NUSIMEP-8: Uranium and plutonium isotope amount ratios in low-level synthetic nitrate solution - Inter-laboratory comparison, Report to participants

The Additional Protocol (AP) authorizes safeguards authorities to verify the absence of undeclared nuclear activities in all parts of a state’s nuclear fuel cycle as well as any other location where nuclear material is or may be present. As a part of the Additional Protocol, environmental sampling has become an important tool for the detection of non-declared nuclear activities. In environmental sampling, swipe samples are collected for bulk and particle analysis. Considering the potential consequences of the analyses, these measurements need to be subjected to a rigorous quality management system. The Nuclear Signatures Inter-laboratory Measurement Evaluation Programme (NUSIMEP) was established in 1996 to support the growing need to trace and measure the isotopic abundances of elements characteristic for the nuclear fuel cycle present in trace amounts in the environment. NUSIMEP-8 focused on measurements of low-level uranium and plutonium in synthetic nitrate solution aiming to support EURATOM safeguards (DG ENER), the IAEA Network of Analytical Laboratories (NWAL) for bulk analysis of environmental samples and laboratories in the field. The NUSIMEP-8 solution was prepared from mixed oxide fuel dissolved in nitric acid with addition of natural uranium and diluted to an environmental level. Participating laboratories in NUSIMEP-8 received one sample solution with undisclosed values of n(238Pu)/n(239Pu), n(240Pu)/n(239Pu), n(241Pu)/n(239Pu), n(242Pu)/n(239Pu) and n(234U)/n(238U), n(235U)/n(238U), n(236U)/n(238U) amount ratios. Those isotope amount ratios were measured by participating laboratories using their routine analytical procedures. Measurement of the major isotope ratios n(235U)/n(238U) and n(240Pu)/n(239Pu) were obligatory; measurement of the minor isotope ratios were optional. 25 laboratories registered for NUSIMEP-8, three withdrew the registration while one laboratory encountered problems with the shipment of the sample. Finally, 19 participants have reported measurement results using different analytical techniques, among those 10 NWAL laboratories. Two participants did not report their results due to technical problems. The participant measurement results have been evaluated against the certified reference values by means of z-scores and zeta-scores in compliance with ISO 13528:2005. The NUSIMEP-8 results were overall satisfactory and in compliance with the IAEA Measurement Quality Goals for the analysis of bulk environmental samples. This report presents the NUSIMEP-8 participant results; including the evaluation of the questionnaire. In addition feedback from the measurement communities in nuclear safeguards, nuclear security and environmental sciences was collected in view of identifying future needs for NUSIMEP inter-laboratory comparisons.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Results of the REIMEP-17 interlaboratory comparison for the measurement of the U and Pu amount content and isotope amount ratios in the synthetic dissolved spent nuclear fuel solution

Reliable measurements are needed for the verification measures of States’ declarations of their nuclear activities in line with international agreements and the EURATOM Treaty. Laboratories carrying out measurements of nuclear material need to follow stringent quality control concepts and are required to demonstrate their measurement capabilities on a regular and timely basis to legal and Safeguards authorities. This includes participation in interlaboratory comparisons (ILCs). In the frame of the Regular European Interlaboratory Measurement Evaluation Programme (REIMEP) a new ILC (REIMEP-17) was jointly organized by the EC-Joint Research Centre-Institute for Reference Materials and Measurements (JRC-IRMM) and EC-Joint Research Centre-Institute for Transuranium Elements (JRC-ITU) for EURATOM and IAEA safeguards laboratories, nuclear plant operators and nuclear material laboratories. The focus in REIMEP-17 was on measurements of the uranium and plutonium amount contents, and isotope amount ratios in synthetic input solutions. Participants received two test samples, REIMEP-17A and REIMEP 17B, with different uranium and plutonium amount contents. Laboratories were requested to report the results with associated uncertainties applying their standard measurement procedures, and had the possibility to benchmark those results against the independent assigned (reference) values and the International Target Values for Measurement Uncertainties in Safeguarding Nuclear Materials (ITV2010). It can be concluded that the participants in REIMEP-17 performed well for the measurements of uranium and plutonium amount content in compliance with the respective ITV2010. In particular, the measurement performance for the isotope amount ratios was very satisfactory for both REIMEP-17 test samples. This confirms the measurement capabilities of laboratories in the field of nuclear material analysis and demonstrates that the stringent ITV2010 are achievable target values under state-of-practice conditions. On the other hand, the spread of results for the minor uranium isotope amount ratios was larger. Moreover, for some of the measurands, differences in the measurement uncertainty estimations provided by laboratories were observed even when using the same instrumental technique. A summary of the participant results is presented and discussed in this paper.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Results of the REIMEP-17 and NUSIMEP-8 inter-laboratory comparisons

