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

Smoke gets in your eyes: re-reading gender in the "nostalgia film"

Upon its release, American Graffiti (George Lucas, 1973) was much admired by critics and audiences alike. Yet, in subsequent years, the film became known for its supposed “flattening of history,” and celebration of patriarchal values. This article demonstrates that such a judgement owes much to Fredric Jameson’s historically contingent work on postmodernism, which argues that American Graffiti constitutes the paradigmatic nostalgia film. In contrast, using close textual analysis, I demonstrate that American Graffiti provides a more complex construction of the past, and of gender, than has hitherto been acknowledged. Far from blindly idealising the early 1960s, the film interrogates the processes through which the period and its gender relations come to be idealised. This article has consequences not only for our understanding of Lucas’ seminal film, but also for the American New Wave, and the “nostalgia” text

The Glasgow Outcome Scale -- 40 years of application and refinement

The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury

NK cells and cancer: you can teach innate cells new tricks

Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer

The mediating role of knowledge management processes in the effective use of artificial intelligence in manufacturing firms

Purpose: This paper aims to provide and empirically test a conceptual model in which artificial intelligence (AI), knowledge management processes (KMPs) and supply chain resilience (SCR) are simultaneously considered in terms of their reciprocal relationships and impact on manufacturing firm performance (MFP). Design/methodology/approach: In the study, six hypotheses have been developed and tested through an empirical survey administered to 120 senior executives of Italian manufacturing firms. The data analysis has been carried out via the partial least squares structural equation modelling approach, using the Advanced Analysis for Composites 2.0 variance-based software program. Findings: Using a conceptual model validated using an empirical survey, the study sheds light on the relationships between AI, KMPs and SCR, as well as their impacts on MFP. In particular, the authors show the positive effects of the adoption of AI on KMPs, as well as the influence of KMPs on SCR and MFP. Finally, the authors demonstrate that KMPs act as a mediator through which AI affects SCR and MFP. Practical implications: This study highlights the critical role of KMPs for manufacturing firms that can deploy AI to stimulate KMPs and through attaining a high level of the latter might succeed in enhancing both their SCR and MFP. Originality/value: This study demonstrates that manufacturing firms interested in properly applying AI to ameliorate their performance and resilience must carefully consider KMPs as a mediator mechanism

The Portrait of a Potential Entrepreneur: The Entrepreneurial Aptitude Test (TAI23\ua9)

The main objective of this work is to present the first validation of the new and shorter version of the Entrepreneurial Aptitude Test (TAI23\ua9). The original version was published Cubico et al. (2010). A cross-sectional, quantitative approach was used involving 977 subjects from three groups, with data collected in different research studies (university students, PhD students and workers). Based on these analyses, the TAI23\ua9 shows interesting psychometrics characteristics, including reliability and validity (concurrent and predictive). The instrument enables the detection of differences in entrepreneurial aptitude and is able to distinguish between entrepreneurs and non-entrepreneurs. The former have significantly higher scores, as do subjects who are oriented to become entrepreneurs or remain in an entrepreneurial role. The TAI23\ua9 shows good correlations with entrepreneurial competencies, and presents five well-defined factors (leadership; self-capability; innovation; problem-solving; goal orientation). The TAI23\ua9 has been proven to be an instrument that permits the definition of the entrepreneurial profile in a synthetic, clear and valid way that can be used in career service processes and in human resources management developmen