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diff --git a/README.html b/README.html index 0ef35547..46dcea8b 100644 --- a/README.html +++ b/README.html @@ -384,9 +384,9 @@ pre code { <div id="general" class="section level3"> <h3>General</h3> <ul> -<li>Highly flexible model specification using <a href="https://pkgdown.jrwb.de/mkin/reference/mkinmod.html"><code>mkinmod</code></a>, including equilibrium reactions and using the single first-order reversible binding (SFORB) model, which will automatically create two latent state variables for the observed variable.</li> -<li>Model solution (forward modelling) in the function <a href="https://pkgdown.jrwb.de/mkin/reference/mkinpredict.html"><code>mkinpredict</code></a> is performed either using the analytical solution for the case of parent only degradation, an eigenvalue based solution if only simple first-order (SFO) or SFORB kinetics are used in the model, or using a numeric solver from the <code>deSolve</code> package (default is <code>lsoda</code>).</li> -<li>The usual one-sided t-test for significant difference from zero is nevertheless shown based on estimators for the untransformed parameters.</li> +<li>Highly flexible model specification using <a href="https://pkgdown.jrwb.de/mkin/reference/mkinmod.html"><code>mkinmod</code></a>, including equilibrium reactions and using the single first-order reversible binding (SFORB) model, which will automatically create two state variables for the observed variable.</li> +<li>Model solution (forward modelling) in the function <a href="https://pkgdown.jrwb.de/mkin/reference/mkinpredict.html"><code>mkinpredict</code></a> is performed either using the analytical solution for the case of parent only degradation or some simple models involving a single transformation product, , an eigenvalue based solution if only simple first-order (SFO) or SFORB kinetics are used in the model, or using a numeric solver from the <code>deSolve</code> package (default is <code>lsoda</code>).</li> +<li>The usual one-sided t-test for significant difference from zero is shown based on estimators for the untransformed parameters.</li> <li>Summary and plotting functions. The <code>summary</code> of an <code>mkinfit</code> object is in fact a full report that should give enough information to be able to approximately reproduce the fit with other tools.</li> <li>The chi-squared error level as defined in the FOCUS kinetics guidance (see below) is calculated for each observed variable.</li> <li>The ‘variance by variable’ error model which is often fitted using Iteratively Reweighted Least Squares (IRLS) can be specified as <code>error_model = "obs"</code>.</li> @@ -399,8 +399,8 @@ pre code { <li>Model comparisons using the Akaike Information Criterion (AIC) are supported which can also be used for non-constant variance. In such cases the FOCUS chi-squared error level is not meaningful.</li> <li>By default, kinetic rate constants and kinetic formation fractions are transformed internally using <a href="https://pkgdown.jrwb.de/mkin/reference/transform_odeparms.html"><code>transform_odeparms</code></a> so their estimators can more reasonably be expected to follow a normal distribution.</li> <li>When parameter estimates are backtransformed to match the model definition, confidence intervals calculated from standard errors are also backtransformed to the correct scale, and will not include meaningless values like negative rate constants or formation fractions adding up to more than 1, which cannot occur in a single experiment with a single defined radiolabel position.</li> -<li>When a metabolite decline phase is not described well by SFO kinetics, SFORB kinetics can be used for the metabolite. Mathematically, the SFORB model is equivalent to the DFOP model used by other tools for biphasic metabolite curves. However, the SFORB model has the advantage that there is a mechanistic interpretation of the model parameters.</li> -<li>Nonlinear mixed-effects models can be created from fits of the same degradation model to different datasets for the same compound by using the <a href="https://pkgdown.jrwb.de/mkin/reference/nlme.mmkin.html">nlme.mmkin</a> and <a href="https://pkgdown.jrwb.de/mkin/reference/saem.html">saem.mmkin</a> and methods. Note that the convergence of the nlme fits depends on the quality of the data. Convergence is better for simple models and data for many groups (e.g. soils). The saem method uses the <code>saemix</code> package as a backend. Analytical solutions suitable for use with this package have been implemented for parent only models and the most important models including one metabolite (SFO-SFO and DFOP-SFO). Fitting other models with <code>saem.mmkin</code>, while it makes use of the compiled ODE models that mkin provides, has longer run times (at least six minutes on my system).