114 research outputs found

    Плазменное получение ценных металлов из отходов переработки отработавшего ядерного топлива

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    Целью ВКР является исследование возможности эффективной плазменной переработки нитратных комплексов палладия в воздушной плазме в виде водносолеоорганических композиций. В процессе исследования проведен расчет показателей горения водносолеорганических композиций на основе этанола и палладия и определены составы горючих композиций, обеспечивающих их энергоэффективную плазменную обработку в воздушной плазме. Проведено термодинамическое моделирование процесса плазменной обработки нитратных комплексов палладия в виде горючих композиций и определены оптимальные режимы для их эффективной плазменной обработки в воздушной плазме.The purpose of the SRS is to investigate the potential of the plasma transformation of palladium nitrate complexes into air plasma in the form of water-organic-organic compositions. In the process of research, the calculation of the parameters of combustion of an aqueous-organic composition based on ethanol and palladium and a certain composition of combustible components, ensuring their energy-efficient plasma treatment in air plasma, was carried out. Thermodynamic modeling of the plasma treatment of palladium nitrate complexes in the form of combustible components has been carried out and the optimal conditions for their effective plasma treatment in air plasma have been determined

    Patient specific real-time PCR in precision medicine – Validation of IG/TR based MRD assessment in lymphoid leukemia

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    Detection of patient- and tumor-specific clonally rearranged immune receptor genes using real-time quantitative (RQ)-PCR is an accepted method in the field of precision medicine for hematologic malignancies. As individual primers are needed for each patient and leukemic clone, establishing performance specifications for the method faces unique challenges. Results for series of diagnostic assays for CLL and ALL patients demonstrate that the analytic performance of the method is not dependent on patients’ disease characteristics. The calibration range is linear between 10-1 and 10-5 for 90% of all assays. The detection limit of the current standardized approach is between 1.8 and 4.8 cells among 100,000 leukocytes. RQ-PCR has about 90% overall agreement to flow cytometry and next generation sequencing as orthogonal methods. Accuracy and precision across different labs, and above and below the clinically applied cutoffs for minimal/measurable residual disease (MRD) demonstrate the robustness of the technique. The here reported comprehensive, IVD-guided analytical validation provides evidence that the personalized diagnostic methodology generates robust, reproducible and specific MRD data when standardized protocols for data generation and evaluation are used. Our approach may also serve as a guiding example of how to accomplish analytical validation of personalized in-house diagnostics under the European IVD Regulation

    Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study

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    Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis, we subsequently used canonical correlation analysis of 176 training cases to project the multidimensional space of all 26 immunophenotypic parameters into 36 2-dimensional plots for each possible pairwise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%), and mantle cell lymphoma (95.4%). Burkitt and CD101 diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD102 diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms

    A model for predicting effect of treatment on progression-free survival using MRD as a surrogate end point in CLL

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    Our objective was to evaluate minimal residual disease (MRD) at the end of induction treatment with chemoimmunotherapy as a surrogate end point for progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) based on 3 randomized, phase 3 clinical trials (ClinicalTrials.gov identifiers NCT00281918, NCT00769522, and NCT02053610). MRD was measured in peripheral blood (PB) from treatment-naïve patients in the CLL8, CLL10, and CLL11 clinical trials, and quantified by 4-color flow cytometry or allele-specific oligonucleotide real-time quantitative polymerase chain reaction. A meta-regression model was developed to predict treatment effect on PFS using treatment effect on PB-MRD. PB-MRD levels were measured in 393, 337, and 474 patients from CLL8, CLL10, and CLL11, respectively. The model demonstrated a statistically significant relationship between treatment effect on PB-MRD and treatment effect on PFS. As the difference between treatment arms in PB-MRD response rates increased, a reduction in the risk of progression or death was observed; for each unit increase in the (log) ratio of MRD2 rates between arms, the log of the PFS hazard ratio decreased by 20.188 (95% confidence interval, 20.321 to 20.055; P 5 .008). External model validation on the REACH trial and sensitivity analyses confirm the robustness and applicability of the surrogacy model. Our surrogacy model supports use of PB-MRD as a primary end point in randomized clinical trials of chemoimmunotherapy in CLL. Additional CLL trial data are required to establish a more precise quantitative relationship between MRD and PFS, and to support general applicability of MRD surrogacy for PFS across diverse patient characteristics, treatment regimens, and different treatment mechanisms of action

    Septic ovarian vein thrombosis after late miscarriage in the 17th SSW

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    Coincidence of congenital left-sided diaphragmatic hernia and ductus venosus agenesis: Relation between altered hemodynamic flow and lung-to-head-ratio?

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    Left-sided diaphragmatic hernia (CDH) as well as ductus venosus agenesis (ADV) are rare complex congenital malformations. We present a case of coincidence of these malformations and an abnormally high lung-head-ratio (LHR). The left-sided liver-up CDH and the ADV were diagnosed in prenatal ultrasound examination. In CDH cases lung volume is decreased due to the herniation of abdominal organs into the thorax. With 1.4 the LHR of our patient exceeded the normal ratio in liver-up CDH cases considerably. One explanation for this unusually high LHR might be an altered blood flow due to the coinciding ADV. In ADV cases less blood bypasses the lung through the foramen ovale. Consecutively pulmonary circulation is improved which may constitute as an advantage in CDH cases. Diagnosis, prognostic factors, physiology, and therapy strategy are discussed

    Extracardiac anomalies in prenatally diagnosed heterotaxy syndrome

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    Objective To assess the incidence and impact of extracardiac anomalies on the prognosis of fetuses with heterotaxy syndrome. Methods All fetuses diagnosed with heterotaxy syndrome by three experienced examiners over a period of 14 years (1999-2013) were reviewed retrospectively. Results In total, 165 fetuses with heterotaxy syndrome were diagnosed in the study period. One hundred and fifty (90.9%) had cardiac defects; extracardiac anomalies that did not involve the spleen were present in 26/165 (15.8%) cases. Of the total study cohort, termination of pregnancy was performed in 49 (29.7%) cases, intrauterine death occurred in 11 (6.7%), postnatal death occurred in 38 (23.0%) and 67 (40.6%) were alive at the latest follow-up, resulting in a total perinatal and pediatric mortality of 59.4%. Among the 105 liveborn neonates, 15 (14.3%) had extracardiac anomalies with significant impact on the postnatal course: one neonate died following repair of an encephalocele, six had successful treatment for various types of intestinal malrotation and/or atresia and one underwent hiatal hernia repair; the remaining seven had biliary atresia, of which five died and the two survivors are awaiting liver transplantation. The status of the spleen was assessed in 93/105 liveborn children and was found to be abnormal in 84/93 (90.3%). There were three cases of lethal sepsis, all associated with asplenia. Of the 38 postnatal deaths, 29 (76.3%) had a cardiac cause, seven (18.4%) had an extracardiac cause and in two (5.2%) the reason was uncertain. Conclusions Although the leading causes of death in fetuses and children with heterotaxy syndrome are cardiac, a small subset of fetuses have extracardiac anomalies with significant impact on outcome. These anomalies often escape prenatal detection, and therefore neonates at risk should be monitored for bowel obstruction, biliary atresia and immune dysfunction in order to allow timely intervention through a multidisciplinary approach. Copyright (C) 2015 ISUOG. Published by John Wiley & Sons Ltd
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