Chronic beryllium disease as a re-emerging occupational disorder possibly misdiagnosed as sarcoidosis : a Swiss study project

Background: Beryllium (Be) is increasingly used worldwide for numerous industrial applications. Occupational exposure to Be may lead to Be sensitization (BeS), a CD4-mediated immune response. BeS may progress to chronic beryllium disease (CBD), a granulomatous lung disorder closely resembling sarcoidosis. The recognition of CBD requires detection of Be exposure at occupational history, and detection of BeS on blood or BAL lymphocytes. Since methods for CBD detection are not routinely available in Switzerland, we hypothesized that CBD cases are not recognized but misdiagnosis as sarcoidosis. Objective: To present an ongoing Swiss study screening patients with sarcoidosis in search of Be exposure, BeS, and CBD. Methods: Both a prospective and a retrospective cohort are being studied. In the prospective cohort, the main steps include: 1) recruitment of 100 consecutive patients with newly diagnosed pulmonary sarcoidosis at 2 centers (Lausanne, Bern). 2) screening for possible occupational Be exposure by self-administered patient questionnaire. 3) standardized detailed occupational interview and clinical visit by occupational health specialist. If step 3 is positive, then 4) blood and BAL sampling for detection of BeS by specifically developed Elispot assay and CFSE flow cytometry, with subsequent comparison to the classical Be lymphocyte proliferation test. If step 4 is positive, then 5) review of medical records and diagnostic revision from sarcoidosis to CBD. 6) appropriate measures for exposure cessation and case reporting to SUVA as occupational disease. The retrospective cohort will include 400 patients with previously diagnosed pulmonary sarcoidosis, either treated or untreated, recruited through the SIOLD Registries. Steps 2 to 5 will be peformed as above, except for a) end of study after step 2 if screening questionnaire does not reveal Be exposure, and b) step 4 done on blood sample only (BAL not needed). Current status: Self-administered screening questionnaire and tools for standardized occupational interview have been developed. BeS testing has been implemented and undergoes validation. Inclusions in the prospective phase have started at both study sites. The retrospective phase is in preparation. Conclusion: The current study status allows to conclude to technical feasibility of the project. The prospective phase if this study is funded by the SUVA. The SIOLD Registries are supported by the Swiss Pulmonary League.

Ghosts in contemporary African diasporic literature : re-visioning history, memory and identity

Starting from the observation that ghosts are strikingly recurrent and prominent figures in late-twentieth African diasporic literature, this dissertation proposes to account for this presence by exploring its various functions. It argues that, beyond the poetic function the ghost performs as metaphor, it also does cultural, theoretical and political work that is significant to the African diaspora in its dealings with issues of history, memory and identity. Toni Morrison's Beloved (1987) serves as a guide for introducing the many forms, qualities and significations of the ghost, which are then explored and analyzed in four chapters that look at Fred D'Aguiar's Feeding the Ghosts (1998), Gloria Naylor's Mama Day (1988), Paule Marshall's Praisesong for the Widow (1983) and a selection of novels, short stories and poetry by Michelle Cliff. Moving thematically through these texts, the discussion shifts from history through memory to identity as it examines how the ghost trope allows the writers to revisit sites of trauma; revise historical narratives that are constituted and perpetuated by exclusions and invisibilities; creatively and critically repossess a past marked by violence, dislocation and alienation and reclaim the diasporic culture it contributed to shaping; destabilize and deconstruct the hegemonic, normative categories and boundaries that delimit race or sexuality and envision other, less limited and limiting definitions of identity. These diverse and interrelated concerns are identified and theorized as participating in a project of "re-vision," a critical project that constitutes an epistemological as much as a political gesture. The author-based structure allows for a detailed analysis of the texts and highlights the distinctive shapes the ghost takes and the particular concerns it serves to address in each writer's literary and political project. However, using the ghost as a guide into these texts, taken collectively, also throws into relief new connections between them and sheds light on the complex ways in which the interplay of history, memory and identity positions them as products of and contributions to an African diasporic (literary) culture. If it insists on the cultural specificity of African diasporic ghosts, tracing its origins to African cultures and spiritualities, the argument also follows gothic studies' common view that ghosts in literary and cultural productions-like other related figures of the living dead-respond to particular conditions and anxieties. Considering the historical and political context in which the texts under study were produced, the dissertation makes connections between the ghosts in them and African diasporic people's disillusionment with the broken promises of the civil rights movement in the United States and of postcolonial independence in the Caribbean. It reads the texts' theoretical concerns and narrative qualities alongside the contestation of traditional historiography by black and postcolonial studies as well as the broader challenge to conventional notions such as truth, reality, meaning, power or identity by poststructuralism, postcolonialism or queer theory. Drawing on these various theoretical approaches and critical tools to elucidate the ghost's deconstructive power for African diasporic writers' concerns, this work ultimately offers a contribution to "speciality studies," which is currently emerging as a new field of scholarship in cultural theory.

