Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Benchmarking nitrogen removal suspended-carrier biofilm systems using dynamic simulation

We are witnessing an enormous growth in biological nitrogen removal from wastewater. It presents specific challenges beyond traditional COD (carbon) removal. A possibility for optimised process design is the use of biomass-supporting media. In this paper, attached growth processes (AGP) are evaluated using dynamic simulations. The advantages of these systems that were qualitatively described elsewhere, are validated quantitatively based on a simulation benchmark for activated sludge treatment systems. This simulation benchmark is extended with a biofilm model that allows for fast and accurate simulation of the conversion of different substrates in a biofilm. The economic feasibility of this system is evaluated using the data generated with the benchmark simulations. Capital savings due to volume reduction and reduced sludge production are weighed out against increased aeration costs. In this evaluation, effluent quality is integrated as well.

Simulation of insect movement with respect to plant architecture and morphogenesis

Developments in computer and three dimensional (3D) digitiser technologies have made it possible to keep track of the broad range of data required to simulate an insect moving around or over the highly heterogeneous habitat of a plant's surface. Properties of plant parts vary within a complex canopy architecture, and insect damage can induce further changes that affect an animal's movements, development and likelihood of survival. Models of plant architectural development based on Lindenmayer systems (L-systems) serve as dynamic platforms for simulation of insect movement, providing ail explicit model of the developing 3D structure of a plant as well as allowing physiological processes associated with plant growth and responses to damage to be described and Simulated. Simple examples of the use of the L-system formalism to model insect movement, operating Lit different spatial scales-from insects foraging on an individual plant to insects flying around plants in a field-are presented. Such models can be used to explore questions about the consequences of changes in environmental architecture and configuration on host finding, exploitation and its population consequences. In effect this model is a 'virtual ecosystem' laboratory to address local as well as landscape-level questions pertinent to plant-insect interactions, taking plant architecture into account. (C) 2002 Elsevier Science B.V. All rights reserved.

Partial automation of database processing of simulation outputs from L-systems models of plant morphogenesis

Models of plant architecture allow us to explore how genotype environment interactions effect the development of plant phenotypes. Such models generate masses of data organised in complex hierarchies. This paper presents a generic system for creating and automatically populating a relational database from data generated by the widely used L-system approach to modelling plant morphogenesis. Techniques from compiler technology are applied to generate attributes (new fields) in the database, to simplify query development for the recursively-structured branching relationship. Use of biological terminology in an interactive query builder contributes towards making the system biologist-friendly. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

An atomistic simulation of solid state sintering using Monte Carlo methods

This paper presents results on the simulation of the solid state sintering of copper wires using Monte Carlo techniques based on elements of lattice theory and cellular automata. The initial structure is superimposed onto a triangular, two-dimensional lattice, where each lattice site corresponds to either an atom or vacancy. The number of vacancies varies with the simulation temperature, while a cluster of vacancies is a pore. To simulate sintering, lattice sites are picked at random and reoriented in terms of an atomistic model governing mass transport. The probability that an atom has sufficient energy to jump to a vacant lattice site is related to the jump frequency, and hence the diffusion coefficient, while the probability that an atomic jump will be accepted is related to the change in energy of the system as a result of the jump, as determined by the change in the number of nearest neighbours. The jump frequency is also used to relate model time, measured in Monte Carlo Steps, to the actual sintering time. The model incorporates bulk, grain boundary and surface diffusion terms and includes vacancy annihilation on the grain boundaries. The predictions of the model were found to be consistent with experimental data, both in terms of the microstructural evolution and in terms of the sintering time. (C) 2002 Elsevier Science B.V. All rights reserved.

Conditional simulation of random fields by successive residuals

This paper presents a new approach to the LU decomposition method for the simulation of stationary and ergodic random fields. The approach overcomes the size limitations of LU and is suitable for any size simulation. The proposed approach can facilitate fast updating of generated realizations with new data, when appropriate, without repeating the full simulation process. Based on a novel column partitioning of the L matrix, expressed in terms of successive conditional covariance matrices, the approach presented here demonstrates that LU simulation is equivalent to the successive solution of kriging residual estimates plus random terms. Consequently, it can be used for the LU decomposition of matrices of any size. The simulation approach is termed conditional simulation by successive residuals as at each step, a small set (group) of random variables is simulated with a LU decomposition of a matrix of updated conditional covariance of residuals. The simulated group is then used to estimate residuals without the need to solve large systems of equations.

