Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

WEC-Sim/WEC-Sim: v6.0

<h2>New Features</h2> <ul> <li>initial commit largeXYDispOption by @dforbush2 in https://github.com/WEC-Sim/WEC-Sim/pull/877</li> <li>Update coordinate system figure by @JiaMiGit in https://github.com/WEC-Sim/WEC-Sim/pull/931</li> <li>Property validation for WEC-Sim objects by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/904</li> <li>Dev: adding ampSpectraForWS function by @dforbush2 in https://github.com/WEC-Sim/WEC-Sim/pull/907</li> <li>Customizable DOFs for plotBEMIO by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/944</li> <li>Calculation_of_Ainf_using_radiationIRF.m by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/946</li> <li>Update citation names by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/954</li> <li>Update getDofNames() by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/957</li> <li>included readCAPYTAINE() argument to explicitly define KH.dat & Hydro… by @dav-og in https://github.com/WEC-Sim/WEC-Sim/pull/962</li> <li>Extract mask variable by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/958</li> <li>Add tests to check that SLX file versions do not exceed R2020b by @H0R5E in https://github.com/WEC-Sim/WEC-Sim/pull/919</li> <li>Products of Inertia in WEC-Sim by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/981</li> <li>Pull bug fixes #954, #999, #1002 from master into dev by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/1011</li> <li>updating readNEMOH based on #983 by @kmruehl in https://github.com/WEC-Sim/WEC-Sim/pull/990</li> <li>Remove 'fixed' mass option from OSWEC input file by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1022 and https://github.com/WEC-Sim/WEC-Sim/pull/1024</li> <li>Save the applied added mass time series by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/1023</li> <li>Update tutorials by @kmruehl in https://github.com/WEC-Sim/WEC-Sim/pull/1030</li> <li>Control applications docs by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1018</li> <li>Update read- and writeBEMIOH5 to allow for pressure integration for mean drift by @nathanmtom in https://github.com/WEC-Sim/WEC-Sim/pull/1046</li> <li>Add function to read h5 file to hydro data structure by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1048</li> <li>Update radiationIRF.m by @nathanmtom in https://github.com/WEC-Sim/WEC-Sim/pull/1045</li> <li>Normalize quaternion to increase simulation robustness by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/1049</li> <li>Plot bemio features by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1034</li> <li>Updates to Morison Element Implementation by @nathanmtom in https://github.com/WEC-Sim/WEC-Sim/pull/1052</li> <li>Moving PTO-Sim to main WEC-Sim library by @jleonqu in https://github.com/WEC-Sim/WEC-Sim/pull/1057</li> <li>Add windows runner to dev branch unit test workflow by @H0R5E in https://github.com/WEC-Sim/WEC-Sim/pull/1061</li> <li>Update docs dependencies by @H0R5E in https://github.com/WEC-Sim/WEC-Sim/pull/1080</li> <li>Type property pto sim by @jleonqu in https://github.com/WEC-Sim/WEC-Sim/pull/1064</li> <li>Added mass updates by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/1058</li> <li>Feature paraview by @agmoore4 in https://github.com/WEC-Sim/WEC-Sim/pull/1081</li> <li>Paraview documentation hyperlink fix by @agmoore4 in https://github.com/WEC-Sim/WEC-Sim/pull/1093</li> <li>use capytaine v2 to compute hydrostatics by @dav-og in https://github.com/WEC-Sim/WEC-Sim/pull/1092</li> <li>Update paraview doc images by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1098</li> <li>readNEMOH update to be compatible with v3.0.0 release (but not QTF) by @nathanmtom in https://github.com/WEC-Sim/WEC-Sim/pull/1087</li> <li>Add simple direct drive PTO model by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1106</li> <li>Control+pto docs by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1108</li> <li>MOST Capabilities - Continuation by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/1127</li> <li>Implement an FIR filter to calculate radiation forces by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/1071</li> <li>Updating documentation to include links for the Advanced Features Web… by @jleonqu in https://github.com/WEC-Sim/WEC-Sim/pull/1126</li> <li>Multiple Wave Spectra by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/1130</li> <li>Update WECSim_Lib_Body_Elements.slx for N Waves Applications by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/1133</li> <li>Update to MoorDyn v2 by @RyanDavies19 in https://github.com/WEC-Sim/WEC-Sim/pull/1134</li> <li>Updating WEC-Sim tests for dev branch by @kmruehl in https://github.com/WEC-Sim/WEC-Sim/pull/1142</li> </ul> <h2>Bug Fixes</h2> <ul> <li>Remove fixed mass option by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/856</li> <li>Move run('stopWecSim') to wecSim.m by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/885</li> <li>Pull bug fixes into dev by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/900</li> <li>Save slx files in 2020b fixes #920 by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/923</li> <li>Fix readCAPYTAINE by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/884</li> <li>Fixes saveViz feature for elevation import by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/929</li> <li>Fix wave elevation import with rampTime = 0 by @jtgrasb in https://github.com/WEC-Sim/WEC-Sim/pull/917</li> <li>readCapytaine_fixes_for_reading_dataformats_correctly by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/947</li> <li>Pull #954 into dev by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/955</li> <li>Bug fix for direction in readCapytaine by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/999</li> <li>Fix sign bug reported on issue #993 by @jleonqu in https://github.com/WEC-Sim/WEC-Sim/pull/1002</li> <li>Dev: reverts PR 910, fixing error in nonLinearBuoyancy by @dforbush2 in https://github.com/WEC-Sim/WEC-Sim/pull/1017</li> <li>Fix the transpose of linear restoring matrix to make roll mode rows to be 0 by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/1032</li> <li>Bugfix resolving documentation build error by @kmruehl in https://github.com/WEC-Sim/WEC-Sim/pull/1059</li> <li>fix_readWAMIT_and_writeBEMIOh5 by @salhus in https://github.com/WEC-Sim/WEC-Sim/pull/1065</li> <li>Pulling master bugfixes into dev by @kmruehl in https://github.com/WEC-Sim/WEC-Sim/pull/1101</li> <li>Bug fixes for v6.0 by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/1136</li> <li>Path fix for BEMIO example by @akeeste in https://github.com/WEC-Sim/WEC-Sim/pull/1144</li> </ul> <h2>New Contributors</h2> <ul> <li>@JiaMiGit made their first contribution in https://github.com/WEC-Sim/WEC-Sim/pull/931</li> <li>@agmoore4 made their first contribution in https://github.com/WEC-Sim/WEC-Sim/pull/1081</li> <li>@RyanDavies19 made their first contribution in https://github.com/WEC-Sim/WEC-Sim/pull/1134</li> </ul> <h2>Issues and Pull Reqeusts</h2> <ul> <li>>130 issues closed since v5.0.1</li> <li>>74 PRs merged since v5.0.1</li> <li><strong>v6.0 Changelog</strong>: https://github.com/WEC-Sim/WEC-Sim/compare/v5.0.1...v6.0</li> </ul&gt