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model.

Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect relationship between these two observations has not been demonstrated. For this reason, we developed a new experimental model to evaluate the possible role of circulating CEA in the facilitation of liver metastases. A CEA-negative subclone from the human colon carcinoma cell line CO115 was transfected either with CEA-cDNA truncated at its 3' end by the deletion of 78 base pairs leading to the synthesis of a secreted form of CEA or with a full-length CEA-cDNA leading to the synthesis of the entire CEA molecule linked to the cell surface by a GPI anchor. Transfectants were selected either for their high CEA secretion (clone CO115-2C2 secreting up to 13 microg CEA per 10(6) cells within 72 h) or for their high CEA membrane expression (clone CO115-5F12 expressing up to 1 x 10(6) CEA molecules per cell). When grafted subcutaneously, CO115-2C2 cells gave rise to circulating CEA levels that were directly related to the tumour volume (from 100 to 1000 ng ml(-1) for tumours ranging from 100 to 1000 mm3), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bearing a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection of three different CEA-expressing human colorectal carcinoma cell lines (LoVo, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneous CEA secreting clone (CO115-2C2), but they were directly related to the metastatic properties of the intrasplenically injected tumour cells.

Référentiels des compétences et des métiers : une approche ontologique

Résumé La mondialisation des marchés, les mutations du contexte économique et enfin l'impact des nouvelles technologies de l'information ont obligé les entreprises à revoir la façon dont elles gèrent leurs capitaux intellectuel (gestion des connaissances) et humain (gestion des compétences). II est communément admis aujourd'hui que ceux-ci jouent un rôle particulièrement stratégique dans l'organisation. L'entreprise désireuse de se lancer dans une politique gestion de ces capitaux devra faire face à différents problèmes. En effet, afin de gérer ces connaissances et ces compétences, un long processus de capitalisation doit être réalisé. Celui-ci doit passer par différentes étapes comme l'identification, l'extraction et la représentation des connaissances et des compétences. Pour cela, il existe différentes méthodes de gestion des connaissances et des compétences comme MASK, CommonKADS, KOD... Malheureusement, ces différentes méthodes sont très lourdes à mettre en oeuvre, et se cantonnent à certains types de connaissances et sont, par conséquent, plus limitées dans les fonctionnalités qu'elles peuvent offrir. Enfin, la gestion des compétences et la gestion des connaissances sont deux domaines dissociés alors qu'il serait intéressant d'unifier ces deux approches en une seule. En effet, les compétences sont très proches des connaissances comme le souligne la définition de la compétence qui suit : « un ensemble de connaissances en action dans un contexte donné ». Par conséquent, nous avons choisi d'appuyer notre proposition sur le concept de compétence. En effet, la compétence est parmi les connaissances de l'entreprise l'une des plus cruciales, en particulier pour éviter la perte de savoir-faire ou pour pouvoir prévenir les besoins futurs de l'entreprise, car derrière les compétences des collaborateurs, se trouve l'efficacité de l'organisation. De plus, il est possible de décrire grâce à la compétence de nombreux autres concepts de l'organisation, comme les métiers, les missions, les projets, les formations... Malheureusement, il n'existe pas réellement de consensus sur la définition de la compétence. D'ailleurs, les différentes définitions existantes, même si elles sont pleinement satisfaisantes pour les experts, ne permettent pas de réaliser un système opérationnel. Dans notre approche; nous abordons la gestion des compétences à l'aide d'une méthode de gestion des connaissances. En effet, de par leur nature même, connaissance et compétence sont intimement liées et donc une telle méthode est parfaitement adaptée à la gestion des compétences. Afin de pouvoir exploiter ces connaissances et ces compétences nous avons dû, dans un premier temps, définir les concepts organisationnels de façon claire et computationnelle. Sur cette base, nous proposons une méthodologie de construction des différents référentiels d'entreprise (référentiel de compétences, des missions, des métiers...). Pour modéliser ces différents référentiels, nous avons choisi l'ontologie, car elle permet d'obtenir des définitions cohérentes et consensuelles aux concepts tout en supportant les diversités langagières. Ensuite, nous cartographions les connaissances de l'entreprise (formations, missions, métiers...) sur ces différentes ontologies afin de pouvoir les exploiter et les diffuser. Notre approche de la gestion des connaissances et de la gestion des compétences a permis la réalisation d'un outil offrant de nombreuses fonctionnalités comme la gestion des aires de mobilités, l'analyse stratégique, les annuaires ou encore la gestion des CV. Abstract The globalization of markets, the easing of economical regulation and finally the impact of new information and communication technologies have obliged firms to re-examine the way they manage their knowledge capital (knowledge management) and their human capital (competence management). It is commonly admitted that knowledge plays a slightly strategical role in the organization. The firms who want to establish one politic of management of these capitals will have to face with different problems. To manage that knowledge, a long process of capitalization must be done. That one has different steps like identification, extraction and representation of knowledge and competences. There are some different methods of knowledge management like MASK, CommonKADS or KOD. Unfortunately, those methods are very difficult to implement and are using only some types of knowledge and are consequently more limited in the functionalities they can offer. Knowledge management and competence management are two different domain where it could be interesting to unify those to one. Indeed, competence is very close than knowledge as underline this definition: "a set of knowledge in action in a specified context". We choose in our approach to rely on the concept of competence. Indeed, the competence is one of crucial knowledge in the company, particularly to avoid the loss of know-how or to prevent future needs. Because behind collaborator's competence, we can find company efficiency. Unfortunately, there is no real consensus on the definition of the concept of competence. Moreover, existing different definitions don't permit to develop an operational system. Among other key concept, we can find jobs, mission, project, and training... Moreover, we approach different problems of the competence management under the angle of the knowledge management. Indeed, knowledge and competence are closely linked. Then, we propose a method to build different company repositories (competence, jobs, projects repositories). To model those different repositories we choose ontology because it permits to obtain coherent and consensual definitions of the concepts with support of linguistics diversities too. This building repositories method coupled with this knowledge and competence management approach permitted the realization of a tool offering functionalities like mobility management, strategical analysis, yellow pages or CV management.

