A necessary flexibility condition of a nondegenerate suspension in Lobachevsky 3-space

We show that some combination of the lengths of all edges of the equator of a flexible suspension in Lobachevsky 3-space is equal to zero (each length is taken either positive or negative in this combination).Comment: 20 pages, 13 figure

Volumes of polytopes in spaces of constant curvature

We overview the volume calculations for polyhedra in Euclidean, spherical and hyperbolic spaces. We prove the Sforza formula for the volume of an arbitrary tetrahedron in $H^3$ and $S^3$. We also present some results, which provide a solution for Seidel problem on the volume of non-Euclidean tetrahedron. Finally, we consider a convex hyperbolic quadrilateral inscribed in a circle, horocycle or one branch of equidistant curve. This is a natural hyperbolic analog of the cyclic quadrilateral in the Euclidean plane. We find a few versions of the Brahmagupta formula for the area of such quadrilateral. We also present a formula for the area of a hyperbolic trapezoid.Comment: 22 pages, 9 figures, 58 reference

Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells

CD1d-restricted invariant natural killer T (iNKT) cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. Activation of iNKT cells can protect against multiple diseases in mice but clinical trials in humans have had limited impact. Clinical studies to date have targeted polyclonal mixtures of iNKT cells and we proposed that their subset compositions will influence therapeutic outcomes. We sorted and expanded iNKT cells from healthy donors and compared the phenotypes, cytotoxic activities and cytokine profiles of the CD4+, CD8α+ and CD4−CD8α− double-negative (DN) subsets. CD4+ iNKT cells expanded more readily than CD8α+ and DN iNKT cells upon mitogen stimulation. CD8α+ and DN iNKT cells most frequently expressed CD56, CD161 and NKG2D and most potently killed CD1d+ cell lines and primary leukemia cells. All iNKT subsets released Th1 (IFN-γ and TNF-α) and Th2 (IL-4, IL-5 and IL-13) cytokines. Relative amounts followed a CD8α>DN>CD4 pattern for Th1 and CD4>DN>CD8α for Th2. All iNKT subsets could simultaneously produce IFN-γ and IL-4, but single-positivity for IFN-γ or IL-4 was strikingly rare in CD4+ and CD8α+ fractions, respectively. Only CD4+ iNKT cells produced IL-9 and IL-10; DN cells released IL-17; and none produced IL-22. All iNKT subsets upregulated CD40L upon glycolipid stimulation and induced IL-10 and IL-12 secretion by dendritic cells. Thus, subset composition of iNKT cells is a major determinant of function. Use of enriched CD8α+, DN or CD4+ iNKT cells may optimally harness the immunoregulatory properties of iNKT cells for treatment of disease

IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells.

Activated CD8 T cells develop cytotoxicity against autologous cells bearing foreign Ags and self/tumor Ags. However, self-specific cytolysis needs to be kept under control to avoid overwhelming immunopathology. After peptide vaccination of melanoma patients, we studied molecular and functional properties of T cell subsets specific for the self/tumor Ag Melan-A/MART-1. Ex vivo analysis revealed three Ag-specific effector memory (EM) populations, as follows: CD28-negative EM (EM28(-)) T cells strongly expressing granzyme/perforin, and two EM28(+) subsets, one with high and the other with low level expression of these cytotoxic proteins. For further functional characterization, we generated 117 stable CD8 T cell clones by ex vivo flow cytometry-based sorting of these subsets. All EM28(-)-derived clones lysed target cells with high efficacy. In contrast, EM28(+)-derived clones were heterogenous, and could be classified in two groups, one with high and the other with low killing capacity, correlating with granzyme/perforin expression. High and low killer phenotypes remained surprisingly stable for several months. However, strongly increased granzyme expression and cytotoxicity were observed after exposure to IL-12. Thus, the data reveal a newly identified subset of CD28(+) conditional killer T cells. Because CD28 can mediate strong costimulatory signals, tight cytotoxicity control, as shown in this study through IL-12, may be particularly important for subsets of T cells expressing CD28

MAGE-A protein and MAGE-A10 gene expressions in liver metastasis in patients with stomach cancer

Tumour samples from 71 patients with stomach cancer, 41 patients with liver metastasis (group A) and 15 patients each in stages II–IV (group B) and stage I (group C) without liver metastasis were analysed. MAGE-A protein expression was evaluated by immunohistochemistry using a 6C1 monoclonal antibody and MAGE-A10 mRNA expression was detected by highly sensitive in situ hybridisation using a cRNA probe. Expressions of MAGE-A protein and MAGE-A10 mRNA in group A were detected in 65.9 and 80.5%, respectively. Both protein and gene showed significantly higher expression in group A than those in groups B (6.7, 26.7%) and C (0, 0%) (P=0.0003, P=<0.0001, respectively). MAGE-A10 mRNA expression in liver metastasis was found in eight (88.9%) out of nine patients. The concordant rate between MAGE-A family protein expression and MAGE-A10 mRNA expression in the primary sites was 81.7% (P<0.0001). MAGE-A10 gene expression was associated with reduced survival duration. The results of this study suggest that MAGE-A10 is a possible target in active immunotherapy for advanced stomach cancer

Les parcours de soins de la maladie rénale chronique : apports des nouvelles données de financement au forfait [Communication]

Congrès national Emois 2023 - Nancy, 16 et 17 mars 2023International audienceIntroductionAfin d'améliorer la prise en charge de la maladie rénale chronique (MRC) de stade 4 et 5, une rémunération forfaitaire (forfait MRC) a été mise en place fin 2019 dans les établissements de santé. Ceci a nécessité un nouveau recueil de données. L'objectif était de décrire la file active de patients au niveau national, ses caractéristiques et son évolution entre 2020 et 2022.MéthodesLes données ont été mises à disposition par l'Agence technique de l'information sur l'hospitalisation (ATIH). Les années complètes 2020 et 2021 ainsi que le premier semestre 2022 ont été considérées. Les variables obligatoires du recueil ont été étudiées: caractéristiques démographiques et cliniques des patients et variables d'activité (consultations avec néphrologue, diététicien.ne, infirmier.ère).RésultatsAu total, 137 289 patients ont été inclus, avec un âge médian de 75 ans, dont 39,6 % étaient des femmes. Parmi eux, 3,9 % sont sortis du forfait, car décédés. La file active de patients déclarés s’élevait à 72 127 en 2020, avec 46 328 nouveaux patients en 2021 et 18 834 en 2022. Le nombre d’établissements bénéficiaires était de 351 en 2020, 366 en 2021, 268 au premier semestre 2022. En 2021, la file active médiane déclarée par un site géographique était de 189 patients IIQ[69-325]. La file active comprenait 75 % de patients au stade 4 (25 % stade 5), proportion stable entre les années. En 2021, 93 % des patients avaient bénéficié d'une consultation avec un néphrologue (96 % en 2020), 43 % avec un.e diététicien.ne (44 % en 2020) et 47 % avec infirmier.ère (49 % 2020).Discussion/ConclusionCette étude offre un premier retour au niveau national d'un nouveau recueil de données soins données dans le cadre d'une nouvelle organisation de l'offre de soins. Un chaînage aux données du SNDS apparait important pour une vision complète du parcours des patients. Des questions demeurent notamment sur la réception et l'utilisation du forfait au niveau local et la place des médecins généralistes au sein de cette nouvelle organisation