L'élastographie ultrasonore dynamique vasculaire : une nouvelle modalité d'imagerie non-invasive pour la caractérisation mécanique de la thrombose veineuse

L’accident thromboembolique veineux, tel que la thrombose veineuse profonde (TVP) ou thrombophlébite des membres inférieurs, est une pathologie vasculaire caractérisée par la formation d’un caillot sanguin causant une obstruction partielle ou totale de la lumière sanguine. Les embolies pulmonaires sont une complication mortelle des TVP qui surviennent lorsque le caillot se détache, circule dans le sang et produit une obstruction de la ramification artérielle irriguant les poumons. La combinaison d’outils et de techniques d’imagerie cliniques tels que les règles de prédiction cliniques (signes et symptômes) et les tests sanguins (D-dimères) complémentés par un examen ultrasonographique veineux (test de compression, écho-Doppler), permet de diagnostiquer les premiers épisodes de TVP. Cependant, la performance de ces outils diagnostiques reste très faible pour la détection de TVP récurrentes. Afin de diriger le patient vers une thérapie optimale, la problématique n’est plus basée sur la détection de la thrombose mais plutôt sur l’évaluation de la maturité et de l’âge du thrombus, paramètres qui sont directement corrélées à ses propriétés mécaniques (e.g. élasticité, viscosité). L’élastographie dynamique (ED) a récemment été proposée comme une nouvelle modalité d’imagerie non-invasive capable de caractériser quantitativement les propriétés mécaniques de tissus. L’ED est basée sur l’analyse des paramètres acoustiques (i.e. vitesse, atténuation, pattern de distribution) d’ondes de cisaillement basses fréquences (10-7000 Hz) se propageant dans le milieu sondé. Ces ondes de cisaillement générées par vibration externe, ou par source interne à l’aide de la focalisation de faisceaux ultrasonores (force de radiation), sont mesurées par imagerie ultrasonore ultra-rapide ou par résonance magnétique. Une méthode basée sur l’ED adaptée à la caractérisation mécanique de thromboses veineuses permettrait de quantifier la sévérité de cette pathologie à des fins d’amélioration diagnostique. Cette thèse présente un ensemble de travaux reliés au développement et à la validation complète et rigoureuse d’une nouvelle technique d’imagerie non-invasive élastographique pour la mesure quantitative des propriétés mécaniques de thromboses veineuses. L’atteinte de cet objectif principal nécessite une première étape visant à améliorer les connaissances sur le comportement mécanique du caillot sanguin (sang coagulé) soumis à une sollicitation dynamique telle qu’en ED. Les modules de conservation (comportement élastique, G’) et de perte (comportement visqueux, G’’) en cisaillement de caillots sanguins porcins sont mesurés par ED lors de la cascade de coagulation (à 70 Hz), et après coagulation complète (entre 50 Hz et 160 Hz). Ces résultats constituent les toutes premières mesures du comportement dynamique de caillots sanguins dans une gamme fréquentielle aussi étendue. L’étape subséquente consiste à mettre en place un instrument innovant de référence (« gold standard »), appelé RheoSpectris, dédié à la mesure de la viscoélasticité hyper-fréquence (entre 10 Hz et 1000 Hz) des matériaux et biomatériaux. Cet outil est indispensable pour valider et calibrer toute nouvelle technique d’élastographie dynamique. Une étude comparative entre RheoSpectris et la rhéométrie classique est réalisée afin de valider des mesures faites sur différents matériaux (silicone, thermoplastique, biomatériaux, gel). L’excellente concordance entre les deux technologies permet de conclure que RheoSpectris est un instrument fiable pour la mesure mécanique à des fréquences difficilement accessibles par les outils actuels. Les bases théoriques d’une nouvelle modalité d’imagerie élastographique, nommée SWIRE (« shear wave induced resonance dynamic elastography »), sont présentées et validées sur des fantômes vasculaires. Cette approche permet de caractériser les propriétés mécaniques d’une inclusion confinée (e.g. caillot sanguin) à partir de sa résonance (amplification du déplacement) produite par la propagation d’ondes de cisaillement judicieusement orientées. SWIRE a également l’avantage d’amplifier l’amplitude de vibration à l’intérieur de l’hétérogénéité afin de faciliter sa détection et sa segmentation. Finalement, la méthode DVT-SWIRE (« Deep venous thrombosis – SWIRE ») est adaptée à la caractérisation de l’élasticité quantitative de thromboses veineuses pour une utilisation en clinique. Cette méthode exploite la première fréquence de résonance mesurée dans la thrombose lors de la propagation d’ondes de cisaillement planes (vibration d’une plaque externe) ou cylindriques (simulation de la force de radiation par génération supersonique). DVT-SWIRE est appliquée sur des fantômes simulant une TVP et les résultats sont comparés à ceux donnés par l’instrument de référence RheoSpectris. Cette méthode est également utilisée avec succès dans une étude ex vivo pour l’évaluation de l’élasticité de thromboses porcines explantées après avoir été induites in vivo par chirurgie.

