Науково-теоретична конференція «Гармонізація науки і вищої освіти в інформаційному суспільстві»

У Києві 30−31 березня 2011 року в Національному авіаційному університеті відбулася науково-теоретична конференція «Гармонізація науки і вищої освіти в інформаційному суспільстві»

Histoire des syndicats de fonctionnaires et du mouvement social en Seine Maritime de 1944 à 1981

In 1944, the National Council of Resistance decides to rebuild a welfare state, in continuation of the Popular Front, that the second World War stops it. The trade unions reunified, in CGT (except CFTC) decide to sustain this program. The trade unions of civil servants from Seine-Maritime organize themselves to take part in this rebuild that they waited for it. What are their demands ? On What do they lean themselves to put them before ? What are their values for which they fight? Do they wait all from the state ? What is their idea of this welfare state ? At least, what means do they use to fight for it and bring it to progress ? Getting the recognition of their freedom union laws, which includes right striking, they agree civil servant status which turn out very protective against their adminstration and its hierarchy. They get too the management of Health Security by their mutual insurances which lead them, in Seine-Maritme, to build a powerful departemental mutual insurance. However, the division of world in two blocks, one liberal and one communist, goes through these trade unions and leads to the break away of 1947 That does not prevent the participation to strikes of 1953 wich they are be able to save their retirement. If they sustain general De Gaulle in his decolonization policy and against seditious generals, they clash him on his institutional, économic and social policy. The strike of 1968 is the culmination of it, throuhgout adjournements. But in order to restore the welfare state that they hope, they must sustain lefts’ candidate, François Mitterrand, in their electoral compaigns of 1974 and 1981, who wins in this last year, in spite of their differences and thanks to the Will of unity of their activists.En 1944, le Conseil national de la Résistance décide de reconstruire un Etat social dans la continuité du Front populaire, avant que le second conflit ne l’interrompe. Les syndicats ouvriers réunifiés dans la CGT (sauf la CFTC) décident de soutenir ce programme. Les syndicats de fonctionnaires de Seine-Maritime s’organisent pour participer à cette reconstruction qu’ils attendaient. Quels sont leurs revendications ? Sur quoi s’appuient-ils pour les mettre en avant ? Quels sont les valeurs qu’ils défendent ? Attendent-ils tout de l’Etat social ? Quelle est leur conception de cet Etat social ? Enfin, quels moyens utilisent-ils pour le défendre et le faire progresser ? Obtenant la reconnaissance de leur liberté syndicale qui comprend le droit de grève, ils acceptent un statut qui se révèle fort protecteur vis-à-vis de l’administration et de sa hiérarchie. Ils obtiennent aussi la gestion de la Sécurité sociale par leurs mutuelles qui les entraînent, en Seine-Maritime, à construire une mutualité départementale unifiée et puissante. Toutefois, la division du monde en deux blocs, un libéral et un communiste, traverse ces syndicats et aboutit à la scission de 1947. Cela n’empêche pas la participation aux grèves de 1953 qui leur permet de sauver leur retraite. S’ils soutiennent le général de Gaulle (1890-1970) dans sa politique de décolonisation et contre les généraux factieux, ils l’affrontent sur sa politique institutionnelle, économique et sociale. La grève de 1968 en est l’aboutissement, par-delà les remises en cause. Mais pour rétablir l’Etat social qu’ils souhaitent, il leur faut soutenir les campagnes électorales de 1974 et 1981 du candidat de la gauche, François Mitterrand (1916-1996), qui l’emporte en 1981, en dépit de leurs divergences et grâce à la volonté unitaire de leurs militants

Аксіологічні виміри душпастирства у творах Іоана Золотоустого

Стаття Світлани Білоус "Аксіологічні виміри душпастирства у творах Іоана Золотоустого" присвячена пошуку джерел духовної опіки над людиною, витоки яких автор бачить у християнському середньовіччі. Життя і творча спадщина Іоана Золотоустого – яскравий приклад пояснення сутності й визначення ціннісної природи душпастирювання крізь призму поняття священства.Статья Светланы Билоус "Аксиологические измерения душпастирства в произведениях Іоана Золотоустого" посвящена поиску источников духовной опеки над человеком, истоки которіх автор видит в христианском средневековье. Жизнь и творческое наследство Иоанна Золотоустого – яркий пример объяснения сущности и определение ценностной природы душпастирства сквозь призму понятия священства.The article by Svitlana Bilous "Axiological dimensions of priesthood in the Ioan Zolotoustyi’s works" is dedicated to finding sources of spiritual care over a human, the origin of which the author sees in the Christian Middle Ages. The life and literary heredity of Ioan Zolotoustyi is a brilliant pattern of explaining the essence and definition of valuable ​​nature of pastoral care through the prism of the concept of the priesthood

