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Sökning: WFRF:(Bottomley D.)

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1.
  • Parker, C., et al. (författare)
  • Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
  • 2013
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:3, s. 213-223
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. Methods In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. Results At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. Conclusions In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.)
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2.
  • Journeau, C., et al. (författare)
  • European Research on the Corium issues within the SARNET network of excellence
  • 2008
  • Ingår i: International Conference on Advances in Nuclear Power Plants, ICAPP 2008. - 9781605607870 ; , s. 1172-1181
  • Konferensbidrag (refereegranskat)abstract
    • Within SARNET, the corium topic covers all the behaviors of corium from early phase of core degradation to in or ex-vessel corium recovery with the exception of corium interaction with water, direct containment heating and fission product release. The corium topic regroups in three work packages the critical mass of competence required to improve significantly the corium behavior knowledge. The spirit of the SARNET networking is to share the knowledge, the facilities and the simulation tools for severe accidents, so to reach a better efficiency and to rationalize the R&D effort at European level. Extensive benchmarking has been launched in most of the areas of research. These benchmarks were mainly dedicated to the recalculation of experiments, while, in the next periods, a larger focus will be given to integral experiments or reactor applications. Eventually, all the knowledge will be accumulated in the ASTEC severe accident simulation code through physical model improvements and extension of validation database. This paper summarizes the progress that has been achieved in the frame of the networking activities. A special focus is placed on the melt pool and debris coolability and corium-concrete interaction, in which, the effects due to multidimensional geometries and heterogeneities has been shown, during SARNET, to play a crucial role and for which further research is still needed.
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4.
  • Almjashev, V.I., et al. (författare)
  • Eutectic crystallization in the FeO(1.5)-UO(2+x)-ZrO(2) system
  • 2009
  • Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 389:1, s. 52-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Results of the investigation of the FeO(1.5)-UO(2+x)-ZrO(2) system in air are presented. The eutectic position and the content of the phases crystallized at this point have been determined. The temperature and the composition of the ternary eutectic are 1323 +/- 7 degrees C and 67.4 +/- 1.0 FeO(1.5), 30.5 +/- 1.0 UO(2+x), 2.1 +/- 0.2 ZrO(2) mol.%, respectively. The solubilities of FeO(1.5) and ZrO(2) in the UO(2+x)(FeO(1.5), ZrO(2)) solid solution correspond to respectively 3.2 and 1.1 mol.%. The solubilities of UO(2) and ZrO(2) in FeO(1.5) are not significant. The existence of a solid solution on the basis of U(Zr)FeO(4) compound is found. The ZrO(2) Solubility in this solid solution is 7.0 mol.%.
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5.
  • Almjashev, V.I., et al. (författare)
  • Phase equilibria in the FeO(1+x)-UO(2)-ZrO(2) system in the FeO(1+x)-enriched domain
  • 2010
  • Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 400:2, s. 119-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental results of the investigation of the FeO(1+x)UO(2)-ZrO(2) system in neutral atmosphere are presented. The ternary eutectic position and the composition of the phases crystallized at this point have been determined. The phase diagram is constructed for the FeO(1+x)-enriched region and the onset melting temperature of 1310 degrees C probably represents a local minimum and so will be a determining factor in this system and its application to safety studies in nuclear reactors.
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6.
  • Almjashev, V.I., et al. (författare)
  • Ternary eutectics in the systems FeO-UO2-ZrO2 and Fe2O3-U3O8-ZrO21
  • 2011
  • Ingår i: Radiochemistry. - 1066-3622. ; 53:1, s. 13-18
  • Tidskriftsartikel (refereegranskat)abstract
    • The systems FeO–UO2–ZrO2 (in inert atmosphere) and Fe2O3–U3O8–ZrO2 (in air) were studied. Forthe FeO–UO2–ZrO2 system, the eutectic temperature was found to be 1310°С, with the following componentconcentrations (mol %): 91.8 FeO, 3.8 UO2, and 4.4 ZrO2. For the Fe2O3–U3O8–ZrO2 system, the eutectictemperature was found to be 1323°С, with the following component concentrations (mol %): 67.4 FeO1.5,30.5 UO2.67, and 2.1 ZrO2. The solubility limits of iron oxides in the phases based on UO2(ZrO2,FeO) andUO2.67(ZrO2,FeO1.5) were determined
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7.
