Prenatal ultrasonographic detection of gastrointestinal obstruction: results from 18 European congenital anomaly registries.

OBJECTIVES: We evaluated the prenatal detection of gastrointestinal obstruction (GIO, including atresia, stenosis, absence or fistula) by routine ultrasonographic examination in an unselected population all over Europe. METHODS: Data from 18 congenital malformation registries in 11 European countries were analysed. These multisource registries used the same methodology. All fetuses/neonates with GIO confirmed within 1 week after birth who had prenatal sonography and were born during the study period (1 July 1996 to 31 December 1998) were included. RESULTS: There were 670 793 births in the area covered and 349 fetuses/neonates had GIO. The prenatal detection rate of GIO was 34%; of these 40% were detected < or = 24 weeks of gestation (WG). A total of 31% (60/192) of the isolated GIO were detected prenatally, as were 38% (59/157) of the associated GIO (p=0.26). The detection rate was 25% for esophageal obstruction (31/122), 52% for duodenal obstruction (33/64), 40% for small intestine obstruction (27/68) and 29% for large intestine obstruction (28/95) (p=0.002). The detection rate was higher in countries with a policy of routine obstetric ultrasound. Fifteen percent of pregnancies were terminated (51/349). Eleven of these had chromosomal anomalies, 31 multiple malformations, eight non-chromosomal recognized syndromes, and one isolated GIO. The participating registries reflect the various national policies for termination of pregnancy (TOP), but TOPs after 24 WG (11/51) do not appear to be performed more frequently in countries with a liberal TOP policy. CONCLUSION: This European study shows that the detection rate of GIO depends on the screening policy and on the sonographic detectability of GIO subgroups.

EUROCAT website data on prenatal detection rates of congenital anomalies.

The EUROCAT website www.eurocat-network.eu publishes prenatal detection rates for major congenital anomalies using data from European population-based congenital anomaly registers, covering 28% of the EU population as well as non-EU countries. Data are updated annually. This information can be useful for comparative purposes to clinicians and public health service managers involved in the antenatal care of pregnant women as well as those interested in perinatal epidemiology.

Compact portable biosensor for arsenic detection in aqueous samples with Escherichia coli bioreporter cells.

We present a compact portable biosensor to measure arsenic As(III) concentrations in water using Escherichia coli bioreporter cells. Escherichia coli expresses green fluorescent protein in a linearly dependent manner as a function of the arsenic concentration (between 0 and 100 μg/L). The device accommodates a small polydimethylsiloxane microfluidic chip that holds the agarose-encapsulated bacteria, and a complete optical illumination/collection/detection system for automated quantitative fluorescence measurements. The device is capable of sampling water autonomously, controlling the whole measurement, storing and transmitting data over GSM networks. We demonstrate highly reproducible measurements of arsenic in drinking water at 10 and 50 μg/L within 100 and 80 min, respectively.

A new, automated, four-colour interphase FISH approach for the simultaneous detection of specific aneuploidies of diagnostic and prognostic significance in high hyperdiploid ALL

In hyperdiploid acute lymphoblastic leukaemia (ALL), the simultaneous occurrence of specific aneuploidies confers a more favourable outcome than hyperdiploidy alone. Interphase (I) FISH complements conventional cytogenetics (CC) through its sensitivity and ability to detect chromosome aberrations in non-dividing cells. To overcome the limits of manual I-FISH, we developed an automated four-colour I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for chromosomes 4, 6, 10 and 17. Parameters established for automatic nucleus selection and signal detection were evaluated (3 controls). Cut-off values were determined (10 controls, 1000 nuclei/case). Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 ALL patients (1500 nuclei/patient) were compared with those by CC. Various combinations of aneuploidies were identified. All clones detected by CC were observed by I-FISH. I-FISH revealed numerous additional abnormal clones, ranging between 0.1% and 31.6%, based on the large number of nuclei evaluated. Four-colour automated I-FISH permits the identification of concurrent aneuploidies of prognostic significance in hyperdiploid ALL. Large numbers of cells can be analysed rapidly by this method. Owing to its high sensitivity, the method provides a powerful tool for the detection of small abnormal clones at diagnosis and during follow up. Compared to CC, it generates a more detailed cytogenetic picture, the biological and clinical significance of which merits further evaluation. Once optimised for a given set of probes, the system can be easily adapted for other probe combinations.

