nlmixr
This is an example of a complex model that can be estimated.
In the example below, a target-mediated drug disposition PK model for nimotuzumab is illustrated (Rodríguez-Vera et al. 2015).
Model Schematic
nlmixr model
library(nlmixr2)
library(xpose)
library(xpose.nlmixr2)
library(ggplot2)
nimo <- function() {
ini({
## Note that the UI can take expressions
## Also note that these initial estimates should be provided on the log-scale
tcl <- log(0.001)
tv1 <- log(1.45)
tQ <- log(0.004)
tv2 <- log(44)
tkss <- log(12)
tkint <- log(0.3)
tksyn <- log(1)
tkdeg <- log(7)
## Initial estimates should be high for SAEM ETAs
eta.cl ~ 2
eta.v1 ~ 2
eta.kss ~ 2
## Also true for additive error (also ignored in SAEM)
add.err <- 10
})
model({
cl <- exp(tcl + eta.cl)
v1 <- exp(tv1 + eta.v1)
Q <- exp(tQ)
v2 <- exp(tv2)
kss <- exp(tkss + eta.kss)
kint <- exp(tkint)
ksyn <- exp(tksyn)
kdeg <- exp(tkdeg)
k <- cl/v1
k12 <- Q/v1
k21 <- Q/v2
eff(0) <- ksyn/kdeg ##initializing compartment
## Concentration is calculated
conc = 0.5*(central/v1-eff-kss)+0.5*sqrt((central/v1-eff-kss)**2+4*kss*central/v1)
d/dt(central) = -(k+k12)*conc*v1+k21*peripheral-kint*eff*conc*v1/(kss+conc)
d/dt(peripheral) = k12*conc*v1-k21*peripheral ##Free Drug second compartment amount
d/dt(eff) = ksyn - kdeg*eff - (kint-kdeg)*conc*eff/(kss+conc)
IPRED=log(conc)
IPRED ~ add(add.err)
})
}Fit
fit <- nlmixr(nimo, nimoData, est="saem")
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00
#>
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00
#>
#> 001: -7.082156 0.240380 -5.322648 3.706002 2.535890 -1.294407 -0.102901 1.975165 1.900000 1.900000 2.150501 1.391724
#> 002: -7.318608 0.337788 -5.472643 3.604174 2.671940 -1.381532 0.004361 1.965802 1.805000 1.805000 2.042976 0.830852
#> 003: -7.004796 0.329353 -5.552719 3.663648 2.576095 -1.342266 0.094213 2.169032 1.714750 1.714750 1.940827 0.704378
#> 004: -6.831052 0.337039 -5.509392 3.581316 2.619975 -1.473308 0.193564 2.039580 1.629012 1.629012 1.843786 0.673922
#> 005: -6.988888 0.327350 -5.438457 3.546217 2.611964 -1.375401 0.032029 2.028963 1.547562 1.547562 1.751597 0.664592
#> 006: -6.877438 0.309723 -5.508254 3.692787 2.673534 -1.385796 -0.048632 1.984854 1.470184 1.470184 1.664017 0.659652
#> 007: -6.898159 0.314886 -5.496362 3.638982 2.747608 -1.255406 -0.026410 1.947620 1.407505 1.396675 1.580816 0.663774
#> 008: -6.957871 0.319272 -5.352725 3.503540 2.776519 -1.197933 0.000427 1.968390 1.337130 1.326841 1.501775 0.670739
#> 009: -6.826759 0.315714 -5.227308 3.580258 2.922322 -1.203666 -0.010643 2.177228 1.270273 1.260499 1.483524 0.661929
#> 010: -7.082397 0.308379 -5.273932 3.611745 2.874421 -1.137025 0.115752 2.203563 1.305004 1.197474 1.517557 0.656455
#> 011: -7.083805 0.294951 -5.267117 3.697103 2.937389 -1.228824 0.136825 2.298366 1.239753 1.137600 1.522041 0.661686
#> 012: -7.229129 0.369998 -5.290768 3.737127 2.879780 -1.195137 0.181972 2.281019 1.177766 1.080720 1.445939 0.660513
#> 013: -7.118783 0.316777 -5.198435 3.808386 3.007388 -1.298448 0.173969 2.200194 1.118877 1.026684 1.545758 0.659895