  • Bakardjieva, S., et al. (författare)
  • Quality improvements of thermodynamic data applied to corium interactions for severe accident modelling in SARNET2
  • 2014
  • Ingår i: Annals of Nuclear Energy. - : Elsevier. - 0306-4549 .- 1873-2100. ; 74, s. 110-124
  • Tidskriftsartikel (refereegranskat)abstract
    • In a severe accident transient, corium composition and its properties determine its behaviour and its potential interactions both with the reactor vessel and in the later phases with the concrete basemat. This, in turn, requires a detailed knowledge of the phases present at temperature and how they are formed. Because it implies mainly the investigation of chemical systems at high temperature, these data are often difficult to obtain or are uncertain if it already exists. Therefore more data are required both to complete the thermodynamic databanks (such as NUCLEA) and to construct accurate equilibrium phase diagrams and to finally contribute to the improvement of the codes simulating these severe accident conditions. The MCCI work package (WP6) of the SARNET 2 Network of Excellence has been addressing these problems. In this framework in large facilities such as VULCANO tests have been performed on the interactions and ablation of UO2-containing melts with concrete. They have been completed by large scale MCCI testing such EPICOR on vessel steel corrosion. In parallel in major EU-funded ISTC projects co-ordinated with national institutes, such as the CORPHAD and PRECOS, smaller, single effect tests have been carried out on the more difficult phase diagrams. These have produced data that can be directly used by databanks and for modelling improvement/validation. From these data significant advances in the melt chemistry and pool behaviour have been made. A selection of experiments from participating institutes are presented in this paper and give hindsight into the major processes and so give clear indications for the future work, especially in light of the Fukushima accident.
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8.
  • Bechta, Sevostian, et al. (författare)
  • CORPHAD and METCOR ISTC projects
  • 2005
  • Ingår i: Proceedings of The first European Review Meeting on Severe Accident Research (ERMSAR-2005).
  • Konferensbidrag (refereegranskat)abstract
    • The ongoing CORPHAD Project (Phase Diagrams for Multicomponent SystemsContaining Corium and Products of its Interaction with NPP Materials) started in August2001. The main aim of the project is to experimentally determine the relevantphysicochemical data on phase diagrams of binary, ternary, quaternary and prototypic multicomponent systems, which are important for analysis and modelling of a severe accident (SA)and efficient planning of severe accident management (SAM) measures. The data should bedirectly used for the European NUCLEA database development and validation. The followingsystems are in the focus of the project: (1) UO2 – FeO, (2) ZrO2 – FeO, (3) SiO2– Fe2O3, (4)UO2 – SiO2, (5) UO2 – ZrO2-FeO, (6) UO2 – ZrO2-FeOy, (7) U-O-Fe, (8) Zr-O-Fe, (9) U-OZr, (10) U-Zr-Fe-O, (11) complex corium mixtures.The experimentally determined data of the listed diagrams include: coordinates ofcharacteristic points (eutectics, peritectics and others); liquidus and solidus concentrationcurves; component solubility limits in the solid phase; tie line coordinates and temperatureconcentration regions of the miscibility gap. Different methodologies are used for the phasediagram study. Classical methods of thermal analysis, like DTA and DSC are combined withmethods specifically developed for corium studies.The METCOR project (Investigation of Corium Melt Interaction with NPP ReactorVessel Steel) started in April 1999. The objectives of the project are to qualify and to quantifyphysico-chemical phenomena of corium melt interaction with reactor vessel steel cooled fromthe outside. The variable parameters of the interaction tests are: oxygen potential in thesystem, corium composition, interaction interface temperature and heat flux from corium tosteel. The medium scale tests with corium mass of about 2 kg are carried out by using highfrequency induction heating of the corium melt in a cold crucible.The METCOR & CORPHAD work-packages are performed by Russian partners inclose collaboration with leading European scientific institutes in the area of corium researchas well as with the European nuclear industry.This paper briefly describes the results obtained in both projects and their possibleapplication for SA analysis and SAM. The paper concludes with recommendations for futureresearch activities in the framework of METCOR and CORPHAD projects.
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9.
