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authorJohannes Ranke <jranke@uni-bremen.de>2022-08-10 16:04:48 +0200
committerJohannes Ranke <jranke@uni-bremen.de>2022-08-10 16:04:48 +0200
commitfcef764f3688b01a4c6e92915ed68c5e54bc165f (patch)
tree7d5f0b43485d2e99e1e0ea999d0ce47b6914839d /docs/dev/reference/dimethenamid_2018.html
parentbc8ce24677e953e003f7904564b7767537e01ca2 (diff)
parent6178249bbb5e9de7cb7f34287ee7de28a68fed6c (diff)
Merge branch 'v1.1.2'
Diffstat (limited to 'docs/dev/reference/dimethenamid_2018.html')
-rw-r--r--docs/dev/reference/dimethenamid_2018.html445
1 files changed, 160 insertions, 285 deletions
diff --git a/docs/dev/reference/dimethenamid_2018.html b/docs/dev/reference/dimethenamid_2018.html
index 5fb94988..7a356284 100644
--- a/docs/dev/reference/dimethenamid_2018.html
+++ b/docs/dev/reference/dimethenamid_2018.html
@@ -22,7 +22,7 @@ constrained by data protection regulations."><meta name="robots" content="noinde
</button>
<span class="navbar-brand">
<a class="navbar-link" href="../index.html">mkin</a>
- <span class="version label label-info" data-toggle="tooltip" data-placement="bottom" title="In-development version">1.1.0</span>
+ <span class="version label label-info" data-toggle="tooltip" data-placement="bottom" title="In-development version">1.1.2</span>
</span>
</div>
@@ -31,7 +31,7 @@ constrained by data protection regulations."><meta name="robots" content="noinde
<a href="../reference/index.html">Functions and data</a>
</li>
<li class="dropdown">
- <a href="#" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-expanded="false">
+ <a href="#" class="dropdown-toggle" data-toggle="dropdown" role="button" data-bs-toggle="dropdown" aria-expanded="false">
Articles
<span class="caret"></span>
@@ -46,6 +46,9 @@ constrained by data protection regulations."><meta name="robots" content="noinde
<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>
@@ -94,7 +97,7 @@ constrained by data protection regulations.</p>
</div>
<div id="ref-usage">
- <div class="sourceCode"><pre class="sourceCode r"><code><span class="va">dimethenamid_2018</span></code></pre></div>
+ <div class="sourceCode"><pre class="sourceCode r"><code><span><span class="va">dimethenamid_2018</span></span></code></pre></div>
</div>
<div id="format">
@@ -117,7 +120,7 @@ specific pieces of information in the comments.</p>
<div id="ref-examples">
<h2>Examples</h2>
- <div class="sourceCode"><pre class="sourceCode r"><code><span class="r-in"><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">dimethenamid_2018</span><span class="op">)</span></span>
+ <div class="sourceCode"><pre class="sourceCode r"><code><span class="r-in"><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">dimethenamid_2018</span><span class="op">)</span></span></span>
<span class="r-out co"><span class="r-pr">#&gt;</span> &lt;mkindsg&gt; holding 7 mkinds objects</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Title $title: Aerobic soil degradation data on dimethenamid-P from the EU assessment in 2018 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Occurrence of observed compounds $observed_n:</span>
@@ -142,296 +145,168 @@ specific pieces of information in the comments.</p>
<span class="r-out co"><span class="r-pr">#&gt;</span> Flaach NA 20</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> BBA 2.2 NA 20</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> BBA 2.3 NA 20</span>
-<span class="r-in"><span class="va">dmta_ds</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">lapply</a></span><span class="op">(</span><span class="fl">1</span><span class="op">:</span><span class="fl">7</span>, <span class="kw">function</span><span class="op">(</span><span class="va">i</span><span class="op">)</span> <span class="op">{</span></span>
-<span class="r-in"> <span class="va">ds_i</span> <span class="op">&lt;-</span> <span class="va">dimethenamid_2018</span><span class="op">$</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">$</span><span class="va">data</span></span>
-<span class="r-in"> <span class="va">ds_i</span><span class="op">[</span><span class="va">ds_i</span><span class="op">$</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>
-<span class="r-in"> <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">$</span><span class="va">f_time_norm</span><span class="op">[</span><span class="va">i</span><span class="op">]</span></span>
-<span class="r-in"> <span class="va">ds_i</span></span>
-<span class="r-in"><span class="op">}</span><span class="op">)</span></span>
-<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">)</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="va">dimethenamid_2018</span><span class="op">$</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>
-<span class="r-in"><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>
-<span class="r-in"><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>
-<span class="r-in"><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></span>
-<span class="r-in"><span class="co"># \dontrun{</span></span>
-<span class="r-in"><span class="va">dfop_sfo3_plus</span> <span class="op">&lt;-</span> <span class="fu"><a href="mkinmod.html">mkinmod</a></span><span class="op">(</span></span>
-<span class="r-in"> DMTA <span class="op">=</span> <span class="fu"><a href="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">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span>
-<span class="r-in"> M23 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span>
-<span class="r-in"> M27 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span>
-<span class="r-in"> M31 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span>
-<span class="r-in"> quiet <span class="op">=</span> <span class="cn">TRUE</span></span>
-<span class="r-in"><span class="op">)</span></span>
-<span class="r-in"><span class="va">f_dmta_mkin_tc</span> <span class="op">&lt;-</span> <span class="fu"><a href="mmkin.html">mmkin</a></span><span class="op">(</span></span>
-<span class="r-in"> <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">"DFOP-SFO3+"</span> <span class="op">=</span> <span class="va">dfop_sfo3_plus</span><span class="op">)</span>,</span>
-<span class="r-in"> <span class="va">dmta_ds</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span></span>
-<span class="r-in"><span class="fu"><a href="nlmixr.mmkin.html">nlmixr_model</a></span><span class="op">(</span><span class="va">f_dmta_mkin_tc</span><span class="op">)</span></span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> With est = 'saem', a different error model is required for each observed variableChanging the error model to 'obs_tc' (Two-component error for each observed variable)</span>
