diff options
Diffstat (limited to 'docs/articles/web_only')
48 files changed, 1581 insertions, 989 deletions
diff --git a/docs/articles/web_only/FOCUS_Z.html b/docs/articles/web_only/FOCUS_Z.html index e4a6cb52..326fc121 100644 --- a/docs/articles/web_only/FOCUS_Z.html +++ b/docs/articles/web_only/FOCUS_Z.html @@ -19,6 +19,8 @@ <![endif]--> </head> <body data-spy="scroll" data-target="#toc"> + + <div class="container template-article"> <header><div class="navbar navbar-default navbar-fixed-top" role="navigation"> <div class="container"> @@ -31,7 +33,7 @@ </button> <span class="navbar-brand"> <a class="navbar-link" href="../../index.html">mkin</a> - <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.0.4</span> + <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.1.0</span> </span> </div> @@ -57,6 +59,9 @@ <a href="../../articles/FOCUS_L.html">Example evaluation of FOCUS Laboratory Data L1 to L3</a> </li> <li> + <a href="../../articles/web_only/dimethenamid_2018.html">Example evaluations of dimethenamid data from 2018 with nonlinear mixed-effects models</a> + </li> + <li> <a href="../../articles/web_only/FOCUS_Z.html">Example evaluation of FOCUS Example Dataset Z</a> </li> <li> @@ -79,7 +84,7 @@ </ul> <ul class="nav navbar-nav navbar-right"> <li> - <a href="https://github.com/jranke/mkin/"> + <a href="https://github.com/jranke/mkin/" class="external-link"> <span class="fab fa-github fa-lg"></span> </a> @@ -94,124 +99,124 @@ - </header><script src="FOCUS_Z_files/header-attrs-2.7/header-attrs.js"></script><script src="FOCUS_Z_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> + </header><script src="FOCUS_Z_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> <div class="col-md-9 contents"> <div class="page-header toc-ignore"> <h1 data-toc-skip>Example evaluation of FOCUS dataset Z</h1> - <h4 class="author">Johannes Ranke</h4> + <h4 data-toc-skip class="author">Johannes Ranke</h4> - <h4 class="date">Last change 16 January 2018 (rebuilt 2021-03-31)</h4> + <h4 data-toc-skip class="date">Last change 16 January 2018 (rebuilt 2022-03-02)</h4> - <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/web_only/FOCUS_Z.rmd"><code>vignettes/web_only/FOCUS_Z.rmd</code></a></small> + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/web_only/FOCUS_Z.rmd" class="external-link"><code>vignettes/web_only/FOCUS_Z.rmd</code></a></small> <div class="hidden name"><code>FOCUS_Z.rmd</code></div> </div> -<p><a href="http://www.jrwb.de">Wissenschaftlicher Berater, Kronacher Str. 12, 79639 Grenzach-Wyhlen, Germany</a><br><a href="http://chem.uft.uni-bremen.de/ranke">Privatdozent at the University of Bremen</a></p> -<div id="the-data" class="section level1"> -<h1 class="hasAnchor"> -<a href="#the-data" class="anchor"></a>The data</h1> +<p><a href="http://www.jrwb.de" class="external-link">Wissenschaftlicher Berater, Kronacher Str. 12, 79639 Grenzach-Wyhlen, Germany</a><br><a href="http://chem.uft.uni-bremen.de/ranke" class="external-link">Privatdozent at the University of Bremen</a></p> +<div class="section level2"> +<h2 id="the-data">The data<a class="anchor" aria-label="anchor" href="#the-data"></a> +</h2> <p>The following code defines the example dataset from Appendix 7 to the FOCUS kinetics report <span class="citation">(FOCUS Work Group on Degradation Kinetics 2014, 354)</span>.</p> <div class="sourceCode" id="cb1"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html">library</a></span><span class="op">(</span><span class="va"><a href="https://pkgdown.jrwb.de/mkin/">mkin</a></span>, quietly <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> +<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="va"><a href="https://pkgdown.jrwb.de/mkin/">mkin</a></span>, quietly <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> <span class="va">LOD</span> <span class="op">=</span> <span class="fl">0.5</span> -<span class="va">FOCUS_2006_Z</span> <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/data.frame.html">data.frame</a></span><span class="op">(</span> - t <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="fl">0.04</span>, <span class="fl">0.125</span>, <span class="fl">0.29</span>, <span class="fl">0.54</span>, <span class="fl">1</span>, <span class="fl">2</span>, <span class="fl">3</span>, <span class="fl">4</span>, <span class="fl">7</span>, <span class="fl">10</span>, <span class="fl">14</span>, <span class="fl">21</span>, +<span class="va">FOCUS_2006_Z</span> <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/data.frame.html" class="external-link">data.frame</a></span><span class="op">(</span> + t <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="fl">0.04</span>, <span class="fl">0.125</span>, <span class="fl">0.29</span>, <span class="fl">0.54</span>, <span class="fl">1</span>, <span class="fl">2</span>, <span class="fl">3</span>, <span class="fl">4</span>, <span class="fl">7</span>, <span class="fl">10</span>, <span class="fl">14</span>, <span class="fl">21</span>, <span class="fl">42</span>, <span class="fl">61</span>, <span class="fl">96</span>, <span class="fl">124</span><span class="op">)</span>, - Z0 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="fl">100</span>, <span class="fl">81.7</span>, <span class="fl">70.4</span>, <span class="fl">51.1</span>, <span class="fl">41.2</span>, <span class="fl">6.6</span>, <span class="fl">4.6</span>, <span class="fl">3.9</span>, <span class="fl">4.6</span>, <span class="fl">4.3</span>, <span class="fl">6.8</span>, + Z0 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">100</span>, <span class="fl">81.7</span>, <span class="fl">70.4</span>, <span class="fl">51.1</span>, <span class="fl">41.2</span>, <span class="fl">6.6</span>, <span class="fl">4.6</span>, <span class="fl">3.9</span>, <span class="fl">4.6</span>, <span class="fl">4.3</span>, <span class="fl">6.8</span>, <span class="fl">2.9</span>, <span class="fl">3.5</span>, <span class="fl">5.3</span>, <span class="fl">4.4</span>, <span class="fl">1.2</span>, <span class="fl">0.7</span><span class="op">)</span>, - Z1 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="fl">18.3</span>, <span class="fl">29.6</span>, <span class="fl">46.3</span>, <span class="fl">55.1</span>, <span class="fl">65.7</span>, <span class="fl">39.1</span>, <span class="fl">36</span>, <span class="fl">15.3</span>, <span class="fl">5.6</span>, <span class="fl">1.1</span>, + Z1 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="fl">18.3</span>, <span class="fl">29.6</span>, <span class="fl">46.3</span>, <span class="fl">55.1</span>, <span class="fl">65.7</span>, <span class="fl">39.1</span>, <span class="fl">36</span>, <span class="fl">15.3</span>, <span class="fl">5.6</span>, <span class="fl">1.1</span>, <span class="fl">1.6</span>, <span class="fl">0.6</span>, <span class="fl">0.5</span> <span class="op">*</span> <span class="va">LOD</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="cn">NA</span><span class="op">)</span>, - Z2 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="cn">NA</span>, <span class="fl">0.5</span> <span class="op">*</span> <span class="va">LOD</span>, <span class="fl">2.6</span>, <span class="fl">3.8</span>, <span class="fl">15.3</span>, <span class="fl">37.2</span>, <span class="fl">31.7</span>, <span class="fl">35.6</span>, <span class="fl">14.5</span>, + Z2 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="cn">NA</span>, <span class="fl">0.5</span> <span class="op">*</span> <span class="va">LOD</span>, <span class="fl">2.6</span>, <span class="fl">3.8</span>, <span class="fl">15.3</span>, <span class="fl">37.2</span>, <span class="fl">31.7</span>, <span class="fl">35.6</span>, <span class="fl">14.5</span>, <span class="fl">0.8</span>, <span class="fl">2.1</span>, <span class="fl">1.9</span>, <span class="fl">0.5</span> <span class="op">*</span> <span class="va">LOD</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="cn">NA</span><span class="op">)</span>, - Z3 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="fl">0.5</span> <span class="op">*</span> <span class="va">LOD</span>, <span class="fl">9.2</span>, <span class="fl">13.1</span>, <span class="fl">22.3</span>, <span class="fl">28.4</span>, <span class="fl">32.5</span>, + Z3 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">0</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="cn">NA</span>, <span class="fl">0.5</span> <span class="op">*</span> <span class="va">LOD</span>, <span class="fl">9.2</span>, <span class="fl">13.1</span>, <span class="fl">22.3</span>, <span class="fl">28.4</span>, <span class="fl">32.5</span>, <span class="fl">25.2</span>, <span class="fl">17.2</span>, <span class="fl">4.8</span>, <span class="fl">4.5</span>, <span class="fl">2.8</span>, <span class="fl">4.4</span><span class="op">)</span><span class="op">)</span> <span class="va">FOCUS_2006_Z_mkin</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkin_wide_to_long.html">mkin_wide_to_long</a></span><span class="op">(</span><span class="va">FOCUS_2006_Z</span><span class="op">)</span></code></pre></div> </div> -<div id="parent-and-one-metabolite" class="section level1"> -<h1 class="hasAnchor"> -<a href="#parent-and-one-metabolite" class="anchor"></a>Parent and one metabolite</h1> +<div class="section level2"> +<h2 id="parent-and-one-metabolite">Parent and one metabolite<a class="anchor" aria-label="anchor" href="#parent-and-one-metabolite"></a> +</h2> <p>The next step is to set up the models used for the kinetic analysis. As the simultaneous fit of parent and the first metabolite is usually straightforward, Step 1 (SFO for parent only) is skipped here. We start with the model 2a, with formation and decline of metabolite Z1 and the pathway from parent directly to sink included (default in mkin).</p> <div class="sourceCode" id="cb2"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">Z.2a</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>Z0 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z1"</span><span class="op">)</span>, Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb4"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.2a</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.2a</span>, <span class="va">FOCUS_2006_Z_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.2a, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with -## value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.2a, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with</span> +<span class="co">## value of zero were removed from the data</span></code></pre> <div class="sourceCode" id="cb6"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.2a</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_1-1.png" width="700"></p> <div class="sourceCode" id="cb7"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/summary.html">summary</a></span><span class="op">(</span><span class="va">m.Z.2a</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> -<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 97.01488 3.301084 29.3888 3.2971e-21 91.66556 102.3642 -## k_Z0 2.23601 0.207078 10.7979 3.3309e-11 1.95303 2.5600 -## k_Z1 0.48212 0.063265 7.6207 2.8154e-08 0.40341 0.5762 -## f_Z0_to_Z1 1.00000 0.094764 10.5525 5.3560e-11 0.00000 1.0000 -## sigma 4.80411 0.635638 7.5579 3.2592e-08 3.52677 6.0815</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.2a</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> +<pre><code><span class="co">## Estimate se_notrans t value Pr(>t) Lower Upper</span> +<span class="co">## Z0_0 97.01488 3.301084 29.3888 3.2971e-21 91.66556 102.3642</span> +<span class="co">## k_Z0 2.23601 0.207078 10.7979 3.3309e-11 1.95303 2.5600</span> +<span class="co">## k_Z1 0.48212 0.063265 7.6207 2.8154e-08 0.40341 0.5762</span> +<span class="co">## f_Z0_to_Z1 1.00000 0.094764 10.5525 5.3560e-11 0.00000 1.0000</span> +<span class="co">## sigma 4.80411 0.635638 7.5579 3.2592e-08 3.52677 6.0815</span></code></pre> <p>As obvious from the parameter summary (the component of the summary), the kinetic rate constant from parent compound Z to sink is very small and the t-test for this parameter suggests that it is not significantly different from zero. This suggests, in agreement with the analysis in the FOCUS kinetics report, to simplify the model by removing the pathway to sink.</p> <p>A similar result can be obtained when formation fractions are used in the model formulation:</p> <div class="sourceCode" id="cb9"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">Z.2a.ff</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>Z0 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z1"</span><span class="op">)</span>, Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>, use_of_ff <span class="op">=</span> <span class="st">"max"</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb11"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.2a.ff</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.2a.ff</span>, <span class="va">FOCUS_2006_Z_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.2a.ff, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with -## value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.2a.ff, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with</span> +<span class="co">## value of zero were removed from the data</span></code></pre> <div class="sourceCode" id="cb13"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.2a.ff</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_2-1.png" width="700"></p> <div class="sourceCode" id="cb14"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/summary.html">summary</a></span><span class="op">(</span><span class="va">m.Z.2a.ff</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> -<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 97.01488 3.301084 29.3888 3.2971e-21 91.66556 102.3642 -## k_Z0 2.23601 0.207078 10.7979 3.3309e-11 1.95303 2.5600 -## k_Z1 0.48212 0.063265 7.6207 2.8154e-08 0.40341 0.5762 -## f_Z0_to_Z1 1.00000 0.094764 10.5525 5.3560e-11 0.00000 1.0000 -## sigma 4.80411 0.635638 7.5579 3.2592e-08 3.52677 6.0815</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.2a.ff</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> +<pre><code><span class="co">## Estimate se_notrans t value Pr(>t) Lower Upper</span> +<span class="co">## Z0_0 97.01488 3.301084 29.3888 3.2971e-21 91.66556 102.3642</span> +<span class="co">## k_Z0 2.23601 0.207078 10.7979 3.3309e-11 1.95303 2.5600</span> +<span class="co">## k_Z1 0.48212 0.063265 7.6207 2.8154e-08 0.40341 0.5762</span> +<span class="co">## f_Z0_to_Z1 1.00000 0.094764 10.5525 5.3560e-11 0.00000 1.0000</span> +<span class="co">## sigma 4.80411 0.635638 7.5579 3.2592e-08 3.52677 6.0815</span></code></pre> <p>Here, the ilr transformed formation fraction fitted in the model takes a very large value, and the backtransformed formation fraction from parent Z to Z1 is practically unity. Here, the covariance matrix used for the calculation of confidence intervals is not returned as the model is overparameterised.</p> <p>A simplified model is obtained by removing the pathway to the sink. </p> <p>In the following, we use the parameterisation with formation fractions in order to be able to compare with the results in the FOCUS guidance, and as it makes it easier to use parameters obtained in a previous fit when adding a further metabolite.</p> <div class="sourceCode" id="cb16"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">Z.3</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>Z0 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z1"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>, use_of_ff <span class="op">=</span> <span class="st">"max"</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb18"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.3</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.3</span>, <span class="va">FOCUS_2006_Z_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.3, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with -## value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.3, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with</span> +<span class="co">## value of zero were removed from the data</span></code></pre> <div class="sourceCode" id="cb20"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.3</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_3-1.png" width="700"></p> <div class="sourceCode" id="cb21"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/summary.html">summary</a></span><span class="op">(</span><span class="va">m.Z.3</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> -<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 97.01488 2.597342 37.352 2.0106e-24 91.67597 102.3538 -## k_Z0 2.23601 0.146904 15.221 9.1477e-15 1.95354 2.5593 -## k_Z1 0.48212 0.041727 11.554 4.8268e-12 0.40355 0.5760 -## sigma 4.80411 0.620208 7.746 1.6110e-08 3.52925 6.0790</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.3</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> +<pre><code><span class="co">## Estimate se_notrans t value Pr(>t) Lower Upper</span> +<span class="co">## Z0_0 97.01488 2.597342 37.352 2.0106e-24 91.67597 102.3538</span> +<span class="co">## k_Z0 2.23601 0.146904 15.221 9.1477e-15 1.95354 2.5593</span> +<span class="co">## k_Z1 0.48212 0.041727 11.554 4.8268e-12 0.40355 0.5760</span> +<span class="co">## sigma 4.80411 0.620208 7.746 1.6110e-08 3.52925 6.0790</span></code></pre> <p>As there is only one transformation product for Z0 and no pathway to sink, the formation fraction is internally fixed to unity.</p> </div> -<div id="metabolites-z2-and-z3" class="section level1"> -<h1 class="hasAnchor"> -<a href="#metabolites-z2-and-z3" class="anchor"></a>Metabolites Z2 and Z3</h1> +<div class="section level2"> +<h2 id="metabolites-z2-and-z3">Metabolites Z2 and Z3<a class="anchor" aria-label="anchor" href="#metabolites-z2-and-z3"></a> +</h2> <p>As suggested in the FOCUS report, the pathway to sink was removed for metabolite Z1 as well in the next step. While this step appears questionable on the basis of the above results, it is followed here for the purpose of comparison. Also, in the FOCUS report, it is assumed that there is additional empirical evidence that Z1 quickly and exclusively hydrolyses to Z2.</p> <div class="sourceCode" id="cb23"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">Z.5</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>Z0 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z1"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z2"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>, use_of_ff <span class="op">=</span> <span class="st">"max"</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb25"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.5</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.5</span>, <span class="va">FOCUS_2006_Z_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.5, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with -## value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.5, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with</span> +<span class="co">## value of zero were removed from the data</span></code></pre> <div class="sourceCode" id="cb27"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.5</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_5-1.png" width="700"></p> @@ -222,45 +227,45 @@ Z2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z3"</span><span class="op">)</span>, Z3 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>, use_of_ff <span class="op">=</span> <span class="st">"max"</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb30"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.FOCUS</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.FOCUS</span>, <span class="va">FOCUS_2006_Z_mkin</span>, parms.ini <span class="op">=</span> <span class="va">m.Z.5</span><span class="op">$</span><span class="va">bparms.ode</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.FOCUS, FOCUS_2006_Z_mkin, parms.ini = m.Z.5$bparms.ode, : -## Observations with value of zero were removed from the data</code></pre> -<pre><code>## Warning in mkinfit(Z.FOCUS, FOCUS_2006_Z_mkin, parms.ini = m.Z.5$bparms.ode, : Optimisation did not converge: -## false convergence (8)</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.FOCUS, FOCUS_2006_Z_mkin, parms.ini = m.Z.5$bparms.ode, :</span> +<span class="co">## Observations with value of zero were removed from the data</span></code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.FOCUS, FOCUS_2006_Z_mkin, parms.ini = m.Z.5$bparms.ode, : Optimisation did not converge:</span> +<span class="co">## false convergence (8)</span></code></pre> <div class="sourceCode" id="cb33"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.FOCUS</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_6-1.png" width="700"></p> <div class="sourceCode" id="cb34"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/summary.html">summary</a></span><span class="op">(</span><span class="va">m.Z.FOCUS</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> -<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 96.838822 1.994274 48.5584 4.0280e-42 92.826981 100.850664 -## k_Z0 2.215393 0.118458 18.7019 1.0413e-23 1.989456 2.466989 -## k_Z1 0.478305 0.028258 16.9266 6.2418e-22 0.424708 0.538666 -## k_Z2 0.451627 0.042139 10.7176 1.6314e-14 0.374339 0.544872 -## k_Z3 0.058692 0.015245 3.8499 1.7803e-04 0.034808 0.098965 -## f_Z2_to_Z3 0.471502 0.058351 8.0805 9.6608e-11 0.357769 0.588274 -## sigma 3.984431 0.383402 10.3923 4.5575e-14 3.213126 4.755736</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.FOCUS</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div> +<pre><code><span class="co">## Estimate se_notrans t value Pr(>t) Lower Upper</span> +<span class="co">## Z0_0 96.838822 1.994274 48.5584 4.0280e-42 92.826981 100.850664</span> +<span class="co">## k_Z0 2.215393 0.118458 18.7019 1.0413e-23 1.989456 2.466989</span> +<span class="co">## k_Z1 0.478305 0.028258 16.9266 6.2418e-22 0.424708 0.538666</span> +<span class="co">## k_Z2 0.451627 0.042139 10.7176 1.6314e-14 0.374339 0.544872</span> +<span class="co">## k_Z3 0.058692 0.015245 3.8499 1.7803e-04 0.034808 0.098965</span> +<span class="co">## f_Z2_to_Z3 0.471502 0.058351 8.0805 9.6608e-11 0.357769 0.588274</span> +<span class="co">## sigma 3.984431 0.383402 10.3923 4.5575e-14 3.213126 4.755736</span></code></pre> <div class="sourceCode" id="cb36"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/endpoints.html">endpoints</a></span><span class="op">(</span><span class="va">m.Z.FOCUS</span><span class="op">)</span></code></pre></div> -<pre><code>## $ff -## Z2_Z3 Z2_sink -## 0.4715 0.5285 -## -## $distimes -## DT50 DT90 -## Z0 0.31288 1.0394 -## Z1 1.44917 4.8141 -## Z2 1.53478 5.0984 -## Z3 11.80986 39.2315</code></pre> +<pre><code><span class="co">## $ff</span> +<span class="co">## Z2_Z3 Z2_sink </span> +<span class="co">## 0.4715 0.5285 </span> +<span class="co">## </span> +<span class="co">## $distimes</span> +<span class="co">## DT50 DT90</span> +<span class="co">## Z0 0.31288 1.0394</span> +<span class="co">## Z1 1.44917 4.8141</span> +<span class="co">## Z2 1.53478 5.0984</span> +<span class="co">## Z3 11.80986 39.2315</span></code></pre> <p>This fit corresponds to the final result chosen in Appendix 7 of the FOCUS report. Confidence intervals returned by mkin are based on internally transformed parameters, however.