  • Bechta, Sevostian, et al. (författare)
  • Corrosion of vessel steel during its interaction with molten corium : Part 2. Model development
  • 2006
  • Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 236:13, s. 1362-1370
  • Tidskriftsartikel (refereegranskat)abstract
    • An experimental examination of the cooled vessel steel corrosion during the interaction with molten corium is presented. The experiments havebeen conducted on “Rasplav-2” test facility and followed up with physico-chemical and metallographic analyses of melt samples and coriumspecimeningots. The results discussed in the first part of the paper have revealed specific corrosion mechanisms for air and inert atmosphere abovethe melt. Models have been proposed based on this information and approximate curves constructed for the estimation of the corrosion rate orcorrosion depth of vessel steel in conditions simulated by the experiments.
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10.
  • Bechta, Sevostian, et al. (författare)
  • Corrosion of vessel steel during its interaction with molten corium : Part 1. Experimental
  • 2006
  • Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 236:17, s. 1810-1829
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper is concerned with corrosion of a cooled vessel steel structure interacting with molten corium in air and neutral (nitrogen) atmospheresduring an in-vessel retention scenario. The data on corrosion kinetics at different temperatures on the heated steel surface, heat flux densities andoxygen potential in the system are presented. The post-test physico-chemical and metallographic analyses of melt samples and the corium–specimeningot have clarified certain mechanisms of steel corrosion taking place during the in-vessel melt interaction.
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11.
  • Bechta, Sevostian, et al. (författare)
  • Experimental study of interactions between suboxidized corium and reactor vessel steel
  • 2006
  • Ingår i: Proceedings of the 2006 International Congress on Advances in Nuclear Power Plants, ICAPP'06. - 0894486985 - 9780894486982 ; , s. 1355-1362
  • Konferensbidrag (refereegranskat)abstract
    • One of the critical factors in the analysis of in-vessel melt retention is the vessel strength. It is, in particular, sensitive to the thickness of intact vessel wall, which, in its turn, depends on the thermal conditions and physicochemical interactions with corium. Physicochemical interaction of prototypic UO2-ZrO2-Zr corium melt and VVER vessel steel was examined during the 2nd Phase of the ISTC METCOR Project. Rasplav-3 test facility was used for conducting four tests, in which the Zr oxidation degree and interaction front temperature were varied; in one of the tests, stainless steel was added to the melt. Direct experimental measurements and posttest analyses were used for determining corrosion kinetics and maximum corrosion depth (i.e. the physicochemical impact of corium on the cooled vessel steel specimens), as well as the steel temperature conditions during the interaction, and finally the structure and composition of crystallized ingots, including the interaction zone. The minimum temperature on the interaction front boundary, which determined its final position and maximum corrosion depth was ∼ 1090°C. An empirical correlation for calculation of corrosion kinetics has been derived.
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12.
  • Bechta, Sevostian, et al. (författare)
  • Interaction between molten corium UO2+X-ZrO2-FeO y and VVER vessel steel
  • 2009
  • Ingår i: Proceeding of International Conference on Advances in Nuclear Power Plants, ICAPP 2008. - : Curran Associates, Inc.. - 9781605607870 ; , s. 210-218
  • Konferensbidrag (refereegranskat)abstract
    • In case of an in-vessel corium retention (1VR) the deterioration of vessel steel properties can be caused both by the steel melting and by its physicochemical interaction with corium. The interaction behavior has been studied in the medium-scale experiments with a prototypic corium within the METCOR project. The resulting experimental data give an insight into the steel corrosion during its interaction with U02+x- Zr02- FeOy melt in air and steam. It has been observed that the corrosion rate is almost the same in air and steam atmosphere; if the temperature on the interaction interface increases beyond a certain level, corrosion intensifies, which is explained by the formation of liquid phases in the interaction zone. The available experimental data have been used for developing a correlation of corrosion rate versus temperature and heat flux.
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13.
  • Bechta, Sevostian, et al. (författare)
  • INTERACTION BETWEEN MOLTEN CORIUM UO2+x-ZrO2-FeOy AND VVER VESSEL STEEL
  • 2010
  • Ingår i: Nuclear Technology. - : American Nuclear Society. - 0029-5450 .- 1943-7471. ; 170:1, s. 210-218
  • Tidskriftsartikel (refereegranskat)abstract
    • In case of in-vessel corium retention during a severe accident in a light water reactor, weakening of the vessel wall and deterioration of the vessel steel properties can be caused both by the melting of the steel and by its physicochemical interaction with corium. The interaction behavior has been studied in medium-scale experiments with prototypic corium. The experiments yielded data for the steel corrosion rate during interaction with UO2+x-ZrO2-FeOy melt in air and steam at different steel surface temperatures and heat fluxes from the corium to the steel. It has been observed that the corrosion rates in air and steam atmosphere are almost the same. Further, if the temperature at the interface increases beyond a certain level, corrosion intensifies. This is explained by the formation of liquid phases in the interaction zone. The available experimental data have been used to develop a correlation for the corrosion rate as afunction of temperature and heat flux.
