Locally Efficient Estimation in Censored Data Models: Theory and Examples

In many applications the observed data can be viewed as a censored high dimensional full data random variable X. By the curve of dimensionality it is typically not possible to construct estimators that are asymptotically efficient at every probability distribution in a semiparametric censored data model of such a high dimensional censored data structure. We provide a general method for construction of one-step estimators that are efficient at a chosen submodel of the full-data model, are still well behaved off this submodel and can be chosen to always improve on a given initial estimator. These one-step estimators rely on good estimators of the censoring mechanism and thus will require a parametric or semiparametric model for the censoring mechanism. We present a general theorem that provides a template for proving the desired asymptotic results. We illustrate the general one-step estimation methods by constructing locally efficient one-step estimators of marginal distributions and regression parameters with right-censored data, current status data and bivariate right-censored data, in all models allowing the presence of time-dependent covariates. The conditions of the asymptotics theorem are rigorously verified in one of the examples and the key condition of the general theorem is verified for all examples.

Marginal Structural Models for Partial Exposure Regimes

Intensive care unit (ICU) patients are ell known to be highly susceptible for nosocomial (i.e. hospital-acquired) infections due to their poor health and many invasive therapeutic treatments. The effects of acquiring such infections in ICU on mortality are however ill understood. Our goal is to quantify these effects using data from the National Surveillance Study of Nosocomial Infections in Intensive Care Units (Belgium). This is a challenging problem because of the presence of time-dependent confounders (such as exposure to mechanical ventilation)which lie on the causal path from infection to mortality. Standard statistical analyses may be severely misleading in such settings and have shown contradicting results. While inverse probability weighting for marginal structural models can be used to accommodate time-dependent confounders, inference for the effect of ?ICU acquired infections on mortality under such models is further complicated (a) by the fact that marginal structural models infer the effect of acquiring infection on a given, fixed day ?in ICU?, which is not well defined when ICU discharge comes prior to that day; (b) by informative censoring of the survival time due to hospital discharge; and (c) by the instability of the inverse weighting estimation procedure. We accommodate these problems by developing inference under a new class of marginal structural models which describe the hazard of death for patients if, possibly contrary to fact, they stayed in the ICU for at least a given number of days s and acquired infection or not on that day. Using these models we estimate that, if patients stayed in the ICU for at least s days, the effect of acquiring infection on day s would be to multiply the subsequent hazard of death by 2.74 (95 per cent conservative CI 1.48; 5.09).

Statistical evaluation of alternative models of human evolution

An appropriate model of recent human evolution is not only important to understand our own history, but it is necessary to disentangle the effects of demography and selection on genome diversity. Although most genetic data support the view that our species originated recently in Africa, it is still unclear if it completely replaced former members of the Homo genus, or if some interbreeding occurred during its range expansion. Several scenarios of modern human evolution have been proposed on the basis of molecular and paleontological data, but their likelihood has never been statistically assessed. Using DNA data from 50 nuclear loci sequenced in African, Asian and Native American samples, we show here by extensive simulations that a simple African replacement model with exponential growth has a higher probability (78%) as compared with alternative multiregional evolution or assimilation scenarios. A Bayesian analysis of the data under this best supported model points to an origin of our species approximately 141 thousand years ago (Kya), an exit out-of-Africa approximately 51 Kya, and a recent colonization of the Americas approximately 10.5 Kya. We also find that the African replacement model explains not only the shallow ancestry of mtDNA or Y-chromosomes but also the occurrence of deep lineages at some autosomal loci, which has been formerly interpreted as a sign of interbreeding with Homo erectus.

Estimating and quantifying uncertainties on level sets using the Vorob'ev expectation and deviation with Gaussian process models

Several methods based on Kriging have recently been proposed for calculating a probability of failure involving costly-to-evaluate functions. A closely related problem is to estimate the set of inputs leading to a response exceeding a given threshold. Now, estimating such a level set—and not solely its volume—and quantifying uncertainties on it are not straightforward. Here we use notions from random set theory to obtain an estimate of the level set, together with a quantification of estimation uncertainty. We give explicit formulae in the Gaussian process set-up and provide a consistency result. We then illustrate how space-filling versus adaptive design strategies may sequentially reduce level set estimation uncertainty.

