Les entreprises au Royaume-Uni

This chapter of the book "Formations et emplois qualifiés. Les transformations dans le Bâtiment en France et au Royaume-Uni" analyses management strategies and organisational changes during a period of continuous crisis. The concept of cascading subcontracting (sous-traitance en cascade) introduced here encapsulates a new phenomenon observed simultaneously in the ever changing organisation of work between and within the firms. This is an important result of a research based on a 34 firm monographic and comparative analysis, with different company sizes from large to small ones. Cascading subcontracting results from a process of externalisation of certain sections of the labour force within leading firms that have found new ways to expand during recessive periods: their restructuring does not necessarily correspond to a reduction of their activity but to a structural reorganisation aiming to maintain or expand their market shares whilst reducing costs, risks and responsibilities. The new combinatorial dynamics associates economic growth and rise of turnovers with externalisation and reduction of employment enhancing a cascading effect on lower ranks of subcontractors that will in turn develop similar principles of restructuring. This concept is going to become a cornerstone of the theory of controlled autonomy, an analytical key of the concentration and fragmentation process.Extrait du livre Formations et emplois qualifiés. Les transformations dans le Bâtiment en France et au Royaume-Uni, ce chapitre analyse la dynamique des firmes et leurs changements organisationnels. Le concept de sous-traitance en cascade, cascading subcontracting, est ici introduit pour désigner un phénomène nouveau mis en évidence grâce à l'enquête menée dans 34 entreprises, grandes, moyennes et petites. La comparaison internationale et l'observation des changements inter et intra-entreprises, montrent l'apparition d'un processus d'externalisation du travail qui ne s'accompagne pas nécessairement d'une réduction d'activité, mais de son maintien, voire de son accroissement : la stratégie managériale des entreprises leaders qui se déploient de cette façon en période de crise, vise simultanément l'extension des parts de marchés et la diminution des coûts salariaux, des risques et des responsabilités. Les fonctions de pilotage pour capter la plus-value s'accompagnent dès lors d'un désengagement du travail d'exécution qui impactent l'organisation de l'ensemble de la branche par un effet en cascade. Cette nouvelle combinatoire associe croissance économique et augmentation du chiffre d'affaires avec externalisation et réduction des effectifs productifs dans les entreprises leaders. Ce concept va devenir une pierre angulaire de la théorie de l'autonomie contrôlée

Les entreprises au Royaume-Uni

This chapter of the book "Formations et emplois qualifiés. Les transformations dans le Bâtiment en France et au Royaume-Uni" analyses management strategies and organisational changes during a period of continuous crisis. The concept of cascading subcontracting (sous-traitance en cascade) introduced here encapsulates a new phenomenon observed simultaneously in the ever changing organisation of work between and within the firms. This is an important result of a research based on a 34 firm monographic and comparative analysis, with different company sizes from large to small ones. Cascading subcontracting results from a process of externalisation of certain sections of the labour force within leading firms that have found new ways to expand during recessive periods: their restructuring does not necessarily correspond to a reduction of their activity but to a structural reorganisation aiming to maintain or expand their market shares whilst reducing costs, risks and responsibilities. The new combinatorial dynamics associates economic growth and rise of turnovers with externalisation and reduction of employment enhancing a cascading effect on lower ranks of subcontractors that will in turn develop similar principles of restructuring. This concept is going to become a cornerstone of the theory of controlled autonomy, an analytical key of the concentration and fragmentation process.Extrait du livre Formations et emplois qualifiés. Les transformations dans le Bâtiment en France et au Royaume-Uni, ce chapitre analyse la dynamique des firmes et leurs changements organisationnels. Le concept de sous-traitance en cascade, cascading subcontracting, est ici introduit pour désigner un phénomène nouveau mis en évidence grâce à l'enquête menée dans 34 entreprises, grandes, moyennes et petites. La comparaison internationale et l'observation des changements inter et intra-entreprises, montrent l'apparition d'un processus d'externalisation du travail qui ne s'accompagne pas nécessairement d'une réduction d'activité, mais de son maintien, voire de son accroissement : la stratégie managériale des entreprises leaders qui se déploient de cette façon en période de crise, vise simultanément l'extension des parts de marchés et la diminution des coûts salariaux, des risques et des responsabilités. Les fonctions de pilotage pour capter la plus-value s'accompagnent dès lors d'un désengagement du travail d'exécution qui impactent l'organisation de l'ensemble de la branche par un effet en cascade. Cette nouvelle combinatoire associe croissance économique et augmentation du chiffre d'affaires avec externalisation et réduction des effectifs productifs dans les entreprises leaders. Ce concept va devenir une pierre angulaire de la théorie de l'autonomie contrôlée

