Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)

Background: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample.Results: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace.Conclusion: Using the proposed mixed-model, we are able to determine thresholds to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed.

Multivariate prediction

The problem of prediction is considered in a multidimensional setting. Extending an idea presented by Barndorff-Nielsen and Cox, a predictive density for a multivariate random variable of interest is proposed. This density has the form of an estimative density plus a correction term. It gives simultaneous prediction regions with coverage error of smaller asymptotic order than the estimative density. A simulation study is also presented showing the magnitude of the improvement with respect to the estimative method.

Les cegueses del coneixement: l'error i la il·lusió a partir de "El cónsul de sodoma"

Podeu consultar el document complet de la "XVI Setmana de Cinema Formatiu" a: http://hdl.handle.net/2445/22523

Subjetividad humana y "error" en la filosofía cartesiana

El presente trabajo, continuando la línea investigadora acerca de las nociones derazón, conciencia y subjetividad en Descartes, tal como se ha defendido en otros artículos ya publicados, aporta un nuevo argumento a una línea de trabajo previamente iniciada, poniendo de relieve que el problema gnoseológico del error viene condicionado por la misma noción cartesiana de racionalidad, y que ésta dista mucho de lo que tradicionalmente se ha entendido como una racionalidad abstracta y formal, libre de los imperativos humanos. Por otro lado, y a la inversa, también se intenta mostrar como el hecho del error contribuye, cartesianamente hablando, a definir un modelo de racionalidad profundamentehumanizada. El artículo, tras una introducción, se propone analizar las relaciones entre los conceptos básicos de racionalidad, dogma, y naturaleza, lo que permitirá a continuación dejar constancia de la copertenencia entre racionalidad y error, para acabar viendo como la libertad humana es la vez, y para ambos, su fundamento último.

Coocurrencia entre ansiedad y autismo: Las hipótesis del error social y de la carga alostática

Introducción. El concepto de comorbilidad en trastornos del neurodesarrollo como el autismo resulta, en ocasiones, ambiguo. La coocurrencia entre ansiedad y autismo es clínicamente signifi cativa; sin embargo, no siempre es fácil diferenciar si se trata de una comorbilidad"real", donde las dos condiciones comórbidas son fenotípica y etiológicamente idénticas a lo que supondría dicha ansiedad en personas con un desarrollo neurotípico; si se trata de una ansiedad fenotípicamente alterada por los procesos patogénicos de los trastornos del espectro autista, resultando en una variante específica de éstos, o si partimos de una comorbilidad falsa derivada de diagnósticos diferenciales poco exactos. Desarrollo. El artículo plantea dos hipótesis explicativas de dicha coocurrencia, que se retroalimentan entre sí y que no dejan de ser una refl exión en voz alta partiendo de las evidencias científi cas con las que contamos. La primera es la hipótesis del"error social", y considera que el desajuste en el comportamiento social de las personas con autismofruto de alteraciones en los procesos de cognición social contribuye a exacerbar la ansiedad en el autismo. La segunda hipótesis, la de la carga alostática, defi ende que la ansiedad es la respuesta a un estrés crónico, al desgaste o agotamiento que produce la hiperactivación de ciertas estructuras del sistema límbico. Conclusiones. Las manifestaciones prototípicas de la ansiedad presentes en la persona con autismo no siempre se relacionan con las mismas variables biopsicosociales evidenciadas en personas sin autismo. Las evidencias apuntan a respuestas hiperreactivas de huida o lucha (hipervigilancia) cuando la persona se encuentra fuera de su zona de confort, y apoyan la hipótesis del"error social" y de la descompensación del mecanismo de alostasis que permite afrontar el estrés.

Random assignment of intervention points in two phase single-case designs: data-division-specific distributions

The present study explores the statistical properties of a randomization test based on the random assignment of the intervention point in a two-phase (AB) single-case design. The focus is on randomization distributions constructed with the values of the test statistic for all possible random assignments and used to obtain p-values. The shape of those distributions is investigated for each specific data division defined by the moment in which the intervention is introduced. Another aim of the study consisted in testing the detection of inexistent effects (i.e., production of false alarms) in autocorrelated data series, in which the assumption of exchangeability between observations may be untenable. In this way, it was possible to compare nominal and empirical Type I error rates in order to obtain evidence on the statistical validity of the randomization test for each individual data division. The results suggest that when either of the two phases has considerably less measurement times, Type I errors may be too probable and, hence, the decision making process to be carried out by applied researchers may be jeopardized.

L'error com a forma de coneixement

" Has comes un error" . " Estas en un error" . " És un error votar aquest parti!" . " És un error votar" . " És un error afirmar que 2 + 3 = 9" . " És un error afirmar que és un error afirmar que 2 + 3 = 5" . " És un error afirmar que, quan dividim, sempre obtenim un nombre més petit" . " És un error que l'existencia precedeixi l'essencia" . " És un error que vulguis enganyar-me" . " És un error afirmar que a = a" ... i així fins a acomplir les il'limitades possibilitats del llenguatge. Qualsevol judici, en la mesura que té un significat, en la mesura que és assertori, és susceptible de ser erroni, de ser fals. Peró, l'error té sempre la mateixa qualitat? Us hem proposat un reguitzell d'exemples. És obvi (si excloem la mentida, que no és error, sinó mentida) que el significat d'" error" (o el seu valor) no és identic en tots els casos.

Impacto de los errores de medicación en una unidad de curas intensivas y grado de implicación de los profesionales de enfermería

El presente estudio identifica los errores de medicación y valora el grado de notificación de estos errores por parte del personal de enfermería en el Servicio de Medicina Intensiva (SMI), del Hospital Universitario Doctor Josep Trueta.Se realizará un estudio observacional, descriptivo y transversal en el hospital de referencia de las comarcas gerundenses durante el año 2013 y 2014.Los sujetos a estudio serán los profesionales enfermeros y los pacientes ingresados en la unidad. Las variables principales son, por un lado, el error de medicación y por otro la notificación del error.El procedimiento de recogida de datos se basará en proporcionar un cuestionario auto administrado al personal de enfermería, caracterizado por seis preguntas con respuestas cerradas, dos de las cuales tienen la opción de ser abiertas.Para el análisis estadístico se utilizará el programa SPSS. Para la obtención de los resultados se realizará un análisis descriptivo univariante. La variable “error de medicación” se expresará como número de casos y en 1.000 pacientes / día. Las demás variables se presentarán mediante frecuencias

A statistical procedure for testing social reciprocity at group, dyadic and individual levels

This paper examines statistical analysis of social reciprocity, that is, the balance between addressing and receiving behaviour in social interactions. Specifically, it focuses on the measurement of social reciprocity by means of directionality and skew-symmetry statistics at different levels. Two statistics have been used as overall measures of social reciprocity at group level: the directional consistency and the skew-symmetry statistics. Furthermore, the skew-symmetry statistic allows social researchers to obtain complementary information at dyadic and individual levels. However, having computed these measures, social researchers may be interested in testing statistical hypotheses regarding social reciprocity. For this reason, it has been developed a statistical procedure, based on Monte Carlo sampling, in order to allow social researchers to describe groups and make statistical decisions.

Statistical modeling of bowing control applied to violin sound synthesis

Excitation-continuous music instrument control patterns are often not explicitly represented in current sound synthesis techniques when applied to automatic performance. Both physical model-based and sample-based synthesis paradigmswould benefit from a flexible and accurate instrument control model, enabling the improvement of naturalness and realism. Wepresent a framework for modeling bowing control parameters inviolin performance. Nearly non-intrusive sensing techniques allow for accurate acquisition of relevant timbre-related bowing control parameter signals.We model the temporal contour of bow velocity, bow pressing force, and bow-bridge distance as sequences of short Bézier cubic curve segments. Considering different articulations, dynamics, and performance contexts, a number of note classes are defined. Contours of bowing parameters in a performance database are analyzed at note-level by following a predefined grammar that dictates characteristics of curve segment sequences for each of the classes in consideration. As a result, contour analysis of bowing parameters of each note yields an optimal representation vector that is sufficient for reconstructing original contours with significant fidelity. From the resulting representation vectors, we construct a statistical model based on Gaussian mixtures suitable for both the analysis and synthesis of bowing parameter contours. By using the estimated models, synthetic contours can be generated through a bow planning algorithm able to reproduce possible constraints caused by the finite length of the bow. Rendered contours are successfully used in two preliminary synthesis frameworks: digital waveguide-based bowed stringphysical modeling and sample-based spectral-domain synthesis.

An efficient algorithm to perform multiple testing in epistasis screening

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn’s disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations.

Statistical modeling of violin bowing parameter contours

We present a framework for modeling right-hand gestures in bowed-string instrument playing, applied to violin. Nearly non-intrusive sensing techniques allow for accurate acquisition of relevant timbre-related bowing gesture parameter cues. We model the temporal contour of bow transversal velocity, bow pressing force, and bow-bridge distance as sequences of short segments, in particular B´ezier cubic curve segments. Considering different articulations, dynamics, andcontexts, a number of note classes is defined. Gesture parameter contours of a performance database are analyzed at note-level by following a predefined grammar that dictatescharacteristics of curve segment sequences for each of the classes into consideration. Based on dynamic programming, gesture parameter contour analysis provides an optimal curve parameter vector for each note. The informationpresent in such parameter vector is enough for reconstructing original gesture parameter contours with significant fidelity. From the resulting representation vectors, weconstruct a statistical model based on Gaussian mixtures, suitable for both analysis and synthesis of bowing gesture parameter contours. We show the potential of the modelby synthesizing bowing gesture parameter contours from an annotated input score. Finally, we point out promising applicationsand developments.

Statistical mechanics of multi-edge networks

Statistical properties of binary complex networks are well understood and recently many attempts have been made to extend this knowledge to weighted ones. There are, however, subtle yet important considerations to be made regarding the nature of the weights used in this generalization. Weights can be either continuous or discrete magnitudes, and in the latter case, they can additionally have undistinguishable or distinguishable nature. This fact has not been addressed in the literature insofar and has deep implications on the network statistics. In this work we face this problem introducing multiedge networks as graphs where multiple (distinguishable) connections between nodes are considered. We develop a statistical mechanics framework where it is possible to get information about the most relevant observables given a large spectrum of linear and nonlinear constraints including those depending both on the number of multiedges per link and their binary projection. The latter case is particularly interesting as we show that binary projections can be understood from multiedge processes. The implications of these results are important as many real-agent-based problems mapped onto graphs require this treatment for a proper characterization of their collective behavior.

JPEG standard uniform quantization error modeling with applications to sequential and progressive operation modes

In this paper we propose a method for computing JPEG quantization matrices for a given mean square error or PSNR. Then, we employ our method to compute JPEG standard progressive operation mode definition scripts using a quantization approach. Therefore, it is no longer necessary to use a trial and error procedure to obtain a desired PSNR and/or definition script, reducing cost. Firstly, we establish a relationship between a Laplacian source and its uniform quantization error. We apply this model to the coefficients obtained in the discrete cosine transform stage of the JPEG standard. Then, an image may be compressed using the JPEG standard under a global MSE (or PSNR) constraint and a set of local constraints determined by the JPEG standard and visual criteria. Secondly, we study the JPEG standard progressive operation mode from a quantization based approach. A relationship between the measured image quality at a given stage of the coding process and a quantization matrix is found. Thus, the definition script construction problem can be reduced to a quantization problem. Simulations show that our method generates better quantization matrices than the classical method based on scaling the JPEG default quantization matrix. The estimation of PSNR has usually an error smaller than 1 dB. This figure decreases for high PSNR values. Definition scripts may be generated avoiding an excessive number of stages and removing small stages that do not contribute during the decoding process with a noticeable image quality improvement.

Bootstrapping a statistical speech translator from a rule-based one

We describe a series of experiments in which we start with English to French and English to Japanese versions of an Open Source rule-based speech translation system for a medical domain, and bootstrap correspondign statistical systems. Comparative evaluation reveals that the rule-based systems are still significantly better than the statistical ones, despite the fact that considerable effort has been invested in tuning both the recognition and translation components; also, a hybrid system only marginally improved recall at the cost of a los in precision. The result suggests that rule-based architectures may still be preferable to statistical ones for safety-critical speech translation tasks.