Impact of extracardiac findings during cardiac MR on patient management and outcome.

BACKGROUND: Cardiac magnetic resonance (CMR) is increasingly used to assess heart diseases. Relevant non-cardiac diseases may also be incidentally found on CMR images. The aim of this study was to determine the prevalence and nature of incidental extra-cardiac findings (IEF) and their clinical impact in non-selected patients referred for CMR. MATERIAL/METHODS: MR images of 762 consecutive patients (515 men, age: 56±18 years) referred for CMR were prospectively interpreted by 2 radiologists blinded for any previous imaging study. IEFs were classified as major when requiring treatment, follow-up, or further investigation. Clinical follow-up was performed by checking hospital information records and by calling referring physicians. The 2 endpoints were: 1) non-cardiac death and new treatment related to major IEFs, and 2) hospitalization related to major IEFs during follow-up. RESULTS: Major IEFs were proven in 129 patients (18.6% of the study population), 14% of those being unknown before CMR. During 15±6 month follow-up, treatment of confirmed major IEFs was initiated in 1.4%, and no non-cardiac deaths occurred. Hospitalization occurred in 8 patients (1.0% of the study population) with confirmed major IEFs and none occurred in the remaining 110 patients with unconfirmed/unexplored major IEFs (p<0.001). CONCLUSIONS: Screening for major IEFs in a population referred for routine CMR changed management in 1.4% of patients. Major IEFs unknown before CMR but without further exploration, however, carried a favorable prognosis over a follow-up period of 15 months.

Du retraité méritant au senior actif : genèse et transformations de la figure sociale de la vieillesse en Suisse

«Crise de l'assurance-vieillesse », «déséquilibre démographique», «vieillissement de la population », « faillite des systèmes de retraite », voilà des expressions qui occupent une place prépondérante dans tes discours portant sur l'avenir de la sécurité sociale aujourd'hui. Les autorités politiques suisses comme européennes font part de leur inquiétude face à la situation d'urgence que présenteraient les « sociétés vieillissantes ». En effet, alors que F assurance-vieillesse s'adressait initialement à une catégorie résiduelle de personnes qui parvenait à vivre plusieurs années au-delà de 65 ans, elle couvre maintenant près d'un cinquième de la population globale. Partant, les autorités fédérales appellent à une restriction des conditions d'accès à la rente de vieillesse. À première vue, les débats qui portent sur cette question dans l'arène politique relèvent de considérations essentiellement techniques liées aux conditions économiques de perpétuation de l'assurances-vieillesse. Il s'agit de modifier les règles d'accès à l'assurance ainsi que le montant des prestations afin d'assainir les caisses tout en faisant face à l'augmentation du nombre de retraités. Ce travail de thèse aborde cette question par une autre approche. Nous partons du postulat que les débats portant sur l'avenir de la politique de la vieillesse sont révélateurs d'une lutte entre acteurs du champ de régulation sociale qui participent d'un travail d'élaboration d'une pensée d'Etat, au sens de P Bourdieu. Cette lutte a pour objet l'imposition de catégories de pensées, soit la définition de ce qu'est un âgé aujourd'hui et de ce qu'il est moralement acceptable d'attendre de lui Nous montrons que cette question peut être comprise à l'aune de l'histoire du traitement social de la vieillesse dont nous relatons ici la genèse et les transformations. Nous soulignons également combien cette pensée d'Etat marque la manière dont les retraités aujourd'hui cherchent à se valoriser face à la déstabilisation de leur statut social. Summary "Crisis of social insurance for older people", "demographic imbalance", "aging of the population", "bankruptcy of pensions systems" ; these are some of the many expressions that today play a importance part in discussion about the future of social security. The Swiss and European political authorities show they are concerned about the crisis that "aging societies" are said to be facing. Indeed, while social insurance for old age used to concern a residual category of people who managet! to live to more than 65 years old, it now covers about a fifth of the global population. Hence, the Federal authorities are calling for a tightening of the conditions for access to retirement benefits. At first glance, the debates in the political arena »elated to (his question mainly deal with technical considerations linked to the economic conditions for the perpetuation of the insurance for old age. Ease of access and the level of the benefits have to be reduced in order to balance the funds, in the face of the rise of the number beneficiaries. This thesis study addresses this question through a different approach. We start from the proposition that debates concerning the future of social policy for old age reveal a struggle between those involved in (he field of social regulation ; this struggle is part of the development of the thought of the State as conceived by P. Bourdieu. The aim of this fight is to impose normative categories of thought, that is to say in relation to our subject, the definition of what an older person is today and what is morally acceptable to expect of him or her. We show that this question can be understood in the light of the the history of the social treatment of old age that we report here. Moreover, we show that this thought of the State explains the way retired people seek to value themselves and confront the destabilisation of their social status.

Inhibitory Receptors Beyond T Cell Exhaustion.

Inhibitory receptors (iRs) are frequently associated with "T cell exhaustion". However, the expression of iRs is also dependent on T cell differentiation and activation. Therapeutic blockade of various iRs, also referred to as "checkpoint blockade", is showing -unprecedented results in the treatment of cancer patients. Consequently, the clinical potential in this field is broad, calling for increased research efforts and rapid refinements in the understanding of iR function. In this review, we provide an overview on the significance of iR expression for the interpretation of T cell functionality. We summarize how iRs have been strongly associated with "T cell exhaustion" and illustrate the parallel evidence on the importance of T cell differentiation and activation for the expression of iRs. The differentiation subsets of CD8 T cells (naïve, effector, and memory cells) show broad and inherent differences in iR expression, while activation leads to strong upregulation of iRs. Therefore, changes in iR expression during an immune response are often concomitant with T cell differentiation and activation. Sustained expression of iRs in chronic infection and in the tumor microenvironment likely reflects a specialized T cell differentiation. In these situations of prolonged antigen exposure and chronic inflammation, T cells are "downtuned" in order to limit tissue damage. Furthermore, we review the novel "checkpoint blockade" treatments and the potential of iRs as biomarkers. Finally, we provide recommendations for the immune monitoring of patients to interpret iR expression data combined with parameters of activation and differentiation of T cells.

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide.

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.

Judicialisation and Direct Democracy. Switzerland's Ban on Minaret Construction

Launched by representatives from the Union démocratique du centre (UDC) with the aim of circumventing political and judicial decisions made at both local and national levels, the 2009 federal popular initiative calling for a ban on the construction of minarets rekindled the stigmatisation of Muslims living in Switzerland. Within the prevalent institutional configuration it moreover revived controversies surrounding issues such as direct democracy versus fundamental rights, or "the will of the people" versus "the power of the judges", whether national or international. "Judicialisation" is a polysemous concept. It is not understood here as the transfer to the courts of matters of political significance - in this instance the public regulation of religion - but as a process of juridification (or juridicalisation) in which court rulings were constantly anticipated in the political debate provoked by the popular initiative.

Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration.

BACKGROUND & AIMS: Knockout studies of the murine Nuclear Factor I-C (NFI-C) transcription factor revealed abnormal skin wound healing and growth of its appendages, suggesting a role in controlling cell proliferation in adult regenerative processes. Liver regeneration following partial hepatectomy (PH) is a well-established regenerative model whereby changes elicited in hepatocytes lead to their rapid and phased proliferation. Although NFI-C is highly expressed in the liver, no hepatic function was yet established for this transcription factor. This study aimed to determine whether NFI-C may play a role in hepatocyte proliferation and liver regeneration. METHODS: Liver regeneration and cell proliferation pathways following two-thirds PH were investigated in NFI-C knockout (ko) and wild-type (wt) mice. RESULTS: We show that the absence of NFI-C impaired hepatocyte proliferation because of plasminogen activator I (PAI-1) overexpression and the subsequent suppression of urokinase plasminogen activator (uPA) activity and hepatocyte growth factor (HGF) signalling, a potent hepatocyte mitogen. This indicated that NFI-C first acts to promote hepatocyte proliferation at the onset of liver regeneration in wt mice. The subsequent transient down regulation of NFI-C, as can be explained by a self-regulatory feedback loop with transforming growth factor beta 1 (TGF-ß1), may limit the number of hepatocytes entering the first wave of cell division and/or prevent late initiations of mitosis. CONCLUSION: NFI-C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.

Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain.

In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial "whole-mount" dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system.