Make tests more platform independent, update docs

author: Johannes Ranke <jranke@uni-bremen.de> 2022-03-02 18:03:54 +0100
committer: Johannes Ranke <jranke@uni-bremen.de> 2022-03-02 18:03:54 +0100
commit: 2bb59c88d49b193f278916ad9cc4de83c0de9604 (patch)
tree: f286bba254d7c5f2d32eeb2b11f6148938b0e1e1 /docs/articles
parent: 351248d07f810ccb6c497633a02cd48ee35526e6 (diff)
65 files changed, 2501 insertions, 1935 deletions
diff --git a/docs/articles/FOCUS_D.html b/docs/articles/FOCUS_D.html
index 1bfba6e5..7ef16ef8 100644
--- a/docs/articles/FOCUS_D.html
+++ b/docs/articles/FOCUS_D.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>
@@ -94,15 +99,15 @@
 
       
 
-      </header><script src="FOCUS_D_files/header-attrs-2.7/header-attrs.js"></script><script src="FOCUS_D_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row">
+      </header><script src="FOCUS_D_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 Example Dataset D</h1>
-                        <h4 class="author">Johannes Ranke</h4>
+                        <h4 data-toc-skip class="author">Johannes Ranke</h4>
             
-            <h4 class="date">Last change 31 January 2019 (rebuilt 2021-03-31)</h4>
+            <h4 data-toc-skip class="date">Last change 31 January 2019 (rebuilt 2022-03-02)</h4>
       
-      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/FOCUS_D.rmd"><code>vignettes/FOCUS_D.rmd</code></a></small>
+      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/FOCUS_D.rmd" class="external-link"><code>vignettes/FOCUS_D.rmd</code></a></small>
       <div class="hidden name"><code>FOCUS_D.rmd</code></div>
 
     </div>
@@ -111,72 +116,72 @@
     
 <p>This is just a very simple vignette showing how to fit a degradation model for a parent compound with one transformation product using <code>mkin</code>. After loading the library we look at the data. We have observed concentrations in the column named <code>value</code> at the times specified in column <code>time</code> for the two observed variables named <code>parent</code> and <code>m1</code>.</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>
-<span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">FOCUS_2006_D</span><span class="op">)</span></code></pre></div>
-<pre><code>##      name time  value
-## 1  parent    0  99.46
-## 2  parent    0 102.04
-## 3  parent    1  93.50
-## 4  parent    1  92.50
-## 5  parent    3  63.23
-## 6  parent    3  68.99
-## 7  parent    7  52.32
-## 8  parent    7  55.13
-## 9  parent   14  27.27
-## 10 parent   14  26.64
-## 11 parent   21  11.50
-## 12 parent   21  11.64
-## 13 parent   35   2.85
-## 14 parent   35   2.91
-## 15 parent   50   0.69
-## 16 parent   50   0.63
-## 17 parent   75   0.05
-## 18 parent   75   0.06
-## 19 parent  100     NA
-## 20 parent  100     NA
-## 21 parent  120     NA
-## 22 parent  120     NA
-## 23     m1    0   0.00
-## 24     m1    0   0.00
-## 25     m1    1   4.84
-## 26     m1    1   5.64
-## 27     m1    3  12.91
-## 28     m1    3  12.96
-## 29     m1    7  22.97
-## 30     m1    7  24.47
-## 31     m1   14  41.69
-## 32     m1   14  33.21
-## 33     m1   21  44.37
-## 34     m1   21  46.44
-## 35     m1   35  41.22
-## 36     m1   35  37.95
-## 37     m1   50  41.19
-## 38     m1   50  40.01
-## 39     m1   75  40.09
-## 40     m1   75  33.85
-## 41     m1  100  31.04
-## 42     m1  100  33.13
-## 43     m1  120  25.15
-## 44     m1  120  33.31</code></pre>
+<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="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">FOCUS_2006_D</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">##      name time  value</span>
+<span class="co">## 1  parent    0  99.46</span>
+<span class="co">## 2  parent    0 102.04</span>
+<span class="co">## 3  parent    1  93.50</span>
+<span class="co">## 4  parent    1  92.50</span>
+<span class="co">## 5  parent    3  63.23</span>
+<span class="co">## 6  parent    3  68.99</span>
+<span class="co">## 7  parent    7  52.32</span>
+<span class="co">## 8  parent    7  55.13</span>
+<span class="co">## 9  parent   14  27.27</span>
+<span class="co">## 10 parent   14  26.64</span>
+<span class="co">## 11 parent   21  11.50</span>
+<span class="co">## 12 parent   21  11.64</span>
+<span class="co">## 13 parent   35   2.85</span>
+<span class="co">## 14 parent   35   2.91</span>
+<span class="co">## 15 parent   50   0.69</span>
+<span class="co">## 16 parent   50   0.63</span>
+<span class="co">## 17 parent   75   0.05</span>
+<span class="co">## 18 parent   75   0.06</span>
+<span class="co">## 19 parent  100     NA</span>
+<span class="co">## 20 parent  100     NA</span>
+<span class="co">## 21 parent  120     NA</span>
+<span class="co">## 22 parent  120     NA</span>
+<span class="co">## 23     m1    0   0.00</span>
+<span class="co">## 24     m1    0   0.00</span>
+<span class="co">## 25     m1    1   4.84</span>
+<span class="co">## 26     m1    1   5.64</span>
+<span class="co">## 27     m1    3  12.91</span>
+<span class="co">## 28     m1    3  12.96</span>
+<span class="co">## 29     m1    7  22.97</span>
+<span class="co">## 30     m1    7  24.47</span>
+<span class="co">## 31     m1   14  41.69</span>
+<span class="co">## 32     m1   14  33.21</span>
+<span class="co">## 33     m1   21  44.37</span>
+<span class="co">## 34     m1   21  46.44</span>
+<span class="co">## 35     m1   35  41.22</span>
+<span class="co">## 36     m1   35  37.95</span>
+<span class="co">## 37     m1   50  41.19</span>
+<span class="co">## 38     m1   50  40.01</span>
+<span class="co">## 39     m1   75  40.09</span>
+<span class="co">## 40     m1   75  33.85</span>
+<span class="co">## 41     m1  100  31.04</span>
+<span class="co">## 42     m1  100  33.13</span>
+<span class="co">## 43     m1  120  25.15</span>
+<span class="co">## 44     m1  120  33.31</span></code></pre>
 <p>Next we specify the degradation model: The parent compound degrades with simple first-order kinetics (SFO) to one metabolite named m1, which also degrades with SFO kinetics.</p>
 <p>The call to mkinmod returns a degradation model. The differential equations represented in R code can be found in the character vector <code>$diffs</code> of the <code>mkinmod</code> object. If a C compiler (gcc) is installed and functional, the differential equation model will be compiled from auto-generated C code.</p>
 <div class="sourceCode" id="cb3"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">SFO_SFO</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fu"><a href="../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"m1"</span><span class="op">)</span>, m1 <span class="op">=</span> <span class="fu"><a href="../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></code></pre></div>
-<pre><code>## Temporary DLL for differentials generated and loaded</code></pre>
+<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre>
 <div class="sourceCode" id="cb5"><pre class="downlit sourceCode r">
-<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/print.html">print</a></span><span class="op">(</span><span class="va">SFO_SFO</span><span class="op">$</span><span class="va">diffs</span><span class="op">)</span></code></pre></div>
-<pre><code>##                                                    parent 
-##                          "d_parent = - k_parent * parent" 
-##                                                        m1 
-## "d_m1 = + f_parent_to_m1 * k_parent * parent - k_m1 * m1"</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">SFO_SFO</span><span class="op">$</span><span class="va">diffs</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">##                                                    parent </span>
+<span class="co">##                          "d_parent = - k_parent * parent" </span>
+<span class="co">##                                                        m1 </span>
+<span class="co">## "d_m1 = + f_parent_to_m1 * k_parent * parent - k_m1 * m1"</span></code></pre>
 <p>We do the fitting without progress report (<code>quiet = TRUE</code>).</p>
 <div class="sourceCode" id="cb7"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">fit</span> <span class="op">&lt;-</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_2006_D</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div>
-<pre><code>## Warning in mkinfit(SFO_SFO, FOCUS_2006_D, quiet = TRUE): Observations with value
-## of zero were removed from the data</code></pre>
+<pre><code><span class="co">## Warning in mkinfit(SFO_SFO, FOCUS_2006_D, quiet = TRUE): Observations with value</span>
+<span class="co">## of zero were removed from the data</span></code></pre>
 <p>A plot of the fit including a residual plot for both observed variables is obtained using the <code>plot_sep</code> method for <code>mkinfit</code> objects, which shows separate graphs for all compounds and their residuals.</p>
 <div class="sourceCode" id="cb9"><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">fit</span>, lpos <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">"topright"</span>, <span class="st">"bottomright"</span><span class="op">)</span><span class="op">)</span></code></pre></div>
+<code class="sourceCode R"><span class="fu"><a href="../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">fit</span>, lpos <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">"topright"</span>, <span class="st">"bottomright"</span><span class="op">)</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_D_files/figure-html/plot-1.png" width="768"></p>
 <p>Confidence intervals for the parameter estimates are obtained using the <code>mkinparplot</code> function.</p>
 <div class="sourceCode" id="cb10"><pre class="downlit sourceCode r">
@@ -184,134 +189,134 @@
 <p><img src="FOCUS_D_files/figure-html/plot_2-1.png" width="768"></p>
 <p>A comprehensive report of the results is obtained using the <code>summary</code> method for <code>mkinfit</code> objects.</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/summary.html">summary</a></span><span class="op">(</span><span class="va">fit</span><span class="op">)</span></code></pre></div>
-<pre><code>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:28 2021 
-## Date of summary: Wed Mar 31 19:18:29 2021 
-## 
-## Equations:
-## d_parent/dt = - k_parent * parent
-## d_m1/dt = + f_parent_to_m1 * k_parent * parent - k_m1 * m1
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 401 model solutions performed in 0.159 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##                   value   type
-## parent_0       100.7500  state
-## k_parent         0.1000 deparm
-## k_m1             0.1001 deparm
-## f_parent_to_m1   0.5000 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##                      value lower upper
-## parent_0        100.750000  -Inf   Inf
-## log_k_parent     -2.302585  -Inf   Inf
-## log_k_m1         -2.301586  -Inf   Inf
-## f_parent_qlogis   0.000000  -Inf   Inf
-## 
-## Fixed parameter values:
-##      value  type
-## m1_0     0 state
-## 
-## 
-## Warning(s): 
-## Observations with value of zero were removed from the data
-## 
-## Results:
-## 
-##        AIC      BIC    logLik
-##   204.4486 212.6365 -97.22429
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##                 Estimate Std. Error   Lower    Upper
-## parent_0        99.60000    1.57000 96.4000 102.8000
-## log_k_parent    -2.31600    0.04087 -2.3990  -2.2330
-## log_k_m1        -5.24700    0.13320 -5.5180  -4.9770
-## f_parent_qlogis  0.05792    0.08926 -0.1237   0.2395
-## sigma            3.12600    0.35850  2.3960   3.8550
-## 
-## Parameter correlation:
-##                   parent_0 log_k_parent   log_k_m1 f_parent_qlogis      sigma
-## parent_0         1.000e+00    5.174e-01 -1.688e-01      -5.471e-01 -1.172e-06
-## log_k_parent     5.174e-01    1.000e+00 -3.263e-01      -5.426e-01 -8.483e-07
-## log_k_m1        -1.688e-01   -3.263e-01  1.000e+00       7.478e-01  8.205e-07
-## f_parent_qlogis -5.471e-01   -5.426e-01  7.478e-01       1.000e+00  1.305e-06
-## sigma           -1.172e-06   -8.483e-07  8.205e-07       1.305e-06  1.000e+00
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##                 Estimate t value    Pr(&gt;t)     Lower     Upper
-## parent_0       99.600000  63.430 2.298e-36 96.400000 1.028e+02
-## k_parent        0.098700  24.470 4.955e-23  0.090820 1.073e-01
-## k_m1            0.005261   7.510 6.165e-09  0.004012 6.898e-03
-## f_parent_to_m1  0.514500  23.070 3.104e-22  0.469100 5.596e-01
-## sigma           3.126000   8.718 2.235e-10  2.396000 3.855e+00
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data   6.398       4 15
-## parent     6.459       2  7
-## m1         4.690       2  8
-## 
-## Resulting formation fractions:
-##                 ff
-## parent_m1   0.5145
-## parent_sink 0.4855
-## 
-## Estimated disappearance times:
-##           DT50   DT90
-## parent   7.023  23.33
-## m1     131.761 437.70
-## 
-## Data:
-##  time variable observed predicted   residual
-##     0   parent    99.46  99.59848 -1.385e-01
-##     0   parent   102.04  99.59848  2.442e+00
-##     1   parent    93.50  90.23787  3.262e+00
-##     1   parent    92.50  90.23787  2.262e+00
-##     3   parent    63.23  74.07319 -1.084e+01
-##     3   parent    68.99  74.07319 -5.083e+00
-##     7   parent    52.32  49.91207  2.408e+00
-##     7   parent    55.13  49.91207  5.218e+00
-##    14   parent    27.27  25.01258  2.257e+00
-##    14   parent    26.64  25.01258  1.627e+00
-##    21   parent    11.50  12.53462 -1.035e+00
-##    21   parent    11.64  12.53462 -8.946e-01
-##    35   parent     2.85   3.14787 -2.979e-01
-##    35   parent     2.91   3.14787 -2.379e-01
-##    50   parent     0.69   0.71624 -2.624e-02
-##    50   parent     0.63   0.71624 -8.624e-02
-##    75   parent     0.05   0.06074 -1.074e-02
-##    75   parent     0.06   0.06074 -7.382e-04
-##     1       m1     4.84   4.80296  3.704e-02
-##     1       m1     5.64   4.80296  8.370e-01
-##     3       m1    12.91  13.02400 -1.140e-01
-##     3       m1    12.96  13.02400 -6.400e-02
-##     7       m1    22.97  25.04476 -2.075e+00
-##     7       m1    24.47  25.04476 -5.748e-01
-##    14       m1    41.69  36.69003  5.000e+00
-##    14       m1    33.21  36.69003 -3.480e+00
-##    21       m1    44.37  41.65310  2.717e+00
-##    21       m1    46.44  41.65310  4.787e+00
-##    35       m1    41.22  43.31313 -2.093e+00
-##    35       m1    37.95  43.31313 -5.363e+00
-##    50       m1    41.19  41.21832 -2.832e-02
-##    50       m1    40.01  41.21832 -1.208e+00
-##    75       m1    40.09  36.44704  3.643e+00
-##    75       m1    33.85  36.44704 -2.597e+00
-##   100       m1    31.04  31.98162 -9.416e-01
-##   100       m1    33.13  31.98162  1.148e+00
-##   120       m1    25.15  28.78984 -3.640e+00
-##   120       m1    33.31  28.78984  4.520e+00</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">fit</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:18 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:18 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - k_parent * parent</span>
+<span class="co">## d_m1/dt = + f_parent_to_m1 * k_parent * parent - k_m1 * m1</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 401 model solutions performed in 0.145 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##                   value   type</span>
+<span class="co">## parent_0       100.7500  state</span>
+<span class="co">## k_parent         0.1000 deparm</span>
+<span class="co">## k_m1             0.1001 deparm</span>
+<span class="co">## f_parent_to_m1   0.5000 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##                      value lower upper</span>
+<span class="co">## parent_0        100.750000  -Inf   Inf</span>
+<span class="co">## log_k_parent     -2.302585  -Inf   Inf</span>
+<span class="co">## log_k_m1         -2.301586  -Inf   Inf</span>
+<span class="co">## f_parent_qlogis   0.000000  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">##      value  type</span>
+<span class="co">## m1_0     0 state</span>
+<span class="co">## </span>
+<span class="co">## </span>
+<span class="co">## Warning(s): </span>
+<span class="co">## Observations with value of zero were removed from the data</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC      BIC    logLik</span>
+<span class="co">##   204.4486 212.6365 -97.22429</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##                 Estimate Std. Error   Lower    Upper</span>
+<span class="co">## parent_0        99.60000    1.57000 96.4000 102.8000</span>
+<span class="co">## log_k_parent    -2.31600    0.04087 -2.3990  -2.2330</span>
+<span class="co">## log_k_m1        -5.24700    0.13320 -5.5180  -4.9770</span>
+<span class="co">## f_parent_qlogis  0.05792    0.08926 -0.1237   0.2395</span>
+<span class="co">## sigma            3.12600    0.35850  2.3960   3.8550</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##                   parent_0 log_k_parent   log_k_m1 f_parent_qlogis      sigma</span>
+<span class="co">## parent_0         1.000e+00    5.174e-01 -1.688e-01      -5.471e-01 -1.172e-06</span>
+<span class="co">## log_k_parent     5.174e-01    1.000e+00 -3.263e-01      -5.426e-01 -8.483e-07</span>
+<span class="co">## log_k_m1        -1.688e-01   -3.263e-01  1.000e+00       7.478e-01  8.205e-07</span>
+<span class="co">## f_parent_qlogis -5.471e-01   -5.426e-01  7.478e-01       1.000e+00  1.305e-06</span>
+<span class="co">## sigma           -1.172e-06   -8.483e-07  8.205e-07       1.305e-06  1.000e+00</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##                 Estimate t value    Pr(&gt;t)     Lower     Upper</span>
+<span class="co">## parent_0       99.600000  63.430 2.298e-36 96.400000 1.028e+02</span>
+<span class="co">## k_parent        0.098700  24.470 4.955e-23  0.090820 1.073e-01</span>
+<span class="co">## k_m1            0.005261   7.510 6.165e-09  0.004012 6.898e-03</span>
+<span class="co">## f_parent_to_m1  0.514500  23.070 3.104e-22  0.469100 5.596e-01</span>
+<span class="co">## sigma           3.126000   8.718 2.235e-10  2.396000 3.855e+00</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data   6.398       4 15</span>
+<span class="co">## parent     6.459       2  7</span>
+<span class="co">## m1         4.690       2  8</span>
+<span class="co">## </span>
+<span class="co">## Resulting formation fractions:</span>
+<span class="co">##                 ff</span>
+<span class="co">## parent_m1   0.5145</span>
+<span class="co">## parent_sink 0.4855</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##           DT50   DT90</span>
+<span class="co">## parent   7.023  23.33</span>
+<span class="co">## m1     131.761 437.70</span>
+<span class="co">## </span>
+<span class="co">## Data:</span>
+<span class="co">##  time variable observed predicted   residual</span>
+<span class="co">##     0   parent    99.46  99.59848 -1.385e-01</span>
+<span class="co">##     0   parent   102.04  99.59848  2.442e+00</span>
+<span class="co">##     1   parent    93.50  90.23787  3.262e+00</span>
+<span class="co">##     1   parent    92.50  90.23787  2.262e+00</span>
+<span class="co">##     3   parent    63.23  74.07319 -1.084e+01</span>
+<span class="co">##     3   parent    68.99  74.07319 -5.083e+00</span>
+<span class="co">##     7   parent    52.32  49.91207  2.408e+00</span>
+<span class="co">##     7   parent    55.13  49.91207  5.218e+00</span>
+<span class="co">##    14   parent    27.27  25.01258  2.257e+00</span>
+<span class="co">##    14   parent    26.64  25.01258  1.627e+00</span>
+<span class="co">##    21   parent    11.50  12.53462 -1.035e+00</span>
+<span class="co">##    21   parent    11.64  12.53462 -8.946e-01</span>
+<span class="co">##    35   parent     2.85   3.14787 -2.979e-01</span>
+<span class="co">##    35   parent     2.91   3.14787 -2.379e-01</span>
+<span class="co">##    50   parent     0.69   0.71624 -2.624e-02</span>
+<span class="co">##    50   parent     0.63   0.71624 -8.624e-02</span>
+<span class="co">##    75   parent     0.05   0.06074 -1.074e-02</span>
+<span class="co">##    75   parent     0.06   0.06074 -7.382e-04</span>
+<span class="co">##     1       m1     4.84   4.80296  3.704e-02</span>
+<span class="co">##     1       m1     5.64   4.80296  8.370e-01</span>
+<span class="co">##     3       m1    12.91  13.02400 -1.140e-01</span>
+<span class="co">##     3       m1    12.96  13.02400 -6.400e-02</span>
+<span class="co">##     7       m1    22.97  25.04476 -2.075e+00</span>
+<span class="co">##     7       m1    24.47  25.04476 -5.748e-01</span>
+<span class="co">##    14       m1    41.69  36.69003  5.000e+00</span>
+<span class="co">##    14       m1    33.21  36.69003 -3.480e+00</span>
+<span class="co">##    21       m1    44.37  41.65310  2.717e+00</span>
+<span class="co">##    21       m1    46.44  41.65310  4.787e+00</span>
+<span class="co">##    35       m1    41.22  43.31313 -2.093e+00</span>
+<span class="co">##    35       m1    37.95  43.31313 -5.363e+00</span>
+<span class="co">##    50       m1    41.19  41.21832 -2.832e-02</span>
+<span class="co">##    50       m1    40.01  41.21832 -1.208e+00</span>
+<span class="co">##    75       m1    40.09  36.44704  3.643e+00</span>
+<span class="co">##    75       m1    33.85  36.44704 -2.597e+00</span>
+<span class="co">##   100       m1    31.04  31.98162 -9.416e-01</span>
+<span class="co">##   100       m1    33.13  31.98162  1.148e+00</span>
+<span class="co">##   120       m1    25.15  28.78984 -3.640e+00</span>
+<span class="co">##   120       m1    33.31  28.78984  4.520e+00</span></code></pre>
   </div>
 