</p> </div> -<div id="using-the-sforb-model" class="section level1"> -<h1 class="hasAnchor"> -<a href="#using-the-sforb-model" class="anchor"></a>Using the SFORB model</h1> +<div class="section level2"> +<h2 id="using-the-sforb-model">Using the SFORB model<a class="anchor" aria-label="anchor" href="#using-the-sforb-model"></a> +</h2> <p>As the FOCUS report states, there is a certain tailing of the time course of metabolite Z3. Also, the time course of the parent compound is not fitted very well using the SFO model, as residues at a certain low level remain.</p> <p>Therefore, an additional model is offered here, using the single first-order reversible binding (SFORB) model for metabolite Z3. As expected, the <span class="math inline">\(\chi^2\)</span> error level is lower for metabolite Z3 using this model and the graphical fit for Z3 is improved. However, the covariance matrix is not returned.</p> <div class="sourceCode" id="cb38"><pre class="downlit sourceCode r"> @@ -268,27 +273,27 @@ Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z2"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z3"</span><span class="op">)</span>, Z3 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFORB"</span><span class="op">)</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb40"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.mkin.1</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.mkin.1</span>, <span class="va">FOCUS_2006_Z_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.mkin.1, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with -## value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.mkin.1, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with</span> +<span class="co">## value of zero were removed from the data</span></code></pre> <div class="sourceCode" id="cb42"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.mkin.1</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_7-1.png" width="700"></p> <div class="sourceCode" id="cb43"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/summary.html">summary</a></span><span class="op">(</span><span class="va">m.Z.mkin.1</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">cov.unscaled</span></code></pre></div> -<pre><code>## NULL</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.mkin.1</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">cov.unscaled</span></code></pre></div> +<pre><code><span class="co">## NULL</span></code></pre> <p>Therefore, a further stepwise model building is performed starting from the stage of parent and two metabolites, starting from the assumption that the model fit for the parent compound can be improved by using the SFORB model.</p> <div class="sourceCode" id="cb45"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">Z.mkin.3</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>Z0 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFORB"</span>, <span class="st">"Z1"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z2"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb47"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.mkin.3</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.mkin.3</span>, <span class="va">FOCUS_2006_Z_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.mkin.3, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with -## value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.mkin.3, FOCUS_2006_Z_mkin, quiet = TRUE): Observations with</span> +<span class="co">## value of zero were removed from the data</span></code></pre> <div class="sourceCode" id="cb49"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.mkin.3</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_9-1.png" width="700"></p> @@ -299,13 +304,14 @@ Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z2"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z3"</span><span class="op">)</span>, Z3 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb52"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.mkin.4</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.mkin.4</span>, <span class="va">FOCUS_2006_Z_mkin</span>, parms.ini <span class="op">=</span> <span class="va">m.Z.mkin.3</span><span class="op">$</span><span class="va">bparms.ode</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.mkin.4, FOCUS_2006_Z_mkin, parms.ini = m.Z.mkin. -## 3$bparms.ode, : Observations with value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.mkin.4, FOCUS_2006_Z_mkin, parms.ini =</span> +<span class="co">## m.Z.mkin.3$bparms.ode, : Observations with value of zero were removed from the</span> +<span class="co">## data</span></code></pre> <div class="sourceCode" id="cb54"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.mkin.4</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_10-1.png" width="700"></p> @@ -315,25 +321,27 @@ Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z2"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>, Z2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z3"</span><span class="op">)</span>, Z3 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFORB"</span><span class="op">)</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb57"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.mkin.5</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.mkin.5</span>, <span class="va">FOCUS_2006_Z_mkin</span>, parms.ini <span class="op">=</span> <span class="va">m.Z.mkin.4</span><span class="op">$</span><span class="va">bparms.ode</span><span class="op">[</span><span class="fl">1</span><span class="op">:</span><span class="fl">4</span><span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.mkin.5, FOCUS_2006_Z_mkin, parms.ini = m.Z.mkin. -## 4$bparms.ode[1:4], : Observations with value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.mkin.5, FOCUS_2006_Z_mkin, parms.ini =</span> +<span class="co">## m.Z.mkin.4$bparms.ode[1:4], : Observations with value of zero were removed from</span> +<span class="co">## the data</span></code></pre> <div class="sourceCode" id="cb59"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.mkin.5</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11-1.png" width="700"></p> <p>The summary view of the backtransformed parameters shows that we get no confidence intervals due to overparameterisation. As the optimized is excessively small, it seems reasonable to fix it to zero.</p> <div class="sourceCode" id="cb60"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">m.Z.mkin.5a</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.mkin.5</span>, <span class="va">FOCUS_2006_Z_mkin</span>, - parms.ini <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="va">m.Z.mkin.5</span><span class="op">$</span><span class="va">bparms.ode</span><span class="op">[</span><span class="fl">1</span><span class="op">:</span><span class="fl">7</span><span class="op">]</span>, + parms.ini <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="va">m.Z.mkin.5</span><span class="op">$</span><span class="va">bparms.ode</span><span class="op">[</span><span class="fl">1</span><span class="op">:</span><span class="fl">7</span><span class="op">]</span>, k_Z3_bound_free <span class="op">=</span> <span class="fl">0</span><span class="op">)</span>, fixed_parms <span class="op">=</span> <span class="st">"k_Z3_bound_free"</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in mkinfit(Z.mkin.5, FOCUS_2006_Z_mkin, parms.ini = c(m.Z.mkin. -## 5$bparms.ode[1:7], : Observations with value of zero were removed from the data</code></pre> +<pre><code><span class="co">## Warning in mkinfit(Z.mkin.5, FOCUS_2006_Z_mkin, parms.ini =</span> +<span class="co">## c(m.Z.mkin.5$bparms.ode[1:7], : Observations with value of zero were removed</span> +<span class="co">## from the data</span></code></pre> <div class="sourceCode" id="cb62"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.mkin.5a</span><span class="op">)</span></code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11a-1.png" width="700"></p> @@ -345,29 +353,29 @@ <p>The endpoints obtained with this model are</p> <div class="sourceCode" id="cb64"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="fu"><a href="../../reference/endpoints.html">endpoints</a></span><span class="op">(</span><span class="va">m.Z.mkin.5a</span><span class="op">)</span></code></pre></div> -<pre><code>## $ff -## Z0_free Z2_Z3 Z2_sink Z3_free -## 1.00000 0.53656 0.46344 1.00000 -## -## $SFORB -## Z0_b1 Z0_b2 Z3_b1 Z3_b2 -## 2.4471322 0.0075125 0.0800069 0.0000000 -## -## $distimes -## DT50 DT90 DT50back DT50_Z0_b1 DT50_Z0_b2 DT50_Z3_b1 DT50_Z3_b2 -## Z0 0.3043 1.1848 0.35666 0.28325 92.266 NA NA -## Z1 1.5148 5.0320 NA NA NA NA NA -## Z2 1.6414 5.4526 NA NA NA NA NA -## Z3 NA NA NA NA NA 8.6636 Inf</code></pre> +<pre><code><span class="co">## $ff</span> +<span class="co">## Z0_free Z2_Z3 Z2_sink Z3_free </span> +<span class="co">## 1.00000 0.53656 0.46344 1.00000 </span> +<span class="co">## </span> +<span class="co">## $SFORB</span> +<span class="co">## Z0_b1 Z0_b2 Z3_b1 Z3_b2 </span> +<span class="co">## 2.4471322 0.0075125 0.0800069 0.0000000 </span> +<span class="co">## </span> +<span class="co">## $distimes</span> +<span class="co">## DT50 DT90 DT50back DT50_Z0_b1 DT50_Z0_b2 DT50_Z3_b1 DT50_Z3_b2</span> +<span class="co">## Z0 0.3043 1.1848 0.35666 0.28325 92.266 NA NA</span> +<span class="co">## Z1 1.5148 5.0320 NA NA NA NA NA</span> +<span class="co">## Z2 1.6414 5.4526 NA NA NA NA NA</span> +<span class="co">## Z3 NA NA NA NA NA 8.6636 Inf</span></code></pre> <p>It is clear the degradation rate of Z3 towards the end of the experiment is very low as DT50_Z3_b2 (the second Eigenvalue of the system of two differential equations representing the SFORB system for Z3, corresponding to the slower rate constant of the DFOP model) is reported to be infinity. However, this appears to be a feature of the data.</p> </div> -<div id="references" class="section level1"> -<h1 class="hasAnchor"> -<a href="#references" class="anchor"></a>References</h1> +<div class="section level2"> +<h2 id="references">References<a class="anchor" aria-label="anchor" href="#references"></a> +</h2> <!-- vim: set foldmethod=syntax: --> <div id="refs" class="references hanging-indent"> <div id="ref-FOCUSkinetics2014"> -<p>FOCUS Work Group on Degradation Kinetics. 2014. <em>Generic Guidance for Estimating Persistence and Degradation Kinetics from Environmental Fate Studies on Pesticides in Eu Registration</em>. 1.1 ed. <a href="http://esdac.jrc.ec.europa.eu/projects/degradation-kinetics">http://esdac.jrc.ec.europa.eu/projects/degradation-kinetics</a>.</p> +<p>FOCUS Work Group on Degradation Kinetics. 2014. <em>Generic Guidance for Estimating Persistence and Degradation Kinetics from Environmental Fate Studies on Pesticides in Eu Registration</em>. 1.1 ed. <a href="http://esdac.jrc.ec.europa.eu/projects/degradation-kinetics" class="external-link">http://esdac.jrc.ec.europa.eu/projects/degradation-kinetics</a>.</p> </div> </div> </div> @@ -384,11 +392,13 @@ <footer><div class="copyright"> - <p>Developed by Johannes Ranke.</p> + <p></p> +<p>Developed by Johannes Ranke.</p> </div> <div class="pkgdown"> - <p>Site built with <a href="https://pkgdown.r-lib.org/">pkgdown</a> 1.6.1.</p> + <p></p> +<p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.2.</p> </div> </footer> @@ -397,5 +407,7 @@ + + </body> </html> diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_1-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_1-1.png Binary files differindex 2e70b207..be652d31 100644 --- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_1-1.png +++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_1-1.png diff --git 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b/docs/articles/web_only/NAFTA_examples.html index 65a71b56..996e5d49 100644 --- a/docs/articles/web_only/NAFTA_examples.html +++ b/docs/articles/web_only/NAFTA_examples.html @@ -19,6 +19,8 @@ <![endif]--> </head> <body data-spy="scroll" data-target="#toc"> + + <div class="container template-article"> <header><div class="navbar navbar-default navbar-fixed-top" role="navigation"> <div class="container"> @@ -31,7 +33,7 @@ </button> <span class="navbar-brand"> <a class="navbar-link" href="../../index.html">mkin</a> - <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.0.4</span> + <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.1.0</span> </span> </div> @@ -57,6 +59,9 @@ <a href="../../articles/FOCUS_L.html">Example evaluation of FOCUS Laboratory Data L1 to L3</a> </li> <li> + <a href="../../articles/web_only/dimethenamid_2018.html">Example evaluations of dimethenamid data from 2018 with nonlinear mixed-effects models</a> + </li> + <li> <a href="../../articles/web_only/FOCUS_Z.html">Example evaluation of FOCUS Example Dataset Z</a> </li> <li> @@ -79,7 +84,7 @@ </ul> <ul class="nav navbar-nav navbar-right"> <li> - <a href="https://github.com/jranke/mkin/"> + <a href="https://github.com/jranke/mkin/" class="external-link"> <span class="fab fa-github fa-lg"></span> </a> @@ -94,908 +99,908 @@ - </header><script src="NAFTA_examples_files/header-attrs-2.7/header-attrs.js"></script><script src="NAFTA_examples_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> + </header><script src="NAFTA_examples_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> <div class="col-md-9 contents"> <div class="page-header toc-ignore"> <h1 data-toc-skip>Evaluation of example datasets from Attachment 1 to the US EPA SOP for the NAFTA guidance</h1> - <h4 class="author">Johannes Ranke</h4> + <h4 data-toc-skip class="author">Johannes Ranke</h4> - <h4 class="date">26 February 2019 (rebuilt 2021-03-31)</h4> + <h4 data-toc-skip class="date">26 February 2019 (rebuilt 2022-03-02)</h4> - <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/web_only/NAFTA_examples.rmd"><code>vignettes/web_only/NAFTA_examples.rmd</code></a></small> + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/web_only/NAFTA_examples.rmd" class="external-link"><code>vignettes/web_only/NAFTA_examples.rmd</code></a></small> <div class="hidden name"><code>NAFTA_examples.rmd</code></div> </div> -<div id="introduction" class="section level1"> -<h1 class="hasAnchor"> -<a href="#introduction" class="anchor"></a>Introduction</h1> +<div class="section level2"> +<h2 id="introduction">Introduction<a class="anchor" aria-label="anchor" href="#introduction"></a> +</h2> <p>In this document, the example evaluations provided in Attachment 1 to the SOP of US EPA for using the NAFTA guidance <span class="citation">(US EPA 2015)</span> are repeated using mkin. The original evaluations reported in the attachment were performed using PestDF in version 0.8.4. Note that PestDF 0.8.13 is the version distributed at the US EPA website today (2019-02-26).</p> <p>The datasets are now distributed with the mkin package.</p> </div> -<div id="examples-where-dfop-did-not-converge-with-pestdf-0-8-4" class="section level1"> -<h1 class="hasAnchor"> -<a href="#examples-where-dfop-did-not-converge-with-pestdf-0-8-4" class="anchor"></a>Examples where DFOP did not converge with PestDF 0.8.4</h1> +<div class="section level2"> +<h2 id="examples-where-dfop-did-not-converge-with-pestdf-0-8-4">Examples where DFOP did not converge with PestDF 0.8.4<a class="anchor" aria-label="anchor" href="#examples-where-dfop-did-not-converge-with-pestdf-0-8-4"></a> +</h2> <p>In attachment 1, it is reported that the DFOP model does not converge for these datasets when PestDF 0.8.4 was used. For all four datasets, the DFOP model can be fitted with mkin (see below). The negative half-life given by PestDF 0.8.4 for these fits appears to be the result of a bug. The results for the other two models (SFO and IORE) are the same.</p> -<div id="example-on-page-5-upper-panel" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-5-upper-panel" class="anchor"></a>Example on page 5, upper panel</h2> +<div class="section level3"> +<h3 id="example-on-page-5-upper-panel">Example on page 5, upper panel<a class="anchor" aria-label="anchor" href="#example-on-page-5-upper-panel"></a> +</h3> <div class="sourceCode" id="cb1"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p5a</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p5a"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb4"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p5a</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p5a</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p5a-1.png" width="700"></p> <div class="sourceCode" id="cb5"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p5a</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 465.21753 56.27506 32.06401 -## -## Critical sum of squares for checking the SFO model: -## [1] 64.4304 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 95.8401 4.67e-21 92.245 99.4357 -## k_parent 0.0102 3.92e-12 0.009 0.0117 -## sigma 4.8230 3.81e-06 3.214 6.4318 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 1.01e+02 NA 9.91e+01 1.02e+02 -## k__iore_parent 1.54e-05 NA 4.08e-06 5.84e-05 -## N_parent 2.57e+00 NA 2.25e+00 2.89e+00 -## sigma 1.68e+00 NA 1.12e+00 2.24e+00 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 9.99e+01 1.41e-26 98.8116 101.0810 -## k1 2.67e-02 5.05e-06 0.0243 0.0295 -## k2 2.26e-12 5.00e-01 0.0000 Inf -## g 6.47e-01 3.67e-06 0.6248 0.6677 -## sigma 1.27e+00 8.91e-06 0.8395 1.6929 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 67.7 2.25e+02 6.77e+01 -## IORE 58.2 1.07e+03 3.22e+02 -## DFOP 55.5 5.59e+11 3.07e+11 -## -## Representative half-life: -## [1] 321.51</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p5a</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 465.21753 56.27506 32.06401 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 64.4304</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 95.8401 4.67e-21 92.245 99.4357</span> +<span class="co">## k_parent 0.0102 3.92e-12 0.009 0.0117</span> +<span class="co">## sigma 4.8230 3.81e-06 3.214 6.4318</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 1.01e+02 NA 9.91e+01 1.02e+02</span> +<span class="co">## k__iore_parent 1.54e-05 NA 4.08e-06 5.84e-05</span> +<span class="co">## N_parent 2.57e+00 NA 2.25e+00 2.89e+00</span> +<span class="co">## sigma 1.68e+00 NA 1.12e+00 2.24e+00</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.99e+01 1.41e-26 98.8116 101.0810</span> +<span class="co">## k1 2.67e-02 5.05e-06 0.0243 0.0295</span> +<span class="co">## k2 2.26e-12 5.00e-01 0.0000 Inf</span> +<span class="co">## g 6.47e-01 3.67e-06 0.6248 0.6677</span> +<span class="co">## sigma 1.27e+00 8.91e-06 0.8395 1.6929</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 67.7 2.25e+02 6.77e+01</span> +<span class="co">## IORE 58.2 1.07e+03 3.22e+02</span> +<span class="co">## DFOP 55.5 5.59e+11 3.07e+11</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 321.51</span></code></pre> </div> -<div id="example-on-page-5-lower-panel" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-5-lower-panel" class="anchor"></a>Example on page 5, lower panel</h2> +<div class="section level3"> +<h3 id="example-on-page-5-lower-panel">Example on page 5, lower panel<a class="anchor" aria-label="anchor" href="#example-on-page-5-lower-panel"></a> +</h3> <div class="sourceCode" id="cb7"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p5b</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p5b"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb10"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p5b</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p5b</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p5b-1.png" width="700"></p> <div class="sourceCode" id="cb11"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p5b</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 94.81123 10.10936 7.55871 -## -## Critical sum of squares for checking the SFO model: -## [1] 11.77879 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 96.497 2.32e-24 94.85271 98.14155 -## k_parent 0.008 3.42e-14 0.00737 0.00869 -## sigma 2.295 1.22e-05 1.47976 3.11036 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 9.85e+01 1.17e-28 9.79e+01 9.92e+01 -## k__iore_parent 1.53e-04 6.50e-03 7.21e-05 3.26e-04 -## N_parent 1.94e+00 5.88e-13 1.76e+00 2.12e+00 -## sigma 7.49e-01 1.63e-05 4.82e-01 1.02e+00 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 9.84e+01 1.24e-27 97.8078 98.9187 -## k1 1.55e-02 4.10e-04 0.0143 0.0167 -## k2 8.63e-12 5.00e-01 0.0000 Inf -## g 6.89e-01 2.92e-03 0.6626 0.7142 -## sigma 6.48e-01 2.38e-05 0.4147 0.8813 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 86.6 2.88e+02 8.66e+01 -## IORE 85.5 7.17e+02 2.16e+02 -## DFOP 83.6 1.32e+11 8.04e+10 -## -## Representative half-life: -## [1] 215.87</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p5b</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 94.81123 10.10936 7.55871 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 11.77879</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 96.497 2.32e-24 94.85271 98.14155</span> +<span class="co">## k_parent 0.008 3.42e-14 0.00737 0.00869</span> +<span class="co">## sigma 2.295 1.22e-05 1.47976 3.11036</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.85e+01 1.17e-28 9.79e+01 9.92e+01</span> +<span class="co">## k__iore_parent 1.53e-04 6.50e-03 7.21e-05 3.26e-04</span> +<span class="co">## N_parent 1.94e+00 5.88e-13 1.76e+00 2.12e+00</span> +<span class="co">## sigma 7.49e-01 1.63e-05 4.82e-01 1.02e+00</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.84e+01 1.24e-27 97.8078 98.9187</span> +<span class="co">## k1 1.55e-02 4.10e-04 0.0143 0.0167</span> +<span class="co">## k2 8.63e-12 5.00e-01 0.0000 Inf</span> +<span class="co">## g 6.89e-01 2.92e-03 0.6626 0.7142</span> +<span class="co">## sigma 6.48e-01 2.38e-05 0.4147 0.8813</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 86.6 2.88e+02 8.66e+01</span> +<span class="co">## IORE 85.5 7.17e+02 2.16e+02</span> +<span class="co">## DFOP 83.6 1.32e+11 8.04e+10</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 215.87</span></code></pre> </div> -<div id="example-on-page-6" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-6" class="anchor"></a>Example on page 6</h2> +<div class="section level3"> +<h3 id="example-on-page-6">Example on page 6<a