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14.
  • Bechta, Sevostian, et al. (författare)
  • New experimental results on the interaction of molten corium with reactor vessel steel
  • 2004
  • Ingår i: Proceedings of the 2004 International Congress on Advances in Nuclear Power Plants, ICAPP'04. - : American Nuclear Society. - 0894486802 ; , s. 1072-1081
  • Konferensbidrag (refereegranskat)abstract
    • In order to justify the concept of in-vessel core melt retention, it is necessary to understand the thermal and physico-chemical phenomena. Especially the interaction of the molten pool with the reactor vessel during outside cooling needs to be understood. These phenomena are very complex, in particular, where interactions with the oxidic melt are concerned. In the early stages of the retention process, the oxidic corium and the vessel steel interact under the conditions of low oxygen potential in the melt. These conditions can be simulated by a molten corium having the composition UO2/ZrO 2Zr, where the degree of Zr-oxidation is in the range between 30 % (C-30) and 100 % (C-100). Corresponding experiments with prototypic melts at low oxygen potentials are being performed in the ISTC METCOR project 2nd phase. These are: MC 5 of corium composition 71w%UO2-29w%ZrO 2 (C-100) in neutral atmosphere (argon), MC 6 of corium composition 76w%UO2-9w%ZrO2-15w%Zr (C∼30), also in argon. In test MC 5, the interaction of molten C-100 corium with a water-cooled steel specimen was studied for the following maximum temperatures at the specimen surface: 1075°C, 1180°C, 1315°C and 1435°C. The total duration of the experiment was ∼ 36 hours. The MC5 test serves as a reference test for determining the characteristics of the interaction between oxidic melt and steel specimen under the conditions of minimum chemical interaction potential. To investigate the effect of substoichiometry, test MC 6 was then performed with suboxidized molten corium C∼30. The maximum surface temperature of the cooled steel specimen was held at ∼ 1400°C. The test duration was ∼ 10 hours. The ablation phenomena were found to differ significantly from those observed both in the reference test, as well as in former tests with oxidized melts, as they involved the formation of a low-melting metallic phase at the interface which contains iron, zirconium and uranium. The paper summarizes the results of the experiments and of the performed posttest analysis for tests MC 5 and MC 6.
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15.
  • Bechta, Sevostian, et al. (författare)
  • Phase diagram of the UO2-FeO1+x system
  • 2007
  • Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 362:1, s. 46-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Phase-relation studies of the UO2–FeO1+x system in an inert atmosphere are presented. The eutectic point has beendetermined, which corresponds to a temperature of (1335 ± 5) C and a UO2 concentration of (4.0 ± 0.1) mol.%. Themaximum solubility of FeO in UO2 at the eutectic temperature has been estimated as (17.0 ± 1.0) mol.%. Liquidus temperaturesfor a wide concentration range have been determined and a phase diagram of the system has been constructed.
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16.
  • Bechta, Sevostian, et al. (författare)
  • Phase diagram of the ZrO2-FeO system
  • 2006
  • Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 348:1-2, s. 114-121
  • Tidskriftsartikel (refereegranskat)abstract
    • The results on the ZrO2–FeO system studies in a neutral atmosphere are presented. The refined eutectic point has beenfound to correspond to a ZrO2 concentration of 10.3 ± 0.6 mol% at 1332 ± 5 C. The ultimate solubility of iron oxide inzirconia has been determined in a broad temperature range, taking into account the ZrO2 polymorphism. A phase diagramof the pseudobinary system in question has been constructed.
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17.