Témoigner avant et après la guérison. Ce que le témoignage fait à la communauté.

Trois ans après avoir témoigné de son mal chronique, une fidèle s'exprime à nouveau devant sa communauté, une Église évangélique de type charismatique. Elle partage la nouvelle de sa guérison miraculeuse. L'analyse comparée de ces récits, ainsi qu'une description ethnographique des célébrations durant lesquelles ils sont émis, montre comment l'énonciation de la croyante est encadrée par le pasteur. Une approche pragmatique et énonciative permet de ressaisir simultanément cet encadrement au plan institutionnel et interactionnel. On verra alors comment cette parole publique contribue à redéfinir la perception que la communauté a de Dieu et d'elle-même. Chacune des situations de témoignage renvoie ainsi à deux façons présentes au sein de l'évangélisme charismatique de se rapporter au surnaturel qui ont un impact sur l'organisation des Églises locales.Three years after sharing publicly about her chronic illness, a believer addresses again her congregation, an Evangelical church with Charismatic leanings. She shares the news of her miraculous healing. A comparative analysis of those testimonies and on ethnographic descriptions of the worship services during which she spoke will show how the pastor frames the believer's enunciation. A pragmatic and enunciative approach recaptures simultaneously both interactional and institutional levels. It will appear that the public speech contributes to redefining the congregation's perception of God and of itself. Both testimony settings show two ways, within Charismatic Evangelism, to refer to the supernatural. Those ways have an impact on the organization of the local churches.

The Hindu Model of Social Organization and the bhakti Movement : the Example of Vallabha's sampradāya

(Résumé de l'ouvrage) This volume addresses research topics within the field of Bhakti literature, the devotional poetry and other compositions of devotional character in the earlier literature of the modern South Asian languages. Its papers range from the roots of the Bhakti tradition in the early history of Krsna to its modern adaptations in nineteenth- and twentieth-century culture. Geographically, they span Bengal to Sind, Panjab to Maharashtra. Contemporary study of the modern Indian languages has broadened the scope of scholarship to consider today's Hindu attitudes, and those of a mixed society, against the background of ancient culture. Here, materials in six modern Asian languages are discussed: Bengali, Gujarati, Hindi in its main literary forms, Marathi, Panjabi and Sindhi; with assessment also of material in Sanskrit, Arabic and Chinese. In addition to studies of literary (and orally transmitted) works in the Krsna or Rama traditions, and of Sufi compositions and their interpretation, there are papers on the early history of sacred sites, the emergence of the religion of Rama, later religious formulations throughout the subcontinent, and the interaction of the Islamic and the Hindu.

