Detecting genetic and nutritional lung cancer risk factors related to folate metabolism using Bayesian generalized linear models

Complex diseases, such as cancer, are caused by various genetic and environmental factors, and their interactions. Joint analysis of these factors and their interactions would increase the power to detect risk factors but is statistically. Bayesian generalized linear models using student-t prior distributions on coefficients, is a novel method to simultaneously analyze genetic factors, environmental factors, and interactions. I performed simulation studies using three different disease models and demonstrated that the variable selection performance of Bayesian generalized linear models is comparable to that of Bayesian stochastic search variable selection, an improved method for variable selection when compared to standard methods. I further evaluated the variable selection performance of Bayesian generalized linear models using different numbers of candidate covariates and different sample sizes, and provided a guideline for required sample size to achieve a high power of variable selection using Bayesian generalize linear models, considering different scales of number of candidate covariates. ^ Polymorphisms in folate metabolism genes and nutritional factors have been previously associated with lung cancer risk. In this study, I simultaneously analyzed 115 tag SNPs in folate metabolism genes, 14 nutritional factors, and all possible genetic-nutritional interactions from 1239 lung cancer cases and 1692 controls using Bayesian generalized linear models stratified by never, former, and current smoking status. SNPs in MTRR were significantly associated with lung cancer risk across never, former, and current smokers. In never smokers, three SNPs in TYMS and three gene-nutrient interactions, including an interaction between SHMT1 and vitamin B12, an interaction between MTRR and total fat intake, and an interaction between MTR and alcohol use, were also identified as associated with lung cancer risk. These lung cancer risk factors are worthy of further investigation.^

Using spatial linear models with SAR and CAR structure to examine Texas lung cancer incidence rates

Scholars have found that socioeconomic status was one of the key factors that influenced early-stage lung cancer incidence rates in a variety of regions. This thesis examined the association between median household income and lung cancer incidence rates in Texas counties. A total of 254 individual counties in Texas with corresponding lung cancer incidence rates from 2004 to 2008 and median household incomes in 2006 were collected from the National Cancer Institute Surveillance System. A simple linear model and spatial linear models with two structures, Simultaneous Autoregressive Structure (SAR) and Conditional Autoregressive Structure (CAR), were used to link median household income and lung cancer incidence rates in Texas. The residuals of the spatial linear models were analyzed with Moran's I and Geary's C statistics, and the statistical results were used to detect similar lung cancer incidence rate clusters and disease patterns in Texas.^

Strategic trade policy and non-linear subsidy : in the case of price competition

In a strategic trade policy, it is assumed, in this paper, that a government changes disbursement or levy method so that the reaction function of home firm approaches infinitely close to that of foreign firm. In the framework of Bertrand-Nash equilibrium, Eaton and Grossman[1986] showed that export tax is preferable to export subsidy. In this paper, it is shown that export subsidy is preferable to export tax in some cases in the framework of Bertrand-Nash equilibrium, considering the uncertainty in demand. Historically, many economists mentioned non-linear subsidy or tax. However, optimum solution of it has not yet been shown. The optimum solution is shown in this paper.

Comparasion of road traffic emission models in Madrid (Spain)

Many cities in Europe have difficulties to meet the air quality standards set by the European legislation, most particularly the annual mean Limit Value for NO2. Road transport is often the main source of air pollution in urban areas and therefore, there is an increasing need to estimate current and future traffic emissions as accurately as possible. As a consequence, a number of specific emission models and emission factors databases have been developed recently. They present important methodological differences and may result in largely diverging emission figures and thus may lead to alternative policy recommendations. This study compares two approaches to estimate road traffic emissions in Madrid (Spain): the COmputer Programme to calculate Emissions from Road Transport (COPERT4 v.8.1) and the Handbook Emission Factors for Road Transport (HBEFA v.3.1), representative of the ‘average-speed’ and ‘traffic situation’ model types respectively. The input information (e.g. fleet composition, vehicle kilometres travelled, traffic intensity, road type, etc.) was provided by the traffic model developed by the Madrid City Council along with observations from field campaigns. Hourly emissions were computed for nearly 15 000 road segments distributed in 9 management areas covering the Madrid city and surroundings. Total annual NOX emissions predicted by HBEFA were a 21% higher than those of COPERT. The discrepancies for NO2 were lower (13%) since resulting average NO2/NOX ratios are lower for HBEFA. The larger differences are related to diesel vehicle emissions under “stop & go” traffic conditions, very common in distributor/secondary roads of the Madrid metropolitan area. In order to understand the representativeness of these results, the resulting emissions were integrated in an urban scale inventory used to drive mesoscale air quality simulations with the Community Multiscale Air Quality (CMAQ) modelling system (1 km2 resolution). Modelled NO2 concentrations were compared with observations through a series of statistics. Although there are no remarkable differences between both model runs, the results suggest that HBEFA may overestimate traffic emissions. However, the results are strongly influenced by methodological issues and limitations of the traffic model. This study was useful to provide a first alternative estimate to the official emission inventory in Madrid and to identify the main features of the traffic model that should be improved to support the application of an emission system based on “real world” emission factors.