Age refinement and basin evolution of the North Rifian Corridor (Morocco) : No evidence for a marine connection during the Messinian Salinity Crisis

The connection between the Mediterranean and the open ocean during the Messinian and the Messinian salinity crisis (MSC) remains largely unsolved; however, such a connection is required to supply the salts required for the formation of the thick evaporite successions deposited during the MSC. A potential candidate for a Mediterranean-Atlantic connection is the northern branch of the Rifian Corridor through Morocco, but existing biostratigraphic constraints of unspecified late Tortonian – Messinian age are insufficient to test the hypothesis. We present new calcareous plankton biostratigraphic data, using among others an improved planktonic foraminiferal zonal scheme that is based on an assemblage- rather than on a typology-based taxonomic concept. The results of this study invariably reveal a late Tortonian age for the youngest open marine sediments in the individual Intramontane Basins in the central part of the North Rifian Corridor (NRC) and no marine sediments of Messinian age have been found. The high sedimentation rates and the observed shallowing in the top part of several NRC successions suggest that, although the marine connection through the NRC may have continued in the earliest Messinian, it was likely closed before ~ 7.0–7.2 Ma, i.e. well before the onset of the MSC. This closure is likely related to a phase of enhanced and localised uplift in the Rif foreland and excludes the North Rifian Corridor as the long-lasting marine connection between the Mediterranean and open ocean during most of the MSC