   <div class="col-md-3 hidden-xs hidden-sm" id="pkgdown-sidebar">
@@ -323,11 +328,13 @@
 
 
       <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>
@@ -336,5 +343,7 @@
   
 
 
+  
+
   </body>
 </html>
diff --git a/docs/articles/FOCUS_D_files/figure-html/plot-1.png b/docs/articles/FOCUS_D_files/figure-html/plot-1.png
index c3a5d56e..f0b51c1f 100644
--- a/docs/articles/FOCUS_D_files/figure-html/plot-1.png
+++ b/docs/articles/FOCUS_D_files/figure-html/plot-1.png
diff --git a/docs/articles/FOCUS_D_files/figure-html/plot_2-1.png b/docs/articles/FOCUS_D_files/figure-html/plot_2-1.png
index 42e48dee..f6180470 100644
--- a/docs/articles/FOCUS_D_files/figure-html/plot_2-1.png
+++ b/docs/articles/FOCUS_D_files/figure-html/plot_2-1.png
diff --git a/docs/articles/FOCUS_L.html b/docs/articles/FOCUS_L.html
index 7074816c..9efea93a 100644
--- a/docs/articles/FOCUS_L.html
+++ b/docs/articles/FOCUS_L.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>
@@ -94,30 +99,30 @@
 
       
 
-      </header><script src="FOCUS_L_files/header-attrs-2.7/header-attrs.js"></script><script src="FOCUS_L_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row">
+      </header><script src="FOCUS_L_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 Laboratory Data L1 to L3</h1>
-                        <h4 class="author">Johannes Ranke</h4>
+                        <h4 data-toc-skip class="author">Johannes Ranke</h4>
             
-            <h4 class="date">Last change 17 November 2016 (rebuilt 2021-03-31)</h4>
+            <h4 data-toc-skip class="date">Last change 17 November 2016 (rebuilt 2022-03-02)</h4>
       
-      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/FOCUS_L.rmd"><code>vignettes/FOCUS_L.rmd</code></a></small>
+      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/FOCUS_L.rmd" class="external-link"><code>vignettes/FOCUS_L.rmd</code></a></small>
       <div class="hidden name"><code>FOCUS_L.rmd</code></div>
 
     </div>
 
     
     
