754 resultados para why-questioning


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The ill effects of second-hand smoke are now well documented. To protect the population from exposure to tobacco smoke, comprehensive smoking bans are necessary as expressed in the WHO Framework Convention on Tobacco Control and its guidelines. Switzerland has only a partial smoking ban full of exceptions which has been in effect since 2010, which reproduces the so-called Spanish model. In September 2012, the Swiss citizens refused a proposal for a more comprehensive ban. This case study examines the reasons behind this rejection and draws some lessons that can be learnt from it.

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Abstract

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RESUME Le diabète de type 1 se définit comme un désordre métabolique d'origine auto-immune qui aboutit à la destruction progressive et sélective de la cellule ß-pancréatique sécrétrice d'insuline. Cette maladie représente 10 % des cas de diabète enregistrés dans la population mondiale, et touche les jeunes de moins de 20 ans. Le traitement médical par insulinothérapie corrige le manque d'hormone mais ne prévient pas les nombreuses complications telles que les atteintes cardiaques, neurologiques, rénales, rétiniennes, et les amputations que la maladie provoque. Le remplacement de la cellule ß par transplantation d'îlots de Langerhans est une alternative prometteuse au traitement médical du diabète de type 1. Cependant la greffe d'îlots est encore un traitement expérimental et ne permet pas un contrôle efficace de la glycémie au long terme chez les patients transplantés, et les raisons de cet échec restent mal comprises. L'obstacle immédiat qui se pose est la purification d'un nombre suffisant d'îlots viables et la perte massive de ces îlots dans les premières heures suite à la greffe. Cette tendance presque systématique de la perte fonctionnelle du greffon immédiatement après la transplantation est connue sous le terme de « primary graft non-function » (PNF). En effet, la procédure d'isolement des îlots provoque la destruction des composantes cellulaires et non cellulaires du tissu pancréatique qui jouent un rôle déterminant dans le processus de survie de l'îlot. De plus, la transplantation elle-même expose les cellules à différents stress, notamment le stress par les cytokines inflammatoires qui encourage la mort cellulaire par apoptose et provoque par la suite le rejet de la greffe. L'ensemble de ces mécanismes aboutit a une perte de la masse d'îlot estimée a plus de 60%. Dans ce contexte, nous nous sommes intéressés à définir les voies majeures de stress qui régissent cette perte massive d'îlot par apoptose lors du processus d'isolement et suite à l'exposition immédiate aux cytokines. L'ensemble des résultats obtenus indique que plusieurs voies de signalisation intracellulaire sont recrutées qui s'activent de manière maximale très tôt lors des premières phases de l'isolement. La mise en culture des îlots deux jours permet aux voies activées de revenir aux taux de base. De ce fait nous proposons une stratégie dite de protection qui doit être 1) initiée aussitôt que possible lors de l'isolement des îlots pancréatiques, 2) devrait probablement bloquer l'activation de ces différentes voies de stress mis en évidence lors de notre étude et 3) devrait inclure la mise en culture des îlots purifiés deux jours après l'isolement et avant la transplantation. RESUME LARGE PUBLIC Le diabète est une maladie qui entraîne un taux anormalement élevé de sucre (glucose) dans le sang du à une insuffisance du pancréas endocrine à produire de l'insuline, une hormone qui régule la glycémie (taux de glucose dans le sang). On distingue deux types majeurs de diabètes; le diabète de type 1 ou juvénile ou encore appelé diabète maigre qui se manifeste souvent pendant l'enfance et qui se traduit par une déficience absolue en insuline. Le diabète de type 2 ou diabète gras est le plus fréquent, et touche les sujets de plus de 40 ans qui souffrent d'obésité et qui se traduit par une dysfonction de la cellule ß avec une incapacité à réguler la glycémie malgré la production d'insuline. Dans le diabète de