57 research outputs found
Upfront Genotyping of DPYD* 2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis
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»
Upfront Genotyping of DPYD* 2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis
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
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
DPYD genotype-guided dose individualization of fluoropyrimidine therapy: A prospective safety and cost-analysis on DPYD variants DPYD*2A, c.2846A>T, c.1679T>G and c.1236G>A
Pharmacogenetic-Pharmacokinetic Interactions in Drug Marketing Authorization Applications via the European Medicines Agency Between 2014 and 2017
This study aimed to determine to which extent data on potential pharmacogenetic-pharmacokinetic (PG-PK) interactions are provided to, and assessed by, the European Medicines Agency (EMA) in novel drug marketing authorization applications (MAAs), and whether regulatory assessment of PG-PK interactions is adequate or could be optimized. For this purpose, we retrospectively analyzed MAAs of small molecule drugs assessed by the EMA between January 2014 and December 2017. As per two key requirements in the EMA’s guideline, we analyzed cases where (i) a single functionally polymorphic drug metabolizing enzyme (DME) metabolizes > 25% of the drug, or (ii) the drug’s PK shows high interindividual variability not explained by other factors than PG. Results showed that, of 113 drugs analyzed, 53 (47%) had ≥ 1 functionally polymorphic DME accounting for > 25% of the drug’s metabolism, yielding 55 gene-drug pairs. For 36 of 53 (68%) of the products, CYP3A4 was the major DME. Compliance with European Union (EU) guidance on PG-PK issues in drug development was notably different for CYP3A4 substrates vs. non-CYP3A4 substrates. Adequate PG-PK data were provided during registration in 89% (16/18) of cases concerning non-CYP3A4 substrates, compared with 32% (12/37) of cases concerning CYP3A4 substrates. Concluding, PG-PK interactions related to non-CYP3A4 substrate drugs were, in general, addressed adequately in EU MAAs. PG-PK information on CYP3A4 substrates was available less frequently, despite some available evidence on the functional relevance of CYP3A4 polymorphisms. A more harmonized approach toward assessment of PG-PK issues in EU MAAs seems warranted, and a discussion on the relevance of CYP3A4 polymorphisms, such as CYP3A4*22, is recommended
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
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