Thermodynamic evaluation of oxidation during brazing process of medium-voltage electrical circuit breakers

International audienceThe present study is a thermodynamic analysis of the different molecular flows occurring during the vacuum brazing of electrical vacuum bottles also called Vacuum In-terrupters (mentioned later as VI). Among the available impurities either coming from the Vacuum Interrupters components materials or from vacuum technology, the analysis is fo-cused on the oxygen since this impurity leads to formation of the more stable compounds, i.e. oxides. During the brazing cycles the resistors of the vacuum furnace and the VI materials including some braze components are the main sources of vapours that partly escape or make deposits on colder parts of the furnace. Vaporization and condensation processes are evaluated, their matter flows quantified and finally their interaction with residual oxygen calculated through a balance between input oxygen from vacuum or neutral gas and the different sources of oxygen coming from the parts under treatment. The enrichment of the VI materials and deposits with oxygen is evaluated as well as the limits required for vacuum conditions. The main conclusion is that present vacuum conditions allow correct working of the brazing sequence but in any other temperature steps or ramps, oxygen is trapped as oxides at the surface of the parts or accumulated in the bulk materials of the furnace

Thermodynamic evaluation of oxidation during brazing process of medium-voltage electrical circuit breakers

International audienceThe present study is a thermodynamic analysis of the different molecular flows occurring during the vacuum brazing of electrical vacuum bottles also called Vacuum In-terrupters (mentioned later as VI). Among the available impurities either coming from the Vacuum Interrupters components materials or from vacuum technology, the analysis is fo-cused on the oxygen since this impurity leads to formation of the more stable compounds, i.e. oxides. During the brazing cycles the resistors of the vacuum furnace and the VI materials including some braze components are the main sources of vapours that partly escape or make deposits on colder parts of the furnace. Vaporization and condensation processes are evaluated, their matter flows quantified and finally their interaction with residual oxygen calculated through a balance between input oxygen from vacuum or neutral gas and the different sources of oxygen coming from the parts under treatment. The enrichment of the VI materials and deposits with oxygen is evaluated as well as the limits required for vacuum conditions. The main conclusion is that present vacuum conditions allow correct working of the brazing sequence but in any other temperature steps or ramps, oxygen is trapped as oxides at the surface of the parts or accumulated in the bulk materials of the furnace

Prevention and treatment of postoperative Crohn's disease recurrence with anti-TNF therapy: A meta-analysis of controlled trials

International audienceBACKGROUND:The magnitude of the efficacy of anti-tumour necrosis factor (TNF) therapy in preventing and treating postoperative Crohn's disease recurrence has yet to be determined.METHODS:We searched MEDLINE, the Cochrane Library, and EMBASE. The primary endpoints, and clinical and endoscopic recurrence, were analysed using the Mantel-Haenszel and DerSimonian and Laird methods.RESULTS:Nine controlled trials (n=362) that evaluated the efficacy of anti-TNF therapy in preventing (n=7) or treating (n=2) postoperative recurrence were included. Anti-TNF therapy was more effective at preventing (n=6) endoscopic recurrence than the control arms (odds ratio 0.05; 95% confidence interval 0.02-0.13, P<0.0001; NNT=1.9). Anti-TNF therapy was more effective at preventing (n=5) clinical recurrence than the control arms (odds ratio 0.10; 95% confidence interval 0.05-0.21, P<0.0001; NNT=2.4). Anti-TNF therapy was more effective than control arms at treating endoscopic postoperative recurrence (n=2; odds ratio 16.64; 95% confidence interval 2.51-110.27, P<0.004; NNT=2.3). Neither heterogeneity nor publication bias was observed.CONCLUSION:Anti-TNF agents may be more effective in preventing clinical and endoscopic postoperative Crohn's disease recurrence than control treatment (thiopurines or mesalamine). Efficacy in treating postoperative Crohn's disease recurrence will require further investigation. Large randomised controlled trials are awaited

Rage in video gaming, characteristics of loss of control among gamers: A qualitative study.