-<span class="r-wrn co"><span class="r-pr">#&gt;</span> <span class="warning">Warning: </span>number of items to replace is not a multiple of replacement length</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> function () </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> {</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> ini({</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_0 = 99</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.DMTA_0 ~ 2.3</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M23 = -3.9</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.log_k_M23 ~ 0.55</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M27 = -4.3</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.log_k_M27 ~ 0.86</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M31 = -4.2</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.log_k_M31 ~ 0.75</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> log_k1 = -2.2</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.log_k1 ~ 0.9</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> log_k2 = -3.8</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.log_k2 ~ 1.6</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> g_qlogis = 0.44</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.g_qlogis ~ 3.1</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_tffm0_1_qlogis = -2.1</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.f_DMTA_tffm0_1_qlogis ~ 0.3</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_tffm0_2_qlogis = -2.2</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.f_DMTA_tffm0_2_qlogis ~ 0.3</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_tffm0_3_qlogis = -2.1</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> eta.f_DMTA_tffm0_3_qlogis ~ 0.3</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> sigma_low_DMTA = 0.7</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> rsd_high_DMTA = 0.026</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> sigma_low_M23 = 0.7</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> rsd_high_M23 = 0.026</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> sigma_low_M27 = 0.7</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> rsd_high_M27 = 0.026</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> sigma_low_M31 = 0.7</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> rsd_high_M31 = 0.026</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> })</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> model({</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_0_model = DMTA_0 + eta.DMTA_0</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA(0) = DMTA_0_model</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k_M23 = exp(log_k_M23 + eta.log_k_M23)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k_M27 = exp(log_k_M27 + eta.log_k_M27)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k_M31 = exp(log_k_M31 + eta.log_k_M31)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k1 = exp(log_k1 + eta.log_k1)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k2 = exp(log_k2 + eta.log_k2)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> g = expit(g_qlogis + eta.g_qlogis)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23 = expit(f_DMTA_tffm0_1_qlogis + eta.f_DMTA_tffm0_1_qlogis)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23 = expit(f_DMTA_tffm0_2_qlogis + eta.f_DMTA_tffm0_2_qlogis)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23 = expit(f_DMTA_tffm0_3_qlogis + eta.f_DMTA_tffm0_3_qlogis)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23 = f_DMTA_tffm0_1</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M27 = f_DMTA_tffm0_2 * (1 - f_DMTA_tffm0_1)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M31 = f_DMTA_tffm0_3 * (1 - f_DMTA_tffm0_2) * </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> (1 - f_DMTA_tffm0_1)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> d/dt(DMTA) = -((k1 * g * exp(-k1 * time) + k2 * (1 - </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> g) * exp(-k2 * time))/(g * exp(-k1 * time) + (1 - </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> g) * exp(-k2 * time))) * DMTA</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> d/dt(M23) = +f_DMTA_to_M23 * ((k1 * g * exp(-k1 * time) + </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> (1 - g) * exp(-k2 * time))) * DMTA - k_M23 * M23</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> d/dt(M27) = +f_DMTA_to_M27 * ((k1 * g * exp(-k1 * time) + </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> (1 - g) * exp(-k2 * time))) * DMTA - k_M27 * M27 + </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k_M31 * M31</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> d/dt(M31) = +f_DMTA_to_M31 * ((k1 * g * exp(-k1 * time) + </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> (1 - g) * exp(-k2 * time))) * DMTA - k_M31 * M31</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA ~ add(sigma_low_DMTA) + prop(rsd_high_DMTA)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> M23 ~ add(sigma_low_M23) + prop(rsd_high_M23)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> M27 ~ add(sigma_low_M27) + prop(rsd_high_M27)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> M31 ~ add(sigma_low_M31) + prop(rsd_high_M31)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> })</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> }</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> &lt;environment: 0x55555fca3790&gt;</span>
-<span class="r-in"><span class="co"># The focei fit takes about four minutes on my system</span></span>
-<span class="r-in"><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>
-<span class="r-in"> <span class="va">f_dmta_nlmixr_focei</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_dmta_mkin_tc</span>, est <span class="op">=</span> <span class="st">"focei"</span>,</span>
-<span class="r-in"> control <span class="op">=</span> <span class="fu">nlmixr</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/foceiControl.html" class="external-link">foceiControl</a></span><span class="op">(</span>print <span class="op">=</span> <span class="fl">500</span><span class="op">)</span><span class="op">)</span></span>
-<span class="r-in"><span class="op">)</span></span>
-<span class="r-wrn co"><span class="r-pr">#&gt;</span> <span class="warning">Warning: </span>number of items to replace is not a multiple of replacement length</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BBBB;">ℹ</span> parameter labels from comments are typically ignored in non-interactive mode</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BBBB;">ℹ</span> Need to run with the source intact to parse comments</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → creating full model...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → pruning branches (`if`/`else`)...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BB00;">✔</span> done</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → loading into <span style="color: #0000BB;">symengine</span> environment...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BB00;">✔</span> done</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → creating full model...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → pruning branches (`if`/`else`)...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BB00;">✔</span> done</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → loading into <span style="color: #0000BB;">symengine</span> environment...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BB00;">✔</span> done</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → calculate jacobian</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:01 </span>
