Labile glycated haemoglobin and carbamylated haemoglobin are still critical points for HbA1c measurement

IntroductionHaemoglobin A1c (HbA1c) is a key analyte for the monitoring of glycemic balance in diabetic patients and is used for diabetes diagnosis in many countries. The potential interference of carbamylated haemoglobin (cHb) and labile glycated haemoglobin (LA1c) on HbA1c assays must remain a matter of vigilance. Such a situation has occurred in our laboratory with a kit replacement on the Bio-Rad Variant™ II testing system, a cation-exchange high performance liquid chromatography (HPLC) system. With this method, LA1c and cHb coeluted in a same peak which may have different consequences on HbA1c values. Materials and methodsThe influence of increasing LA1c and cHb values on HbA1c results was studied with in vitro glycation and carbamylation of samples. Samples from patients with high and normal blood urea concentrations were assayed by HPLC and immunological assay. ResultsWe observed that the degree of interference greatly varied depending on the nature of the interfering Hb fractions found under the so-called “LA1c peak”. Thus, we have decided to apply a decision tree using “LA1c” thresholds depending on: (i) the retention time, (ii) the shape of the peak, (iii) other analytes, like urea. If the peak recognized as “LA1c” is mainly formed by LA1c, we consider that there is no interference until 4%. If the peak is mainly formed by cHb, we consider an interference threshold equal to 2%. ConclusionsThis situation reminds that cHb and LA1c remain critical issues in chromatography-based HbA1c assays and that adapted criteria must be set up for result interpretation

Modulation of drug sensitivity in yeast cells by the ATP‐binding domain of human DNA topoisomerase IIα

Epipodophyllotoxins are effective antitumour drugs that trap eukaryotic DNA topoisomerase II in a covalent complex with DNA. Based on DNA cleavage assays, the mode of interaction of these drugs was proposed to involve amino acid residues of the catalytic site. An in vitro binding study, however, revealed two potential binding sites for etoposide within human DNA topoisomerase IIα (htopoIIα), one in the catalytic core of the enzyme and one in the ATP‐binding N‐terminal domain. Here we have tested how N‐terminal mutations that reduce the affinity of the site for etoposide or ATP affect the sensitivity of yeast cells to etoposide. Surprisingly, when introduced into full‐length enzymes, mutations that lower the drug binding capacity of the N‐terminal domain in vitro render yeast more sensitive to epipodophyllotoxins. Consistently, when the htopoIIα N‐terminal domain alone is overexpressed in the presence of yeast topoII, cells become more resistant to etoposide. Point mutations that weaken etoposide binding eliminate this resistance phenotype. We argue that the N‐terminal ATP‐binding pocket competes with the active site of the holoenzyme for binding etoposide both in cis and in trans with different outcomes, suggesting that each topoisomerase II monomer has two non‐equivalent drug‐binding site

