The micronucleus assay as a biological dosimeter of in vivo ionising radiation exposure

Biological dosimetry, based on the analysis of micronuclei (MN) in the cytokinesis-block micronucleus (CBMN) assay can be used as an alternative method for scoring dicentric chromosomes in the field of radiation protection. Biological dosimetry or Biodosimetry, is mainly performed, in addition to physical dosimetry, with the aim of individual dose assessment. Many studies have shown that the number of radiation-induced MN is strongly correlated with dose and quality of radiation. The CBMN assay has become, in the last years, a thoroughly validated and standardised technique to evaluate in vivo radiation exposure of occupational, medical and accidentally exposed individuals. Compared to the gold standard, the dicentric assay, the CBMN assay has the important advantage of allowing economical, easy and quick analysis. The main disadvantage of the CBMN assay is related to the variable micronucleus ( MN) background frequency, by which only in vivo exposures in excess of 0.2-0.3 Gy X-rays can be detected. In the last years, several improvements have been achieved, with the ultimate goals (i) of further increasing the sensitivity of the CBMN assay for low-dose detection by combining the assay with a fluorescence in situ hybridisation centromere staining technique, (ii) of increasing the specificity of the test for radiation by scoring nucleoplasmic bridges in binucleated cells and (iii) of making the assay optimally suitable for rapid automated analysis of a large number of samples, viz. in case of a large-scale radiation accident. The development of a combined automated MN-centromere scoring procedure remains a challenge for the future, as it will allow systematic biomonitoring of radiation workers exposed to low-dose radiation

Sol–gel processing and characterization of (RE-Y)-zirconia powders for thermal barrier coatings

The effect of doping on the structural, morphological and thermal properties of ZrO2–XO1.5 (X=Y, La, Sm, Er) solid solutions for thermal barrier (TBC) applications was investigated. Oxide powders of various compositions from 9.7 to 40 mol% XO1.5 (X=Y, La, Sm, Er) were synthesised by the sol–gel route. The structural analysis of the powders was performed using X-ray diffraction analysis coupled with Rietveld refinements and the measurement of their specific surface area with the BET method. For each rare earth dopant, the morphology of the powders varies from monoliths to agglomerates of thinner particles when the doping amount increases. In order to determine the specific heat, the thermal diffusivity at room temperature and the thermal expansion coefficient of some selected compositions, DSC, laser thermal diffusivity and hightemperature dilatometry measurements were performed on samples densified by Spark Plasma Sintering. Working thermal characterisation indicated that zirconia doped with 30 mol% SmO1.5 and ErO1.5 have better insulation properties and a lower thermal expansion coefficient than our reference YSZ ceramic. These various compositions are very promising for the elaboration of multilayer TBCs by the sol–gel process

Optimizing urothelial cell preparation for the human urinary micronucleus assay

Biological monitoring of early genotoxic effects in urothelial cells using the urinary micronucleus (MNu) assay is promising for early detection of cancer, such as bladder carcinoma. But many problems are encountered, the major being the poorly differential staining of cells, particularly in women having an important amount of squamous cells. We have optimized the protocol and obtained a differential staining of the cell types present in urine on 10 subjects. Following Carnoy I fixation and Papanicolaou staining, urothelial cells were blue while most squamous cells were pink. This differential staining allowed for optimization of the MNu assay on a single urine void, for both females and males. Even if our MNu means were comparable to the literature, the great variation in reported MNu results could reside in the ability of scorers to distinguish correctly between urothelial and squamous cells. When monitoring exposed populations, this erroneous distinction could largely influence the results, even more in women’s urine samples. Given a situation where exposure would not increase micronuclei frequency in vaginal squamous cells, their erroneous analysis in the MNu assay could mask an early genotoxic effect. Therefore, as transitional cell carcinoma of the bladder originates from transformed urothelial cells, restricting micronuclei analysis to urothelial cells could yield a more precise estimate of cancer risk in exposed populations. Moreover, it is hoped that the improvements proposed in this paper will allow for an easier implementation of the MNu assay in various set-ups and enhance its specificity, since MNu are considered a suitable biomarker

COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research

Suivi des volumes plasmatique, interstitiel et intracellulaire pendant l'hémodialyse par bioimpédance multifréquence et mesure d'hématocrite

Le suivi des volumes hydriques du patient hémodialysé permet d'accroître l'efficacité des traitements et d'aider à la détermination du poids sec. Le but de cette thèse est d'améliorer les techniques d'évaluation des volumes hydriques du corps en hémodialyse. Les volumes extra et intracellulaires sont obtenus par bioimpédance, le volume plasmatique par mesures d'hématocrite optique ou ultrasonore. La précision des mesures d'hématocrite par ultrason pu être améliorée grâce à une modélisation précise de la variation des différents composés sanguins lors de l'ultrafiltration. Nous avons proposé une nouvelle modélisation électrique des compartiments hydriques, qui permet de mesurer la variation d'eau totale avec plus de précision. Trois méthodes de détermination du poids sec par impédance ont été analysées et améliorées. Les erreurs de la méthode d'impédance dues aux changements de position ou à la variation de la résistivité de l'extracellulaire en hémodialyse ont été étudiées.The goal of this thesis was to improve measurement techniques of fluid volume variations in patients during hemodialysis. Extra and intra cellulars volumes were measured by bioimpedance spectroscopy and plasmatic volume change were determined from hematocrit measurements by optical or ultrasound methods. We have proposed a new and more accurate method for measuring hematocrit by ultrasound by taking into account the simultaneous concentration of hemoglobin and plasma protein concentration due to ultrafiltration. We have also tested a new method for measuring total body water from its resistance at high frequency which is more accurate in dialysis. We have also discussed artifacts due to position changes and fluid resistivity changE?s during dialysis as weil as three methods for dry weight determination.COMPIEGNE-BU (601592101) / SudocSudocFranceF