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

Contiene 3 ficheros adicionales con información suplementaria.-- et al.[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.The authors thank the "Genoma España" and Genome Canada joint R+D+I projects in human health, plants and aquiculture; the former "Departament d'Universitats i Societat de la Informació" (DURSI) and the "Departament de Salut", from the Catalan Autonomous Government (2005SGR00008 - Generalitat de Catalunya); the Instituto de Salud Carlos III (PI041126, CIBER-ESP), the EU's Sixth Framework Programme [FP6-2005-LIFESCIHEALTH-7; ANEUPLOIDY No. 037627] and Fundación Areces (U-2006-FARECES-O).Peer reviewe

Incorporating Breast Asymmetry Studies into CADx Systems

Breast cancer is one of the global leading causes of death among women, and an early detection is of uttermost importance to reduce mortality rates. Screening mammograms, in which radiologists rely only on their eyesight, are one of the most used early detection methods. However, characteristics, such as the asymmetry between breasts, a feature that could be very difficult to visually quantize, is key to breast cancer detection. Due to the highly heterogeneous and deformable structure of the breast itself, incorporating asymmetry measurements into an automated detection system is still a challenge. In this study, we proposed the use of a bilateral registration algorithm as an effective way to automatically measure mirror asymmetry. Furthermore, this information was fed to a machine learning algorithm to improve the accuracy of the model. In this study, 449 subjects (197 with calcifications, 207 with masses, and 45 healthy subjects) from a public database were used to train and evaluate the proposed methodology. Using this procedure, we were able to independently identify subjects with calcifications (accuracy = 0.825, AUC = 0.882) and masses (accuracy = 0.698, AUC = 0.807) from healthy subjects

Dafny with traits: verifying object oriented programs

Dafny is a programming language supporting verified high level programming. It has many features that a modern programming language has, like classes, generic classes, functions, and, methods. However, some aspects of object oriented programming do not exist in Dafny. For instance, it is not possible to write programs with classes and subclasses and then verify the subclasses. In order to enrich the language with the mentioned feature, this thesis introduces traits to Dafny. A trait in Dafny may introduce states, methods and functions with or without bodies. A class, then, inherits from a trait and may override the body-less methods and functions. There are also specifications for methods and functions in a trait that specify the intention of a particular method or function. In terms of the specifications, the class must provide the specifications, for annotating the functions and methods, possibly stronger. This has the drawback of repeating the specifications but it also increases readability as one can look at the class and immediately figure out what specifications govern the behavior of a method or a function. The new feature, traits, provides polymorphism, information hiding, and reusability. Dynamic dispatch is now also available with the help of the introduced traits

VOLUMEN 16, NÚMERO 30 (1983-1984)

PROYECTO GEOTÉRMICO CHILES - CERRO NEGRO. Lozano, E.; Cruz, L.ZONAS HIDROGEOLÓGICAS DE COLOMBIA. Lobo-Guerrero, A.ESTUDIO GEOQUÍMICO Y PETROGRÁFICO DE ROCAS SUBVOLCÁNICAS ENTRE LA QUEBRADA CHIRAPOTO Y EL RÍO ARQUÍA (DEPARTAMENTO DE ANTIOQUIA Y CALDAS). Sánchez, L. H.; Parra, R. A.; Ortíz, F.GEOLOGÍA Y EXPERIENCIAS CONSTRUCTIVAS EN EL TÚNEL TUNJITA. Tejada, S. E.CONTRIBUCIÓN AL CONOCIMIENTO DEL PALEOZOICO SUPERIOR EN LA SECCIÓN QUETAME - VILLAVICENCIO. Cortés, R.; De La Espriella, R.TECTÓNICA GRAVITACIONAL EN LA CORDILLERA ORIENTAL AL ESTE DE LA FALLA DE BOYACÁ (DEPARTAMENTO DE BOYACÁ). Reyes, Ch. I.AMBIENTES GEOLÓGICOS URANÍFEROS EN COLOMBIA. Ortega Montero, C

VOLUMEN 16, NÚMERO 30 (1983-1984)