-<div id="laboratory-data-l1" class="section level1">
-<h1 class="hasAnchor">
-<a href="#laboratory-data-l1" class="anchor"></a>Laboratory Data L1</h1>
+<div class="section level2">
+<h2 id="laboratory-data-l1">Laboratory Data L1<a class="anchor" aria-label="anchor" href="#laboratory-data-l1"></a>
+</h2>
 <p>The following code defines example dataset L1 from the FOCUS kinetics report, p. 284:</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="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">FOCUS_2006_L1</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/rep.html">rep</a></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="fl">0</span>, <span class="fl">1</span>, <span class="fl">2</span>, <span class="fl">3</span>, <span class="fl">5</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">21</span>, <span class="fl">30</span><span class="op">)</span>, each <span class="op">=</span> <span class="fl">2</span><span class="op">)</span>,
-  parent <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">88.3</span>, <span class="fl">91.4</span>, <span class="fl">85.6</span>, <span class="fl">84.5</span>, <span class="fl">78.9</span>, <span class="fl">77.6</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">FOCUS_2006_L1</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/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="fl">0</span>, <span class="fl">1</span>, <span class="fl">2</span>, <span class="fl">3</span>, <span class="fl">5</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">21</span>, <span class="fl">30</span><span class="op">)</span>, each <span class="op">=</span> <span class="fl">2</span><span class="op">)</span>,
+  parent <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">88.3</span>, <span class="fl">91.4</span>, <span class="fl">85.6</span>, <span class="fl">84.5</span>, <span class="fl">78.9</span>, <span class="fl">77.6</span>,
              <span class="fl">72.0</span>, <span class="fl">71.9</span>, <span class="fl">50.3</span>, <span class="fl">59.4</span>, <span class="fl">47.0</span>, <span class="fl">45.1</span>,
              <span class="fl">27.7</span>, <span class="fl">27.3</span>, <span class="fl">10.0</span>, <span class="fl">10.4</span>, <span class="fl">2.9</span>, <span class="fl">4.0</span><span class="op">)</span><span class="op">)</span>
 <span class="va">FOCUS_2006_L1_mkin</span> <span class="op">&lt;-</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_L1</span><span class="op">)</span></code></pre></div>
@@ -125,94 +130,94 @@
 <p>Since mkin version 0.9-32 (July 2014), we can use shorthand notation like <code>"SFO"</code> for parent only degradation models. The following two lines fit the model and produce the summary report of the model fit. This covers the numerical analysis given in the FOCUS report.</p>
 <div class="sourceCode" id="cb2"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">m.L1.SFO</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="va">FOCUS_2006_L1_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>
-<span class="fu"><a href="https://rdrr.io/r/base/summary.html">summary</a></span><span class="op">(</span><span class="va">m.L1.SFO</span><span class="op">)</span></code></pre></div>
-<pre><code>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:31 2021 
-## Date of summary: Wed Mar 31 19:18:31 2021 
-## 
-## Equations:
-## d_parent/dt = - k_parent * parent
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 133 model solutions performed in 0.032 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##          value   type
-## parent_0 89.85  state
-## k_parent  0.10 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##                  value lower upper
-## parent_0     89.850000  -Inf   Inf
-## log_k_parent -2.302585  -Inf   Inf
-## 
-## Fixed parameter values:
-## None
-## 
-## Results:
-## 
-##        AIC     BIC    logLik
-##   93.88778 96.5589 -43.94389
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##              Estimate Std. Error  Lower  Upper
-## parent_0       92.470    1.28200 89.740 95.200
-## log_k_parent   -2.347    0.03763 -2.428 -2.267
-## sigma           2.780    0.46330  1.792  3.767
-## 
-## Parameter correlation:
-##                parent_0 log_k_parent      sigma
-## parent_0      1.000e+00    6.186e-01 -1.516e-09
-## log_k_parent  6.186e-01    1.000e+00 -3.124e-09
-## sigma        -1.516e-09   -3.124e-09  1.000e+00
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##          Estimate t value    Pr(&gt;t)    Lower   Upper
-## parent_0 92.47000   72.13 8.824e-21 89.74000 95.2000
-## k_parent  0.09561   26.57 2.487e-14  0.08824  0.1036
-## sigma     2.78000    6.00 1.216e-05  1.79200  3.7670
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data   3.424       2  7
-## parent     3.424       2  7
-## 
-## Estimated disappearance times:
-##         DT50  DT90
-## parent 7.249 24.08
-## 
-## Data:
-##  time variable observed predicted residual
-##     0   parent     88.3    92.471  -4.1710
-##     0   parent     91.4    92.471  -1.0710
-##     1   parent     85.6    84.039   1.5610
-##     1   parent     84.5    84.039   0.4610
-##     2   parent     78.9    76.376   2.5241
-##     2   parent     77.6    76.376   1.2241
-##     3   parent     72.0    69.412   2.5884
-##     3   parent     71.9    69.412   2.4884
-##     5   parent     50.3    57.330  -7.0301
-##     5   parent     59.4    57.330   2.0699
-##     7   parent     47.0    47.352  -0.3515
-##     7   parent     45.1    47.352  -2.2515
-##    14   parent     27.7    24.247   3.4528
-##    14   parent     27.3    24.247   3.0528
-##    21   parent     10.0    12.416  -2.4163
-##    21   parent     10.4    12.416  -2.0163
-##    30   parent      2.9     5.251  -2.3513
-##    30   parent      4.0     5.251  -1.2513</code></pre>
+<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.L1.SFO</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:22 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:22 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - k_parent * parent</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 133 model solutions performed in 0.032 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##          value   type</span>
+<span class="co">## parent_0 89.85  state</span>
+<span class="co">## k_parent  0.10 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##                  value lower upper</span>
+<span class="co">## parent_0     89.850000  -Inf   Inf</span>
+<span class="co">## log_k_parent -2.302585  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">## None</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC     BIC    logLik</span>
+<span class="co">##   93.88778 96.5589 -43.94389</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##              Estimate Std. Error  Lower  Upper</span>
+<span class="co">## parent_0       92.470    1.28200 89.740 95.200</span>
+<span class="co">## log_k_parent   -2.347    0.03763 -2.428 -2.267</span>
+<span class="co">## sigma           2.780    0.46330  1.792  3.767</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##                parent_0 log_k_parent      sigma</span>
+<span class="co">## parent_0      1.000e+00    6.186e-01 -1.516e-09</span>
+<span class="co">## log_k_parent  6.186e-01    1.000e+00 -3.124e-09</span>
+<span class="co">## sigma        -1.516e-09   -3.124e-09  1.000e+00</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##          Estimate t value    Pr(&gt;t)    Lower   Upper</span>
+<span class="co">## parent_0 92.47000   72.13 8.824e-21 89.74000 95.2000</span>
+<span class="co">## k_parent  0.09561   26.57 2.487e-14  0.08824  0.1036</span>
+<span class="co">## sigma     2.78000    6.00 1.216e-05  1.79200  3.7670</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data   3.424       2  7</span>
+<span class="co">## parent     3.424       2  7</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##         DT50  DT90</span>
+<span class="co">## parent 7.249 24.08</span>
+<span class="co">## </span>
+<span class="co">## Data:</span>
+<span class="co">##  time variable observed predicted residual</span>
+<span class="co">##     0   parent     88.3    92.471  -4.1710</span>
+<span class="co">##     0   parent     91.4    92.471  -1.0710</span>
+<span class="co">##     1   parent     85.6    84.039   1.5610</span>
+<span class="co">##     1   parent     84.5    84.039   0.4610</span>
+<span class="co">##     2   parent     78.9    76.376   2.5241</span>
+<span class="co">##     2   parent     77.6    76.376   1.2241</span>
+<span class="co">##     3   parent     72.0    69.412   2.5884</span>
+<span class="co">##     3   parent     71.9    69.412   2.4884</span>
+<span class="co">##     5   parent     50.3    57.330  -7.0301</span>
+<span class="co">##     5   parent     59.4    57.330   2.0699</span>
+<span class="co">##     7   parent     47.0    47.352  -0.3515</span>
+<span class="co">##     7   parent     45.1    47.352  -2.2515</span>
+<span class="co">##    14   parent     27.7    24.247   3.4528</span>
+<span class="co">##    14   parent     27.3    24.247   3.0528</span>
+<span class="co">##    21   parent     10.0    12.416  -2.4163</span>
+<span class="co">##    21   parent     10.4    12.416  -2.0163</span>
+<span class="co">##    30   parent      2.9     5.251  -2.3513</span>
+<span class="co">##    30   parent      4.0     5.251  -1.2513</span></code></pre>
 <p>A plot of the fit is obtained with the plot function for mkinfit objects.</p>
 <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">m.L1.SFO</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</span>, main <span class="op">=</span> <span class="st">"FOCUS L1 - SFO"</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">m.L1.SFO</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</span>, main <span class="op">=</span> <span class="st">"FOCUS L1 - SFO"</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-4-1.png" width="576"></p>
 <p>The residual plot can be easily obtained by</p>
 <div class="sourceCode" id="cb5"><pre class="downlit sourceCode r">
@@ -221,566 +226,566 @@
 <p>For comparison, the FOMC model is fitted as well, and the <span class="math inline">\(\chi^2\)</span> error level is checked.</p>
 <div class="sourceCode" id="cb6"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">m.L1.FOMC</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="st">"FOMC"</span>, <span class="va">FOCUS_2006_L1_mkin</span>, quiet<span class="op">=</span><span class="cn">TRUE</span><span class="op">)</span></code></pre></div>
-<pre><code>## Warning in mkinfit("FOMC", FOCUS_2006_L1_mkin, quiet = TRUE): Optimisation did not converge:
-## false convergence (8)</code></pre>
+<pre><code><span class="co">## Warning in mkinfit("FOMC", FOCUS_2006_L1_mkin, quiet = TRUE): Optimisation did not converge:</span>
+<span class="co">## false convergence (8)</span></code></pre>
 <div class="sourceCode" id="cb8"><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">m.L1.FOMC</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</span>, main <span class="op">=</span> <span class="st">"FOCUS L1 - FOMC"</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">m.L1.FOMC</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</span>, main <span class="op">=</span> <span class="st">"FOCUS L1 - FOMC"</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-6-1.png" width="576"></p>
 <div class="sourceCode" id="cb9"><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.L1.FOMC</span>, data <span class="op">=</span> <span class="cn">FALSE</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>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:32 2021 
-## Date of summary: Wed Mar 31 19:18:32 2021 
-## 
-## Equations:
-## d_parent/dt = - (alpha/beta) * 1/((time/beta) + 1) * parent
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 369 model solutions performed in 0.083 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##          value   type
-## parent_0 89.85  state
-## alpha     1.00 deparm
-## beta     10.00 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##               value lower upper
-## parent_0  89.850000  -Inf   Inf
-## log_alpha  0.000000  -Inf   Inf
-## log_beta   2.302585  -Inf   Inf
-## 
-## Fixed parameter values:
-## None
-## 
-## 
-## Warning(s): 
-## Optimisation did not converge:
-## false convergence (8)
-## 
-## Results:
-## 
-##        AIC      BIC   logLik
-##   95.88781 99.44929 -43.9439
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##           Estimate Std. Error  Lower  Upper
-## parent_0     92.47     1.2820 89.720 95.220
-## log_alpha    13.78        NaN    NaN    NaN
-## log_beta     16.13        NaN    NaN    NaN
-## sigma         2.78     0.4598  1.794  3.766
-## 
-## Parameter correlation:
-##            parent_0 log_alpha log_beta     sigma
-## parent_0  1.0000000       NaN      NaN 0.0001671
-## log_alpha       NaN         1      NaN       NaN
-## log_beta        NaN       NaN        1       NaN
-## sigma     0.0001671       NaN      NaN 1.0000000
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##           Estimate t value Pr(&gt;t)  Lower  Upper
-## parent_0 9.247e+01      NA     NA 89.720 95.220
-## alpha    9.658e+05      NA     NA     NA     NA
-## beta     1.010e+07      NA     NA     NA     NA
-## sigma    2.780e+00      NA     NA  1.794  3.766
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data   3.619       3  6
-## parent     3.619       3  6
-## 
-## Estimated disappearance times:
-##        DT50  DT90 DT50back
-## parent 7.25 24.08     7.25</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.L1.FOMC</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
+<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">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:22 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:22 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - (alpha/beta) * 1/((time/beta) + 1) * parent</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 369 model solutions performed in 0.082 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##          value   type</span>
+<span class="co">## parent_0 89.85  state</span>
+<span class="co">## alpha     1.00 deparm</span>
+<span class="co">## beta     10.00 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##               value lower upper</span>
+<span class="co">## parent_0  89.850000  -Inf   Inf</span>
+<span class="co">## log_alpha  0.000000  -Inf   Inf</span>
+<span class="co">## log_beta   2.302585  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">## None</span>
+<span class="co">## </span>
+<span class="co">## </span>
+<span class="co">## Warning(s): </span>
+<span class="co">## Optimisation did not converge:</span>
+<span class="co">## false convergence (8)</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC      BIC   logLik</span>
+<span class="co">##   95.88781 99.44929 -43.9439</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##           Estimate Std. Error  Lower  Upper</span>
+<span class="co">## parent_0     92.47     1.2820 89.720 95.220</span>
+<span class="co">## log_alpha    13.78        NaN    NaN    NaN</span>
+<span class="co">## log_beta     16.13        NaN    NaN    NaN</span>
+<span class="co">## sigma         2.78     0.4598  1.794  3.766</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##            parent_0 log_alpha log_beta     sigma</span>
+<span class="co">## parent_0  1.0000000       NaN      NaN 0.0001671</span>
+<span class="co">## log_alpha       NaN         1      NaN       NaN</span>
+<span class="co">## log_beta        NaN       NaN        1       NaN</span>
+<span class="co">## sigma     0.0001671       NaN      NaN 1.0000000</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##           Estimate t value Pr(&gt;t)  Lower  Upper</span>
+<span class="co">## parent_0 9.247e+01      NA     NA 89.720 95.220</span>
+<span class="co">## alpha    9.658e+05      NA     NA     NA     NA</span>
+<span class="co">## beta     1.010e+07      NA     NA     NA     NA</span>
+<span class="co">## sigma    2.780e+00      NA     NA  1.794  3.766</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data   3.619       3  6</span>
+<span class="co">## parent     3.619       3  6</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##        DT50  DT90 DT50back</span>
+<span class="co">## parent 7.25 24.08     7.25</span></code></pre>
 <p>We get a warning that the default optimisation algorithm <code>Port</code> did not converge, which is an indication that the model is overparameterised, <em>i.e.</em> contains too many parameters that are ill-defined as a consequence.</p>
 <p>And in fact, due to the higher number of parameters, and the lower number of degrees of freedom of the fit, the <span class="math inline">\(\chi^2\)</span> error level is actually higher for the FOMC model (3.6%) than for the SFO model (3.4%). Additionally, the parameters <code>log_alpha</code> and <code>log_beta</code> internally fitted in the model have excessive confidence intervals, that span more than 25 orders of magnitude (!) when backtransformed to the scale of <code>alpha</code> and <code>beta</code>. Also, the t-test for significant difference from zero does not indicate such a significant difference, with p-values greater than 0.1, and finally, the parameter correlation of <code>log_alpha</code> and <code>log_beta</code> is 1.000, clearly indicating that the model is overparameterised.</p>
 <p>The <span class="math inline">\(\chi^2\)</span> error levels reported in Appendix 3 and Appendix 7 to the FOCUS kinetics report are rounded to integer percentages and partly deviate by one percentage point from the results calculated by mkin. The reason for this is not known. However, mkin gives the same <span class="math inline">\(\chi^2\)</span> error levels as the kinfit package and the calculation routines of the kinfit package have been extensively compared to the results obtained by the KinGUI software, as documented in the kinfit package vignette. KinGUI was the first widely used standard package in this field. Also, the calculation of <span class="math inline">\(\chi^2\)</span> error levels was compared with KinGUII, CAKE and DegKin manager in a project sponsored by the German Umweltbundesamt <span class="citation">(Ranke 2014)</span>.</p>
 </div>
-<div id="laboratory-data-l2" class="section level1">
-<h1 class="hasAnchor">
-<a href="#laboratory-data-l2" class="anchor"></a>Laboratory Data L2</h1>
+<div class="section level2">
+<h2 id="laboratory-data-l2">Laboratory Data L2<a class="anchor" aria-label="anchor" href="#laboratory-data-l2"></a>
+</h2>
 <p>The following code defines example dataset L2 from the FOCUS kinetics report, p. 287:</p>
 <div class="sourceCode" id="cb14"><pre class="downlit sourceCode r">
-<code class="sourceCode R"><span class="va">FOCUS_2006_L2</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/rep.html">rep</a></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="fl">0</span>, <span class="fl">1</span>, <span class="fl">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">28</span><span class="op">)</span>, each <span class="op">=</span> <span class="fl">2</span><span class="op">)</span>,
-  parent <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">96.1</span>, <span class="fl">91.8</span>, <span class="fl">41.4</span>, <span class="fl">38.7</span>,
+<code class="sourceCode R"><span class="va">FOCUS_2006_L2</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/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="fl">0</span>, <span class="fl">1</span>, <span class="fl">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">28</span><span class="op">)</span>, each <span class="op">=</span> <span class="fl">2</span><span class="op">)</span>,
+  parent <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">96.1</span>, <span class="fl">91.8</span>, <span class="fl">41.4</span>, <span class="fl">38.7</span>,
              <span class="fl">19.3</span>, <span class="fl">22.3</span>, <span class="fl">4.6</span>, <span class="fl">4.6</span>,
              <span class="fl">2.6</span>, <span class="fl">1.2</span>, <span class="fl">0.3</span>, <span class="fl">0.6</span><span class="op">)</span><span class="op">)</span>
 <span class="va">FOCUS_2006_L2_mkin</span> <span class="op">&lt;-</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_L2</span><span class="op">)</span></code></pre></div>
-<div id="sfo-fit-for-l2" class="section level2">
-<h2 class="hasAnchor">
-<a href="#sfo-fit-for-l2" class="anchor"></a>SFO fit for L2</h2>
+<div class="section level3">
+<h3 id="sfo-fit-for-l2">SFO fit for L2<a class="anchor" aria-label="anchor" href="#sfo-fit-for-l2"></a>
+</h3>
 <p>Again, the SFO model is fitted and the result is plotted. The residual plot can be obtained simply by adding the argument <code>show_residuals</code> to the plot command.</p>
 <div class="sourceCode" id="cb15"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">m.L2.SFO</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="va">FOCUS_2006_L2_mkin</span>, quiet<span class="op">=</span><span class="cn">TRUE</span><span class="op">)</span>
-<span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">m.L2.SFO</span>, show_residuals <span class="op">=</span> <span class="cn">TRUE</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</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">m.L2.SFO</span>, show_residuals <span class="op">=</span> <span class="cn">TRUE</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</span>,
      main <span class="op">=</span> <span class="st">"FOCUS L2 - SFO"</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-8-1.png" width="672"></p>
 <p>The <span class="math inline">\(\chi^2\)</span> error level of 14% suggests that the model does not fit very well. This is also obvious from the plots of the fit, in which we have included the residual plot.</p>
 <p>In the FOCUS kinetics report, it is stated that there is no apparent systematic error observed from the residual plot up to the measured DT90 (approximately at day 5), and there is an underestimation beyond that point.</p>
 <p>We may add that it is difficult to judge the random nature of the residuals just from the three samplings at days 0, 1 and 3. Also, it is not clear <em>a priori</em> why a consistent underestimation after the approximate DT90 should be irrelevant. However, this can be rationalised by the fact that the FOCUS fate models generally only implement SFO kinetics.</p>
 </div>
-<div id="fomc-fit-for-l2" class="section level2">
-<h2 class="hasAnchor">
-<a href="#fomc-fit-for-l2" class="anchor"></a>FOMC fit for L2</h2>
+<div class="section level3">
+<h3 id="fomc-fit-for-l2">FOMC fit for L2<a class="anchor" aria-label="anchor" href="#fomc-fit-for-l2"></a>
+</h3>
 <p>For comparison, the FOMC model is fitted as well, and the <span class="math inline">\(\chi^2\)</span> error level is checked.</p>
 <div class="sourceCode" id="cb16"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">m.L2.FOMC</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="st">"FOMC"</span>, <span class="va">FOCUS_2006_L2_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>
-<span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">m.L2.FOMC</span>, show_residuals <span class="op">=</span> <span class="cn">TRUE</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">m.L2.FOMC</span>, show_residuals <span class="op">=</span> <span class="cn">TRUE</span>,
      main <span class="op">=</span> <span class="st">"FOCUS L2 - FOMC"</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-9-1.png" width="672"></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/summary.html">summary</a></span><span class="op">(</span><span class="va">m.L2.FOMC</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
-<pre><code>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:32 2021 
-## Date of summary: Wed Mar 31 19:18:32 2021 
-## 
-## Equations:
-## d_parent/dt = - (alpha/beta) * 1/((time/beta) + 1) * parent
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 239 model solutions performed in 0.05 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##          value   type
-## parent_0 93.95  state
-## alpha     1.00 deparm
-## beta     10.00 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##               value lower upper
-## parent_0  93.950000  -Inf   Inf
-## log_alpha  0.000000  -Inf   Inf
-## log_beta   2.302585  -Inf   Inf
-## 
-## Fixed parameter values:
-## None
-## 
-## Results:
-## 
-##        AIC      BIC    logLik
-##   61.78966 63.72928 -26.89483
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##           Estimate Std. Error    Lower   Upper
-## parent_0   93.7700     1.6130 90.05000 97.4900
-## log_alpha   0.3180     0.1559 -0.04149  0.6776
-## log_beta    0.2102     0.2493 -0.36460  0.7850
-## sigma       2.2760     0.4645  1.20500  3.3470
-## 
-## Parameter correlation:
-##             parent_0  log_alpha   log_beta      sigma
-## parent_0   1.000e+00 -1.151e-01 -2.085e-01 -7.828e-09
-## log_alpha -1.151e-01  1.000e+00  9.741e-01 -1.602e-07
-## log_beta  -2.085e-01  9.741e-01  1.000e+00 -1.372e-07
-## sigma     -7.828e-09 -1.602e-07 -1.372e-07  1.000e+00
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##          Estimate t value    Pr(&gt;t)   Lower  Upper
-## parent_0   93.770  58.120 4.267e-12 90.0500 97.490
-## alpha       1.374   6.414 1.030e-04  0.9594  1.969
-## beta        1.234   4.012 1.942e-03  0.6945  2.192
-## sigma       2.276   4.899 5.977e-04  1.2050  3.347
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data   6.205       3  3
-## parent     6.205       3  3
-## 
-## Estimated disappearance times:
-##          DT50  DT90 DT50back
-## parent 0.8092 5.356    1.612</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.L2.FOMC</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:23 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:23 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - (alpha/beta) * 1/((time/beta) + 1) * parent</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 239 model solutions performed in 0.049 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##          value   type</span>
+<span class="co">## parent_0 93.95  state</span>
+<span class="co">## alpha     1.00 deparm</span>
+<span class="co">## beta     10.00 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##               value lower upper</span>
+<span class="co">## parent_0  93.950000  -Inf   Inf</span>
+<span class="co">## log_alpha  0.000000  -Inf   Inf</span>
+<span class="co">## log_beta   2.302585  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">## None</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC      BIC    logLik</span>
+<span class="co">##   61.78966 63.72928 -26.89483</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##           Estimate Std. Error    Lower   Upper</span>
+<span class="co">## parent_0   93.7700     1.6130 90.05000 97.4900</span>
+<span class="co">## log_alpha   0.3180     0.1559 -0.04149  0.6776</span>
+<span class="co">## log_beta    0.2102     0.2493 -0.36460  0.7850</span>
+<span class="co">## sigma       2.2760     0.4645  1.20500  3.3470</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##             parent_0  log_alpha   log_beta      sigma</span>
+<span class="co">## parent_0   1.000e+00 -1.151e-01 -2.085e-01 -7.828e-09</span>
+<span class="co">## log_alpha -1.151e-01  1.000e+00  9.741e-01 -1.602e-07</span>
+<span class="co">## log_beta  -2.085e-01  9.741e-01  1.000e+00 -1.372e-07</span>
+<span class="co">## sigma     -7.828e-09 -1.602e-07 -1.372e-07  1.000e+00</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##          Estimate t value    Pr(&gt;t)   Lower  Upper</span>
+<span class="co">## parent_0   93.770  58.120 4.267e-12 90.0500 97.490</span>
+<span class="co">## alpha       1.374   6.414 1.030e-04  0.9594  1.969</span>
+<span class="co">## beta        1.234   4.012 1.942e-03  0.6945  2.192</span>
+<span class="co">## sigma       2.276   4.899 5.977e-04  1.2050  3.347</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data   6.205       3  3</span>
+<span class="co">## parent     6.205       3  3</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##          DT50  DT90 DT50back</span>
+<span class="co">## parent 0.8092 5.356    1.612</span></code></pre>
 <p>The error level at which the <span class="math inline">\(\chi^2\)</span> test passes is much lower in this case. Therefore, the FOMC model provides a better description of the data, as less experimental error has to be assumed in order to explain the data.</p>
 </div>
-<div id="dfop-fit-for-l2" class="section level2">
-<h2 class="hasAnchor">
-<a href="#dfop-fit-for-l2" class="anchor"></a>DFOP fit for L2</h2>
+<div class="section level3">
+<h3 id="dfop-fit-for-l2">DFOP fit for L2<a class="anchor" aria-label="anchor" href="#dfop-fit-for-l2"></a>
+</h3>
 <p>Fitting the four parameter DFOP model further reduces the <span class="math inline">\(\chi^2\)</span> error level.</p>
 <div class="sourceCode" id="cb19"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">m.L2.DFOP</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="st">"DFOP"</span>, <span class="va">FOCUS_2006_L2_mkin</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>
-<span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">m.L2.DFOP</span>, show_residuals <span class="op">=</span> <span class="cn">TRUE</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</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">m.L2.DFOP</span>, show_residuals <span class="op">=</span> <span class="cn">TRUE</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</span>,
      main <span class="op">=</span> <span class="st">"FOCUS L2 - DFOP"</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-10-1.png" width="672"></p>
 <div class="sourceCode" id="cb20"><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.L2.DFOP</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
-<pre><code>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:33 2021 
-## Date of summary: Wed Mar 31 19:18:33 2021 
-## 
-## Equations:
-## d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
-##            time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
-##            * parent
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 581 model solutions performed in 0.134 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##          value   type
-## parent_0 93.95  state
-## k1        0.10 deparm
-## k2        0.01 deparm
-## g         0.50 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##              value lower upper
-## parent_0 93.950000  -Inf   Inf
-## log_k1   -2.302585  -Inf   Inf
-## log_k2   -4.605170  -Inf   Inf
-## g_qlogis  0.000000  -Inf   Inf
-## 
-## Fixed parameter values:
-## None
-## 
-## Results:
-## 
-##        AIC      BIC    logLik
-##   52.36695 54.79148 -21.18347
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##          Estimate Std. Error      Lower     Upper
-## parent_0   93.950  9.998e-01    91.5900   96.3100
-## log_k1      3.112  1.842e+03 -4353.0000 4359.0000
-## log_k2     -1.088  6.285e-02    -1.2370   -0.9394
-## g_qlogis   -0.399  9.946e-02    -0.6342   -0.1638
-## sigma       1.414  2.886e-01     0.7314    2.0960
-## 
-## Parameter correlation:
-##            parent_0     log_k1     log_k2   g_qlogis      sigma
-## parent_0  1.000e+00  6.783e-07 -3.390e-10  2.665e-01 -2.967e-10
-## log_k1    6.783e-07  1.000e+00  1.116e-04 -2.196e-04 -1.031e-05
-## log_k2   -3.390e-10  1.116e-04  1.000e+00 -7.903e-01  2.917e-09
-## g_qlogis  2.665e-01 -2.196e-04 -7.903e-01  1.000e+00 -4.408e-09
-## sigma    -2.967e-10 -1.031e-05  2.917e-09 -4.408e-09  1.000e+00
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##          Estimate   t value    Pr(&gt;t)   Lower   Upper
-## parent_0  93.9500 9.397e+01 2.036e-12 91.5900 96.3100
-## k1        22.4800 5.553e-04 4.998e-01  0.0000     Inf
-## k2         0.3369 1.591e+01 4.697e-07  0.2904  0.3909
-## g          0.4016 1.680e+01 3.238e-07  0.3466  0.4591
-## sigma      1.4140 4.899e+00 8.776e-04  0.7314  2.0960
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data    2.53       4  2
-## parent      2.53       4  2
-## 
-## Estimated disappearance times:
-##          DT50  DT90 DT50back DT50_k1 DT50_k2
-## parent 0.5335 5.311    1.599 0.03084   2.058</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.L2.DFOP</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:23 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:23 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *</span>
+<span class="co">##            time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))</span>
+<span class="co">##            * parent</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 581 model solutions performed in 0.131 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##          value   type</span>
+<span class="co">## parent_0 93.95  state</span>
+<span class="co">## k1        0.10 deparm</span>
+<span class="co">## k2        0.01 deparm</span>
+<span class="co">## g         0.50 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##              value lower upper</span>
+<span class="co">## parent_0 93.950000  -Inf   Inf</span>
+<span class="co">## log_k1   -2.302585  -Inf   Inf</span>
+<span class="co">## log_k2   -4.605170  -Inf   Inf</span>
+<span class="co">## g_qlogis  0.000000  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">## None</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC      BIC    logLik</span>
+<span class="co">##   52.36695 54.79148 -21.18347</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##          Estimate Std. Error      Lower     Upper</span>
+<span class="co">## parent_0   93.950  9.998e-01    91.5900   96.3100</span>
+<span class="co">## log_k1      3.112  1.842e+03 -4353.0000 4359.0000</span>
+<span class="co">## log_k2     -1.088  6.285e-02    -1.2370   -0.9394</span>
+<span class="co">## g_qlogis   -0.399  9.946e-02    -0.6342   -0.1638</span>
+<span class="co">## sigma       1.414  2.886e-01     0.7314    2.0960</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##            parent_0     log_k1     log_k2   g_qlogis      sigma</span>
+<span class="co">## parent_0  1.000e+00  6.783e-07 -3.390e-10  2.665e-01 -2.967e-10</span>
+<span class="co">## log_k1    6.783e-07  1.000e+00  1.116e-04 -2.196e-04 -1.031e-05</span>
+<span class="co">## log_k2   -3.390e-10  1.116e-04  1.000e+00 -7.903e-01  2.917e-09</span>
+<span class="co">## g_qlogis  2.665e-01 -2.196e-04 -7.903e-01  1.000e+00 -4.408e-09</span>
+<span class="co">## sigma    -2.967e-10 -1.031e-05  2.917e-09 -4.408e-09  1.000e+00</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##          Estimate   t value    Pr(&gt;t)   Lower   Upper</span>
+<span class="co">## parent_0  93.9500 9.397e+01 2.036e-12 91.5900 96.3100</span>
+<span class="co">## k1        22.4800 5.553e-04 4.998e-01  0.0000     Inf</span>
+<span class="co">## k2         0.3369 1.591e+01 4.697e-07  0.2904  0.3909</span>
+<span class="co">## g          0.4016 1.680e+01 3.238e-07  0.3466  0.4591</span>
+<span class="co">## sigma      1.4140 4.899e+00 8.776e-04  0.7314  2.0960</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data    2.53       4  2</span>
+<span class="co">## parent      2.53       4  2</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##          DT50  DT90 DT50back DT50_k1 DT50_k2</span>
+<span class="co">## parent 0.5335 5.311    1.599 0.03084   2.058</span></code></pre>
 <p>Here, the DFOP model is clearly the best-fit model for dataset L2 based on the chi^2 error level criterion. However, the failure to calculate the covariance matrix indicates that the parameter estimates correlate excessively. Therefore, the FOMC model may be preferred for this dataset.</p>
 </div>
 </div>
-<div id="laboratory-data-l3" class="section level1">
-<h1 class="hasAnchor">
-<a href="#laboratory-data-l3" class="anchor"></a>Laboratory Data L3</h1>
+<div class="section level2">
+<h2 id="laboratory-data-l3">Laboratory Data L3<a class="anchor" aria-label="anchor" href="#laboratory-data-l3"></a>
+</h2>
 <p>The following code defines example dataset L3 from the FOCUS kinetics report, p. 290.</p>
 <div class="sourceCode" id="cb22"><pre class="downlit sourceCode r">
-<code class="sourceCode R"><span class="va">FOCUS_2006_L3</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">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">30</span>, <span class="fl">60</span>, <span class="fl">91</span>, <span class="fl">120</span><span class="op">)</span>,
-  parent <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">97.8</span>, <span class="fl">60</span>, <span class="fl">51</span>, <span class="fl">43</span>, <span class="fl">35</span>, <span class="fl">22</span>, <span class="fl">15</span>, <span class="fl">12</span><span class="op">)</span><span class="op">)</span>
+<code class="sourceCode R"><span class="va">FOCUS_2006_L3</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">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">30</span>, <span class="fl">60</span>, <span class="fl">91</span>, <span class="fl">120</span><span class="op">)</span>,
+  parent <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">97.8</span>, <span class="fl">60</span>, <span class="fl">51</span>, <span class="fl">43</span>, <span class="fl">35</span>, <span class="fl">22</span>, <span class="fl">15</span>, <span class="fl">12</span><span class="op">)</span><span class="op">)</span>
 <span class="va">FOCUS_2006_L3_mkin</span> <span class="op">&lt;-</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_L3</span><span class="op">)</span></code></pre></div>
-<div id="fit-multiple-models" class="section level2">
-<h2 class="hasAnchor">
-<a href="#fit-multiple-models" class="anchor"></a>Fit multiple models</h2>
+<div class="section level3">
+<h3 id="fit-multiple-models">Fit multiple models<a class="anchor" aria-label="anchor" href="#fit-multiple-models"></a>
+</h3>
 <p>As of mkin version 0.9-39 (June 2015), we can fit several models to one or more datasets in one call to the function <code>mmkin</code>. The datasets have to be passed in a list, in this case a named list holding only the L3 dataset prepared above.</p>
 <div class="sourceCode" id="cb23"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="co"># Only use one core here, not to offend the CRAN checks</span>
-<span class="va">mm.L3</span> <span class="op">&lt;-</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">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"FOMC"</span>, <span class="st">"DFOP"</span><span class="op">)</span>, cores <span class="op">=</span> <span class="fl">1</span>,
-               <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="st">"FOCUS L3"</span> <span class="op">=</span> <span class="va">FOCUS_2006_L3_mkin</span><span class="op">)</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>
-<span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">mm.L3</span><span class="op">)</span></code></pre></div>
+<span class="va">mm.L3</span> <span class="op">&lt;-</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">"FOMC"</span>, <span class="st">"DFOP"</span><span class="op">)</span>, cores <span class="op">=</span> <span class="fl">1</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="st">"FOCUS L3"</span> <span class="op">=</span> <span class="va">FOCUS_2006_L3_mkin</span><span class="op">)</span>, quiet <span class="op">=</span> <span class="cn">TRUE</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">mm.L3</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-12-1.png" width="700"></p>
 <p>The <span class="math inline">\(\chi^2\)</span> error level of 21% as well as the plot suggest that the SFO model does not fit very well. The FOMC model performs better, with an error level at which the <span class="math inline">\(\chi^2\)</span> test passes of 7%. Fitting the four parameter DFOP model further reduces the <span class="math inline">\(\chi^2\)</span> error level considerably.</p>
 </div>
-<div id="accessing-mmkin-objects" class="section level2">
-<h2 class="hasAnchor">
-<a href="#accessing-mmkin-objects" class="anchor"></a>Accessing mmkin objects</h2>
+<div class="section level3">
+<h3 id="accessing-mmkin-objects">Accessing mmkin objects<a class="anchor" aria-label="anchor" href="#accessing-mmkin-objects"></a>
+</h3>
 <p>The objects returned by mmkin are arranged like a matrix, with models as a row index and datasets as a column index.</p>
 <p>We can extract the summary and plot for <em>e.g.</em> the DFOP fit, using square brackets for indexing which will result in the use of the summary and plot functions working on mkinfit objects.</p>
 <div class="sourceCode" id="cb24"><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">mm.L3</span><span class="op">[[</span><span class="st">"DFOP"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div>
-<pre><code>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:33 2021 
-## Date of summary: Wed Mar 31 19:18:33 2021 
-## 
-## Equations:
-## d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
-##            time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
-##            * parent
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 376 model solutions performed in 0.081 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##          value   type
-## parent_0 97.80  state
-## k1        0.10 deparm
-## k2        0.01 deparm
-## g         0.50 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##              value lower upper
-## parent_0 97.800000  -Inf   Inf
-## log_k1   -2.302585  -Inf   Inf
-## log_k2   -4.605170  -Inf   Inf
-## g_qlogis  0.000000  -Inf   Inf
-## 
-## Fixed parameter values:
-## None
-## 
-## Results:
-## 
-##        AIC      BIC    logLik
-##   32.97732 33.37453 -11.48866
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##          Estimate Std. Error   Lower      Upper
-## parent_0  97.7500    1.01900 94.5000 101.000000
-## log_k1    -0.6612    0.10050 -0.9812  -0.341300
-## log_k2    -4.2860    0.04322 -4.4230  -4.148000
-## g_qlogis  -0.1739    0.05270 -0.3416  -0.006142
-## sigma      1.0170    0.25430  0.2079   1.827000
-## 
-## Parameter correlation:
-##            parent_0     log_k1     log_k2   g_qlogis      sigma
-## parent_0  1.000e+00  1.732e-01  2.282e-02  4.009e-01 -9.664e-08
-## log_k1    1.732e-01  1.000e+00  4.945e-01 -5.809e-01  7.147e-07
-## log_k2    2.282e-02  4.945e-01  1.000e+00 -6.812e-01  1.022e-06