+<span class="r-in"><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></span>
+<span class="r-in"><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">$</span><span class="va">data</span></span></span>
+<span class="r-in"><span> <span class="va">ds_i</span><span class="op">[</span><span class="va">ds_i</span><span class="op">$</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></span>
+<span class="r-in"><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">$</span><span class="va">f_time_norm</span><span class="op">[</span><span class="va">i</span><span class="op">]</span></span></span>
+<span class="r-in"><span> <span class="va">ds_i</span></span></span>
+<span class="r-in"><span><span class="op">}</span><span class="op">)</span></span></span>
+<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">)</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="va">dimethenamid_2018</span><span class="op">$</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></span>
+<span class="r-in"><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></span>
+<span class="r-in"><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></span>
+<span class="r-in"><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></span></span>
+<span class="r-in"><span><span class="co"># \dontrun{</span></span></span>
+<span class="r-in"><span><span class="co"># We don't use DFOP for the parent compound, as this gives numerical</span></span></span>
+<span class="r-in"><span><span class="co"># instabilities in the fits</span></span></span>
+<span class="r-in"><span><span class="va">sfo_sfo3p</span> <span class="op">&lt;-</span> <span class="fu"><a href="mkinmod.html">mkinmod</a></span><span class="op">(</span></span></span>
+<span class="r-in"><span> DMTA <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</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">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span></span>
+<span class="r-in"><span> M23 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span></span>
+<span class="r-in"><span> M27 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span></span>
+<span class="r-in"><span> M31 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span></span>
+<span class="r-in"><span> quiet <span class="op">=</span> <span class="cn">TRUE</span></span></span>
+<span class="r-in"><span><span class="op">)</span></span></span>
+<span class="r-in"><span><span class="va">dmta_sfo_sfo3p_tc</span> <span class="op">&lt;-</span> <span class="fu"><a href="mmkin.html">mmkin</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="st">"SFO-SFO3+"</span> <span class="op">=</span> <span class="va">sfo_sfo3p</span><span class="op">)</span>,</span></span>
+<span class="r-in"><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></span></span>
+<span class="r-in"><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">dmta_sfo_sfo3p_tc</span><span class="op">)</span></span></span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> &lt;mmkin&gt; object</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Status of individual fits:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> dataset</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> model Calke Borstel Flaach BBA 2.2 BBA 2.3 Elliot</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SFO-SFO3+ OK OK OK OK OK OK </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> OK: No warnings</span>
+<span class="r-in"><span><span class="co"># The default (test_log_parms = FALSE) gives an undue</span></span></span>
+<span class="r-in"><span><span class="co"># influence of ill-defined rate constants that have</span></span></span>
+<span class="r-in"><span><span class="co"># extremely small values:</span></span></span>
+<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html" class="external-link">plot</a></span><span class="op">(</span><span class="fu"><a href="mixed.html">mixed</a></span><span class="op">(</span><span class="va">dmta_sfo_sfo3p_tc</span><span class="op">)</span>, test_log_parms <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></span></span>
+<span class="r-plt img"><img src="dimethenamid_2018-1.png" alt="" width="700" height="433"></span>
+<span class="r-in"><span><span class="co"># If we disregards ill-defined rate constants, the results</span></span></span>
+<span class="r-in"><span><span class="co"># look more plausible, but the truth is likely to be in</span></span></span>
+<span class="r-in"><span><span class="co"># between these variants</span></span></span>
+<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html" class="external-link">plot</a></span><span class="op">(</span><span class="fu"><a href="mixed.html">mixed</a></span><span class="op">(</span><span class="va">dmta_sfo_sfo3p_tc</span><span class="op">)</span>, test_log_parms <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span></span>
+<span class="r-plt img"><img src="dimethenamid_2018-2.png" alt="" width="700" height="433"></span>
+<span class="r-in"><span><span class="co"># We can also specify a default value for the failing</span></span></span>
+<span class="r-in"><span><span class="co"># log parameters, to mimic FOCUS guidance</span></span></span>
+<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html" class="external-link">plot</a></span><span class="op">(</span><span class="fu"><a href="mixed.html">mixed</a></span><span class="op">(</span><span class="va">dmta_sfo_sfo3p_tc</span><span class="op">)</span>, test_log_parms <span class="op">=</span> <span class="cn">TRUE</span>,</span></span>
+<span class="r-in"><span> default_log_parms <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">1000</span><span class="op">)</span></span></span>
+<span class="r-plt img"><img src="dimethenamid_2018-3.png" alt="" width="700" height="433"></span>
+<span class="r-in"><span><span class="co"># As these attempts are not satisfying, we use nonlinear mixed-effects models</span></span></span>
+<span class="r-in"><span><span class="co"># f_dmta_nlme_tc &lt;- nlme(dmta_sfo_sfo3p_tc)</span></span></span>
+<span class="r-in"><span><span class="co"># nlme reaches maxIter = 50 without convergence</span></span></span>
+<span class="r-in"><span><span class="va">f_dmta_saem_tc</span> <span class="op">&lt;-</span> <span class="fu"><a href="saem.html">saem</a></span><span class="op">(</span><span class="va">dmta_sfo_sfo3p_tc</span><span class="op">)</span></span></span>
+<span class="r-in"><span><span class="co"># I am commenting out the convergence plot as rendering them</span></span></span>
+<span class="r-in"><span><span class="co"># with pkgdown fails (at least without further tweaks to the</span></span></span>
+<span class="r-in"><span><span class="co"># graphics device used)</span></span></span>
+<span class="r-in"><span><span class="co">#saemix::plot(f_dmta_saem_tc$so, plot.type = "convergence")</span></span></span>