Multisensor change detection with nonlinear canonical correlation

The analysis of multi-modal and multi-sensor images is nowadays of paramount importance for Earth Observation (EO) applications. There exist a variety of methods that aim at fusing the different sources of information to obtain a compact representation of such datasets. However, for change detection existing methods are often unable to deal with heterogeneous image sources and very few consider possible nonlinearities in the data. Additionally, the availability of labeled information is very limited in change detection applications. For these reasons, we present the use of a semi-supervised kernel-based feature extraction technique. It incorporates a manifold regularization accounting for the geometric distribution and jointly addressing the small sample problem. An exhaustive example using Landsat 5 data illustrates the potential of the method for multi-sensor change detection.

RECHERCHE TRANSLATIONNELLE EN NEUROSCIENCES PSYCHIATRIQUES: DE L'ANIMAL MODELE DE SCHIZOPHRENIE A LA DETECTION D'UNE DESORIENTATION SPATIALE, PRATIQUE OU SYMBOLIQUE CHEZ DES PATIENTS

La modélisation, chez l'animal, de maladies psychiatriques telles que la schizophrénie repose sur différentes démarches visant à induire des perturbations cérébrales similaires à celles observées dans la maladie. Nous avons cherché à étudier chez le rat les effets d'une diminution (50%) transitoire en glutathion (GSH) durant le développement (PND 5 à PND 16) à partir de l'implication, chez des adultes, des conséquences de cette perturbation dans des mécanismes fondamentaux de traitement de l'information sensorielle. Cette thèse évalue et documente les déficits de compétences de navigation spatiale dans ce modèle. Nous avons mis en évidence des effets comportementaux à partir de l'identification de différences particulières dans des tâches d'orientation: des difficultés, chez les rats ayant subi un déficit en GSH, à élaborer une représentation globale de l'environnement dans lequel ils se déplacent, difficultés compensées par une attention particulière aux détails visuels le composant. Cette stratégie réactive compensatoire est efficace lorsque les conditions permettent un ajustement continu aux repères visuels environnementaux. Elle ne permet cependant pas des prédictions et des attentes sur ce qui devrait être rencontré et perçu dans une certaine direction, dès qu'une partie des informations visuelles familières disparaît. Il faudrait pour cela une capacité fondée sur une représentation abstraite, à distance des modalités sensorielles qui en ont permis son élaboration. Notre thèse soutient que les déficits, supposés participer à l'émergence de certains symptômes de la maladie, auraient également des conséquences sur l'élaboration de la représentation spatiale nécessaire à des capacités d'orientation effectives et symboliques. - The study of a psychiatric disease such as schizophrenia in an animal model relies on different approaches attempting to replicate brain perturbations similar to those observed in the illness. In the present work, behavioural consequences of a functional deficit in brain connectivity and coordination were assessed in rats with a transitory glutathione (GSH) deficit induced during the postnatal development (PND 5-PND 16) with daily injections of BSO (1- buthionine-(S,R)- sulfoximine). We searched for a theoretical syndrome associating ecologically relevant behavioural adaptive deficits and resulting from the weakening of sensory integration processes. Our results revealed significant and specific deficit of BSO treated rats in spatial orientation tasks designed to test for cognitive mapping abilities. Treated rats behaved as if impaired in the proactive strategies supported by an abstract representation such as a cognitive map. In contrast their performances were preserved whenever the environmental conditions allowed for adaptative reactive strategies, an equivalent of the visual affordances described by Gibson (1958). This supports our thesis that BSO treated rats expressed difficulties in elaborating a global representation of the environment. This deficit was completely - or - partially compensated by the development of an increased attention to the environment's visual details. This compensatory reactive strategy requires a rich environment allowing for continuous adjustment to visual cues. However, such adjustment doesn't allow to predictions and expectancies about what should be met and perceived in a certain direction, when familiar visual spatial cues are missing. Such competencies require orientation based on the use of an abstract spatial representation, independent from the specific sensory modalities that have participated to its elaboration. The impairment of BSO rats such spatial representation could result from a deficit in the integration and organization of perceptual information. Our model leads to the hypothesis that these fundamental deficits might account for certain symptoms of schizophrenia. They would also interfere with in the capacity to elaborate spatial representation necessary for optimal orientation in natural, artificial or symbolic environment.

