On hyperbolic once-punctured-torus bundles III: Comparing two tessellations of the complex plane

To each once-punctured-torus bundle, $T_\phi$, over the circle with pseudo-Anosov monodromy $\phi$, there are associated two tessellations of the complex plane: one, $\Delta(\phi)$, is (the projection from $\infty$ of) the triangulation of a horosphere at $\infty$ induced by the canonical decomposition into ideal tetrahedra, and the other, $CW(\phi)$, is a fractal tessellation given by the Cannon-Thurston map of the fiber group switching back and forth between gray and white each time it passes through $\infty$. In this paper, we study the relation between $\Delta(\phi)$ and $CW(\phi)$.Comment: Version 1. 43 pages. 13 .eps figure

Relative Hyperbolicity, Trees of Spaces and Cannon-Thurston Maps

We prove the existence of continuous boundary extensions (Cannon-Thurston maps) for the inclusion of a vertex space into a tree of (strongly) relatively hyperbolic spaces satisfying the qi-embedded condition. This implies the same result for inclusion of vertex (or edge) subgroups in finite graphs of (strongly) relatively hyperbolic groups. This generalises a result of Bowditch for punctured surfaces in 3 manifolds and a result of Mitra for trees of hyperbolic metric spaces.Comment: 27pgs No figs, v3: final version, incorporating referee's comments, to appear in Geometriae Dedicat

A Combination Theorem for Metric Bundles

We define metric bundles/metric graph bundles which provide a purely topological/coarse-geometric generalization of the notion of trees of metric spaces a la Bestvina-Feighn in the special case that the inclusions of the edge spaces into the vertex spaces are uniform coarsely surjective quasi-isometries. We prove the existence of quasi-isometric sections in this generality. Then we prove a combination theorem for metric (graph) bundles (including exact sequences of groups) that establishes sufficient conditions, particularly flaring, under which the metric bundles are hyperbolic. We use this to give examples of surface bundles over hyperbolic disks, whose universal cover is Gromov-hyperbolic. We also show that in typical situations, flaring is also a necessary condition.Comment: v3: Major revision: 56 pages 5 figures. Many details added. Characterization of convex cocompact subgroups of mapping class groups of surfaces with punctures in terms of relative hyperbolicity given v4: Final version incorporating referee comments: 63 pages 5 figures. To appear in Geom. Funct. Ana

Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria

Background: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. Objectives: The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. Methods: Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (60 mL/min/1.73 m2) and UACR (300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. Results: A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR 300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). Conclusions: Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791

Expression of costimulatory molecules in the bovine corpus luteum

BACKGROUND: Bovine luteal parenchymal cells express class II major histocompatibility complex (MHC) molecules and stimulate class II MHC-dependent activation of T cells in vitro. The ability of a class II MHC-expressing cell type to elicit a response from T cells in vivo is also dependent on expression of costimulatory molecules by the antigen presenting cell and delivery of a costimulatory signal to the T cell. Whether bovine luteal parenchymal cells express costimulatory molecules and can deliver the costimulatory signal is currently unknown. METHODS: Bovine luteal tissue was collected during the early (day 5; day of estrus = day 0), mid (day 11–12), or late (day 18) luteal phase of the estrous cycle, and at 0, 0.5, 1, 4, 12 or 24 hours following administration of PGF2alpha to cows on day 10 of the estrous cycle. Northern analysis was used to measure CD80 or CD86 mRNA concentrations in luteal tissue samples. Mixed luteal parenchymal cell cultures and purified luteal endothelial cell cultures were prepared, and real-time RT-PCR was used to examine the presence of CD80 and CD86 mRNA in each culture type. Monoclonal antibodies to CD80 and CD86 were added to a mixed luteal parenchymal cell-T cell co-culture in vitro T cell proliferation assay to assess the functional significance of costimulatory molecules on activation of T lymphocytes by luteal parenchymal cells. RESULTS: Northern analysis revealed CD80 and CD86 mRNAs in luteal tissue, with greatest steady-state concentrations at midcycle. CD80 and CD86 mRNAs were detected in mixed luteal parenchymal cell cultures, but only slight amounts of CD80 (and not CD86) mRNA were detected in cultures of luteal endothelial cells. Luteinizing hormone, PGF2alpha and TNF-alpha were without effect on concentrations of CD80 or CD86 mRNA in mixed luteal parenchymal cells cultures. Anti-CD80 or anti-CD86 monoclonal antibodies inhibited T cell proliferation in the in vitro T cell proliferation assay. CONCLUSION: It can be concluded from this study that parenchymal cells within the bovine CL express functional costimulatory molecules that facilitate interactions between with T cells, and these components of the antigen presentation pathway are expressed maximally in the midcycle CL

High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer.

To evaluate and compare autocrine expression and production of interleukin-6 (IL-6), a pleiotropic cytokine involved in the resistance to cytotoxic agents and inhibition of anti-tumor immune function in endometrial carcinoma in vitro as well as in vivo. PATIENTS AND METHODS: IL-6 gene expression levels were evaluated in twenty-four primary endometrial tumors including 14 endometrioid carcinomas (EC) and 10 uterine serous papillary carcinoma (USPC) as well as in normal control endometrial cells (NEC) by real-time PCR. Secretion of IL-6 protein by 6 primary endometrial tumor cultures including USPC and EC was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) in vitro. Finally, IL-6 concentration in 71 serum samples including 20 apparently healthy women, 19 women with benign abdominal diseases, 19 women with primary EC, and 13 USPC patients was studied. RESULTS: IL-6 gene expression levels were significantly higher in USPC when compared to EC (mean copy number by RT-PCR = 313 +/- 55 vs. 53 +/- 11, USPC vs. EC, respectively: P < 0.01). IL-6 serum concentrations between normal healthy females (range 0.01-21.23 pg/ml; mean 3.1 pg/ml) and benign disease patients (range 0.01-95.77 pg/ml; mean 13.07 pg/ml) were not statistically different. In contrast, significantly higher levels of IL-6 were detected in both patients with EC (range 2.86-82.13 pg/ml; mean 20.43 pg/ml) and patients with UPSC (range 16.3-500.1 pg/ml; mean 125.7 pg/ml) when compared to the healthy females (P < 0.01), with a mean serum IL-6 level in USPC patients 6.1-fold higher when compared to EC patients (P < 0.03). Accordingly, higher levels of IL-6 secretion were noted in primary USPC cell lines (mean 3121 pg/ml, range between 1099 and 5017 pg/ml/10(5) cells/48 h) when compared to primary EC (mean 88, range between 19 and 112 pg/ml/10(5) cells/48 h) (P < 0.01) in vitro. CONCLUSIONS: IL-6 is highly expressed in USPC, and it is released in high concentration in the serum of USPC patients. IL-6 may be a novel biomarker for USPC. Drugs used to inhibit the expression of IL-6 or the IL-6 signal transduction pathway may potentially be highly beneficial in USP