type 1, la destruction de la cellule ß est programmée (apoptose) et est majoritairement provoquée par des médiateurs inflammatoires appelés cytokines qui sont produites localement par des cellules inflammatoires du système immunitaire qui envahissent la cellule ß-pancréatiques. Les cytokines activent différentes voies de signalisation parmi lesquelles on distingue celles des Mitogen-Activated Protein Kinase (MAPKs) composées de trois familles de MAPKs: ERK1/2, p38, et JNK, et la voie NF-κB. Le traitement médical par injections quotidiennes d'insuline permet de contrôler la glycémie mais ne prévient pas les nombreuses complications secondaires liées à cette maladie. La greffe d'îlots de Langerhans est une alternative possible au traitement médical, considérée avantageuse comparée a la greffe du pancréas entier. En effet l'embolisation d'îlots dans le foie par injection intraportale constitue une intervention simple sans complications majeures. Néanmoins la technique de préparation d'îlots altère la fonction endocrine et cause la perte massive d'îlots pancréatiques. De plus, la transplantation elle-même expose la cellule ß à différents stress, notamment le stress par les cytokines inflammatoires qui provoque le rejet de greffon cellulaire. Dans la perspective d'augmenter les rendements des îlots purifiés, nous nous sommes intéressés à définir les voies majeures de stress qui régissent cette perte massive d'îlot lors du processus d'isolement et suite à l'exposition immédiate aux cytokines après transplantation. L'ensemble de ces résultats indique que le stress induit lors de l'isolement des îlots et celui des cytokines recrute différentes voies de signalisation intracellulaire (JNK, p38 et NF-κB) qui s'additionnent entre-elles pour altérer la fonction et la viabilité de l'îlot. De ce fait une stratégie doit être mise en place pour bloquer toute action synergique entre ces différentes voies activées pour améliorer la viabilité et la fonction de la cellule ß lors du greffon cellulaire. SUMMARY Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the progressive and selective destruction of the pancreatic ß-cells that secrete insulin, leading to absolute insulin deficiency. T1DM accounts for about 10% of all diabetes cases, affecting persons younger than 20 years of age. Medical treatment using daily exogenous insulin injection corrects hormone deficiency but does not prevent devastating complications such as heart attack, neuropathy, kidney failure, blindness, and amputation caused by the disease. Pancreatic islet transplantation (PIT) is one strategy that holds promise to cure patients with T1DM, but purified pancreatic islet grafts have failed to maintain long-term glucose homeostasis in human recipients, the reasons for this failure being still poorly understood. There is however a more immediate problem with islet grafting that is dependent upon poor islet recovery from donors and early islet loss following the first hours of grafting. This tendency of islet grafts to fail to function within a short period after transplantation is termed primary graft non-function (PNF). Indeed, the islet isolation procedure itself destroys cellular and non-cellular components of the pancreas that may play a role in supporting islet survival. Further, islet transplantation exposes cells to a variety of stressful stimuli, notably pro-inflammatory cytokines that encourage ß-cell death by apoptosis and lead to early graft failure. Altogether these mechanisms lead to an estimated loss of 60% of the total islet mass. Here, we have mapped the major intracellular stress signaling pathways that may mediate human islet loss by apoptosis during isolation and following cytokine attack. We found that several stress pathways are maximally activated from the earliest stages of the isolation procedure. Culturing islet for two days allow for the activated pathways to return to basal levels. We propose that protective strategies should 1) be initiated as early as possible during isolation of the islets, 2) should probably target the activated stress pathways that we uncovered during our studies and 3) should include culturing islets for two days post-isolation and prior transplantation.