A comparison of the imaging characteristics of the new Kodak Hyper Speed G film with the current T-MAT G/RA film and the CR 9000 system.

Three standard radiation qualities (RQA 3, RQA 5 and RQA 9) and two screens, Kodak Lanex Regular and Insight Skeletal, were used to compare the imaging performance and dose requirements of the new Kodak Hyper Speed G and the current Kodak T-MAT G/RA medical x-ray films. The noise equivalent quanta (NEQ) and detective quantum efficiencies (DQE) of the four screen-film combinations were measured at three gross optical densities and compared with the characteristics for the Kodak CR 9000 system with GP (general purpose) and HR (high resolution) phosphor plates. The new Hyper Speed G film has double the intrinsic sensitivity of the T-MAT G/RA film and a higher contrast in the high optical density range for comparable exposure latitude. By providing both high sensitivity and high spatial resolution, the new film significantly improves the compromise between dose and image quality. As expected, the new film has a higher noise level and a lower signal-to-noise ratio than the standard film, although in the high frequency range this is compensated for by a better resolution, giving better DQE results--especially at high optical density. Both screen-film systems outperform the phosphor plates in terms of MTF and DQE for standard imaging conditions (Regular screen at RQA 5 and RQA 9 beam qualities). At low energy (RQA 3), the CR system has a comparable low-frequency DQE to screen-film systems when used with a fine screen at low and middle optical densities, and a superior low-frequency DQE at high optical density.

Incidence of hypo- and hyper-capnia in a cross-sectional European cohort of ventilated newborn infants

OBJECTIVE To determine the incidence of hypo- and hyper-capnia in a European cohort of ventilated newborn infants. DESIGN AND SETTING Two-point cross-sectional prospective study in 173 European neonatal intensive care units. PATIENTS AND METHODS Patient characteristics, ventilator settings and measurements, and blood gas analyses were collected for endotracheally ventilated newborn infants on two separate dates. RESULTS A total of 1569 blood gas analyses were performed in 508 included patients with a mean±SD Pco2 of 48±12 mm Hg or 6.4±1.6 kPa (range 17-104 mm Hg or 2.3-13.9 kPa). Hypocapnia (Pco2<30 mm Hg or 4 kPa) and hypercapnia (Pco2>52 mm Hg or 7 kPa) was present in, respectively, 69 (4%) and 492 (31%) of the blood gases. Hypocapnia was most common in the first 3 days of life (7.3%) and hypercapnia after the first week of life (42.6%). Pco2 was significantly higher in preterm infants (49 mm Hg or 6.5 kPa) than term infants (43 mm Hg or 5.7 kPa) and significantly lower during pressure-limited ventilation (47 mm Hg or 6.3±1.6 kPa) compared with volume-targeted ventilation (51 mm Hg or 6.8±1.7 kPa) and high-frequency ventilation (50 mm Hg or 6.7±1.7 kPa). CONCLUSIONS This study shows that hypocapnia is a relatively uncommon finding during neonatal ventilation. The higher incidence of hypercapnia may suggest that permissive hypercapnia has found its way into daily clinical practice.

Compound Heterozygous Rag2 Mutations Mimicking Hyper Igm Syndrome.

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Elevated Micronucleus Frequency In Patients With Type 2 Diabetes, Dyslipidemia And Periodontitis.

