Social Inequalities of Functioning and Perceived Health in Switzerland–A Representative Cross-Sectional Analysis

Many people worldwide live with a disability, i.e. limitations in functioning. The prevalence is expected to increase due to demographic change and the growing importance of non-communicable disease and injury. To date, many epidemiological studies have used simple dichotomous measures of disability, even though the WHO's International Classification of Functioning, Disability, and Health (ICF) provides a multi-dimensional framework of functioning. We aimed to examine associations of socio-economic status (SES) and social integration in 3 core domains of functioning (impairment, pain, limitations in activity and participation) and perceived health. We conducted a secondary analysis of representative cross-sectional data of the Swiss Health Survey 2007 including 10,336 female and 8,424 male Swiss residents aged 15 or more. Guided by a theoretical ICF-based model, 4 mixed effects Poisson regressions were fitted in order to explain functioning and perceived health by indicators of SES and social integration. Analyses were stratified by age groups (15–30, 31–54, ≥55 years). In all age groups, SES and social integration were significantly associated with functional and perceived health. Among the functional domains, impairment and pain were closely related, and both were associated with limitations in activity and participation. SES, social integration and functioning were related to perceived health. We found pronounced social inequalities in functioning and perceived health, supporting our theoretical model. Social factors play a significant role in the experience of health, even in a wealthy country such as Switzerland. These findings await confirmation in other, particularly lower resourced settings

Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells

Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion–metastasis cascade remain poorly understood. Here, we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b+/Ly6G+neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their cross-talk with host cells and disseminating carcinoma cells. SIGNIFICANCE: This study provides important insights into the systemic contributions of neutrophils to cancer metastasis by identifying how neutrophils facilitate intermediate steps of the invasion–metastasis cascade. We demonstrate that neutrophils suppress natural killer cell activity and increase extravasation of tumor cells.Human Frontier Science Program (Strasbourg, France) (fellowship LT00728/2008-L)Charles King Trust FoundationMassachusetts Institute of Technology. Ludwig Center for Cancer ResearchCancer Research Institute (New York, N.Y.) (Irvington Fellowship)National Institutes of Health (U.S.) (grant P01 CA080111)National Institutes of Health (U.S.) (grant CA163109

The Good, the Bad and the Ugly: A Study of the Organization through the Lens of Popular Films of the Western World

This chapter examined portrayals of the morality of organizations using the lens of Western films. The work explored six decades of film, analyzing the organizational contexts and their agents, in order to understand filmmakers’ and audiences’ perceptions of organizational settings. In order to examine the organization as an entity within film, this chapter provided a content analysis of plot summaries from a purposefully selected body of top grossing box office films spanning 60 years. The plot summaries constituted a strong basis for identifying the characteristics of the organization as they are largely descriptive in nature and as such do not offer any evaluation or analysis of the film. Any assumptions about the character of organizations (or their members/employees) are unconscious, and as such they constitute a verbal description of what competent observers would say has occurred within the film. The plots were coded to reveal perceptions of positive, neutral, or negative organizational contexts and actions. This approach exposed the filmmakers symbolic placing of the organization in order to provide backdrops for the narrative. The plot analysis revealed that throughout the decades there has been a sophisticated portrayal in film of the role of the organization and the agents therein. A generally negative view of organizational contexts was demonstrated, with only religion and education shown as positive within the films selected. It was recognized that there would be value in extending this research to analyze a larger body of works. The selection criteria resulted in a wide but not comprehensive corpus of film genres. The body of works was sufficient to reveal the complexity of attitudes to organizational values and delivery which has evolved through time. Different selection criteria and more substantial narrative text could serve to confirm these results. Further implications for future research were discussed. While in the real-life sphere, there has been an emphasis on organizational standards and “corporate governance” delivering ethical exemplars, the film contexts highlight the complexities of delivering trusted organizations. The reality that there remains the potential for organizational corruption is well understood by the general public and clearly depicted within the film world. The conceptual contribution is original as limited work has been conducted on the organizational context in films. This work revealed the possibility of using this approach to further develop a greater understanding of perceptions of organizations

Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with traits needed to complete many of the steps leading to metastasis formation, but its contributions specifically to the late step of extravasation remain understudied. We find that breast cancer cells that have undergone an EMT extravasate more efficiently from blood vessels both in vitro and in vivo. Analysis of gene expression changes associated with the EMT program led to the identification of an EMT-induced cell-surface protein, podocalyxin (PODXL), as a key mediator of extravasation in mesenchymal breast and pancreatic carcinoma cells. PODXL promotes extravasation through direct interaction of its intracellular domain with the cytoskeletal linker protein ezrin. Ezrin proceeds to establish dorsal cortical polarity, enabling the transition of cancer cells from a non-polarized, rounded cell morphology to an invasive extravasation-competent shape. Hence, the EMT program can directly enhance the efficiency of extravasation and subsequent metastasis formation through a PODXL-ezrin signaling axis. Keyword: metastasis; EMT; extravasation; PODXL; ezrinNational Institutes of Health (U.S.) (Grant R01-CA078461

Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis

Key Points CN/AML patients have a high frequency of CSF3R and RUNX1 mutations. CSF3R and RUNX1 mutations induce elevated proliferation of CD34+ cells.</jats:p