New Diagnostic Real-Time PCR for Specific Detection of Mycoplasma hominis DNA.

Mycoplasma hominis is a fastidious micro-organism causing genital and extragenital infections. We developed a specific real-time PCR that exhibits high sensitivity and low intrarun and interrun variabilities. When applied to clinical samples, this quantitative PCR allowed to confirm the role of M. hominis in three patients with severe extragenital infections.

On-farm animal welfare assessment in dairy cattle: improved lameness detection

Estudi realitzat a partir d’una estada a la University of British Columbia, Canada, entre 2010 i 2012. Primerament es va desenvolupar una escala per mesurar coixeses (amb valors de l’1 al 5). Aquesta escala es va utilitzar per estudiar l’associació entre factors de risc a nivell de granja (disseny de le instal.lacions i maneig) i la prevalencia de coixeses a Nord America. Les dades es van recollir en un total de 40 granges al Nord Est dels E.E.U.U (NE) i 39 a California (CA) . Totes les vaques del group mes productiu es van categoritzar segons la severitat de les coixeses: sanes, coixes i severament coixes. La prevalencia de coixeses en general fou del 55 % a NE i del 31% a CA. La prevalencia de coixeses severes fou del 8% a NE i del 4% a Ca. A NE, les coixeses en general increntaren amb la presencia de serradura als llits i disminuiren en granjes grans, amb major quantitat de llit i acces a pastura. Les coixeses mes severes incrementaren amb la falta d’higiene als llit i amb la presencia de serradura als llits, i disminuiren amb la quantitat de llit proveit, l’us de sorra als llits i amb la mida de la granja. A CA, les coixeses en general incrementaren amb la falta d’higiene al llit, i disminuiren amb la mida de la granja, la presencia de terres de goma, l’increment d’espai als cubicles , l’espai a l’abeuredor i la desinfeccio de les peulles. Les coixeses severes incrementaren amb la falta d’higiene al llit i disminuixen amb la frequencia de neteja del corral. En conclusio, canvis en el maneig i el disseny de les instal.lacions poden ajudar a disminuir la prevalencia de coixeses, tot i que les estrategies a seguir variaran segons la regio.

Combination of fluorescence microscopy and nanomotion detection to characterize bacteria.

Antibiotic-resistant pathogens are a major health concern in everyday clinical practice. Because their detection by conventional microbial techniques requires minimally 24 h, some of us have recently introduced a nanomechanical sensor, which can reveal motion at the nanoscale. By monitoring the fluctuations of the sensor, this technique can evidence the presence of bacteria and their susceptibility to antibiotics in less than 1 h. Their amplitude correlates to the metabolism of the bacteria and is a powerful tool to characterize these microorganisms at low densities. This technique is new and calls for an effort to optimize its protocol and determine its limits. Indeed, many questions remain unanswered, such as the detection limits or the correlation between the bacterial distribution on the sensor and the detection's output. In this work, we couple fluorescence microscopy to the nanomotion investigation to determine the optimal experimental protocols and to highlight the effect of the different bacterial distributions on the sensor.