class="anchor" aria-label="anchor" href="#example-on-page-6"></a> +</h3> <div class="sourceCode" id="cb13"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p6</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p6"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb16"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p6</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p6</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p6-1.png" width="700"></p> <div class="sourceCode" id="cb17"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p6</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 188.45361 51.00699 42.46931 -## -## Critical sum of squares for checking the SFO model: -## [1] 58.39888 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 94.7759 7.29e-24 92.3478 97.2039 -## k_parent 0.0179 8.02e-16 0.0166 0.0194 -## sigma 3.0696 3.81e-06 2.0456 4.0936 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 97.12446 2.63e-26 95.62461 98.62431 -## k__iore_parent 0.00252 1.95e-03 0.00134 0.00472 -## N_parent 1.49587 4.07e-13 1.33896 1.65279 -## sigma 1.59698 5.05e-06 1.06169 2.13227 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 9.66e+01 1.57e-25 95.3476 97.8979 -## k1 2.55e-02 7.33e-06 0.0233 0.0278 -## k2 3.22e-11 5.00e-01 0.0000 Inf -## g 8.61e-01 7.55e-06 0.8314 0.8867 -## sigma 1.46e+00 6.93e-06 0.9661 1.9483 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 38.6 1.28e+02 3.86e+01 -## IORE 34.0 1.77e+02 5.32e+01 -## DFOP 34.1 1.01e+10 2.15e+10 -## -## Representative half-life: -## [1] 53.17</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p6</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 188.45361 51.00699 42.46931 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 58.39888</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 94.7759 7.29e-24 92.3478 97.2039</span> +<span class="co">## k_parent 0.0179 8.02e-16 0.0166 0.0194</span> +<span class="co">## sigma 3.0696 3.81e-06 2.0456 4.0936</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 97.12446 2.63e-26 95.62461 98.62431</span> +<span class="co">## k__iore_parent 0.00252 1.95e-03 0.00134 0.00472</span> +<span class="co">## N_parent 1.49587 4.07e-13 1.33896 1.65279</span> +<span class="co">## sigma 1.59698 5.05e-06 1.06169 2.13227</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.66e+01 1.57e-25 95.3476 97.8979</span> +<span class="co">## k1 2.55e-02 7.33e-06 0.0233 0.0278</span> +<span class="co">## k2 3.22e-11 5.00e-01 0.0000 Inf</span> +<span class="co">## g 8.61e-01 7.55e-06 0.8314 0.8867</span> +<span class="co">## sigma 1.46e+00 6.93e-06 0.9661 1.9483</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 38.6 1.28e+02 3.86e+01</span> +<span class="co">## IORE 34.0 1.77e+02 5.32e+01</span> +<span class="co">## DFOP 34.1 1.01e+10 2.15e+10</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 53.17</span></code></pre> </div> -<div id="example-on-page-7" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-7" class="anchor"></a>Example on page 7</h2> +<div class="section level3"> +<h3 id="example-on-page-7">Example on page 7<a class="anchor" aria-label="anchor" href="#example-on-page-7"></a> +</h3> <div class="sourceCode" id="cb19"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p7</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p7"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb22"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p7</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p7</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p7-1.png" width="700"></p> <div class="sourceCode" id="cb23"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p7</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 3661.661 3195.030 3174.145 -## -## Critical sum of squares for checking the SFO model: -## [1] 3334.194 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 96.41796 4.80e-53 93.32245 99.51347 -## k_parent 0.00735 7.64e-21 0.00641 0.00843 -## sigma 7.94557 1.83e-15 6.46713 9.42401 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 9.92e+01 NA 9.55e+01 1.03e+02 -## k__iore_parent 1.60e-05 NA 1.45e-07 1.77e-03 -## N_parent 2.45e+00 NA 1.35e+00 3.54e+00 -## sigma 7.42e+00 NA 6.04e+00 8.80e+00 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 9.89e+01 9.44e-49 95.4640 102.2573 -## k1 1.81e-02 1.75e-01 0.0116 0.0281 -## k2 3.63e-10 5.00e-01 0.0000 Inf -## g 6.06e-01 2.19e-01 0.4826 0.7178 -## sigma 7.40e+00 2.97e-15 6.0201 8.7754 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 94.3 3.13e+02 9.43e+01 -## IORE 96.7 1.51e+03 4.55e+02 -## DFOP 96.4 3.77e+09 1.91e+09 -## -## Representative half-life: -## [1] 454.55</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p7</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 3661.661 3195.030 3174.145 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 3334.194</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 96.41796 4.80e-53 93.32245 99.51347</span> +<span class="co">## k_parent 0.00735 7.64e-21 0.00641 0.00843</span> +<span class="co">## sigma 7.94557 1.83e-15 6.46713 9.42401</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.92e+01 NA 9.55e+01 1.03e+02</span> +<span class="co">## k__iore_parent 1.60e-05 NA 1.45e-07 1.77e-03</span> +<span class="co">## N_parent 2.45e+00 NA 1.35e+00 3.54e+00</span> +<span class="co">## sigma 7.42e+00 NA 6.04e+00 8.80e+00</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.89e+01 9.44e-49 95.4640 102.2573</span> +<span class="co">## k1 1.81e-02 1.75e-01 0.0116 0.0281</span> +<span class="co">## k2 3.63e-10 5.00e-01 0.0000 Inf</span> +<span class="co">## g 6.06e-01 2.19e-01 0.4826 0.7178</span> +<span class="co">## sigma 7.40e+00 2.97e-15 6.0201 8.7754</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 94.3 3.13e+02 9.43e+01</span> +<span class="co">## IORE 96.7 1.51e+03 4.55e+02</span> +<span class="co">## DFOP 96.4 3.77e+09 1.91e+09</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 454.55</span></code></pre> </div> </div> -<div id="examples-where-the-representative-half-life-deviates-from-the-observed-dt50" class="section level1"> -<h1 class="hasAnchor"> -<a href="#examples-where-the-representative-half-life-deviates-from-the-observed-dt50" class="anchor"></a>Examples where the representative half-life deviates from the observed DT50</h1> -<div id="example-on-page-8" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-8" class="anchor"></a>Example on page 8</h2> +<div class="section level2"> +<h2 id="examples-where-the-representative-half-life-deviates-from-the-observed-dt50">Examples where the representative half-life deviates from the observed DT50<a class="anchor" aria-label="anchor" href="#examples-where-the-representative-half-life-deviates-from-the-observed-dt50"></a> +</h2> +<div class="section level3"> +<h3 id="example-on-page-8">Example on page 8<a class="anchor" aria-label="anchor" href="#example-on-page-8"></a> +</h3> <p>For this dataset, the IORE fit does not converge when the default starting values used by mkin for the IORE model are used. Therefore, a lower value for the rate constant is used here.</p> <div class="sourceCode" id="cb25"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="va">p8</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p8"</span><span class="op">]</span><span class="op">]</span>, parms.ini <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span>k__iore_parent <span class="op">=</span> <span class="fl">1e-3</span><span class="op">)</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<code class="sourceCode R"><span class="va">p8</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p8"</span><span class="op">]</span><span class="op">]</span>, parms.ini <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span>k__iore_parent <span class="op">=</span> <span class="fl">1e-3</span><span class="op">)</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb28"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p8</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p8</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p8-1.png" width="700"></p> <div class="sourceCode" id="cb29"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p8</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 1996.9408 444.9237 547.5616 -## -## Critical sum of squares for checking the SFO model: -## [1] 477.4924 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 88.16549 6.53e-29 83.37344 92.95754 -## k_parent 0.00803 1.67e-13 0.00674 0.00957 -## sigma 7.44786 4.17e-10 5.66209 9.23363 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 9.77e+01 7.03e-35 9.44e+01 1.01e+02 -## k__iore_parent 6.14e-05 3.20e-02 2.12e-05 1.78e-04 -## N_parent 2.27e+00 4.23e-18 2.00e+00 2.54e+00 -## sigma 3.52e+00 5.36e-10 2.67e+00 4.36e+00 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 95.70619 8.99e-32 91.87941 99.53298 -## k1 0.02500 5.25e-04 0.01422 0.04394 -## k2 0.00273 6.84e-03 0.00125 0.00597 -## g 0.58835 2.84e-06 0.36595 0.77970 -## sigma 3.90001 6.94e-10 2.96260 4.83741 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 86.3 287 86.3 -## IORE 53.4 668 201.0 -## DFOP 55.6 517 253.0 -## -## Representative half-life: -## [1] 201.03</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p8</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 1996.9408 444.9237 547.5616 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 477.4924</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 88.16549 6.53e-29 83.37344 92.95754</span> +<span class="co">## k_parent 0.00803 1.67e-13 0.00674 0.00957</span> +<span class="co">## sigma 7.44786 4.17e-10 5.66209 9.23363</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.77e+01 7.03e-35 9.44e+01 1.01e+02</span> +<span class="co">## k__iore_parent 6.14e-05 3.20e-02 2.12e-05 1.78e-04</span> +<span class="co">## N_parent 2.27e+00 4.23e-18 2.00e+00 2.54e+00</span> +<span class="co">## sigma 3.52e+00 5.36e-10 2.67e+00 4.36e+00</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 95.70619 8.99e-32 91.87941 99.53298</span> +<span class="co">## k1 0.02500 5.25e-04 0.01422 0.04394</span> +<span class="co">## k2 0.00273 6.84e-03 0.00125 0.00597</span> +<span class="co">## g 0.58835 2.84e-06 0.36595 0.77970</span> +<span class="co">## sigma 3.90001 6.94e-10 2.96260 4.83741</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 86.3 287 86.3</span> +<span class="co">## IORE 53.4 668 201.0</span> +<span class="co">## DFOP 55.6 517 253.0</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 201.03</span></code></pre> </div> </div> -<div id="examples-where-sfo-was-not-selected-for-an-abiotic-study" class="section level1"> -<h1 class="hasAnchor"> -<a href="#examples-where-sfo-was-not-selected-for-an-abiotic-study" class="anchor"></a>Examples where SFO was not selected for an abiotic study</h1> -<div id="example-on-page-9-upper-panel" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-9-upper-panel" class="anchor"></a>Example on page 9, upper panel</h2> +<div class="section level2"> +<h2 id="examples-where-sfo-was-not-selected-for-an-abiotic-study">Examples where SFO was not selected for an abiotic study<a class="anchor" aria-label="anchor" href="#examples-where-sfo-was-not-selected-for-an-abiotic-study"></a> +</h2> +<div class="section level3"> +<h3 id="example-on-page-9-upper-panel">Example on page 9, upper panel<a class="anchor" aria-label="anchor" href="#example-on-page-9-upper-panel"></a> +</h3> <div class="sourceCode" id="cb31"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p9a</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p9a"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb34"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p9a</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p9a</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p9a-1.png" width="700"></p> <div class="sourceCode" id="cb35"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p9a</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 839.35238 88.57064 9.93363 -## -## Critical sum of squares for checking the SFO model: -## [1] 105.5678 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 88.1933 3.06e-12 79.9447 96.4419 -## k_parent 0.0409 2.07e-07 0.0324 0.0516 -## sigma 7.2429 3.92e-05 4.4768 10.0090 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 9.89e+01 1.12e-16 9.54e+01 1.02e+02 -## k__iore_parent 1.93e-05 1.13e-01 3.49e-06 1.06e-04 -## N_parent 2.91e+00 1.45e-09 2.50e+00 3.32e+00 -## sigma 2.35e+00 5.31e-05 1.45e+00 3.26e+00 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 9.85e+01 2.54e-20 97.390 99.672 -## k1 1.38e-01 3.52e-05 0.131 0.146 -## k2 9.02e-13 5.00e-01 0.000 Inf -## g 6.52e-01 8.13e-06 0.642 0.661 -## sigma 7.88e-01 6.13e-02 0.481 1.095 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 16.9 5.63e+01 1.69e+01 -## IORE 11.6 3.37e+02 1.01e+02 -## DFOP 10.5 1.38e+12 7.69e+11 -## -## Representative half-life: -## [1] 101.43</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p9a</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 839.35238 88.57064 9.93363 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 105.5678</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 88.1933 3.06e-12 79.9447 96.4419</span> +<span class="co">## k_parent 0.0409 2.07e-07 0.0324 0.0516</span> +<span class="co">## sigma 7.2429 3.92e-05 4.4768 10.0090</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.89e+01 1.12e-16 9.54e+01 1.02e+02</span> +<span class="co">## k__iore_parent 1.93e-05 1.13e-01 3.49e-06 1.06e-04</span> +<span class="co">## N_parent 2.91e+00 1.45e-09 2.50e+00 3.32e+00</span> +<span class="co">## sigma 2.35e+00 5.31e-05 1.45e+00 3.26e+00</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 9.85e+01 2.54e-20 97.390 99.672</span> +<span class="co">## k1 1.38e-01 3.52e-05 0.131 0.146</span> +<span class="co">## k2 9.02e-13 5.00e-01 0.000 Inf</span> +<span class="co">## g 6.52e-01 8.13e-06 0.642 0.661</span> +<span class="co">## sigma 7.88e-01 6.13e-02 0.481 1.095</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 16.9 5.63e+01 1.69e+01</span> +<span class="co">## IORE 11.6 3.37e+02 1.01e+02</span> +<span class="co">## DFOP 10.5 1.38e+12 7.69e+11</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 101.43</span></code></pre> <p>In this example, the residuals of the SFO indicate a lack of fit of this model, so even if it was an abiotic experiment, the data do not suggest a simple exponential decline.</p> </div> -<div id="example-on-page-9-lower-panel" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-9-lower-panel" class="anchor"></a>Example on page 9, lower panel</h2> +<div class="section level3"> +<h3 id="example-on-page-9-lower-panel">Example on page 9, lower panel<a class="anchor" aria-label="anchor" href="#example-on-page-9-lower-panel"></a> +</h3> <div class="sourceCode" id="cb37"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p9b</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p9b"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in sqrt(diag(covar)): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(diag(covar_notrans)): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(1/diag(V)): NaNs produced</code></pre> -<pre><code>## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is -## doubtful</code></pre> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar_notrans)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(1/diag(V)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is</span> +<span class="co">## doubtful</span></code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb44"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p9b</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p9b</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p9b-1.png" width="700"></p> <div class="sourceCode" id="cb45"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p9b</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 35.64867 23.22334 35.64867 -## -## Critical sum of squares for checking the SFO model: -## [1] 28.54188 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 94.7123 2.15e-19 93.178 96.2464 -## k_parent 0.0389 4.47e-14 0.037 0.0408 -## sigma 1.5957 1.28e-04 0.932 2.2595 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 93.863 2.32e-18 92.4565 95.269 -## k__iore_parent 0.127 1.85e-02 0.0504 0.321 -## N_parent 0.711 1.88e-05 0.4843 0.937 -## sigma 1.288 1.76e-04 0.7456 1.830 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 94.7123 1.61e-16 93.1355 96.2891 -## k1 0.0389 1.08e-04 0.0266 0.0569 -## k2 0.0389 2.23e-04 0.0255 0.0592 -## g 0.5256 NaN NA NA -## sigma 1.5957 2.50e-04 0.9135 2.2779 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 17.8 59.2 17.8 -## IORE 18.4 49.2 14.8 -## DFOP 17.8 59.2 17.8 -## -## Representative half-life: -## [1] 14.8</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p9b</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 35.64867 23.22334 35.64867 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 28.54188</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 94.7123 2.15e-19 93.178 96.2464</span> +<span class="co">## k_parent 0.0389 4.47e-14 0.037 0.0408</span> +<span class="co">## sigma 1.5957 1.28e-04 0.932 2.2595</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 93.863 2.32e-18 92.4565 95.269</span> +<span class="co">## k__iore_parent 0.127 1.85e-02 0.0504 0.321</span> +<span class="co">## N_parent 0.711 1.88e-05 0.4843 0.937</span> +<span class="co">## sigma 1.288 1.76e-04 0.7456 1.830</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 94.7123 1.61e-16 93.1355 96.2891</span> +<span class="co">## k1 0.0389 1.08e-04 0.0266 0.0569</span> +<span class="co">## k2 0.0389 2.23e-04 0.0255 0.0592</span> +<span class="co">## g 0.5256 NaN NA NA</span> +<span class="co">## sigma 1.5957 2.50e-04 0.9135 2.2779</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 17.8 59.2 17.8</span> +<span class="co">## IORE 18.4 49.2 14.8</span> +<span class="co">## DFOP 17.8 59.2 17.8</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 14.8</span></code></pre> <p>Here, mkin gives a longer slow DT50 for the DFOP model (17.8 days) than PestDF (13.5 days). Presumably, this is related to the fact that PestDF gives a negative value for the proportion of the fast degradation which should be between 0 and 1, inclusive. This parameter is called f in PestDF and g in mkin. In mkin, it is restricted to the interval from 0 to 1.</p> </div> -<div id="example-on-page-10" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-10" class="anchor"></a>Example on page 10</h2> +<div class="section level3"> +<h3 id="example-on-page-10">Example on page 10<a class="anchor" aria-label="anchor" href="#example-on-page-10"></a> +</h3> <div class="sourceCode" id="cb47"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p10</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p10"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in sqrt(diag(covar)): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(1/diag(V)): NaNs produced</code></pre> -<pre><code>## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is -## doubtful</code></pre> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(1/diag(V)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is</span> +<span class="co">## doubtful</span></code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb53"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p10</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p10</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p10-1.png" width="700"></p> <div class="sourceCode" id="cb54"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p10</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 899.4089 336.4348 899.4089 -## -## Critical sum of squares for checking the SFO model: -## [1] 413.4841 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 101.7315 6.42e-11 91.9259 111.5371 -## k_parent 0.0495 1.70e-07 0.0404 0.0607 -## sigma 8.0152 1.28e-04 4.6813 11.3491 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 96.86 3.32e-12 90.848 102.863 -## k__iore_parent 2.96 7.91e-02 0.687 12.761 -## N_parent 0.00 5.00e-01 -0.372 0.372 -## sigma 4.90 1.77e-04 2.837 6.968 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 101.7315 1.41e-09 91.6534 111.8097 -## k1 0.0495 6.58e-03 0.0303 0.0809 -## k2 0.0495 2.60e-03 0.0410 0.0598 -## g 0.4487 5.00e-01 NA NA -## sigma 8.0152 2.50e-04 4.5886 11.4418 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 14.0 46.5 14.00 -## IORE 16.4 29.4 8.86 -## DFOP 14.0 46.5 14.00 -## -## Representative half-life: -## [1] 8.86</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p10</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 899.4089 336.4348 899.4089 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 413.4841</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 101.7315 6.42e-11 91.9259 111.5371</span> +<span class="co">## k_parent 0.0495 1.70e-07 0.0404 0.0607</span> +<span class="co">## sigma 8.0152 1.28e-04 4.6813 11.3491</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 96.86 3.32e-12 90.848 102.863</span> +<span class="co">## k__iore_parent 2.96 7.91e-02 0.687 12.761</span> +<span class="co">## N_parent 0.00 5.00e-01 -0.372 0.372</span> +<span class="co">## sigma 4.90 1.77e-04 2.837 6.968</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 101.7315 1.41e-09 91.6534 111.8097</span> +<span class="co">## k1 0.0495 6.58e-03 0.0303 0.0809</span> +<span class="co">## k2 0.0495 2.60e-03 0.0410 0.0598</span> +<span class="co">## g 0.4487 5.00e-01 NA NA</span> +<span class="co">## sigma 8.0152 2.50e-04 4.5886 11.4418</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 14.0 46.5 14.00</span> +<span class="co">## IORE 16.4 29.4 8.86</span> +<span class="co">## DFOP 14.0 46.5 14.00</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 8.86</span></code></pre> <p>Here, a value below N is given for the IORE model, because the data suggests a faster decline towards the end of the experiment, which appears physically rather unlikely in the case of a photolysis study. It seems PestDF does not constrain N to values above zero, thus the slight difference in IORE model parameters between PestDF and mkin.