Head‐to‐Head comparison of consensus‐recommended platelet function tests to assess P2Y12 Inhibition : insights for multi‐center trials

The vasodilator‐associated stimulated phosphoprotein (VASP) phosphorylation level is a highly specific method to assess P2Y12 receptor inhibition. Traditionally, VASP phosphorylation is analyzed by flow cytometry, which is laborious and restricted to specialized laboratories. Recently, a simple ELISA kit has been commercialized. The primary objective of this study was to compare the performance of VASP assessment by ELISA and flow cytometry in relation to functional platelet aggregation testing by Multiplate® whole‐blood aggregometry. Blood from 24 healthy volunteers was incubated with increasing concentration of a P2Y12 receptor inhibitor (AR‐C 66096). Platelet function testing was carried out simultaneously by Multiplate® aggregometry and by VASP assessment through ELISA and flow cytometry. As expected, increasing concentrations of the P2Y12 receptor inhibitor induced a proportional inhibition of platelet aggregation and P2Y12 receptor activation across the modalities. Platelet reactivity index values of both ELISA‐ and flow cytometry‐ based VASP assessment methods correlated strongly (r = 0.87, p < 0.0001) and showed minimal bias (1.05%). Correlation with Multiplate® was slightly higher for the flow cytometry‐based VASP assay (r = 0.79, p < 0.0001) than for the ELISA‐based assay (r = 0.69, p < 0.0001). Intraclass correlation (ICC) was moderate for all the assays tested (ICC between 0.62 and 0.84). However, categorization into low, optimal, or high platelet reactivity based on these assays was strongly concordant (κ between 0.86 and 0.92). In conclusion, the consensus‐recommended assays with their standardized cut‐offs should not be used interchangeably in multi‐center clinical studies but, rather, they should be standardized throughout sites

On the effects of uniform and non-uniform sea-level rise on European Shelf tides

International audienceIn theory, sea-level rise (SLR) has not only a direct linear effect on the total instantaneous water level, but also an indirect effect on tide, surge, waves and induced sediment transport. Focusing on the SLR effect on the water level, the total water level x can be written: x=xT,0+xS,0+SLR+IWith xT,0 and xS,0 being respectively the tide and the surge water level contributions for SLR=0. SLR is the sea-level rise contribution and I the term of interaction between xT,0, xS,0 and SLR. Several studies have investigated the effects of SLR on the tides of the western European continental shelf (mainly the M2 component). We further investigate this issue using a modelling based approach, considering uniform SLR scenarios from 0.25m to +10 m above present day sea level.Assuming that coastal defenses are constructed along present day shorelines, the patterns of change in high tide levels (annual maximum water level) are spatially similar, regardless of the magnitude of sealevel rise (i.e., the sign of the change remains the same, regardless of the SLR scenario) over most of the area (70%). Notable increases in high tide levels occur especially in the northern Irish Sea, the southern part of the North Sea and the German Bight, and decreases occur mainly in the western English Channel. These changes are generally proportional to SLR, as long as SLR remains smaller than 2 m. Depending on the location, they can account for +/15% of regional SLR. High tide levels and the M2 component exhibit slightly different patterns. Analysis of the 12 largest tidal components highlights the need to take into account at least the M2, S2, N2, M4, MS4 and MN4 components when investigating the effects of SLR on tides. Changes in high tide levels are much less proportional to SLR when flooding is allowed, in particular in the German Bight. However, some areas (e.g., the English Channel) are not very sensitive to this option, meaning that the effects of SLR would be predictable in these areas, even if future coastal defense strategies are ignored. Additional numerical computations show that SLR induced tidal changes result from the competition between reductions in bed friction damping, changes in resonance properties and increased reflection at the coast, i.e., local and non local processes.The above results are based on the assumption that sea level will rise uniformly. However, future sea-level rise will display regional variability. We therefore analyze to what extent tidal changes induced by a uniform or a non-uniform SLR would be significantly different by considering a synthetic idealized nonuniform SLR field, based on Slangen et al. (2014). This SLR scenario corresponds to the current state of knowledge of the regional variability of future sea-level rise on the European continental shelf, given a global mean sea-level rise of 0.5 m by 2100 and the RCP4.5 climate change scenario. The preliminary estimate of tidal changes by 2100 under a plausible non-uniform SLR scenario shows that even if changes display similar patterns, high water levels appear to be sensitive to the non-uniformity of SLR

A-site order in rhombohedral perovskite-like oxides La2-xSrxCoTiO6 (0.6 <= x <= 1.0)

The evolution of the room-temperature structure of the oxide series LaSrCoTiO (0.6 ≤ x ≤ 1.0) was studied as a function of the Sr content using different diffraction techniques and applying the symmetry-adapted modes formalism (AMPLIMODES). The title compounds adopt perovskite-like structures of rhombohedral symmetry with an octahedral tilting scheme (aaa) with either space group R3¯c or R32. The latter symmetry is observed in those cases (for x ≃ 0.6) where additional rock-salt-like ordering of La and Sr is produced in the perovskite A sites. Two composition-driven phase transitions are observed in the whole series LaSrCoTiO (0.0 ≤ x ≤ 1.0). Using the concept of internal pressure, the effect of doping with Sr on the structure can be properly discussed. Both phase transitions seem to be of first order since they can be associated with discontinuities either in the entropy or in the structure. The first transition (P2/n → Pnma) occurs as the B cations become totally disordered. Along the whole compositional range the modes responsible for the out-of-phase tilting of BO6 octahedra remain active, but those associated with the in-phase octahedral tilting vanish for x ≥ 0.6, this being associated with the second transition (Pnma → R3¯c). Finally, for x = 1.0 the three pseudo-cubic cell parameters become very similar, pointing to a transition to a cubic structure which could be obtained by applying pressure or raising the temperature.We thank Ministerio de Economía y Competitividad and Comunidad de Madrid for funding the projects MAT2013-46452-C4-1-R, MAT2013-46452-C4-4-R, PIB2010JP-00181 and S2013/MIT-2753, respectively. Financial support from Universidad San Pablo is also acknowledged. We acknowledge Consejo Superior de Investigaciones Científicas for financial support and for provision of synchrotron radiation facilities, and we would like to thank beamline staff for assistance in using the BM25-SpLine line