Letter regarding Zhao et al. entitled "DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia"

Zhao et al. investigated the association between germline genetic polymorphisms in DPYD, the gene encoding dihydropyrimidine dehydrogenase, and (1) the risk of developing pediatric acute lymphoblastic leukemia and (2) outcome of acute lymphoblastic leukemia following the treatment with 5-fluorouracil plus oxaliplatin (FOLFOX). The authors found that the common DPYD variant c.85T>C (rs1801265, DPYD*9A) was significantly associated with (1) risk of developing pediatric acute lymphoblastic leukemia, (2) complete response rate, (3) event-free survival, and (4) treatment-related toxicity. The authors conclude that patients carrying the c.85T>C C allele have an increased risk of developing acute lymphoblastic leukemia and have inferior outcome, and that DPYD c.85T>C can be used as a guide for individualized treatment and the decision to utilize 5-fluorouracil in acute lymphoblastic leukemia patients. In our view, the published article gives rise to multiple critical issues regarding the study's rationale and the methodology used, which strongly question the validity of the authors' conclusions

Letter regarding Zhao et al. entitled "DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia"

Zhao et al. investigated the association between germline genetic polymorphisms in DPYD, the gene encoding dihydropyrimidine dehydrogenase, and (1) the risk of developing pediatric acute lymphoblastic leukemia and (2) outcome of acute lymphoblastic leukemia following the treatment with 5-fluorouracil plus oxaliplatin (FOLFOX). The authors found that the common DPYD variant c.85T>C (rs1801265, DPYD*9A) was significantly associated with (1) risk of developing pediatric acute lymphoblastic leukemia, (2) complete response rate, (3) event-free survival, and (4) treatment-related toxicity. The authors conclude that patients carrying the c.85T>C C allele have an increased risk of developing acute lymphoblastic leukemia and have inferior outcome, and that DPYD c.85T>C can be used as a guide for individualized treatment and the decision to utilize 5-fluorouracil in acute lymphoblastic leukemia patients. In our view, the published article gives rise to multiple critical issues regarding the study's rationale and the methodology used, which strongly question the validity of the authors' conclusions

Haplotype structure defines effects of common DPYD variants c.85T > C (rs1801265) and c.496A > G (rs2297595) on dihydropyrimidine dehydrogenase activity: Implication for 5-fluorouracil toxicity.

AIMS The aim of this study was to identify risk variants and haplotypes that impair dihydropyrimidine dehydrogenase (DPD) activity and are, therefore, candidate risk variants for severe toxicity to 5-fluorouracil (5-FU) chemotherapy. METHODS Plasma dihydrouracil/uracil (UH2 /U) ratios were measured as a population marker for DPD activity in a total of 1382 subjects from 4 independent studies. Genotype and haplotype correlations with UH2 /U ratios were assessed. RESULTS Significantly lower UH2 /U ratios (panova A (rs3918290), -46.0% for DPYD c.1679T > G (rs55886062), -37.1%, for DPYD c.2846A > T (rs67376798), and -13.2% for DPYD c.1129-5923C > G (rs75017182). An additional variant, DPYD c.496A > G (rs2297595), was also associated with lower UH2 /U ratios (P G, which consisted of the common variant c.85T > C (rs1801265) and the risk variant c.1129-5923C > G. Both haplotypes carrying c.496A > G were associated with decreased UH2 /U ratios (H3, P = .003, MD: -9.6%; H5, P = .002, MD: -16.9%). A haplotype carrying only the variant c.85T > C (H2) was associated with elevated ratios (P = .004, MD: +8.6%). CONCLUSIONS Based on our data, DPYD-c.496A > G is a strong candidate risk allele for 5-FU toxicity. Our data suggest that DPYD-c.85T > C might be protective; however, the deleterious impacts of the linked alleles c.496A > G and c.1129-5923C > G likely limit this effect in patients. The possible protective effect of c.85T > C and linkage disequilibrium with c.496A > G and c.1129-5923C > G may have hampered prior association studies and should be considered in future clinical studies

Pharmacogenetic variants associated with outcome in patients with advanced gastric cancer treated with fluoropyrimidine and platinum-based triplet combinations : a pooled analysis of three prospective studies

The main treatment for advanced gastric cancer is fluoropyrimidine and platinum-based chemotherapy. We investigated the clinical validitiy of 19 candidate pharmacogenetic variants in ENOSF1 (enolase superfamily member 1), TYMS, CDA, MTHFR, TYMP, DPYD, ERCC1, ERCC2, GSTP1, GSTT1, GSTM1, CYP3A4 and CYP3A5 in relation to overall survival (OS), progression-free survival, objective response rate (ORR) and toxicity in 185 patients receiving triplet chemotherapy. The formal significance threshold was P<0.0026. TYMS VNTR (variable number of 28-bp tandem repeats) 3 R/3 R genotype was formally associated with inferior ORR (odds ratio (OR) 0.3, P=0.0025), whereas ENOSF1 rs2612091 G/G was nominally associated with OS after adjustment for TYMS 3 R/3 R (hazard ratio (HR) 1.5, P=0.041). In a subgroup analysis of patients with locally advanced disease (n=33), ENOSF1 rs2612091 was strongly associated with OS (HR 6.5, P=0.001). CYP3A4*22/CYP3A5*3 genotype was nominally associated with grade 3/4 toxicity in patients receiving docetaxel-containing chemotherapy (P=0.0175). This is the first study suggesting that ENOSF1 rs2612091 is prognostic or predictive of OS in gastric cancer. This finding requires prospective validation.The Pharmacogenomics Journal advance online publication, 20 December 2016; doi:10.1038/tpj.2016.81

Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma

Quantification of the endogenous dihydropyrimidine dehydrogenase (DPD) substrate uracil (U) and the reaction product dihydrouracil (UH2) in plasma might be suitable for identification of patients at risk of fluoropyrimidine-induced toxicity as a result of DPD deficiency. In this paper, we describe the development and validation of a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantification of U and UH2 in human plasma. Analytes were extracted by protein precipitation, chromatographically separated on an Acquity UPLC(®) HSS T3 column with gradient elution and analyzed with a tandem mass spectrometer equipped with an electrospray ionization source. U was quantified in the negative ion mode and UH2 in the positive ion mode. Stable isotopes for U and UH2 were used as internal standards. Total chromatographic run time was 5min. Validated concentration ranges for U and UH2 were from 1 to 100ng/mL and 10 to 1000ng/mL, respectively. Inter-assay bias and inter-assay precision for U were within ±2.8% and ≤12.4%. For UH2, inter-assay bias and inter-assay precision were within ±2.9% and ≤7.2%. Adequate stability of U and UH2 in dry extract, final extract, stock solution and plasma was demonstrated. Stability of U and UH2 in whole blood was only satisfactory when stored up to 4hours at 2-8°C, but not at ambient temperatures. An accurate, precise and sensitive UPLC-MS/MS assay for quantification of U and UH2 in plasma was developed. This assay is now applied to support clinical studies with fluoropyrimidine drugs

Baclofen overdose treated with continuous venovenous hemofiltration

Purpose: Overdose with baclofen, a derivative of the inhibitory neurotransmitter γ-aminobutyric acid, may lead to severe respiratory and central nervous system depression and can be life-threatening. Prolonged half-lives of baclofen, of up to 34 h, have been reported in patients after overdose. Hemodialysis has proven to be a successful approach to improve clearance of baclofen, but the value of continuous venovenous hemofiltration (CVVH) is unclear. We applied CVVH in a patient with acute baclofen overdose. Methods: Pharmacokinetic measurements of baclofen in serum and hemofiltrate were made at six time points after hospital admission. Baclofen concentration-time data were analyzed using non-compartmental methods, and the relative contribution of clearance by hemofiltration to total baclofen clearance was calculated. Results: Baclofen concentrations in serum varied between 1.81 and 0.05 mg/L. Concentrations of baclofen in hemofiltrate were within the same range (between 0.74 and 0.05 mg/L), and the elimination half-life during hemofiltration was estimated at 4.8 h. Total clearance and clearance via hemofiltration were estimated at 6.6 and 2.4 L/h, indicating that clearance could be increased by approximately 57 % by applying hemofiltration. Conclusions: The presented case demonstrates the usefulness of CVVH in the treatment of baclofen overdose and indicates that CVVH can be used as an alternative to hemodialysis in patients with overdose of baclofen