-## g_qlogis  4.009e-01 -5.809e-01 -6.812e-01  1.000e+00 -7.926e-07
-## sigma    -9.664e-08  7.147e-07  1.022e-06 -7.926e-07  1.000e+00
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##          Estimate t value    Pr(&gt;t)    Lower     Upper
-## parent_0 97.75000  95.960 1.248e-06 94.50000 101.00000
-## k1        0.51620   9.947 1.081e-03  0.37490   0.71090
-## k2        0.01376  23.140 8.840e-05  0.01199   0.01579
-## g         0.45660  34.920 2.581e-05  0.41540   0.49850
-## sigma     1.01700   4.000 1.400e-02  0.20790   1.82700
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data   2.225       4  4
-## parent     2.225       4  4
-## 
-## Estimated disappearance times:
-##         DT50 DT90 DT50back DT50_k1 DT50_k2
-## parent 7.464  123    37.03   1.343   50.37
-## 
-## Data:
-##  time variable observed predicted residual
-##     0   parent     97.8     97.75  0.05396
-##     3   parent     60.0     60.45 -0.44933
-##     7   parent     51.0     49.44  1.56338
-##    14   parent     43.0     43.84 -0.83632
-##    30   parent     35.0     35.15 -0.14707
-##    60   parent     22.0     23.26 -1.25919
-##    91   parent     15.0     15.18 -0.18181
-##   120   parent     12.0     10.19  1.81395</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">mm.L3</span><span class="op">[[</span><span class="st">"DFOP"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:24 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:24 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *</span>
+<span class="co">##            time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))</span>
+<span class="co">##            * parent</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 376 model solutions performed in 0.079 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##          value   type</span>
+<span class="co">## parent_0 97.80  state</span>
+<span class="co">## k1        0.10 deparm</span>
+<span class="co">## k2        0.01 deparm</span>
+<span class="co">## g         0.50 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##              value lower upper</span>
+<span class="co">## parent_0 97.800000  -Inf   Inf</span>
+<span class="co">## log_k1   -2.302585  -Inf   Inf</span>
+<span class="co">## log_k2   -4.605170  -Inf   Inf</span>
+<span class="co">## g_qlogis  0.000000  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">## None</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC      BIC    logLik</span>
+<span class="co">##   32.97732 33.37453 -11.48866</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##          Estimate Std. Error   Lower      Upper</span>
+<span class="co">## parent_0  97.7500    1.01900 94.5000 101.000000</span>
+<span class="co">## log_k1    -0.6612    0.10050 -0.9812  -0.341300</span>
+<span class="co">## log_k2    -4.2860    0.04322 -4.4230  -4.148000</span>
+<span class="co">## g_qlogis  -0.1739    0.05270 -0.3416  -0.006142</span>
+<span class="co">## sigma      1.0170    0.25430  0.2079   1.827000</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##            parent_0     log_k1     log_k2   g_qlogis      sigma</span>
+<span class="co">## parent_0  1.000e+00  1.732e-01  2.282e-02  4.009e-01 -9.664e-08</span>
+<span class="co">## log_k1    1.732e-01  1.000e+00  4.945e-01 -5.809e-01  7.147e-07</span>
+<span class="co">## log_k2    2.282e-02  4.945e-01  1.000e+00 -6.812e-01  1.022e-06</span>
+<span class="co">## g_qlogis  4.009e-01 -5.809e-01 -6.812e-01  1.000e+00 -7.926e-07</span>
+<span class="co">## sigma    -9.664e-08  7.147e-07  1.022e-06 -7.926e-07  1.000e+00</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##          Estimate t value    Pr(&gt;t)    Lower     Upper</span>
+<span class="co">## parent_0 97.75000  95.960 1.248e-06 94.50000 101.00000</span>
+<span class="co">## k1        0.51620   9.947 1.081e-03  0.37490   0.71090</span>
+<span class="co">## k2        0.01376  23.140 8.840e-05  0.01199   0.01579</span>
+<span class="co">## g         0.45660  34.920 2.581e-05  0.41540   0.49850</span>
+<span class="co">## sigma     1.01700   4.000 1.400e-02  0.20790   1.82700</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data   2.225       4  4</span>
+<span class="co">## parent     2.225       4  4</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##         DT50 DT90 DT50back DT50_k1 DT50_k2</span>
+<span class="co">## parent 7.464  123    37.03   1.343   50.37</span>
+<span class="co">## </span>
+<span class="co">## Data:</span>
+<span class="co">##  time variable observed predicted residual</span>
+<span class="co">##     0   parent     97.8     97.75  0.05396</span>
+<span class="co">##     3   parent     60.0     60.45 -0.44933</span>
+<span class="co">##     7   parent     51.0     49.44  1.56338</span>
+<span class="co">##    14   parent     43.0     43.84 -0.83632</span>
+<span class="co">##    30   parent     35.0     35.15 -0.14707</span>
+<span class="co">##    60   parent     22.0     23.26 -1.25919</span>
+<span class="co">##    91   parent     15.0     15.18 -0.18181</span>
+<span class="co">##   120   parent     12.0     10.19  1.81395</span></code></pre>
 <div class="sourceCode" id="cb26"><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">mm.L3</span><span class="op">[[</span><span class="st">"DFOP"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</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">mm.L3</span><span class="op">[[</span><span class="st">"DFOP"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span>, show_errmin <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-13-1.png" width="700"></p>
 <p>Here, a look to the model plot, the confidence intervals of the parameters and the correlation matrix suggest that the parameter estimates are reliable, and the DFOP model can be used as the best-fit model based on the <span class="math inline">\(\chi^2\)</span> error level criterion for laboratory data L3.</p>
 <p>This is also an example where the standard t-test for the parameter <code>g_ilr</code> is misleading, as it tests for a significant difference from zero. In this case, zero appears to be the correct value for this parameter, and the confidence interval for the backtransformed parameter <code>g</code> is quite narrow.</p>
 </div>
 </div>
-<div id="laboratory-data-l4" class="section level1">
-<h1 class="hasAnchor">
-<a href="#laboratory-data-l4" class="anchor"></a>Laboratory Data L4</h1>
+<div class="section level2">
+<h2 id="laboratory-data-l4">Laboratory Data L4<a class="anchor" aria-label="anchor" href="#laboratory-data-l4"></a>
+</h2>
 <p>The following code defines example dataset L4 from the FOCUS kinetics report, p. 293:</p>
 <div class="sourceCode" id="cb27"><pre class="downlit sourceCode r">
-<code class="sourceCode R"><span class="va">FOCUS_2006_L4</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">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">30</span>, <span class="fl">60</span>, <span class="fl">91</span>, <span class="fl">120</span><span class="op">)</span>,
-  parent <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">96.6</span>, <span class="fl">96.3</span>, <span class="fl">94.3</span>, <span class="fl">88.8</span>, <span class="fl">74.9</span>, <span class="fl">59.9</span>, <span class="fl">53.5</span>, <span class="fl">49.0</span><span class="op">)</span><span class="op">)</span>
+<code class="sourceCode R"><span class="va">FOCUS_2006_L4</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">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">30</span>, <span class="fl">60</span>, <span class="fl">91</span>, <span class="fl">120</span><span class="op">)</span>,
+  parent <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">96.6</span>, <span class="fl">96.3</span>, <span class="fl">94.3</span>, <span class="fl">88.8</span>, <span class="fl">74.9</span>, <span class="fl">59.9</span>, <span class="fl">53.5</span>, <span class="fl">49.0</span><span class="op">)</span><span class="op">)</span>
 <span class="va">FOCUS_2006_L4_mkin</span> <span class="op">&lt;-</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_L4</span><span class="op">)</span></code></pre></div>
 <p>Fits of the SFO and FOMC models, plots and summaries are produced below:</p>
 <div class="sourceCode" id="cb28"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="co"># Only use one core here, not to offend the CRAN checks</span>
-<span class="va">mm.L4</span> <span class="op">&lt;-</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">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"FOMC"</span><span class="op">)</span>, cores <span class="op">=</span> <span class="fl">1</span>,
-               <span class="fu"><a href="https://rdrr.io/r/base/list.html">list</a></span><span class="op">(</span><span class="st">"FOCUS L4"</span> <span class="op">=</span> <span class="va">FOCUS_2006_L4_mkin</span><span class="op">)</span>,
+<span class="va">mm.L4</span> <span class="op">&lt;-</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">"FOMC"</span><span class="op">)</span>, cores <span class="op">=</span> <span class="fl">1</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="st">"FOCUS L4"</span> <span class="op">=</span> <span class="va">FOCUS_2006_L4_mkin</span><span class="op">)</span>,
                quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>
-<span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html">plot</a></span><span class="op">(</span><span class="va">mm.L4</span><span class="op">)</span></code></pre></div>
+<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">mm.L4</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_L_files/figure-html/unnamed-chunk-15-1.png" width="700"></p>
 <p>The <span class="math inline">\(\chi^2\)</span> error level of 3.3% as well as the plot suggest that the SFO model fits very well. The error level at which the <span class="math inline">\(\chi^2\)</span> test passes is slightly lower for the FOMC model. However, the difference appears negligible.</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/summary.html">summary</a></span><span class="op">(</span><span class="va">mm.L4</span><span class="op">[[</span><span class="st">"SFO"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
-<pre><code>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:34 2021 
-## Date of summary: Wed Mar 31 19:18:34 2021 
-## 
-## Equations:
-## d_parent/dt = - k_parent * parent
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 142 model solutions performed in 0.03 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##          value   type
-## parent_0  96.6  state
-## k_parent   0.1 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##                  value lower upper
-## parent_0     96.600000  -Inf   Inf
-## log_k_parent -2.302585  -Inf   Inf
-## 
-## Fixed parameter values:
-## None
-## 
-## Results:
-## 
-##        AIC      BIC    logLik
-##   47.12133 47.35966 -20.56067
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##              Estimate Std. Error  Lower   Upper
-## parent_0       96.440    1.69900 92.070 100.800
-## log_k_parent   -5.030    0.07059 -5.211  -4.848
-## sigma           3.162    0.79050  1.130   5.194
-## 
-## Parameter correlation:
-##               parent_0 log_k_parent     sigma
-## parent_0     1.000e+00    5.938e-01 3.387e-07
-## log_k_parent 5.938e-01    1.000e+00 5.830e-07
-## sigma        3.387e-07    5.830e-07 1.000e+00
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##           Estimate t value    Pr(&gt;t)     Lower     Upper
-## parent_0 96.440000   56.77 1.604e-08 92.070000 1.008e+02
-## k_parent  0.006541   14.17 1.578e-05  0.005455 7.842e-03
-## sigma     3.162000    4.00 5.162e-03  1.130000 5.194e+00
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data   3.287       2  6
-## parent     3.287       2  6
-## 
-## Estimated disappearance times:
-##        DT50 DT90
-## parent  106  352</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">mm.L4</span><span class="op">[[</span><span class="st">"SFO"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:25 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:25 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - k_parent * parent</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 142 model solutions performed in 0.029 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##          value   type</span>
+<span class="co">## parent_0  96.6  state</span>
+<span class="co">## k_parent   0.1 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##                  value lower upper</span>
+<span class="co">## parent_0     96.600000  -Inf   Inf</span>
+<span class="co">## log_k_parent -2.302585  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">## None</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC      BIC    logLik</span>
+<span class="co">##   47.12133 47.35966 -20.56067</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##              Estimate Std. Error  Lower   Upper</span>
+<span class="co">## parent_0       96.440    1.69900 92.070 100.800</span>
+<span class="co">## log_k_parent   -5.030    0.07059 -5.211  -4.848</span>
+<span class="co">## sigma           3.162    0.79050  1.130   5.194</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##               parent_0 log_k_parent     sigma</span>
+<span class="co">## parent_0     1.000e+00    5.938e-01 3.387e-07</span>
+<span class="co">## log_k_parent 5.938e-01    1.000e+00 5.830e-07</span>
+<span class="co">## sigma        3.387e-07    5.830e-07 1.000e+00</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##           Estimate t value    Pr(&gt;t)     Lower     Upper</span>
+<span class="co">## parent_0 96.440000   56.77 1.604e-08 92.070000 1.008e+02</span>
+<span class="co">## k_parent  0.006541   14.17 1.578e-05  0.005455 7.842e-03</span>
+<span class="co">## sigma     3.162000    4.00 5.162e-03  1.130000 5.194e+00</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data   3.287       2  6</span>
+<span class="co">## parent     3.287       2  6</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##        DT50 DT90</span>
+<span class="co">## parent  106  352</span></code></pre>
 <div class="sourceCode" id="cb31"><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">mm.L4</span><span class="op">[[</span><span class="st">"FOMC"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
-<pre><code>## mkin version used for fitting:    1.0.4 
-## R version used for fitting:       4.0.4 
-## Date of fit:     Wed Mar 31 19:18:34 2021 
-## Date of summary: Wed Mar 31 19:18:34 2021 
-## 
-## Equations:
-## d_parent/dt = - (alpha/beta) * 1/((time/beta) + 1) * parent
-## 
-## Model predictions using solution type analytical 
-## 
-## Fitted using 224 model solutions performed in 0.046 s
-## 
-## Error model: Constant variance 
-## 
-## Error model algorithm: OLS 
-## 
-## Starting values for parameters to be optimised:
-##          value   type
-## parent_0  96.6  state
-## alpha      1.0 deparm
-## beta      10.0 deparm
-## 
-## Starting values for the transformed parameters actually optimised:
-##               value lower upper
-## parent_0  96.600000  -Inf   Inf
-## log_alpha  0.000000  -Inf   Inf
-## log_beta   2.302585  -Inf   Inf
-## 
-## Fixed parameter values:
-## None
-## 
-## Results:
-## 
-##        AIC      BIC    logLik
-##   40.37255 40.69032 -16.18628
-## 
-## Optimised, transformed parameters with symmetric confidence intervals:
-##           Estimate Std. Error   Lower    Upper
-## parent_0   99.1400     1.2670 95.6300 102.7000
-## log_alpha  -0.3506     0.2616 -1.0770   0.3756
-## log_beta    4.1740     0.3938  3.0810   5.2670
-## sigma       1.8300     0.4575  0.5598   3.1000
-## 
-## Parameter correlation:
-##             parent_0  log_alpha   log_beta      sigma
-## parent_0   1.000e+00 -4.696e-01 -5.543e-01 -2.468e-07
-## log_alpha -4.696e-01  1.000e+00  9.889e-01  2.478e-08
-## log_beta  -5.543e-01  9.889e-01  1.000e+00  5.211e-08
-## sigma     -2.468e-07  2.478e-08  5.211e-08  1.000e+00
-## 
-## Backtransformed parameters:
-## Confidence intervals for internally transformed parameters are asymmetric.
-## t-test (unrealistically) based on the assumption of normal distribution
-## for estimators of untransformed parameters.
-##          Estimate t value    Pr(&gt;t)   Lower   Upper
-## parent_0  99.1400  78.250 7.993e-08 95.6300 102.700
-## alpha      0.7042   3.823 9.365e-03  0.3407   1.456
-## beta      64.9800   2.540 3.201e-02 21.7800 193.900
-## sigma      1.8300   4.000 8.065e-03  0.5598   3.100
-## 
-## FOCUS Chi2 error levels in percent:
-##          err.min n.optim df
-## All data   2.029       3  5
-## parent     2.029       3  5
-## 
-## Estimated disappearance times:
-##         DT50 DT90 DT50back
-## parent 108.9 1644    494.9</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">mm.L4</span><span class="op">[[</span><span class="st">"FOMC"</span>, <span class="fl">1</span><span class="op">]</span><span class="op">]</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></code></pre></div>
+<pre><code><span class="co">## mkin version used for fitting:    1.1.0 </span>
+<span class="co">## R version used for fitting:       4.1.2 </span>
+<span class="co">## Date of fit:     Wed Mar  2 13:44:25 2022 </span>
+<span class="co">## Date of summary: Wed Mar  2 13:44:25 2022 </span>
+<span class="co">## </span>
+<span class="co">## Equations:</span>
+<span class="co">## d_parent/dt = - (alpha/beta) * 1/((time/beta) + 1) * parent</span>
+<span class="co">## </span>
+<span class="co">## Model predictions using solution type analytical </span>
+<span class="co">## </span>
+<span class="co">## Fitted using 224 model solutions performed in 0.045 s</span>
+<span class="co">## </span>
+<span class="co">## Error model: Constant variance </span>
+<span class="co">## </span>
+<span class="co">## Error model algorithm: OLS </span>
+<span class="co">## </span>
+<span class="co">## Starting values for parameters to be optimised:</span>
+<span class="co">##          value   type</span>
+<span class="co">## parent_0  96.6  state</span>
+<span class="co">## alpha      1.0 deparm</span>
+<span class="co">## beta      10.0 deparm</span>
+<span class="co">## </span>
+<span class="co">## Starting values for the transformed parameters actually optimised:</span>
+<span class="co">##               value lower upper</span>
+<span class="co">## parent_0  96.600000  -Inf   Inf</span>
+<span class="co">## log_alpha  0.000000  -Inf   Inf</span>
+<span class="co">## log_beta   2.302585  -Inf   Inf</span>
+<span class="co">## </span>
+<span class="co">## Fixed parameter values:</span>
+<span class="co">## None</span>
+<span class="co">## </span>
+<span class="co">## Results:</span>
+<span class="co">## </span>
+<span class="co">##        AIC      BIC    logLik</span>
+<span class="co">##   40.37255 40.69032 -16.18628</span>
+<span class="co">## </span>
+<span class="co">## Optimised, transformed parameters with symmetric confidence intervals:</span>
+<span class="co">##           Estimate Std. Error   Lower    Upper</span>
+<span class="co">## parent_0   99.1400     1.2670 95.6300 102.7000</span>
+<span class="co">## log_alpha  -0.3506     0.2616 -1.0770   0.3756</span>
+<span class="co">## log_beta    4.1740     0.3938  3.0810   5.2670</span>
+<span class="co">## sigma       1.8300     0.4575  0.5598   3.1000</span>
+<span class="co">## </span>
+<span class="co">## Parameter correlation:</span>
+<span class="co">##             parent_0  log_alpha   log_beta      sigma</span>
+<span class="co">## parent_0   1.000e+00 -4.696e-01 -5.543e-01 -2.468e-07</span>
+<span class="co">## log_alpha -4.696e-01  1.000e+00  9.889e-01  2.478e-08</span>
+<span class="co">## log_beta  -5.543e-01  9.889e-01  1.000e+00  5.211e-08</span>
+<span class="co">## sigma     -2.468e-07  2.478e-08  5.211e-08  1.000e+00</span>
+<span class="co">## </span>
+<span class="co">## Backtransformed parameters:</span>
+<span class="co">## Confidence intervals for internally transformed parameters are asymmetric.</span>
+<span class="co">## t-test (unrealistically) based on the assumption of normal distribution</span>
+<span class="co">## for estimators of untransformed parameters.</span>
+<span class="co">##          Estimate t value    Pr(&gt;t)   Lower   Upper</span>
+<span class="co">## parent_0  99.1400  78.250 7.993e-08 95.6300 102.700</span>
+<span class="co">## alpha      0.7042   3.823 9.365e-03  0.3407   1.456</span>
+<span class="co">## beta      64.9800   2.540 3.201e-02 21.7800 193.900</span>
+<span class="co">## sigma      1.8300   4.000 8.065e-03  0.5598   3.100</span>
+<span class="co">## </span>
+<span class="co">## FOCUS Chi2 error levels in percent:</span>
+<span class="co">##          err.min n.optim df</span>
+<span class="co">## All data   2.029       3  5</span>
+<span class="co">## parent     2.029       3  5</span>
+<span class="co">## </span>
+<span class="co">## Estimated disappearance times:</span>
+<span class="co">##         DT50 DT90 DT50back</span>
+<span class="co">## parent 108.9 1644    494.9</span></code></pre>
 </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-ranke2014">
 <p>Ranke, Johannes. 2014. “Prüfung und Validierung von Modellierungssoftware als Alternative zu ModelMaker 4.0.” Umweltbundesamt Projektnummer 27452.</p>
@@ -800,11 +805,13 @@
 
