Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis.

During epithelial ovarian cancer (EOC) progression, intraperitoneally disseminating tumor cells and multicellular aggregates (MCAs) present in ascites fluid adhere to the peritoneum and induce retraction of the peritoneal mesothelial monolayer prior to invasion of the collagen-rich submesothelial matrix and proliferation into macro-metastases. Clinical studies have shown heterogeneity among EOC metastatic units with respect to cadherin expression profiles and invasive behavior; however, the impact of distinct cadherin profiles on peritoneal anchoring of metastatic lesions remains poorly understood. In the current study, we demonstrate that metastasis-associated behaviors of ovarian cancer cells and MCAs are influenced by cellular cadherin composition. Our results show that mesenchymal N-cadherin-expressing (Ncad+) cells and MCAs invade much more efficiently than E-cadherin-expressing (Ecad+) cells. Ncad+ MCAs exhibit rapid lateral dispersal prior to penetration of three-dimensional collagen matrices. When seeded as individual cells, lateral migration and cell-cell junction formation precede matrix invasion. Neutralizing the Ncad extracellular domain with the monoclonal antibody GC-4 suppresses lateral dispersal and cell penetration of collagen gels. In contrast, use of a broad-spectrum matrix metalloproteinase (MMP) inhibitor (GM6001) to block endogenous membrane type 1 matrix metalloproteinase (MT1-MMP) activity does not fully inhibit cell invasion. Using intact tissue explants, Ncad+ MCAs were also shown to efficiently rupture peritoneal mesothelial cells, exposing the submesothelial collagen matrix. Acquisition of Ncad by Ecad+ cells increased mesothelial clearance activity but was not sufficient to induce matrix invasion. Furthermore, co-culture of Ncad+ with Ecad+ cells did not promote a 'leader-follower' mode of collective cell invasion, demonstrating that matrix remodeling and creation of invasive micro-tracks are not sufficient for cell penetration of collagen matrices in the absence of Ncad. Collectively, our data emphasize the role of Ncad in intraperitoneal seeding of EOC and provide the rationale for future studies targeting Ncad in preclinical models of EOC metastasis

Risk factors associated with myopia in schoolchildren in Ireland

Aim To examine the demographic and social factors associated with myopia in schoolchildren in Ireland. Methods Thirty-seven schools participated, representing a mix of urban and rural schools and schools in socioeconomically disadvantaged and non-disadvantaged areas in Ireland. Examination included cyclopleged autorefraction (1% cyclopentolate hydrochloride). Height and weight of participants were measured. Parents filled in a participant’s lifestyle questionnaire, including questions on daily screen time use and daylight exposure. Myopia was defined as spherical equivalent ≤−0.50 D. Results Data from 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), were examined. Myopia prevalence was significantly higher in children aged 12–13 years old (OR=7.7, 95%CI 5.1 to 11.6, p\u3c0.001) and significantly associated with non-white ethnicity (OR=3.7, 95% CI 2.5 to 5.3, p\u3c0.001). Controlling for age group and ethnicity, myopia prevalence was also significantly linked with height (p\u3c0.001) and higher in participants in the following groups: using screens \u3e3 hours per day (OR=3.7, 95% CI 2.1 to 6.3, p\u3c0.001), obesity (OR=2.7, 95% CI 1.9 to 3.9, p\u3c0.001), sedentary lifestyle (OR=2.9, 95% CI 1.9 to 4.4, p\u3c0.001), frequently reading/writing (OR=2.2, 95% CI 1.4 to 3.5, p=0.001), less daylight exposure during summer time (OR=5.00, 95% CI 2.4 to 10.3, p\u3c0.001), spring season births (OR=1.9, 95% CI 1.1 to 3.3, p=0.02), paternal history of myopia (OR=2.4, 95% CI 1.8 to 3.3, p\u3c0.001) and bottle fed for the first three months of life (OR=1.7, 95% CI 1.3 to 2.5, p=0.02). Conclusions The associations found between myopia prevalence in schoolchildren in Ireland and demographic and lifestyle factors suggest that longitudinal research investigating the associations between myopia prevalence and these factors may be beneficial in advising preventative public health programmes

