Powers of the likelihood ratio test and the correlation test using empirical bayes estimates for various shrinkages in population pharmacokinetics.

International audienceWe compared the powers of the likelihood ratio test (LRT) and the Pearson correlation test (CT) from empirical Bayes estimates (EBEs) for various designs and shrinkages in the context of nonlinear mixed-effect modeling. Clinical trial simulation was performed with a simple pharmacokinetic model with various weight (WT) effects on volume (V). Data sets were analyzed with NONMEM 7.2 using first-order conditional estimation with interaction and stochastic approximation expectation maximization algorithms. The powers of LRT and CT in detecting the link between individual WT and V or clearance were computed to explore hidden or induced correlations, respectively. Although the different designs and variabilities could be related to the large shrinkage of the EBEs, type 1 errors and powers were similar in LRT and CT in all cases. Power was mostly influenced by covariate effect size and, to a lesser extent, by the informativeness of the design. Further studies with more models are needed

Extended Edge States in Finite Hall Systems

We study edge states of a random Schroedinger operator for an electron submitted to a magnetic field in a finite macroscopic two dimensional system of linear dimensions equal to L. The y direction is L-periodic and in the x direction the electron is confined by two smoothly increasing parallel boundary potentials. We prove that, with large probability, for an energy range in the first spectral gap of the bulk Hamiltonian, the spectrum of the full Hamiltonian consists only on two sets of eigenenergies whose eigenfuntions have average velocities which are strictly positive/negative, uniformly with respect to the size of the system. Our result gives a well defined meaning to the notion of edge states for a finite cylinder with two boundaries, and extends previous studies on systems with only one boundary.Comment: 24 pages, 1 figure; Submitte

New bonded assembly configuration for dynamic mechanical analysis of adhesives

A new sample configuration has been developed in order to study molecular mobility of an adhesive in a bonded assembly configuration by dynamic mechanical analysis. The torsional rectangular mode is used to provide a shear solicitation all along the adherend/adhesive interface. The initial mechanical properties of each assembly's constituent are first investigated as reference. The modulus of aluminum foils used as substrates exhibits a classic elastic component and a slight viscous part due to microstructural changes or stress relaxation. Four relaxation modes are highlighted and identified for epoxy adhesive tested as a bulk material. Its viscoelastic behavior is compared to the one of adhesive tested in assembly configuration. The relaxation modes of the adhesive remain visible in spite of the sample stiffening by aluminum foils. Relaxation modes comparison shows that the temperature of loss modulus associated with the mechanical manifestation of glass transition slightly increases for the assembly configuration. Energy losses during this relaxation are much higher in the assembly configuration. Influence of rigid aluminum substrates is discussed in terms of the adhesively bonded joint solicitation mode

Rivaroxabananddabigatraninpatientsundergoing catheter ablation of atrial fibrillation

Aims: The recent availability of the novel oral anticoagulants (NOACs) may have led to a change in the anticoagulation regimens of patients referred to catheter ablation of atrial fibrillation (AF). Preliminary data exist concerning dabigatran, but information regarding the safety and efficacy of rivaroxaban in this setting is currently scarce. Methods: and results Of the 556 consecutive eligible patients (age 61.0 ± 9.6; 74.6% men; 61.2% paroxysmal AF) undergoing AF catheter ablation in our centre (October 2012 to September 2013) and enroled in a systematic standardized 30-day follow-up period: 192 patients were under vitamin K antagonists (VKAs), 188 under rivaroxaban, and 176 under dabigatran. Peri-procedural mortality and significant systemic or pulmonary thromboembolism (efficacy outcome), as well as bleeding events (safety outcome) during the 30 days following the ablation were evaluated according to anticoagulation regimen. During a 12-month time interval, the use of the NOACs in this population rose from <10 to 70%. Overall, the rate of events was low with no significant differences regarding: thrombo-embolic events in 1.3% (VKA 2.1%; rivaroxaban 1.1%; dabigatran 0.6%; P = 0.410); major bleeding in 2.3% (VKA 4.2%; rivaroxaban 1.6%; dabigatran 1.1%; P = 0.112), and minor bleeding 1.4% (VKA 2.1%; rivaroxaban 1.6%; dabigatran 0.6%; P = 0.464). No fatal events were observed. Conclusion: The use of the NOAC in patients undergoing catheter ablation of AF has rapidly evolved (seven-fold) over 1 year. These preliminary data suggest that rivaroxaban and dabigatran in the setting of catheter ablation of AF are efficient and safe, compared with the traditional VKA

Structure of the calcium pyrophosphate monohydrate phase (Ca2P2O7·H2O): towards understanding the dehydration process in calcium pyrophosphate hydrates