+<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/summary.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">f_dmta_saem_tc</span><span class="op">)</span></span></span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> saemix version used for fitting: 3.1 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> mkin version used for pre-fitting: 1.1.2 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> R version used for fitting: 4.2.1 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Date of fit: Wed Aug 10 15:24:12 2022 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Date of summary: Wed Aug 10 15:24:12 2022 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Equations:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> d_DMTA/dt = - k_DMTA * DMTA</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> d_M23/dt = + f_DMTA_to_M23 * k_DMTA * DMTA - k_M23 * M23</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> d_M27/dt = + f_DMTA_to_M27 * k_DMTA * DMTA - k_M27 * M27 + k_M31 * M31</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> d_M31/dt = + f_DMTA_to_M31 * k_DMTA * DMTA - k_M31 * M31</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Data:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> 563 observations of 4 variable(s) grouped in 6 datasets</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Model predictions using solution type deSolve </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Fitted in 791.863 s</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Using 300, 100 iterations and 9 chains</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Variance model: Two-component variance function </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Mean of starting values for individual parameters:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_0 log_k_DMTA log_k_M23 log_k_M27 log_k_M31 f_DMTA_ilr_1 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> 95.5662 -2.9048 -3.8130 -4.1600 -4.1486 0.1341 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_ilr_2 f_DMTA_ilr_3 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> 0.1385 -1.6700 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → calculate sensitivities</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:03 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Fixed degradation parameter values:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> None</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → calculate ∂(f)/∂(η)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:01 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Results:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → calculate ∂(R²)/∂(η)</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:08 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Likelihood computed by importance sampling</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> AIC BIC logLik</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> 2276 2272 -1120</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → finding duplicate expressions in inner model...</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:07 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Optimised parameters:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> est. lower upper</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_0 88.5943 84.3961 92.7925</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_DMTA -3.0466 -3.5609 -2.5322</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M23 -4.0684 -4.9340 -3.2029</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M27 -3.8628 -4.2627 -3.4628</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M31 -3.9803 -4.4804 -3.4801</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_ilr_1 0.1304 -0.2186 0.4795</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_ilr_2 0.1490 -0.2559 0.5540</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_ilr_3 -1.3970 -1.6976 -1.0964</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → optimizing duplicate expressions in inner model...</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:06 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Correlation: </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_0 l__DMTA lg__M23 lg__M27 lg__M31 f_DMTA__1 f_DMTA__2</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_DMTA 0.0309 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M23 -0.0231 -0.0031 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M27 -0.0381 -0.0048 0.0039 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_M31 -0.0251 -0.0031 0.0021 0.0830 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_ilr_1 -0.0046 -0.0006 0.0417 -0.0437 0.0328 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_ilr_2 -0.0008 -0.0002 0.0214 -0.0270 -0.0909 -0.0361 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_ilr_3 -0.1832 -0.0135 0.0434 0.0804 0.0395 -0.0070 0.0059 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → finding duplicate expressions in EBE model...</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:00 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Random effects:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> est. lower upper</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.DMTA_0 3.3651 -0.9649 7.6951</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k_DMTA 0.6415 0.2774 1.0055</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k_M23 1.0176 0.3809 1.6543</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k_M27 0.4538 0.1522 0.7554</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k_M31 0.5684 0.1905 0.9464</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.f_DMTA_ilr_1 0.4111 0.1524 0.6699</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.f_DMTA_ilr_2 0.4788 0.1808 0.7768</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> SD.f_DMTA_ilr_3 0.3501 0.1316 0.5685</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → optimizing duplicate expressions in EBE model...</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> [====|====|====|====|====|====|====|====|====|====] 0:00:00 </span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Variance model:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> est. lower upper</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> a.1 0.9349 0.8409 1.029</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> b.1 0.1344 0.1178 0.151</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → compiling inner model...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BB00;">✔</span> done</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → finding duplicate expressions in FD model...