Risk factors associated with myopia in schoolchildren in Ireland

Aim To examine the demographic and social factors associated with myopia in schoolchildren in Ireland. Methods Thirty-seven schools participated, representing a mix of urban and rural schools and schools in socioeconomically disadvantaged and non-disadvantaged areas in Ireland. Examination included cyclopleged autorefraction (1% cyclopentolate hydrochloride). Height and weight of participants were measured. Parents filled in a participant’s lifestyle questionnaire, including questions on daily screen time use and daylight exposure. Myopia was defined as spherical equivalent ≤−0.50 D. Results Data from 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), were examined. Myopia prevalence was significantly higher in children aged 12–13 years old (OR=7.7, 95%CI 5.1 to 11.6, p\u3c0.001) and significantly associated with non-white ethnicity (OR=3.7, 95% CI 2.5 to 5.3, p\u3c0.001). Controlling for age group and ethnicity, myopia prevalence was also significantly linked with height (p\u3c0.001) and higher in participants in the following groups: using screens \u3e3 hours per day (OR=3.7, 95% CI 2.1 to 6.3, p\u3c0.001), obesity (OR=2.7, 95% CI 1.9 to 3.9, p\u3c0.001), sedentary lifestyle (OR=2.9, 95% CI 1.9 to 4.4, p\u3c0.001), frequently reading/writing (OR=2.2, 95% CI 1.4 to 3.5, p=0.001), less daylight exposure during summer time (OR=5.00, 95% CI 2.4 to 10.3, p\u3c0.001), spring season births (OR=1.9, 95% CI 1.1 to 3.3, p=0.02), paternal history of myopia (OR=2.4, 95% CI 1.8 to 3.3, p\u3c0.001) and bottle fed for the first three months of life (OR=1.7, 95% CI 1.3 to 2.5, p=0.02). Conclusions The associations found between myopia prevalence in schoolchildren in Ireland and demographic and lifestyle factors suggest that longitudinal research investigating the associations between myopia prevalence and these factors may be beneficial in advising preventative public health programmes

Refractive error and visual impairment in Ireland schoolchildren

Aim To report refractive error prevalence and visual impairment in Republic of Ireland (henceforth \u27Ireland\u27) schoolchildren. Methods The Ireland Eye Study examined 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), in Ireland between June 2016 and January 2018. Participating schools were selected by stratified random sampling, representing a mix of school type (primary/postprimary), location (urban/rural) and socioeconomic status (disadvantaged/advantaged). Examination included monocular logarithm of the minimum angle of resolution (logMAR) presenting visual acuity (with spectacles if worn) and cycloplegic autorefraction (1% Cyclopentolate Hydrochloride). Parents completed a questionnaire to ascertain participants’ lifestyle. Results The prevalence of myopia (spherical equivalent refraction (SER): ≤−0.50 D), hyperopia (SER: ≥+2.00 D) and astigmatism (≤−1.00 DC) among participants aged 6–7 years old was 3.3%, 25% and 19.2%, respectively, and among participants aged 12–13 years old was 19.9%, 8.9% and 15.9%, respectively. Astigmatic axes were predominately with-the-rule. The prevalence of ‘better eye’ presenting visual impairment (≥0.3 logMAR, with spectacles, if worn) was 3.7% among younger and 3.4% among older participants. Participants in minority groups (Traveller and non-white) were significantly more likely to present with presenting visual impairment in the ‘better eye’. Conclusions The Ireland Eye Study is the first population-based study to report on refractive error prevalence and visual impairment in Ireland. Myopia prevalence is similar to comparable studies of white European children, but the levels of presenting visual impairment are markedly higher than those reported for children living in Northern Ireland, suggesting barriers exist in accessing eye care

Moving beyond the ‘language problem': developing an understanding of the intersections of health, language and immigration status in interpreter-mediated health encounters