Calcium pyrophosphate hydrate (CPP, Ca2P2O7·nH2O) and calcium orthophosphate compounds (including apatite, octa­calcium phosphate etc.) are among the most prevalent pathological calcifications in joints. Even though only two dihydrated forms of CPP (CPPD) have been detected in vivo (monoclinic and triclinic CPPD), investigations of other hydrated forms such as tetra­hydrated or amorphous CPP are relevant to a further understanding of the physicochemistry of those phases of biological inter­est. The synthesis of single crystals of calcium pyrophosphate monohydrate (CPPM; Ca2P2O7·H2O) by diffusion in silica gel at ambient temperature and the structural analysis of this phase are reported in this paper. Complementarily, data from synchrotron X-ray diffraction on a CPPM powder sample have been fitted to the crystal parameters. Finally, the relationship between the resolved structure for the CPPM phase and the structure of the tetra­hydrated calcium pyrophosphate [beta] phase (CPPT-[beta]) is discussed

Enthalpy relaxation phenomena of epoxy adhesive in operational configuration: Thermal, mechanical and dielectric analyses

Thermal cycling in space environment can cause physical aging of polymers used in structural adhesive bonded joint. Later, they can initiate failure. A methodology to follow physical aging effects on their thermal, mechanical and dielectric properties is applied to a commercial epoxy adhesive. The analytic description, using Tool, Narayanaswamy and Moynihan model gives a good description of the enthalpy relaxation. It is completed by a phenomenological analysis of the evolution of the adhesive thermal transitions, mechanical properties and molecular mobility. Testedsamples with bondedassembly are representative ofin service configurations. The influence of physical aging on the adhesive and the associated bonded assemblies is analyzed

Intermixture of extended edge and localized bulk energy levels in macroscopic Hall systems

We study the spectrum of a random Schroedinger operator for an electron submitted to a magnetic field in a finite but macroscopic two dimensional system of linear dimensions equal to L. The y direction is periodic and in the x direction the electron is confined by two smooth increasing boundary potentials. The eigenvalues of the Hamiltonian are classified according to their associated quantum mechanical current in the y direction. Here we look at an interval of energies inside the first Landau band of the random operator for the infinite plane. In this energy interval, with large probability, there exist O(L) eigenvalues with positive or negative currents of O(1). Between each of these there exist O(L^2) eigenvalues with infinitesimal current O(exp(-cB(log L)^2)). We explain what is the relevance of this analysis to the integer quantum Hall effect.Comment: 29 pages, no figure

Goulphar: rapid access and expertise for standard two-color microarray normalization methods

BACKGROUND: Raw data normalization is a critical step in microarray data analysis because it directly affects data interpretation. Most of the normalization methods currently used are included in the R/BioConductor packages but it is often difficult to identify the most appropriate method. Furthermore, the use of R commands for functions and graphics can introduce mistakes that are difficult to trace. We present here a script written in R that provides a flexible means of access to and monitoring of data normalization for two-color microarrays. This script combines the power of BioConductor and R analysis functions and reduces the amount of R programming required. RESULTS: Goulphar was developed in and runs using the R language and environment. It combines and extends functions found in BioConductor packages (limma and marray) to correct for dye biases and spatial artifacts. Goulphar provides a wide range of optional and customizable filters for excluding incorrect signals during the pre-processing step. It displays informative output plots, enabling the user to monitor the normalization process, and helps adapt the normalization method appropriately to the data. All these analyses and graphical outputs are presented in a single PDF report. CONCLUSION: Goulphar provides simple, rapid access to the power of the R/BioConductor statistical analysis packages, with precise control and visualization of the results obtained. Complete documentation, examples and online forms for setting script parameters are available from

Cardiopulmonary responses and muscle strength influence running performance parameters differently at different slopes

The analysis of trail-running performance appears to be complex and cardio-respiratory and muscular factors could have a variable importance depending on the inclination. Our study aims to determine the role of these parameters in performance. 13 subjects with heterogeneous levels participated in the study. They carried out 7 visits including 3 maximal aerobic speed (MAS) test at 1, 10 and 25% slope on treadmill, 3 endurance tests at 100% of the MAS reached at 1, 10 and 25% and an evaluation on isokinetic ergometer at different speeds (60-180-240 {\textdegree}/s). Gas exchange measured during the incremental tests. We were able to identify 2 groups, a performance and a recreational group. We observe a difference in VO2max, MAS at 1 and 10%, and maximal aerobic ascensional speed (MAaS) at 25%, between the 2 groups but no difference in VO2max and exhaustion time at 100% MAS between the different conditions (1-10-25%). Interestingly, at ventilatory thresholds the metabolic parameters, expressed as absolute or relative values, are similar between conditions (10-25%) while the ascensional speed are different. This study suggests that the measurement of ascensional speed is not as relevant as heart rate for controlling intensity given the variety of slope gradients in trail-running races