An identifiability analysis of a parent-metabolite pharmacokinetic model for ivabradine.

The paper considers the structural identifiability of a parent–metabolite pharmacokinetic model for ivabradine and one of its metabolites. The model, which is linear, is considered initially for intravenous administration of ivabradine, and then for a combined intravenous and oral administration. In both cases, the model is shown to be unidentifiable. Simplification of the model (for both forms of administration) to that proposed by Duffull et al. (1) results in a globally structurally identifiable model. The analysis could be applied to the modeling of any drug undergoing first-pass metabolism, with plasma concentrations available from drug and metabolite.

On estimation and identifiability issues of sex-linked inheritance with a case study of pigmentation in Swiss barn owl (Tyto alba)

Genetic evaluation using animal models or pedigree-based models generally assume only autosomal inheritance. Bayesian animal models provide a flexible framework for genetic evaluation, and we show how the model readily can accommodate situations where the trait of interest is influenced by both autosomal and sex-linked inheritance. This allows for simultaneous calculation of autosomal and sex-chromosomal additive genetic effects. Inferences were performed using integrated nested Laplace approximations (INLA), a nonsampling-based Bayesian inference methodology. We provide a detailed description of how to calculate the inverse of the X- or Z-chromosomal additive genetic relationship matrix, needed for inference. The case study of eumelanic spot diameter in a Swiss barn owl (Tyto alba) population shows that this trait is substantially influenced by variation in genes on the Z-chromosome (sigma(2)(z) = 0.2719 and sigma(2)(a) = 0.4405). Further, a simulation study for this study system shows that the animal model accounting for both autosomal and sex-chromosome-linked inheritance is identifiable, that is, the two effects can be distinguished, and provides accurate inference on the variance components.

Identifiability of diffusion and sorption parameters from in situ diffusion experiments by using simultaneously tracer dilution and claystone data

In situ diffusion experiments are performed in geological formations at underground research laboratories to overcome the limitations of laboratory diffusion experiments and investigate scale effects. Tracer concentrations are monitored at the injection interval during the experiment (dilution data) and measured from host rock samples around the injection interval at the end of the experiment (overcoring data). Diffusion and sorption parameters are derived from the inverse numerical modeling of the measured tracer data. The identifiability and the uncertainties of tritium and Na-22(+) diffusion and sorption parameters are studied here by synthetic experiments having the same characteristics as the in situ diffusion and retention (DR) experiment performed on Opalinus Clay. Contrary to previous identifiability analyses of in situ diffusion experiments, which used either dilution or overcoring data at approximate locations, our analysis of the parameter identifiability relies simultaneously on dilution and overcoring data, accounts for the actual position of the overcoring samples in the claystone, uses realistic values of the standard deviation of the measurement errors, relies on model identification criteria to select the most appropriate hypothesis about the existence of a borehole disturbed zone and addresses the effect of errors in the location of the sampling profiles. The simultaneous use of dilution and overcoring data provides accurate parameter estimates in the presence of measurement errors, allows the identification of the right hypothesis about the borehole disturbed zone and diminishes other model uncertainties such as those caused by errors in the volume of the circulation system and the effective diffusion coefficient of the filter. The proper interpretation of the experiment requires the right hypothesis about the borehole disturbed zone. A wrong assumption leads to large estimation errors. The use of model identification criteria helps in the selection of the best model. Small errors in the depth of the overcoring samples lead to large parameter estimation errors. Therefore, attention should be paid to minimize the errors in positioning the depth of the samples. The results of the identifiability analysis do not depend on the particular realization of random numbers. (C) 2012 Elsevier B.V. All rights reserved.

Testing Independence in High Dimensions & Identifiability of Graphical Models

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

Identifiability and definiteness in Chinese

This article explores how the pragmatic notion of identfiability is encoded in Chinese. It presents a detailed analysis of the distinctive linguistic devices, including lexical, morphological, and position in sentence, which are employed in Chinese to indicate the interpretation of referents in respect of identifiability. Of the major determiners in Chinese, demonstratives are developing uses of a definite article, and yi 'one' + classier has developed uses of an indefinite article, although morphologically and in some cases also functionally they have not yet been fully grammaticalized. What makes Chinese further different from languages like English is the interpretation in this regard of what are called indeterminate lexical encodings, which include bare NPs and cardinality expressions. They by themselves are neutral in respect of the interpretation of identifiability. For indeterminate expressions, there is a strong but seldom absolute correlation between the interpretation of identiability or nonidentfiability and their occurrence in different positions in a sentence. Unlike the cases with several other languages without articles like Czech, Hindi, and Indonesian, the features of definiteness and indefiniteness cannot be obligatorily and uniquely specified for nominal expressions in Chinese. The findings in this article lead to the conclusion that definiteness as a grammatical category defined in the narrow sense has not been fully developed in Chinese.

A Parameter Estimation and Identifiability Analysis Methodology Applied to a Street Canyon Air Pollution Model

Mathematical models are increasingly used in environmental science thus increasing the importance of uncertainty and sensitivity analyses. In the present study, an iterative parameter estimation and identifiability analysis methodology is applied to an atmospheric model – the Operational Street Pollution Model (OSPMr). To assess the predictive validity of the model, the data is split into an estimation and a prediction data set using two data splitting approaches and data preparation techniques (clustering and outlier detection) are analysed. The sensitivity analysis, being part of the identifiability analysis, showed that some model parameters were significantly more sensitive than others. The application of the determined optimal parameter values was shown to succesfully equilibrate the model biases among the individual streets and species. It was as well shown that the frequentist approach applied for the uncertainty calculations underestimated the parameter uncertainties. The model parameter uncertainty was qualitatively assessed to be significant, and reduction strategies were identified.

Closed-loop model re-identification of processes under MPC with zone control

This work deals with a procedure for model re-identification of a process in closed loop with ail already existing commercial MPC. The controller considered here has a two-layer structure where the upper layer performs a target calculation based on a simplified steady-state optimization of the process. Here, it is proposed a methodology where a test signal is introduced in a tuning parameter of the target calculation layer. When the outputs are controlled by zones instead of at fixed set points, the approach allows the continuous operation of the process without an excessive disruption of the operating objectives as process constraints and product specifications remain satisfied during the identification test. The application of the method is illustrated through the simulation of two processes of the oil refining industry. (c) 2008 Elsevier Ltd. All rights reserved.

The generalized inverse Weibull distribution

The inverse Weibull distribution has the ability to model failure rates which are quite common in reliability and biological studies. A three-parameter generalized inverse Weibull distribution with decreasing and unimodal failure rate is introduced and studied. We provide a comprehensive treatment of the mathematical properties of the new distribution including expressions for the moment generating function and the rth generalized moment. The mixture model of two generalized inverse Weibull distributions is investigated. The identifiability property of the mixture model is demonstrated. For the first time, we propose a location-scale regression model based on the log-generalized inverse Weibull distribution for modeling lifetime data. In addition, we develop some diagnostic tools for sensitivity analysis. Two applications of real data are given to illustrate the potentiality of the proposed regression model.

A peaceful pyramid? Hierarchy and anonymity in newspaper comment sections

Several studies have linked deindividuation to an increase in aggression and incivility. This paper seeks to ascertain the influence of anonymity and hierarchy in online aggression by comparing two different newspaper comment sections: one with a hierarchical system and the other with an equalitarian setting. This study distinguishes itself form previous works by analyzing systems where identification is optional and where identified and anonymous users coexist. The hierarchical solution might be relevant to dissuade aggression when optional identifiability is seen as an essential asset. Results show that a hierarchical system provides some improvements in terms of civility and comment moderation, but that poor implementation of the hierarchy causes perversions in the system and affects its effectiveness.

Back to square one: Identification issues in DSGE models

We investigate identifiability issues in DSGE models and their consequences for parameter estimation and model evaluation when the objective function measures the distance between estimated and model impulse responses. We show that observational equivalence, partial and weak identification problems are widespread, that they lead to biased estimates, unreliable t-statistics and may induce investigators to select false models. We examine whether different objective functions affect identification and study how small samples interact with parameters and shock identification. We provide diagnostics and tests to detect identification failures and apply them to a state-of-the-art model.

Comment to "Weak instruments robust tests in GMM and the New Keynesian Phillips curve" by Frank Kleibergen and Sophocles Mavroeidis

I discuss the identifiability of a structural New Keynesian Phillips curve when it is embedded in a small scale dynamic stochastic general equilibrium model. Identification problems emerge because not all the structural parameters are recoverable from the semi-structural ones and because the objective functions I consider are poorly behaved. The solution and the moment mappings are responsible for the problems.

The application of trend surface models to the analysis of time factors in Swiss cancer mortality.

To study different temporal components on cancer mortality (age, period and cohort) methods of graphic representation were applied to Swiss mortality data from 1950 to 1984. Maps using continuous slopes ("contour maps") and based on eight tones of grey according to the absolute distribution of rates were used to represent the surfaces defined by the matrix of various age-specific rates. Further, progressively more complex regression surface equations were defined, on the basis of two independent variables (age/cohort) and a dependent one (each age-specific mortality rate). General patterns of trends in cancer mortality were thus identified, permitting definition of important cohort (e.g., upwards for lung and other tobacco-related neoplasms, or downwards for stomach) or period (e.g., downwards for intestines or thyroid cancers) effects, besides the major underlying age component. For most cancer sites, even the lower order (1st to 3rd) models utilised provided excellent fitting, allowing immediate identification of the residuals (e.g., high or low mortality points) as well as estimates of first-order interactions between the three factors, although the parameters of the main effects remained still undetermined. Thus, the method should be essentially used as summary guide to illustrate and understand the general patterns of age, period and cohort effects in (cancer) mortality, although they cannot conceptually solve the inherent problem of identifiability of the three components.

Impulse response recovery of linear systems through weighted cumulant slice

Identifiability of the so-called ω-slice algorithm is proven for ARMA linear systems. Although proofs were developed in the past for the simpler cases of MA and AR models, they were not extendible to general exponential linear systems. The results presented in this paper demonstrate a unique feature of the ω-slice method, which is unbiasedness and consistency when order is overdetermined, regardless of the IIR or FIR nature of the underlying system, and numerical robustness.

Modeling reaction kinetics and mass transfer in ozonation in water solutions

This dissertation is based on four articles dealing with modeling of ozonation. The literature part of this considers some models for hydrodynamics in bubble column simulation. A literature review of methods for obtaining mass transfer coefficients is presented. The methods presented to obtain mass transfer are general models and can be applied to any gas-liquid system. Ozonation reaction models and methods for obtaining stoichiometric coefficients and reaction rate coefficients for ozonation reactions are discussed in the final section of the literature part. In the first article, ozone gas-liquid mass transfer into water in a bubble column was investigated for different pH values. A more general method for estimation of mass transfer and Henry’s coefficient was developed from the Beltrán method. The ozone volumetric mass transfer coefficient and the Henry’s coefficient were determined simultaneously by parameter estimation using a nonlinear optimization method. A minor dependence of the Henry’s law constant on pH was detected at the pH range 4 - 9. In the second article, a new method using the axial dispersion model for estimation of ozone self-decomposition kinetics in a semi-batch bubble column reactor was developed. The reaction rate coefficients for literature equations of ozone decomposition and the gas phase dispersion coefficient were estimated and compared with the literature data. The reaction order in the pH range 7-10 with respect to ozone 1.12 and 0.51 the hydroxyl ion were obtained, which is in good agreement with literature. The model parameters were determined by parameter estimation using a nonlinear optimization method. Sensitivity analysis was conducted using object function method to obtain information about the reliability and identifiability of the estimated parameters. In the third article, the reaction rate coefficients and the stoichiometric coefficients in the reaction of ozone with the model component p-nitrophenol were estimated at low pH of water using nonlinear optimization. A novel method for estimation of multireaction model parameters in ozonation was developed. In this method the concentration of unknown intermediate compounds is presented as a residual COD (chemical oxygen demand) calculated from the measured COD and the theoretical COD for the known species. The decomposition rate of p-nitrophenol on the pathway producing hydroquinone was found to be about two times faster than the p-nitrophenol decomposition rate on the pathway producing 4- nitrocatechol. In the fourth article, the reaction kinetics of p-nitrophenol ozonation was studied in a bubble column at pH 2. Using the new reaction kinetic model presented in the previous article, the reaction kinetic parameters, rate coefficients, and stoichiometric coefficients as well as the mass transfer coefficient were estimated with nonlinear estimation. The decomposition rate of pnitrophenol was found to be equal both on the pathway producing hydroquinone and on the path way producing 4-nitrocathecol. Comparison of the rate coefficients with the case at initial pH 5 indicates that the p-nitrophenol degradation producing 4- nitrocathecol is more selective towards molecular ozone than the reaction producing hydroquinone. The identifiability and reliability of the estimated parameters were analyzed with the Marcov chain Monte Carlo (MCMC) method. @All rights reserved. No part of the publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the author.

Statistical Analysis and Numerics of Heat Exchanger Models

The identifiability of the parameters of a heat exchanger model without phase change was studied in this Master’s thesis using synthetically made data. A fast, two-step Markov chain Monte Carlo method (MCMC) was tested with a couple of case studies and a heat exchanger model. The two-step MCMC-method worked well and decreased the computation time compared to the traditional MCMC-method. The effect of measurement accuracy of certain control variables to the identifiability of parameters was also studied. The accuracy used did not seem to have a remarkable effect to the identifiability of parameters. The use of the posterior distribution of parameters in different heat exchanger geometries was studied. It would be computationally most efficient to use the same posterior distribution among different geometries in the optimisation of heat exchanger networks. According to the results, this was possible in the case when the frontal surface areas were the same among different geometries. In the other cases the same posterior distribution can be used for optimisation too, but that will give a wider predictive distribution as a result. For condensing surface heat exchangers the numerical stability of the simulation model was studied. As a result, a stable algorithm was developed.