Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures

Objective To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters. Design Prospective, open-label, long-term mechanism of action study. Setting University clinic. Methods MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6–36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation. Results Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and IL-8 (r=0.25, p=0.01 for swollen joints). Significant decreases from baseline were observed in serum IL-1B, IL-6 and IL-8 concentrations. The most significant changes were observed for IL-6 (p<0.001). Significant increases from baseline were observed in IL-2 release from PBMCs ex vivo (p<0.01). In parallel, multiple statistically significant correlations were observed between MTX PKC measures and immune parameters. The change in swollen joint count correlated inversely with the change in area under the curve (AUC) for MTX (r=−0.63, p=0.007). Conclusions MTX therapy of patients with RA is accompanied by a variety of changes in serum cytokine expression, which in turn correlate strongly with clinical disease activity and MTX pharmacokinetics (PKCs). These data strongly support the notion that MTX mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion

Magnetic structure of the edge-sharing copper oxide chain compound NaCu2O2

Single-crystal neutron diffraction has been used to determine the incommensurate magnetic structure of NaCu2O2, a compound built up of chains of edge-sharing CuO4 plaquettes. Magnetic structures compatible with the lattice symmetry were identified by a group-theoretical analysis, and their magnetic structure factors were compared to the experimentally observed Bragg intensities. In conjunction with other experimental data, this analysis yields an elliptical helix structure in which both the helicity and the polarization plane alternate among copper-oxide chains. This magnetic ground state is discussed in the context of the recently reported multiferroic properties of other copper-oxide chain compounds

Exciton doublet in the Mott-Hubbard LiCuVO4_4 insulator identified by spectral ellipsometry

Spectroscopic ellipsometry was used to study the dielectric function of LiCuVO$_{4}$, a compound comprised of chains of edge-sharing CuO$_4$ plaquettes, in the spectral range (0.75 - 6.5) eV at temperatures (7-300) K. For photon polarization along the chains, the data reveal a weak but well-resolved two-peak structure centered at 2.15 and 2.95 eV whose spectral weight is strongly enhanced upon cooling near the magnetic ordering temperature. We identify these features as an exciton doublet in the Mott-Hubbard gap that emerges as a consequence of the Coulomb interaction between electrons on nearest and next-nearest neighbor sites along the chains. Our results and methodology can be used to address the role of the long-range Coulomb repulsion for compounds with doped copper-oxide chains and planes.Comment: 4 pages with 4 figures and EPAPS supplementary online material (3 pages with 4 figures), accepted in Phys. Rev. Let

Evidence of a bond-nematic phase in LiCuVO4

Polarized and unpolarized neutron scattering experiments on the frustrated ferromagnetic spin-1/2 chain LiCuVO4 show that the phase transition at HQ of 8 Tesla is driven by quadrupolar fluctuations and that dipolar correlations are short-range with moments parallel to the applied magnetic field in the high-field phase. Heat-capacity measurements evidence a phase transition into this high-field phase, with an anomaly clearly different from that at low magnetic fields. Our experimental data are consistent with a picture where the ground state above HQ has a next-nearest neighbour bond-nematic order along the chains with a fluid-like coherence between weakly coupled chains.Comment: 5 pages, 4 figures. To appear in Phys. Rev. Let

Evidence of secondary relaxations in the dielectric spectra of ionic liquids

We investigated the dynamics of a series of room temperature ionic liquids based on the same 1-butyl-3-methyl imidazolium cation and different anions by means of broadband dielectric spectroscopy covering 15 decades in frequency (10^(-6)-10^9 Hz), and in the temperature range from 400 K down to 35 K. An ionic conductivity is observed above the glass transition temperature T_{g} with a relaxation in the electric modulus representation. Below T_{g}, two relaxation processes appear, with the same features as the secondary relaxations typically observed in molecular glasses. The activation energy of the secondary processes and their dependence on the anion are different. The slower process shows the characteristics of an intrinsic Johari-Goldstein relaxation, in particular an activation energy E_{beta}=24k_{B}T_{g} is found, as observed in molecular glasses.Comment: Major revision, submitted to Phys. Rev. Let

Signatures of Electronic Correlations in Optical Properties of LaFeAsO1−x_{1-x}Fx_x

Spectroscopic ellipsometry is used to determine the dielectric function of the superconducting LaFeAsO$_{0.9}$F$_{0.1}$ ($T_c$ = 27 K) and undoped LaFeAsO polycrystalline samples in the wide range 0.01-6.5 eV at temperatures 10 $\leq T \leq$ 350 K. The free charge carrier response in both samples is heavily damped with the effective carrier density as low as 0.040$\pm$0.005 electrons per unit cell. The spectral weight transfer in the undoped LaFeAsO associated with opening of the pseudogap at about 0.65 eV is restricted at energies below 2 eV. The spectra of superconducting LaFeAsO$_{0.9}$F$_{0.1}$ reveal a significant transfer of the spectral weight to a broad optical band above 4 eV with increasing temperature. Our data may imply that the electronic states near the Fermi surface are strongly renormalized due to electron-phonon and/or electron-electron interactions.Comment: 4 pages, 4 figures, units in Fig.2 adde

Vote-Independence: A Powerful Privacy Notion for Voting Protocols

International audienceRecently an attack on ballot privacy in Helios has been discovered [20], which is essentially based on copying other voter's votes. To capture this and similar attacks, we extend the classical threat model and introduce a new security notion for voting protocols: Vote-Independence. We give a formal definition and analyze its relationship to established privacy properties such as Vote-Privacy, Receipt-Freeness and Coercion-Resistance. In particular we show that even Coercion-Resistant protocols do not necessarily ensure Vote-Independence

Electronic and phononic properties of the chalcopyrite CuGaS2

The availability of ab initio electronic calculations and the concomitant techniques for deriving the corresponding lattice dynamics have been profusely used for calculating thermodynamic and vibrational properties of semiconductors, as well as their dependence on isotopic masses. The latter have been compared with experimental data for elemental and binary semiconductors with different isotopic compositions. Here we present theoretical and experimental data for several vibronic and thermodynamic properties of CuGa2, a canonical ternary semiconductor of the chalcopyrite family. Among these properties are the lattice parameters, the phonon dispersion relations and densities of states (projected on the Cu, Ga, and S constituents), the specific heat and the volume thermal expansion coefficient. The calculations were performed with the ABINIT and VASP codes within the LDA approximation for exchange and correlation and the results are compared with data obtained on samples with the natural isotope composition for Cu, Ga and S, as well as for isotope enriched samples.Comment: 9 pages, 8 Figures, submitted to Phys. Rev