Apprentissage incrémental et reconnaissance d'écriture manuscrite à la volée

International audienceSoumission: Jeune-chercheur Mots-clés: Reconnaissance de gestes manuscrites, Evolving Fuzzy System (EFS), concept drifts, clustering incrémental, apprentissage incrémental en-ligne. Avec la multiplication des appareils intégrant des interfaces tactiles, l'interaction homme-machine tactile ou stylet s'est démocratisée. Malgré cela, aujourd'hui encore, l'interaction repose le plus souvent sur un jeu de gestes imposés par le système, facilitant la reconnaissance au détriment de la flexibilité pour l'utilisateur. Il a cependant été montré par [1] qu'un utilisateur s'approprie plus facilement les gestes de commandes s'il peut les personnaliser. De nombreuses applications pourraient tirer profit d'une telle personnalisation pour offrir un interaction personnalisée plus intuitive. Dans ce contexte, l'utilisateur peut ajouter de nouveaux gestes à chaque instant de l'utilisation du système il peut aussi progressivement modifier la forme de ses gestes. Pour concevoir ce type d'interaction, il est nécessaire d'utiliser un système d'apprentissage évolutif capable notamment de changer sa structure à partir de très peu de données pour réagir au changement de concepts (ajout de classes, modification de gestes). Les systèmes de reconnaisse évolutif (evolving fuzzy system (EFS)) tel que les ANYA-type fuzzy system [2] ou Evolve [3] sont des approches offrant une grande capacité d'évolution de par la flexibilité de leur structure modélisée par des règles d'inférences floues. Pour autant la modélisation de la détection et de la dérive des concepts n'est pas suffisamment stable dans ces systèmes pouvant conduire à une sur ou sous création de règles. Nos travaux de recherche se focalisent sur ce dernier point pour améliorer l'adaptation du système aux concepts par la modification et la création des règles d'inférences floues. Actuellement le système Evolve s'adapte aux dérives graduelles grâce à une mise a jour des règles à l'arrivée de chaque nouveau geste, mais échoue lorsqu'il doit faire face à une dérive brutale. De manière générale, il est compliqué pour un système de s'adapter efficacement à la fois aux dérives brutales et au dérives graduelles. Pour amorcer ce travail, nous explorons ici une nouvelle approche permettant de remettre à jour les anciennes règles en symbiose avec la création de nouvelles. Nous avons dans un premier temps exploré cette piste en conservant les données d'apprentissage pour simplifier la mise en oeuvre. De meilleurs résultats sur l'adaptation aux données sont déjà observés sur des données artificielles. Une étude comparative avec d'autres approches comme [4] a été menée sur des benchmarks de référence. Dans un second temps, on souhaite s'affranchir du stockage des données d'apprentissages. Nous proposons actuellement de faire du clustering incrémental sur deux couches en parallèle pour chacune des règles. La première couche est constituée d'un cluster qui évolue au fil de l'eau comme utilisé actuellement dans Evolve (pour suivre les changement de concepts graduels) tandis que la seconde couche travail directement sur deux clusters qui évoluent incrémentalement pour anticiper au plus tôt la détection et la modélisation d'une dérive de concept brutale (ajout d'un nouveau geste, forte déformation des gestes existants. .. .). Nous présenterons donc les problématiques sous-tendus par ce challenge ainsi que les premiers résultats obtenus

Is the typicality of “Provence Rosé wines” only a matter of color?

Aims: Given the diversity of French dry Rosé wines, Provence Rosé producers (France) wish to evaluate the typicality of their wines in order to better identify their typical characteristics. A clear pink color is one of them but they would also like to identify some specific odors and aromas. Here, we address these issues by: (i) assessing whether the identity of Provence Rosé wines is perceptible by tasting and shared by professionals based on specific odors and aromas (disregarding color as indicator using black glasses), and (ii) evaluating the impact of color on Provence Rosé wine typicality. Methods and results: Complementary methods were used: exemplarity measurements by a panel of wine professionals, sensory evaluation by a trained expert panel, and color assessment. It was confirmed that Provence Rosé wine typicality is based on color because the clearest wines were found to be more typical. However, typicality in odors and aromas was also demonstrated. Using black glasses, wine professionals from Provence agreed on ‘citrus fruit’, ‘exotic fruit’ and ‘fresh floral’ odors and aromas being typical attributes of Provence Rosé wines. Next, when using transparent glasses, the color of the wines clearly modified the perception of exemplarity. Conclusion: There is no single sensory profile of typical Provence Rosé wines. Variability within the sensory profiles of this specific Rosé wine area was observed, but some common aromatic and visual characteristics were identified. Significance and impact of the study: These results could be used as a marketing tool to better highlight the specific intrinsic characteristics of Provence Rosé wines. It will now be interesting to investigate the Provence area further in order to evaluate potential sub-area specificities linked to “terroir” factors

Features and distribution of CD8 T cells with human leukocyte antigen class I-specific receptor expression in chronic hepatitis C.: NKRs+ CD8 T cells in chronic Hepatitis C.

