<!DOCTYPE html> <!-- 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>Aerobic soil degradation data on dimethenamid and dimethenamid-P from the EU assessment in 2018 — dimethenamid_2018 • 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="Aerobic soil degradation data on dimethenamid and dimethenamid-P from the EU assessment in 2018 — dimethenamid_2018"><meta property="og:description" content="The datasets were extracted from the active substance evaluation dossier published by EFSA. 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Kinetic evaluations shown for these datasets are intended to illustrate and advance kinetic modelling. The fact that these data and some results are shown here does not imply a license to use them in the context of pesticide registrations, as the use of the data may be 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> <div id="format"> <h2>Format</h2> <p>An <a href="mkindsg.html">mkindsg</a> object grouping seven datasets with some meta information</p> </div> <div id="source"> <h2>Source</h2> <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 id="details"> <h2>Details</h2> <p>The R code used to create this data object is installed with this package in the 'dataset_generation' directory. In the code, page numbers are given for specific pieces of information in the comments.</p> </div> <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> <span class="r-out co"><span class="r-pr">#></span> <mkindsg> holding 7 mkinds objects</span> <span class="r-out co"><span class="r-pr">#></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">#></span> Occurrence of observed compounds $observed_n:</span> <span class="r-out co"><span class="r-pr">#></span> DMTAP M23 M27 M31 DMTA </span> <span class="r-out co"><span class="r-pr">#></span> 3 7 7 7 4 </span> <span class="r-out co"><span class="r-pr">#></span> Time normalisation factors $f_time_norm:</span> <span class="r-out co"><span class="r-pr">#></span> [1] 1.0000000 0.9706477 1.2284784 1.2284784 0.6233856 0.7678922 0.6733938</span> <span class="r-out co"><span class="r-pr">#></span> Meta information $meta:</span> <span class="r-out co"><span class="r-pr">#></span> study usda_soil_type study_moisture_ref_type rel_moisture</span> <span class="r-out co"><span class="r-pr">#></span> Calke Unsworth 2014 Sandy loam pF2 1.00</span> <span class="r-out co"><span class="r-pr">#></span> Borstel Staudenmaier 2009 Sand pF1 0.50</span> <span class="r-out co"><span class="r-pr">#></span> Elliot 1 Wendt 1997 Clay loam pF2.5 0.75</span> <span class="r-out co"><span class="r-pr">#></span> Elliot 2 Wendt 1997 Clay loam pF2.5 0.75</span> <span class="r-out co"><span class="r-pr">#></span> Flaach König 1996 Sandy clay loam pF1 0.40</span> <span class="r-out co"><span class="r-pr">#></span> BBA 2.2 König 1995 Loamy sand pF1 0.40</span> <span class="r-out co"><span class="r-pr">#></span> BBA 2.3 König 1995 Sandy loam pF1 0.40</span> <span class="r-out co"><span class="r-pr">#></span> study_ref_moisture temperature</span> <span class="r-out co"><span class="r-pr">#></span> Calke NA 20</span> <span class="r-out co"><span class="r-pr">#></span> Borstel 23.00 20</span> <span class="r-out co"><span class="r-pr">#></span> Elliot 1 33.37 23</span> <span class="r-out co"><span class="r-pr">#></span> Elliot 2 33.37 23</span> <span class="r-out co"><span class="r-pr">#></span> Flaach NA 20</span> <span class="r-out co"><span class="r-pr">#></span> BBA 2.2 NA 20</span> <span class="r-out co"><span class="r-pr">#></span> BBA 2.3 NA 20</span> <span class="r-in"><span class="va">dmta_ds</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">lapply</a></span><span class="op">(</span><span class="fl">1</span><span class="op">:</span><span class="fl">7</span>, <span class="kw">function</span><span class="op">(</span><span class="va">i</span><span class="op">)</span> <span class="op">{</span></span> <span class="r-in"> <span class="va">ds_i</span> <span class="op"><-</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">ds</span><span class="op">[[</span><span class="va">i</span><span class="op">]</span><span class="op">]</span><span class="op">$</span><span class="va">data</span></span> <span class="r-in"> <span class="va">ds_i</span><span class="op">[</span><span class="va">ds_i</span><span class="op">$</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"><-</span> <span class="st">"DMTA"</span></span> <span class="r-in"> <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op"><-</span> <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op">*</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">f_time_norm</span><span class="op">[</span><span class="va">i</span><span class="op">]</span></span> <span class="r-in"> <span class="va">ds_i</span></span> <span class="r-in"><span class="op">}</span><span class="op">)</span></span> <span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">)</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="va">dimethenamid_2018</span><span class="op">$</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"><-</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"><-</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"><-</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"><-</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"><-</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">#></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">#></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">#></span> function () </span> <span class="r-out co"><span class="r-pr">#></span> {</span> <span class="r-out co"><span class="r-pr">#></span> ini({</span> <span class="r-out co"><span class="r-pr">#></span> DMTA_0 = 99</span> <span class="r-out co"><span class="r-pr">#></span> eta.DMTA_0 ~ 2.3</span> <span class="r-out co"><span class="r-pr">#></span> log_k_M23 = -3.9</span> <span class="r-out co"><span class="r-pr">#></span> eta.log_k_M23 ~ 0.55</span> <span class="r-out co"><span class="r-pr">#></span> log_k_M27 = -4.3</span> <span class="r-out co"><span class="r-pr">#></span> eta.log_k_M27 ~ 0.86</span> <span class="r-out co"><span class="r-pr">#></span> log_k_M31 = -4.2</span> <span class="r-out co"><span class="r-pr">#></span> eta.log_k_M31 ~ 0.75</span> <span class="r-out co"><span class="r-pr">#></span> log_k1 = -2.2</span> <span class="r-out co"><span class="r-pr">#></span> eta.log_k1 ~ 0.9</span> <span class="r-out co"><span class="r-pr">#></span> log_k2 = -3.8</span> <span class="r-out co"><span class="r-pr">#></span> eta.log_k2 ~ 1.6</span> <span class="r-out co"><span class="r-pr">#></span> g_qlogis = 0.44</span> <span class="r-out co"><span class="r-pr">#></span> eta.g_qlogis ~ 3.1</span> <span class="r-out co"><span class="r-pr">#></span> f_DMTA_tffm0_1_qlogis = -2.1</span> <span class="r-out co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_1_qlogis ~ 0.3</span> <span class="r-out co"><span class="r-pr">#></span> f_DMTA_tffm0_2_qlogis = -2.2</span> <span class="r-out co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_2_qlogis ~ 0.3</span> <span class="r-out co"><span class="r-pr">#></span> f_DMTA_tffm0_3_qlogis = -2.1</span> <span class="r-out co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_3_qlogis ~ 0.3</span> <span class="r-out co"><span class="r-pr">#></span> sigma_low_DMTA = 0.7</span> <span class="r-out co"><span class="r-pr">#></span> rsd_high_DMTA = 0.026</span> <span class="r-out co"><span class="r-pr">#></span> sigma_low_M23 = 0.7</span> <span class="r-out co"><span class="r-pr">#></span> rsd_high_M23 = 0.026</span> <span class="r-out co"><span class="r-pr">#></span> sigma_low_M27 = 0.7</span> <span class="r-out co"><span class="r-pr">#></span> rsd_high_M27 = 0.026</span> <span class="r-out co"><span class="r-pr">#></span> sigma_low_M31 = 0.7</span> <span class="r-out co"><span class="r-pr">#></span> rsd_high_M31 = 0.026</span> <span class="r-out co"><span class="r-pr">#></span> })</span> <span class="r-out co"><span class="r-pr">#></span> model({</span> <span class="r-out co"><span class="r-pr">#></span> DMTA_0_model = DMTA_0 + eta.DMTA_0</span> <span class="r-out co"><span class="r-pr">#></span> DMTA(0) = DMTA_0_model</span> <span class="r-out co"><span class="r-pr">#></span> k_M23 = exp(log_k_M23 + eta.log_k_M23)</span> <span class="r-out co"><span class="r-pr">#></span> k_M27 = exp(log_k_M27 + eta.log_k_M27)</span> <span class="r-out co"><span class="r-pr">#></span> k_M31 = exp(log_k_M31 + eta.log_k_M31)</span> <span class="r-out co"><span class="r-pr">#></span> k1 = exp(log_k1 + eta.log_k1)</span> <span class="r-out co"><span class="r-pr">#></span> k2 = exp(log_k2 + eta.log_k2)</span> <span class="r-out co"><span class="r-pr">#></span> g = expit(g_qlogis + eta.g_qlogis)</span> <span class="r-out co"><span class="r-pr">#></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">#></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">#></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">#></span> f_DMTA_to_M23 = f_DMTA_tffm0_1</span> <span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M27 = f_DMTA_tffm0_2 * (1 - f_DMTA_tffm0_1)</span> <span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M31 = f_DMTA_tffm0_3 * (1 - f_DMTA_tffm0_2) * </span> <span class="r-out co"><span class="r-pr">#></span> (1 - f_DMTA_tffm0_1)</span> <span class="r-out co"><span class="r-pr">#></span> d/dt(DMTA) = -((k1 * g * exp(-k1 * time) + k2 * (1 - </span> <span class="r-out co"><span class="r-pr">#></span> g) * exp(-k2 * time))/(g * exp(-k1 * time) + (1 - </span> <span class="r-out co"><span class="r-pr">#></span> g) * exp(-k2 * time))) * DMTA</span> <span class="r-out co"><span class="r-pr">#></span> d/dt(M23) = +f_DMTA_to_M23 * ((k1 * g * exp(-k1 * time) + </span> <span class="r-out co"><span class="r-pr">#></span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span> <span class="r-out co"><span class="r-pr">#></span> (1 - g) * exp(-k2 * time))) * DMTA - k_M23 * M23</span> <span class="r-out co"><span class="r-pr">#></span> d/dt(M27) = +f_DMTA_to_M27 * ((k1 * g * exp(-k1 * time) + </span> <span class="r-out co"><span class="r-pr">#></span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span> <span class="r-out co"><span class="r-pr">#></span> (1 - g) * exp(-k2 * time))) * DMTA - k_M27 * M27 + </span> <span class="r-out co"><span class="r-pr">#></span> k_M31 * M31</span> <span class="r-out co"><span class="r-pr">#></span> d/dt(M31) = +f_DMTA_to_M31 * ((k1 * g * exp(-k1 * time) + </span> <span class="r-out co"><span class="r-pr">#></span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span> <span class="r-out co"><span class="r-pr">#></span> (1 - g) * exp(-k2 * time))) * DMTA - k_M31 * M31</span> <span class="r-out co"><span class="r-pr">#></span> DMTA ~ add(sigma_low_DMTA) + prop(rsd_high_DMTA)</span> <span class="r-out co"><span class="r-pr">#></span> M23 ~ add(sigma_low_M23) + prop(rsd_high_M23)</span> <span class="r-out co"><span class="r-pr">#></span> M27 ~ add(sigma_low_M27) + prop(rsd_high_M27)</span> <span class="r-out co"><span class="r-pr">#></span> M31 ~ add(sigma_low_M31) + prop(rsd_high_M31)</span> <span class="r-out co"><span class="r-pr">#></span> })</span> <span class="r-out co"><span class="r-pr">#></span> }</span> <span class="r-out co"><span class="r-pr">#></span> <environment: 0x55555fca3790></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"><-</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">#></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">#></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">#></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">#></span> → creating full model...</span> <span class="r-msg co"><span class="r-pr">#></span> → pruning branches (`if`/`else`)...</span> <span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> <span class="r-msg co"><span class="r-pr">#></span> → loading into <span style="color: #0000BB;">symengine</span> environment...</span> <span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> <span class="r-msg co"><span class="r-pr">#></span> → creating full model...</span> <span class="r-msg co"><span class="r-pr">#></span> → pruning branches (`if`/`else`)...</span> <span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> <span class="r-msg co"><span class="r-pr">#></span> → loading into <span style="color: #0000BB;">symengine</span> environment...</span> <span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> <span class="r-msg co"><span class="r-pr">#></span> → calculate jacobian</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:01 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → calculate sensitivities</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:03 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → calculate ∂(f)/∂(η)</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:01 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → calculate ∂(R²)/∂(η)</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:08 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → finding duplicate expressions in inner model...</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:07 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → optimizing duplicate expressions in inner model...</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:06 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → finding duplicate expressions in EBE model...</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:00 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → optimizing duplicate expressions in EBE model...</span> <span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:00 </span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → compiling inner model...</span> <span class="r-msg co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> <span class="r-msg co"><span class="r-pr">#></span> → finding duplicate expressions in FD model...</span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → optimizing duplicate expressions in FD model...</span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> → compiling EBE model...</span> <span class="r-msg co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> <span class="r-msg co"><span class="r-pr">#></span> → compiling events FD model...</span> <span class="r-msg co"><span class="r-pr">#></span> </span> <span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> <span class="r-msg co"><span class="r-pr">#></span> Model:</span> <span class="r-msg co"><span class="r-pr">#></span> cmt(DMTA);</span> <span class="r-msg co"><span class="r-pr">#></span> cmt(M23);</span> <span class="r-msg co"><span class="r-pr">#></span> cmt(M27);</span> <span class="r-msg co"><span class="r-pr">#></span> cmt(M31);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_14~ETA[1]+THETA[1];</span> <span class="r-msg co"><span class="r-pr">#></span> DMTA(0)=rx_expr_14;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_15~ETA[5]+THETA[5];</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_16~ETA[7]+THETA[7];</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_17~ETA[6]+THETA[6];</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_24~exp(rx_expr_15);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_25~exp(rx_expr_17);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_29~t*rx_expr_24;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_30~t*rx_expr_25;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_31~exp(-(rx_expr_16));</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_35~1+rx_expr_31;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_40~1/(rx_expr_35);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_42~(rx_expr_40);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_43~1-rx_expr_42;</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> rx_expr_18~ETA[2]+THETA[2];</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_26~exp(rx_expr_18);</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> rx_expr_19~ETA[3]+THETA[3];</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_20~ETA[4]+THETA[4];</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_21~1-f_DMTA_tffm0_1;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_27~exp(rx_expr_19);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_28~exp(rx_expr_20);</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> rx_expr_22~1-f_DMTA_tffm0_2;</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> rx_expr_0~CMT==4;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_1~CMT==2;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_2~CMT==1;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_3~CMT==3;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_4~1-(rx_expr_0);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_5~1-(rx_expr_1);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_6~1-(rx_expr_3);</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> rx_expr_7~(rx_expr_1);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_8~(rx_expr_3);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_9~(rx_expr_0);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_13~(rx_expr_5);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_32~rx_expr_13*(rx_expr_2);</span> <span class="r-msg co"><span class="r-pr">#></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">#></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">#></span> rx_low_~0;</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_10~M31*(rx_expr_0);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_11~M27*(rx_expr_3);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_12~M23*(rx_expr_1);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_23~DMTA*(rx_expr_5);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_36~rx_expr_23*(rx_expr_2);</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> rx_expr_33~Rx_pow_di(THETA[12],2);</span> <span class="r-msg co"><span class="r-pr">#></span> rx_expr_34~Rx_pow_di(THETA[11],2);</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> DMTA_0=THETA[1];</span> <span class="r-msg co"><span class="r-pr">#></span> log_k_M23=THETA[2];</span> <span class="r-msg co"><span class="r-pr">#></span> log_k_M27=THETA[3];</span> <span class="r-msg co"><span class="r-pr">#></span> log_k_M31=THETA[4];</span> <span class="r-msg co"><span class="r-pr">#></span> log_k1=THETA[5];</span> <span class="r-msg co"><span class="r-pr">#></span> log_k2=THETA[6];</span> <span class="r-msg co"><span class="r-pr">#></span> g_qlogis=THETA[7];</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_tffm0_1_qlogis=THETA[8];</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_tffm0_2_qlogis=THETA[9];</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_tffm0_3_qlogis=THETA[10];</span> <span class="r-msg co"><span class="r-pr">#></span> sigma_low=THETA[11];</span> <span class="r-msg co"><span class="r-pr">#></span> rsd_high=THETA[12];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.DMTA_0=ETA[1];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.log_k_M23=ETA[2];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.log_k_M27=ETA[3];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.log_k_M31=ETA[4];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.log_k1=ETA[5];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.log_k2=ETA[6];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.g_qlogis=ETA[7];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_1_qlogis=ETA[8];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_2_qlogis=ETA[9];</span> <span