PROYECTO GEOTÉRMICO CHILES - CERRO NEGRO. Lozano, E.; Cruz, L.ZONAS HIDROGEOLÓGICAS DE COLOMBIA. Lobo-Guerrero, A.ESTUDIO GEOQUÍMICO Y PETROGRÁFICO DE ROCAS SUBVOLCÁNICAS ENTRE LA QUEBRADA CHIRAPOTO Y EL RÍO ARQUÍA (DEPARTAMENTO DE ANTIOQUIA Y CALDAS). Sánchez, L. H.; Parra, R. A.; Ortíz, F.GEOLOGÍA Y EXPERIENCIAS CONSTRUCTIVAS EN EL TÚNEL TUNJITA. Tejada, S. E.CONTRIBUCIÓN AL CONOCIMIENTO DEL PALEOZOICO SUPERIOR EN LA SECCIÓN QUETAME - VILLAVICENCIO. Cortés, R.; De La Espriella, R.TECTÓNICA GRAVITACIONAL EN LA CORDILLERA ORIENTAL AL ESTE DE LA FALLA DE BOYACÁ (DEPARTAMENTO DE BOYACÁ). Reyes, Ch. I.AMBIENTES GEOLÓGICOS URANÍFEROS EN COLOMBIA. Ortega Montero, C

Sensitivity to change of the Beach Questionnaire to behaviour, attitudes and knowledge related to sun exposure: quasi-experimental before-after study

Background: Health questionnaires must present accredited measurement properties such as validity, reliability and sensitivity to change, the latter being essential for interventions to be planned and for evaluating their effectiveness. The aim of this study was to evaluate the sensitivity to change of a Beach Questionnaire.Methods: Quasi-experimental before-after study carried out in 2011, for a study population of adolescents attending schools in the Costa del Sol. First, the questionnaire was administered to the adolescents, after which a multicomponent educational intervention was carried out; finally, three months later, the same questionnaire was re-administered to the same adolescents. Changes were assessed in the categories of each item, using the McNemar test, and the changes in the scores, standardised to a range of 0–100, using the Student t test for paired samples, and including the mean of the differences and the 95% confidence interval. The level of statistical significance was set at p < 0.05.Results: 228 adolescents, aged 14–17 years, and 55.3% were girls. Statistically significant changes were observed in sunburn experiences, exposure to the sun at mid-day and attitudes to sun exposure and suncreams. For the seven items related to knowledge about sun exposure, a higher rate of correct answers was observed. The analysis of changes, within the standardised range, revealed a significant improvement in the scores for sun exposure habits (MD 4.33; CI 95% 2.2-6.5), attitudes to sun exposure (MD 2.22; CI 95% 1.2-3.2) and knowledge (MD 9.10; CI 95% 7.1-11.1), but not in those for sun-protection practices (MD 0.23; CI 95% -1.2-1.7).Conclusions: The Beach Questionnaire on behaviour, attitudes and knowledge related to sun exposure is the first such instrument in Spanish language to provide sufficient sensitivity to change. It constitutes a useful tool for epidemiologic research into photoprotection and for skin cancer prevention programmes.The authors would like to acknowledge support from the Research Department of the Costa del Sol Hospital

Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

Objective: Erectile dysfunction (ED) is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural dysfunction involving nitric oxide (NO) are usually implicated in the pathophysiology of the diabetic ED, but the underlying mechanisms are unclear. The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR), an experimental model of metabolic syndrome/prediabetes. Methods and Results: Electrical field stimulation (EFS) under non-adrenergic non-cholinergic (NANC) conditions evoked relaxations that were significantly reduced in penile arteries of OZR compared with those of lean Zucker rats (LZR). Blockade of NO synthase (NOS) inhibited neural relaxations in both LZR and OZR, while saturating concentrations of the NOS substrate L-arginine reversed the inhibition and restored relaxations in OZR to levels in arteries from LZR. nNOS expression was unchanged in arteries from OZR compared to LZR and nNOS selective inhibition decreased the EFS relaxations in LZR but not in OZR, while endothelium removal did not alter these responses in either strain. Superoxide anion production and nitro-tyrosine immunostaining were elevated in the erectile tissue from OZR. Treatment with the NADPH oxidase inhibitor apocynin or acute incubation with the NOS cofactor tetrahydrobiopterin (BH4) restored neural relaxations in OZR to levels in control arteries, while inhibition of the enzyme of BH4 synthesis GTP-cyclohydrolase (GCH) reduced neural relaxations i