Confidence in measurement results is established via reference materials, reference measurements and inter-laboratory comparisons. The Institute for Reference Materials and Measurements of the Joint Research Centre of the European Commission (EC-JRC-IRMM) has a long time experience in the development of nuclear isotopic reference materials and in the organisation of inter-laboratory comparisons (ILCs) in compliance with the respective international ISO guides. The Regular European Inter-laboratory measurement Evaluation Programme (REIMEP) was established at IRMM in 1982 for carrying out external quality control of the measurements for the elements characteristic of the nuclear fuel cycle, while the Nuclear Signatures Inter-laboratory Measurement Evaluation Programme (NUSIMEP) aims to provide test samples for the measurement of trace amounts of nuclear material in environmental matrices. Participants in REIMEP/NUSIMEP can benchmark their measurement results against independent and traceable reference values, assessing their measurement capabilities in line with international or national quality goals. The REIMEP-17 and NUSIMEP-8 certified test samples were prepared from dissolution of mixed oxide fuel in nitric acid and addition of natural uranium. In REIMEP-17 laboratories received two test samples with undisclosed values of the U, Pu amount content and U and Pu isotope amount ratios. The certified test sample REIMEP-17A had a concentration typical for undiluted input solution whereas REIMEP 17B was a diluted fraction thereof. The NUSIMEP-8 certified test sample was prepared by further gravimetrical dilution of REIMEP-17B. Measurement of the n(235U)/n(238U) and n(240Pu)/n(239Pu) ratios were obligatory while the measurement of other ratios were optional. Laboratories were asked to apply their routine analytical procedures and report the results with associated measurement uncertainty. The participant results have been evaluated against the independent certified reference value by means of z and zeta scores in compliance with ISO 13528:2005. In general, the REIMEP-17 results were satisfactory and in compliance with the International Target Values for Measurement Uncertainties in Safeguarding Nuclear Materials (ITV2010). The NUSIMEP-8 results were overall satisfactory and met the International Atomic Energy Agency Measurement Quality Goals (IAEA-SGAS-QC) for the analysis of bulk environmental samples.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

REIMEP-17: Plutonium and uranium amount content, and isotope amount ratios in synthetic input solution - Inter-laboratory comparison, Report to participants

Nuclear safeguards is based on international agreements and in the EU has the rank of European law (Euratom Treaty, Chapter VII, Euratom regulation 302/2005) ensuring that materials usable in both peaceful and military applications – such as uranium and plutonium – are used for peaceful purposes only. Physical verification measurements at nuclear facilities, such as reprocessing and fuel fabrication plants, are a part of safeguards inspections. The reliability of measurement results in nuclear material accountancy and verification is indispensable for an effective safeguards system. A new external quality control campaign, REIMEP-17 on "Plutonium and uranium amount content, and isotope amount ratios in synthetic input solution" was organised by JRC-IRMM in cooperation with JRC-ITU, particularly for EURATOM safeguards (DG ENER) laboratories and the IAEA Network of Analytical Laboratories for nuclear material analysis (IAEA-NWAL), as well as for laboratories from industry and experts in the field. Participating laboratories in REIMEP-17 received two samples with undisclosed U, Pu amount content and n(238Pu)/n(239Pu), n(240Pu)/n(239Pu), n(241Pu)/n(239Pu) n(242Pu)/n(239Pu) and n(234U)/n(238U), n(235U)/n(238U), n(236U)/n(238U) amount ratio values. One of the samples, REIMEP 17A had uranium and plutonium amount contents typical for undiluted spent nuclear fuel input solution and the other sample, REIMEP-17B was a diluted fraction of it. The participants were requested to apply their standard analytical procedures and report the results with the associated uncertainties. The laboratories were also requested to complete and return a questionnaire so that an overall picture of the laboratories’ capabilities could be made. REIMEP-17 was announced to participants in April 2012. Sixteen laboratories registered for REIMEP 17. Due to delays in the shipment of the samples and problems with the transport containers, three laboratories were not able to receive the samples. Three laboratories withdrew their participation. Consequently, the deadline for submitting the results had to be extended until July 1, 2013. In the end JRC-IRMM received results from nine laboratories; one laboratory did not submit the results. The reported measurement results have been evaluated against the independent reference values by means of z-scores and zeta-scores in compliance with international guidelines. In general the REIMEP-17 participants' results were satisfactory and in compliance with the International Target Values for Measurement Uncertainties in Safeguarding Nuclear Materials (ITV2010). This report presents the REIMEP-17 participants' results; including the evaluation of the questionnaire.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer

In a personalized treatment designed for a patient with pancreatic cancer resistant to other treatments, the success of Mitomycin C (MMC) has been highlighted. This was revealed in a murine xenograft tumor model encompassing pancreatic adenocarcinoma cells extracted from the patient. The patient was found to exhibit a biallelic inactivation of the PALB2 gene, involved in DNA repair in addition to another mutation in the TSC2 gene that induces susceptibility of the tumor to therapeutic targets of the PI3K-mTOR pathway. The aim of the study was to apply metabolomics to elucidate the modes of action of each therapy, suggesting why MMC was so successful in this patient and why it could be a more popular choice in future pancreatic cancer treatment. The effectiveness of MMC compared to rapamycin (RM), another relevant therapeutic agent has been evaluated through liquid- and gas-chromatography mass spectrometry-based metabolomic analyses of the xenograft tumors. The relative concentrations of many metabolites in the xenograft tumors were found to be increased by MMC relative to other treatments (RM and a combination of both), including a number that are involved in central carbon metabolism (CCM). Metabolic fingerprinting revealed statistically significantly altered pathways including, but not restricted to, the pentose phosphate pathway, glycolysis, TCA cycle, purine metabolism, fatty acid biosynthesis, in addition to many significant lipid and amino acid alterations. Given the genetic background of the patient, it was expected that the combined therapy would be most effective; however, the most effective was MMC alone. It is proposed that the effectiveness of MMC is owed to its direct effect on CCM, a vital region of tumor metabolism

Preparation and Certification of Large-Sized Dried (LSD) Spike – IRMM-1027s

Large-Sized Dried (LSD) spikes are used as a fundamental part of the fissile material control of irradiated nuclear fuel and have been provided on a regular basis to safeguards authorities and industry for more than 10 years. This report describes the preparation and certification of a new batch of LSD spikes. IRMM-1027s is a dried nitrate material in cellulose acetate butyrate (CAB), certified for the mass of uranium and plutonium and the uranium and plutonium isotope amount ratios per unit. The material was produced in compliance with ISO/IEC 17034:2016 and certified in accordance with ISO Guide 35:2006. The certified reference materials uranium metal EC NRM 101, enriched uranium metal NBL CRM 116-A and plutonium metal CETAMA MP2 were used as starting materials to prepare the mother solution. This solution was dispensed into individual units by means of an automated robot system and dried down. A solution of an organic substance, cellulose acetate butyrate (CAB) was dried on the spike material as a stabiliser to retain the dried material at the bottom of the vial. In total 950 units were produced. Between-unit homogeneity was quantified and stability during dispatch and storage were assessed in accordance with ISO Guide 35:2006. The certified values for the uranium and plutonium isotope amount ratios were obtained from the gravimetric preparation of the mother solution, taking into account the mass, purity and isotopic composition of the starting materials. The certified values for the mass of plutonium and uranium per unit were established by isotope dilution thermal ionisation mass spectrometry (ID-TIMS) on randomly selected units. External verification measurements were performed by isotope dilution mass spectrometry (IDMS) and thermal ionisation mass spectrometry (TIMS) on randomly selected units of IRMM-1027s. Uncertainties of the certified values were estimated in compliance with the Guide to the Expression of Uncertainty in Measurement (GUM) and include uncertainties related to possible inhomogeneity and to characterisation. The main purpose of this material is for use as a spike isotopic reference material to measure the plutonium and uranium amount content of spent nuclear fuel solutions using IDMS. Each unit contains about 55 mg of uranium with a relative mass fraction m(235U)/m(U) of 19.0 % and 1.7 mg of plutonium with a relative mass fraction m(239Pu)/m(Pu) of 97.8 % as dried nitrates in CAB. The whole amount of sample per unit has to be used for analysis.JRC.G.2-Standards for Nuclear Safety, Security and Safeguard

The role of food and nutrition in the prevention and pathogenesis of atherosclerosis development

Nowadays it is known that atherosclerotic changes in the arteries occur very early. Occur in practically the entire population of western civilization countries and show rapid progression over the years. As a result of chronic inflammatory process, which lasts even several dozen years, the developing atherosclerosis gradually destroys all layers of the arterials walls. Studies indicate that two diets recommended for atherosclerosis prevention and treatment are the DASCH diet (Dietary Approaches to Stop Hypertension), especially in relation to blood pressure control, and the Mediterranean diet. In the treatment of atherosclerosis, it is extremely important to exclude factors that increase the risk of this disease. It is important to emphasize that the conversion of energy consumed from fats to that from simple carbohydrates results in reduction of HDL C (high density lipoproteins cholesterol) concentration

New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.This research was supported by the Polish National Science Center (2014/13/N/NZ7/04231), the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2014-58920R), by the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) (PI14-01427), and by the quality-promoting subsidy from the Ministry of Science and Higher Education of Poland, Leading National Research Centre (KNOW programme 2012-2017). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

New biochemical insights into the mechanisms of pulmonary arterial hypertension in humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia

Background: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. Methods: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(−) groups, according to the development of BPD. Results: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. Conclusions: BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD