hydrothermal plume at the Mid-Atlantic Ridge show that Cd is scavenged from the dissolved phase, leaving the remnant dissolved Cd isotopically heavier. Constraining the significance of these marine sinks for dissolved Cd is important, not only for our understanding of the marine biogeochemical cycling of Cd in the modern oceans, but also for the successful application of the microfossil Cd/Ca proxy and the development of δ114Cd as a tracer for past-ocean biogeochemical cycling

Starlikeness of Libera transformation (II) (Applications of Complex Function Theory to Differential Equations)

The GEOTRACES Intermediate Data Product 2017 (IDP2017) is the second publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2016. The IDP2017 includes data from the Atlantic, Pacific, Arctic, Southern and Indian oceans, with about twice the data volume of the previous IDP2014. For the first time, the IDP2017 contains data for a large suite of biogeochemical parameters as well as aerosol and rain data characterising atmospheric trace element and isotope (TEI) sources. The TEI data in the IDP2017 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at crossover stations. The IDP2017 consists of two parts: (1) a compilation of digital data for more than 450 TEIs as well as standard hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing an on-line atlas that includes more than 590 section plots and 130 animated 3D scenes. The digital data are provided in several formats, including ASCII, Excel spreadsheet, netCDF, and Ocean Data View collection. Users can download the full data packages or make their own custom selections with a new on-line data extraction service. In addition to the actual data values, the IDP2017 also contains data quality flags and 1-σ data error values where available. Quality flags and error values are useful for data filtering and for statistical analysis. Metadata about data originators, analytical methods and original publications related to the data are linked in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2017 as section plots and rotating 3D scenes. The basin-wide 3D scenes combine data from many cruises and provide quick overviews of large-scale tracer distributions. These 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of tracer plumes near ocean margins or along ridges. The IDP2017 is the result of a truly international effort involving 326 researchers from 25 countries. This publication provides the critical reference for unpublished data, as well as for studies that make use of a large cross-section of data from the IDP2017. This article is part of a special issue entitled: Conway GEOTRACES - edited by Tim M. Conway, Tristan Horner, Yves Plancherel, and Aridane G. González