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Effect of Gevokizumab on Interleukin-1 beta-Mediated Cytochrome P450 3A4 and Drug Transporter Repression in Cultured Human Hepatocytes

International audienceBackground and objectives - Gevokizumab is a potent anti-interleukin (IL)-1β neutralizing monoclonal antibody (mAb), which may be used for treating inflammatory or autoimmune diseases. The present study was designed to characterize the potential effects of this mAb towards well-established IL-1β-mediated repression of hepatic drug detoxifying proteins, like cytochrome P450 (CYP) 3A4 and drug transporters. Methods - Primary cultured human hepatocytes were exposed to various concentrations of IL-1β in the absence or presence of gevokizumab (5 µg/mL); mRNA expression and activity of CYP3A4 and transporters were next determined. Results - Gevokizumab was found to down-modulate, but not abolish, the repression of CYP3A4 and drug transporter mRNAs caused by IL-1β in human hepatocytes, through shifting up IL-1β half maximal inhibitory concentration (IC) values by factors ranging from 6.8 to 10.4. The mAb concomitantly shifted IL-1β IC values towards CYP3A4 activity from 22.0 pg/mL (in the absence of gevokizumab) to 796 pg/mL (in the presence of gevokizumab) and counteracted the decrease of organic anion-transporting polypeptide activity occurring in response to 50 pg/mL IL-1β, but not that occurring at higher IL-1β concentration (1000 pg/mL). Conclusion - Gevokizumab attenuates, but not abolishes, IL-1β-mediated functional repression of CYP3A4 and drug transporters in human hepatocytes, which agrees with the fact that the mAb is considered as a modulator and not a blocker of IL-1β signaling. This attenuation of IL-1β-mediated down-regulation of hepatic detoxifying proteins by gevokizumab may have to be evaluated in terms of potential therapeutic protein drug-drug interactions when considering future development and therapeutic uses of this IL-1β neutralizing mAb

Inhibition of canalicular and sinusoidal taurocholate efflux by cholestatic drugs in human hepatoma HepaRG cells

International audienceHepaRG cells are highly-differentiated human hepatoma cells, which are increasingly recognized as a convenient cellular model for in vitro evaluation of hepatic metabolism, transport and/or toxicity of drugs. The present study was designed to evaluate whether HepaRG cells can also be useful for studying drug-mediated inhibition of canalicular and/or sinusoidal hepatic efflux of bile acids, which constitutes a major mechanism of drug-induced liver toxicity (DILI). For this purpose, HepaRG cells, initially loaded with the bile acid taurocholate (TC), were re-incubated in TC-free transport assay medium, in the presence or absence of calcium or drugs, before analysis of TC retention. This method allowed to objectivise and quantitatively measure biliary and sinusoidal efflux of TC from HepaRG cells, through distinguishing cellular and canalicular compartments. In particular, time-course analysis of the TC-free re-incubation period of HepaRG cells, i.e., the efflux period, indicated that a 20 min-efflux period allowed to reach biliary and sinusoidal excretion indexes for TC around 80 % and 60 %, respectively. Addition of the prototypical cholestatic drugs bosentan, cyclosporin A, glibenclamide or troglitazone during the TC-free efflux phase period was demonstrated to markedly inhibit canalicular and sinusoidal secretion of TC, whereas, by contrast, incubation with the non-cholestatic compounds salicylic acid or flumazenil was without effect. Such data therefore support the use of human HepaRG cells for in vitro predicting DILIs due to inhibition of hepatic bile acid secretion, using a biphasic TC loading/efflux assay. This article is protected by copyright. All rights reserved

Rage in video gaming, characteristics of loss of control among gamers: A qualitative study

