A full pedigree based method for the statistical assessment of genetic anticipation

Genetic anticipation is defined as a decrease in age of onset or increase in severity as the disorder is transmitted through subsequent generations. Anticipation has been noted in the literature for over a century. Recently, anticipation in several diseases including Huntington's Disease, Myotonic Dystrophy and Fragile X Syndrome were shown to be caused by expansion of triplet repeats. Anticipation effects have also been observed in numerous mental disorders (e.g. Schizophrenia, Bipolar Disorder), cancers (Li-Fraumeni Syndrome, Leukemia) and other complex diseases. ^ Several statistical methods have been applied to determine whether anticipation is a true phenomenon in a particular disorder, including standard statistical tests and newly developed affected parent/affected child pair methods. These methods have been shown to be inappropriate for assessing anticipation for a variety of reasons, including familial correlation and low power. Therefore, we have developed family-based likelihood modeling approaches to model the underlying transmission of the disease gene and penetrance function and hence detect anticipation. These methods can be applied in extended families, thus improving the power to detect anticipation compared with existing methods based only upon parents and children. The first method we have proposed is based on the regressive logistic hazard model. This approach models anticipation by a generational covariate. The second method allows alleles to mutate as they are transmitted from parents to offspring and is appropriate for modeling the known triplet repeat diseases in which the disease alleles can become more deleterious as they are transmitted across generations. ^ To evaluate the new methods, we performed extensive simulation studies for data simulated under different conditions to evaluate the effectiveness of the algorithms to detect genetic anticipation. Results from analysis by the first method yielded empirical power greater than 87% based on the 5% type I error critical value identified in each simulation depending on the method of data generation and current age criteria. Analysis by the second method was not possible due to the current formulation of the software. The application of this method to Huntington's Disease and Li-Fraumeni Syndrome data sets revealed evidence for a generation effect in both cases. ^

Statistical and methodological challenges for disaster preparedness and medical needs assessment in Rio Grande Valley of Texas

In recent years, disaster preparedness through assessment of medical and special needs persons (MSNP) has taken a center place in public eye in effect of frequent natural disasters such as hurricanes, storm surge or tsunami due to climate change and increased human activity on our planet. Statistical methods complex survey design and analysis have equally gained significance as a consequence. However, there exist many challenges still, to infer such assessments over the target population for policy level advocacy and implementation. ^ Objective. This study discusses the use of some of the statistical methods for disaster preparedness and medical needs assessment to facilitate local and state governments for its policy level decision making and logistic support to avoid any loss of life and property in future calamities. ^ Methods. In order to obtain precise and unbiased estimates for Medical Special Needs Persons (MSNP) and disaster preparedness for evacuation in Rio Grande Valley (RGV) of Texas, a stratified and cluster-randomized multi-stage sampling design was implemented. US School of Public Health, Brownsville surveyed 3088 households in three counties namely Cameron, Hidalgo, and Willacy. Multiple statistical methods were implemented and estimates were obtained taking into count probability of selection and clustering effects. Statistical methods for data analysis discussed were Multivariate Linear Regression (MLR), Survey Linear Regression (Svy-Reg), Generalized Estimation Equation (GEE) and Multilevel Mixed Models (MLM) all with and without sampling weights. ^ Results. Estimated population for RGV was 1,146,796. There were 51.5% female, 90% Hispanic, 73% married, 56% unemployed and 37% with their personal transport. 40% people attained education up to elementary school, another 42% reaching high school and only 18% went to college. Median household income is less than $15,000/year. MSNP estimated to be 44,196 (3.98%) [95% CI: 39,029; 51,123]. All statistical models are in concordance with MSNP estimates ranging from 44,000 to 48,000. MSNP estimates for statistical methods are: MLR (47,707; 95% CI: 42,462; 52,999), MLR with weights (45,882; 95% CI: 39,792; 51,972), Bootstrap Regression (47,730; 95% CI: 41,629; 53,785), GEE (47,649; 95% CI: 41,629; 53,670), GEE with weights (45,076; 95% CI: 39,029; 51,123), Svy-Reg (44,196; 95% CI: 40,004; 48,390) and MLM (46,513; 95% CI: 39,869; 53,157). ^ Conclusion. RGV is a flood zone, most susceptible to hurricanes and other natural disasters. People in the region are mostly Hispanic, under-educated with least income levels in the U.S. In case of any disaster people in large are incapacitated with only 37% have their personal transport to take care of MSNP. Local and state government’s intervention in terms of planning, preparation and support for evacuation is necessary in any such disaster to avoid loss of precious human life. ^ Key words: Complex Surveys, statistical methods, multilevel models, cluster randomized, sampling weights, raking, survey regression, generalized estimation equations (GEE), random effects, Intracluster correlation coefficient (ICC).^

Performance recovery from exercise: A review from a statistical point of view

Background. Research into methods for recovery from fatigue due to exercise is a popular topic among sport medicine, kinesiology and physical therapy. However, both the quantity and quality of studies and a clear solution of recovery are lacking. An analysis of the statistical methods in the existing literature of performance recovery can enhance the quality of research and provide some guidance for future studies. Methods: A literature review was performed using SCOPUS, SPORTDiscus, MEDLINE, CINAHL, Cochrane Library and Science Citation Index Expanded databases to extract the studies related to performance recovery from exercise of human beings. Original studies and their statistical analysis for recovery methods including Active Recovery, Cryotherapy/Contrast Therapy, Massage Therapy, Diet/Ergogenics, and Rehydration were examined. Results: The review produces a Research Design and Statistical Method Analysis Summary. Conclusion: Research design and statistical methods can be improved by using the guideline from the Research Design and Statistical Method Analysis Summary. This summary table lists the potential issues and suggested solutions, such as, sample size calculation, sports specific and research design issues consideration, population and measure markers selection, statistical methods for different analytical requirements, equality of variance and normality of data, post hoc analyses and effect size calculation.^

A computerized statistical framework for coalescent analysis

Coalescent theory represents the most significant progress in theoretical population genetics in the past three decades. The coalescent theory states that all genes or alleles in a given population are ultimately inherited from a single ancestor shared by all members of the population, known as the most recent common ancestor. It is now widely recognized as a cornerstone for rigorous statistical analyses of molecular data from population [1]. The scientists have developed a large number of coalescent models and methods[2,3,4,5,6], which are not only applied in coalescent analysis and process, but also in today’s population genetics and genome studies, even public health. The thesis aims at completing a statistical framework based on computers for coalescent analysis. This framework provides a large number of coalescent models and statistic methods to assist students and researchers in coalescent analysis, whose results are presented in various formats as texts, graphics and printed pages. In particular, it also supports to create new coalescent models and statistical methods. ^

Multivariate methods for correlated effects sizes

Current statistical methods for estimation of parametric effect sizes from a series of experiments are generally restricted to univariate comparisons of standardized mean differences between two treatments. Multivariate methods are presented for the case in which effect size is a vector of standardized multivariate mean differences and the number of treatment groups is two or more. The proposed methods employ a vector of independent sample means for each response variable that leads to a covariance structure which depends only on correlations among the $p$ responses on each subject. Using weighted least squares theory and the assumption that the observations are from normally distributed populations, multivariate hypotheses analogous to common hypotheses used for testing effect sizes were formulated and tested for treatment effects which are correlated through a common control group, through multiple response variables observed on each subject, or both conditions.^ The asymptotic multivariate distribution for correlated effect sizes is obtained by extending univariate methods for estimating effect sizes which are correlated through common control groups. The joint distribution of vectors of effect sizes (from $p$ responses on each subject) from one treatment and one control group and from several treatment groups sharing a common control group are derived. Methods are given for estimation of linear combinations of effect sizes when certain homogeneity conditions are met, and for estimation of vectors of effect sizes and confidence intervals from $p$ responses on each subject. Computational illustrations are provided using data from studies of effects of electric field exposure on small laboratory animals. ^

Organic-walled dinoflagellate cysts analysis and statistical analysis of 116 surface sediment samples from the eastern Indian Ocean

Assemblages of organic-walled dinoflagellate cysts (dinocysts) from 116 marine surface samples have been analysed to assess the relationship between the spatial distribution of dinocysts and modern local environmental conditions [e.g. sea surface temperature (SST), sea surface salinity (SSS), productivity] in the eastern Indian Ocean. Results from the percentage analysis and statistical methods such as multivariate ordination analysis and end-member modelling, indicate the existence of three distinct environmental and oceanographic regions in the study area. Region 1 is located in western and eastern Indonesia and controlled by high SSTs and a low nutrient content of the surface waters. The Indonesian Throughflow (ITF) region (Region 2) is dominated by heterotrophic dinocyst species reflecting the region's high productivity. Region 3 is encompassing the area offshore north-west and west Australia which is characterised by the water masses of the Leeuwin Current, a saline and nutrient depleted southward current featuring energetic eddies.

Vision-based vehicle detection and tracking with a mobile camera using a statistical framework

En esta tesis se aborda la detección y el seguimiento automático de vehículos mediante técnicas de visión artificial con una cámara monocular embarcada. Este problema ha suscitado un gran interés por parte de la industria automovilística y de la comunidad científica ya que supone el primer paso en aras de la ayuda a la conducción, la prevención de accidentes y, en última instancia, la conducción automática. A pesar de que se le ha dedicado mucho esfuerzo en los últimos años, de momento no se ha encontrado ninguna solución completamente satisfactoria y por lo tanto continúa siendo un tema de investigación abierto. Los principales problemas que plantean la detección y seguimiento mediante visión artificial son la gran variabilidad entre vehículos, un fondo que cambia dinámicamente debido al movimiento de la cámara, y la necesidad de operar en tiempo real. En este contexto, esta tesis propone un marco unificado para la detección y seguimiento de vehículos que afronta los problemas descritos mediante un enfoque estadístico. El marco se compone de tres grandes bloques, i.e., generación de hipótesis, verificación de hipótesis, y seguimiento de vehículos, que se llevan a cabo de manera secuencial. No obstante, se potencia el intercambio de información entre los diferentes bloques con objeto de obtener el máximo grado posible de adaptación a cambios en el entorno y de reducir el coste computacional. Para abordar la primera tarea de generación de hipótesis, se proponen dos métodos complementarios basados respectivamente en el análisis de la apariencia y la geometría de la escena. Para ello resulta especialmente interesante el uso de un dominio transformado en el que se elimina la perspectiva de la imagen original, puesto que este dominio permite una búsqueda rápida dentro de la imagen y por tanto una generación eficiente de hipótesis de localización de los vehículos. Los candidatos finales se obtienen por medio de un marco colaborativo entre el dominio original y el dominio transformado. Para la verificación de hipótesis se adopta un método de aprendizaje supervisado. Así, se evalúan algunos de los métodos de extracción de características más populares y se proponen nuevos descriptores con arreglo al conocimiento de la apariencia de los vehículos. Para evaluar la efectividad en la tarea de clasificación de estos descriptores, y dado que no existen bases de datos públicas que se adapten al problema descrito, se ha generado una nueva base de datos sobre la que se han realizado pruebas masivas. Finalmente, se presenta una metodología para la fusión de los diferentes clasificadores y se plantea una discusión sobre las combinaciones que ofrecen los mejores resultados. El núcleo del marco propuesto está constituido por un método Bayesiano de seguimiento basado en filtros de partículas. Se plantean contribuciones en los tres elementos fundamentales de estos filtros: el algoritmo de inferencia, el modelo dinámico y el modelo de observación. En concreto, se propone el uso de un método de muestreo basado en MCMC que evita el elevado coste computacional de los filtros de partículas tradicionales y por consiguiente permite que el modelado conjunto de múltiples vehículos sea computacionalmente viable. Por otra parte, el dominio transformado mencionado anteriormente permite la definición de un modelo dinámico de velocidad constante ya que se preserva el movimiento suave de los vehículos en autopistas. Por último, se propone un modelo de observación que integra diferentes características. En particular, además de la apariencia de los vehículos, el modelo tiene en cuenta también toda la información recibida de los bloques de procesamiento previos. El método propuesto se ejecuta en tiempo real en un ordenador de propósito general y da unos resultados sobresalientes en comparación con los métodos tradicionales. ABSTRACT This thesis addresses on-road vehicle detection and tracking with a monocular vision system. This problem has attracted the attention of the automotive industry and the research community as it is the first step for driver assistance and collision avoidance systems and for eventual autonomous driving. Although many effort has been devoted to address it in recent years, no satisfactory solution has yet been devised and thus it is an active research issue. The main challenges for vision-based vehicle detection and tracking are the high variability among vehicles, the dynamically changing background due to camera motion and the real-time processing requirement. In this thesis, a unified approach using statistical methods is presented for vehicle detection and tracking that tackles these issues. The approach is divided into three primary tasks, i.e., vehicle hypothesis generation, hypothesis verification, and vehicle tracking, which are performed sequentially. Nevertheless, the exchange of information between processing blocks is fostered so that the maximum degree of adaptation to changes in the environment can be achieved and the computational cost is alleviated. Two complementary strategies are proposed to address the first task, i.e., hypothesis generation, based respectively on appearance and geometry analysis. To this end, the use of a rectified domain in which the perspective is removed from the original image is especially interesting, as it allows for fast image scanning and coarse hypothesis generation. The final vehicle candidates are produced using a collaborative framework between the original and the rectified domains. A supervised classification strategy is adopted for the verification of the hypothesized vehicle locations. In particular, state-of-the-art methods for feature extraction are evaluated and new descriptors are proposed by exploiting the knowledge on vehicle appearance. Due to the lack of appropriate public databases, a new database is generated and the classification performance of the descriptors is extensively tested on it. Finally, a methodology for the fusion of the different classifiers is presented and the best combinations are discussed. The core of the proposed approach is a Bayesian tracking framework using particle filters. Contributions are made on its three key elements: the inference algorithm, the dynamic model and the observation model. In particular, the use of a Markov chain Monte Carlo method is proposed for sampling, which circumvents the exponential complexity increase of traditional particle filters thus making joint multiple vehicle tracking affordable. On the other hand, the aforementioned rectified domain allows for the definition of a constant-velocity dynamic model since it preserves the smooth motion of vehicles in highways. Finally, a multiple-cue observation model is proposed that not only accounts for vehicle appearance but also integrates the available information from the analysis in the previous blocks. The proposed approach is proven to run near real-time in a general purpose PC and to deliver outstanding results compared to traditional methods.

Comparison of Airborne Laser Scanning Methods for Estimating Forest Structure Indicators Based on Lorenz Curves

The purpose of this study was to compare a number of state-of-the-art methods in airborne laser scan- ning (ALS) remote sensing with regards to their capacity to describe tree size inequality and other indi- cators related to forest structure. The indicators chosen were based on the analysis of the Lorenz curve: Gini coefficient ( GC ), Lorenz asymmetry ( LA ), the proportions of basal area ( BALM ) and stem density ( NSLM ) stocked above the mean quadratic diameter. Each method belonged to one of these estimation strategies: (A) estimating indicators directly; (B) estimating the whole Lorenz curve; or (C) estimating a complete tree list. Across these strategies, the most popular statistical methods for area-based approach (ABA) were used: regression, random forest (RF), and nearest neighbour imputation. The latter included distance metrics based on either RF (NN–RF) or most similar neighbour (MSN). In the case of tree list esti- mation, methods based on individual tree detection (ITD) and semi-ITD, both combined with MSN impu- tation, were also studied. The most accurate method was direct estimation by best subset regression, which obtained the lowest cross-validated coefficients of variation of their root mean squared error CV(RMSE) for most indicators: GC (16.80%), LA (8.76%), BALM (8.80%) and NSLM (14.60%). Similar figures [CV(RMSE) 16.09%, 10.49%, 10.93% and 14.07%, respectively] were obtained by MSN imputation of tree lists by ABA, a method that also showed a number of additional advantages, such as better distributing the residual variance along the predictive range. In light of our results, ITD approaches may be clearly inferior to ABA with regards to describing the structural properties related to tree size inequality in for- ested areas.

Computational Methods for Identifying Hypertrophic Cardiomyopathy using 12-lead ECG

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease where the heart muscle is partially thickened and blood flow is - potentially fatally - obstructed. It is one of the leading causes of sudden cardiac death in young people. Electrocardiography (ECG) and Echocardiography (Echo) are the standard tests for identifying HCM and other cardiac abnormalities. The American Heart Association has recommended using a pre-participation questionnaire for young athletes instead of ECG or Echo tests due to considerations of cost and time involved in interpreting the results of these tests by an expert cardiologist. Initially we set out to develop a classifier for automated prediction of young athletes’ heart conditions based on the answers to the questionnaire. Classification results and further in-depth analysis using computational and statistical methods indicated significant shortcomings of the questionnaire in predicting cardiac abnormalities. Automated methods for analyzing ECG signals can help reduce cost and save time in the pre-participation screening process by detecting HCM and other cardiac abnormalities. Therefore, the main goal of this dissertation work is to identify HCM through computational analysis of 12-lead ECG. ECG signals recorded on one or two leads have been analyzed in the past for classifying individual heartbeats into different types of arrhythmia as annotated primarily in the MIT-BIH database. In contrast, we classify complete sequences of 12-lead ECGs to assign patients into two groups: HCM vs. non-HCM. The challenges and issues we address include missing ECG waves in one or more leads and the dimensionality of a large feature-set. We address these by proposing imputation and feature-selection methods. We develop heartbeat-classifiers by employing Random Forests and Support Vector Machines, and propose a method to classify full 12-lead ECGs based on the proportion of heartbeats classified as HCM. The results from our experiments show that the classifiers developed using our methods perform well in identifying HCM. Thus the two contributions of this thesis are the utilization of computational and statistical methods for discovering shortcomings in a current screening procedure and the development of methods to identify HCM through computational analysis of 12-lead ECG signals.

Statistical models of accidents on interchange ramps and speed-change lanes.

Federal Highway Administration, Office of Safety and Traffic Operations, Washington, D.C.

Statistical views of transportation safety.

Mode of access: Internet.

Statistical Hurdle Models for Single Cell Gene Expression: Differential Expression and Graphical Modeling

Thesis (Ph.D.)--University of Washington, 2016-06

Purchasing Power Parities for Industry Comparisons Using Weighted Elteto-Koves-Szulc (EKS) Methods

This study has three main objectives. First, it develops a generalization of the commonly used EKS method to multilateral price comparisons. It is shown that the EKS system can be generalized so that weights can be attached to each of the link comparisons used in the EKS computations. These weights can account for differing levels of reliability of the underlying binary comparisons. Second, various reliability measures and corresponding weighting schemes are presented and their merits discussed. Finally, these new methods are applied to an international data set of manufacturing prices from the ICOP project. Although theoretically superior, it appears that the empirical impact of the weighted EKS method is generally small compared to the unweighted EKS. It is also found that this impact is larger when it is applied at lower levels of aggregation. Finally, the importance of using sector specific PPPs in assessing relative levels of manufacturing productivity is indicated.

Modelling pre-clearing vegetation distribution using GIS-integrated statistical, ecological and data models: A case study from the wet tropics of Northeastern Australia

Traditional vegetation mapping methods use high cost, labour-intensive aerial photography interpretation. This approach can be subjective and is limited by factors such as the extent of remnant vegetation, and the differing scale and quality of aerial photography over time. An alternative approach is proposed which integrates a data model, a statistical model and an ecological model using sophisticated Geographic Information Systems (GIS) techniques and rule-based systems to support fine-scale vegetation community modelling. This approach is based on a more realistic representation of vegetation patterns with transitional gradients from one vegetation community to another. Arbitrary, though often unrealistic, sharp boundaries can be imposed on the model by the application of statistical methods. This GIS-integrated multivariate approach is applied to the problem of vegetation mapping in the complex vegetation communities of the Innisfail Lowlands in the Wet Tropics bioregion of Northeastern Australia. The paper presents the full cycle of this vegetation modelling approach including sampling sites, variable selection, model selection, model implementation, internal model assessment, model prediction assessments, models integration of discrete vegetation community models to generate a composite pre-clearing vegetation map, independent data set model validation and model prediction's scale assessments. An accurate pre-clearing vegetation map of the Innisfail Lowlands was generated (0.83r(2)) through GIS integration of 28 separate statistical models. This modelling approach has good potential for wider application, including provision of. vital information for conservation planning and management; a scientific basis for rehabilitation of disturbed and cleared areas; a viable method for the production of adequate vegetation maps for conservation and forestry planning of poorly-studied areas. (c) 2006 Elsevier B.V. All rights reserved.