#> 014: -7.107046 0.296195 -5.247466 3.826552 3.068812 -1.449512 0.198110 2.171824 1.062934 0.975350 1.468470 0.664803
#> 015: -7.101186 0.342107 -5.262732 3.789245 3.006193 -1.467174 0.209708 2.105610 1.173838 0.926582 1.395047 0.661338
#> 016: -7.054116 0.293809 -5.404022 3.710325 2.800496 -1.446669 0.248707 2.016275 1.115146 0.880253 1.325294 0.661297
#> 017: -6.900522 0.299893 -5.468624 3.730384 2.913575 -1.388838 0.287952 2.001241 1.059389 0.836241 1.259030 0.662951
#> 018: -6.847400 0.259424 -5.462242 3.782073 2.941709 -1.430433 0.325918 2.151714 1.006419 0.794429 1.196078 0.674475
#> 019: -6.753272 0.299121 -5.510133 3.743449 2.954801 -1.441600 0.390829 2.220912 0.956098 0.754707 1.136274 0.665982
#> 020: -6.837756 0.315087 -5.621735 3.778400 2.916021 -1.288673 0.366226 2.244962 1.106701 0.716972 1.079461 0.667779
#> 021: -6.893220 0.306474 -5.591735 3.473458 2.872476 -1.289627 0.381579 2.338688 1.255998 0.681123 1.025488 0.670320
#> 022: -7.005703 0.363949 -5.581785 3.500052 2.745047 -1.268654 0.294263 2.201461 1.193198 0.647067 0.974213 0.668004
#> 023: -6.939491 0.324638 -5.455178 3.494135 2.667590 -1.310115 0.298623 2.255601 1.133538 0.614714 0.925503 0.653433
#> 024: -6.885500 0.269202 -5.425549 3.477327 2.519646 -1.295313 0.341746 2.453918 1.201937 0.583978 0.879227 0.657180
#> 025: -7.003679 0.329172 -5.462586 3.450449 2.399445 -1.392637 0.407089 2.493273 1.141840 0.554779 0.835266 0.657478
#> 026: -6.998503 0.308081 -5.503414 3.378182 2.240570 -1.395307 0.507344 2.538508 1.084748 0.527040 0.793503 0.652995
#> 027: -6.983049 0.251959 -5.415440 3.357185 2.331519 -1.429724 0.469920 2.487613 1.053474 0.500688 0.753828 0.653142
#> 028: -7.064152 0.281134 -5.428507 3.340922 2.360536 -1.343881 0.489512 2.441413 1.031793 0.475654 0.744672 0.656158
#> 029: -7.153328 0.259568 -5.408880 3.332953 2.419550 -1.396986 0.552957 2.412138 1.038802 0.451871 0.755118 0.654489
#> 030: -7.137799 0.269775 -5.430981 3.324828 2.505459 -1.450748 0.544276 2.356400 0.986862 0.429278 0.717362 0.654892
#> 031: -7.278104 0.306992 -5.462212 3.347481 2.481115 -1.393738 0.510631 2.404250 0.937519 0.407814 0.681494 0.653134
#> 032: -7.366002 0.296299 -5.462750 3.354325 2.493465 -1.385500 0.511527 2.445562 0.890643 0.387423 0.647419 0.659970
#> 033: -7.126602 0.319700 -5.438877 3.445812 2.471803 -1.441491 0.498690 2.510886 0.846111 0.368052 0.615049 0.662377
#> 034: -7.011533 0.319809 -5.457466 3.448620 2.549336 -1.433274 0.440205 2.477871 0.803806 0.349649 0.601210 0.661287
#> 035: -7.030069 0.328177 -5.430406 3.521252 2.568902 -1.477423 0.431840 2.497634 0.777766 0.332167 0.571150 0.669577
#> 036: -6.790538 0.306774 -5.527834 3.622364 2.476747 -1.425994 0.382638 2.494380 0.738878 0.315558 0.542592 0.668018
#> 037: -6.800334 0.270544 -5.414146 3.402385 2.582889 -1.400895 0.474395 2.576823 0.818234 0.299781 0.560308 0.659367
#> 038: -6.779983 0.198230 -5.460225 3.326120 2.459665 -1.312269 0.425136 2.498573 0.777322 0.284791 0.532293 0.662861
#> 039: -6.671886 0.254019 -5.570037 3.257240 2.441459 -1.403449 0.505908 2.453239 0.738456 0.270552 0.552395 0.655443
#> 040: -6.801421 0.264928 -5.582054 3.187304 2.426505 -1.432948 0.510497 2.418150 0.701533 0.257024 0.524775 0.661263