Introduction: Online forums devoted to video games dedicate discussions to a phenomenon named “rage” that produces difficulties for gamers. Rage is described as expressing violent and impulsive reactions through excessive frustration or bad faith while gaming. The description of “rage” is close to the description of “tilt” in the context of online poker. The aim of this qualitative study was to describe rage as it occurs in online video games and to identify its etiology and consequences.Method: A qualitative study included 24 gamers aged between 18 and 30 years old. Semi-directive interviews were conducted and participants completed an online survey. Two researchers rated each interview using the thematic analysis method, and reported an agreement rate of 83%. Results: Rage was described by gamers as a change in the manner of playing caused by a feeling of frustration during the game. Rage has components that are behavioral (aggressive behaviors), cognitive (poor decision-making) and emotional (anger). Rage can be contagious among gamers and may result in the loss of the game and a “rage quit”, in other words an abrupt cessation of the game.Discussion: Rage is a phenomenon of loss of control that occurs while playing an online video game. It has similar characteristics to tilt in online poker. However, the outcomes of tilt and rage are different and might lead to opposite relations with addiction behaviors

Rage in Video Gaming, Characteristics of Loss of Control Among Gamers: A Qualitative Study

International audienceOnline forums devoted to video games dedicate discussions to a phenomenon called "rage" that produces difficulties for gamers. Rage is described as expressing violent and impulsive reactions through excessive frustration or bad faith while gaming. The aim of this qualitative study was to describe rage as it occurs in online video games and to identify its etiology and consequences. A qualitative study included 24 gamers aged 18-30 years. Semidirective interviews were conducted, and participants completed an online survey. Two researchers rated each interview using the thematic analysis method and reported an agreement rate of 83%. The gamers described rage as a change in the manner of playing caused by a feeling of frustration during the game. Rage has components that are behavioral (aggressive behaviors), cognitive (poor decision making), and emotional (anger). Rage can be contagious among gamers and may result in the loss of the game and a "rage quit," an abrupt cessation of the game. Rage appears of prime importance to regulate rage episodes and targeting emotion regulation, which can be used as a hook for the prevention of problematic gaming. Public Policy Relevance Statement Rage is a phenomenon of behavioral, emotional, and cognitive loss of control that occurs while playing an online video game. Rage could have consequences on the psychological well-being of players and their teammates. Players seek to control rage episodes to perform in the game; rage could also be a gateway for prevention

Association Between 6-Thioguanine Nucleotides Levels and Clinical Remission in Inflammatory Disease

International audienceBACKGROUND:A previous meta-analysis suggested that 6-thioguanine nucleotides levels are associated with clinical remission in inflammatory bowel disease. It was criticized because of the relatively small number of patients included in this meta-analysis and heterogeneity between studies. Recent studies provided conflicting results, and the source of those discrepancies has yet to be explored.METHODS:A comprehensive, computerized literature search was conducted in Medline, ISI Web of Science, and EMBASE until December 31, 2012. A combined odd ratio with its 95% confidence interval was calculated using a fixed effects model based on the Mantel-Haenszel method. Between-study heterogeneity was assessed using Cochran's Q statistic.RESULTS:Seventeen studies enrolling 2049 patients with inflammatory bowel disease were analyzed. A significant heterogeneity was found in the overall analysis (P = 0.005). As heterogeneity among studies could be explained by differences in metabolite assay methods, an analysis including only studies using the reference method by Lennard et al (N = 10) was performed, and the pooled odds ratio for clinical remission among patients with 6-thioguanine nucleotides levels over a cut-off value between 230 and 260 pmol/8.10^8 RBC was 3.15 (95% confidence interval, 2.41-4.11).CONCLUSIONS:This meta-analysis clearly establishes an association between 6-thioguanine nucleotides levels and clinical remission rates in patients with inflammatory bowel disease and explains the heterogeneity of results among selected studies. The lack of standardization in 6-thioguanine nucleotides assays is responsible for recent contradictory results. Whether therapeutic drug monitoring of thiopurines should be systematically used in clinical practice in inflammatory bowel disease to improve disease outcomes will require further investigation