</p> </div> </div> -<div id="the-dt50-was-not-observed-during-the-study" class="section level1"> -<h1 class="hasAnchor"> -<a href="#the-dt50-was-not-observed-during-the-study" class="anchor"></a>The DT50 was not observed during the study</h1> -<div id="example-on-page-11" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-11" class="anchor"></a>Example on page 11</h2> +<div class="section level2"> +<h2 id="the-dt50-was-not-observed-during-the-study">The DT50 was not observed during the study<a class="anchor" aria-label="anchor" href="#the-dt50-was-not-observed-during-the-study"></a> +</h2> +<div class="section level3"> +<h3 id="example-on-page-11">Example on page 11<a class="anchor" aria-label="anchor" href="#example-on-page-11"></a> +</h3> <div class="sourceCode" id="cb56"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p11</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p11"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb59"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p11</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p11</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p11-1.png" width="700"></p> <div class="sourceCode" id="cb60"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p11</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 579.6805 204.7932 144.7783 -## -## Critical sum of squares for checking the SFO model: -## [1] 251.6944 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 96.15820 4.83e-13 90.24934 1.02e+02 -## k_parent 0.00321 4.71e-05 0.00222 4.64e-03 -## sigma 6.43473 1.28e-04 3.75822 9.11e+00 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 1.05e+02 NA 9.90e+01 1.10e+02 -## k__iore_parent 3.11e-17 NA 1.35e-20 7.18e-14 -## N_parent 8.36e+00 NA 6.62e+00 1.01e+01 -## sigma 3.82e+00 NA 2.21e+00 5.44e+00 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 1.05e+02 9.47e-13 99.9990 109.1224 -## k1 4.41e-02 5.95e-03 0.0296 0.0658 -## k2 9.94e-13 5.00e-01 0.0000 Inf -## g 3.22e-01 1.45e-03 0.2814 0.3650 -## sigma 3.22e+00 3.52e-04 1.8410 4.5906 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 2.16e+02 7.18e+02 2.16e+02 -## IORE 9.73e+02 1.37e+08 4.11e+07 -## DFOP 3.07e+11 1.93e+12 6.98e+11 -## -## Representative half-life: -## [1] 41148170</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p11</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 579.6805 204.7932 144.7783 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 251.6944</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 96.15820 4.83e-13 90.24934 1.02e+02</span> +<span class="co">## k_parent 0.00321 4.71e-05 0.00222 4.64e-03</span> +<span class="co">## sigma 6.43473 1.28e-04 3.75822 9.11e+00</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 1.05e+02 NA 9.90e+01 1.10e+02</span> +<span class="co">## k__iore_parent 3.11e-17 NA 1.35e-20 7.18e-14</span> +<span class="co">## N_parent 8.36e+00 NA 6.62e+00 1.01e+01</span> +<span class="co">## sigma 3.82e+00 NA 2.21e+00 5.44e+00</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 1.05e+02 9.47e-13 99.9990 109.1224</span> +<span class="co">## k1 4.41e-02 5.95e-03 0.0296 0.0658</span> +<span class="co">## k2 9.94e-13 5.00e-01 0.0000 Inf</span> +<span class="co">## g 3.22e-01 1.45e-03 0.2814 0.3650</span> +<span class="co">## sigma 3.22e+00 3.52e-04 1.8410 4.5906</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 2.16e+02 7.18e+02 2.16e+02</span> +<span class="co">## IORE 9.73e+02 1.37e+08 4.11e+07</span> +<span class="co">## DFOP 3.07e+11 1.93e+12 6.98e+11</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 41148170</span></code></pre> <p>In this case, the DFOP fit reported for PestDF resulted in a negative value for the slower rate constant, which is not possible in mkin. The other results are in agreement.</p> </div> </div> -<div id="n-is-less-than-1-and-the-dfop-rate-constants-are-like-the-sfo-rate-constant" class="section level1"> -<h1 class="hasAnchor"> -<a href="#n-is-less-than-1-and-the-dfop-rate-constants-are-like-the-sfo-rate-constant" class="anchor"></a>N is less than 1 and the DFOP rate constants are like the SFO rate constant</h1> +<div class="section level2"> +<h2 id="n-is-less-than-1-and-the-dfop-rate-constants-are-like-the-sfo-rate-constant">N is less than 1 and the DFOP rate constants are like the SFO rate constant<a class="anchor" aria-label="anchor" href="#n-is-less-than-1-and-the-dfop-rate-constants-are-like-the-sfo-rate-constant"></a> +</h2> <p>In the following three examples, the same results are obtained with mkin as reported for PestDF. As in the case on page 10, the N values below 1 are deemed unrealistic and appear to be the result of an overparameterisation.</p> -<div id="example-on-page-12-upper-panel" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-12-upper-panel" class="anchor"></a>Example on page 12, upper panel</h2> +<div class="section level3"> +<h3 id="example-on-page-12-upper-panel">Example on page 12, upper panel<a class="anchor" aria-label="anchor" href="#example-on-page-12-upper-panel"></a> +</h3> <div class="sourceCode" id="cb62"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p12a</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p12a"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in summary.mkinfit(x): Could not calculate correlation; no covariance -## matrix</code></pre> -<pre><code>## Warning in sqrt(diag(covar)): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(diag(covar_notrans)): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(1/diag(V)): NaNs produced</code></pre> -<pre><code>## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is -## doubtful</code></pre> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## Warning in summary.mkinfit(x): Could not calculate correlation; no covariance</span> +<span class="co">## matrix</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar_notrans)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(1/diag(V)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is</span> +<span class="co">## doubtful</span></code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb70"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p12a</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p12a</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p12a-1.png" width="700"></p> <div class="sourceCode" id="cb71"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p12a</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 695.4440 220.0685 695.4440 -## -## Critical sum of squares for checking the SFO model: -## [1] 270.4679 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 100.521 8.75e-12 92.461 108.581 -## k_parent 0.124 3.61e-08 0.104 0.148 -## sigma 7.048 1.28e-04 4.116 9.980 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 96.823 NA NA NA -## k__iore_parent 2.436 NA NA NA -## N_parent 0.263 NA NA NA -## sigma 3.965 NA NA NA -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 100.521 2.74e-10 92.2366 108.805 -## k1 0.124 2.53e-05 0.0908 0.170 -## k2 0.124 2.52e-02 0.0456 0.339 -## g 0.793 NaN NA NA -## sigma 7.048 2.50e-04 4.0349 10.061 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 5.58 18.5 5.58 -## IORE 6.49 13.2 3.99 -## DFOP 5.58 18.5 5.58 -## -## Representative half-life: -## [1] 3.99</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p12a</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 695.4440 220.0685 695.4440 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 270.4679</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 100.521 8.75e-12 92.461 108.581</span> +<span class="co">## k_parent 0.124 3.61e-08 0.104 0.148</span> +<span class="co">## sigma 7.048 1.28e-04 4.116 9.980</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 96.823 NA NA NA</span> +<span class="co">## k__iore_parent 2.436 NA NA NA</span> +<span class="co">## N_parent 0.263 NA NA NA</span> +<span class="co">## sigma 3.965 NA NA NA</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 100.521 2.74e-10 92.2366 108.805</span> +<span class="co">## k1 0.124 2.53e-05 0.0908 0.170</span> +<span class="co">## k2 0.124 2.52e-02 0.0456 0.339</span> +<span class="co">## g 0.793 NaN NA NA</span> +<span class="co">## sigma 7.048 2.50e-04 4.0349 10.061</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 5.58 18.5 5.58</span> +<span class="co">## IORE 6.49 13.2 3.99</span> +<span class="co">## DFOP 5.58 18.5 5.58</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 3.99</span></code></pre> </div> -<div id="example-on-page-12-lower-panel" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-12-lower-panel" class="anchor"></a>Example on page 12, lower panel</h2> +<div class="section level3"> +<h3 id="example-on-page-12-lower-panel">Example on page 12, lower panel<a class="anchor" aria-label="anchor" href="#example-on-page-12-lower-panel"></a> +</h3> <div class="sourceCode" id="cb73"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p12b</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p12b"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in qt(alpha/2, rdf): NaNs produced</code></pre> -<pre><code>## Warning in qt(1 - alpha/2, rdf): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(diag(covar_notrans)): NaNs produced</code></pre> -<pre><code>## Warning in pt(abs(tval), rdf, lower.tail = FALSE): NaNs produced</code></pre> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## Warning in qt(alpha/2, rdf): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in qt(1 - alpha/2, rdf): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar_notrans)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in pt(abs(tval), rdf, lower.tail = FALSE): NaNs produced</span></code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb80"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p12b</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p12b</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p12b-1.png" width="700"></p> <div class="sourceCode" id="cb81"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p12b</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 58.90242 19.06353 58.90242 -## -## Critical sum of squares for checking the SFO model: -## [1] 51.51756 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 97.6840 0.00039 85.9388 109.4292 -## k_parent 0.0589 0.00261 0.0431 0.0805 -## sigma 3.4323 0.04356 -1.2377 8.1023 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 95.523 0.0055 74.539157 116.51 -## k__iore_parent 0.333 0.1433 0.000717 154.57 -## N_parent 0.568 0.0677 -0.989464 2.13 -## sigma 1.953 0.0975 -5.893100 9.80 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 97.6840 NaN NaN NaN -## k1 0.0589 NaN NA NA -## k2 0.0589 NaN NA NA -## g 0.6473 NaN NA NA -## sigma 3.4323 NaN NaN NaN -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 11.8 39.1 11.80 -## IORE 12.9 31.4 9.46 -## DFOP 11.8 39.1 11.80 -## -## Representative half-life: -## [1] 9.46</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p12b</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 58.90242 19.06353 58.90242 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 51.51756</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 97.6840 0.00039 85.9388 109.4292</span> +<span class="co">## k_parent 0.0589 0.00261 0.0431 0.0805</span> +<span class="co">## sigma 3.4323 0.04356 -1.2377 8.1023</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 95.523 0.0055 74.539157 116.51</span> +<span class="co">## k__iore_parent 0.333 0.1433 0.000717 154.57</span> +<span class="co">## N_parent 0.568 0.0677 -0.989464 2.13</span> +<span class="co">## sigma 1.953 0.0975 -5.893100 9.80</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 97.6840 NaN NaN NaN</span> +<span class="co">## k1 0.0589 NaN NA NA</span> +<span class="co">## k2 0.0589 NaN NA NA</span> +<span class="co">## g 0.6473 NaN NA NA</span> +<span class="co">## sigma 3.4323 NaN NaN NaN</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 11.8 39.1 11.80</span> +<span class="co">## IORE 12.9 31.4 9.46</span> +<span class="co">## DFOP 11.8 39.1 11.80</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 9.46</span></code></pre> </div> -<div id="example-on-page-13" class="section level2"> -<h2 class="hasAnchor"> -<a href="#example-on-page-13" class="anchor"></a>Example on page 13</h2> +<div class="section level3"> +<h3 id="example-on-page-13">Example on page 13<a class="anchor" aria-label="anchor" href="#example-on-page-13"></a> +</h3> <div class="sourceCode" id="cb83"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p13</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p13"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb86"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p13</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p13</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p13-1.png" width="700"></p> <div class="sourceCode" id="cb87"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p13</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 174.5971 142.3951 174.5971 -## -## Critical sum of squares for checking the SFO model: -## [1] 172.131 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 92.73500 5.99e-17 89.61936 95.85065 -## k_parent 0.00258 2.42e-09 0.00223 0.00299 -## sigma 3.41172 7.07e-05 2.05455 4.76888 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 91.6016 6.34e-16 88.53086 94.672 -## k__iore_parent 0.0396 2.36e-01 0.00207 0.759 -## N_parent 0.3541 1.46e-01 -0.35153 1.060 -## sigma 3.0811 9.64e-05 1.84296 4.319 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 92.73500 NA 8.95e+01 95.92118 -## k1 0.00258 NA 4.14e-04 0.01611 -## k2 0.00258 NA 1.74e-03 0.00383 -## g 0.16452 NA 0.00e+00 1.00000 -## sigma 3.41172 NA 2.02e+00 4.79960 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 269 892 269 -## IORE 261 560 169 -## DFOP 269 892 269 -## -## Representative half-life: -## [1] 168.51</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p13</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 174.5971 142.3951 174.5971 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 172.131</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 92.73500 5.99e-17 89.61936 95.85065</span> +<span class="co">## k_parent 0.00258 2.42e-09 0.00223 0.00299</span> +<span class="co">## sigma 3.41172 7.07e-05 2.05455 4.76888</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 91.6016 6.34e-16 88.53086 94.672</span> +<span class="co">## k__iore_parent 0.0396 2.36e-01 0.00207 0.759</span> +<span class="co">## N_parent 0.3541 1.46e-01 -0.35153 1.060</span> +<span class="co">## sigma 3.0811 9.64e-05 1.84296 4.319</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 92.73500 NA 8.95e+01 95.92118</span> +<span class="co">## k1 0.00258 NA 4.14e-04 0.01611</span> +<span class="co">## k2 0.00258 NA 1.74e-03 0.00383</span> +<span class="co">## g 0.16452 NA 0.00e+00 1.00000</span> +<span class="co">## sigma 3.41172 NA 2.02e+00 4.79960</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 269 892 269</span> +<span class="co">## IORE 261 560 169</span> +<span class="co">## DFOP 269 892 269</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 168.51</span></code></pre> </div> </div> -<div id="dt50-not-observed-in-the-study-and-dfop-problems-in-pestdf" class="section level1"> -<h1 class="hasAnchor"> -<a href="#dt50-not-observed-in-the-study-and-dfop-problems-in-pestdf" class="anchor"></a>DT50 not observed in the study and DFOP problems in PestDF</h1> +<div class="section level2"> +<h2 id="dt50-not-observed-in-the-study-and-dfop-problems-in-pestdf">DT50 not observed in the study and DFOP problems in PestDF<a class="anchor" aria-label="anchor" href="#dt50-not-observed-in-the-study-and-dfop-problems-in-pestdf"></a> +</h2> <div class="sourceCode" id="cb89"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p14</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p14"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in sqrt(diag(covar)): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(1/diag(V)): NaNs produced</code></pre> -<pre><code>## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is -## doubtful</code></pre> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(1/diag(V)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is</span> +<span class="co">## doubtful</span></code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb95"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p14</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p14</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p14-1.png" width="700"></p> <div class="sourceCode" id="cb96"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p14</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 48.43249 28.67746 27.26248 -## -## Critical sum of squares for checking the SFO model: -## [1] 32.83337 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 99.47124 2.06e-30 98.42254 1.01e+02 -## k_parent 0.00279 3.75e-15 0.00256 3.04e-03 -## sigma 1.55616 3.81e-06 1.03704 2.08e+00 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 1.00e+02 NA NaN NaN -## k__iore_parent 9.44e-08 NA NaN NaN -## N_parent 3.31e+00 NA NaN NaN -## sigma 1.20e+00 NA 0.796 1.6 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 1.00e+02 2.96e-28 99.40280 101.2768 -## k1 9.53e-03 1.20e-01 0.00638 0.0143 -## k2 6.08e-12 5.00e-01 0.00000 Inf -## g 3.98e-01 2.19e-01 0.30481 0.4998 -## sigma 1.17e+00 7.68e-06 0.77406 1.5610 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 2.48e+02 8.25e+02 2.48e+02 -## IORE 4.34e+02 2.22e+04 6.70e+03 -## DFOP 3.05e+10 2.95e+11 1.14e+11 -## -## Representative half-life: -## [1] 6697.44</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p14</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 48.43249 28.67746 27.26248 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 32.83337</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 99.47124 2.06e-30 98.42254 1.01e+02</span> +<span class="co">## k_parent 0.00279 3.75e-15 0.00256 3.04e-03</span> +<span class="co">## sigma 1.55616 3.81e-06 1.03704 2.08e+00</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 1.00e+02 NA NaN NaN</span> +<span class="co">## k__iore_parent 9.44e-08 NA NaN NaN</span> +<span class="co">## N_parent 3.31e+00 NA NaN NaN</span> +<span class="co">## sigma 1.20e+00 NA 0.796 1.6</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 1.00e+02 2.96e-28 99.40280 101.2768</span> +<span class="co">## k1 9.53e-03 1.20e-01 0.00638 0.0143</span> +<span class="co">## k2 6.08e-12 5.00e-01 0.00000 Inf</span> +<span class="co">## g 3.98e-01 2.19e-01 0.30481 0.4998</span> +<span class="co">## sigma 1.17e+00 7.68e-06 0.77406 1.5610</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 2.48e+02 8.25e+02 2.48e+02</span> +<span class="co">## IORE 4.34e+02 2.22e+04 6.70e+03</span> +<span class="co">## DFOP 3.05e+10 2.95e+11 1.14e+11</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 6697.44</span></code></pre> <p>The slower rate constant reported by PestDF is negative, which is not physically realistic, and not possible in mkin. The other fits give the same results in mkin and PestDF.</p> </div> -<div id="n-is-less-than-1-and-dfop-fraction-parameter-is-below-zero" class="section level1"> -<h1 class="hasAnchor"> -<a href="#n-is-less-than-1-and-dfop-fraction-parameter-is-below-zero" class="anchor"></a>N is less than 1 and DFOP fraction parameter is below zero</h1> +<div class="section level2"> +<h2 id="n-is-less-than-1-and-dfop-fraction-parameter-is-below-zero">N is less than 1 and DFOP fraction parameter is below zero<a class="anchor" aria-label="anchor" href="#n-is-less-than-1-and-dfop-fraction-parameter-is-below-zero"></a> +</h2> <div class="sourceCode" id="cb98"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p15a</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p15a"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb101"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p15a</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p15a</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p15a-1.png" width="700"></p> <div class="sourceCode" id="cb102"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p15a</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 245.5248 135.0132 245.5248 -## -## Critical sum of squares for checking the SFO model: -## [1] 165.9335 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 97.96751 2.00e-15 94.32049 101.615 -## k_parent 0.00952 4.93e-09 0.00824 0.011 -## sigma 4.18778 1.28e-04 2.44588 5.930 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 95.874 2.94e-15 92.937 98.811 -## k__iore_parent 0.629 2.11e-01 0.044 8.982 -## N_parent 0.000 5.00e-01 -0.642 0.642 -## sigma 3.105 1.78e-04 1.795 4.416 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 97.96751 2.85e-13 94.21913 101.7159 -## k1 0.00952 6.28e-02 0.00250 0.0363 -## k2 0.00952 1.27e-04 0.00646 0.0140 -## g 0.21241 5.00e-01 0.00000 1.0000 -## sigma 4.18778 2.50e-04 2.39747 5.9781 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 72.8 242 72.8 -## IORE 76.3 137 41.3 -## DFOP 72.8 242 72.8 -## -## Representative half-life: -## [1] 41.33</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p15a</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 245.5248 135.0132 245.5248 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 165.9335</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 97.96751 2.00e-15 94.32049 101.615</span> +<span class="co">## k_parent 0.00952 4.93e-09 0.00824 0.011</span> +<span class="co">## sigma 4.18778 1.28e-04 2.44588 5.930</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 95.874 2.94e-15 92.937 98.811</span> +<span class="co">## k__iore_parent 0.629 2.11e-01 0.044 8.982</span> +<span class="co">## N_parent 0.000 5.00e-01 -0.642 0.642</span> +<span class="co">## sigma 3.105 1.78e-04 1.795 4.416</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 97.96751 2.85e-13 94.21913 101.7159</span> +<span class="co">## k1 0.00952 6.28e-02 0.00250 0.0363</span> +<span class="co">## k2 0.00952 1.27e-04 0.00646 0.0140</span> +<span class="co">## g 0.21241 5.00e-01 0.00000 1.0000</span> +<span class="co">## sigma 4.18778 2.50e-04 2.39747 5.9781</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 72.8 242 72.8</span> +<span class="co">## IORE 76.3 137 41.3</span> +<span class="co">## DFOP 72.8 242 72.8</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 41.33</span></code></pre> <div class="sourceCode" id="cb104"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p15b</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p15b"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## Warning in sqrt(diag(covar)): NaNs produced</code></pre> -<pre><code>## Warning in sqrt(1/diag(V)): NaNs produced</code></pre> -<pre><code>## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is -## doubtful</code></pre> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The half-life obtained from the IORE model may be used</code></pre> +<pre><code><span class="co">## Warning in sqrt(diag(covar)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in sqrt(1/diag(V)): NaNs produced</span></code></pre> +<pre><code><span class="co">## Warning in cov2cor(ans$covar): diag(.) had 0 or NA entries; non-finite result is</span> +<span class="co">## doubtful</span></code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The half-life obtained from the IORE model may be used</span></code></pre> <div class="sourceCode" id="cb110"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p15b</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p15b</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p15b-1.png" width="700"></p> <div class="sourceCode" id="cb111"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p15b</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 106.91629 68.55574 106.91629 -## -## Critical sum of squares for checking the SFO model: -## [1] 84.25618 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 1.01e+02 3.06e-17 98.31594 1.03e+02 -## k_parent 4.86e-03 2.48e-10 0.00435 5.42e-03 -## sigma 2.76e+00 1.28e-04 1.61402 3.91e+00 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 99.83 1.81e-16 97.51349 102.14 -## k__iore_parent 0.38 3.22e-01 0.00352 41.05 -## N_parent 0.00 5.00e-01 -1.07696 1.08 -## sigma 2.21 2.57e-04 1.23245 3.19 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 1.01e+02 NA 9.82e+01 1.04e+02 -## k1 4.86e-03 NA 8.63e-04 2.73e-02 -## k2 4.86e-03 NA 3.21e-03 7.35e-03 -## g 1.88e-01 NA NA NA -## sigma 2.76e+00 NA 1.58e+00 3.94e+00 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 143 474 143.0 -## IORE 131 236 71.2 -## DFOP 143 474 143.0 -## -## Representative half-life: -## [1] 71.18</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p15b</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 106.91629 68.55574 106.91629 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 84.25618</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 1.01e+02 3.06e-17 98.31594 1.03e+02</span> +<span class="co">## k_parent 4.86e-03 2.48e-10 0.00435 5.42e-03</span> +<span class="co">## sigma 2.76e+00 1.28e-04 1.61402 3.91e+00</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 99.83 1.81e-16 97.51349 102.14</span> +<span class="co">## k__iore_parent 0.38 3.22e-01 0.00352 41.05</span> +<span class="co">## N_parent 0.00 5.00e-01 -1.07696 1.08</span> +<span class="co">## sigma 2.21 2.57e-04 1.23245 3.19</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 1.01e+02 NA 9.82e+01 1.04e+02</span> +<span class="co">## k1 4.86e-03 NA 8.63e-04 2.73e-02</span> +<span class="co">## k2 4.86e-03 NA 3.21e-03 7.35e-03</span> +<span class="co">## g 1.88e-01 NA NA NA</span> +<span class="co">## sigma 2.76e+00 NA 1.58e+00 3.94e+00</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 143 474 143.0</span> +<span class="co">## IORE 131 236 71.2</span> +<span class="co">## DFOP 143 474 143.0</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 71.18</span></code></pre> <p>In mkin, only the IORE fit is affected (deemed unrealistic), as the fraction parameter of the DFOP model is restricted to the interval between 0 and 1 in mkin. The SFO fits give the same results for both mkin and PestDF.