</li> +<li>When a metabolite decline phase is not described well by SFO kinetics, SFORB kinetics can be used for the metabolite. Mathematically, the SFORB model is equivalent to the DFOP model. However, the SFORB model has the advantage that there is a mechanistic interpretation of the model parameters.</li> +<li>Nonlinear mixed-effects models (hierarchical models) can be created from fits of the same degradation model to different datasets for the same compound by using the <a href="https://pkgdown.jrwb.de/mkin/reference/nlme.mmkin.html">nlme.mmkin</a> and <a href="https://pkgdown.jrwb.de/mkin/reference/saem.html">saem.mmkin</a> methods. Note that the convergence of the nlme fits depends on the quality of the data. Convergence is better for simple models and data for many groups (e.g. soils). The saem method uses the <code>saemix</code> package as a backend. Analytical solutions suitable for use with this package have been implemented for parent only models and the most important models including one metabolite (SFO-SFO and DFOP-SFO). Fitting other models with <code>saem.mmkin</code>, while it makes use of the compiled ODE models that mkin provides, has longer run times (from a couple of minutes to more than an hour).</li> </ul> </div> <div id="performance" class="section level3"> @@ -429,8 +429,8 @@ pre code { <p>The first <code>mkin</code> code was <a href="https://r-forge.r-project.org/scm/viewvc.php?view=rev&root=kinfit&revision=8">published on 11 May 2010</a> and the <a href="https://cran.r-project.org/src/contrib/Archive/mkin/">first CRAN version</a> on 18 May 2010.</p> <p>In 2011, Bayer Crop Science started to distribute an R based successor to KinGUI named KinGUII whose R code is based on <code>mkin</code>, but which added, among other refinements, a closed source graphical user interface (GUI), iteratively reweighted least squares (IRLS) optimisation of the variance for each of the observed variables, and Markov Chain Monte Carlo (MCMC) simulation functionality, similar to what is available e.g. in the <code>FME</code> package.</p> <p>Somewhat in parallel, Syngenta has sponsored the development of an <code>mkin</code> and KinGUII based GUI application called CAKE, which also adds IRLS and MCMC, is more limited in the model formulation, but puts more weight on usability. CAKE is available for download from the <a href="https://cake-kinetics.org">CAKE website</a>, where you can also find a zip archive of the R scripts derived from <code>mkin</code>, published under the GPL license.</p> -<p>Finally, there is <a href="https://github.com/zhenglei-gao/KineticEval">KineticEval</a>, which contains a further development of the scripts used for KinGUII, so the different tools will hopefully be able to learn from each other in the future as well.</p> -<p>Thanks to René Lehmann, formerly working at the Umweltbundesamt, for the nice cooperation cooperation on parameter transformations, especially the isometric log-ratio transformation that is now used for formation fractions in case there are more than two transformation targets.</p> +<p>Finally, there is <a href="https://github.com/zhenglei-gao/KineticEval">KineticEval</a>, which contains some further development of the scripts used for KinGUII.</p> +<p>Thanks to René Lehmann, formerly working at the Umweltbundesamt, for the nice cooperation on parameter transformations, especially the isometric log-ratio transformation that is now used for formation fractions in case there are more than two transformation targets.</p> <p>Many inspirations for improvements of mkin resulted from doing kinetic evaluations of degradation data for my clients while working at Harlan Laboratories and at Eurofins Regulatory AG, and now as an independent consultant.</p> <p>Funding was received from the Umweltbundesamt in the course of the projects</p> <ul> @@ -441,7 +441,8 @@ pre code { <li>Project Number 120667 (Development of objective criteria for the evaluation of the visual fit in the kinetic evaluation of degradation data, 2019-2020)</li> <li>Project Number 146839 (Checking the feasibility of using mixed-effects models for the derivation of kinetic modelling parameters from degradation studies, 2020-2021)</li> </ul> -<p>Thanks are due also to Emmanuelle Comets, maintainer of the saemix package, for the nice collaboration on using the SAEM algorithm and its implementation in saemix for the evaluation of chemical degradation data.</p> +<p>Thanks to everyone involved for collaboration and support!</p> +<p>Thanks are due also to Emmanuelle Comets, maintainer of the saemix package, for her interest and support for using the SAEM algorithm and its implementation in saemix for the evaluation of chemical degradation data.</p> </div> <div id="references" class="section level2"> <h2>References</h2> |