Regulatory CD8 T cells that recognize Qa-1 expressed by CD4 T-helper cells inhibit rejection of heart allografts

Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)-CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1-restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection

The behaviour of repeat visitors to museums: Review and empirical findings

This study presents a theoretical and operational framework for analysing repeat visit to museums. Starting from the literature on repeat visit in tourism, the specificities of these cultural attractions are made explicit through a review of theoretical and applied works. Consistently with previous contributors, the paper suggests that the analysis of actual past behaviours has to be preferred to the one of attitudes. The application of proper econometric models is also remarked in order to put into account individual profiles. Information coming from three techniques is then used in an integrated way in order to provide a more comprehensive view of the phenomenon. Evidence from an ad hoc survey suggests the necessity to give a greater attention to perceived cultural value during the visit, promoting cultural events during the week and addressed to children, and taking care of those visitors that come from far places also through an integrated tourist supply. © 2013 Springer Science+Business Media Dordrecht

The appropriate management of persisting pain after spine surgery: a European panel study with recommendations based on the RAND/UCLA method

Purpose: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS. Methods: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1–3 and 7–9). Results: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability. Conclusions: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care. Graphical abstract: These slides can be retrieved under Electronic Supplementary Material. [Figure not available: see fulltext.

Hydrothermal Stability of Ordered Surfactant-Templated Titania

International audienceIn this study, we have investigated the hydrothermal stability of mesostructured titania having either amorphous or nanocrystalline walls. On the basis of Raman, XRD, and N-2 adsorption-desorption analysis, we have shown that the alteration of the mesostructure is mainly due to the appearance or the growth of anatase particles during the treatment into boiling water. Transformation of amorphous TiO2 into the anatase nuclei is catalyzed by water, which adsorbs to the titania surface to form bridges between surface OH groups of different octaedra. Then, the growth of the nuclei leads to a progressive loss of the mesopore ordering, which is accompanied by a decrease in the specific surface area. Consequently, the growth of the anatase particles involves a complete collapse of the mesostructure. A comparison of the characteristics of the materials with amorphous and nanocrystalline walls also provides evidence that the latter are more stable when treated with boiling water. Finally, the photocatalytic activity of the two kinds of titania materials, after different immersion times into boiling water, has been also tested on the photodegradation of methyl orange

Multi-scale modeling of polymer nanocomposites

Mean-field (MF) homogenization describes composite behavior based on average stress/strain tensors on phase and composite level and combines analytical formulae with numerical simulation. MF can handle coated inclusions, which is important for nanocomposite modeling because the coating properties can emulate the force between nanoparticles. Also for matrix-particle interaction, the coating can represent a real, new phase, e.g. matrix material with density variations. Two-level homogenization is applied to densely packed clusters of particles and voids. To verify MF predictions, realistic FE models are constructed representing microstructure geometry, including cluster size distribution from image analysis. The MF predicted stiffness, obtained in seconds, are less than 5% off the FE predicted stiffness, obtained in hours. In FEA, the coating can represent electron tunneling and percolation, increasing composite conductivity with many orders of magnitude. Results are compared with experimental data from industrial partner.Anglai