  • Bechta, Sevostian, et al. (författare)
  • Phase transformation in the binary section of the UO2-FeO-Fe system
  • 2007
  • Ingår i: Radiochemistry (New York, N.Y.). - 1066-3622 .- 1608-3288. ; 49:1, s. 20-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Phase transformations in the oxide binary section of the UO2-FeO-Fe ternary system were studied. The melting onset point of the UO2-FeO heterogeneous system (1335±5°C) was determined and the fusion curve of this system was constructed. The limiting solubility of FeO in the UO2 solid solution was measured. The changes in crystal parameters in formation of the solid solution were determined. Uranium dioxide was found to be insoluble in the wüstite phase (FeO).
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18.
  • Bechta, Sevostian, et al. (författare)
  • VVER vessel steel corrosion at interaction with molten corium in oxidizing atmosphere
  • 2009
  • Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 239:6, s. 1103-1112
  • Tidskriftsartikel (refereegranskat)abstract
    • The long-term in-vessel corium retention (IVR) in the lower head bears a risk of the vessel wall deterioration caused by steel corrosion. The ISTC METCOR Project has studied physicochemical impact of prototypic coria having different compositions in air and steam and has generated valuable experimental data on vessel steel corrosion. It is found that the corrosion rate is sensitive to corium composition, but the composition of oxidizing above-melt atmosphere (air, steam) has practically no influence on it. A model of the corrosion process that integrates the experimental data, is proposed and used for development of correlations.
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19.
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20.
  • Fernandez, J, et al. (författare)
  • EMMA: The European mouse mutant archive
  • 2010
  • Ingår i: TRANSGENIC RESEARCH. - 0962-8819. ; 19:2, s. 327-328
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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21.
  • Journeau, C., et al. (författare)
  • Safest roadmap for corium experimental research in Europe
  • 2018
  • Ingår i: ASCE-ASME J of Risk & Uncertainty in Engineering Systems Part B. - : ASME Press. - 2332-9017 .- 2332-9025. ; 4:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe accident facilities for European safety targets (SAFEST) is a European project networking the European experimental laboratories focused on the investigation of a nuclear power plant (NPP) severe accident (SA) with reactor core melting and formation of hazardous material system known as corium. The main objective of the project is to establish coordinated activities, enabling the development of a common vision and severe accident research roadmaps for the next years, and of the management structure to achieve these goals. In this frame, a European roadmap on severe accident experimental research has been developed to define research challenges to contribute to further reinforcement of Gen II and III NPP safety. The roadmap takes into account different SA phenomena and issues identified and prioritized in the analyses of severe accidents at commercial NPPs and in the results of the recent European stress tests carried out after the Fukushima accident. Nineteen relevant issues related to reactor core meltdown accidents have been selected during these efforts. These issues have been compared to a survey of the European SA research experimental facilities and corium analysis laboratories. Finally, the coherence between European infrastructures and R&D needs has been assessed and a table linking issues and infrastructures has been derived. The comparison shows certain important lacks in SA research infrastructures in Europe, especially in the domains of core late reflooding impact on source term, reactor pressure vessel failure and molten core release modes, spent fuel pool (SFP) accidents, as well as the need for a large-scale experimental facility operating with up to 500 kg of chemically prototypic corium melt.
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22.
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23.
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24.
  • Mlassoedov, A., et al. (författare)
  • Severe accident facilities for European safety targets : The safest project
  • 2015
  • Ingår i: International Topical Meeting on Nuclear Reactor Thermal Hydraulics 2015, NURETH 2015. - : American Nuclear Society. - 9781510811843 ; , s. 4604-4616
  • Konferensbidrag (refereegranskat)abstract
    • Severe accident with core meltdown is a threat to the containment integrity. As Chernobyl and Fukushima accidents demonstrate, significant release of radioactive products into the environment can have severe consequences both for people's health and the country's economy. Severe accidents arc the focus of considerable research involving substantial human and financial resources worldwide. The research field encompasses many challenging phenomena, complicated by high temperatures and presence of radioactive materials. No individual country has sufficient resources to address all important phenomena within the framework of a national research programme, therefore optimised use of resources and the collaboration at European and international level is very important. One of the mam objectives of the SAFEST project of the 7th EU framework programme is integrating European severe accident research facilities into a pan-European laboratory for study of corium behaviour in severe accidents The resources of this laboratory will be provided to other interested European partners for better understanding of possible accident scenarios and phenomena in order to improve safety of existing and. in the long-term, of future reactors. The SAFEST consortium will be able to address several severe accident issues related to accident analysis and corium behaviour. It will be a valuable asset for the fulfilment of the severe accident R&D programmes that arc being set up after Fukushima and the subsequent European stress tests, addressing both national and European objectives.
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25.
  • Parker, Christopher C., et al. (författare)
  • Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial
  • 2018
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 73:3, s. 427-435
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. Objective: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. Design, setting, and participants: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving >= 1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. Outcome measurements and statistical analysis: All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics. Results and limitations: During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up. Conclusions: Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns.
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26.
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27.
  • Almyashev, V. I., et al. (författare)
  • Oxidation effects during corium melt in-vessel retention
  • 2016
  • Ingår i: Nuclear Engineering and Design. - : Elsevier. - 0029-5493 .- 1872-759X. ; 305, s. 389-399
  • Tidskriftsartikel (refereegranskat)abstract
    • In the in-vessel corium retention studies conducted on the Rasplav-3 test facility within the ISTC METCOR-P project and OECD MASCA program, experiments were made to investigate transient processes taking place during the oxidation of prototypic molten corium. Qualitative and quantitative data have been produced on the sensitivity of melt oxidation rate to the type of oxidant, melt composition, molten pool surface characteristics. The oxidation rate is a governing factor for additional heat generation and hydrogen release; also for the time of secondary inversion of oxidic and metallic layers of corium molten pool.
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28.
  • Bakardjieva, S., et al. (författare)
  • Improvement of the European thermodynamic database NUCLEA
  • 2010
  • Ingår i: Progress in nuclear energy (New series). - : Elsevier BV. - 0149-1970 .- 1878-4224. ; 52:1, s. 84-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Modelling of corium behaviour during a severe accident requires knowledge of the phases present at equilibrium for a given corium composition, temperature and pressure. The thermodynamic database NUCLEA in combination with a Gibbs Energy minimizer is the European reference tool to achieve this goal. This database has been improved thanks to the analysis of bibliographical data and to EU-funded experiments performed within the SARNET network, PLINIUS as well as the ISTC CORPHAD and EVAN projects. To assess the uncertainty range associated with Energy Dispersive X-ray analyses, a round-robin exercise has been launched in which a UO2-containing corium-concrete interaction sample from VULCANO has been analyzed by three European laboratories with satisfactorily small differences.
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29.
  • Bakardjieva, S., et al. (författare)
  • Improvement of the European thermodynamic database NUCLEA in the frame of EU-funded experiments
  • 2008
  • Ingår i: Proceedings of the 3<sup>rd</sup> European Review Meeting on Severe Accident Research (ERMSAR 2008).
  • Konferensbidrag (refereegranskat)abstract
    • Modelling of corium behaviour during a severe accident requires knowledge of the phases present at equilibrium for a given corium composition, temperature and pressure. The thermodynamic database NUCLEA in combination with a Gibbs Energy minimizer is theEuropean reference tool to achieve this goal. Within SARNET, this database has beenimproved thanks to the analysis of bibliographical data and to EU0funded experimentsperformed within the SARNET network, PLINIUS as well as the ISTC CORPHAD and EVAN projects. To assess the uncertainty range associated with Energy Dispersive X-ray analyses, a round robin exercise has been launched in which a UO2-containing coriumconcrete interaction sample from VULCANO has been analyzed by three European laboratories with satisfactorily small differences.
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30.
  • Bechta, Sevostian, et al. (författare)
  • Corium phase equilibria based on MASCA, METCOR and CORPHAD results
  • 2008
  • Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 238:10, s. 2761-2771
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental data on component partitioning between suboxidized corium melt and steel in the invessel melt retention (IVR) conditions are compared. The data are produced within the OECD MASCAprogram and the ISTC CORPHAD project under close-to-isothermal conditions and in the ISTC METCORproject under thermal gradient conditions. Chemical equilibrium in the U–Zr–Fe(Cr,Ni,. . .)–O system isreached in all experiments. In MASCA tests the molten pool formed under inert atmosphere has twoimmiscible liquids, oxygen-enriched (oxidic) and oxygen-depleted (metallic), resulting of the miscibilitygap of the mentioned system. Sub-system data of the U–Zr–Fe(Cr,Ni,. . .)–O phase diagram investigatedwithin the ISTC CORPHAD project are interpreted in relation with the MASCA results. In METCOR teststhe equilibrium is established between oxidic liquid and mushy metallic part of the system. Results ofcomparison are discussed and the implications for IVR noted.
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31.
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32.
  • Bechta, Sevostian, et al. (författare)
  • Influence of corium oxidation on fission product release from molten pool
  • 2010
  • Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 240:5, s. 1229-1241
  • Tidskriftsartikel (refereegranskat)abstract
    • Qualitative and quantitative determination of the release of low-volatile fission products and core materialsfrom molten oxidic corium was investigated in the EVAN project under the auspices of ISTC. Theexperiments carried out in a cold crucible with induction heating and RASPLAV test facility are described.The results are discussed in terms of reactor application; in particular, pool configuration, melt oxidationkinetics, critical influence of melt surface temperature and oxidation index on the fission productrelease rate, aerosol particle composition and size distribution. The relevance of measured high releaseof Sr from the molten pool for the reactor application is highlighted. Comparisons of the experimentaldata with those from the COLIMA CA-U3 test and the VERCORS tests, as well as with predictions fromIVTANTHERMO and GEMINI/NUCLEA codes are made. Recommendations for further investigations areproposed following the major observations and discussions.
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33.
  • Bechta, Sevostian, et al. (författare)
  • VVER steel corrosion during in-vessel retention of corium melt
  • 2008
  • Ingår i: Proceedings of the 3<sup>rd</sup> European Review Meeting on Severe Accident Research (ERMSAR 2008).
  • Konferensbidrag (refereegranskat)abstract
    • Physicochemical phenomena taking place at the corium-steel interaction during theexternal cooling of reactor vessel can result in high-temperature steel corrosion and thinningof the vessel wall. The ISTC METCOR project's experimental studies have shown that themain factors influencing corrosion depth and kinetics are oxygen potential, melt compositionand steel interfacial temperature but also melt – vessel heat flux.Experimental data are used for building a model for VVER vessel steel corrosion undercorium thermochemical loads and for correlations to quantitatively analyze the influence ofcorrosion on the rector vessel thinning. The finite-element calculations, in which thedeveloped models of corrosion and heat transfer in corium pool were used, were able toreproduce the temperature and stress-and-strain vessel condition.
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34.
  • Bottomley, D., et al. (författare)
  • Severe accident research in the core degradation area : An example of effective international cooperation between the European Union (EU) and the Commonwealth of Independent States (CIS) by the International Science and Technology Center
  • 2012
  • Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 252, s. 226-241
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Science and Technology Center (ISTC) was set up in Moscow to support non-proliferation of sensitive knowledge and technologies in biological, chemical and nuclear domains by engaging scientists in peaceful research programmes with a broad international cooperation. The paper has two following objectives: to describe the organization of complex, international, experimental and analytical research of material processes under extreme conditions similar to those of severe accidents in nuclear reactors and, to inform briefly about some results of these studies. The main forms of ISTC activity are Research Projects and Supporting Programs. In the Research Projects informal contact expert groups (CEGs) were set up by ISTC to improve coordination between adjacent projects and to encourage international collaboration. The European Commission was the first to use this. The CEG members - experts from the national institutes and industry - evaluated and managed the projects' scientific results from initial stage of proposal formulation until the final reporting. They were often involved directly in the project's details by joining the Steering Committees of the project. The Contact Expert Group for Severe Accidents and Management (CEG-SAM) is one of these groups, five project groups from this area from the total of 30 funded projects during 10 years of activity are detailed to demonstrate this: (1) QUENCH-VVER from RIAR, Dimitrovgrad and IBRAE, Moscow, and PARAMETER projects (SF1-SF4) from LUCH, Podolsk and IBRAE, Moscow; these concerned a detailed study of bundle quenching from high temperature; (2) Reactor Core Degradation; a modelling project simulating the fuel rod degradation and loss of geometry from IBRAE, Moscow; (3) METCOR projects from NITI, St. Petersburg on the interaction of core melt with reactor vessel steel; (4) INVECOR project, NNE Kurchatov City, Kazakhstan; this is a large-scale facility to examine the vessel steel retention of 60 kg corium during the decay heat; and finally, (5) CORPHAD and PRECOS projects, NITI, St. Petersburg undertook a systematic examination of refractory ceramics relevant to in-vessel and ex-vessel coria, particularly examining poorly characterised, limited data or experimentally difficult systems.
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35.
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36.
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37.
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38.
  • Khabensky, V. B., et al. (författare)
  • Effect of temperature gradient on chemical element partitioning in corium pool during in-vessel retention
  • 2018
  • Ingår i: Nuclear Engineering and Design. - : Elsevier Ltd. - 0029-5493 .- 1872-759X. ; 327, s. 82-91
  • Tidskriftsartikel (refereegranskat)abstract
    • The paper presents some results of the ISTC (International Science and Technology Center)-financed project ‘Investigation of Corium Melt Interaction with NPP Reactor Vessel Steel’ (METCOR). In the METCOR experiments the metallic phase of a two-liquid system was produced by the interaction between hot suboxidized corium and cooled VVER vessel steel, with the steel being corroded. Models of corrosion mechanisms in the considered conditions are used to systematize data on the limiting temperature of corrosion/(dissolution) of the vessel steel. A considerable influence of thermal gradient conditions is shown, which has to be taken into account in the analysis of molten pool behaviour. 
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39.
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40.
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41.
  • Wagner, Ryan G., et al. (författare)
  • Prevalence and risk factors for active convulsive epilepsy in rural northeast South Africa
  • 2014
  • Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 108:4, s. 782-791
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Epilepsy is among the most common neurological disorders there are few large, population-based studies of the prevalence and risk southern Africa. Methods: From August 2008 to February 2009, as part of a multi-site study, we undertook a three-stage, population-based study, embedded within the Agincourt health and socio-demographic surveillance system, to estimate the prevalence and identify risk factors of active convulsive epilepsy (ACE) in a rural South African population. Results: The crude prevalence of ACE, after adjusting for non-response and the sensitivity of the screening method, was 7.0/1,000 individuals (95%CI 6.4-7.6) with significant geographic heterogeneity across the study area. Being male (OR= 2.3; 95%CI 1.6-3.2), family history of seizures (OR =4.0; 95%CI 2.0-8.1), a sibling with seizures (OR = 7.0; 95%CI 1.6-31.7), problems after delivery (OR= 5.9; 95%CI 1.2-24.6), and history of snoring (OR =6.5; 95%CI 4.5-9.5) were significantly associated with ACE. For children, their mother's exposure to some formal schooling was protective (OR = 0.30; 95%CI 0.11-0.84) after controlling for age and sex. Human immunodeficiency virus was not found to be associated with ACE. Conclusions: ACE is less frequent in this part of rural South Africa than other parts of sub-Saharan Africa. Improving obstetric services could prevent epilepsy. The relationship between snoring and ACE requires further investigation, as does the relative contribution of genetic and environmental factors to examine the increased risk in those with a family history of epilepsy. (C) 2014 Elsevier B.V. All rights reserved.
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42.
  • Weis, J., et al. (författare)
  • Sensitivity to change of the EORTC quality of life module measuring cancer-related fatigue (EORTC QlQ-Fa12): Results from the international psychometric validation
  • 2019
  • Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 28, s. 1753-1761
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) has developed a multidimensional instrument measuring cancer-related fatigue, the EORTC QLQ-FA12. The analysis of sensitivity to change is an essential part of psychometric validation. With this study, we investigated the EORTC QLQ-FA12's sensitivity to change. Methods The methodology follows the EORTC guidelines of EORTC QLG for phase IV validation of modules. We included cancer patients undergoing curative and palliative treatment at t1 and followed them up prospectively over the course of their treatment (t2) and 4 weeks after completion of treatment (t3). Data were collected prospectively at 17 sites in 11 countries. Sensitivity to change was investigated using analysis of variance. Results A total sample of 533 patients was enrolled with various tumour types, different stages of cancer, and receiving either curative treatment (n=311) or palliative treatment (n=222). Over time all fatigue scores were significantly higher in the palliative treatment group compared with the curative group (p < .001). Physical fatigue increased with medium effect size over the course of treatment in the curative group (standardized response mean [SRM] (t1,t2) = 0.44]. After treatment physical [SRM (t2,t3) = 0.39], emotional [SRM (t2,t3)= 0.28] and cognitive fatigue (SRM [t2,t3] = 0.22) declined significantly in the curative group. In the palliative group, emotional (SRM [t2,t3] = 0.18) as well as cognitive [SRM [t2,t3] = 0.26) fatigue increases significantly. Conclusions The EORTC-QLQ-FA12 proved to identify clinically significant changes in fatigue in the course of curative and palliative cancer treatment.
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