 
       <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>
@@ -813,5 +820,7 @@
   
 
 
+  
+
   </body>
 </html>
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+<!-- Generated by pkgdown: do not edit by hand --><html lang="en"><head><meta http-equiv="Content-Type" content="text/html; charset=UTF-8"><meta charset="utf-8"><meta http-equiv="X-UA-Compatible" content="IE=edge"><meta name="viewport" content="width=device-width, initial-scale=1.0"><title>Articles • mkin</title><!-- jquery --><script src="https://cdnjs.cloudflare.com/ajax/libs/jquery/3.4.1/jquery.min.js" integrity="sha256-CSXorXvZcTkaix6Yvo6HppcZGetbYMGWSFlBw8HfCJo=" crossorigin="anonymous"></script><!-- Bootstrap --><link rel="stylesheet" href="https://cdnjs.cloudflare.com/ajax/libs/twitter-bootstrap/3.4.1/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous"><script src="https://cdnjs.cloudflare.com/ajax/libs/twitter-bootstrap/3.4.1/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script><!-- bootstrap-toc --><link rel="stylesheet" href="../bootstrap-toc.css"><script src="../bootstrap-toc.js"></script><!-- Font Awesome icons --><link rel="stylesheet" href="https://cdnjs.cloudflare.com/ajax/libs/font-awesome/5.12.1/css/all.min.css" integrity="sha256-mmgLkCYLUQbXn0B1SRqzHar6dCnv9oZFPEC1g1cwlkk=" crossorigin="anonymous"><link rel="stylesheet" href="https://cdnjs.cloudflare.com/ajax/libs/font-awesome/5.12.1/css/v4-shims.min.css" integrity="sha256-wZjR52fzng1pJHwx4aV2AO3yyTOXrcDW7jBpJtTwVxw=" crossorigin="anonymous"><!-- clipboard.js --><script src="https://cdnjs.cloudflare.com/ajax/libs/clipboard.js/2.0.6/clipboard.min.js" integrity="sha256-inc5kl9MA1hkeYUt+EC3BhlIgyp/2jDIyBLS6k3UxPI=" crossorigin="anonymous"></script><!-- headroom.js --><script src="https://cdnjs.cloudflare.com/ajax/libs/headroom/0.11.0/headroom.min.js" integrity="sha256-AsUX4SJE1+yuDu5+mAVzJbuYNPHj/WroHuZ8Ir/CkE0=" crossorigin="anonymous"></script><script src="https://cdnjs.cloudflare.com/ajax/libs/headroom/0.11.0/jQuery.headroom.min.js" integrity="sha256-ZX/yNShbjqsohH1k95liqY9Gd8uOiE1S4vZc+9KQ1K4=" crossorigin="anonymous"></script><!-- pkgdown --><link href="../pkgdown.css" rel="stylesheet"><script src="../pkgdown.js"></script><meta property="og:title" content="Articles"><!-- mathjax --><script src="https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.5/MathJax.js" integrity="sha256-nvJJv9wWKEm88qvoQl9ekL2J+k/RWIsaSScxxlsrv8k=" crossorigin="anonymous"></script><script src="https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.5/config/TeX-AMS-MML_HTMLorMML.js" integrity="sha256-84DKXVJXs0/F8OTMzX4UR909+jtl4G7SPypPavF+GfA=" crossorigin="anonymous"></script><!--[if lt IE 9]>
 <script src="https://oss.maxcdn.com/html5shiv/3.7.3/html5shiv.min.js"></script>
 <script src="https://oss.maxcdn.com/respond/1.4.2/respond.min.js"></script>
-<![endif]-->
+<![endif]--></head><body data-spy="scroll" data-target="#toc">
+    
 
-
-
-  </head>
-
-  <body data-spy="scroll" data-target="#toc">
     <div class="container template-article-index">
-      <header>
-      <div class="navbar navbar-default navbar-fixed-top" role="navigation">
+      <header><div class="navbar navbar-default navbar-fixed-top" role="navigation">
   <div class="container">
     <div class="navbar-header">
       <button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#navbar" aria-expanded="false">
@@ -71,13 +17,12 @@
       </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">1.0.5</span>
+        <span class="version label label-default" data-toggle="tooltip" data-placement="bottom" title="Released version">1.1.0</span>
       </span>
     </div>
 
     <div id="navbar" class="navbar-collapse collapse">
-      <ul class="nav navbar-nav">
-        <li>
+      <ul class="nav navbar-nav"><li>
   <a href="../reference/index.html">Functions and data</a>
 </li>
 <li class="dropdown">
@@ -86,8 +31,7 @@
      
     <span class="caret"></span>
   </a>
-  <ul class="dropdown-menu" role="menu">
-    <li>
+  <ul class="dropdown-menu" role="menu"><li>
       <a href="../articles/mkin.html">Introduction to mkin</a>
     </li>
     <li>
@@ -97,6 +41,9 @@
       <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>
@@ -111,30 +58,23 @@
     <li>
       <a href="../articles/web_only/benchmarks.html">Some benchmark timings</a>
     </li>
-  </ul>
-</li>
+  </ul></li>
 <li>
   <a href="../news/index.html">News</a>
 </li>
-      </ul>
-      <ul class="nav navbar-nav navbar-right">
-        <li>
-  <a href="https://github.com/jranke/mkin/">
+      </ul><ul class="nav navbar-nav navbar-right"><li>
+  <a href="https://github.com/jranke/mkin/" class="external-link">
     <span class="fab fa-github fa-lg"></span>
      
   </a>
 </li>
-      </ul>
-      
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+      </ul></div><!--/.nav-collapse -->
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 </div><!--/.navbar -->
 
       
 
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-
-<div class="row">
+      </header><div class="row">
   <div class="col-md-9 contents">
     <div class="page-header">
       <h1>Articles</h1>
@@ -144,45 +84,43 @@
       <h3>All vignettes</h3>
       <p class="section-desc"></p>
 
-      <dl>
-        <dt><a href="FOCUS_D.html">Example evaluation of FOCUS Example Dataset D</a></dt>
-        <dd></dt>
-        <dt><a href="FOCUS_L.html">Example evaluation of FOCUS Laboratory Data L1 to L3</a></dt>
-        <dd></dt>
-        <dt><a href="mkin.html">Introduction to mkin</a></dt>
-        <dd></dt>
-        <dt><a href="twa.html">Calculation of time weighted average concentrations with mkin</a></dt>
-        <dd></dt>
-        <dt><a href="web_only/FOCUS_Z.html">Example evaluation of FOCUS dataset Z</a></dt>
-        <dd></dt>
-        <dt><a href="web_only/NAFTA_examples.html">Evaluation of example datasets from Attachment 1 to the US EPA SOP for the NAFTA guidance</a></dt>
-        <dd></dt>
-        <dt><a href="web_only/benchmarks.html">Benchmark timings for mkin</a></dt>
-        <dd></dt>
-        <dt><a href="web_only/compiled_models.html">Performance benefit by using compiled model definitions in mkin</a></dt>
-        <dd></dt>
-      </dl>
-    </div>
+      <dl><dt><a href="FOCUS_D.html">Example evaluation of FOCUS Example Dataset D</a></dt>
+        <dd>
+        </dd><dt><a href="FOCUS_L.html">Example evaluation of FOCUS Laboratory Data L1 to L3</a></dt>
+        <dd>
+        </dd><dt><a href="mkin.html">Introduction to mkin</a></dt>
+        <dd>
+        </dd><dt><a href="twa.html">Calculation of time weighted average concentrations with mkin</a></dt>
+        <dd>
+        </dd><dt><a href="web_only/FOCUS_Z.html">Example evaluation of FOCUS dataset Z</a></dt>
+        <dd>
+        </dd><dt><a href="web_only/NAFTA_examples.html">Evaluation of example datasets from Attachment 1 to the US EPA SOP for the NAFTA guidance</a></dt>
+        <dd>
+        </dd><dt><a href="web_only/benchmarks.html">Benchmark timings for mkin</a></dt>
+        <dd>
+        </dd><dt><a href="web_only/compiled_models.html">Performance benefit by using compiled model definitions in mkin</a></dt>
+        <dd>
+        </dd><dt><a href="web_only/dimethenamid_2018.html">Example evaluations of the dimethenamid data from 2018</a></dt>
+        <dd>
+      </dd></dl></div>
   </div>
 </div>
 
 
-      <footer>
-      <div class="copyright">
-  <p>Developed by Johannes Ranke.</p>
+      <footer><div class="copyright">
+  <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>
 
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+      </footer></div>
 
   
 
 
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+  
 
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diff --git a/docs/articles/mkin.html b/docs/articles/mkin.html
index a0fccc16..e51356ee 100644
--- a/docs/articles/mkin.html
+++ b/docs/articles/mkin.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>
@@ -94,28 +99,28 @@
 
       
 
-      </header><script src="mkin_files/header-attrs-2.7/header-attrs.js"></script><script src="mkin_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row">
+      </header><script src="mkin_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>Introduction to mkin</h1>
-                        <h4 class="author">Johannes Ranke</h4>
+                        <h4 data-toc-skip class="author">Johannes Ranke</h4>
             
-            <h4 class="date">Last change 15 February 2021 (rebuilt 2021-03-31)</h4>
+            <h4 data-toc-skip class="date">Last change 15 February 2021 (rebuilt 2022-03-02)</h4>
       
-      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/mkin.rmd"><code>vignettes/mkin.rmd</code></a></small>
+      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/mkin.rmd" class="external-link"><code>vignettes/mkin.rmd</code></a></small>
       <div class="hidden name"><code>mkin.rmd</code></div>
 
     </div>
 
     
     
-<p><a href="https://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="abstract" class="section level1">
-<h1 class="hasAnchor">
-<a href="#abstract" class="anchor"></a>Abstract</h1>
+<p><a href="https://www.jrwb.de" class="external-link">Wissenschaftlicher Berater, Kronacher Str. 12, 79639 Grenzach-Wyhlen, Germany</a><br> Privatdozent at the University of Freiburg</p>
+<div class="section level2">
+<h2 id="abstract">Abstract<a class="anchor" aria-label="anchor" href="#abstract"></a>
+</h2>
 <p>In the regulatory evaluation of chemical substances like plant protection products (pesticides), biocides and other chemicals, degradation data play an important role. For the evaluation of pesticide degradation experiments, detailed guidance has been developed, based on nonlinear optimisation. The <code>R</code> add-on package <code>mkin</code> implements fitting some of the models recommended in this guidance from within R and calculates some statistical measures for data series within one or more compartments, for parent and metabolites.</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="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="co"># Define the kinetic model</span>
 <span class="va">m_SFO_SFO_SFO</span> <span class="op">&lt;-</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="st">"M2"</span><span class="op">)</span>,
@@ -124,12 +129,12 @@
 
 
 <span class="co"># Produce model predictions using some arbitrary parameters</span>
-<span class="va">sampling_times</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="fl">0</span>, <span class="fl">1</span>, <span class="fl">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">28</span>, <span class="fl">60</span>, <span class="fl">90</span>, <span class="fl">120</span><span class="op">)</span>
+<span class="va">sampling_times</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="fl">0</span>, <span class="fl">1</span>, <span class="fl">3</span>, <span class="fl">7</span>, <span class="fl">14</span>, <span class="fl">28</span>, <span class="fl">60</span>, <span class="fl">90</span>, <span class="fl">120</span><span class="op">)</span>
 <span class="va">d_SFO_SFO_SFO</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinpredict.html">mkinpredict</a></span><span class="op">(</span><span class="va">m_SFO_SFO_SFO</span>,
-  <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span>k_parent <span class="op">=</span> <span class="fl">0.03</span>,
-    f_parent_to_M1 <span class="op">=</span> <span class="fl">0.5</span>, k_M1 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/Log.html">log</a></span><span class="op">(</span><span class="fl">2</span><span class="op">)</span><span class="op">/</span><span class="fl">100</span>,
-    f_M1_to_M2 <span class="op">=</span> <span class="fl">0.9</span>, k_M2 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/Log.html">log</a></span><span class="op">(</span><span class="fl">2</span><span class="op">)</span><span class="op">/</span><span class="fl">50</span><span class="op">)</span>,
-  <span class="fu"><a href="https://rdrr.io/r/base/c.html">c</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fl">100</span>, M1 <span class="op">=</span> <span class="fl">0</span>, M2 <span class="op">=</span> <span class="fl">0</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>k_parent <span class="op">=</span> <span class="fl">0.03</span>,
+    f_parent_to_M1 <span class="op">=</span> <span class="fl">0.5</span>, k_M1 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/Log.html" class="external-link">log</a></span><span class="op">(</span><span class="fl">2</span><span class="op">)</span><span class="op">/</span><span class="fl">100</span>,
+    f_M1_to_M2 <span class="op">=</span> <span class="fl">0.9</span>, k_M2 <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/Log.html" class="external-link">log</a></span><span class="op">(</span><span class="fl">2</span><span class="op">)</span><span class="op">/</span><span class="fl">50</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>parent <span class="op">=</span> <span class="fl">100</span>, M1 <span class="op">=</span> <span class="fl">0</span>, M2 <span class="op">=</span> <span class="fl">0</span><span class="op">)</span>,
   <span class="va">sampling_times</span><span class="op">)</span>
 
 <span class="co"># Generate a dataset by adding normally distributed errors with</span>
@@ -142,31 +147,31 @@
 <span class="va">f_SFO_SFO_SFO</span> <span class="op">&lt;-</span> <span class="fu"><a href="../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">m_SFO_SFO_SFO</span>, <span class="va">d_SFO_SFO_SFO_err</span><span class="op">[[</span><span class="fl">1</span><span class="op">]</span><span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span>
 