CD8(+) T cells represent a sizable component of the liver inflammatory infiltrate in chronic hepatitis C and are thought to contribute to immune-mediated tissue injury. Because chronic stimulation may promote the expression by CD8(+) T cells of distinct human leukocyte antigen class I-specific natural killer cell receptors (NKRs) susceptible to both inhibiting effector functions and promoting cell survival, we examined the distribution and characteristics of CD8(+) T cells with such receptors in chronic hepatitis C patients. NKR CD8(+) T cells were detectable in liver and peripheral blood from hepatitis C virus (HCV)-infected patients but were not major subsets. However, the frequency of NKG2A(+) CD8(+) in the liver and in a lesser extent in the peripheral blood was positively correlated to histological activity in HCV-infected patients. No such correlation was found with KIR(+) T cells in liver in HCV-infected patients and with the both NKR CD8(+) T cells in hepatitis B virus (HBV) infected patients. Circulating CD8(+) T cells expressing KIRs exhibited phenotypic features of memory T cells with exacerbated expression of the senescence marker CD57 in patients. NKG2A(+)CD8(+) T cells were committed T cells that appeared less differentiated than KIR(+)CD8(+) T cells. In HCV-infected patients, their content in perforin was low and similar to that observed in NKG2A(-)CD8(+) T cells; this scenario was not observed in healthy subjects and HBV-infected patients. Both NKG2A and KIRs could inhibit the response of HCV-specific CD8(+) T cells ex vivo. CONCLUSION: These results support the concept that an accumulation in the liver parenchyma of NKR(+)CD8(+) T cells that have functional alterations could be responsible for liver lesions. They provide novel insights into the complexity of liver-infiltrating CD8(+) T cells in chronic hepatitis C and reveal that distinct subsets of antigen-experienced CD8(+) T cells are differentially sensitive to the pervasive influence of HCV

Dynamique paysagère tardiglaciaire et holocène dans la vallée du Loir à Pezou (Loir-et-Cher) : développements méthodologiques et premiers résultats

Dans la vallée du Loir, une recherche a été initiée dans le cadre d’une thèse de doctorat à l’université d’Angers (J. Piana, en cours). L’objectif de l’étude est de reconstituer la trajectoire paysagère de la vallée du Loir au cours des derniers 15 000 ans (sous le contrôle des facteurs climatiques et anthropiques qui se sont exercés à l’échelle du bassin-versant) à partir d’un diagnostic des formes paysagères (construction et évolution des lits fluviaux et de la plaine alluviale, végétation, parcellaire, pratiques culturales…) et de l’identification des processus dynamiques qui les ont transformées et transmises (crise, rupture, héritage, résilience…). Dans le bassin-versant moyen du Loir (secteur de Pezou), les premiers résultats révèlent un enregistrement sédimentaire fin et permettent d’entrevoir l’évolution des paysages de la vallée en relation avec les changements climatiques et les occupations humaines au cours du Tardiglaciaire et de l’Holocène. Au début de l’Holocène, les paysages fluviaux héritent de morphologies à chenaux multiples mises en place durant le dernier glaciaire (Weichsélien). La transition Tardiglaciaire-Holocène est marquée par une métamorphose vers un système à chenal unique et un comblement argilo-tourbeux des bras secondaires. Ce comblement se poursuit jusqu’au Néolithique, période durant laquelle le changement de l’activité fluviale conduit à une nouvelle phase d’incision et vraisemblablement à une réactivation des bras latéraux. À l’Âge du Fer, une importante déforestation, associée à la pratique de l’élevage et de l’agriculture est mise en évidence. À partir de la période gallo-romaine, le contrôle anthropique des processus hydro-sédimentaires est croissant et conduit à l’augmentation de l’érosion des versants et à une forte aggradation verticale de la plaine alluviale de la vallée du Loir. Des travaux en cours visent à affiner la résolution temporelle de cette variabilité paysagère et à spatialiser cette dernière au sein de la vallée et du bassin-versant du Loir.In the Loir River valley, a research was started within a PhD thesis at Angers University (J. Piana, in progress). The study’s goal is to reconstitute the landscape trajectory of the Loir River fluvial space over the last 15.000 years (taking into account climate and anthropogenic driving factors at the level of the watershed) on the basis of the landscape forms analysis (building and evolution of river beds and alluvial plain, vegetation, cadastre, cultural practices) and identifying dynamical processes which transform and transmit those forms (crisis, rupture, heritage, resiliency…). First results, in the Middle Loir River watershed (sector of Pezou) show high-resolution fluvial records and lead to an overview of the landscape evolution of the valley in relation to climatic change and human settlements during the Lateglacial and the Holocene. At the beginning of the Holocene, fluvial landscapes inherite from a Weichselian multi-channel pattern. The Lateglacial-Holocene transition is marked by a metamorphosis to a meandering pattern and a clayey-peaty infilling of the abandoned channels. This filling runs until the Neolithic period. Then, an increased fluvial activity leads to a new incision period and probably to a reactivation of the lateral channels. From Iron Age, we observe an important deforestation, the opening of the vegetal landscape and the practice of cattle raising activity. From the Gallo-roman period, anthropogenic control on sedimentary processes is increasing and leads to slope wearing and aggradation in the alluvial plain

Evaluation of the analytical performances of the Cobas c513 analyser for HbA1c assay

Introduction: Haemoglobin A1c (HbA1c) is considered to be the gold standard for the follow-up of glycaemic control in patients with diabetes mellitus and is also a diagnostic tool. Accordingly, reliable and efficient methods must be used for its quantification. Roche Diagnostics have recently adapted the Tina-quant® HbA1c Third Generation immunoassay on a fully dedicated analyser, the Cobas c513, which allows a high throughput of up to 400 samples per hour. The present article deals with the evaluation of the analytical performances of this system which has been recently introduced to the market. Materials and methods: Precision, comparison with two ion-exchange high-performance liquid chromatography (HPLC) methods (Variant II and D-100 systems, BioRad Laboratories) using Passing Bablok and Bland-Altman analyses, accuracy and interference of the most frequent haemoglobin (Hb) variants on HbA1c measurement were evaluated. Results: Precision was high, with coefficients of variation lower than 1.1% (HbA1c values expressed in National Glycohemoglobin Standardization Program units, 1.7% for values expressed in International Federation of Clinical Chemistry and Laboratory Medicine [IFCC] units). The comparison study showed similar results with the two HPLC systems. The analysis of samples with IFCC-assigned values showed high methodological accuracy. Finally, no interference of bilirubin, triglycerides and common Hb variants (Hb AC, AD, AE, AS) was observed. Conclusions: This evaluation showed that the analytical performance of the Cobas c513 analyser for HbA1c assay makes it suitable for a routine use in clinical chemistry laboratories

Complete Genome Sequence of the Piezophilic, Mesophilic, Sulfate-Reducing Bacterium Desulfovibrio hydrothermalis AM13(T.).

International audienceDesulfovibrio hydrothermalis AM13(T) is a piezophilic, mesophilic, hydrogenotrophic sulfate-reducing bacterium collected from a deep-sea hydrothermal chimney on the East Pacific Rise (2,600 m depth, 13°N). We report the genome sequence of this bacterium, which includes a 3,702,934-bp chromosome and a circular plasmid of 5,328 bp

Urinary incontinence related to perineal muscle strength in the first trimester of pregnancy: cross-sectional study

Objective To analyze pelvic floor muscle strength (PFMS), urinary continence and quality of life related to urinary incontinence (UI) of women in the first trimester of pregnancy. Method Cross-sectional study with a sample of 500 women who started prenatal care in a complementary healthcare facility in Guarulhos, state of São Paulo, from 2012 and 2013. Pelvic floor muscle strength was evaluated through perineometry. The pregnant women who presented UI answered the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Results It was found that maternal age (OR=1.06; CI95% 1.02-1.11) and prior UI (OR=15.12; 95%CI 8.19-27.92) are the variables that, in tandem, best explain the occurrence of UI at the beginning of pregnancy. The mean score on the ICIQ-SF was 8.2 (SD=3.9), considered a moderate impact on quality of life. Conclusion Older pregnant women with prior UI are more likely to have UI in the first trimester of pregnancy.
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Women’s pelvic floor muscle strength and urinary and anal incontinence after childbirth: a cross-sectional study

Abstract OBJECTIVE To analyse pelvic floor muscle strength (PFMS) and urinary and anal incontinence (UI and AI) in the postpartum period. METHOD Cross-sectional study carried out with women in their first seven months after child birth. Data were collected through interviews, perineometry (Peritron™), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). RESULTS 128 women participated in the study. The PFMS mean was 33.1 (SD=16.0) cmH2O and the prevalence of UI and AI was 7.8% and 5.5%, respectively. In the multiple analyses, the variables associated with PFMS were type of birth and cohabitation with a partner. Newborn’s weight, previous pregnancy, UI during pregnancy, and sexual activity showed an association with UI after child birth. Only AI prior to pregnancy was associated with AI after childbirth. CONCLUSION Vaginal birth predisposes to the reduction of PFMS, and caesarean section had a protective effect to its reduction. The occurrence of UI during pregnancy is a predictor of UI after childbirth, and women with previous pregnancies and newborns with higher weights are more likely to have UI after childbirth.AI prior to pregnancy is the only risk factor for its occurrence after childbirth. Associations between PFMS and cohabitation with a partner, and between UI and sexual activity do not make possible to conclude that these variables are directly associated