class="r-msg co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_3_qlogis=ETA[10];</span> <span class="r-msg co"><span class="r-pr">#></span> DMTA_0_model=rx_expr_14;</span> <span class="r-msg co"><span class="r-pr">#></span> k_M23=rx_expr_26;</span> <span class="r-msg co"><span class="r-pr">#></span> k_M27=rx_expr_27;</span> <span class="r-msg co"><span class="r-pr">#></span> k_M31=rx_expr_28;</span> <span class="r-msg co"><span class="r-pr">#></span> k1=rx_expr_24;</span> <span class="r-msg co"><span class="r-pr">#></span> k2=rx_expr_25;</span> <span class="r-msg co"><span class="r-pr">#></span> g=1/(rx_expr_35);</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=1/(1+exp(-(ETA[8]+THETA[8])));</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=1/(1+exp(-(ETA[9]+THETA[9])));</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=1/(1+exp(-(ETA[10]+THETA[10])));</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=f_DMTA_tffm0_1;</span> <span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M27=(rx_expr_21)*f_DMTA_tffm0_2;</span> <span class="r-msg co"><span class="r-pr">#></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">#></span> tad=tad();</span> <span class="r-msg co"><span class="r-pr">#></span> dosenum=dosenum();</span> <span class="r-msg co"><span class="r-pr">#></span> Needed Covariates:</span> <span class="r-msg co"><span class="r-pr">#></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">#></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 <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- 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$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 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 <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$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 <- 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 <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- 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 <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$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]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- 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$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- 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">#></span> Timing stopped at: 119.8 9.331 129.2</span> <span class="r-msg co"><span class="r-pr">#></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">#></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">#></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"><-</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">#></span> DINTDY- T (=R1) illegal </span> <span class="r-out co"><span class="r-pr">#></span> In above message, R1 = 115.507</span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-out co"><span class="r-pr">#></span> T not in interval TCUR - HU (= R1) to TCUR (=R2) </span> <span class="r-out co"><span class="r-pr">#></span> In above message, R1 = 112.133, R2 = 113.577</span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-out co"><span class="r-pr">#></span> DLSODA- At T (=R1), too much accuracy requested </span> <span class="r-out co"><span class="r-pr">#></span> for precision of machine.. See TOLSF (=R2) </span> <span class="r-out co"><span class="r-pr">#></span> In above message, R1 = 55.3899, R2 = nan</span> <span class="r-out co"><span class="r-pr">#></span> </span> <span class="r-err co"><span class="r-pr">#></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">#></span> Timing stopped at: 11.84 0.008 11.85</span> <span class="r-msg co"><span class="r-pr">#></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"><-</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">#></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">#></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">#></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">#></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">#></span> Timing stopped at: 0.892 0.004 0.896</span> <span class="r-msg co"><span class="r-pr">#></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">#></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">#></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">#></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> </code></pre></div> </div> </div> <div class="col-md-3 hidden-xs hidden-sm" id="pkgdown-sidebar"> <nav id="toc" data-toggle="toc" class="sticky-top"><h2 data-toc-skip>Contents</h2> </nav></div> </div> <footer><div class="copyright"> <p></p><p>Developed by Johannes Ranke.</p> </div> <div class="pkgdown"> <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.2.</p> </div> </footer></div> </body></html>