</p> </div> -<div id="the-dfop-fraction-parameter-is-greater-than-1" class="section level1"> -<h1 class="hasAnchor"> -<a href="#the-dfop-fraction-parameter-is-greater-than-1" class="anchor"></a>The DFOP fraction parameter is greater than 1</h1> +<div class="section level2"> +<h2 id="the-dfop-fraction-parameter-is-greater-than-1">The DFOP fraction parameter is greater than 1<a class="anchor" aria-label="anchor" href="#the-dfop-fraction-parameter-is-greater-than-1"></a> +</h2> <div class="sourceCode" id="cb113"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">p16</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p16"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div> -<pre><code>## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</code></pre> -<pre><code>## The representative half-life of the IORE model is longer than the one corresponding</code></pre> -<pre><code>## to the terminal degradation rate found with the DFOP model.</code></pre> -<pre><code>## The representative half-life obtained from the DFOP model may be used</code></pre> +<pre><code><span class="co">## The SFO model is rejected as S_SFO is equal or higher than the critical value S_c</span></code></pre> +<pre><code><span class="co">## The representative half-life of the IORE model is longer than the one corresponding</span></code></pre> +<pre><code><span class="co">## to the terminal degradation rate found with the DFOP model.</span></code></pre> +<pre><code><span class="co">## The representative half-life obtained from the DFOP model may be used</span></code></pre> <div class="sourceCode" id="cb118"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">p16</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">p16</span><span class="op">)</span></code></pre></div> <p><img src="NAFTA_examples_files/figure-html/p16-1.png" width="700"></p> <div class="sourceCode" id="cb119"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">p16</span><span class="op">)</span></code></pre></div> -<pre><code>## Sums of squares: -## SFO IORE DFOP -## 3831.804 2062.008 1550.980 -## -## Critical sum of squares for checking the SFO model: -## [1] 2247.348 -## -## Parameters: -## $SFO -## Estimate Pr(>t) Lower Upper -## parent_0 71.953 2.33e-13 60.509 83.40 -## k_parent 0.159 4.86e-05 0.102 0.25 -## sigma 11.302 1.25e-08 8.308 14.30 -## -## $IORE -## Estimate Pr(>t) Lower Upper -## parent_0 8.74e+01 2.48e-16 7.72e+01 97.52972 -## k__iore_parent 4.55e-04 2.16e-01 3.48e-05 0.00595 -## N_parent 2.70e+00 1.21e-08 1.99e+00 3.40046 -## sigma 8.29e+00 1.61e-08 6.09e+00 10.49062 -## -## $DFOP -## Estimate Pr(>t) Lower Upper -## parent_0 88.5333 7.40e-18 79.9836 97.083 -## k1 18.8461 5.00e-01 0.0000 Inf -## k2 0.0776 1.41e-05 0.0518 0.116 -## g 0.4733 1.41e-09 0.3674 0.582 -## sigma 7.1902 2.11e-08 5.2785 9.102 -## -## -## DTx values: -## DT50 DT90 DT50_rep -## SFO 4.35 14.4 4.35 -## IORE 1.48 32.1 9.67 -## DFOP 0.67 21.4 8.93 -## -## Representative half-life: -## [1] 8.93</code></pre> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">p16</span><span class="op">)</span></code></pre></div> +<pre><code><span class="co">## Sums of squares:</span> +<span class="co">## SFO IORE DFOP </span> +<span class="co">## 3831.804 2062.008 1550.980 </span> +<span class="co">## </span> +<span class="co">## Critical sum of squares for checking the SFO model:</span> +<span class="co">## [1] 2247.348</span> +<span class="co">## </span> +<span class="co">## Parameters:</span> +<span class="co">## $SFO</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 71.953 2.33e-13 60.509 83.40</span> +<span class="co">## k_parent 0.159 4.86e-05 0.102 0.25</span> +<span class="co">## sigma 11.302 1.25e-08 8.308 14.30</span> +<span class="co">## </span> +<span class="co">## $IORE</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 8.74e+01 2.48e-16 7.72e+01 97.52972</span> +<span class="co">## k__iore_parent 4.55e-04 2.16e-01 3.48e-05 0.00595</span> +<span class="co">## N_parent 2.70e+00 1.21e-08 1.99e+00 3.40046</span> +<span class="co">## sigma 8.29e+00 1.61e-08 6.09e+00 10.49062</span> +<span class="co">## </span> +<span class="co">## $DFOP</span> +<span class="co">## Estimate Pr(>t) Lower Upper</span> +<span class="co">## parent_0 88.5333 7.40e-18 79.9836 97.083</span> +<span class="co">## k1 18.8461 5.00e-01 0.0000 Inf</span> +<span class="co">## k2 0.0776 1.41e-05 0.0518 0.116</span> +<span class="co">## g 0.4733 1.41e-09 0.3674 0.582</span> +<span class="co">## sigma 7.1902 2.11e-08 5.2785 9.102</span> +<span class="co">## </span> +<span class="co">## </span> +<span class="co">## DTx values:</span> +<span class="co">## DT50 DT90 DT50_rep</span> +<span class="co">## SFO 4.35 14.4 4.35</span> +<span class="co">## IORE 1.48 32.1 9.67</span> +<span class="co">## DFOP 0.67 21.4 8.93</span> +<span class="co">## </span> +<span class="co">## Representative half-life:</span> +<span class="co">## [1] 8.93</span></code></pre> <p>In PestDF, the DFOP fit seems to have stuck in a local minimum, as mkin finds a solution with a much lower <span class="math inline">\(\chi^2\)</span> error level. As the half-life from the slower rate constant of the DFOP model is larger than the IORE derived half-life, the NAFTA recommendation obtained with mkin is to use the DFOP representative half-life of 8.9 days.</p> </div> -<div id="conclusions" class="section level1"> -<h1 class="hasAnchor"> -<a href="#conclusions" class="anchor"></a>Conclusions</h1> +<div class="section level2"> +<h2 id="conclusions">Conclusions<a class="anchor" aria-label="anchor" href="#conclusions"></a> +</h2> <p>The results obtained with mkin deviate from the results obtained with PestDF either in cases where one of the interpretive rules would apply, i.e. the IORE parameter N is less than one or the DFOP k values obtained with PestDF are equal to the SFO k values, or in cases where the DFOP model did not converge, which often lead to negative rate constants returned by PestDF.</p> <p>Therefore, mkin appears to suitable for kinetic evaluations according to the NAFTA guidance.</p> </div> -<div id="references" class="section level1 unnumbered"> -<h1 class="hasAnchor"> -<a href="#references" class="anchor"></a>References</h1> +<div class="section level2"> +<h2 class="unnumbered" id="references">References<a class="anchor" aria-label="anchor" href="#references"></a> +</h2> <div id="refs" class="references hanging-indent"> <div id="ref-usepa2015"> <p>US EPA. 2015. “Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half-Life Values and Characterizing Pesticide Degradation.”</p> @@ -1015,11 +1020,13 @@ <footer><div class="copyright"> - <p>Developed by Johannes Ranke.</p> + <p></p> +<p>Developed by Johannes Ranke.</p> </div> <div class="pkgdown"> - <p>Site built with <a href="https://pkgdown.r-lib.org/">pkgdown</a> 1.6.1.</p> + <p></p> +<p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.2.</p> </div> </footer> @@ -1028,5 +1035,7 @@ + + </body> </html> diff --git 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template-article"> <header><div class="navbar navbar-default navbar-fixed-top" role="navigation"> <div class="container"> @@ -31,7 +33,7 @@ </button> <span class="navbar-brand"> <a class="navbar-link" href="../../index.html">mkin</a> - <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.0.4</span> + <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.1.0</span> </span> </div> @@ -57,6 +59,9 @@ <a href="../../articles/FOCUS_L.html">Example evaluation of FOCUS Laboratory Data L1 to L3</a> </li> <li> + <a href="../../articles/web_only/dimethenamid_2018.html">Example evaluations of dimethenamid data from 2018 with nonlinear mixed-effects models</a> + </li> + <li> <a href="../../articles/web_only/FOCUS_Z.html">Example evaluation of FOCUS Example Dataset Z</a> </li> <li> @@ -79,7 +84,7 @@ </ul> <ul class="nav navbar-nav navbar-right"> <li> - <a href="https://github.com/jranke/mkin/"> + <a href="https://github.com/jranke/mkin/" class="external-link"> <span class="fab fa-github fa-lg"></span> </a> @@ -94,15 +99,15 @@ - </header><script src="benchmarks_files/header-attrs-2.7/header-attrs.js"></script><script src="benchmarks_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> + </header><script src="benchmarks_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> <div class="col-md-9 contents"> <div class="page-header toc-ignore"> <h1 data-toc-skip>Benchmark timings for mkin</h1> - <h4 class="author">Johannes Ranke</h4> + <h4 data-toc-skip class="author">Johannes Ranke</h4> - <h4 class="date">Last change 13 May 2020 (rebuilt 2021-03-31)</h4> + <h4 data-toc-skip class="date">Last change 13 May 2020 (rebuilt 2022-03-02)</h4> - <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/web_only/benchmarks.rmd"><code>vignettes/web_only/benchmarks.rmd</code></a></small> + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/web_only/benchmarks.rmd" class="external-link"><code>vignettes/web_only/benchmarks.rmd</code></a></small> <div class="hidden name"><code>benchmarks.rmd</code></div> </div> @@ -110,17 +115,17 @@ <p>Each system is characterized by its CPU type, the operating system type and the mkin version. Currently only values for one system are available. A compiler was available, so if no analytical solution was available, compiled ODE models are used.</p> -<div id="test-cases" class="section level2"> -<h2 class="hasAnchor"> -<a href="#test-cases" class="anchor"></a>Test cases</h2> +<div class="section level2"> +<h2 id="test-cases">Test cases<a class="anchor" aria-label="anchor" href="#test-cases"></a> +</h2> <p>Parent only:</p> <div class="sourceCode" id="cb1"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span class="va">FOCUS_C</span> <span class="op"><-</span> <span class="va">FOCUS_2006_C</span> -<span class="va">FOCUS_D</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/subset.html">subset</a></span><span class="op">(</span><span class="va">FOCUS_2006_D</span>, <span class="va">value</span> <span class="op">!=</span> <span class="fl">0</span><span class="op">)</span> -<span class="va">parent_datasets</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">FOCUS_C</span>, <span class="va">FOCUS_D</span><span class="op">)</span> +<span class="va">FOCUS_D</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/saemix/man/subset.html" class="external-link">subset</a></span><span class="op">(</span><span class="va">FOCUS_2006_D</span>, <span class="va">value</span> <span class="op">!=</span> <span class="fl">0</span><span class="op">)</span> +<span class="va">parent_datasets</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">FOCUS_C</span>, <span class="va">FOCUS_D</span><span class="op">)</span> -<span class="va">t1</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"FOMC"</span>, <span class="st">"DFOP"</span>, <span class="st">"HS"</span><span class="op">)</span>, <span class="va">parent_datasets</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t2</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"FOMC"</span>, <span class="st">"DFOP"</span>, <span class="st">"HS"</span><span class="op">)</span>, <span class="va">parent_datasets</span>, +<span class="va">t1</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"FOMC"</span>, <span class="st">"DFOP"</span>, <span class="st">"HS"</span><span class="op">)</span>, <span class="va">parent_datasets</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> +<span class="va">t2</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"FOMC"</span>, <span class="st">"DFOP"</span>, <span class="st">"HS"</span><span class="op">)</span>, <span class="va">parent_datasets</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span></code></pre></div> <p>One metabolite:</p> <div class="sourceCode" id="cb2"><pre class="downlit sourceCode r"> @@ -133,10 +138,10 @@ <span class="va">DFOP_SFO</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span> parent <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"FOMC"</span>, <span class="st">"m1"</span><span class="op">)</span>, m1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span> -<span class="va">t3</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">SFO_SFO</span>, <span class="va">FOMC_SFO</span>, <span class="va">DFOP_SFO</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">FOCUS_D</span><span class="op">)</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t4</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">SFO_SFO</span>, <span class="va">FOMC_SFO</span>, <span class="va">DFOP_SFO</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">FOCUS_D</span><span class="op">)</span>, +<span class="va">t3</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">SFO_SFO</span>, <span class="va">FOMC_SFO</span>, <span class="va">DFOP_SFO</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">FOCUS_D</span><span class="op">)</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> +<span class="va">t4</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">SFO_SFO</span>, <span class="va">FOMC_SFO</span>, <span class="va">DFOP_SFO</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">FOCUS_D</span><span class="op">)</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t5</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">SFO_SFO</span>, <span class="va">FOMC_SFO</span>, <span class="va">DFOP_SFO</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">FOCUS_D</span><span class="op">)</span>, +<span class="va">t5</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">SFO_SFO</span>, <span class="va">FOMC_SFO</span>, <span class="va">DFOP_SFO</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">FOCUS_D</span><span class="op">)</span>, error_model <span class="op">=</span> <span class="st">"obs"</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span></code></pre></div> <p>Two metabolites, synthetic data:</p> <div class="sourceCode" id="cb3"><pre class="downlit sourceCode r"> @@ -145,7 +150,7 @@ M2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>, use_of_ff <span class="op">=</span> <span class="st">"max"</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> -<span class="va">m_synth_DFOP_par</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"DFOP"</span>, <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="st">"M1"</span>, <span class="st">"M2"</span><span class="op">)</span><span class="op">)</span>, +<span class="va">m_synth_DFOP_par</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"DFOP"</span>, <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"M1"</span>, <span class="st">"M2"</span><span class="op">)</span><span class="op">)</span>, M1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>, M2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>, use_of_ff <span class="op">=</span> <span class="st">"max"</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> @@ -154,31 +159,31 @@ <span class="va">DFOP_par_c</span> <span class="op"><-</span> <span class="va">synthetic_data_for_UBA_2014</span><span class="op">[[</span><span class="fl">12</span><span class="op">]</span><span class="op">]</span><span class="op">$</span><span class="va">data</span> -<span class="va">t6</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">m_synth_SFO_lin</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">SFO_lin_a</span><span class="op">)</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t7</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">m_synth_DFOP_par</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">DFOP_par_c</span><span class="op">)</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> +<span class="va">t6</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">m_synth_SFO_lin</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">SFO_lin_a</span><span class="op">)</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> +<span class="va">t7</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">m_synth_DFOP_par</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">DFOP_par_c</span><span class="op">)</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t8</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">m_synth_SFO_lin</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">SFO_lin_a</span><span class="op">)</span>, +<span class="va">t8</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">m_synth_SFO_lin</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">SFO_lin_a</span><span class="op">)</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t9</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">m_synth_DFOP_par</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">DFOP_par_c</span><span class="op">)</span>, +<span class="va">t9</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">m_synth_DFOP_par</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">DFOP_par_c</span><span class="op">)</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t10</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">m_synth_SFO_lin</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">SFO_lin_a</span><span class="op">)</span>, +<span class="va">t10</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">m_synth_SFO_lin</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">SFO_lin_a</span><span class="op">)</span>, error_model <span class="op">=</span> <span class="st">"obs"</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span> -<span class="va">t11</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">m_synth_DFOP_par</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="va">DFOP_par_c</span><span class="op">)</span>, +<span class="va">t11</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span><span class="fu">mmkin_bench</span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">m_synth_DFOP_par</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">DFOP_par_c</span><span class="op">)</span>, error_model <span class="op">=</span> <span class="st">"obs"</span><span class="op">)</span><span class="op">)</span><span class="op">[[</span><span class="st">"elapsed"</span><span class="op">]</span><span class="op">]</span></code></pre></div> <div class="sourceCode" id="cb4"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="va">mkin_benchmarks</span><span class="op">[</span><span class="va">system_string</span>, <span class="fu"><a href="https://rdrr.io/r/base/paste.html">paste0</a></span><span class="op">(</span><span class="st">"t"</span>, <span class="fl">1</span><span class="op">:</span><span class="fl">11</span><span class="op">)</span><span class="op">]</span> <span class="op"><-</span> - <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="va">t1</span>, <span class="va">t2</span>, <span class="va">t3</span>, <span class="va">t4</span>, <span class="va">t5</span>, <span class="va">t6</span>, <span class="va">t7</span>, <span class="va">t8</span>, <span class="va">t9</span>, <span class="va">t10</span>, <span class="va">t11</span><span class="op">)</span> -<span class="fu"><a href="https://rdrr.io/r/base/save.html">save</a></span><span class="op">(</span><span class="va">mkin_benchmarks</span>, file <span class="op">=</span> <span class="st">"~/git/mkin/vignettes/web_only/mkin_benchmarks.rda"</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="va">mkin_benchmarks</span><span class="op">[</span><span class="va">system_string</span>, <span class="fu"><a href="https://rdrr.io/r/base/paste.html" class="external-link">paste0</a></span><span class="op">(</span><span class="st">"t"</span>, <span class="fl">1</span><span class="op">:</span><span class="fl">11</span><span class="op">)</span><span class="op">]</span> <span class="op"><-</span> + <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="va">t1</span>, <span class="va">t2</span>, <span class="va">t3</span>, <span class="va">t4</span>, <span class="va">t5</span>, <span class="va">t6</span>, <span class="va">t7</span>, <span class="va">t8</span>, <span class="va">t9</span>, <span class="va">t10</span>, <span class="va">t11</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/base/save.html" class="external-link">save</a></span><span class="op">(</span><span class="va">mkin_benchmarks</span>, file <span class="op">=</span> <span class="st">"~/git/mkin/vignettes/web_only/mkin_benchmarks.rda"</span><span class="op">)</span></code></pre></div> </div> -<div id="results" class="section level2"> -<h2 class="hasAnchor"> -<a href="#results" class="anchor"></a>Results</h2> +<div class="section level2"> +<h2 id="results">Results<a class="anchor" aria-label="anchor" href="#results"></a> +</h2> <p>Currently, we only have benchmark information on one system, therefore only the mkin version is shown with the results below. Timings are in seconds, shorter is better. All results were obtained by serial, i.e. not using multiple computing cores.