Efficacy and safety of 0.1% ciclosporin A cationic emulsion in dry eye disease: a pooled analysis of two double-masked, randomised, vehicle-controlled phase III clinical studies

Background/aim To assess the treatment effect of 0.1% ciclosporin A cationic emulsion (CsA CE) versus vehicle on signs/symptoms of dry eye disease (DED) in various subgroups (moderate-to-severe DED/severe DED/ Sjogren's syndrome (SS)/SS with severe DED). Methods Pooled data were analysed from two similar phase III studies: SICCANOVE (moderate-to-severe DED) and SANSIKA (severe DED with severe keratitis). In both studies, patients aged >= 18 years received CsA CE 0.1% (n=395) or vehicle (n=339) once daily for 6 months. A composite responder efficacy endpoint (corneal fluorescein staining-Ocular Surface Disease Index (CFSOSDI) at month 6) was used to evaluate the efficacy of CsA CE in alleviating signs/symptoms of DED (response defined as improvement of >= 2 grades in CFS and >= 30% in OSDI (baseline to month 6)). Human leucocyte antigen-DR (HLA-DR) conjunctival expression was used as a biomarker of ocular surface inflammation. Results CsA CE-treated patients were significantly more likely to be CFS-OSDI responders than vehicletreated patients in the overall (OR 1.66, 95% CI 1.11 to 2.50;P=0.015), severe DED (1.80, 1.04 to 3.19;P=0.038) and SS with severe DED (3.37, 1.20 to 11.19;P=0.030) populations. The difference was not significant for CsA CE versus vehicle for the overall Sjogren's population (OR 1.77, CI 0.89 to 3.66;P=0.109). CsA CE also significantly reduced median HLA-DR expression versus vehicle at 6 months (P=0.002). Conclusion Pooled phase III data indicate CsA CE produced significant improvement in signs/symptoms versus vehicle in patients with moderate-to-severe DED (especially in those with severe keratitis), including patients with SS with severe DED

Non-local thermodynamic equilibrium inversions from a 3D MHD chromospheric model

The structure of the solar chromosphere is believed to be governed by magnetic fields, even in quiet-Sun regions that have a relatively weak photospheric field. During the past decade inversion methods have emerged as powerful tools for analyzing the chromosphere of active regions. The applicability of inversions to infer the stratification of the physical conditions in a dynamic 3D solar chromosphere has not yet been studied in detail. This study aims to establish the diagnostic capabilities of non-local thermodynamical equilibrium (NLTE) inversion techniques of Stokes profiles induced by the Zeeman effect in the Ca II 8542 line. We computed the Ca II atomic level populations in a snapshot from a 3D radiation-MHD simulation of the quiet solar atmosphere in non-LTE using the 3D radiative transfer code Multi3d. These populations were used to compute synthetic full-Stokes profiles in the Ca II 8542 line using 1.5D radiative transfer and the inversion code Nicole. The profiles were then spectrally degraded to account for finite filter width and Gaussian noise was added to account for finite photon flux. These profiles were inverted using Nicole and the results were compared with the original model atmosphere. Our NLTE inversions applied to quiet-Sun synthetic observations provide reasonably good estimates of the chromospheric magnetic field, line-of-sight velocities and somewhat less accurate, but still very useful, estimates of the temperature. Three dimensional scattering of photons cause cool pockets in the chromosphere to be invisible in the line profile and consequently they are also not recovered by the inversions. To successfully detect Stokes linear polarization in this quiet snapshot, a noise level below 10^{-3.5} is necessary.Comment: Accepted for publication in Astronomy & Astrophysic

Análisis de la adhesión de recubrimientos del sistema Y2O3-Al2O3-SiO2 sobre sustratos de interés para la industria aeroespacial