Radar track segmentation with cubic splines for collision risk models in high density terminal areas

This paper presents a method to segment airplane radar tracks in high density terminal areas where the air traffic follows trajectories with several changes in heading, speed and altitude. The radar tracks are modelled with different types of segments, straight lines, cubic spline function and shape preserving cubic function. The longitudinal, lateral and vertical deviations are calculated for terminal manoeuvring area scenarios. The most promising model of the radar tracks resulted from a mixed interpolation using straight lines for linear segments and spline cubic functions for curved segments. A sensitivity analysis is used to optimise the size of the window for the segmentation process.

Some recent applications of non-linear models to the engineering practice

The Department of Structural Analysis of the University of Santander has been for a longtime involved in the solution of the country´s practical engineering problems. Some of these have required the use of non-conventional methods of analysis, in order to achieve adequate engineering answers. As an example of the increasing application of non-linear computer codes in the nowadays engineering practice, some cases will be briefly presented. In each case, only the main features of the problem involved and the solution used to solve it will be shown

M-AARE - Coupling atmospheric, hydrological, hydrodynamic and damage models in the Aare river basin, Switzerland

The triggering mechanism and the temporal evolution of large flood events, especially of worst-case scenarios, are not yet fully understood. Consequently, the cumulative losses of extreme floods are unknown. To study the link between weather conditions, discharges and flood losses it is necessary to couple atmospheric, hydrological, hydrodynamic and damage models. The objective of the M-AARE project is to test the potentials and opportunities of a model chain that relates atmospheric conditions to flood losses or risks. The M-AARE model chain is a set of coupled models consisting of four main components: the precipitation module, the hydrology module, the hydrodynamic module, and the damage module. The models are coupled in a cascading framework with harmonized time-steps. First exploratory applications show that the one way coupling of the WRF-PREVAH-BASEMENT models has been achieved and provides promising new insights for a better understanding of key aspects in flood risk analysis.

Designs for generalized linear models with several variables and model uncertainty

Standard factorial designs sometimes may be inadequate for experiments that aim to estimate a generalized linear model, for example, for describing a binary response in terms of several variables. A method is proposed for finding exact designs for such experiments that uses a criterion allowing for uncertainty in the link function, the linear predictor, or the model parameters, together with a design search. Designs are assessed and compared by simulation of the distribution of efficiencies relative to locally optimal designs over a space of possible models. Exact designs are investigated for two applications, and their advantages over factorial and central composite designs are demonstrated.

A note on DEA models in technology selection:an improvement of Karsak and Ahiska's approach

This paper introduces a compact form for the maximum value of the non-Archimedean in Data Envelopment Analysis (DEA) models applied for the technology selection, without the need to solve a linear programming (LP). Using this method the computational performance the common weight multi-criteria decision-making (MCDM) DEA model proposed by Karsak and Ahiska (International Journal of Production Research, 2005, 43(8), 1537-1554) is improved. This improvement is significant when computational issues and complexity analysis are a concern.

Grating and plaid masks indicate linear summation in a contrast gain pool

In human vision, the response to luminance contrast at each small region in the image is controlled by a more global process where suppressive signals are pooled over spatial frequency and orientation bands. But what rules govern summation among stimulus components within the suppressive pool? We addressed this question by extending a pedestal plus pattern mask paradigm to use a stimulus with up to three mask components: a vertical 1 c/deg pedestal, plus pattern masks made from either a grating (orientation = -45°) or a plaid (orientation = ±45°), with component spatial frequency of 3 c/deg. The overall contrast of both types of pattern mask was fixed at 20% (i.e., plaid component contrasts were 10%). We found that both of these masks transformed conventional dipper functions (threshold vs. pedestal contrast with no pattern mask) in exactly the same way: The dipper region was raised and shifted to the right, but the dipper handles superimposed. This equivalence of the two pattern masks indicates that contrast summation between the plaid components was perfectly linear prior to the masking stage. Furthermore, the pattern masks did not drive the detecting mechanism above its detection threshold because they did not abolish facilitation by the pedestal (Foley, 1994). Therefore, the pattern masking could not be attributed to within-channel masking, suggesting that linear summation of contrast signals takes place within a suppressive contrast gain pool. We present a quantitative model of the effects and discuss the implications for neurophysiological models of the process. © 2004 ARVO.

Hidden state models for time series

Amongst all the objectives in the study of time series, uncovering the dynamic law of its generation is probably the most important. When the underlying dynamics are not available, time series modelling consists of developing a model which best explains a sequence of observations. In this thesis, we consider hidden space models for analysing and describing time series. We first provide an introduction to the principal concepts of hidden state models and draw an analogy between hidden Markov models and state space models. Central ideas such as hidden state inference or parameter estimation are reviewed in detail. A key part of multivariate time series analysis is identifying the delay between different variables. We present a novel approach for time delay estimating in a non-stationary environment. The technique makes use of hidden Markov models and we demonstrate its application for estimating a crucial parameter in the oil industry. We then focus on hybrid models that we call dynamical local models. These models combine and generalise hidden Markov models and state space models. Probabilistic inference is unfortunately computationally intractable and we show how to make use of variational techniques for approximating the posterior distribution over the hidden state variables. Experimental simulations on synthetic and real-world data demonstrate the application of dynamical local models for segmenting a time series into regimes and providing predictive distributions.

Datasets, features, learning, and models in visual recognition

Visual recognition is a fundamental research topic in computer vision. This dissertation explores datasets, features, learning, and models used for visual recognition. In order to train visual models and evaluate different recognition algorithms, this dissertation develops an approach to collect object image datasets on web pages using an analysis of text around the image and of image appearance. This method exploits established online knowledge resources (Wikipedia pages for text; Flickr and Caltech data sets for images). The resources provide rich text and object appearance information. This dissertation describes results on two datasets. The first is Berg’s collection of 10 animal categories; on this dataset, we significantly outperform previous approaches. On an additional set of 5 categories, experimental results show the effectiveness of the method. Images are represented as features for visual recognition. This dissertation introduces a text-based image feature and demonstrates that it consistently improves performance on hard object classification problems. The feature is built using an auxiliary dataset of images annotated with tags, downloaded from the Internet. Image tags are noisy. The method obtains the text features of an unannotated image from the tags of its k-nearest neighbors in this auxiliary collection. A visual classifier presented with an object viewed under novel circumstances (say, a new viewing direction) must rely on its visual examples. This text feature may not change, because the auxiliary dataset likely contains a similar picture. While the tags associated with images are noisy, they are more stable when appearance changes. The performance of this feature is tested using PASCAL VOC 2006 and 2007 datasets. This feature performs well; it consistently improves the performance of visual object classifiers, and is particularly effective when the training dataset is small. With more and more collected training data, computational cost becomes a bottleneck, especially when training sophisticated classifiers such as kernelized SVM. This dissertation proposes a fast training algorithm called Stochastic Intersection Kernel Machine (SIKMA). This proposed training method will be useful for many vision problems, as it can produce a kernel classifier that is more accurate than a linear classifier, and can be trained on tens of thousands of examples in two minutes. It processes training examples one by one in a sequence, so memory cost is no longer the bottleneck to process large scale datasets. This dissertation applies this approach to train classifiers of Flickr groups with many group training examples. The resulting Flickr group prediction scores can be used to measure image similarity between two images. Experimental results on the Corel dataset and a PASCAL VOC dataset show the learned Flickr features perform better on image matching, retrieval, and classification than conventional visual features. Visual models are usually trained to best separate positive and negative training examples. However, when recognizing a large number of object categories, there may not be enough training examples for most objects, due to the intrinsic long-tailed distribution of objects in the real world. This dissertation proposes an approach to use comparative object similarity. The key insight is that, given a set of object categories which are similar and a set of categories which are dissimilar, a good object model should respond more strongly to examples from similar categories than to examples from dissimilar categories. This dissertation develops a regularized kernel machine algorithm to use this category dependent similarity regularization. Experiments on hundreds of categories show that our method can make significant improvement for categories with few or even no positive examples.

A new method for conditioning stochastic groundwater flow models in fractured media

Many geological formations consist of crystalline rocks that have very low matrix permeability but allow flow through an interconnected network of fractures. Understanding the flow of groundwater through such rocks is important in considering disposal of radioactive waste in underground repositories. A specific area of interest is the conditioning of fracture transmissivities on measured values of pressure in these formations. This is the process where the values of fracture transmissivities in a model are adjusted to obtain a good fit of the calculated pressures to measured pressure values. While there are existing methods to condition transmissivity fields on transmissivity, pressure and flow measurements for a continuous porous medium there is little literature on conditioning fracture networks. Conditioning fracture transmissivities on pressure or flow values is a complex problem because the measurements are not linearly related to the fracture transmissivities and they are also dependent on all the fracture transmissivities in the network. We present a new method for conditioning fracture transmissivities on measured pressure values based on the calculation of certain basis vectors; each basis vector represents the change to the log transmissivity of the fractures in the network that results in a unit increase in the pressure at one measurement point whilst keeping the pressure at the remaining measurement points constant. The fracture transmissivities are updated by adding a linear combination of basis vectors and coefficients, where the coefficients are obtained by minimizing an error function. A mathematical summary of the method is given. This algorithm is implemented in the existing finite element code ConnectFlow developed and marketed by Serco Technical Services, which models groundwater flow in a fracture network. Results of the conditioning are shown for a number of simple test problems as well as for a realistic large scale test case.

Transferability of environmental favourability models in geographic space: The case of the Iberian desman (Galemys pyrenaicus) in Portugal and Spain

Transferring distribution models between different geographical areas may be problematic, as the performance of models outside their original scope is hard to predict. A modelling procedure is needed that gets the gist of the environmental descriptors of a distribution area, without either overfitting to the training data or overestimating the species’ distribution potential.We tested the transferability power of the favourability function, a generalized linear model, on the distribution of the Iberian desman (Galemys pyrenaicus) in the Iberian territories of Portugal and Spain.We also tested the effects of two of the main potential constraints on model transferability: the analysed ranges of the predictor variables, and the completeness of the species distribution data. We modelled 10 km×10km presence/absence data from Portugal and Spain separately, extrapolated each model to the other country, and compared predictions with observations. The Spanish model, despite arguably containing more false absences, showed good predictive ability in Portugal. The Portuguese model, whose predictors ranged between only a subset of the values observed in Spain, overestimated desman distribution when transferred.We discuss possible reasons for this differential model behaviour, and highlight the importance of this kind of models for prediction and conservation applications

Inter-individual variability in temporal structure of the basketball shoot

This study analyzed inter-individual variability of the temporal structure applied in basketball throwing. Ten experienced male athletes in basketball throwing were filmed and a number of kinematic movement parameters analyzed. A biomechanical model provided the relative timing of the shoulder, elbow and wrist joint movements. Inter-individual variability was analyzed using sequencing and relative timing of tem phases of the throw. To compare the variability of the movement phases between subjects a discriminant analysis and an ANOVA were applied. The Tukey test was applied to determine where differences occurred. The significance level was p = 0.05. Inter-individual variability was explained by three concomitant factors: (a) a precision control strategy, (b) a velocity control strategy and (c) intrinsic characteristics of the subjects. Therefore, despite the fact that some actions are common to the basketball throwing pattern each performed demonstrated particular and individual characteristics.