The over-production of reactive oxygen species (ROS) can cause oxidative damage to a large number of molecules, including DNA, and has been associated with the pathogenesis of several disorders, such as diabetes mellitus (DM), dyslipidemia and periodontitis (PD). We hypothesise that the presence of these diseases could proportionally increase the DNA damage. The aim of this study was to assess the micronucleus frequency (MNF), as a biomarker for DNA damage, in individuals with type 2 DM, dyslipidemia and PD. One hundred and fifty patients were divided into five groups based upon diabetic, dyslipidemic and periodontal status (Group 1 - poor controlled DM with dyslipidemia and PD; Group 2 - well-controlled DM with dyslipidemia and PD; Group 3 - without DM with dyslipidemia and PD; Group 4 - without DM, without dyslipidemia and with PD; and Group 5 - without DM, dyslipidemia and PD). Blood analyses were carried out for fasting plasma glucose, HbA1c and lipid profile. Periodontal examinations were performed, and venous blood was collected and processed for micronucleus (MN) assay. The frequency of micronuclei was evaluated by cell culture cytokinesis-block MN assay. The general characteristics of each group were described by the mean and standard deviation and the data were submitted to the Mann-Whitney, Kruskal-Wallis, Multiple Logistic Regression and Spearman tests. The Groups 1, 2 and 3 were similarly dyslipidemic presenting increased levels of total cholesterol, low density lipoprotein cholesterol and triglycerides. Periodontal tissue destruction and local inflammation were significantly more severe in diabetics, particularly in Group 1. Frequency of bi-nucleated cells with MN and MNF, as well as nucleoplasmic bridges, were significantly higher for poor controlled diabetics with dyslipidemia and PD in comparison with those systemically healthy, even after adjusting for age, and considering Bonferroni's correction. Elevated frequency of micronuclei was found in patients affected by type 2 diabetes, dyslipidemia and PD. This result suggests that these three pathologies occurring simultaneously promote an additional role to produce DNA impairment. In addition, the micronuclei assay was useful as a biomarker for DNA damage in individuals with chronic degenerative diseases.

Frequency Of The Allelic Variant C.1150t > C In Exon 10 Of The Fibroblast Growth Factor Receptor 3 (fgfr3) Gene Is Not Increased In Patients With Pathogenic Mutations And Related Chondrodysplasia Phenotypes.

Mutations in the FGFR3 gene cause the phenotypic spectrum of FGFR3 chondrodysplasias ranging from lethal forms to the milder phenotype seen in hypochondroplasia (Hch). The p.N540K mutation in the FGFR3 gene occurs in ∼70% of individuals with Hch, and nearly 30% of individuals with the Hch phenotype have no mutations in the FGFR3, which suggests genetic heterogeneity. The identification of a severe case of Hch associated with the typical mutation c.1620C > A and the occurrence of a c.1150T > C change that resulted in a p.F384L in exon 10, together with the suspicion that this second change could be a modulator of the phenotype, prompted us to investigate this hypothesis in a cohort of patients. An analysis of 48 patients with FGFR3 chondrodysplasia phenotypes and 330 healthy (control) individuals revealed no significant difference in the frequency of the C allele at the c.1150 position (p = 0.34). One patient carrying the combination `pathogenic mutation plus the allelic variant c.1150T > C' had a typical achondroplasia (Ach) phenotype. In addition, three other patients with atypical phenotypes showed no association with the allelic variant. Together, these results do not support the hypothesis of a modulatory role for the c.1150T > C change in the FGFR3 gene.

Explosive Synchronization With Partial Degree-frequency Correlation.

Networks of Kuramoto oscillators with a positive correlation between the oscillators frequencies and the degree of their corresponding vertices exhibit so-called explosive synchronization behavior, which is now under intensive investigation. Here we study and discuss explosive synchronization in a situation that has not yet been considered, namely when only a part, typically a small part, of the vertices is subjected to a degree-frequency correlation. Our results show that in order to have explosive synchronization, it suffices to have degree-frequency correlations only for the hubs, the vertices with the highest degrees. Moreover, we show that a partial degree-frequency correlation does not only promotes but also allows explosive synchronization to happen in networks for which a full degree-frequency correlation would not allow it. We perform a mean-field analysis and our conclusions were corroborated by exhaustive numerical experiments for synthetic networks and also for the undirected and unweighed version of a typical benchmark biological network, namely the neural network of the worm Caenorhabditis elegans. The latter is an explicit example where partial degree-frequency correlation leads to explosive synchronization with hysteresis, in contrast with the fully correlated case, for which no explosive synchronization is observed.

Enhanced D1 And D2 Inhibitions Induced By Low-frequency Trains Of Conditioning Stimuli: Differential Effects On H- And T-reflexes And Possible Mechanisms.