En la industria aeroespacial se necesitan materiales ligeros que tengan unas altas prestaciones mecánicas combinadas con una baja densidad. El carburo de silicio, el carbono reforzado con fibra de carbono y el carburo de silicio reforzado con fibra de carbono son materiales que cumplen con estos requisitos, pero a altas temperaturas presentan problemas de oxidación. Una de las formas más efectivas de prevenir este fenómeno es la utilización de recubrimientos cerámicos, cuya correcta adhesión sobre los distintos sustratos es fundamental para garantizar su funcionamiento. En el caso del presente trabajo, se analiza la adhesión de recubrimientos vítreos del sistema Y2O3-Al2O3-SiO2 obtenidos mediante proyección térmica por llama oxiacetilénica. Para ello, se realizan ensayos de rayado a carga creciente analizando el tipo y la carga de fallo y su relación con las propiedades elásticas y mecánicas de los recubrimientos. Los resultados indican que la adhesión sobre los sustratos carburo de silicio y carburo de silicio reforzado con fibra de carbono es buena, mientras que el carbono reforzado con fibra de carbono no es un material adecuado para recubrir

Cellular integrin ¿5ß1 and exosomal adam17 mediate the binding and uptake of exosomes produced by colorectal carcinoma cells

Approximately 25% of colorectal cancer (CRC) patients develop peritoneal metastasis, a condition associated with a bleak prognosis. The CRC peritoneal dissemination cascade involves the shedding of cancer cells from the primary tumor, their transport through the peritoneal cavity, their adhesion to the peritoneal mesothelial cells (PMCs) that line all peritoneal organs, and invasion of cancer cells through this mesothelial cell barrier and underlying stroma to establish new metastatic foci. Exosomes produced by cancer cells have been shown to influence many processes related to cancer progression and metastasis. In epithelial ovarian cancer these extracellular vesicles (EVs) have been shown to favor different steps of the peritoneal dissemination cascade by changing the functional phenotype of cancer cells and PMCs. Little is currently known, however, about the roles played by exosomes in the pathogenesis and peritoneal metastasis cascade of CRC and especially about the molecules that mediate their interaction and uptake by target PMCs and tumor cells. We isolated exosomes by sizeexclusion chromatography from CRC cells and performed cell-adhesion assays to immobilized exosomes in the presence of blocking antibodies against surface proteins and measured the uptake of fluorescently-labelled exosomes. We report here that the interaction between integrin 5 1 on CRC cells (and PMCs) and its ligand ADAM17 on exosomes mediated the binding and uptake of CRC-derived exosomes. Furthermore, this process was negatively regulated by the expression of tetraspanin CD9 on exosome

Model selection for spectro-polarimetric inversions

Inferring magnetic and thermodynamic information from spectropolarimetric observations relies on the assumption of a parameterized model atmosphere whose parameters are tuned by comparison with observations. Often, the choice of the underlying atmospheric model is based on subjective reasons. In other cases, complex models are chosen based on objective reasons (for instance, the necessity to explain asymmetries in the Stokes profiles) but it is not clear what degree of complexity is needed. The lack of an objective way of comparing models has, sometimes, led to opposing views of the solar magnetism because the inferred physical scenarios are essentially different. We present the first quantitative model comparison based on the computation of the Bayesian evidence ratios for spectropolarimetric observations. Our results show that there is not a single model appropriate for all profiles simultaneously. Data with moderate signal-to-noise ratios favor models without gradients along the line-of-sight. If the observations shows clear circular and linear polarization signals above the noise level, models with gradients along the line are preferred. As a general rule, observations with large signal-to-noise ratios favor more complex models. We demonstrate that the evidence ratios correlate well with simple proxies. Therefore, we propose to calculate these proxies when carrying out standard least-squares inversions to allow for model comparison in the future.Comment: 16 pages, 2 figures, 8 tables, accepted for publication in Ap

Hormone replacement therapy and risk of epithelial ovarian cancer

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case–control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32–4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% Cl 1.54–5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours. © 1999 Cancer Research Campaig