 <span class="co"># Plot the results separately for parent and metabolites</span>
-<span class="fu"><a href="../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">f_SFO_SFO_SFO</span>, lpos <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">"topright"</span>, <span class="st">"bottomright"</span>, <span class="st">"bottomright"</span><span class="op">)</span><span class="op">)</span></code></pre></div>
+<span class="fu"><a href="../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">f_SFO_SFO_SFO</span>, lpos <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">"topright"</span>, <span class="st">"bottomright"</span>, <span class="st">"bottomright"</span><span class="op">)</span><span class="op">)</span></code></pre></div>
 <p><img src="mkin_files/figure-html/unnamed-chunk-2-1.png" width="768"></p>
 </div>
-<div id="background" class="section level1">
-<h1 class="hasAnchor">
-<a href="#background" class="anchor"></a>Background</h1>
+<div class="section level2">
+<h2 id="background">Background<a class="anchor" aria-label="anchor" href="#background"></a>
+</h2>
 <p>The <code>mkin</code> package <span class="citation">(Ranke 2021)</span> implements the approach to degradation kinetics recommended in the kinetics report provided by the FOrum for Co-ordination of pesticide fate models and their USe <span class="citation">(FOCUS Work Group on Degradation Kinetics 2006, 2014)</span>. It covers data series describing the decline of one compound, data series with transformation products (commonly termed metabolites) and data series for more than one compartment. It is possible to include back reactions. Therefore, equilibrium reactions and equilibrium partitioning can be specified, although this often leads to an overparameterisation of the model.</p>
 <p>When the first <code>mkin</code> code was published in 2010, the most commonly used tools for fitting more complex kinetic degradation models to experimental data were KinGUI <span class="citation">(Schäfer et al. 2007)</span>, a MATLAB based tool with a graphical user interface that was specifically tailored to the task and included some output as proposed by the FOCUS Kinetics Workgroup, and ModelMaker, a general purpose compartment based tool providing infrastructure for fitting dynamic simulation models based on differential equations to data.</p>
-<p>The ‘mkin’ code was first uploaded to the BerliOS development platform. When this was taken down, the version control history was imported into the R-Forge site (see <em>e.g.</em> <a href="https://cgit.jrwb.de/mkin/commit/?id=30cbb4092f6d2d3beff5800603374a0d009ad770">the initial commit on 11 May 2010</a>), where the code is still being updated.</p>
+<p>The ‘mkin’ code was first uploaded to the BerliOS development platform. When this was taken down, the version control history was imported into the R-Forge site (see <em>e.g.</em> <a href="https://cgit.jrwb.de/mkin/commit/?id=30cbb4092f6d2d3beff5800603374a0d009ad770" class="external-link">the initial commit on 11 May 2010</a>), where the code is still being updated.</p>
 <p>At that time, the R package <code>FME</code> (Flexible Modelling Environment) <span class="citation">(Soetaert and Petzoldt 2010)</span> was already available, and provided a good basis for developing a package specifically tailored to the task. The remaining challenge was to make it as easy as possible for the users (including the author of this vignette) to specify the system of differential equations and to include the output requested by the FOCUS guidance, such as the <span class="math inline">\(\chi^2\)</span> error level as defined in this guidance.</p>
 <p>Also, <code>mkin</code> introduced using analytical solutions for parent only kinetics for improved optimization speed. Later, Eigenvalue based solutions were introduced to <code>mkin</code> for the case of linear differential equations (<em>i.e.</em> where the FOMC or DFOP models were not used for the parent compound), greatly improving the optimization speed for these cases. This, has become somehow obsolete, as the use of compiled code described below gives even faster execution times.</p>
 <p>The possibility to specify back-reactions and a biphasic model (SFORB) for metabolites were present in <code>mkin</code> from the very beginning.</p>
-<div id="derived-software-tools" class="section level2">
-<h2 class="hasAnchor">
-<a href="#derived-software-tools" class="anchor"></a>Derived software tools</h2>
+<div class="section level3">
+<h3 id="derived-software-tools">Derived software tools<a class="anchor" aria-label="anchor" href="#derived-software-tools"></a>
+</h3>
 <p>Soon after the publication of <code>mkin</code>, two derived tools were published, namely KinGUII (developed at Bayer Crop Science) and CAKE (commissioned to Tessella by Syngenta), which added a graphical user interface (GUI), and added fitting by iteratively reweighted least squares (IRLS) and characterisation of likely parameter distributions by Markov Chain Monte Carlo (MCMC) sampling.</p>
 <p>CAKE focuses on a smooth use experience, sacrificing some flexibility in the model definition, originally allowing only two primary metabolites in parallel. The current version 3.4 of CAKE released in May 2020 uses a scheme for up to six metabolites in a flexible arrangement and supports biphasic modelling of metabolites, but does not support back-reactions (non-instantaneous equilibria).</p>
 <p>KinGUI offers an even more flexible widget for specifying complex kinetic models. Back-reactions (non-instantaneous equilibria) were supported early on, but until 2014, only simple first-order models could be specified for transformation products. Starting with KinGUII version 2.1, biphasic modelling of metabolites was also available in KinGUII.</p>
-<p>A further graphical user interface (GUI) that has recently been brought to a decent degree of maturity is the browser based GUI named <code>gmkin</code>. Please see its <a href="https://pkgdown.jrwb.de/gmkin/">documentation page</a> and <a href="https://pkgdown.jrwb.de/gmkin/articles/gmkin_manual.html">manual</a> for further information.</p>
+<p>A further graphical user interface (GUI) that has recently been brought to a decent degree of maturity is the browser based GUI named <code>gmkin</code>. Please see its <a href="https://pkgdown.jrwb.de/gmkin/" class="external-link">documentation page</a> and <a href="https://pkgdown.jrwb.de/gmkin/articles/gmkin_manual.html" class="external-link">manual</a> for further information.</p>
 <p>A comparison of scope, usability and numerical results obtained with these tools has been recently been published by <span class="citation">Ranke, Wöltjen, and Meinecke (2018)</span>.</p>
 </div>
 </div>
-<div id="unique-features" class="section level1">
-<h1 class="hasAnchor">
-<a href="#unique-features" class="anchor"></a>Unique features</h1>
+<div class="section level2">
+<h2 id="unique-features">Unique features<a class="anchor" aria-label="anchor" href="#unique-features"></a>
+</h2>
 <p>Currently, the main unique features available in <code>mkin</code> are</p>
 <ul>
 <li>the <a href="https://pkgdown.jrwb.de/mkin/articles/web_only/compiled_models.html">speed increase</a> by using compiled code when a compiler is present,</li>
@@ -177,66 +182,66 @@
 </ul>
 <p>The iteratively reweighted least squares fitting of different variances for each variable as introduced by <span class="citation">Gao et al. (2011)</span> has been available in mkin since <a href="https://pkgdown.jrwb.de/mkin/news/index.html#mkin-0-9-22-2013-10-26">version 0.9-22</a>. With <a href="https://pkgdown.jrwb.de/mkin/news/index.html#mkin-0-9-49-5-2019-07-04">release 0.9.49.5</a>, the IRLS algorithm has been complemented by direct or step-wise maximisation of the likelihood function, which makes it possible not only to fit the variance by variable error model but also a <a href="https://pkgdown.jrwb.de/mkin/reference/sigma_twocomp.html">two-component error model</a> inspired by error models developed in analytical chemistry <span class="citation">(Ranke and Meinecke 2019)</span>.</p>
 </div>
-<div id="internal-parameter-transformations" class="section level1">
-<h1 class="hasAnchor">
-<a href="#internal-parameter-transformations" class="anchor"></a>Internal parameter transformations</h1>
+<div class="section level2">
+<h2 id="internal-parameter-transformations">Internal parameter transformations<a class="anchor" aria-label="anchor" href="#internal-parameter-transformations"></a>
+</h2>
 <p>For rate constants, the log transformation is used, as proposed by Bates and Watts <span class="citation">(1988, 77, 149)</span>. Approximate intervals are constructed for the transformed rate constants <span class="citation">(compare Bates and Watts 1988, 135)</span>, <em>i.e.</em> for their logarithms. Confidence intervals for the rate constants are then obtained using the appropriate backtransformation using the exponential function.</p>
 <p>In the first version of <code>mkin</code> allowing for specifying models using formation fractions, a home-made reparameterisation was used in order to ensure that the sum of formation fractions would not exceed unity.</p>
 <p>This method is still used in the current version of KinGUII (v2.1 from April 2014), with a modification that allows for fixing the pathway to sink to zero. CAKE uses penalties in the objective function in order to enforce this constraint.</p>
 <p>In 2012, an alternative reparameterisation of the formation fractions was proposed together with René Lehmann <span class="citation">(Ranke and Lehmann 2012)</span>, based on isometric logratio transformation (ILR). The aim was to improve the validity of the linear approximation of the objective function during the parameter estimation procedure as well as in the subsequent calculation of parameter confidence intervals. In the current version of mkin, a logit transformation is used for parameters that are bound between 0 and 1, such as the g parameter of the DFOP model.</p>
-<div id="confidence-intervals-based-on-transformed-parameters" class="section level2">
-<h2 class="hasAnchor">
-<a href="#confidence-intervals-based-on-transformed-parameters" class="anchor"></a>Confidence intervals based on transformed parameters</h2>
+<div class="section level3">
+<h3 id="confidence-intervals-based-on-transformed-parameters">Confidence intervals based on transformed parameters<a class="anchor" aria-label="anchor" href="#confidence-intervals-based-on-transformed-parameters"></a>
+</h3>
 <p>In the first attempt at providing improved parameter confidence intervals introduced to <code>mkin</code> in 2013, confidence intervals obtained from FME on the transformed parameters were simply all backtransformed one by one to yield asymmetric confidence intervals for the backtransformed parameters.</p>
 <p>However, while there is a 1:1 relation between the rate constants in the model and the transformed parameters fitted in the model, the parameters obtained by the isometric logratio transformation are calculated from the set of formation fractions that quantify the paths to each of the compounds formed from a specific parent compound, and no such 1:1 relation exists.</p>
 <p>Therefore, parameter confidence intervals for formation fractions obtained with this method only appear valid for the case of a single transformation product, where currently the logit transformation is used for the formation fraction.</p>
 <p>The confidence intervals obtained by backtransformation for the cases where a 1:1 relation between transformed and original parameter exist are considered by the author of this vignette to be more accurate than those obtained using a re-estimation of the Hessian matrix after backtransformation, as implemented in the FME package.</p>
 </div>
-<div id="parameter-t-test-based-on-untransformed-parameters" class="section level2">
-<h2 class="hasAnchor">
-<a href="#parameter-t-test-based-on-untransformed-parameters" class="anchor"></a>Parameter t-test based on untransformed parameters</h2>
+<div class="section level3">
+<h3 id="parameter-t-test-based-on-untransformed-parameters">Parameter t-test based on untransformed parameters<a class="anchor" aria-label="anchor" href="#parameter-t-test-based-on-untransformed-parameters"></a>
+</h3>
 <p>The standard output of many nonlinear regression software packages includes the results from a test for significant difference from zero for all parameters. Such a test is also recommended to check the validity of rate constants in the FOCUS guidance <span class="citation">(FOCUS Work Group on Degradation Kinetics 2014, 96ff)</span>.</p>
 <p>It has been argued that the precondition for this test, <em>i.e.</em> normal distribution of the estimator for the parameters, is not fulfilled in the case of nonlinear regression <span class="citation">(Ranke and Lehmann 2015)</span>. However, this test is commonly used by industry, consultants and national authorities in order to decide on the reliability of parameter estimates, based on the FOCUS guidance mentioned above. Therefore, the results of this one-sided t-test are included in the summary output from <code>mkin</code>.</p>
 <p>As it is not reasonable to test for significant difference of the transformed parameters (<em>e.g.</em> <span class="math inline">\(log(k)\)</span>) from zero, the t-test is calculated based on the model definition before parameter transformation, <em>i.e.</em> in a similar way as in packages that do not apply such an internal parameter transformation. A note is included in the <code>mkin</code> output, pointing to the fact that the t-test is based on the unjustified assumption of normal distribution of the parameter estimators.</p>
 </div>
 </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-bates1988">
 <p>Bates, D., and D. Watts. 1988. <em>Nonlinear Regression and Its Applications</em>. Wiley-Interscience.</p>
 </div>
 <div id="ref-FOCUS2006">
-<p>FOCUS Work Group on Degradation Kinetics. 2006. <em>Guidance Document on Estimating Persistence and Degradation Kinetics from Environmental Fate Studies on Pesticides in Eu Registration. Report of the Focus Work Group on Degradation Kinetics</em>. <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. 2006. <em>Guidance Document on Estimating Persistence and Degradation Kinetics from Environmental Fate Studies on Pesticides in Eu Registration. Report of the Focus Work Group on Degradation Kinetics</em>. <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 id="ref-FOCUSkinetics2014">
-<p>———. 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>———. 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 id="ref-gao11">
 <p>Gao, Z., J. W. Green, J. Vanderborght, and W. Schmitt. 2011. “Improving Uncertainty Analysis in Kinetic Evaluations Using Iteratively Reweighted Least Squares.” Journal. <em>Environmental Science and Technology</em> 45: 4429–37.</p>
 </div>
 <div id="ref-pkg:mkin">
-<p>Ranke, J. 2021. <em>‘mkin‘: Kinetic Evaluation of Chemical Degradation Data</em>. <a href="https://CRAN.R-project.org/package=mkin">https://CRAN.R-project.org/package=mkin</a>.</p>
+<p>Ranke, J. 2021. <em>‘mkin‘: Kinetic Evaluation of Chemical Degradation Data</em>. <a href="https://CRAN.R-project.org/package=mkin" class="external-link">https://CRAN.R-project.org/package=mkin</a>.</p>
 </div>
 <div id="ref-ranke2012">
 <p>Ranke, J., and R. Lehmann. 2012. “Parameter Reliability in Kinetic Evaluation of Environmental Metabolism Data - Assessment and the Influence of Model Specification.” In <em>SETAC World 20-24 May</em>. Berlin.</p>
 </div>
 <div id="ref-ranke2015">
-<p>———. 2015. “To T-Test or Not to T-Test, That Is the Question.” In <em>XV Symposium on Pesticide Chemistry 2-4 September 2015</em>. Piacenza. <a href="http://chem.uft.uni-bremen.de/ranke/posters/piacenza_2015.pdf">http://chem.uft.uni-bremen.de/ranke/posters/piacenza_2015.pdf</a>.</p>
+<p>———. 2015. “To T-Test or Not to T-Test, That Is the Question.” In <em>XV Symposium on Pesticide Chemistry 2-4 September 2015</em>. Piacenza. <a href="http://chem.uft.uni-bremen.de/ranke/posters/piacenza_2015.pdf" class="external-link">http://chem.uft.uni-bremen.de/ranke/posters/piacenza_2015.pdf</a>.</p>
 </div>
 <div id="ref-ranke2019">
-<p>Ranke, Johannes, and Stefan Meinecke. 2019. “Error Models for the Kinetic Evaluation of Chemical Degradation Data.” <em>Environments</em> 6 (12). <a href="https://doi.org/10.3390/environments6120124">https://doi.org/10.3390/environments6120124</a>.</p>
+<p>Ranke, Johannes, and Stefan Meinecke. 2019. “Error Models for the Kinetic Evaluation of Chemical Degradation Data.” <em>Environments</em> 6 (12). <a href="https://doi.org/10.3390/environments6120124" class="external-link">https://doi.org/10.3390/environments6120124</a>.</p>
 </div>
 <div id="ref-ranke2018">
-<p>Ranke, Johannes, Janina Wöltjen, and Stefan Meinecke. 2018. “Comparison of Software Tools for Kinetic Evaluation of Chemical Degradation Data.” <em>Environmental Sciences Europe</em> 30 (1): 17. <a href="https://doi.org/10.1186/s12302-018-0145-1">https://doi.org/10.1186/s12302-018-0145-1</a>.</p>
+<p>Ranke, Johannes, Janina Wöltjen, and Stefan Meinecke. 2018. “Comparison of Software Tools for Kinetic Evaluation of Chemical Degradation Data.” <em>Environmental Sciences Europe</em> 30 (1): 17. <a href="https://doi.org/10.1186/s12302-018-0145-1" class="external-link">https://doi.org/10.1186/s12302-018-0145-1</a>.</p>
 </div>
 <div id="ref-schaefer2007">
 <p>Schäfer, D., B. Mikolasch, P. Rainbird, and B. Harvey. 2007. “KinGUI: A New Kinetic Software Tool for Evaluations According to FOCUS Degradation Kinetics.” In <em>Proceedings of the Xiii Symposium Pesticide Chemistry</em>, edited by Del Re A. A. M., Capri E., Fragoulis G., and Trevisan M., 916–23. Piacenza.</p>
 </div>
 <div id="ref-soetaert2010">
-<p>Soetaert, Karline, and Thomas Petzoldt. 2010. “Inverse Modelling, Sensitivity and Monte Carlo Analysis in R Using Package FME.” <em>Journal of Statistical Software</em> 33 (3): 1–28. <a href="https://www.jstatsoft.org/v33/i03/">https://www.jstatsoft.org/v33/i03/</a>.</p>
+<p>Soetaert, Karline, and Thomas Petzoldt. 2010. “Inverse Modelling, Sensitivity and Monte Carlo Analysis in R Using Package FME.” <em>Journal of Statistical Software</em> 33 (3): 1–28. <a href="https://doi.org/10.18637/jss.v033.i03" class="external-link">https://doi.org/10.18637/jss.v033.i03</a>.</p>
 </div>
 </div>
 </div>
@@ -253,11 +258,13 @@
 
 
       <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>
@@ -266,5 +273,7 @@
   
 
 
+  
+
   </body>
 </html>
diff --git a/docs/articles/mkin_files/figure-html/unnamed-chunk-2-1.png b/docs/articles/mkin_files/figure-html/unnamed-chunk-2-1.png
index 8a182047..63246387 100644
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diff --git a/docs/articles/twa.html b/docs/articles/twa.html
index 167f60d3..5b1c333d 100644
--- a/docs/articles/twa.html
+++ b/docs/articles/twa.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>
@@ -94,15 +99,15 @@
 
       
 
-      </header><script src="twa_files/header-attrs-2.7/header-attrs.js"></script><script src="twa_files/accessible-code-block-0.0.1/empty-anchor.js"></script><div class="row">
+      </header><script src="twa_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>Calculation of time weighted average concentrations with mkin</h1>
-                        <h4 class="author">Johannes Ranke</h4>
+                        <h4 data-toc-skip class="author">Johannes Ranke</h4>
             
-            <h4 class="date">Last change 18 September 2019 (rebuilt 2021-03-31)</h4>
+            <h4 data-toc-skip class="date">Last change 18 September 2019 (rebuilt 2022-03-02)</h4>
       
-      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/master/vignettes/twa.rmd"><code>vignettes/twa.rmd</code></a></small>
+      <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/twa.rmd" class="external-link"><code>vignettes/twa.rmd</code></a></small>
       <div class="hidden name"><code>twa.rmd</code></div>
 
