Identification of Limiting Case Between DBA and SBDBA (CL Break Area Sensitivity): A New Model for the Boron Injection System

Atucha-2 is a Siemens-designed PHWR reactor under construction in the Republic of Argentina. Its geometrical complexity and (e.g., oblique Control Rods, Positive Void coefficient) required a developed and validated complex three dimensional (3D) neutron kinetics (NK) coupled thermal hydraulic (TH) model. Reactor shut-down is obtained by oblique CRs and, during accidental conditions, by an emergency shut-down system (JDJ) injecting a highly concentrated boron solution (boron clouds) in the moderator tank, the boron clouds reconstruction is obtained using a CFD (CFX) code calculation. A complete LBLOCA calculation implies the application of the RELAP5-3D© system code. Within the framework of the third Agreement “NA-SA – University of Pisa” a new RELAP5-3D control system for the boron injection system was developed and implemented in the validated coupled RELAP5-3D/NESTLE model of the Atucha 2 NPP. The aim of this activity is to find out the limiting case (maximum break area size) for the Peak Cladding Temperature for LOCAs under fixed boundary conditions

Microbiological quality and resistance to an artificial gut environment of two probiotic formulations

The quality control of probiotic products is the focus of numerous organizations worldwide. Several studies have highlighted the poor microbiological quality of many commercial probiotic formulations in terms of the identity of the contained microorganisms, viability, and purity, thus precluding the expected health benefits and representing a potential health risk for consumers. In this paper, we analyzed the contents of two probiotic formulations, one composed of an encapsulated mixture of lactobacilli and bifidobacteria, and one by a lyophilized yeast. The microorganisms contained in the products were quantified and identified using up-to-date methodologies, such as MALDI-TOF MS and metagenomic analysis. Moreover, as acid and bile tolerance is included among the criteria used to select probiotic microorganisms, in vitro tests were performed to evaluate the behavior of the formulations in conditions mimicking the harsh gastric environment and the intestinal fluids. Our results indicate the high quality of the formulations in terms of the enumeration and identification of the contained organisms, as well as the absence of contaminants. Moreover, both products tolerated the acidic conditions well, with encapsulation providing further protection for the microorganisms. A good tolerance to the simulated artificial intestinal conditions was also evidenced for both preparations

Adverse events during longterm low-dose glucocorticoid treatment of polymyalgia rheumatica: a retrospective study

To assess the occurrence of adverse events in a cohort of patients with polymyalgia rheumatica (PMR), treated with low-dose glucocorticoids (GC). METHODS: This was a retrospective study by review of medical records. RESULTS: We identified 222 patients who had a mean duration of followup of 60 ± 22 months and a mean duration of GC therapy of 46 ± 22 months. We found that 95 patients (43%) had at least 1 adverse event after a mean duration of GC therapy of 31 ± 22 months and a mean cumulative dose of 3.4 ± 2.4 g. In particular, 55 developed osteoporosis, 31 had fragility fractures; 27 developed arterial hypertension; 11 diabetes mellitus; 9 acute myocardial infarction; 3 stroke; and 2 peripheral arterial disease. Univariate analysis showed that the duration of GC treatment was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), arterial hypertension (p < 0.005), and acute myocardial infarction (p < 0.05). Cumulative GC dose was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), and arterial hypertension (p < 0.01). The adverse events occurred more frequently after 2 years of treatment. Multivariate analysis showed that GC duration was significantly associated with osteoporosis (adjusted OR 1.02, 95% CI 1.02-1.05) and arterial hypertension (adjusted OR 1.03, 95% CI 1.01-1.06); GC cumulative dose was significantly associated with fragility fractures (adjusted OR 1.4, 95% CI 1.03-1.8). CONCLUSION: Longterm, low-dose GC treatment of PMR is associated with serious adverse events such as osteoporosis, fractures, and arterial hypertension; these adverse events occur mostly after 2 years of treatment

Digital droplet PCR is a specific and sensitive tool for detecting IDH2 mutations in acute myeloid leukemia patients

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) interfere with cellular metabolism contributing to oncogenesis. Mutations of IDH2 at R140 and R172 residues are observed in 20% of acute myeloid leukemias (AML), and the availability of the IDH2 inhibitor Enasidenib made IDH2 mutational screening a clinical need. The aim of this study was to set a new quantitative polymerase chain reaction (PCR) technique, the drop-off digital droplet PCR (drop-off ddPCR), as a sensitive and accurate tool for detecting IDH2 mutations. With this technique we tested 60 AML patients. Sanger sequencing identified 8/60 (13.5%) mutated cases, while ddPCR and the amplification refractory mutation system (ARMS) PCR, used as a reference technique, identified mutations in 13/60 (21.6%) cases. When the outcome of IDH2-mutated was compared to that of wild-type patients, no significant difference in terms of quality of response, overall survival, or progression-free survival was observed. Finally, we monitored IDH2 mutations during follow-up in nine cases, finding that IDH2 can be considered a valid marker of minimal residual disease (MRD) in 2/3 of our patients. In conclusion, a rapid screening of IDH2 mutations is now a clinical need well satisfied by ddPCR, but the role of IDH2 as a marker for MRD still remains a matter of debate

