104 research outputs found
Appealing Outcomes: A Study for the Overturn Rate of Canada\u27s Appellate Courts
This commentary discusses the rate at which Canada\u27s appellate courts are overturned by the Supreme Court of Canada. By deconstructing the overturn rate, the authors identify and compare various factors that affect the rate at which appeals are pursued, considered, and allowed. The data reveal that decisions from the British Columbia, Quebec, and Newfoundland & Labrador courts of appeal are overturned more often than those from their counterparts. Conversely, the Ontario and Saskatchewan courts of appeal exhibit overturn rates below the national average. The analysis suggests that the underlying drivers giving rise to the unusually high or low overturn rates, however, differ from province to province, and this provides possible avenues for further investigation
Appealing Outcomes: A Study for the Overturn Rate of Canada\u27s Appellate Courts
This commentary discusses the rate at which Canada\u27s appellate courts are overturned by the Supreme Court of Canada. By deconstructing the overturn rate, the authors identify and compare various factors that affect the rate at which appeals are pursued, considered, and allowed. The data reveal that decisions from the British Columbia, Quebec, and Newfoundland & Labrador courts of appeal are overturned more often than those from their counterparts. Conversely, the Ontario and Saskatchewan courts of appeal exhibit overturn rates below the national average. The analysis suggests that the underlying drivers giving rise to the unusually high or low overturn rates, however, differ from province to province, and this provides possible avenues for further investigation
Involvement of the Cytokine MIF in the Snail Host Immune Response to the Parasite Schistosoma mansoni
We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions
Macrophage Migration Inhibitory Factor Antagonist Blocks the Development of Endometriosis In Vivo
Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue
Small-molecule inhibitors of macrophage migration inhibitory factor(MIF) as an emerging class of therapeutics for immune disorders
Macrophage migration inhibitory factor (MIF) is an important cytokine for which an increasing number of functions is being described in the pathogenesis of inflammation and cancer. Nevertheless, the availability of potent and druglike MIF inhibitors that are well-characterized in relevant disease models remains limited. Development of highly potent and selective small-molecule MIF inhibitors and validation of their use in relevant disease models will advance drug discovery. In this review, we provide an overview of recent advances in the identification of MIF as a pharmacological target in the pathogenesis of inflammatory diseases and cancer. We also give an overview of the current developments in the discovery and design of
small-molecule MIF inhibitors and define future aims in this fiel
Reopening the Langelier—Mignault Debate on Unauthorized Transactions Involving a Minor's Property
Under section 213 C.C.Q., immovables, enterprises, and important pieces of family property belonging to a minor can only be sold in cases of necessity, and only then with prior authorization from the court or the tutorship council. What is the legal status, therefore, of a contract of sale of a minor's property made by his tutor in violation of this provision? This question inspired a vigorous debate in both France and Quebec throughout the nineteenth century. Mignault "settled'' this debate in 1896 by declaring such a contract to be tainted with relative nullity. Now, over a century later, the law's attitude toward the protection of minors has changed significantly, which makes it appropriate to revisit Mignault's thesis. This paper argues that the sanction of relative nullity is inconsistent with both the text and underlying policy objectives of the section, and that an alternative approach must be adopted.Selon l’article 213 C.c.Q., les immeubles, les entreprises et les biens importants à caractère familial appartenant à un mineur ne peuvent être vendus qu’en cas de nécessité et avec une autorisation préalable du tribunal ou du conseil de tutelle. Quel est alors le statut juridique d’un contrat de vente d’un bien appartenant à un mineur faite par son tuteur en violation de cet article ? Cette question a été à l’origine d’un vigoureux débat, en France ainsi qu’au Québec, au cours du 19e siècle. Mignault le trancha en 1896 en déclarant un tel contrat entaché de nullité relative. Aujourd’hui, plus d’une centaine d’années plus tard, la position du législateur à l’égard de la protection des mineurs a beaucoup évolué, ce qui nécessite une réévaluation de la solution apportée par Mignault. Cet article soutient que la sanction de nullité relative va à l’encontre du libellé et des objectifs de l’article 213 C.c.Q. et qu’une approche alternative doit être adoptée
- …