</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Backtransformed parameters:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> est. lower upper</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_0 88.59431 84.396147 92.79246</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> k_DMTA 0.04752 0.028413 0.07948</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> k_M23 0.01710 0.007198 0.04064</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> k_M27 0.02101 0.014084 0.03134</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> k_M31 0.01868 0.011329 0.03080</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23 0.14498 NA NA</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M27 0.12056 NA NA</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> f_DMTA_to_M31 0.11015 NA NA</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → optimizing duplicate expressions in FD model...</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Resulting formation fractions:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> ff</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_M23 0.1450</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_M27 0.1206</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_M31 0.1101</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA_sink 0.6243</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → compiling EBE model...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BB00;">✔</span> done</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> → compiling events FD model...</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BB00;">✔</span> done</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Model:</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> cmt(DMTA);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> cmt(M23);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> cmt(M27);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> cmt(M31);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_14~ETA[1]+THETA[1];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> DMTA(0)=rx_expr_14;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_15~ETA[5]+THETA[5];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_16~ETA[7]+THETA[7];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_17~ETA[6]+THETA[6];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_24~exp(rx_expr_15);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_25~exp(rx_expr_17);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_29~t*rx_expr_24;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_30~t*rx_expr_25;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_31~exp(-(rx_expr_16));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_35~1+rx_expr_31;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_40~1/(rx_expr_35);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_42~(rx_expr_40);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_43~1-rx_expr_42;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> d/dt(DMTA)=-DMTA*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_18~ETA[2]+THETA[2];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_26~exp(rx_expr_18);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> d/dt(M23)=-rx_expr_26*M23+DMTA*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_1/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_19~ETA[3]+THETA[3];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_20~ETA[4]+THETA[4];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_21~1-f_DMTA_tffm0_1;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_27~exp(rx_expr_19);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_28~exp(rx_expr_20);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> d/dt(M27)=-rx_expr_27*M27+rx_expr_28*M31+DMTA*(rx_expr_21)*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_2/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_22~1-f_DMTA_tffm0_2;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> d/dt(M31)=-rx_expr_28*M31+DMTA*(rx_expr_22)*(rx_expr_21)*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_3/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_0~CMT==4;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_1~CMT==2;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_2~CMT==1;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_3~CMT==3;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_4~1-(rx_expr_0);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_5~1-(rx_expr_1);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_6~1-(rx_expr_3);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_yj_~(rx_expr_4)*((2*(rx_expr_5)*(rx_expr_2)+2*(rx_expr_1))*(rx_expr_6)+2*(rx_expr_3))+2*(rx_expr_0);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_7~(rx_expr_1);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_8~(rx_expr_3);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_9~(rx_expr_0);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_13~(rx_expr_5);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_32~rx_expr_13*(rx_expr_2);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_lambda_~(rx_expr_4)*((rx_expr_32+rx_expr_7)*(rx_expr_6)+rx_expr_8)+rx_expr_9;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_hi_~(rx_expr_4)*((rx_expr_32+rx_expr_7)*(rx_expr_6)+rx_expr_8)+rx_expr_9;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_low_~0;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_10~M31*(rx_expr_0);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_11~M27*(rx_expr_3);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_12~M23*(rx_expr_1);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_23~DMTA*(rx_expr_5);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_36~rx_expr_23*(rx_expr_2);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_pred_=(rx_expr_4)*((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_33~Rx_pow_di(THETA[12],2);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_expr_34~Rx_pow_di(THETA[11],2);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rx_r_=(rx_expr_4)*((rx_expr_33*Rx_pow_di(((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6)),2)+rx_expr_34)*(rx_expr_3)+((rx_expr_1)*(rx_expr_33*Rx_pow_di(((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2)),2)+rx_expr_34)+(rx_expr_33*Rx_pow_di(((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2)),2)+rx_expr_34)*(rx_expr_5)*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_33*Rx_pow_di(((rx_expr_4)*((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))),2)+rx_expr_34);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> DMTA_0=THETA[1];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> log_k_M23=THETA[2];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> log_k_M27=THETA[3];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> log_k_M31=THETA[4];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> log_k1=THETA[5];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> log_k2=THETA[6];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> g_qlogis=THETA[7];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_tffm0_1_qlogis=THETA[8];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_tffm0_2_qlogis=THETA[9];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_tffm0_3_qlogis=THETA[10];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> sigma_low=THETA[11];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> rsd_high=THETA[12];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.DMTA_0=ETA[1];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.log_