Duplications of KIAA1549 and BRAF screening by Droplet Digital PCR from formalin-fixed paraffin-embedded DNA is an accurate alternative for KIAA1549-BRAF fusion detection in pilocytic astrocytomas

Pilocytic astrocytomas represent the most common glioma subtype in young patients and account for 5.4% of all gliomas. They are characterized by alterations in the RAS–MAP kinase pathway, the most frequent being a tandem duplication on chromosome 7q34 involving the BRAF gene, resulting in oncogenic BRAF fusion proteins. BRAF fusion involving the KIAA1549 gene is a hallmark of pilocytic astrocytoma, but it has also been recorded in rare cases of gangliogliomas, 1p/19q co-deleted oligodendroglial tumors, and it is also a common feature of disseminated oligodendroglial-like leptomeningeal neoplasm. In some difficult cases, evidence for KIAA1549-BRAF fusion is of utmost importance for the diagnosis. Moreover, because the KIAA1549-BRAF fusion constitutively activates the MAP kinase pathway, it represents a target for drugs such as MEK inhibitors, and therefore, the detection of this genetic abnormality is highly relevant in the context of clinical trials applying such new approaches. In the present study, we aimed to use the high sensitivity of Droplet Digital PCR (DDPCR™) to predict KIAA1549-BRAF fusion on very small amounts of formalin-fixed paraffin-embedded tissue in routine practice. Therefore, we analyzed a training cohort of 55 pilocytic astrocytomas in which the KIAA1549-BRAF fusion status was known by RNA sequencing used as our gold standard technique. Then, we analyzed a prospective cohort of 40 pilocytic astrocytomas, 27 neuroepithelial tumors remaining difficult to classify (pilocytic astrocytoma versus ganglioglioma or diffuse glioma), 15 dysembryoplastic neuroepithelial tumors, and 18 gangliogliomas. We could demonstrate the usefulness and high accuracy (100% sensitivity and specificity when compared to RNA sequencing) of DDPCR™ to assess the KIAA1549-BRAF fusion from very low amounts of DNA isolated from formalin-fixed paraffin-embedded specimens. BRAF duplication is both necessary and sufficient to predict this fusion in most cases and we propose that this single analysis could be used in routine practice to save time, money, and precious tissue

Avidity of influenza-specific memory CD8+ T-cell populations decays over time compromising antiviral immunity

Decline of cell-mediated immunity is often attributed to decaying T-cell numbers and their distribution in peripheral organs. This study examined the hypothesis that qualitative as well as quantitative changes contribute to the declining efficacy of CD8+ T-cell memory. Using a model of influenza virus infection, where loss of protective CD8+ T-cell immunity was observed 6 months postinfection, we found no decline in antigen-specific T-cell numbers or migration to the site of secondary infection. There was, however, a large reduction in antigen-specific CD8+ T-cell degranulation, cytokine secretion, and polyfunctionality. A profound loss of high-avidity T cells over time indicated that failure to confer protective immunity resulted from the inferior functional capacity of remaining low avidity cells. These data imply that high-avidity central memory T cells wane with declining antigen levels, leaving lower avidity T cells with reduced functional capabilities

Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Ingolotti, Mariana. Universidad Austral; ArgentinaFil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Espinoza, Jaime A.. Universidad Adolfo Ibañez; Chile. Universidad de La Frontera; ChileFil: Gidekel, Manuel. Universidad Adolfo Ibañez; ChileFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Matar, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentin

Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor

Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma. Their in vivo expansion is often observed with advanced disease. In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen. Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma. Interestingly, this population is oligoclonal and displays a clear memory phenotype. However, a detailed study of these cells indicated that they are unlikely to be directly specific for melanoma, so that their in vivo expansion may have been driven by an exogenous antigen. Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen. Finally, we discuss potential perspectives regarding the role of such cells in heterologous immunity, by influencing the balance between protective immunity and pathology, e.g. in the case of melanoma developmen

Accelerated immune senescence in HIV infection

International audiencen.

Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging