61 research outputs found

    Comparing all-optical switching in synthetic-ferrimagnetic multilayers and alloys

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    We present an experimental and theoretical investigation of all-optical switching by single femtosecond laser pulses. Our experimental results demonstrate that, unlike rare earth-transition metal ferrimagnetic alloys, Pt/Co/[Ni/Co]N_N/Gd can be switched in the absence of a magnetization compensation temperature, indicative for strikingly different switching conditions. In order to understand the underlying mechanism, we model the laser-induced magnetization dynamics in Co/Gd bilayers and GdCo alloys on an equal footing, using an extension of the microscopic three-temperature model to multiple magnetic sublattices and including exchange scattering. In agreement with our experimental observations, the model shows that Co/Gd bilayers can be switched for an arbitrary thickness of the Co layer, i.e, even far away from compensating the total Co and Gd magnetic moment. We identify the switching mechanism in Co/Gd bilayers as a front of reversed Co magnetization that nucleates at the Co/Gd interface and propagates through the Co layer driven by exchange scattering.Comment: Published versio

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

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

    Trends in Drug Costs and Overall Survival in Patients with Metastatic Non-small Cell Lung Cancer in The Netherlands Diagnosed from 2008 Through 2014

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    BACKGROUND: The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). METHODS: All patients diagnosed (in 2008-2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. RESULTS: Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years (p = 0.437 and p = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011-2014 compared with 2008-2010. CONCLUSION: This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years

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

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    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

    A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer

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    Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide. Objective: We aimed to develop alternative dosing regimens to reduce drug expenses. Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development. Results: We found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure. Conclusions: Dosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice.</p

    Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial

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    INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan. METHODS AND ANALYSIS: This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult pa

    CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer

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    Background: Although radical surgery remains the cornerstone of cure in resectable gastric cancer, survival remains poor. Current evidence-based (neo)adjuvant strategies have shown to improve outcome, including perioperative chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy. However, these regimens suffer from poor patient compliance, particularly in the postoperative phase of treatment. The CRITICS-II trial aims to optimize preoperative treatment by comparing three treatment regimens: (1) chemotherapy, (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy. Methods: In this multicentre phase II non-comparative study, patients with clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2) 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event-free survival, 1 year after randomisation (events are local and/or regional recurrence or progression, distant recurrence, or death from any cause). Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers. Discussion: The aim of this study is to select the most promising among three preoperative treatment arms in patients with resectable gastric adenocarcinoma. This treatment regimen will subsequently be compared with the standard therapy in a phase III trial

    Is Fluorouracil-Induced Severe Toxicity in DPYD*2A

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