Health systems internationally are dealing with greater diversity in patient populations. However the focus on ‘the language problem’ has meant little attention is paid to diversity within and between migrant populations; and how interpreted consultations are influenced by intersecting migratory, ethnicity and sociodemographic variables. Our analysis of the experiences of patients, health care providers and interpreters in Scotland evidences the need to move beyond language, addressing multiple hidden inequalities in health care access and provision that operate in both clinic and, especially, home-based settings. We call for a practice-evidenced research agenda promoting cultural communication across health care and home settings, acknowledging immigration status as a social determinant of health. Sur le plan international, des systèmes de santé font face à une diversité croissante dans ses populations de patients. Cependant, l’accent sur ‘le problème de langue’ se traduit dans une manque d’attention à la diversité a l’intérieur même et entre des populations des migrants; et la façon par laquelle des variables migratoire, ethnique et sociodémographique influencent elles-mêmes des consultations interprétées. Notre analyse des expériences des patients, des professionnels fournissant de soins de santé et des interprètes offre des preuves du besoin de dépasser le problème de langue. Et en faisant cela, nous adressons des multiples inégalités, souvent cachées dans des contextes de soins de santé, dans les milieux clinique et domicile. Nous proposons un programme de recherche basé sur la pratique, qui favorise la communication culturelle dans des milieux clinique et domicile, et qui reconnait le statut d’immigration comme un déterminant social de la santé

The potassic sedimentary rocks in Gale Crater, Mars, as seen by ChemCam on board Curiosity

The Mars Science Laboratory rover Curiosity encountered potassium-rich clastic sedimentary rocks at two sites in Gale Crater, the waypoints Cooperstown and Kimberley. These rocks include several distinct meters thick sedimentary outcrops ranging from fine sandstone to conglomerate, interpreted to record an ancient fluvial or fluvio-deltaic depositional system. From ChemCam Laser-Induced Breakdown Spectroscopy (LIBS) chemical analyses, this suite of sedimentary rocks has an overall mean K2O abundance that is more than 5 times higher than that of the average Martian crust. The combined analysis of ChemCam data with stratigraphic and geographic locations reveals that the mean K2O abundance increases upward through the stratigraphic section. Chemical analyses across each unit can be represented as mixtures of several distinct chemical components, i.e., mineral phases, including K-bearing minerals, mafic silicates, Fe-oxides, and Fe-hydroxide/oxyhydroxides. Possible K-bearing minerals include alkali feldspar (including anorthoclase and sanidine) and K-bearing phyllosilicate such as illite. Mixtures of different source rocks, including a potassium-rich rock located on the rim and walls of Gale Crater, are the likely origin of observed chemical variations within each unit. Physical sorting may have also played a role in the enrichment in K in the Kimberley formation. The occurrence of these potassic sedimentary rocks provides additional evidence for the chemical diversity of the crust exposed at Gale Crater

The Relationship Between Macular Pigment and Visual Performance

This study was designed to assess whether macular pigment optical density (MPOD) is associated with visual performance. One hundred and forty-two young healthy subjects were recruited. Macular pigment optical density and visual performance were assessed by psychophysical tests including best corrected visual acuity (BCVA), mesopic and photopic contrast sensitivity, glare sensitivity, photostress recovery time (PRT). Measures of central visual function, including BCVA and contrast sensitivity, were positively associated with MPOD (p \u3c 0.05, for all). Photostress recovery and glare sensitivity were unrelated to MPOD (p \u3e 0.05). A longitudinal, placebo-controlled and randomized supplementation trial will be required to ascertain whether augmentation of MPOD can influence visual performance

Instantons and Monopoles in General Abelian Gauges

A relation between the total instanton number and the quantum-numbers of magnetic monopoles that arise in general Abelian gauges in SU(2) Yang-Mills theory is established. The instanton number is expressed as the sum of the `twists' of all monopoles, where the twist is related to a generalized Hopf invariant. The origin of a stronger relation between instantons and monopoles in the Polyakov gauge is discussed.Comment: 28 pages, 8 figures; comments added to put work into proper contex

Large sulfur isotope fractionations in Martian sediments at Gale crater

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA’s Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of δ34S range from −47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods