A Method for Assessing the Retention of Trace Elements in Human Body Using Neural Network Technology

© 2017 Yulia Tunakova et al. Models that describe the trace element status formation in the human organism are essential for a correction of micromineral (trace elements) deficiency. A direct trace element retention assessment in the body is difficult due to the many internal mechanisms. The trace element retention is determined by the amount and the ratio of incoming and excreted substance. So, the concentration of trace elements in drinking water characterizes the intake, whereas the element concentration in urine characterizes the excretion. This system can be interpreted as three interrelated elements that are in equilibrium. Since many relationships in the system are not known, the use of standard mathematical models is difficult. The artificial neural network use is suitable for constructing a model in the best way because it can take into account all dependencies in the system implicitly and process inaccurate and incomplete data. We created several neural network models to describe the retentions of trace elements in the human body. On the model basis, we can calculate the microelement levels in the body, knowing the trace element levels in drinking water and urine. These results can be used in health care to provide the population with safe drinking water

Bayesian model selection validates a biokinetic model for zirconium processing in humans.

ABSTRACT: BACKGROUND: In radiation protection, biokinetic models for zirconium processing are of crucial importance in dose estimation and further risk analysis for humans exposed to this radioactive substance. They provide limiting values of detrimental effects and build the basis for applications in internal dosimetry, the prediction for radioactive zirconium retention in various organs as well as retrospective dosimetry. Multi-compartmental models are the tool of choice for simulating the processing of zirconium. Although easily interpretable, determining the exact compartment structure and interaction mechanisms is generally daunting. In the context of observing the dynamics of multiple compartments, Bayesian methods provide efficient tools for model inference and selection. RESULTS: We are the first to apply a Markov chain Monte Carlo approach to compute Bayes factors for the evaluation of two competing models for zirconium processing in the human body after ingestion. Based on in vivo measurements of human plasma and urine levels we were able to show that a recently published model is superior to the standard model of the International Commission on Radiological Protection. The Bayes factors were estimated by means of the numerically stable thermodynamic integration in combination with a recently developed copula based Metropolis-Hastings sampler. CONCLUSIONS: In contrast to the standard model the novel model predicts lower accretion of zirconium in bones. This results in lower levels of noxious doses for exposed individuals. Moreover, the Bayesian approach allows for retrospective dose assessment, including credible intervals for the initially ingested zirconium, in a significantly more reliable fashion than previously possible. All methods presented here are readily applicable to many modeling tasks in systems biology

Bayesian inference for infectious disease transmission models based on ordinary differential equations

Predicting the epidemiological effects of new vaccination programmes through mathematical-statistical transmission modelling is of increasing importance for the German Standing Committee on Vaccination. Such models commonly capture large populations utilizing a compartmental structure with its dynamics being governed by a system of ordinary differential equations (ODEs). Unfortunately, these ODE-based models are generally computationally expensive to solve, which poses a challenge for any statistical procedure inferring corresponding model parameters from disease surveillance data. Thus, in practice parameters are often fixed based on epidemiological knowledge hence ignoring uncertainty. A Bayesian inference framework incorporating this prior knowledge promises to be a more suitable approach allowing for additional parameter flexibility. This thesis is concerned with statistical methods for performing Bayesian inference of ODE-based models. A posterior approximation approach based on a Gaussian distribution around the posterior mode through its respective observed Fisher information is presented. By employing a newly proposed method for adjusting the likelihood impact in terms of using a power posterior, the approximation procedure is able to account for the residual autocorrelation in the data given the model. As an alternative to this approximation approach, an adaptive Metropolis-Hastings algorithm is described which is geared towards an efficient posterior sampling in the case of a high-dimensional parameter space and considerable parameter collinearities. In order to identify relevant model components, Bayesian model selection criteria based on the marginal likelihood of the data are applied. The estimation of the marginal likelihood for each considered model is performed via a newly proposed approach which utilizes the available posterior sample obtained from the preceding Metropolis-Hastings algorithm. Furthermore, the thesis contains an application of the presented methods by predicting the epidemiological effects of introducing rotavirus childhood vaccination in Germany. Again, an ODE-based compartmental model accounting for the most relevant transmission aspects of rotavirus is presented. After extending the model with vaccination mechanisms, it becomes possible to estimate the rotavirus vaccine effectiveness through routinely collected surveillance data. By employing the Bayesian framework, model predictions on the future epidemiological development assuming a high vaccination coverage rate incorporate uncertainty regarding both model structure and parameters. The forecast suggests that routine vaccination may cause a rotavirus incidence increase among older children and elderly, but drastically reduces the disease burden among the target group of young children, even beyond the expected direct vaccination effect by means of herd protection. Altogether, this thesis provides a statistical perspective on the modelling of routine vaccination effects in order to assist decision making under uncertainty. The presented methodology is thereby easily applicable to other infectious diseases such as influenza