</p> <p>Benchmarks for all available error models are shown.</p> -<div id="parent-only" class="section level3"> -<h3 class="hasAnchor"> -<a href="#parent-only" class="anchor"></a>Parent only</h3> +<div class="section level3"> +<h3 id="parent-only">Parent only<a class="anchor" aria-label="anchor" href="#parent-only"></a> +</h3> <p>Constant variance (t1) and two-component error model (t2) for four models fitted to two datasets, i.e. eight fits for each test.</p> <table class="table"> <thead><tr class="header"> @@ -237,12 +242,17 @@ <td align="right">1.867</td> <td align="right">3.450</td> </tr> +<tr class="odd"> +<td align="left">1.1.0</td> +<td align="right">1.938</td> +<td align="right">3.517</td> +</tr> </tbody> </table> </div> -<div id="one-metabolite" class="section level3"> -<h3 class="hasAnchor"> -<a href="#one-metabolite" class="anchor"></a>One metabolite</h3> +<div class="section level3"> +<h3 id="one-metabolite">One metabolite<a class="anchor" aria-label="anchor" href="#one-metabolite"></a> +</h3> <p>Constant variance (t3), two-component error model (t4), and variance by variable (t5) for three models fitted to one dataset, i.e. three fits for each test.</p> <table class="table"> <thead><tr class="header"> @@ -312,12 +322,18 @@ <td align="right">6.364</td> <td align="right">2.820</td> </tr> +<tr class="odd"> +<td align="left">1.1.0</td> +<td align="right">1.470</td> +<td align="right">6.508</td> +<td align="right">2.894</td> +</tr> </tbody> </table> </div> -<div id="two-metabolites" class="section level3"> -<h3 class="hasAnchor"> -<a href="#two-metabolites" class="anchor"></a>Two metabolites</h3> +<div class="section level3"> +<h3 id="two-metabolites">Two metabolites<a class="anchor" aria-label="anchor" href="#two-metabolites"></a> +</h3> <p>Constant variance (t6 and t7), two-component error model (t8 and t9), and variance by variable (t10 and t11) for one model fitted to one dataset, i.e. one fit for each test.</p> <table class="table"> <thead><tr class="header"> @@ -420,6 +436,15 @@ <td align="right">1.936</td> <td align="right">2.826</td> </tr> +<tr class="odd"> +<td align="left">1.1.0</td> +<td align="right">0.810</td> +<td align="right">1.264</td> +<td align="right">1.503</td> +<td align="right">3.096</td> +<td align="right">1.984</td> +<td align="right">2.847</td> +</tr> </tbody> </table> </div> @@ -437,11 +462,13 @@ <footer><div class="copyright"> - <p>Developed by Johannes Ranke.</p> + <p></p> +<p>Developed by Johannes Ranke.</p> </div> <div class="pkgdown"> - <p>Site built with <a href="https://pkgdown.r-lib.org/">pkgdown</a> 1.6.1.</p> + <p></p> +<p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.2.</p> </div> </footer> @@ -450,5 +477,7 @@ + + </body> </html> diff --git a/docs/articles/web_only/compiled_models.html b/docs/articles/web_only/compiled_models.html index ce8d8481..35ea6f27 100644 --- a/docs/articles/web_only/compiled_models.html +++ b/docs/articles/web_only/compiled_models.html @@ -19,6 +19,8 @@ <![endif]--> </head> <body data-spy="scroll" data-target="#toc"> + + <div class="container template-article"> <header><div class="navbar navbar-default navbar-fixed-top" role="navigation"> <div class="container"> @@ -31,7 +33,7 @@ </button> <span class="navbar-brand"> <a class="navbar-link" href="../../index.html">mkin</a> - <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.0.3</span> + <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.1.0</span> </span> </div> @@ -57,6 +59,9 @@ <a href="../../articles/FOCUS_L.html">Example evaluation of FOCUS Laboratory Data L1 to L3</a> </li> <li> + <a href="../../articles/web_only/dimethenamid_2018.html">Example evaluations of dimethenamid data from 2018 with nonlinear mixed-effects models</a> + </li> + <li> <a href="../../articles/web_only/FOCUS_Z.html">Example evaluation of FOCUS Example Dataset Z</a> </li> <li> @@ -79,7 +84,7 @@ </ul> <ul class="nav navbar-nav navbar-right"> <li> - <a href="https://github.com/jranke/mkin/"> + <a href="https://github.com/jranke/mkin/" class="external-link"> <span class="fab fa-github fa-lg"></span> </a> @@ -94,53 +99,53 @@ - </header><script src="compiled_models_files/header-attrs-2.6/header-attrs.js"></script><script src="compiled_models_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> + </header><script src="compiled_models_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> <div class="col-md-9 contents"> <div class="page-header toc-ignore"> <h1 data-toc-skip>Performance benefit by using compiled model definitions in mkin</h1> - <h4 class="author">Johannes Ranke</h4> + <h4 data-toc-skip class="author">Johannes Ranke</h4> - <h4 class="date">2021-02-15</h4> + <h4 data-toc-skip class="date">2022-03-02</h4> - <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/web_only/compiled_models.rmd"><code>vignettes/web_only/compiled_models.rmd</code></a></small> + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/web_only/compiled_models.rmd" class="external-link"><code>vignettes/web_only/compiled_models.rmd</code></a></small> <div class="hidden name"><code>compiled_models.rmd</code></div> </div> -<div id="how-to-benefit-from-compiled-models" class="section level2"> -<h2 class="hasAnchor"> -<a href="#how-to-benefit-from-compiled-models" class="anchor"></a>How to benefit from compiled models</h2> +<div class="section level2"> +<h2 id="how-to-benefit-from-compiled-models">How to benefit from compiled models<a class="anchor" aria-label="anchor" href="#how-to-benefit-from-compiled-models"></a> +</h2> <p>When using an mkin version equal to or greater than 0.9-36 and a C compiler is available, you will see a message that the model is being compiled from autogenerated C code when defining a model using mkinmod. Starting from version 0.9.49.9, the <code><a href="../../reference/mkinmod.html">mkinmod()</a></code> function checks for presence of a compiler using</p> <div class="sourceCode" id="cb1"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu">pkgbuild</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/pkgbuild/man/has_compiler.html">has_compiler</a></span><span class="op">(</span><span class="op">)</span></code></pre></div> -<p>In previous versions, it used <code><a href="https://rdrr.io/r/base/Sys.which.html">Sys.which("gcc")</a></code> for this check.</p> +<code class="sourceCode R"><span class="fu">pkgbuild</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/pkgbuild/man/has_compiler.html" class="external-link">has_compiler</a></span><span class="op">(</span><span class="op">)</span></code></pre></div> +<p>In previous versions, it used <code>Sys.which("gcc")</code> for this check.</p> <p>On Linux, you need to have the essential build tools like make and gcc or clang installed. On Debian based linux distributions, these will be pulled in by installing the build-essential package.</p> <p>On MacOS, which I do not use personally, I have had reports that a compiler is available by default.</p> <p>On Windows, you need to install Rtools and have the path to its bin directory in your PATH variable. You do not need to modify the PATH variable when installing Rtools. Instead, I would recommend to put the line</p> <div class="sourceCode" id="cb2"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/Sys.setenv.html">Sys.setenv</a></span><span class="op">(</span>PATH <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/paste.html">paste</a></span><span class="op">(</span><span class="st">"C:/Rtools/bin"</span>, <span class="fu"><a href="https://rdrr.io/r/base/Sys.getenv.html">Sys.getenv</a></span><span class="op">(</span><span class="st">"PATH"</span><span class="op">)</span>, sep<span class="op">=</span><span class="st">";"</span><span class="op">)</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/Sys.setenv.html" class="external-link">Sys.setenv</a></span><span class="op">(</span>PATH <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/paste.html" class="external-link">paste</a></span><span class="op">(</span><span class="st">"C:/Rtools/bin"</span>, <span class="fu"><a href="https://rdrr.io/r/base/Sys.getenv.html" class="external-link">Sys.getenv</a></span><span class="op">(</span><span class="st">"PATH"</span><span class="op">)</span>, sep<span class="op">=</span><span class="st">";"</span><span class="op">)</span><span class="op">)</span></code></pre></div> <p>into your .Rprofile startup file. This is just a text file with some R code that is executed when your R session starts. It has to be named .Rprofile and has to be located in your home directory, which will generally be your Documents folder. You can check the location of the home directory used by R by issuing</p> <div class="sourceCode" id="cb3"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/Sys.getenv.html">Sys.getenv</a></span><span class="op">(</span><span class="st">"HOME"</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/Sys.getenv.html" class="external-link">Sys.getenv</a></span><span class="op">(</span><span class="st">"HOME"</span><span class="op">)</span></code></pre></div> </div> -<div id="comparison-with-other-solution-methods" class="section level2"> -<h2 class="hasAnchor"> -<a href="#comparison-with-other-solution-methods" class="anchor"></a>Comparison with other solution methods</h2> +<div class="section level2"> +<h2 id="comparison-with-other-solution-methods">Comparison with other solution methods<a class="anchor" aria-label="anchor" href="#comparison-with-other-solution-methods"></a> +</h2> <p>First, we build a simple degradation model for a parent compound with one metabolite, and we remove zero values from the dataset.</p> <div class="sourceCode" id="cb4"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html">library</a></span><span class="op">(</span><span class="st"><a href="https://pkgdown.jrwb.de/mkin/">"mkin"</a></span>, quietly <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> +<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="st"><a href="https://pkgdown.jrwb.de/mkin/">"mkin"</a></span>, quietly <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> <span class="va">SFO_SFO</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span> parent <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"m1"</span><span class="op">)</span>, m1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> <div class="sourceCode" id="cb6"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="va">FOCUS_D</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/subset.html">subset</a></span><span class="op">(</span><span class="va">FOCUS_2006_D</span>, <span class="va">value</span> <span class="op">!=</span> <span class="fl">0</span><span class="op">)</span></code></pre></div> +<code class="sourceCode R"><span class="va">FOCUS_D</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/saemix/man/subset.html" class="external-link">subset</a></span><span class="op">(</span><span class="va">FOCUS_2006_D</span>, <span class="va">value</span> <span class="op">!=</span> <span class="fl">0</span><span class="op">)</span></code></pre></div> <p>We can compare the performance of the Eigenvalue based solution against the compiled version and the R implementation of the differential equations using the benchmark package. In the output of below code, the warnings about zero being removed from the FOCUS D dataset are suppressed. Since mkin version 0.9.49.11, an analytical solution is also implemented, which is included in the tests below.</p> <div class="sourceCode" id="cb7"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="kw">if</span> <span class="op">(</span><span class="kw"><a href="https://rdrr.io/r/base/library.html">require</a></span><span class="op">(</span><span class="va"><a href="http://rbenchmark.googlecode.com">rbenchmark</a></span><span class="op">)</span><span class="op">)</span> <span class="op">{</span> - <span class="va">b.1</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/rbenchmark/man/benchmark.html">benchmark</a></span><span class="op">(</span> +<code class="sourceCode R"><span class="kw">if</span> <span class="op">(</span><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">require</a></span><span class="op">(</span><span class="va"><a href="http://rbenchmark.googlecode.com" class="external-link">rbenchmark</a></span><span class="op">)</span><span class="op">)</span> <span class="op">{</span> + <span class="va">b.1</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/rbenchmark/man/benchmark.html" class="external-link">benchmark</a></span><span class="op">(</span> <span class="st">"deSolve, not compiled"</span> <span class="op">=</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">SFO_SFO</span>, <span class="va">FOCUS_D</span>, solution_type <span class="op">=</span> <span class="st">"deSolve"</span>, use_compiled <span class="op">=</span> <span class="cn">FALSE</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>, @@ -152,50 +157,50 @@ solution_type <span class="op">=</span> <span class="st">"analytical"</span>, use_compiled <span class="op">=</span> <span class="cn">FALSE</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>, replications <span class="op">=</span> <span class="fl">1</span>, order <span class="op">=</span> <span class="st">"relative"</span>, - columns <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="st">"test"</span>, <span class="st">"replications"</span>, <span class="st">"relative"</span>, <span class="st">"elapsed"</span><span class="op">)</span><span class="op">)</span> - <span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">b.1</span><span class="op">)</span> + columns <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"test"</span>, <span class="st">"replications"</span>, <span class="st">"relative"</span>, <span class="st">"elapsed"</span><span class="op">)</span><span class="op">)</span> + <span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">b.1</span><span class="op">)</span> <span class="op">}</span> <span class="kw">else</span> <span class="op">{</span> - <span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="st">"R package rbenchmark is not available"</span><span class="op">)</span> + <span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="st">"R package rbenchmark is not available"</span><span class="op">)</span> <span class="op">}</span></code></pre></div> -<pre><code>## test replications relative elapsed -## 4 analytical 1 1.000 0.181 -## 3 deSolve, compiled 1 1.812 0.328 -## 2 Eigenvalue based 1 2.088 0.378 -## 1 deSolve, not compiled 1 45.923 8.312</code></pre> +<pre><code><span class="co">## test replications relative elapsed</span> +<span class="co">## 4 analytical 1 1.000 0.216</span> +<span class="co">## 3 deSolve, compiled 1 1.708 0.369</span> +<span class="co">## 2 Eigenvalue based 1 1.866 0.403</span> +<span class="co">## 1 deSolve, not compiled 1 34.009 7.346</span></code></pre> <p>We see that using the compiled model is by more than a factor of 10 faster than using deSolve without compiled code.</p> </div> -<div id="model-without-analytical-solution" class="section level2"> -<h2 class="hasAnchor"> -<a href="#model-without-analytical-solution" class="anchor"></a>Model without analytical solution</h2> +<div class="section level2"> +<h2 id="model-without-analytical-solution">Model without analytical solution<a class="anchor" aria-label="anchor" href="#model-without-analytical-solution"></a> +</h2> <p>This evaluation is also taken from the example section of mkinfit. No analytical solution is available for this system, and now Eigenvalue based solution is possible, so only deSolve using with or without compiled code is available.</p> <div class="sourceCode" id="cb9"><pre class="downlit sourceCode r"> -<code class="sourceCode R"><span class="kw">if</span> <span class="op">(</span><span class="kw"><a href="https://rdrr.io/r/base/library.html">require</a></span><span class="op">(</span><span class="va"><a href="http://rbenchmark.googlecode.com">rbenchmark</a></span><span class="op">)</span><span class="op">)</span> <span class="op">{</span> +<code class="sourceCode R"><span class="kw">if</span> <span class="op">(</span><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">require</a></span><span class="op">(</span><span class="va"><a href="http://rbenchmark.googlecode.com" class="external-link">rbenchmark</a></span><span class="op">)</span><span class="op">)</span> <span class="op">{</span> <span class="va">FOMC_SFO</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span> parent <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"FOMC"</span>, <span class="st">"m1"</span><span class="op">)</span>, m1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span> <span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span> - <span class="va">b.2</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/rbenchmark/man/benchmark.html">benchmark</a></span><span class="op">(</span> + <span class="va">b.2</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/rbenchmark/man/benchmark.html" class="external-link">benchmark</a></span><span class="op">(</span> <span class="st">"deSolve, not compiled"</span> <span class="op">=</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">FOMC_SFO</span>, <span class="va">FOCUS_D</span>, use_compiled <span class="op">=</span> <span class="cn">FALSE</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>, <span class="st">"deSolve, compiled"</span> <span class="op">=</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">FOMC_SFO</span>, <span class="va">FOCUS_D</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>, replications <span class="op">=</span> <span class="fl">1</span>, order <span class="op">=</span> <span class="st">"relative"</span>, - columns <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span><span class="st">"test"</span>, <span class="st">"replications"</span>, <span class="st">"relative"</span>, <span class="st">"elapsed"</span><span class="op">)</span><span class="op">)</span> - <span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">b.2</span><span class="op">)</span> - <span class="va">factor_FOMC_SFO</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/Round.html">round</a></span><span class="op">(</span><span class="va">b.2</span><span class="op">[</span><span class="st">"1"</span>, <span class="st">"relative"</span><span class="op">]</span><span class="op">)</span> + columns <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"test"</span>, <span class="st">"replications"</span>, <span class="st">"relative"</span>, <span class="st">"elapsed"</span><span class="op">)</span><span class="op">)</span> + <span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">b.2</span><span class="op">)</span> + <span class="va">factor_FOMC_SFO</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/Round.html" class="external-link">round</a></span><span class="op">(</span><span class="va">b.2</span><span class="op">[</span><span class="st">"1"</span>, <span class="st">"relative"</span><span class="op">]</span><span class="op">)</span> <span class="op">}</span> <span class="kw">else</span> <span class="op">{</span> <span class="va">factor_FOMC_SFO</span> <span class="op"><-</span> <span class="cn">NA</span> - <span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="st">"R package benchmark is not available"</span><span class="op">)</span> + <span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="st">"R package benchmark is not available"</span><span class="op">)</span> <span class="op">}</span></code></pre></div> -<pre><code>## Temporary DLL for differentials generated and loaded</code></pre> -<pre><code>## test replications relative elapsed -## 2 deSolve, compiled 1 1.000 0.486 -## 1 deSolve, not compiled 1 31.597 15.356</code></pre> -<p>Here we get a performance benefit of a factor of 32 using the version of the differential equation model compiled from C code!</p> -<p>This vignette was built with mkin 1.0.3 on</p> -<pre><code>## R version 4.0.3 (2020-10-10) -## Platform: x86_64-pc-linux-gnu (64-bit) -## Running under: Debian GNU/Linux bullseye/sid</code></pre> -<pre><code>## CPU model: AMD Ryzen 7 1700 Eight-Core Processor</code></pre> +<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre> +<pre><code><span class="co">## test replications relative elapsed</span> +<span class="co">## 2 deSolve, compiled 1 1.000 0.533</span> +<span class="co">## 1 deSolve, not compiled 1 25.146 13.403</span></code></pre> +<p>Here we get a performance benefit of a factor of 25 using the version of the differential equation model compiled from C code!</p> +<p>This vignette was built with mkin 1.1.0 on</p> +<pre><code><span class="co">## R version 4.1.2 (2021-11-01)</span> +<span class="co">## Platform: x86_64-pc-linux-gnu (64-bit)</span> +<span class="co">## Running under: Debian GNU/Linux 11 (bullseye)</span></code></pre> +<pre><code><span class="co">## CPU model: AMD Ryzen 7 1700 Eight-Core Processor</span></code></pre> </div> </div> @@ -210,11 +215,13 @@ <footer><div class="copyright"> - <p>Developed by Johannes Ranke.</p> + <p></p> +<p>Developed by Johannes Ranke.</p> </div> <div class="pkgdown"> - <p>Site built with <a href="https://pkgdown.r-lib.org/">pkgdown</a> 1.6.1.</p> + <p></p> +<p>Site built with <a href="https://pkgdown.r-lib.org/" 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src="dimethenamid_2018_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row"> + <div class="col-md-9 contents"> + <div class="page-header toc-ignore"> + <h1 data-toc-skip>Example evaluations of the dimethenamid data from 2018</h1> + <h4 data-toc-skip class="author">Johannes Ranke</h4> + + <h4 data-toc-skip class="date">Last change 10 February 2022, built on 02 Mär 2022</h4> + + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/web_only/dimethenamid_2018.rmd" class="external-link"><code>vignettes/web_only/dimethenamid_2018.rmd</code></a></small> + <div class="hidden name"><code>dimethenamid_2018.rmd</code></div> + + </div> + + + +<p><a href="http://www.jrwb.de" class="external-link">Wissenschaftlicher Berater, Kronacher Str. 12, 79639 Grenzach-Wyhlen, Germany</a></p> +<div class="section level2"> +<h2 id="introduction">Introduction<a class="anchor" aria-label="anchor" href="#introduction"></a> +</h2> +<p>During the preparation of the journal article on nonlinear mixed-effects models in degradation kinetics <span class="citation">(Ranke et al. 2021)</span> and the analysis of the dimethenamid degradation data analysed therein, a need for a more detailed analysis using not only nlme and saemix, but also nlmixr for fitting the mixed-effects models was identified, as many model variants do not converge when fitted with nlme, and not all relevant error models can be fitted with saemix.