Katholieke Universiteit Leuven

About: Katholieke Universiteit Leuven is a education organization based out in Leuven, Belgium. It is known for research contribution in the topics: Population & Context (language use). The organization has 61109 authors who have published 176584 publications receiving 6210872 citations.

Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis

Abstract: A B S T R AC T BACKGROUND Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti–interleukin-1β monoclonal antibody, in two trials. METHODS In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilo gram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, pa tients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to pla cebo (74% of patients in the canakinumab group had no flare, vs. 25% in the pla

Performance Management in the Public Sector

Abstract: 1. Introduction 2. Defining the Concepts 3. The History of Performance Management 4. Performance Measurement 5. Incorporation of Performance Information 6. The use of Performance Information 7. Users 8. Non-use 9. The Effects of Using Performance Information 10. The Future of Performance Management

Locally compact quantum groups

Abstract: These lecture notes are intended as an introduction to the theory of locally compact quantum groups that are studied in the framework of operator algebras, i.e. C*-algebras and von Neumann algebras. The presentation revolves around the definition of a locally compact quantum group as given in [KuV00a] and [KuV03].

Lomustine and Bevacizumab in Progressive Glioblastoma

Abstract: BACKGROUND: Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. METHODS: We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients). The methylation status of the promoter of O6methylguanine–DNA methyltransferase (MGMT) was assessed. Healthrelated quality of life and neurocognitive function were evaluated at baseline and every 12 weeks. The primary end point of the trial was overall survival. RESULTS: A total of 437 patients underwent randomization. The median number of 6week treatment cycles was three in the combination group and one in the monotherapy group. With 329 overall survival events (75.3%), the combination therapy did not provide a survival advantage; the median overall survival was 9.1 months (95% confidence interval [CI], 8.1 to 10.1) in the combination group and 8.6 months (95% CI, 7.6 to 10.4) in the monotherapy group (hazard ratio for death, 0.95; 95% CI, 0.74 to 1.21; P=0.65). Locally assessed progression-free survival was 2.7 months longer in the combination group than in the monotherapy group: 4.2 months versus 1.5 months (hazard ratio for disease progression or death, 0.49; 95% CI, 0.39 to 0.61; P<0.001). Grade 3 to 5 adverse events occurred in 63.6% of the patients in the combination group and 38.1% of the patients in the monotherapy group. The addition of bevacizumab to lomustine affected neither healthrelated quality of life nor neurocognitive function. The MGMT status was prognostic. CONCLUSIONS: Despite somewhat prolonged progressionfree survival, treatment with lomustine plus bevacizumab did not confer a survival advantage over treatment with lomustine alone in patients with progressive glioblastoma. (Funded by an unrestricted educational grant from F. Hoffmann–La Roche and by the EORTC Cancer Research Fund; EORTC 26101 ClinicalTrials.gov number, NCT01290939; EudraCT number, 201002321830.)

Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria

Abstract: Autophagy and apoptosis are two important and interconnected stress-response mechanisms. However, the molecular interplay between these two pathways is not fully understood. To study the fate and function of autophagic proteins at the onset of apoptosis, we used a cellular model system in which autophagy precedes apoptosis. IL-3 depletion of Ba/F3 cells caused caspase (casp)-mediated cleavage of Beclin-1 and PI3KC3, two crucial components of the autophagy-inducing complex. We identified two casp cleavage sites in Beclin-1, TDVD133 and DQLD149, cleavage at which yields fragments lacking the autophagy-inducing capacity. Noteworthy, the C-terminal fragment, Beclin-1-C, localized predominantly at the mitochondria and sensitized the cells to apoptosis. Moreover, on isolated mitochondria, recombinant Beclin-1-C was able to induce the release of proapoptotic factors. These findings point to a mechanism by which casp-dependent generation of Beclin-1-C creates an amplifying loop enhancing apoptosis upon growth factor withdrawal.