k_M23=ETA[2];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.log_k_M27=ETA[3];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.log_k_M31=ETA[4];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.log_k1=ETA[5];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.log_k2=ETA[6];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.g_qlogis=ETA[7];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.f_DMTA_tffm0_1_qlogis=ETA[8];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.f_DMTA_tffm0_2_qlogis=ETA[9];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> eta.f_DMTA_tffm0_3_qlogis=ETA[10];</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> DMTA_0_model=rx_expr_14;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> k_M23=rx_expr_26;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> k_M27=rx_expr_27;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> k_M31=rx_expr_28;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> k1=rx_expr_24;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> k2=rx_expr_25;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> g=1/(rx_expr_35);</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23=1/(1+exp(-(ETA[8]+THETA[8])));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23=1/(1+exp(-(ETA[9]+THETA[9])));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23=1/(1+exp(-(ETA[10]+THETA[10])));</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_to_M23=f_DMTA_tffm0_1;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_to_M27=(rx_expr_21)*f_DMTA_tffm0_2;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> f_DMTA_to_M31=(rx_expr_22)*(rx_expr_21)*f_DMTA_tffm0_3;</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> tad=tad();</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> dosenum=dosenum();</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Needed Covariates:</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> [1] "f_DMTA_tffm0_1" "f_DMTA_tffm0_2" "f_DMTA_tffm0_3" "CMT" </span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt &lt;- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control &lt;- do.call(foceiControl, control) } if (is.null(env)) { .ret &lt;- new.env(parent = emptyenv()) } else { .ret &lt;- env } .ret$origData &lt;- data .ret$etaNames &lt;- etaNames .ret$thetaFixed &lt;- fixed .ret$control &lt;- control .ret$control$focei.mu.ref &lt;- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel &lt;- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel &lt;- TRUE model &lt;- RxODE::rxGetLin(PKpars) pred &lt;- eval(parse(text = "function(){return(Central);}")) } .square &lt;- function(x) x * x .ret$diagXformInv &lt;- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err &lt;- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames &lt;- .parNames &lt;- c() .ret$adjLik &lt;- control$adjLik .mixed &lt;- !is.null(inits$OMGA) &amp;&amp; length(inits$OMGA) &gt; 0 if (!exists("noLik", envir = .ret)) { .atol &lt;- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol &lt;- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol &lt;- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol &lt;- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model &lt;- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol &lt;- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol &lt;- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol &lt;- .atol .ret$control$rxControl$rtol &lt;- .rtol .ssAtol &lt;- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol &lt;- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol &lt;- .ssAtol .ret$control$rxControl$ssRtol &lt;- .ssRtol } .covNames &lt;- .parNames &lt;- RxODE::rxParams(.ret$model$pred.only) .covNames &lt;- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) &lt;- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs &lt;- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) &gt; 0) { .covNames &lt;- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) &gt; 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars &lt;- .ret$model$extra.pars } else { if (.ret$noLik) { .atol &lt;- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol &lt;- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model &lt;- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol &lt;- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol &lt;- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol &lt;- .atol .ret$control$rxControl$rtol &lt;- .rtol } .covNames &lt;- .parNames &lt;- RxODE::rxParams(.ret$model$pred.only) .covNames &lt;- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) &lt;- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs &lt;- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) &gt; 0) { .covNames &lt;- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) &gt; 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars &lt;- .ret$model$extra.pars } else { .extraPars &lt;- NULL } } .ret$skipCov &lt;- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp &lt;- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) &lt; length(inits$THTA)) { .tmp &lt;- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp &lt;- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr &lt;- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr &lt;- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp &lt;- (.tmp | .uifErr) } .ret$skipCov &lt;- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref &lt;- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms &lt;- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms &lt;- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) &amp;&amp; (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms &lt;- thetaNames } .ret$thetaNames &lt;- .nms .thetaReset$thetaNames &lt;- .nms if (length(lower) == 1) { lower &lt;- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper &lt;- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars &lt;- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) &gt; 0) { inits$THTA &lt;- c(inits$THTA, .ret$model$extra.pars) .lowerErr &lt;- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr &lt;- rep(Inf, length(.ret$model$extra.pars)) lower &lt;- c(lower, .lowerErr) upper &lt;- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID &lt;- 0 if (is.null(data$AMT)) data$AMT &lt;- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] &lt;- as.double(data[[.v]]) } .ret$dataSav &lt;- data .ds &lt;- data[data$EVID != 0 &amp; data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w &lt;- which(tolower(names(data)) == "limit") .limitName &lt;- NULL if (length(.w) == 1L) { .limitName &lt;- names(data)[.w] } .censName &lt;- NULL .w &lt;- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName &lt;- names(data[.w]) } data &lt;- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w &lt;- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] &lt;- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh &lt;- .parseOM(inits$OMGA) .nlh &lt;- sapply(.lh, length) .osplt &lt;- rep(1:length(.lh), .nlh) .lini &lt;- list(inits$THTA, unlist(.lh)) .nlini &lt;- sapply(.lini, length) .nsplt &lt;- rep(1:length(.lini), .nlini) .om0 &lt;- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames &lt;- .ret$etaNames } else { .ret$etaNames &lt;- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv &lt;- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType &lt;- .ret$rxInv$xType .om0a &lt;- .om0 .om0a &lt;- .om0a/control$diagOmegaBoundLower .om0b &lt;- .om0 .om0b &lt;- .om0b * control$diagOmegaBoundUpper .om0a &lt;- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b &lt;- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf &lt;- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower &lt;- with(.omdf, ifelse(a &gt; b, b, a)) .omdf$lower &lt;- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower &lt;- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper &lt;- with(.omdf, ifelse(a &lt; b, b, a)) .omdf$upper &lt;- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper &lt;- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega &lt;- length(.omdf$lower) .ret$control$neta &lt;- sum(.omdf$diag) .ret$control$ntheta &lt;- length(lower) .ret$control$nfixed &lt;- sum(fixed) lower &lt;- c(lower, .omdf$lower) upper &lt;- c(upper, .omdf$upper) } else { .ret$control$nomega &lt;- 0 .ret$control$neta &lt;- 0 .ret$xType &lt;- -1 .ret$control$ntheta &lt;- length(lower) .ret$control$nfixed &lt;- sum(fixed) } .ret$lower &lt;- lower .ret$upper &lt;- upper .ret$thetaIni &lt;- inits$THTA .scaleC &lt;- double(length(lower)) if (is.null(control$scaleC)) { .scaleC &lt;- rep(NA_real_, length(lower)) } else { .scaleC &lt;- as.double(control$scaleC) if (length(lower) &gt; length(.scaleC)) { .scaleC &lt;- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) &lt; length(.scaleC)) { .scaleC &lt;- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC &lt;- .scaleC if (exists("uif", envir = .ret)) { .ini &lt;- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] &lt;- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] &lt;- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] &lt;- 1 } .ini &lt;- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] &lt;- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] &lt;- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] &lt;- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b &lt;- .ret$logitThetasLow[.i] .c &lt;- .ret$logitThetasHi[.i] .a &lt;- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] &lt;- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) &lt;- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) &amp; !is.null(control$etaMat)) { .ret$etaMat &lt;- control$etaMat } else { .ret$etaMat &lt;- etaMat } .ret$setupTime &lt;- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp &lt;- .ret$uif$logThetasList .ret$logThetas &lt;- .tmp[[1]] .ret$logThetasF &lt;- .tmp[[2]] .tmp &lt;- .ret$uif$logitThetasList .ret$logitThetas &lt;- .tmp[[1]] .ret$logitThetasF &lt;- .tmp[[2]] .tmp &lt;- .ret$uif$logitThetasListLow .ret$logitThetasLow &lt;- .tmp[[1]] .ret$logitThetasLowF &lt;- .tmp[[2]] .tmp &lt;- .ret$uif$logitThetasListHi .ret$logitThetasHi &lt;- .tmp[[1]] .ret$logitThetasHiF &lt;- .tmp[[2]] .tmp &lt;- .ret$uif$probitThetasList .ret$probitThetas &lt;- .tmp[[1]] .ret$probitThetasF &lt;- .tmp[[2]] .tmp &lt;- .ret$uif$probitThetasListLow .ret$probitThetasLow &lt;- .tmp[[1]] .ret$probitThetasLowF &lt;- .tmp[[2]] .tmp &lt;- .ret$uif$probitThetasListHi .ret$probitThetasHi &lt;- .tmp[[1]] .ret$probitThetasHiF &lt;- .tmp[[2]] } else { .ret$logThetasF &lt;- integer(0) .ret$logitThetasF &lt;- integer(0) .ret$logitThetasHiF &lt;- numeric(0) .ret$logitThetasLowF &lt;- numeric(0) .ret$logitThetas &lt;- integer(0) .ret$logitThetasHi &lt;- numeric(0) .ret$logitThetasLow &lt;- numeric(0) .ret$probitThetasF &lt;- integer(0) .ret$probitThetasHiF &lt;- numeric(0) .ret$probitThetasLowF &lt;- numeric(0) .ret$probitThetas &lt;- integer(0) .ret$probitThetasHi &lt;- numeric(0) .ret$probitThetasLow &lt;- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params &lt;- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan &lt;- length(.ret$thetaIni) .ret$nobs &lt;- sum(data$EVID == 0) } } .ret$control$printTop &lt;- TRUE .ret$control$nF &lt;- 0 .est0 &lt;- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq &lt;- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq &lt;- 0L } .fitFun &lt;- function(.ret) { this.env &lt;- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 &lt;- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm &lt;- names(.ret$thetaIni) .ret$thetaIni &lt;- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta &lt;- .thetaReset$omegaTheta .ret$control$printTop &lt;- FALSE .ret$etaMat &lt;- .thetaReset$etaMat .ret$control$etaMat &lt;- .thetaReset$etaMat .ret$control$maxInnerIterations &lt;- .thetaReset$maxInnerIterations .ret$control$nF &lt;- .thetaReset$nF .ret$control$gillRetC &lt;- .thetaReset$gillRetC .ret$control$gillRet &lt;- .thetaReset$gillRet .ret$control$gillRet &lt;- .thetaReset$gillRet .ret$control$gillDf &lt;- .thetaReset$gillDf .ret$control$gillDf2 &lt;- .thetaReset$gillDf2 .ret$control$gillErr &lt;- .thetaReset$gillErr .ret$control$rEps &lt;- .thetaReset$rEps .ret$control$aEps &lt;- .thetaReset$aEps .ret$control$rEpsC &lt;- .thetaReset$rEpsC .ret$control$aEpsC &lt;- .thetaReset$aEpsC .ret$control$c1 &lt;- .thetaReset$c1 .ret$control$c2 &lt;- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations &lt;- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun &lt;- .bobyqa .ret$control$outerOpt &lt;- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 &lt;- try(.fitFun(.ret)) .n &lt;- 1 while (inherits(.ret0, "try-error") &amp;&amp; control$maxOuterIterations != 0 &amp;&amp; .n &lt;= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF &lt;- 0 .estNew &lt;- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew &lt;- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] &lt; lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] &gt; upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni &lt;- .estNew .ret0 &lt;- try(.fitFun(.ret)) .n &lt;- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret &lt;- .ret0 if (exists("parHistData", .ret)) { .tmp &lt;- .ret$parHistData .tmp &lt;- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter &lt;- .tmp$iter .tmp &lt;- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked &lt;- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) &lt;- c("val", "par", "iter") .ret$parHist &lt;- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas &lt;- .ret$ranef .thetas &lt;- .ret$fixef .pars &lt;- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink &lt;- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table &lt;- tableControl() } if (control$calcTables) { .ret &lt;- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop):</span> Not all the covariates are in the dataset.</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Timing stopped at: 119.8 9.331 129.2</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Timing stopped at: 120 9.331 129.3</span>
-<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/summary.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_focei</span><span class="op">)</span></span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in summary(f_dmta_nlmixr_focei):</span> object 'f_dmta_nlmixr_focei' not found</span>
