Ageing PSA incorporating effectiveness of maintenance and testing

This paper proposes a new approach to Ageing Probabilistic Safety Assessment (APSA) modelling, which is intended to be used to support risk-informed decisions on the effectiveness of maintenance management programs and technical specification requirements of critical equipment of Nuclear Power Plants (NPP) within the framework of the Risk Informed Decision Making according to R.G. 1.174 principles. This approach focuses on the incorporation of not only equipment ageing but also effectiveness of maintenance and efficiency of surveillance testing explicitly into APSA models and data. An example of application is presented, which centres on a critical safety-related equipment of a NPP in order to evaluate the risk impact of considering different approaches to APSA and the combined effect of equipment ageing and maintenance and testing alternatives along NPP design life. The risk impact of the several alternatives is quantified and the results shows that such risk depends largely on the model parameters, such as ageing factor, maintenance effectiveness, test efficiency.Authors are grateful to the Spanish Ministry of Science and Innovation for the financial support of this work (Research Project ENE2013-45540-R) and the Doctoral Fellow (BES-2011-043906).Martón Lluch, I.; Sánchez Galdón, AI.; Martorell Alsina, SS. (2015). Ageing PSA incorporating effectiveness of maintenance and testing. Reliability Engineering and System Safety. 139:131-140. https://doi.org/10.1016/j.ress.2015.03.022S13114013

Handbook of methods for risk-based analysis of technical specifications

Technical Specifications (TS) requirements for nuclear power plants define the Limiting Conditions for Operations (LCOs) and Surveillance Requirements (SRs) to assure safety during operation. In general, these requirements are based on deterministic analyses and engineering judgments. Improvements in these requirements are facilitated by the availability of plant-specific Probabilistic Risk Assessments (PRAs). The US Nuclear Regulatory Commission (USNRC) Office of Research sponsored research to develop systematic, risk-based methods to improve various aspects of TS requirements. A handbook of methods summarizing such risk-based approaches has been completed in 1994. It is expected that this handbook will provide valuable input to NRC`s present work in developing guidance for using PRA in risk-informed regulation. The handbook addresses reliability and risk-based methods for evaluating allowed outage times (AOTs), action statements requiring shutdown where shutdown risk may be substantial, surveillance test intervals (STIs), managing plant configurations, and scheduling maintenance

The Necessary and Sufficient Conditions for Representing Lipschitz Bivariate Functions as a Difference of Two Convex Functions

In the article the necessary and sufficient conditions for a representation of Lipschitz function of two variables as a difference of two convex functions are formulated. An algorithm of this representation is given. The outcome of this algorithm is a sequence of pairs of convex functions that converge uniformly to a pair of convex functions if the conditions of the formulated theorems are satisfied. A geometric interpretation is also given

Skyrme-Rpa Description of Dipole Giant Resonance in Heavy and Superheavy Nuclei

The E1(T=1) isovector dipole giant resonance (GDR) in heavy and super-heavy deformed nuclei is analyzed over a sample of 18 rare-earth nuclei, 4 actinides and three chains of super-heavy elements (Z=102, 114 and 120). Basis of the description is self-consistent separable RPA (SRPA) using the Skyrme force SLy6. The self-consistent model well reproduces the experimental data (energies and widths) in the rare-earth and actinide region. The trend of the resonance peak energies follows the estimates from collective models, showing a bias to the volume mode for the rare-earths isotopes and a mix of volume and surface modes for actinides and super-heavy elements. The widths of the GDR are mainly determined by the Landau fragmentation which in turn is found to be strongly influenced by deformation. A deformation splitting of the GDR can contribute about one third to the width and about 1 MeV further broadening can be associated to mechanism beyond the mean-field description (escape, coupling with complex configurations).Comment: 9 pages, 12 figures, 2 table

Mutations and SNPs of human cardiac sodium channel alpha subunit gene (SCN5A) in Japanese patients with Brugada syndrome

Background: Brugada syndrome is an inherited arrhythmogenic disease characterized by right bundle branch block pattern and ST segment elevation, leading to the change of V1 to V3 on electrocardiogram, and an increased risk of sudden cardiac death resulting from ventricular fibrillation. The sodium channel alpha 5 subunit (SCN5A) gene encodes a cardiac voltage-dependent sodium channel, and SCN5A mutations have been reported in Brugada syndrome. However, single nucleotide polymorphisms (SNPs) and gene mutations have not been well investigated in Japanese patients with Brugada syndrome. Methods and Results: The SCN5A gene was examined in 58 patients by using PCR and the ABI 3130xl sequencer, revealing 17 SNP patterns and 13 mutations. Of the 13 mutations, 8 were missense mutations (with amino acid change), 4 were silent mutations (without amino acid change), and one case was a mutation within the splicing junction. Six of the eight missense mutations were novel mutations. Interestingly, we detected an R1664H mutation, which was identified originally in long QT syndrome. Conclusion: We found 13 mutations of the SCN5A gene in 58 patients with Brugada syndrome. The disease may be attributable to some of the mutations and SNPs

Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients

Background Axitinib is an oral, potent and selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3. We report on data obtained from 18 Japanese patients with advanced solid tumors in two phase I trials that evaluated the safety, pharmacokinetics and antitumor activity of axitinib and also examined potential biomarkers. Methods Six patients received a single 5-mg dose of axitinib followed by 5 mg twice daily (BID), and an additional six patients received axitinib 5 mg BID only. Another six patients received axitinib at 5-mg, 7-mg and 10-mg single doses followed by 5 mg BID. Results Plasma pharmacokinetics following single doses of axitinib was generally linear. Common treatment-related adverse events were fatigue (83%), anorexia (72%), diarrhea (67%), hand–foot syndrome (67%) and hypertension (61%). Sixteen patients (89%) experienced thyroid-stimulating hormone (TSH) elevation. Grade 3/4 toxicities included hypertension (33%) and fatigue (28%). No grade 3/4 fatigue occurred in patients who started thyroid hormone replacement therapy when TSH was elevated. Thyroglobulin elevation was observed in all patients who continued treatment with axitinib for ≥3 months. Abnormal TSH correlated with exposure to axitinib (r = 0.72). Decrease in soluble (s) VEGFR-2 levels significantly correlated with exposure to axitinib (r = –0.94). Axitinib showed antitumor activity across multiple tumor types. Conclusions Axitinib-related thyroid dysfunction could be due to a direct effect on the thyroid gland. Grade 3/4 fatigue and hypothyroidism appear to be controllable with use of thyroid hormone replacement therapy. sVEGFR-2 and TSH may act as biomarkers of axitinib plasma exposure