     </div>
@@ -140,10 +145,10 @@
 <p><span class="math display">\[f_\textrm{twa} = \frac{1}{t} \left(
   \frac{1}{k_1} \left( 1 - e^{- k_1 t_b} \right) +
   \frac{e^{- k_1 t_b}}{k_2} \left( 1 - e^{- k_2 (t - t_b)} \right)  \right) \]</span></p>
-<p>Note that a method for calculating maximum moving window time weighted average concentrations for a model fitted by ‘mkinfit’ or from parent decline model parameters is included in the <code><a href="../reference/max_twa_parent.html">max_twa_parent()</a></code> function. If the same is needed for metabolites, the function <code><a href="https://pkgdown.jrwb.de/pfm/reference/max_twa.html">pfm::max_twa()</a></code> from the ‘pfm’ package can be used.</p>
+<p>Note that a method for calculating maximum moving window time weighted average concentrations for a model fitted by ‘mkinfit’ or from parent decline model parameters is included in the <code><a href="../reference/max_twa_parent.html">max_twa_parent()</a></code> function. If the same is needed for metabolites, the function <code><a href="https://pkgdown.jrwb.de/pfm/reference/max_twa.html" class="external-link">pfm::max_twa()</a></code> from the ‘pfm’ package can be used.</p>
 <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>
@@ -157,11 +162,13 @@
 
 
       <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>
@@ -170,5 +177,7 @@
   
 
 
+  
+
   </body>
 </html>
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">&lt;-</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">&lt;-</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">&lt;-</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">$</span><span class="va">bpar</span></code></pre></div>
-<pre><code>##            Estimate se_notrans t value     Pr(&gt;t)    Lower    Upper
-## Z0_0       97.01488   3.301084 29.3888 3.2971e-21 91.66556 102.3642
-## k_Z0        2.23601   0.207078 10.7979 3.3309e-11  1.95303   2.5600
-## k_Z1        0.48212   0.063265  7.6207 2.8154e-08  0.40341   0.5762
-## f_Z0_to_Z1  1.00000   0.094764 10.5525 5.3560e-11  0.00000   1.0000
-## sigma       4.80411   0.635638  7.5579 3.2592e-08  3.52677   6.0815</code></pre>
+<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.2a</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div>
+<pre><code><span class="co">##            Estimate se_notrans t value     Pr(&gt;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">&lt;-</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">&lt;-</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">$</span><span class="va">bpar</span></code></pre></div>
-<pre><code>##            Estimate se_notrans t value     Pr(&gt;t)    Lower    Upper
-## Z0_0       97.01488   3.301084 29.3888 3.2971e-21 91.66556 102.3642
-## k_Z0        2.23601   0.207078 10.7979 3.3309e-11  1.95303   2.5600
-## k_Z1        0.48212   0.063265  7.6207 2.8154e-08  0.40341   0.5762
-## f_Z0_to_Z1  1.00000   0.094764 10.5525 5.3560e-11  0.00000   1.0000
-## sigma       4.80411   0.635638  7.5579 3.2592e-08  3.52677   6.0815</code></pre>
+<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.2a.ff</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div>
+<pre><code><span class="co">##            Estimate se_notrans t value     Pr(&gt;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">&lt;-</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">&lt;-</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">$</span><span class="va">bpar</span></code></pre></div>
-<pre><code>##       Estimate se_notrans t value     Pr(&gt;t)    Lower    Upper
-## Z0_0  97.01488   2.597342  37.352 2.0106e-24 91.67597 102.3538
-## k_Z0   2.23601   0.146904  15.221 9.1477e-15  1.95354   2.5593
-## k_Z1   0.48212   0.041727  11.554 4.8268e-12  0.40355   0.5760
-## sigma  4.80411   0.620208   7.746 1.6110e-08  3.52925   6.0790</code></pre>
+<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">m.Z.3</span>, data <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">$</span><span class="va">bpar</span></code></pre></div>
+<pre><code><span class="co">##       Estimate se_notrans t value     Pr(&gt;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">&lt;-</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">&lt;-</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">&lt;-</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(&gt;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(&gt;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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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$bparms.ode, : Observations with value of zero were removed from the</span>
+<span class="co">## data</span></code></pre>
 <div class="sourceCode" id="cb54"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="fu"><a href="../../reference/plot.mkinfit.html">plot_sep</a></span><span class="op">(</span><span class="va">m.Z.mkin.4</span><span class="op">)</span></code></pre></div>
 <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_10-1.png" width="700"></p>
@@ -315,25 +321,27 @@
                     Z1 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z2"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,
                     Z2 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"Z3"</span><span class="op">)</span>,
                     Z3 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFORB"</span><span class="op">)</span><span class="op">)</span></code></pre></div>
-<pre><code>## Temporary DLL for differentials generated and loaded</code></pre>
+<pre><code><span class="co">## Temporary DLL for differentials generated and loaded</span></code></pre>
 <div class="sourceCode" id="cb57"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">m.Z.mkin.5</span> <span class="op">&lt;-</span> <span class="fu"><a href="../../reference/mkinfit.html">mkinfit</a></span><span class="op">(</span><span class="va">Z.mkin.5</span>, <span class="va">FOCUS_2006_Z_mkin</span>,
                       parms.ini <span class="op">=</span> <span class="va">m.Z.mkin.4</span><span class="op">$</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">&lt;-</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
index 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 a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_10-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_10-1.png
index 4a205020..bc6efaf7 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_10-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_10-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11-1.png
index 8b07d497..55c1b645 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11a-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11a-1.png
index 4765c9fe..8e63cd04 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11a-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11a-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11b-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11b-1.png
index e005446b..3902e059 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11b-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11b-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_2-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_2-1.png
index 2e70b207..be652d31 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_2-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_2-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_3-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_3-1.png
index f06ee667..59524035 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_3-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_3-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_5-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_5-1.png
index b8e0e900..d95cac25 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_5-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_5-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_6-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_6-1.png
index 14dd7805..cb333a1c 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_6-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_6-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_7-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_7-1.png
index 414bc941..d87105fb 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_7-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_7-1.png
diff --git a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_9-1.png b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_9-1.png
index 0a83f8ea..db807f14 100644
--- a/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_9-1.png
+++ b/docs/articles/web_only/FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_9-1.png
diff --git a/docs/articles/web_only/NAFTA_examples.html 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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">## $DFOP</span>
+<span class="co">##          Estimate   Pr(&gt;t)    Lower    Upper</span>
+<span class="co">## parent_0 97.96751 2.85e-13 94.21913 101.7159</span>
+<span class="co">## k1        0.00952 6.28e-02  0.00250   0.0363</span>
+<span class="co">## k2        0.00952 1.27e-04  0.00646   0.0140</span>
+<span class="co">## g         0.21241 5.00e-01  0.00000   1.0000</span>
+<span class="co">## sigma     4.18778 2.50e-04  2.39747   5.9781</span>
+<span class="co">## </span>
+<span class="co">## </span>
+<span class="co">## DTx values:</span>
+<span class="co">##      DT50 DT90 DT50_rep</span>
+<span class="co">## SFO  72.8  242     72.8</span>
+<span class="co">## IORE 76.3  137     41.3</span>
+<span class="co">## DFOP 72.8  242     72.8</span>
+<span class="co">## </span>
+<span class="co">## Representative half-life:</span>
+<span class="co">## [1] 41.33</span></code></pre>
 <div class="sourceCode" id="cb104"><pre class="downlit sourceCode r">
 <code class="sourceCode R"><span class="va">p15b</span> <span class="op">&lt;-</span> <span class="fu"><a href="../../reference/nafta.html">nafta</a></span><span class="op">(</span><span class="va">NAFTA_SOP_Attachment</span><span class="op">[[</span><span class="st">"p15b"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></code></pre></div>
-<pre><code>## Warning in sqrt(diag(covar)): NaNs produced</code></pre>
-<pre><code>## Warning in sqrt(1/diag(V)): NaNs produced</code></pre>
-<pre><code>## Warning in cov2cor(ans$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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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">&lt;-</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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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(&gt;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>
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--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p15a-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p15a-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p15b-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p15b-1.png
index a40bd581..6b9ba98c 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p15b-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p15b-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p16-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p16-1.png
index 690c91ef..72df855b 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p16-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p16-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p5a-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p5a-1.png
index c1284b83..391dfb95 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p5a-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p5a-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p5b-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p5b-1.png
index d40ad7e7..db90244b 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p5b-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p5b-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p6-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p6-1.png
index 8c2ae01b..a33372e8 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p6-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p6-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p7-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p7-1.png
index fbf566f7..d64ea98d 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p7-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p7-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p8-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p8-1.png
index 1e137ddf..5cd6c806 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p8-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p8-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p9a-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p9a-1.png
index efc16dda..61359ea6 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p9a-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p9a-1.png
diff --git a/docs/articles/web_only/NAFTA_examples_files/figure-html/p9b-1.png b/docs/articles/web_only/NAFTA_examples_files/figure-html/p9b-1.png
index 53addbd2..85790b1e 100644
--- a/docs/articles/web_only/NAFTA_examples_files/figure-html/p9b-1.png
+++ b/docs/articles/web_only/NAFTA_examples_files/figure-html/p9b-1.png
diff --git a/docs/articles/web_only/benchmarks.html b/docs/articles/web_only/benchmarks.html
index 290906c1..2eea3cb2 100644
--- a/docs/articles/web_only/benchmarks.html
+++ b/docs/articles/web_only/benchmarks.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>
@@ -94,15 +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">&lt;-</span> <span class="va">FOCUS_2006_C</span>
-<span class="va">FOCUS_D</span> <span class="op">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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/" class="external-link">pkgdown</a> 2.0.2.</p>
 </div>
 
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@@ -223,5 +230,7 @@
   
 
 
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diff --git a/docs/articles/web_only/dimethenamid_2018.html b/docs/articles/web_only/dimethenamid_2018.html
new file mode 100644
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+++ b/docs/articles/web_only/dimethenamid_2018.html
@@ -0,0 +1,518 @@
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+  <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">&lt;-</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">&lt;-</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">$</span><span class="va">name</span> <span class="op">==</span> <span class="st">"DMTAP"</span>, <span class="st">"name"</span><span class="op">]</span> <span class="op">&lt;-</span>  <span class="st">"DMTA"</span>
+  <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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>&lt;mmkin&gt; 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">&lt;-</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 &lt;- nlme(f_parent_mkin_const["DFOP", ])</span>
+<span class="va">f_parent_nlme_sfo_tc</span> <span class="op">&lt;-</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">&lt;-</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  &lt;.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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></code></pre></div>
+<p><img src="dimethenamid_2018_files/figure-html/f_parent_saemix_sfo_const-1.png" width="700"></p>
+<p>Obviously the default number of iterations is sufficient to reach convergence. This can also be said for the SFO fit using the two-component error model.</p>
+<div class="sourceCode" id="cb16"><pre class="downlit sourceCode r">
+<code class="sourceCode R"><span class="va">f_parent_saemix_sfo_tc</span> <span class="op">&lt;-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>,
+  control <span class="op">=</span> <span class="va">saemix_control</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span>
+<span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_parent_saemix_sfo_tc</span><span class="op">$</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">&lt;-</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">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></code></pre></div>
+<p><img src="dimethenamid_2018_files/figure-html/f_parent_saemix_dfop_const-1.png" width="700"></p>
+<p>This is improved when the DFOP model is fitted with the two-component error model. Convergence of the variance of k2 is enhanced, it remains more or less stable already after 200 iterations of the first phase.</p>
+<div class="sourceCode" id="cb18"><pre class="downlit sourceCode r">
+<code class="sourceCode R"><span class="va">f_parent_saemix_dfop_tc</span> <span class="op">&lt;-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>,
+  control <span class="op">=</span> <span class="va">saemix_control</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span>
+<span class="va">f_parent_saemix_dfop_tc_moreiter</span> <span class="op">&lt;-</span> <span class="fu">mkin</span><span class="fu">::</span><span class="fu"><a href="../../reference/saem.html">saem</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>,
+  control <span class="op">=</span> <span class="va">saemix_control_moreiter</span>, transformations <span class="op">=</span> <span class="st">"saemix"</span><span class="op">)</span>
+<span class="fu"><a href="https://rdrr.io/pkg/saemix/man/plot-SaemixObject-ANY-method.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</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">&lt;-</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">$</span><span class="va">so</span><span class="op">)</span></code></pre></div>
+<pre><code>Likelihoods calculated by importance sampling</code></pre>
+<div class="sourceCode" id="cb21"><pre class="downlit sourceCode r">
+<code class="sourceCode R"><span class="fu"><a href="https://rdrr.io/r/base/colnames.html" class="external-link">rownames</a></span><span class="op">(</span><span class="va">AIC_parent_saemix</span><span class="op">)</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span>
+  <span class="st">"SFO const"</span>, <span class="st">"SFO tc"</span>, <span class="st">"DFOP const"</span>, <span class="st">"DFOP tc"</span>, <span class="st">"DFOP tc more iterations"</span><span class="op">)</span>
+<span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">AIC_parent_saemix</span><span class="op">)</span></code></pre></div>
+<pre><code>                           AIC    BIC
+SFO const               796.38 795.34
+SFO tc                  798.38 797.13
+DFOP const              705.75 703.88
+DFOP tc                 665.65 663.57
+DFOP tc more iterations 665.88 663.80</code></pre>
+<p>In order to check the influence of the likelihood calculation algorithms implemented in saemix, the likelihood from Gaussian quadrature is added to the best fit, and the AIC values obtained from the three methods are compared.</p>
+<div class="sourceCode" id="cb23"><pre class="downlit sourceCode r">
+<code class="sourceCode R"><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</span><span class="va">so</span> <span class="op">&lt;-</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">$</span><span class="va">so</span><span class="op">)</span>
+<span class="va">AIC_parent_saemix_methods</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span>
+  is <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc</span><span class="op">$</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">&lt;-</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">$</span><span class="va">so</span> <span class="op">&lt;-</span>
+  <span class="fu">saemix</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/llgq.saemix.html" class="external-link">llgq.saemix</a></span><span class="op">(</span><span class="va">f_parent_saemix_dfop_tc_defaults</span><span class="op">$</span><span class="va">so</span><span class="op">)</span>
+<span class="va">AIC_parent_saemix_methods_defaults</span> <span class="op">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">&lt;-</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">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div>
+<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_sfo_tc-1.png" width="700"></p>
+<p>For DFOP with constant variance, the convergence plots show considerable instability of the fit, which indicates overparameterisation which was already observed above for this model combination. Also note that the variance of k2 approximates zero, which was already observed in the saemix fits of the DFOP model.</p>
+<div class="sourceCode" id="cb33"><pre class="downlit sourceCode r">
+<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_dfop_const</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_const</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>,
+  control <span class="op">=</span> <span class="va">nlmixr_saem_control_800</span><span class="op">)</span>
+<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_dfop_const</span><span class="op">$</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">&lt;-</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">$</span><span class="va">nm</span><span class="op">)</span></code></pre></div>
+<p><img src="dimethenamid_2018_files/figure-html/f_parent_nlmixr_saem_dfop_tc-1.png" width="700"></p>
+<p>To check if an increase in the number of iterations improves the fit, we repeat the fit with 1000 iterations for the burn in phase and 300 iterations for the second phase.</p>
+<div class="sourceCode" id="cb35"><pre class="downlit sourceCode r">
+<code class="sourceCode R"><span class="va">f_parent_nlmixr_saem_dfop_tc_moreiter</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_parent_mkin_tc</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span>, est <span class="op">=</span> <span class="st">"saem"</span>,
+  control <span class="op">=</span> <span class="va">nlmixr_saem_control_moreiter</span><span class="op">)</span>
+<span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/traceplot.html" class="external-link">traceplot</a></span><span class="op">(</span><span class="va">f_parent_nlmixr_saem_dfop_tc_moreiter</span><span class="op">$</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">&lt;-</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">&lt;-</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>
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+  </body>
+</html>
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+
+document.addEventListener('DOMContentLoaded', function() {
+  const codeList = document.getElementsByClassName("sourceCode");
+  for (var i = 0; i < codeList.length; i++) {
+    var linkList = codeList[i].getElementsByTagName('a');
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author	Johannes Ranke <jranke@uni-bremen.de>	2022-03-02 18:03:54 +0100
committer	Johannes Ranke <jranke@uni-bremen.de>	2022-03-02 18:03:54 +0100
commit	2bb59c88d49b193f278916ad9cc4de83c0de9604 (patch)
tree	f286bba254d7c5f2d32eeb2b11f6148938b0e1e1 /docs/articles
parent	351248d07f810ccb6c497633a02cd48ee35526e6 (diff)