Research needs in allergy: an EAACI position paper, in collaboration with EFA.

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

Die Arbeit: eine Re-Vision = Le travail: une re-vision

Was ist Arbeit? Ein notwendiges Übel, eine den Menschen erst zum Menschen machende Notwendigkeit, ein Mittel sich selbst zu verwirklichen, eine notwendige Struktur, die den Menschen gesund hält, ja sogar therapiert oder bloss eine unter vielen Möglichkeiten, mit dem Leben etwas anzufangen? Arbeit wurde schon immer mehrdeutig gefasst. Zwölf Autoren aus dem französischen und deutschen Kulturkreis diskutieren, was Arbeit ist und war. Die Beiträge aus Philosophie, Recht, Sozialwissenschaften, aber auch Kunstwissenschaften kreisen um vier wesentliche Spannungen des Begriffs Arbeit: die Arbeit der Frau, die Sichtbarkeit oder Sichtbarmachung der Arbeit, das Verhältnis von Arbeit zu anderen menschlichen Tätigkeiten, der Sinn und das Erleben der Arbeit mit dem allgegenwärtigen Stress, mit dem die heutige Arbeit verknüpft wird. Qu'est-ce que le travail? Un mal nécessaire, une nécessité pour faire des hommes des êtres humains, un moyen de se réaliser, une structure nécessaire qui maintient les êtres humains en santé, voire même les soigne, ou simplement une possibilité parmi d'autres de faire quelque chose de sa vie? Le terme de travail comprend un large éventail de significations. Douze auteurs de culture française et allemande discutent de ce qu'est le travail et de ce qu'il était. Les contributions issues de la philosophie, du droit, des sciences sociales, mais aussi des arts s'articulent autour de quatre dimensions essentielles du concept de travail: le travail des femmes, la visibilité ou la mise en évidence du travail, le lien entre le travail et les autres activités humaines, la recherche de sens et le vécu du travail avec le stress quotidien qui est aujourd'hui étroitement lié au travail.

Identification of cancer stem cells in Ewing's sarcoma

Summary : Cancer stem cells (CSC) that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been demonstrated to date. Here, we .identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESPY), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in NOD/SCID mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic and chondrogenic lineages. Quantitative Real-Time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133- counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells (ET-CSC) and demonstration of their mesenchymal stem cell properties, a critical step toward a better biological understanding and rational therapeutic targeting of these tumors. Résumé : Des cellules souches tumorales avec des propriétés exclusives d'initiation tumorale ont récemment été identifiées dans différents types de cancers, permettant ainsi d'espérer le développement de thérapies plus efficaces. Cependant, l'existence de telles cellules dans les sarcomes, un sous-groupe de cancers d'origine mésenchymateuse très agressifs, n'a pas encore été démontrée. Dans ce travail de recherche, nous identifions et caractérisons des cellules souches tumorales dans le sarcome d'Ewing, une tumeur pédiatrique très agressive vraisemblablement dérivée de cellules souches mésenchymateuses (MSC). Afin de séparer des populations cellulaires dans des échantillons primaires de sarcome d'Ewing, nous avons utilisé des billes magnétiques couplées à des anticorps monoclonaux. Ceci nous a permis d'isoler une sous-population de cellules tumorales CD133+ qui ont la capacité d'initier et de maintenir la croissance tumorale dans des xénotransplantations en série effectuées dans des souris immunodéficientes NOD/SCID. Ces cellules reétablissent à chaque passage in vivo le phénotype de la tumeur d'origine ainsi que son organisation hiérarchique. En accord avec la plasticité des MSC, des tests de différentiation in vitro ont montré que les cellules CD133+ maintiennent la capacité de se différentier en adipocytes, ostéocytes et chondrocytes. Une analyse par PCR quantitative de gènes impliqués dans le maintien des cellules souches a montré que les cellules CD133+ expriment un niveau beaucoup plus élevé de OCT4 and NANOG que les cellules CD133-. En résumé, nos observations constituent la première identification de cellules souches tumorales dans le sarcome d'Ewing et démontrent leur propriété de cellules souches mésenchymateuses. Ceci constitue une étape clé vers une meilleure compréhension biologique et une meilleure approche thérapeutique de ces tumeurs.