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Recent advances in genetics led to significant improvement in the field of childhood epilepsies diagnosis and physiopathology. Genetic testing is indicated by geneticist who is himself guided by the pediatric neurological approach. In rare circumstance, genetic etiology affects the clinical management. Cost remains the main limitation. Those new genetic tools are the first step toward a better understanding of seizure mechanism and therefore more efficient treatments.

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Hypertensive patients often experience poor adherence to treatment, a frequent cause of uncontrolled blood pressure. In this study, we have evaluated whether or not the use of electronic monitoring for drug adherence is a useful approach to identify and correct compliance problems in hypertensive patients, which may ultimately enhance the effect of antihypertensive therapy. Sixty-nine treated patients with an office blood pressure greater than 140/90 mm Hg were enrolled in this study. With patient consent, current antihypertensive therapy was dispensed in electronic pillboxes that record the time and date of each opening without changing the drug regimen. The intention was to provide physicians with objective measurements of drug compliance. The monitoring of compliance per se without any other intervention induced a marked decrease of blood pressure in the whole group (from 159/104Â+/-23/12 mm Hg to 143/92Â+/-20/15, meansÂ+/-standard deviation, p less than 0.001). A complete normalization of blood pressure (less than 140/90 mm Hg) was obtained in one third of the patients (group 1, n=23) during the monitoring period. A significant improvement of blood pressure control was found in another third (group 2, n=23), whereas in the remaining patients (group 3, n=23) no change in blood pressure was observed. The distribution of individual compliance values, as well as the mean compliances was comparable in the three subgroups. Conversely, the compliance reports have identified several potentially overtreated patients in group 1, a large number of patients with a poor adherence to the prescribed therapy in all groups, and patients who clearly needed a change in pharmacotherapy mainly in group 3. Thus, our results suggest that electronic monitoring of compliance can considerably enhance the efficacy of antihypertensive therapy in patients with uncontrolled hypertension. This procedure should be used more extensively in clinical practice whenever the blood pressure response to therapy appears insufficient. (c)2000 by Le Jacq Communications, Inc.

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Classroom research on achievement goals has revealed that performance-approach goals (goals to outperform others) positively predict exam performance whereas performance-avoidance goals (goals not to perform more poorly than others) negatively predict it. Because prior classroom research has primarily utilized multiplechoice exam performance, the first aim of the present study was to extend these findings to a different measure of exam performance (oral examination). The second aim of this research was to test the mediating role of perceived difficulty. Participants were 49 4th year psychology students of the University of Geneva. Participants answered a questionnaire assessing their level of performance-approach and performance-avoidance goal endorsement in one of their classes as well as the perceived difficulty of this class for themselves. Results indicated that performance-approach goals significantly and positively predicted exam grades. Performance-avoidance goals significantly and negatively predicted grades. Both of these relationships were mediated by the perceived difficulty of the class for oneself. Thus, the links previously observed between performance goals and exam performance were replicated on an oral exam. Perceived difficulty is discussed as a key dimension responsible for these findings.

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This study presents new evidence concerning the uneven processes of industrialization innineteenth century Spain and Italy based on a disaggregate analysis of the productivesectors from which the behaviour of the aggregate indices is comprised. The use of multivariate time-series analysis techniques can aid our understanding and characterization of these two processes of industrialization. The identification of those sectors with key rolesin leading industrial growth provides new evidence concerning the factors that governed thebehaviour of the aggregates in the two economies. In addition, the analysis of the existenceof interindustry linkages reveals the scale of the industrialization process, and wheresignificant differences exist, accounts for many of the divergences recorded in the historiography for the period 1850-1913.

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Gout is the most common inflammatory arthritis and one in which pathogenesis and risk factors are best understood. One of the treatment objectives in current guidelines is 'cure'. However, audits show that only a minority of patients with gout receive adequate advice and treatment. Suboptimal care and outcomes reflect inappropriately negative perceptions of the disease, both in patients and providers. Historically, gout has been portrayed as a benign and even comical condition that is self-inflicted through overeating and alcohol excess. Doctors often focus on managing acute attacks rather than viewing gout as a chronic progressive crystal deposition disease. Urate-lowering treatment is underprescribed and often underdosed. Appropriate education of patients and doctors, catalysed by recent introduction of new urate-lowering treatments after many years with no drug development in the field, may help to overcome these barriers and improve management of this easily diagnosed and curable form of potentially severe arthritis.

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The aim of this article is to read accurately the novel by M. A. Riera from the point of view of the Classical Tradition and, specifically, from the perspective of the evident Platonic tradition ¿the most metaphysical Platonic love- upon which it is based. In the author¿s opinion, only this accurate reading makes us understand why certain values coming from Paganism and which were considered as such cannot be restored by the Platonic Western world.

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The aim of this article is to show not only what is the role played by eros in the Physics of the Ancient Stoicism but also to discover the meaning of the allegorical fellatio, a cosmogonal fellatio, which was introduced by Chrysippus in his Erotic Letters. The meaning of this intellectual boldness becomes quite clear if the texts are analyzed in accordance with the allegorical interpretation developed by the Stoics and when we also analyze the enodatio nominum of the word stóma.