Mechanically evoked reflexes have been postulated to be less sensitive to presynaptic inhibition (PSI) than the H-reflex. This has implications on investigations of spinal cord neurophysiology that are based on the T-reflex. Preceding studies have shown an enhanced effect of PSI on the H-reflex when a train of ~10 conditioning stimuli at 1 Hz was applied to the nerve of the antagonist muscle. The main questions to be addressed in the present study are if indeed T-reflexes are less sensitive to PSI and whether (and to what extent and by what possible mechanisms) the effect of low frequency conditioning, found previously for the H-reflex, can be reproduced on T-reflexes from the soleus muscle. We explored two different conditioning-to-test (C-T) intervals: 15 and 100 ms (corresponding to D1 and D2 inhibitions, respectively). Test stimuli consisted of either electrical pulses applied to the posterior tibial nerve to elicit H-reflexes or mechanical percussion to the Achilles tendon to elicit T-reflexes. The 1 Hz train of conditioning electrical stimuli delivered to the common peroneal nerve induced a stronger effect of PSI as compared to a single conditioning pulse, for both reflexes (T and H), regardless of C-T-intervals. Moreover, the conditioning train of pulses (with respect to a single conditioning pulse) was proportionally more effective for T-reflexes as compared to H-reflexes (irrespective of the C-T interval), which might be associated with the differential contingent of Ia afferents activated by mechanical and electrical test stimuli. A conceivable explanation for the enhanced PSI effect in response to a train of stimuli is the occurrence of homosynaptic depression at synapses on inhibitory interneurons interposed within the PSI pathway. The present results add to the discussion of the sensitivity of the stretch reflex pathway to PSI and its functional role.

Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA) in a large group of Brazilian patients

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6 % in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30 % of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

Recalled and recorded bowel habits confirm early onset and high frequency of constipation in day-care nursery children

CONTEXT: Mothers recall early-onset constipation in children attending gastroenterology clinics. OBJECTIVES: To study the bowel habit of young children in the community to determine, first, whether early-onset constipation is confirmed in this setting and, second, the agreement between recalled and recorded bowel habit. METHODS:Defecation data of 57 children aged 6.0-40.7 mo were obtained by maternal recall (questionnaire on predominant stool characteristics) and by record (1,934 defecations registered prospectively at home and in the nursery). The bowel habit was classified according to stool frequency and proportion of stool characteristics (soft, hard and/or runny). Two criteria were used to classify recorded data, since the cutoff point for hard stools to identify constipation is undefined in children: predominant criterion and adult criterion, respectively with >50% and >25% of stools with altered consistency. Bowel habit categories were: adequate, constipation, functional diarrhea and "other bowel habit". Nonparametric statistics, and the Kappa index for agreement between recalled and recorded bowel habit, were used. RESULTS: Constipation occurred in 17.5%, 10.5%, 19.3% of the children by recall, the predominant and the adult criteria, respectively. Constipation was the main recalled alteration, vs 12.3% "other bowel habit". Only one child classified as having functional diarrhea (by the adult criterion). Agreement between recalled and recorded bowel habit was fair for constipation, by the predominant and the adult criteria (K = 0.28 and 0.24, respectively), but only slight (K <0.16) for other bowel habit categories. Individual data, however, pointed to a better relationship between recalled constipation and the adult rather than the predominant criterion. CONCLUSIONS: Frequent early-onset constipation was confirmed. Fair agreement between recalled and recorded constipation by the two used criteria indicates that recalled data are quite reliable to detect constipation.

Validation of a food frequency questionnaire to assess the consumption of carotenoids, fruits and vegetables among adolescents: the method of triads

The aim of this study was to validate the intake of carotenoids, fruits and vegetables estimated by the Food Frequency Questionnaire for Adolescents (FFQA) using the method of triads. Blood samples were collected from 80 elementary school adolescents to assess serum levels of β-carotene. Partial correlation coefficients (r) were calculated between an estimated intake of carotenoids, fruits and vegetables and the serum levels of β-carotene. Validity coefficients were calculated using the method of triads. With the exception of carotenoids, partial r from the food frequency questionnaire (FFQ) were greater than those of the 24-hour recall (24hR). The fruit/vegetable group showed the highest partial r for the FFQ (r = 0.235) and the 24hR (r = 0.137). The highest validity coefficient was obtained for the vegetable group, as assessed by the FFQ (r = 0.873). On average, the validity coefficient values for the FFQ were greater than those obtained for the 24hR or the β-carotene serum levels. The FFQA is an accurate tool for estimating the intake of carotenoids, fruits and vegetables in this population group.