-<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_focei</span><span class="op">)</span></span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in plot(f_dmta_nlmixr_focei):</span> object 'f_dmta_nlmixr_focei' not found</span>
-<span class="r-in"><span class="co"># Using saemix takes about 18 minutes</span></span>
-<span class="r-in"><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>
-<span class="r-in"> <span class="va">f_dmta_saemix</span> <span class="op">&lt;-</span> <span class="fu"><a href="saem.html">saem</a></span><span class="op">(</span><span class="va">f_dmta_mkin_tc</span>, test_log_parms <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span>
-<span class="r-in"><span class="op">)</span></span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> DINTDY- T (=R1) illegal </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> In above message, R1 = 115.507</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> T not in interval TCUR - HU (= R1) to TCUR (=R2) </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> In above message, R1 = 112.133, R2 = 113.577</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> DLSODA- At T (=R1), too much accuracy requested </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> for precision of machine.. See TOLSF (=R2) </span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> In above message, R1 = 55.3899, R2 = nan</span>
-<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in out[available, var]:</span> (subscript) logical subscript too long</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Timing stopped at: 11.84 0.008 11.85</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Timing stopped at: 12.16 0.008 12.17</span>
-<span class="r-in"></span>
-<span class="r-in"><span class="co"># nlmixr with est = "saem" is pretty fast with default iteration numbers, most</span></span>
-<span class="r-in"><span class="co"># of the time (about 2.5 minutes) is spent for calculating the log likelihood at the end</span></span>
-<span class="r-in"><span class="co"># The likelihood calculated for the nlmixr fit is much lower than that found by saemix</span></span>
-<span class="r-in"><span class="co"># Also, the trace plot and the plot of the individual predictions is not</span></span>
-<span class="r-in"><span class="co"># convincing for the parent. It seems we are fitting an overparameterised</span></span>
-<span class="r-in"><span class="co"># model, so the result we get strongly depends on starting parameters and control settings.</span></span>
-<span class="r-in"><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>
-<span class="r-in"> <span class="va">f_dmta_nlmixr_saem</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_dmta_mkin_tc</span>, est <span class="op">=</span> <span class="st">"saem"</span>,</span>
-<span class="r-in"> control <span class="op">=</span> <span class="fu">nlmixr</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/saemControl.html" class="external-link">saemControl</a></span><span class="op">(</span>print <span class="op">=</span> <span class="fl">500</span>, logLik <span class="op">=</span> <span class="cn">TRUE</span>, nmc <span class="op">=</span> <span class="fl">9</span><span class="op">)</span><span class="op">)</span></span>
-<span class="r-in"><span class="op">)</span></span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> With est = 'saem', a different error model is required for each observed variableChanging the error model to 'obs_tc' (Two-component error for each observed variable)</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BBBB;">ℹ</span> parameter labels from comments are typically ignored in non-interactive mode</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> <span style="color: #00BBBB;">ℹ</span> Need to run with the source intact to parse comments</span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in eval(substitute(expr), data, enclos = parent.frame()):</span> Cannot run SAEM since some of the parameters are not mu-referenced (eta.f_DMTA_tffm0_1_qlogis, eta.f_DMTA_tffm0_2_qlogis, eta.f_DMTA_tffm0_3_qlogis)</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Timing stopped at: 0.892 0.004 0.896</span>
-<span class="r-msg co"><span class="r-pr">#&gt;</span> Timing stopped at: 1.096 0.005 1.1</span>
-<span class="r-in"><span class="fu">traceplot</span><span class="op">(</span><span class="va">f_dmta_nlmixr_saem</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in traceplot(f_dmta_nlmixr_saem$nm):</span> could not find function "traceplot"</span>
-<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/summary.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_saem</span><span class="op">)</span></span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in summary(f_dmta_nlmixr_saem):</span> object 'f_dmta_nlmixr_saem' not found</span>
-<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_saem</span><span class="op">)</span></span>
-<span class="r-err co"><span class="r-pr">#&gt;</span> <span class="error">Error in plot(f_dmta_nlmixr_saem):</span> object 'f_dmta_nlmixr_saem' not found</span>
-<span class="r-in"><span class="co"># }</span></span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> Estimated disappearance times:</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DT50 DT90</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> DMTA 14.59 48.45</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> M23 40.52 134.62</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> M27 32.99 109.60</span>
+<span class="r-out co"><span class="r-pr">#&gt;</span> M31 37.11 123.26</span>
+<span class="r-in"><span><span class="co"># As the confidence interval for the random effects of DMTA_0</span></span></span>
+<span class="r-in"><span><span class="co"># includes zero, we could try an alternative model without</span></span></span>
+<span class="r-in"><span><span class="co"># such random effects</span></span></span>
+<span class="r-in"><span><span class="co"># f_dmta_saem_tc_2 &lt;- saem(dmta_sfo_sfo3p_tc,</span></span></span>
+<span class="r-in"><span><span class="co"># covariance.model = diag(c(0, rep(1, 7))))</span></span></span>
+<span class="r-in"><span><span class="co"># saemix::plot(f_dmta_saem_tc_2$so, plot.type = "convergence")</span></span></span>
+<span class="r-in"><span><span class="co"># This does not perform better judged by AIC and BIC</span></span></span>
+<span class="r-in"><span><span class="co"># saemix::compare.saemix(f_dmta_saem_tc$so, f_dmta_saem_tc_2$so)</span></span></span>
+<span class="r-in"><span><span class="co"># }</span></span></span>
</code></pre></div>
</div>
</div>
@@ -446,7 +321,7 @@ specific pieces of information in the comments.</p>
</div>
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- <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.2.</p>
+ <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.6.</p>
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