</p> +<p>This vignette is an attempt to satisfy this need.</p> +</div> +<div class="section level2"> +<h2 id="data">Data<a class="anchor" aria-label="anchor" href="#data"></a> +</h2> +<p>Residue data forming the basis for the endpoints derived in the conclusion on the peer review of the pesticide risk assessment of dimethenamid-P published by the European Food Safety Authority (EFSA) in 2018 <span class="citation">(EFSA 2018)</span> were transcribed from the risk assessment report <span class="citation">(Rapporteur Member State Germany, Co-Rapporteur Member State Bulgaria 2018)</span> which can be downloaded from the Open EFSA repository <a href="https://open.efsa.europa.eu" class="external-link">https://open.efsa.europa.eu/study-inventory/EFSA-Q-2014-00716</a>.</p> +<p>The data are <a href="https://pkgdown.jrwb.de/mkin/reference/dimethenamid_2018.html">available in the mkin package</a>. The following code (hidden by default, please use the button to the right to show it) treats the data available for the racemic mixture dimethenamid (DMTA) and its enantiomer dimethenamid-P (DMTAP) in the same way, as no difference between their degradation behaviour was identified in the EU risk assessment. The observation times of each dataset are multiplied with the corresponding normalisation factor also available in the dataset, in order to make it possible to describe all datasets with a single set of parameters.</p> +<p>Also, datasets observed in the same soil are merged, resulting in dimethenamid (DMTA) data from six soils.</p> +<div class="sourceCode" id="cb1"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="va"><a href="https://pkgdown.jrwb.de/mkin/">mkin</a></span>, quietly <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> +<span class="va">dmta_ds</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">lapply</a></span><span class="op">(</span><span class="fl">1</span><span class="op">:</span><span class="fl">7</span>, <span class="kw">function</span><span class="op">(</span><span class="va">i</span><span class="op">)</span> <span class="op">{</span> + <span class="va">ds_i</span> <span class="op"><-</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">ds</span><span class="op">[[</span><span class="va">i</span><span class="op">]</span><span class="op">]</span><span class="op">$</span><span class="va">data</span> + <span class="va">ds_i</span><span class="op">[</span><span class="va">ds_i</span><span class="op">$</span><span class="va">name</span> <span class="op">==</span> <span class="st">"DMTAP"</span>, <span class="st">"name"</span><span class="op">]</span> <span class="op"><-</span> <span class="st">"DMTA"</span> + <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op"><-</span> <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op">*</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">f_time_norm</span><span class="op">[</span><span class="va">i</span><span class="op">]</span> + <span class="va">ds_i</span> +<span class="op">}</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">)</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">ds</span>, <span class="kw">function</span><span class="op">(</span><span class="va">ds</span><span class="op">)</span> <span class="va">ds</span><span class="op">$</span><span class="va">title</span><span class="op">)</span> +<span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/cbind.html" class="external-link">rbind</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 1"</span><span class="op">]</span><span class="op">]</span>, <span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 2"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span> +<span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 1"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="cn">NULL</span> +<span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 2"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="cn">NULL</span></code></pre></div> +</div> +<div class="section level2"> +<h2 id="parent-degradation">Parent degradation<a class="anchor" aria-label="anchor" href="#parent-degradation"></a> +</h2> +<p>We evaluate the observed degradation of the parent compound using simple exponential decline (SFO) and biexponential decline (DFOP), using constant variance (const) and a two-component variance (tc) as error models.</p> +<div class="section level3"> +<h3 id="separate-evaluations">Separate evaluations<a class="anchor" aria-label="anchor" href="#separate-evaluations"></a> +</h3> +<p>As a first step, to get a visual impression of the fit of the different models, we do separate evaluations for each soil using the mmkin function from the mkin package:</p> +<div class="sourceCode" id="cb2"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_mkin_const</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mmkin.html">mmkin</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"DFOP"</span><span class="op">)</span>, <span class="va">dmta_ds</span>, + error_model <span class="op">=</span> <span class="st">"const"</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span> +<span class="va">f_parent_mkin_tc</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mmkin.html">mmkin</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"DFOP"</span><span class="op">)</span>, <span class="va">dmta_ds</span>, + error_model <span class="op">=</span> <span class="st">"tc"</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> +<p>The plot of the individual SFO fits shown below suggests that at least in some datasets the degradation slows down towards later time points, and that the scatter of the residuals error is smaller for smaller values (panel to the right):</p> +<div class="sourceCode" id="cb3"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="fu"><a href="../../reference/mixed.html">mixed</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span><span class="op">)</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_mkin_sfo_const-1.png" width="700"></p> +<p>Using biexponential decline (DFOP) results in a slightly more random scatter of the residuals:</p> +<div class="sourceCode" id="cb4"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="fu"><a href="../../reference/mixed.html">mixed</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span><span class="op">)</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_mkin_dfop_const-1.png" width="700"></p> +<p>The population curve (bold line) in the above plot results from taking the mean of the individual transformed parameters, i.e. of log k1 and log k2, as well as of the logit of the g parameter of the DFOP model). Here, this procedure does not result in parameters that represent the degradation well, because in some datasets the fitted value for k2 is extremely close to zero, leading to a log k2 value that dominates the average. This is alleviated if only rate constants that pass the t-test for significant difference from zero (on the untransformed scale) are considered in the averaging:</p> +<div class="sourceCode" id="cb5"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="fu"><a href="../../reference/mixed.html">mixed</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span><span class="op">)</span>, test_log_parms <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_mkin_dfop_const_test-1.png" width="700"></p> +<p>While this is visually much more satisfactory, such an average procedure could introduce a bias, as not all results from the individual fits enter the population curve with the same weight. This is where nonlinear mixed-effects models can help out by treating all datasets with equally by fitting a parameter distribution model together with the degradation model and the error model (see below).</p> +<p>The remaining trend of the residuals to be higher for higher predicted residues is reduced by using the two-component error model:</p> +<div class="sourceCode" id="cb6"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="fu"><a href="../../reference/mixed.html">mixed</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span><span class="op">)</span>, test_log_parms <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_mkin_dfop_tc_test-1.png" width="700"></p> +<p>However, note that in the case of using this error model, the fits to the Flaach and BBA 2.3 datasets appear to be ill-defined, indicated by the fact that they did not converge:</p> +<div class="sourceCode" id="cb7"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span><span class="op">)</span></code></pre></div> +<pre><code><mmkin> object +Status of individual fits: + + dataset +model Calke Borstel Flaach BBA 2.2 BBA 2.3 Elliot + DFOP OK OK C OK C OK + +OK: No warnings +C: Optimisation did not converge: +iteration limit reached without convergence (10)</code></pre> +</div> +<div class="section level3"> +<h3 id="nonlinear-mixed-effects-models">Nonlinear mixed-effects models<a class="anchor" aria-label="anchor" href="#nonlinear-mixed-effects-models"></a> +</h3> +<p>Instead of taking a model selection decision for each of the individual fits, we fit nonlinear mixed-effects models (using different fitting algorithms as implemented in different packages) and do model selection using all available data at the same time. In order to make sure that these decisions are not unduly influenced by the type of algorithm used, by implementation details or by the use of wrong control parameters, we compare the model selection results obtained with different R packages, with different algorithms and checking control parameters.</p> +<div class="section level4"> +<h4 id="nlme">nlme<a class="anchor" aria-label="anchor" href="#nlme"></a> +</h4> +<p>The nlme package was the first R extension providing facilities to fit nonlinear mixed-effects models. We would like to do model selection from all four combinations of degradation models and error models based on the AIC. However, fitting the DFOP model with constant variance and using default control parameters results in an error, signalling that the maximum number of 50 iterations was reached, potentially indicating overparameterisation. Nevertheless, the algorithm converges when the two-component error model is used in combination with the DFOP model. This can be explained by the fact that the smaller residues observed at later sampling times get more weight when using the two-component error model which will counteract the tendency of the algorithm to try parameter combinations unsuitable for fitting these data.</p> +<div class="sourceCode" id="cb9"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="va"><a href="https://svn.r-project.org/R-packages/trunk/nlme/" class="external-link">nlme</a></span><span class="op">)</span> +<span class="va">f_parent_nlme_sfo_const</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlme/man/nlme.html" class="external-link">nlme</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span><span class="op">)</span> +<span class="co"># f_parent_nlme_dfop_const <- nlme(f_parent_mkin_const["DFOP", ])</span> +<span class="va">f_parent_nlme_sfo_tc</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlme/man/nlme.html" class="external-link">nlme</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span><span class="op">)</span> +<span class="va">f_parent_nlme_dfop_tc</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlme/man/nlme.html" class="external-link">nlme</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span><span class="op">)</span></code></pre></div> +<p>Note that a certain degree of overparameterisation is also indicated by a warning obtained when fitting DFOP with the two-component error model (‘false convergence’ in the ‘LME step’ in iteration 3). However, as this warning does not occur in later iterations, and specifically not in the last of the 6 iterations, we can ignore this warning.</p> +<p>The model comparison function of the nlme package can directly be applied to these fits showing a much lower AIC for the DFOP model fitted with the two-component error model. Also, the likelihood ratio test indicates that this difference is significant as the p-value is below 0.0001.</p> +<div class="sourceCode" id="cb10"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/stats/anova.html" class="external-link">anova</a></span><span class="op">(</span> + <span class="va">f_parent_nlme_sfo_const</span>, <span class="va">f_parent_nlme_sfo_tc</span>, <span class="va">f_parent_nlme_dfop_tc</span> +<span class="op">)</span></code></pre></div> +<pre><code> Model df AIC BIC logLik Test L.Ratio p-value +f_parent_nlme_sfo_const 1 5 796.60 811.82 -393.30 +f_parent_nlme_sfo_tc 2 6 798.60 816.86 -393.30 1 vs 2 0.00 0.998 +f_parent_nlme_dfop_tc 3 10 671.91 702.34 -325.96 2 vs 3 134.69 <.0001</code></pre> +<p>In addition to these fits, attempts were also made to include correlations between random effects by using the log Cholesky parameterisation of the matrix specifying them. The code used for these attempts can be made visible below.</p> +<div class="sourceCode" id="cb12"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_nlme_sfo_const_logchol</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlme/man/nlme.html" class="external-link">nlme</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, + random <span class="op">=</span> <span class="fu">nlme</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/nlme/man/pdLogChol.html" class="external-link">pdLogChol</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">DMTA_0</span> <span class="op">~</span> <span class="fl">1</span>, <span class="va">log_k_DMTA</span> <span class="op">~</span> <span class="fl">1</span><span class="op">)</span><span class="op">)</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/stats/anova.html" class="external-link">anova</a></span><span class="op">(</span><span class="va">f_parent_nlme_sfo_const</span>, <span class="va">f_parent_nlme_sfo_const_logchol</span><span class="op">)</span> +<span class="va">f_parent_nlme_sfo_tc_logchol</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlme/man/nlme.html" class="external-link">nlme</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, + random <span class="op">=</span> <span class="fu">nlme</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/nlme/man/pdLogChol.html" class="external-link">pdLogChol</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">DMTA_0</span> <span class="op">~</span> <span class="fl">1</span>, <span class="va">log_k_DMTA</span> <span class="op">~</span> <span class="fl">1</span><span class="op">)</span><span class="op">)</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/stats/anova.html" class="external-link">anova</a></span><span class="op">(</span><span class="va">f_parent_nlme_sfo_tc</span>, <span class="va">f_parent_nlme_sfo_tc_logchol</span><span class="op">)</span> +<span class="va">f_parent_nlme_dfop_tc_logchol</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlme/man/nlme.html" class="external-link">nlme</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, + random <span class="op">=</span> <span class="fu">nlme</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/nlme/man/pdLogChol.html" class="external-link">pdLogChol</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">DMTA_0</span> <span class="op">~</span> <span class="fl">1</span>, <span class="va">log_k1</span> <span class="op">~</span> <span class="fl">1</span>, <span class="va">log_k2</span> <span class="op">~</span> <span class="fl">1</span>, <span class="va">g_qlogis</span> <span class="op">~</span> <span class="fl">1</span><span class="op">)</span><span class="op">)</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/stats/anova.html" class="external-link">anova</a></span><span class="op">(</span><span class="va">f_parent_nlme_dfop_tc</span>, <span class="va">f_parent_nlme_dfop_tc_logchol</span><span class="op">)</span></code></pre></div> +<p>While the SFO variants converge fast, the additional parameters introduced by this lead to convergence warnings for the DFOP model. The model comparison clearly show that adding correlations between random effects does not improve the fits.</p> +<p>The selected model (DFOP with two-component error) fitted to the data assuming no correlations between random effects is shown below.</p> +<div class="sourceCode" id="cb13"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_parent_nlme_dfop_tc</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/plot_parent_nlme-1.png" width="700"></p> +</div> +<div class="section level4"> +<h4 id="saemix">saemix<a class="anchor" aria-label="anchor" href="#saemix"></a> +</h4> +<p>The saemix package provided the first Open Source implementation of the Stochastic Approximation to the Expectation Maximisation (SAEM) algorithm. SAEM fits of degradation models can be conveniently performed using an interface to the saemix package available in current development versions of the mkin package.</p> +<p>The corresponding SAEM fits of the four combinations of degradation and error models are fitted below. As there is no convergence criterion implemented in the saemix package, the convergence plots need to be manually checked for every fit. As we will compare the SAEM implementation of saemix to the results obtained using the nlmixr package later, we define control settings that work well for all the parent data fits shown in this vignette.</p> +<div class="sourceCode" id="cb14"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="va">saemix</span><span class="op">)</span> +<span class="va">saemix_control</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/saemix/man/saemixControl.html" class="external-link">saemixControl</a></span><span class="op">(</span>nbiter.saemix <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">800</span>, <span class="fl">300</span><span class="op">)</span>, nb.chains <span class="op">=</span> <span class="fl">15</span>, + print <span class="op">=</span> <span class="cn">FALSE</span>, save <span class="op">=</span> <span class="cn">FALSE</span>, save.graphs <span class="op">=</span> <span class="cn">FALSE</span>, displayProgress <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span> +<span class="va">saemix_control_moreiter</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/saemix/man/saemixControl.html" class="external-link">saemixControl</a></span><span class="op">(</span>nbiter.saemix <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">1600</span>, <span class="fl">300</span><span class="op">)</span>, nb.chains <span class="op">=</span> <span class="fl">15</span>, + print <span class="op">=</span> <span class="cn">FALSE</span>, save <span class="op">=</span> <span class="cn">FALSE</span>, save.graphs <span class="op">=</span> <span class="cn">FALSE</span>, displayProgress <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span> +<span class="va">saemix_control_10k</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/saemix/man/saemixControl.html" class="external-link">saemixControl</a></span><span class="op">(</span>nbiter.saemix <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">10000</span>, <span class="fl">300</span><span class="op">)</span>, nb.chains <span class="op">=</span> <span class="fl">15</span>, + print <span class="op">=</span> <span class="cn">FALSE</span>, save <span class="op">=</span> <span class="cn">FALSE</span>, save.graphs <span class="op">=</span> <span class="cn">FALSE</span>, displayProgress <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div> +<p>The convergence plot for the SFO model using constant variance is shown below.</p> +<div class="sourceCode" id="cb15"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_saemix_sfo_const</span> <span class="op"><-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>, + control <span class="op">=</span> <span class="va">saemix_control</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_parent_saemix_sfo_const</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_saemix_sfo_const-1.png" width="700"></p> +<p>Obviously the default number of iterations is sufficient to reach convergence. This can also be said for the SFO fit using the two-component error model.</p> +<div class="sourceCode" id="cb16"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_saemix_sfo_tc</span> <span class="op"><-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>, + control <span class="op">=</span> <span class="va">saemix_control</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_parent_saemix_sfo_tc</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_saemix_sfo_tc-1.png" width="700"></p> +<p>When fitting the DFOP model with constant variance (see below), parameter convergence is not as unambiguous.</p> +<div class="sourceCode" id="cb17"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_saemix_dfop_const</span> <span class="op"><-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>, + control <span class="op">=</span> <span class="va">saemix_control</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_const</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_saemix_dfop_const-1.png" width="700"></p> +<p>This is improved when the DFOP model is fitted with the two-component error model. Convergence of the variance of k2 is enhanced, it remains more or less stable already after 200 iterations of the first phase.</p> +<div class="sourceCode" id="cb18"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_saemix_dfop_tc</span> <span class="op"><-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>, + control <span class="op">=</span> <span class="va">saemix_control</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span> +<span class="va">f_parent_saemix_dfop_tc_moreiter</span> <span class="op"><-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>, + control <span class="op">=</span> <span class="va">saemix_control_moreiter</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_saemix_dfop_tc-1.png" width="700"></p> +<p>Doubling the number of iterations in the first phase of the algorithm leads to a slightly lower likelihood, and therefore to slightly higher AIC and BIC values. With even more iterations, the algorithm stops with an error message. This is related to the variance of k2 approximating zero. This has been submitted as a <a href="https://github.com/saemixdevelopment/saemixextension/issues/29" class="external-link">bug to the saemix package</a>, as the algorithm does not converge in this case.