Assessing the validity of a food frequency questionnaire among low-income women in São Paulo, southeastern Brazil

This study describes the validity of a food frequency questionnaire (FFQ) in 93 low-income women (20-65 years), participating in a case-control study in São Paulo, Brazil. Two FFQ (FFQ1 and FFQ2, 12 months apart) and three 24-hour dietary recalls (24hR) were conducted between 2003 and 2004 to estimate dietary intake during the past year. The Pearson correlation coefficients (crude, energy-adjusted and de-attenuated) were used for comparisons between FFQ and 24hR. The agreement between the methods was further examined by the Bland-Altman analysis. For the assessment of long-term reliability, the energy-adjusted intra-class correlation coefficients were mostly around 0.40, but higher for vitamin A and folate (0.50-0.56). Energy-adjusted, attenuation-corrected Pearson validity correlations between FFQ and DR ranged from 0.30-0.54 for macronutrients to 0.20-0.48 for micronutrients, with higher value for calcium (0.75). There were small proportions of grossly misclassified nutrient intakes, while Bland-Altman plots indicated that the FFQ is accurate in assessing nutrient intake at a group level.

Matched case-control study evaluating the frequency of the main agents associated with neonatal diarrhea in piglets

A case-control study was carried out in litters of 1 to 7-day-old piglets to identify the main infectious agents involved with neonatal diarrhea in pigs. Fecal samples (n=276) from piglets were collected on pig farms in the State of Rio Grande do Sul, Brazil, from May to September 2007. Litters with diarrhea were considered cases (n=129) and normal litters (n=147) controls. The samples were examined by latex agglutination test, PAGE, conventional isolating techniques, ELISA, PCR, and microscopic methods in order to detect rotavirus, bacterial pathogens (Escherichia coli, Clostridium perfringens type A and C, and Clostridium difficile), and parasites (Coccidian and Cryptosporidium spp.). Outbreaks of diarrhea were not observed during sampling. At least one agent was detected in fecal samples on 25 out of 28 farms (89.3%) and in 16 farms (57.1%) more than one agent was found. The main agents diagnosed were Coccidia (42.86%) and rotavirus (39.29%). The main agents identified in litters with diarrhea were Clostridium difficile (10.6%), Clostridium perfringens type A (8.8%) and rotavirus (7.5%); in control litters, Clostridium difficile (16.6%) and Coccidian (8.5%). Beta hemolytic Escherichia coli and Clostridium perfringens type C were not detected. When compared with controls, no agent was significantly associated with diarrhea in case litters. These findings stress the need for caution in the interpretation of laboratorial diagnosis of mild diarrhea in neonatal pigs, as the sole detection of an agent does not necessarily indicate that it is the cause of the problem.

Time-frequency and time-scale analysis of Barkhausen noise signals

Carrying out information about the microstructure and stress behaviour of ferromagnetic steels, magnetic Barkhausen noise (MBN) has been used as a basis for effective non-destructive testing methods, opening new areas in industrial applications. One of the factors that determines the quality and reliability of the MBN analysis is the way information is extracted from the signal. Commonly, simple scalar parameters are used to characterize the information content, such as amplitude maxima and signal root mean square. This paper presents a new approach based on the time-frequency analysis. The experimental test case relates the use of MBN signals to characterize hardness gradients in a AISI4140 steel. To that purpose different time-frequency (TFR) and time-scale (TSR) representations such as the spectrogram, the Wigner-Ville distribution, the Capongram, the ARgram obtained from an AutoRegressive model, the scalogram, and the Mellingram obtained from a Mellin transform are assessed. It is shown that, due to nonstationary characteristics of the MBN, TFRs can provide a rich and new panorama of these signals. Extraction techniques of some time-frequency parameters are used to allow a diagnostic process. Comparison with results obtained by the classical method highlights the improvement on the diagnosis provided by the method proposed.

Power Secant Method applied to natural frequency extraction of Timoshenko beam structures

This work deals with an improved plane frame formulation whose exact dynamic stiffness matrix (DSM) presents, uniquely, null determinant for the natural frequencies. In comparison with the classical DSM, the formulation herein presented has some major advantages: local mode shapes are preserved in the formulation so that, for any positive frequency, the DSM will never be ill-conditioned; in the absence of poles, it is possible to employ the secant method in order to have a more computationally efficient eigenvalue extraction procedure. Applying the procedure to the more general case of Timoshenko beams, we introduce a new technique, named ""power deflation"", that makes the secant method suitable for the transcendental nonlinear eigenvalue problems based on the improved DSM. In order to avoid overflow occurrences that can hinder the secant method iterations, limiting frequencies are formulated, with scaling also applied to the eigenvalue problem. Comparisons with results available in the literature demonstrate the strength of the proposed method. Computational efficiency is compared with solutions obtained both by FEM and by the Wittrick-Williams algorithm.