Multi-scale label interaction to improve object detection and segmentation

The project aims at advancing the state of the art in the use of context information for classification of image and video data. The use of context in the classification of images has been showed of great importance to improve the performance of actual object recognition systems. In our project we proposed the concept of Multi-scale Feature Labels as a general and compact method to exploit the local and global context. The feature extraction from the discriminative probability or classification confidence label field is of great novelty. Moreover the use of a multi-scale representation of the feature labels lead to a compact and efficient description of the context. The goal of the project has been also to provide a general-purpose method and prove its suitability in different image/video analysis problem. The two-year project generated 5 journal publications (plus 2 under submission), 10 conference publications (plus 2 under submission) and one patent (plus 1 pending). Of these publications, a relevant number make use of the main result of this project to improve the results in detection and/or segmentation of objects.

Dose reconstruction in the context of tomotherapy

In vivo dosimetry is a way to verify the radiation dose delivered to the patient in measuring the dose generally during the first fraction of the treatment. It is the only dose delivery control based on a measurement performed during the treatment. In today's radiotherapy practice, the dose delivered to the patient is planned using 3D dose calculation algorithms and volumetric images representing the patient. Due to the high accuracy and precision necessary in radiation treatments, national and international organisations like ICRU and AAPM recommend the use of in vivo dosimetry. It is also mandatory in some countries like France. Various in vivo dosimetry methods have been developed during the past years. These methods are point-, line-, plane- or 3D dose controls. A 3D in vivo dosimetry provides the most information about the dose delivered to the patient, with respect to ID and 2D methods. However, to our knowledge, it is generally not routinely applied to patient treatments yet. The aim of this PhD thesis was to determine whether it is possible to reconstruct the 3D delivered dose using transmitted beam measurements in the context of narrow beams. An iterative dose reconstruction method has been described and implemented. The iterative algorithm includes a simple 3D dose calculation algorithm based on the convolution/superposition principle. The methodology was applied to narrow beams produced by a conventional 6 MV linac. The transmitted dose was measured using an array of ion chambers, as to simulate the linear nature of a tomotherapy detector. We showed that the iterative algorithm converges quickly and reconstructs the dose within a good agreement (at least 3% / 3 mm locally), which is inside the 5% recommended by the ICRU. Moreover it was demonstrated on phantom measurements that the proposed method allows us detecting some set-up errors and interfraction geometry modifications. We also have discussed the limitations of the 3D dose reconstruction for dose delivery error detection. Afterwards, stability tests of the tomotherapy MVCT built-in onboard detector was performed in order to evaluate if such a detector is suitable for 3D in-vivo dosimetry. The detector showed stability on short and long terms comparable to other imaging devices as the EPIDs, also used for in vivo dosimetry. Subsequently, a methodology for the dose reconstruction using the tomotherapy MVCT detector is proposed in the context of static irradiations. This manuscript is composed of two articles and a script providing further information related to this work. In the latter, the first chapter introduces the state-of-the-art of in vivo dosimetry and adaptive radiotherapy, and explains why we are interested in performing 3D dose reconstructions. In chapter 2 a dose calculation algorithm implemented for this work is reviewed with a detailed description of the physical parameters needed for calculating 3D absorbed dose distributions. The tomotherapy MVCT detector used for transit measurements and its characteristics are described in chapter 3. Chapter 4 contains a first article entitled '3D dose reconstruction for narrow beams using ion chamber array measurements', which describes the dose reconstruction method and presents tests of the methodology on phantoms irradiated with 6 MV narrow photon beams. Chapter 5 contains a second article 'Stability of the Helical TomoTherapy HiArt II detector for treatment beam irradiations. A dose reconstruction process specific to the use of the tomotherapy MVCT detector is presented in chapter 6. A discussion and perspectives of the PhD thesis are presented in chapter 7, followed by a conclusion in chapter 8. The tomotherapy treatment device is described in appendix 1 and an overview of 3D conformai- and intensity modulated radiotherapy is presented in appendix 2. - La dosimétrie in vivo