The assessment of minimal residual disease versus that of somatic mutations for predicting the outcome of acute myeloid leukemia patients

Background: In addition to morphological and cytogenetic features, acute myeloid leukemias are characterized by mutations that can be used for target-therapy; also the minimal/measurable residual disease (MRD) could be an important prognostic factor. The purpose of this retrospective study was to investigate if somatic mutations could represent an additional prognostic value in respect of MRD alone. Method: At baseline, 98 patients were tested for NPM1, FLT3, and for WT1 expression; 31 for ASXL1, TET2, IDH1, IDH2, N-RAS, WT1, c-KIT, RUNX1, and DNMT3A. The same genes have been also tested after induction and consolidation. Results: Overall, 60.2% of our patients resulted mutated: 24.5% carried mutations of FLT3-ITD, 38.7% of NPM1, 48.4% of c-KIT, 25.8% of N-RAS and 19.3% of IDH2. The probability of achieving a complete response (CR) was higher for younger patients, with low ELN risk score, NPM1-mutated, with low WT1 levels, and without FLT3. The presence of additional mutations represented a poor predictive factor: only 19% of these cases achieved CR in comparison to 43% of subjects without any of it. Concerning survival, it was conditioned by a lower ELN risk score, younger age, reduction &gt; 1 log of the NPM1 mutational burden, disappearance of FLT3 mutations and lower WT1 expression. Regarding the role of the additional mutations, they impaired the outcome of 20% of the already MRD-negative patients. Concerning the possibility of predicting relapse, we observed an increase of the NPM1 mutational burden at the time-point immediately preceding the relapse (about 2 months earlier) in 50% of subjects. Similarly concerning WT1, an increase of its expression anticipated disease recurrence in 64% of cases. Conclusions: We demonstrated that additional somatic mutations are able to impair outcome of the already MRD-negative subjects. About MRD, we suggest a prognostic role also for the WT1 expression. Finally, we considered as relevant the assessment of NPM1 quantity clearance instead of the presence/absence of mutations alone. Still remains in doubt the utility in terms of long-term prognosis of a baseline more complex mutational screening; we could hypothesize that it would be useful for those patients where other markers are not available or who reached the MRD negativity

Implementing Obliquely Inserted Control Rods Into RELAP5-3D/NESTLE Model for Atucha-2

Atucha-2 is a Siemens-designed pressurized heavy water reactor located in Argentina. Its geometrical complexity and peculiarity [e.g., oblique control rods (CRs) and positive void coefficient] required a developed and validated complex three-dimensional (3-D) neutron kinetics (NK) model. In the framework of the agreement between NA-SA (Nucleo-electrica Argentina Sociedad Anonima) and the University of Pisa, a detailed NESTLE (3-D NK code) model of the Atucha-2 nuclear power plant (NPP) was developed. This document summarizes the procedures for implementing oblique CRs into the RELAP5/NESTLE model: A particular arrangement of the RELAP5/NESTLE CR insertion mode for oblique CRs and an implementation into the homogenized two-group cross sections of ad hoc calculated correction factors (these parameters were obtained by previously executed Monte Carlo calculations) were developed. Some applications, among the scenarios selected to perform safety analysis (Final Safety Analysis Report) of the Atucha-2 NPP (CNA-II), are also reported: preliminary scram rod worth, analysis of a CR ejection accident, and a CR faulty withdrawal

Generalized lymphatic anomaly: A case report

Complex Lymphatic Anomalies are a group of rare diseases characterized by a non-neoplastic proliferation of lymphatic vessels. They include Generalized Lymphatic Anomalies and Kaposiform Lymphangiomatosis (both with involvement of visceral organs and bone with multifocal and non-progressive osteolysis) and Gorham-Stout Disease (characterized by a predominant involvement of bone with destruction of the bone matrix causing absorption of bone - the so-called "vanishing bone" disease - and a far less frequent visceral involvement). Because of the rarity of these diseases, the diagnosis may be confused by their similar clinical presentation. We describe a case of a young man with Generalized Lymphatic Anomalies with a diffuse involvement of the skeleton and of the spleen. The aim of this report is to point out the characteristics of different types of lymphatic anomalies to allow a correct diagnosis and a more adequate therap