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- Bechta, Sevostian, et al.
(author)
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On the EU-Japan roadmap for experimental research on corium behavior
- 2019
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In: Annals of Nuclear Energy. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4549 .- 1873-2100. ; 124, s. 541-547
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Journal article (peer-reviewed)abstract
- A joint research roadmap between Europe and Japan has been developed in severe accident field of light water reactors, focusing particularly on reactor core melt (corium) behavior. The development of this roadmap is one of the main targets of the ongoing EU project SAFEST. This paper presents information about ongoing severe accident studies in the area of corium behavior, rationales and comparison of research priorities identified in different projects and documents, expert ranking of safety issues, and finally the research areas and topics and their priorities suggested for the EU Japan roadmap and future bilateral collaborations. These results provide useful guidelines for (i) assessment of long-term goals and proposals for experimental support needed for proper understanding, interpretation and learning lessons of the Fukushima accident; (ii) analysis of severe accident phenomena; (iii) development of accident prevention and mitigation strategies, and corresponding technical measures; (iv) study of corium samples in European and Japanese laboratories; and (v) preparation of Fukushima site decommissioning.
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| 3. |
- Huang-Doran, Isabel, et al.
(author)
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Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations.
- 2016
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In: JCI insight. - 2379-3708. ; 1:17
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Journal article (peer-reviewed)abstract
- Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis. In 3 of these 4, plasma adiponectin was preserved, as in insulin receptor dysfunction. The fourth patient and her healthy mother had low plasma adiponectin associated with a potentially novel mutation, p.Asp231Ala, in adiponectin itself. Cells studied from one patient with the p.Tyr657X PIK3R1 mutation expressed abundant truncated PIK3R1 products and showed severely reduced insulin-stimulated association of mutant but not WT p85α with IRS1, but normal downstream signaling. In 3T3-L1 preadipocytes, mutant p85α overexpression attenuated insulin-induced AKT phosphorylation and adipocyte differentiation. Thus, PIK3R1 C-terminal mutations impair insulin signaling only in some cellular contexts and produce a subphenotype of insulin resistance resembling INSR dysfunction but unlike AKT2 dysfunction, implicating PI3K in the pathogenesis of key components of the metabolic syndrome.
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| 4. |
- Journeau, Christophe, et al.
(author)
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SAFEST ROADMAP FOR CORIUM EXPERIMENTAL RESEARCH IN EUROPE
- 2016
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In: PROCEEDINGS OF THE 24TH INTERNATIONAL CONFERENCE ON NUCLEAR ENGINEERING, 2016, VOL 4. - : ASME Press. - 9780791850046
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Conference paper (peer-reviewed)abstract
- SAFEST (Severe Accident Facilities for European Safety Targets) is a European project networking the European corium experimental laboratories with the objective to establish coordination activities, enabling the development of a common vision and research roadmaps for the next years, and of the management structure to achieve these goals. In this frame, a European roadmap on corium experimental research has been written to define research challenges to contribute to further reinforcement of Gen II and III NPP safety. It is based on the research priorities deteimined by SARNET SARP group as well as those from the recently formulated in the NUGENIA Roadmap for severe accidents and the recently published NUGENIA Global Vision report. It also takes into account issues identified in the analysis of the European stress tests and from the interpretation of the Fukushima accident. 19 relevant issues related to corium have been selected during these prioritization efforts. These issues have been compared to a survey of the European corium 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. It shows a few lacks in EU corium infrastructures, especially in the domains of core late reflooding impact on source term, Reactor Pressure Vessel failure and corium release, Spent Fuel Pool accidents, as well as the need for a large mass (100500 kg) prototypic corium facility.
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| 5. |
- Parker, Christopher C., et al.
(author)
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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
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 73:3, s. 427-435
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Journal article (peer-reviewed)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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