Spatial and temporal patterns in Australian wheat yield and their relationship with ENSO

Spatial and temporal variability in wheat production in Australia is dominated by rainfall occurrence. The length of historical production records is inadequate, however, to analyse spatial and temporal patterns conclusively. In this study we used modelling and simulation to identify key spatial patterns in Australian wheat yield, identify groups of years in the historical record in which spatial patterns were similar, and examine association of those wheat yield year groups with indicators of the El Nino Southern Oscillation (ENSO). A simple stress index model was trained on 19 years of Australian Bureau of Statistics shire yield data (1975-93). The model was then used to simulate shire yield from 1901 to 1999 for all wheat-producing shires. Principal components analysis was used to determine the dominating spatial relationships in wheat yield among shires. Six major components of spatial variability were found. Five of these represented near spatially independent zones across the Australian wheatbelt that demonstrated coherent temporal (annual) variability in wheat yield. A second orthogonal component was required to explain the temporal variation in New South Wales. The principal component scores were used to identify high- and low-yielding years in each zone. Year type groupings identified in this way were tested for association with indicators of ENSO. Significant associations were found for all zones in the Australian wheatbelt. Associations were as strong or stronger when ENSO indicators preceding the wheat season (April-May phases of the Southern Oscillation Index) were used rather than indicators based on classification during the wheat season. Although this association suggests an obvious role for seasonal climate forecasting in national wheat crop forecasting, the discriminatory power of the ENSO indicators, although significant, was not strong. By examining the historical years forming the wheat yield analog sets within each zone, it may be possible to identify novel climate system or ocean-atmosphere features that may be causal and, hence, most useful in improving seasonal forecasting schemes.

Analysis of adsorption data of graphitized thermal carbon black with a DFT-lattice gas theory

In this paper we analyzed the adsorption of gases and vapors on graphitised thermal carbon black by using a modified DFT-lattice theory, in which we assume that the behavior of the first layer in the adsorption film is different from those of second and higher layers. The effects of various parameters on the topology of the adsorption isotherm were first investigated, and the model was then applied in the analysis of adsorption data of numerous substances on carbon black. We have found that the first layer in the adsorption film behaves differently from the second and higher layers in such a way that the adsorbate-adsorbate interaction energy in the first layer is less than that of second and higher layers, and the same is observed for the partition function. Furthermore, the adsorbate-adsorbate and adsorbate-adsorbent interaction energies obtained from the fitting are consistently lower than the corresponding values obtained from the viscosity data and calculated from the Lorentz-Berthelot rule, respectively.

An overview of APSIM, a model designed for farming systems simulation

The Agricultural Production Systems Simulator (APSIM) is a modular modelling framework that has been developed by the Agricultural Production Systems Research Unit in Australia. APSIM was developed to simulate biophysical process in farming systems, in particular where there is interest in the economic and ecological outcomes of management practice in the face of climatic risk. The paper outlines APSIM's structure and provides details of the concepts behind the different plant, soil and management modules. These modules include a diverse range of crops, pastures and trees, soil processes including water balance, N and P transformations, soil pH, erosion and a full range of management controls. Reports of APSIM testing in a diverse range of systems and environments are summarised. An example of model performance in a long-term cropping systems trial is provided. APSIM has been used in a broad range of applications, including support for on-farm decision making, farming systems design for production or resource management objectives, assessment of the value of seasonal climate forecasting, analysis of supply chain issues in agribusiness activities, development of waste management guidelines, risk assessment for government policy making and as a guide to research and education activity. An extensive citation list for these model testing and application studies is provided. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Fitting genetic models to twin data with binary and ordered categorical responses: A comparison of structural equation modelling and Bayesian hierarchical models

We compare Bayesian methodology utilizing free-ware BUGS (Bayesian Inference Using Gibbs Sampling) with the traditional structural equation modelling approach based on another free-ware package, Mx. Dichotomous and ordinal (three category) twin data were simulated according to different additive genetic and common environment models for phenotypic variation. Practical issues are discussed in using Gibbs sampling as implemented by BUGS to fit subject-specific Bayesian generalized linear models, where the components of variation may be estimated directly. The simulation study (based on 2000 twin pairs) indicated that there is a consistent advantage in using the Bayesian method to detect a correct model under certain specifications of additive genetics and common environmental effects. For binary data, both methods had difficulty in detecting the correct model when the additive genetic effect was low (between 10 and 20%) or of moderate range (between 20 and 40%). Furthermore, neither method could adequately detect a correct model that included a modest common environmental effect (20%) even when the additive genetic effect was large (50%). Power was significantly improved with ordinal data for most scenarios, except for the case of low heritability under a true ACE model. We illustrate and compare both methods using data from 1239 twin pairs over the age of 50 years, who were registered with the Australian National Health and Medical Research Council Twin Registry (ATR) and presented symptoms associated with osteoarthritis occurring in joints of the hand.

An EM-based Semi-Parametric Mixture Model Approach to the Regression Analysis of Competing-Risks Data

We consider a mixture model approach to the regression analysis of competing-risks data. Attention is focused on inference concerning the effects of factors on both the probability of occurrence and the hazard rate conditional on each of the failure types. These two quantities are specified in the mixture model using the logistic model and the proportional hazards model, respectively. We propose a semi-parametric mixture method to estimate the logistic and regression coefficients jointly, whereby the component-baseline hazard functions are completely unspecified. Estimation is based on maximum likelihood on the basis of the full likelihood, implemented via an expectation-conditional maximization (ECM) algorithm. Simulation studies are performed to compare the performance of the proposed semi-parametric method with a fully parametric mixture approach. The results show that when the component-baseline hazard is monotonic increasing, the semi-parametric and fully parametric mixture approaches are comparable for mildly and moderately censored samples. When the component-baseline hazard is not monotonic increasing, the semi-parametric method consistently provides less biased estimates than a fully parametric approach and is comparable in efficiency in the estimation of the parameters for all levels of censoring. The methods are illustrated using a real data set of prostate cancer patients treated with different dosages of the drug diethylstilbestrol. Copyright (C) 2003 John Wiley Sons, Ltd.

Voxel-based registration of simulated and real patient CBCT data for accurate dental implant pose estimation

The success of dental implant-supported prosthesis is directly linked to the accuracy obtained during implant’s pose estimation (position and orientation). Although traditional impression techniques and recent digital acquisition methods are acceptably accurate, a simultaneously fast, accurate and operator-independent methodology is still lacking. Hereto, an image-based framework is proposed to estimate the patient-specific implant’s pose using cone-beam computed tomography (CBCT) and prior knowledge of implanted model. The pose estimation is accomplished in a threestep approach: (1) a region-of-interest is extracted from the CBCT data using 2 operator-defined points at the implant’s main axis; (2) a simulated CBCT volume of the known implanted model is generated through Feldkamp-Davis-Kress reconstruction and coarsely aligned to the defined axis; and (3) a voxel-based rigid registration is performed to optimally align both patient and simulated CBCT data, extracting the implant’s pose from the optimal transformation. Three experiments were performed to evaluate the framework: (1) an in silico study using 48 implants distributed through 12 tridimensional synthetic mandibular models; (2) an in vitro study using an artificial mandible with 2 dental implants acquired with an i-CAT system; and (3) two clinical case studies. The results shown positional errors of 67±34μm and 108μm, and angular misfits of 0.15±0.08º and 1.4º, for experiment 1 and 2, respectively. Moreover, in experiment 3, visual assessment of clinical data results shown a coherent alignment of the reference implant. Overall, a novel image-based framework for implants’ pose estimation from CBCT data was proposed, showing accurate results in agreement with dental prosthesis modelling requirements.

Semi-automatic 3D Segmentation Of Costal Cartilage In CT Data From Pectus Excavatum Patients

One of the current frontiers in the clinical management of Pectus Excavatum (PE) patients is the prediction of the surgical outcome prior to the intervention. This can be done through computerized simulation of the Nuss procedure, which requires an anatomically correct representation of the costal cartilage. To this end, we take advantage of the costal cartilage tubular structure to detect it through multi-scale vesselness filtering. This information is then used in an interactive 2D initialization procedure which uses anatomical maximum intensity projections of 3D vesselness feature images to efficiently initialize the 3D segmentation process. We identify the cartilage tissue centerlines in these projected 2D images using a livewire approach. We finally refine the 3D cartilage surface through region-based sparse field level-sets. We have tested the proposed algorithm in 6 noncontrast CT datasets from PE patients. A good segmentation performance was found against reference manual contouring, with an average Dice coefficient of 0.75±0.04 and an average mean surface distance of 1.69±0.30mm. The proposed method requires roughly 1 minute for the interactive initialization step, which can positively contribute to an extended use of this tool in clinical practice, since current manual delineation of the costal cartilage can take up to an hour.

Simulation of default events in a CDX and estimation of the spread

The portfolio generating the iTraxx EUR index is modeled by coupled Markov chains. Each of the industries of the portfolio evolves according to its own Markov transition matrix. Using a variant of the method of moments, the model parameters are estimated from a data set of Standard and Poor's. Swap spreads are evaluated by Monte-Carlo simulations. Along with an actuarially fair spread, at least squares spread is considered.

Energy and ancillary services joint market simulation

In order to develop a flexible simulator, a variety of models for Ancillary Services (AS) negotiation has been implemented in MASCEM – a multi-agent system competitive electricity markets simulator. In some of these models, the energy and the AS are addressed simultaneously while in other models they are addressed separately. This paper presents an energy and ancillary services joint market simulation. This paper proposes a deterministic approach for solving the energy and ancillary services joint market. A case study based on the dispatch of Regulation Down, Regulation Up, Spinning Reserve, and Non-Spinning Reserve services is used to demonstrate that the use of the developed methodology is suitable for solving this kind of optimization problem. The presented case study is based on CAISO real AS market data considers fifteen bids.