</p> +<p>An alternative way to fit DFOP in combination with the two-component error model is to use the model formulation with transformed parameters as used per default in mkin. When using this option, convergence is slower, but eventually the algorithm stops as well with the same error message.</p> +<p>The four combinations (SFO/const, SFO/tc, DFOP/const and DFOP/tc) and the version with increased iterations can be compared using the model comparison function of the saemix package:</p> +<div class="sourceCode" id="cb19"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">AIC_parent_saemix</span> <span class="op"><-</span> <span class="fu">saemix</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/compare.saemix.html" class="external-link">compare.saemix</a></span><span class="op">(</span> + <span class="va">f_parent_saemix_sfo_const</span><span class="op">$</span><span class="va">so</span>, + <span class="va">f_parent_saemix_sfo_tc</span><span class="op">$</span><span class="va">so</span>, + <span class="va">f_parent_saemix_dfop_const</span><span class="op">$</span><span class="va">so</span>, + <span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span>, + <span class="va">f_parent_saemix_dfop_tc_moreiter</span><span class="op">$</span><span class="va">so</span><span class="op">)</span></code></pre></div> +<pre><code>Likelihoods calculated by importance sampling</code></pre> +<div class="sourceCode" id="cb21"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/colnames.html" class="external-link">rownames</a></span><span class="op">(</span><span class="va">AIC_parent_saemix</span><span class="op">)</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span> + <span class="st">"SFO const"</span>, <span class="st">"SFO tc"</span>, <span class="st">"DFOP const"</span>, <span class="st">"DFOP tc"</span>, <span class="st">"DFOP tc more iterations"</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">AIC_parent_saemix</span><span class="op">)</span></code></pre></div> +<pre><code> AIC BIC +SFO const 796.38 795.34 +SFO tc 798.38 797.13 +DFOP const 705.75 703.88 +DFOP tc 665.65 663.57 +DFOP tc more iterations 665.88 663.80</code></pre> +<p>In order to check the influence of the likelihood calculation algorithms implemented in saemix, the likelihood from Gaussian quadrature is added to the best fit, and the AIC values obtained from the three methods are compared.</p> +<div class="sourceCode" id="cb23"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span> <span class="op"><-</span> + <span class="fu">saemix</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/llgq.saemix.html" class="external-link">llgq.saemix</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span><span class="op">)</span> +<span class="va">AIC_parent_saemix_methods</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span> + is <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span>, method <span class="op">=</span> <span class="st">"is"</span><span class="op">)</span>, + gq <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span>, method <span class="op">=</span> <span class="st">"gq"</span><span class="op">)</span>, + lin <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span>, method <span class="op">=</span> <span class="st">"lin"</span><span class="op">)</span> +<span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">AIC_parent_saemix_methods</span><span class="op">)</span></code></pre></div> +<pre><code> is gq lin +665.65 665.68 665.11 </code></pre> +<p>The AIC values based on importance sampling and Gaussian quadrature are very similar. Using linearisation is known to be less accurate, but still gives a similar value. In order to illustrate that the comparison of the three method depends on the degree of convergence obtained in the fit, the same comparison is shown below for the fit using the defaults for the number of iterations and the number of MCMC chains.</p> +<div class="sourceCode" id="cb25"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_saemix_dfop_tc_defaults</span> <span class="op"><-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span><span class="op">)</span> +<span class="va">f_parent_saemix_dfop_tc_defaults</span><span class="op">$</span><span class="va">so</span> <span class="op"><-</span> + <span class="fu">saemix</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/llgq.saemix.html" class="external-link">llgq.saemix</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc_defaults</span><span class="op">$</span><span class="va">so</span><span class="op">)</span> +<span class="va">AIC_parent_saemix_methods_defaults</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span> + is <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc_defaults</span><span class="op">$</span><span class="va">so</span>, method <span class="op">=</span> <span class="st">"is"</span><span class="op">)</span>, + gq <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc_defaults</span><span class="op">$</span><span class="va">so</span>, method <span class="op">=</span> <span class="st">"gq"</span><span class="op">)</span>, + lin <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc_defaults</span><span class="op">$</span><span class="va">so</span>, method <span class="op">=</span> <span class="st">"lin"</span><span class="op">)</span> +<span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">AIC_parent_saemix_methods_defaults</span><span class="op">)</span></code></pre></div> +<pre><code> is gq lin +668.27 718.36 666.49 </code></pre> +</div> +<div class="section level4"> +<h4 id="nlmixr">nlmixr<a class="anchor" aria-label="anchor" href="#nlmixr"></a> +</h4> +<p>In the last years, a lot of effort has been put into the nlmixr package which is designed for pharmacokinetics, where nonlinear mixed-effects models are routinely used, but which can also be used for related data like chemical degradation data. A current development branch of the mkin package provides an interface between mkin and nlmixr. Here, we check if we get equivalent results when using a refined version of the First Order Conditional Estimation (FOCE) algorithm used in nlme, namely the First Order Conditional Estimation with Interaction (FOCEI), and the SAEM algorithm as implemented in nlmixr.</p> +<p>First, the focei algorithm is used for the four model combinations.</p> +<div class="sourceCode" id="cb27"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="va"><a href="https://github.com/nlmixrdevelopment/nlmixr" class="external-link">nlmixr</a></span><span class="op">)</span> +<span class="va">f_parent_nlmixr_focei_sfo_const</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"focei"</span><span class="op">)</span> +<span class="va">f_parent_nlmixr_focei_sfo_tc</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"focei"</span><span class="op">)</span> +<span class="va">f_parent_nlmixr_focei_dfop_const</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"focei"</span><span class="op">)</span> +<span class="va">f_parent_nlmixr_focei_dfop_tc</span><span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"focei"</span><span class="op">)</span></code></pre></div> +<p>For the SFO model with constant variance, the AIC values are the same, for the DFOP model, there are significant differences between the AIC values. These may be caused by different solutions that are found, but also by the fact that the AIC values for the nlmixr fits are calculated based on Gaussian quadrature, not on linearisation.</p> +<div class="sourceCode" id="cb28"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">aic_nlmixr_focei</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span> + <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_focei_sfo_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_focei_sfo_tc</span><span class="op">$</span><span class="va">nm</span>, + <span class="va">f_parent_nlmixr_focei_dfop_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_focei_dfop_tc</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span>, + <span class="va">AIC</span><span class="op">)</span> +<span class="va">aic_nlme</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span> + <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">f_parent_nlme_sfo_const</span>, <span class="cn">NA</span>, <span class="va">f_parent_nlme_sfo_tc</span>, <span class="va">f_parent_nlme_dfop_tc</span><span class="op">)</span>, + <span class="kw">function</span><span class="op">(</span><span class="va">x</span><span class="op">)</span> <span class="kw">if</span> <span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/NA.html" class="external-link">is.na</a></span><span class="op">(</span><span class="va">x</span><span class="op">[</span><span class="fl">1</span><span class="op">]</span><span class="op">)</span><span class="op">)</span> <span class="cn">NA</span> <span class="kw">else</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">x</span><span class="op">)</span><span class="op">)</span> +<span class="va">aic_nlme_nlmixr_focei</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/data.frame.html" class="external-link">data.frame</a></span><span class="op">(</span> + <span class="st">"Degradation model"</span> <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"SFO"</span>, <span class="st">"DFOP"</span>, <span class="st">"DFOP"</span><span class="op">)</span>, + <span class="st">"Error model"</span> <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/rep.html" class="external-link">rep</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"constant variance"</span>, <span class="st">"two-component"</span><span class="op">)</span>, <span class="fl">2</span><span class="op">)</span>, + <span class="st">"AIC (nlme)"</span> <span class="op">=</span> <span class="va">aic_nlme</span>, + <span class="st">"AIC (nlmixr with FOCEI)"</span> <span class="op">=</span> <span class="va">aic_nlmixr_focei</span>, + check.names <span class="op">=</span> <span class="cn">FALSE</span> +<span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">aic_nlme_nlmixr_focei</span><span class="op">)</span></code></pre></div> +<pre><code> Degradation model Error model AIC (nlme) AIC (nlmixr with FOCEI) +1 SFO constant variance 796.60 796.60 +2 SFO two-component NA 798.64 +3 DFOP constant variance 798.60 745.87 +4 DFOP two-component 671.91 740.42</code></pre> +<p>Secondly, we use the SAEM estimation routine and check the convergence plots. The control parameters, which were also used for the saemix fits, are defined beforehand.</p> +<div class="sourceCode" id="cb30"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">nlmixr_saem_control_800</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/saemControl.html" class="external-link">saemControl</a></span><span class="op">(</span>logLik <span class="op">=</span> <span class="cn">TRUE</span>, + nBurn <span class="op">=</span> <span class="fl">800</span>, nEm <span class="op">=</span> <span class="fl">300</span>, nmc <span class="op">=</span> <span class="fl">15</span><span class="op">)</span> +<span class="va">nlmixr_saem_control_moreiter</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/saemControl.html" class="external-link">saemControl</a></span><span class="op">(</span>logLik <span class="op">=</span> <span class="cn">TRUE</span>, + nBurn <span class="op">=</span> <span class="fl">1600</span>, nEm <span class="op">=</span> <span class="fl">300</span>, nmc <span class="op">=</span> <span class="fl">15</span><span class="op">)</span> +<span class="va">nlmixr_saem_control_10k</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/saemControl.html" class="external-link">saemControl</a></span><span class="op">(</span>logLik <span class="op">=</span> <span class="cn">TRUE</span>, + nBurn <span class="op">=</span> <span class="fl">10000</span>, nEm <span class="op">=</span> <span class="fl">1000</span>, nmc <span class="op">=</span> <span class="fl">15</span><span class="op">)</span></code></pre></div> +<p>Then we fit SFO with constant variance</p> +<div class="sourceCode" id="cb31"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_sfo_const</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>, + control <span class="op">=</span> <span class="va">nlmixr_saem_control_800</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_sfo_const</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_sfo_const-1.png" width="700"></p> +<p>and SFO with two-component error.</p> +<div class="sourceCode" id="cb32"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_sfo_tc</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>, + control <span class="op">=</span> <span class="va">nlmixr_saem_control_800</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_sfo_tc</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_sfo_tc-1.png" width="700"></p> +<p>For DFOP with constant variance, the convergence plots show considerable instability of the fit, which indicates overparameterisation which was already observed above for this model combination. Also note that the variance of k2 approximates zero, which was already observed in the saemix fits of the DFOP model.</p> +<div class="sourceCode" id="cb33"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_dfop_const</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>, + control <span class="op">=</span> <span class="va">nlmixr_saem_control_800</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_dfop_const</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_dfop_const-1.png" width="700"></p> +<p>For DFOP with two-component error, a less erratic convergence is seen, but the variance of k2 again approximates zero.</p> +<div class="sourceCode" id="cb34"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_dfop_tc</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>, + control <span class="op">=</span> <span class="va">nlmixr_saem_control_800</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_dfop_tc</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_dfop_tc-1.png" width="700"></p> +<p>To check if an increase in the number of iterations improves the fit, we repeat the fit with 1000 iterations for the burn in phase and 300 iterations for the second phase.</p> +<div class="sourceCode" id="cb35"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_dfop_tc_moreiter</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>, + control <span class="op">=</span> <span class="va">nlmixr_saem_control_moreiter</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_dfop_tc_moreiter</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_dfop_tc_1k-1.png" width="700"></p> +<p>Here the fit looks very similar, but we will see below that it shows a higher AIC than the fit with 800 iterations in the burn in phase. Next we choose 10 000 iterations for the burn in phase and 1000 iterations for the second phase for comparison with saemix.</p> +<div class="sourceCode" id="cb36"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_dfop_tc_10k</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>, + control <span class="op">=</span> <span class="va">nlmixr_saem_control_10k</span><span class="op">)</span> +<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_dfop_tc_10k</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div> +<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_dfop_tc_10k-1.png" width="700"></p> +<p>The AIC values are internally calculated using Gaussian quadrature.</p> +<div class="sourceCode" id="cb37"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_sfo_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_saem_sfo_tc</span><span class="op">$</span><span class="va">nm</span>, + <span class="va">f_parent_nlmixr_saem_dfop_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_saem_dfop_tc</span><span class="op">$</span><span class="va">nm</span>, + <span class="va">f_parent_nlmixr_saem_dfop_tc_moreiter</span><span class="op">$</span><span class="va">nm</span>, + <span class="va">f_parent_nlmixr_saem_dfop_tc_10k</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div> +<pre><code> df AIC +f_parent_nlmixr_saem_sfo_const$nm 5 798.71 +f_parent_nlmixr_saem_sfo_tc$nm 6 808.64 +f_parent_nlmixr_saem_dfop_const$nm 9 1995.96 +f_parent_nlmixr_saem_dfop_tc$nm 10 664.96 +f_parent_nlmixr_saem_dfop_tc_moreiter$nm 10 4464.93 +f_parent_nlmixr_saem_dfop_tc_10k$nm 10 Inf</code></pre> +<p>We can see that again, the DFOP/tc model shows the best goodness of fit. However, increasing the number of burn-in iterations from 800 to 1600 results in a higher AIC. If we further increase the number of iterations to 10 000 (burn-in) and 1000 (second phase), the AIC cannot be calculated for the nlmixr/saem fit, confirming that this fit does not converge properly with the SAEM algorithm.</p> +</div> +<div class="section level4"> +<h4 id="comparison">Comparison<a class="anchor" aria-label="anchor" href="#comparison"></a> +</h4> +<p>The following table gives the AIC values obtained with the three packages using the same control parameters (800 iterations burn-in, 300 iterations second phase, 15 chains).</p> +<div class="sourceCode" id="cb39"><pre class="downlit sourceCode r"> +<code class="sourceCode R"><span class="va">AIC_all</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/data.frame.html" class="external-link">data.frame</a></span><span class="op">(</span> + check.names <span class="op">=</span> <span class="cn">FALSE</span>, + <span class="st">"Degradation model"</span> <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"SFO"</span>, <span class="st">"DFOP"</span>, <span class="st">"DFOP"</span><span class="op">)</span>, + <span class="st">"Error model"</span> <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"const"</span>, <span class="st">"tc"</span>, <span class="st">"const"</span>, <span class="st">"tc"</span><span class="op">)</span>, + nlme <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_nlme_sfo_const</span><span class="op">)</span>, <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_nlme_sfo_tc</span><span class="op">)</span>, <span class="cn">NA</span>, <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_nlme_dfop_tc</span><span class="op">)</span><span class="op">)</span>, + nlmixr_focei <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_focei_sfo_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_focei_sfo_tc</span><span class="op">$</span><span class="va">nm</span>, + <span class="va">f_parent_nlmixr_focei_dfop_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_focei_dfop_tc</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span>, <span class="va">AIC</span><span class="op">)</span>, + saemix <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">f_parent_saemix_sfo_const</span><span class="op">$</span><span class="va">so</span>, <span class="va">f_parent_saemix_sfo_tc</span><span class="op">$</span><span class="va">so</span>, + <span class="va">f_parent_saemix_dfop_const</span><span class="op">$</span><span class="va">so</span>, <span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span><span class="op">)</span>, <span class="va">AIC</span><span class="op">)</span>, + nlmixr_saem <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_sfo_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_saem_sfo_tc</span><span class="op">$</span><span class="va">nm</span>, + <span class="va">f_parent_nlmixr_saem_dfop_const</span><span class="op">$</span><span class="va">nm</span>, <span class="va">f_parent_nlmixr_saem_dfop_tc</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span>, <span class="va">AIC</span><span class="op">)</span> +<span class="op">)</span> +<span class="fu">kable</span><span class="op">(</span><span class="va">AIC_all</span><span class="op">)</span></code></pre></div> +<table class="table"> +<thead><tr class="header"> +<th align="left">Degradation model</th> +<th align="left">Error model</th> +<th align="right">nlme</th> +<th align="right">nlmixr_focei</th> +<th align="right">saemix</th> +<th align="right">nlmixr_saem</th> +</tr></thead> +<tbody> +<tr class="odd"> +<td align="left">SFO</td> +<td align="left">const</td> +<td align="right">796.60</td> +<td align="right">796.60</td> +<td align="right">796.38</td> +<td align="right">798.71</td> +</tr> +<tr class="even"> +<td align="left">SFO</td> +<td align="left">tc</td> +<td align="right">798.60</td> +<td align="right">798.64</td> +<td align="right">798.38</td> +<td align="right">808.64</td> +</tr> +<tr class="odd"> +<td align="left">DFOP</td> +<td align="left">const</td> +<td align="right">NA</td> +<td align="right">745.87</td> +<td align="right">705.75</td> +<td align="right">1995.96</td> +</tr> +<tr class="even"> +<td align="left">DFOP</td> +<td align="left">tc</td> +<td align="right">671.91</td> +<td align="right">740.42</td> +<td align="right">665.65</td> +<td align="right">664.96</td> +</tr> +</tbody> +</table> +</div> +</div> +</div> +<div class="section level2"> +<h2 id="references">References<a class="anchor" aria-label="anchor" href="#references"></a> +</h2> +<!-- vim: set foldmethod=syntax: --> +<div id="refs" class="references hanging-indent"> +<div id="ref-efsa_2018_dimethenamid"> +<p>EFSA. 2018. “Peer Review of the Pesticide Risk Assessment of the Active Substance Dimethenamid-P.” <em>EFSA Journal</em> 16 (4): 5211.</p> +</div> +<div id="ref-ranke2021"> +<p>Ranke, Johannes, Janina Wöltjen, Jana Schmidt, and Emmanuelle Comets. 2021. “Taking Kinetic Evaluations of Degradation Data to the Next Level with Nonlinear Mixed-Effects Models.” <em>Environments</em> 8 (8). <a href="https://doi.org/10.3390/environments8080071" class="external-link">https://doi.org/10.3390/environments8080071</a>.</p> +</div> +<div id="ref-dimethenamid_rar_2018_b8"> +<p>Rapporteur Member State Germany, Co-Rapporteur Member State Bulgaria. 2018. “Renewal Assessment Report Dimethenamid-P Volume 3 - B.8 Environmental fate and behaviour, Rev. 2 - November 2017.” <a href="https://open.efsa.europa.eu/study-inventory/EFSA-Q-2014-00716" class="external-link">https://open.efsa.europa.eu/study-inventory/EFSA-Q-2014-00716</a>.</p> +</div> +</div> +</div> + </div> + + <div class="col-md-3 hidden-xs hidden-sm" id="pkgdown-sidebar"> + + <nav id="toc" data-toggle="toc"><h2 data-toc-skip>Contents</h2> + </nav> +</div> + +</div> + + + + <footer><div class="copyright"> + <p></p> +<p>Developed by Johannes Ranke.</p> +</div> + +<div class="pkgdown"> + <p></p> +<p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.2.</p> +</div> + + </footer> +</div> + + + + + + + </body> +</html> diff --git a/docs/articles/web_only/dimethenamid_2018_files/accessible-code-block-0.0.1/empty-anchor.js b/docs/articles/web_only/dimethenamid_2018_files/accessible-code-block-0.0.1/empty-anchor.js new file mode 100644 index 00000000..ca349fd6 --- /dev/null +++ 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