Stochastic search for semiparametric linear regression models

This paper introduces and analyzes a stochastic search method for parameter estimation in linear regression models in the spirit of Beran and Millar [Ann. Statist. 15(3) (1987) 1131–1154]. The idea is to generate a random finite subset of a parameter space which will automatically contain points which are very close to an unknown true parameter. The motivation for this procedure comes from recent work of Dümbgen et al. [Ann. Statist. 39(2) (2011) 702–730] on regression models with log-concave error distributions.

Radiocarbon dating of modern peat profiles: Pre- and post-bomb C-14 variations in the construction of age-depth models

We present studies of 9 modern (up to 400-yr-old) peat sections from Slovenia, Switzerland, Austria, Italy, and Finland. Precise radiocarbon dating of modern samples is possible due to the large bomb peak of atmospheric 14C concentration in 1963 and the following rapid decline in the 14C level. All the analyzed 14C profiles appeared concordant with the shape of the bomb peak of atmospheric 14C concentration, integrated over some time interval with a length specific to the peat section. In the peat layers covered by the bomb peak, calendar ages of individual peat samples could be determined almost immediately, with an accuracy of 23 yr. In the pre-bomb sections, the calendar ages of individual dated samples are determined in the form of multi-modal probability distributions of about 300 yr wide (about AD 16501950). However, simultaneous use of the post-bomb and pre-bomb 14C dates, and lithological information, enabled the rejection of most modes of probability distributions in the pre-bomb section. In effect, precise age-depth models of the post-bomb sections have been extended back in time, into the wiggly part of the 14C calibration curve.

Replications of fundamental research models in ultra high dilutions 1994 and 2015 - update on a bibliometric study

INTRODUCTION This paper focuses exclusively on experimental models with ultra high dilutions (i.e. beyond 10(-23)) that have been submitted to replication scrutiny. It updates previous surveys, considers suggestions made by the research community and compares the state of replication in 1994 with that in 2015. METHODS Following literature research, biochemical, immunological, botanical, cell biological and zoological studies on ultra high dilutions (potencies) were included. Reports were grouped into initial studies, laboratory-internal, multicentre and external replications. Repetition could yield either comparable, or zero, or opposite results. The null-hypothesis was that test and control groups would not be distinguishable (zero effect). RESULTS A total of 126 studies were found. From these, 28 were initial studies. When all 98 replicative studies were considered, 70.4% (i.e. 69) reported a result comparable to that of the initial study, 20.4% (20) zero effect and 9.2% (9) an opposite result. Both for the studies until 1994 and the studies 1995-2015 the null-hypothesis (dominance of zero results) should be rejected. Furthermore, the odds of finding a comparable result are generally higher than of finding an opposite result. Although this is true for all three types of replication studies, the fraction of comparable studies diminishes from laboratory-internal (total 82.9%) to multicentre (total 75%) to external (total 48.3%), while the fraction of opposite results was 4.9%, 10.7% and 13.8%. Furthermore, it became obvious that the probability of an external replication producing comparable results is bigger for models that had already been further scrutinized by the initial researchers. CONCLUSIONS We found 28 experimental models which underwent replication. In total, 24 models were replicated with comparable results, 12 models with zero effect, and 6 models with opposite results. Five models were externally reproduced with comparable results. We encourage further replications of studies in order to learn more about the model systems used.

On the complexity of radiation models for PV energy production calculation

Several authors have analysed the changes of the probability density function of the solar radiation with different time resolutions. Some others have approached to study the significance of these changes when produced energy calculations are attempted. We have undertaken different transformations to four Spanish databases in order to clarify the interrelationship between radiation models and produced energy estimations. Our contribution is straightforward: the complexity of a solar radiation model needed for yearly energy calculations, is very low. Twelve values of monthly mean of solar radiation are enough to estimate energy with errors below 3%. Time resolutions better than hourly samples do not improve significantly the result of energy estimations.

A stochastic model updating method for parameter variability quantification based on response surface models and Monte Carlo simulation

Stochastic model updating must be considered for quantifying uncertainties inherently existing in real-world engineering structures. By this means the statistical properties,instead of deterministic values, of structural parameters can be sought indicating the parameter variability. However, the implementation of stochastic model updating is much more complicated than that of deterministic methods particularly in the aspects of theoretical complexity and low computational efficiency. This study attempts to propose a simple and cost-efficient method by decomposing a stochastic updating process into a series of deterministic ones with the aid of response surface models and Monte Carlo simulation. The response surface models are used as surrogates for original FE models in the interest of programming simplification, fast response computation and easy inverse optimization. Monte Carlo simulation is adopted for generating samples from the assumed or measured probability distributions of responses. Each sample corresponds to an individual deterministic inverse process predicting the deterministic values of parameters. Then the parameter means and variances can be statistically estimated based on all the parameter predictions by running all the samples. Meanwhile, the analysis of variance approach is employed for the evaluation of parameter variability significance. The proposed method has been demonstrated firstly on a numerical beam and then a set of nominally identical steel plates tested in the laboratory. It is found that compared with the existing stochastic model updating methods, the proposed method presents similar accuracy while its primary merits consist in its simple implementation and cost efficiency in response computation and inverse optimization.

An interactive method of fuzzy probability elicitation in risk analysis

Expert knowledge is used to assign probabilities to events in many risk analysis models. However, experts sometimes find it hard to provide specific values for these probabilities, preferring to express vague or imprecise terms that are mapped using a previously defined fuzzy number scale. The rigidity of these scales generates bias in the probability elicitation process and does not allow experts to adequately express their probabilistic judgments. We present an interactive method for extracting a fuzzy number from experts that represents their probabilistic judgments for a given event, along with a quality measure of the probabilistic judgments, useful in a final information filtering and analysis sensitivity process.

Analysis of the influence of the different variables involved in a damage progression probability model

Motivated by these difficulties, Castillo et al. (2012) made some suggestions on how to build consistent stochastic models avoiding the selection of easy to use mathematical functions, which were replaced by those resulting from a set of properties to be satisfied by the model.

Generation of human computational models with machine learning

Services in smart environments pursue to increase the quality of people?s lives. The most important issues when developing this kind of environments is testing and validating such services. These tasks usually imply high costs and annoying or unfeasible real-world testing. In such cases, artificial societies may be used to simulate the smart environment (i.e. physical environment, equipment and humans). With this aim, the CHROMUBE methodology guides test engineers when modeling human beings. Such models reproduce behaviors which are highly similar to the real ones. Originally, these models are based on automata whose transitions are governed by random variables. Automaton?s structure and the probability distribution functions of each random variable are determined by a manual test and error process. In this paper, it is presented an alternative extension of this methodology which avoids the said manual process. It is based on learning human behavior patterns automatically from sensor data by using machine learning techniques. The presented approach has been tested on a real scenario, where this extension has given highly accurate human behavior models,

Visual attention and perception models for assessing quality in 2D and 3D stereoscopic video

La medida de calidad de vídeo sigue siendo necesaria para definir los criterios que caracterizan una señal que cumpla los requisitos de visionado impuestos por el usuario. Las nuevas tecnologías, como el vídeo 3D estereoscópico o formatos más allá de la alta definición, imponen nuevos criterios que deben ser analizadas para obtener la mayor satisfacción posible del usuario. Entre los problemas detectados durante el desarrollo de esta tesis doctoral se han determinado fenómenos que afectan a distintas fases de la cadena de producción audiovisual y tipo de contenido variado. En primer lugar, el proceso de generación de contenidos debe encontrarse controlado mediante parámetros que eviten que se produzca el disconfort visual y, consecuentemente, fatiga visual, especialmente en lo relativo a contenidos de 3D estereoscópico, tanto de animación como de acción real. Por otro lado, la medida de calidad relativa a la fase de compresión de vídeo emplea métricas que en ocasiones no se encuentran adaptadas a la percepción del usuario. El empleo de modelos psicovisuales y diagramas de atención visual permitirían ponderar las áreas de la imagen de manera que se preste mayor importancia a los píxeles que el usuario enfocará con mayor probabilidad. Estos dos bloques se relacionan a través de la definición del término saliencia. Saliencia es la capacidad del sistema visual para caracterizar una imagen visualizada ponderando las áreas que más atractivas resultan al ojo humano. La saliencia en generación de contenidos estereoscópicos se refiere principalmente a la profundidad simulada mediante la ilusión óptica, medida en términos de distancia del objeto virtual al ojo humano. Sin embargo, en vídeo bidimensional, la saliencia no se basa en la profundidad, sino en otros elementos adicionales, como el movimiento, el nivel de detalle, la posición de los píxeles o la aparición de caras, que serán los factores básicos que compondrán el modelo de atención visual desarrollado. Con el objetivo de detectar las características de una secuencia de vídeo estereoscópico que, con mayor probabilidad, pueden generar disconfort visual, se consultó la extensa literatura relativa a este tema y se realizaron unas pruebas subjetivas preliminares con usuarios. De esta forma, se llegó a la conclusión de que se producía disconfort en los casos en que se producía un cambio abrupto en la distribución de profundidades simuladas de la imagen, aparte de otras degradaciones como la denominada “violación de ventana”. A través de nuevas pruebas subjetivas centradas en analizar estos efectos con diferentes distribuciones de profundidades, se trataron de concretar los parámetros que definían esta imagen. Los resultados de las pruebas demuestran que los cambios abruptos en imágenes se producen en entornos con movimientos y disparidades negativas elevadas que producen interferencias en los procesos de acomodación y vergencia del ojo humano, así como una necesidad en el aumento de los tiempos de enfoque del cristalino. En la mejora de las métricas de calidad a través de modelos que se adaptan al sistema visual humano, se realizaron también pruebas subjetivas que ayudaron a determinar la importancia de cada uno de los factores a la hora de enmascarar una determinada degradación. Los resultados demuestran una ligera mejora en los resultados obtenidos al aplicar máscaras de ponderación y atención visual, los cuales aproximan los parámetros de calidad objetiva a la respuesta del ojo humano. ABSTRACT Video quality assessment is still a necessary tool for defining the criteria to characterize a signal with the viewing requirements imposed by the final user. New technologies, such as 3D stereoscopic video and formats of HD and beyond HD oblige to develop new analysis of video features for obtaining the highest user’s satisfaction. Among the problems detected during the process of this doctoral thesis, it has been determined that some phenomena affect to different phases in the audiovisual production chain, apart from the type of content. On first instance, the generation of contents process should be enough controlled through parameters that avoid the occurrence of visual discomfort in observer’s eye, and consequently, visual fatigue. It is especially necessary controlling sequences of stereoscopic 3D, with both animation and live-action contents. On the other hand, video quality assessment, related to compression processes, should be improved because some objective metrics are adapted to user’s perception. The use of psychovisual models and visual attention diagrams allow the weighting of image regions of interest, giving more importance to the areas which the user will focus most probably. These two work fields are related together through the definition of the term saliency. Saliency is the capacity of human visual system for characterizing an image, highlighting the areas which result more attractive to the human eye. Saliency in generation of 3DTV contents refers mainly to the simulated depth of the optic illusion, i.e. the distance from the virtual object to the human eye. On the other hand, saliency is not based on virtual depth, but on other features, such as motion, level of detail, position of pixels in the frame or face detection, which are the basic features that are part of the developed visual attention model, as demonstrated with tests. Extensive literature involving visual comfort assessment was looked up, and the development of new preliminary subjective assessment with users was performed, in order to detect the features that increase the probability of discomfort to occur. With this methodology, the conclusions drawn confirmed that one common source of visual discomfort was when an abrupt change of disparity happened in video transitions, apart from other degradations, such as window violation. New quality assessment was performed to quantify the distribution of disparities over different sequences. The results confirmed that abrupt changes in negative parallax environment produce accommodation-vergence mismatches derived from the increasing time for human crystalline to focus the virtual objects. On the other side, for developing metrics that adapt to human visual system, additional subjective tests were developed to determine the importance of each factor, which masks a concrete distortion. Results demonstrated slight improvement after applying visual attention to objective metrics. This process of weighing pixels approximates the quality results to human eye’s response.

A conditional probability analysis of cystic fibrosis transmembrane conductance regulator gating indicates that ATP has multiple effects during the gating cycle

ATP-binding cassette (ABC) transporters bind and hydrolyze ATP. In the cystic fibrosis transmembrane conductance regulator Cl− channel, this interaction with ATP generates a gating cycle between a closed (C) and two open (O1 and O2) conformations. To understand better how ATP controls channel activity, we examined gating transitions from the C to the O1 and O2 states and from these open states to the C conformation. We made three main observations. First, we found that the channel can open into either the O1 or O2 state, that the frequency of transitions to both states was increased by ATP concentration, and that ATP increased the relative proportion of openings into O1 vs. O2. These results indicate that ATP can interact with the closed state to open the channel in at least two ways, which may involve binding to nucleotide-binding domains (NBDs) NBD1 and NBD2. Second, ATP prolonged the burst duration and altered the way in which the channel closed. These data suggest that ATP also interacts with the open channel. Third, the channel showed runs of specific types of open–closed transitions. This finding suggests a mechanism with more than one cycle of gating transitions. These data suggest models to explain how ATP influences conformational transitions in cystic fibrosis transmembrane conductance regulator and perhaps other ABC transporters.