est une technique utilisée pour vérifier la dose délivrée au patient en faisant une mesure, généralement pendant la première séance du traitement. Il s'agit de la seule technique de contrôle de la dose délivrée basée sur une mesure réalisée durant l'irradiation du patient. La dose au patient est calculée au moyen d'algorithmes 3D utilisant des images volumétriques du patient. En raison de la haute précision nécessaire lors des traitements de radiothérapie, des organismes nationaux et internationaux tels que l'ICRU et l'AAPM recommandent l'utilisation de la dosimétrie in vivo, qui est devenue obligatoire dans certains pays dont la France. Diverses méthodes de dosimétrie in vivo existent. Elles peuvent être classées en dosimétrie ponctuelle, planaire ou tridimensionnelle. La dosimétrie 3D est celle qui fournit le plus d'information sur la dose délivrée. Cependant, à notre connaissance, elle n'est généralement pas appliquée dans la routine clinique. Le but de cette recherche était de déterminer s'il est possible de reconstruire la dose 3D délivrée en se basant sur des mesures de la dose transmise, dans le contexte des faisceaux étroits. Une méthode itérative de reconstruction de la dose a été décrite et implémentée. L'algorithme itératif contient un algorithme simple basé sur le principe de convolution/superposition pour le calcul de la dose. La dose transmise a été mesurée à l'aide d'une série de chambres à ionisations alignées afin de simuler la nature linéaire du détecteur de la tomothérapie. Nous avons montré que l'algorithme itératif converge rapidement et qu'il permet de reconstruire la dose délivrée avec une bonne précision (au moins 3 % localement / 3 mm). De plus, nous avons démontré que cette méthode permet de détecter certaines erreurs de positionnement du patient, ainsi que des modifications géométriques qui peuvent subvenir entre les séances de traitement. Nous avons discuté les limites de cette méthode pour la détection de certaines erreurs d'irradiation. Par la suite, des tests de stabilité du détecteur MVCT intégré à la tomothérapie ont été effectués, dans le but de déterminer si ce dernier peut être utilisé pour la dosimétrie in vivo. Ce détecteur a démontré une stabilité à court et à long terme comparable à d'autres détecteurs tels que les EPIDs également utilisés pour l'imagerie et la dosimétrie in vivo. Pour finir, une adaptation de la méthode de reconstruction de la dose a été proposée afin de pouvoir l'implémenter sur une installation de tomothérapie. Ce manuscrit est composé de deux articles et d'un script contenant des informations supplémentaires sur ce travail. Dans ce dernier, le premier chapitre introduit l'état de l'art de la dosimétrie in vivo et de la radiothérapie adaptative, et explique pourquoi nous nous intéressons à la reconstruction 3D de la dose délivrée. Dans le chapitre 2, l'algorithme 3D de calcul de dose implémenté pour ce travail est décrit, ainsi que les paramètres physiques principaux nécessaires pour le calcul de dose. Les caractéristiques du détecteur MVCT de la tomothérapie utilisé pour les mesures de transit sont décrites dans le chapitre 3. Le chapitre 4 contient un premier article intitulé '3D dose reconstruction for narrow beams using ion chamber array measurements', qui décrit la méthode de reconstruction et présente des tests de la méthodologie sur des fantômes irradiés avec des faisceaux étroits. Le chapitre 5 contient un second article intitulé 'Stability of the Helical TomoTherapy HiArt II detector for treatment beam irradiations'. Un procédé de reconstruction de la dose spécifique pour l'utilisation du détecteur MVCT de la tomothérapie est présenté au chapitre 6. Une discussion et les perspectives de la thèse de doctorat sont présentées au chapitre 7, suivies par une conclusion au chapitre 8. Le concept de la tomothérapie est exposé dans l'annexe 1. Pour finir, la radiothérapie «informationnelle 3D et la radiothérapie par modulation d'intensité sont présentées dans l'annexe 2.

Human synthetic lethal inference as potential anti-cancer target gene detection

Background: Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results: In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates.Conclusions: Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.

Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations.

Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 × 10(-8)); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGFBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p < 0.05). We estimated a 20% gain in statistical power with long-term average (LTA) as compared to single-visit BP association studies. Using LTA analysis, we identified genetic loci influencing BP. LTA might be one way of increasing the power of genetic associations for continuous traits in extant samples for other phenotypes that are measured serially over time.

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

Background: Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results: Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion:This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.