#> 041: -6.867235 0.280701 -5.643455 3.254848 2.508290 -1.478873 0.516456 2.354902 0.719071 0.258599 0.498537 0.658930
#> 042: -6.780870 0.297515 -5.625829 3.229796 2.525800 -1.423885 0.545876 2.247574 0.704235 0.262364 0.473610 0.656337
#> 043: -7.000980 0.308498 -5.643916 3.368084 2.518038 -1.448837 0.571972 2.253661 0.838864 0.261131 0.449929 0.660254
#> 044: -6.881316 0.361812 -5.676801 3.302498 2.485286 -1.378273 0.610588 2.406006 0.796921 0.287254 0.427433 0.659041
#> 045: -6.992270 0.311070 -5.460939 3.297823 2.493164 -1.394428 0.574134 2.346399 0.987389 0.272891 0.406061 0.657335
#> 046: -6.937286 0.255586 -5.505305 3.189254 2.469744 -1.477122 0.595653 2.387849 0.938020 0.259247 0.385758 0.657275
#> 047: -6.910055 0.278884 -5.524470 3.291595 2.395307 -1.531927 0.560231 2.426453 0.891119 0.261829 0.366470 0.657160
#> 048: -7.067394 0.288722 -5.510406 3.356396 2.365454 -1.578588 0.642720 2.429590 0.846563 0.296891 0.348147 0.655746
#> 049: -6.923328 0.270119 -5.450789 3.414379 2.366448 -1.585423 0.629513 2.466967 0.893002 0.282046 0.330739 0.658189
#> 050: -6.975794 0.288132 -5.435516 3.347858 2.392924 -1.608769 0.643707 2.417948 0.932213 0.277081 0.314202 0.648781
#> 051: -6.875901 0.353712 -5.416865 3.611819 2.462963 -1.660868 0.661059 2.438330 0.970314 0.294981 0.298492 0.652593
#> 052: -6.765307 0.271983 -5.391472 3.626409 2.527210 -1.643741 0.684367 2.440789 0.921799 0.288411 0.283568 0.655201
#> 053: -6.620037 0.310457 -5.451163 3.854368 2.628403 -1.630681 0.646037 2.405277 0.875709 0.273990 0.269389 0.661798
#> 054: -6.541914 0.322377 -5.602161 3.918050 2.661677 -1.588618 0.619825 2.408575 0.831923 0.260291 0.255920 0.656715
#> 055: -6.373490 0.295359 -5.581440 3.790033 2.702007 -1.567283 0.614160 2.346308 0.843537 0.265659 0.284322 0.657369
#> 056: -6.361577 0.312322 -5.637698 3.785505 2.787302 -1.527121 0.574659 2.272041 0.801360 0.252376 0.270106 0.659265
#> 057: -6.297834 0.286892 -5.705691 3.762464 2.794607 -1.540606 0.548523 2.251223 0.761292 0.239758 0.276525 0.662021
#> 058: -6.402065 0.258021 -5.810660 3.777895 2.758826 -1.493502 0.544410 2.192527 0.862540 0.263461 0.262699 0.656946
#> 059: -6.488559 0.275667 -5.779645 3.824903 2.822481 -1.496432 0.516002 2.169180 0.941809 0.280023 0.249564 0.661064
#> 060: -6.537952 0.322100 -5.844695 4.198486 2.774870 -1.501122 0.532435 2.161901 0.894719 0.287462 0.237086 0.663263
#> 061: -6.416021 0.343720 -5.758680 3.940205 2.650611 -1.499860 0.520846 2.224032 0.849983 0.273089 0.225231 0.664169
#> 062: -6.310170 0.299830 -5.611265 3.839088 2.686540 -1.439855 0.487623 2.288302 0.807484 0.259434 0.213970 0.663122
#> 063: -6.294908 0.311997 -5.540899 3.862490 2.707261 -1.423113 0.494748 2.327657 0.767109 0.246462 0.203271 0.660175
#> 064: -6.366629 0.316682 -5.694336 3.936071 2.652013 -1.427522 0.492013 2.282279 0.835532 0.234139 0.193108 0.670102
#> 065: -6.180801 0.364973 -5.741631 3.493918 2.689585 -1.489510 0.476151 2.215031 0.793756 0.235573 0.183452 0.667527
#> 066: -6.179648 0.348374 -5.749013 3.402021 2.762067 -1.490865 0.520905 2.185092 0.929906 0.254211 0.174280 0.661183
#> 067: -6.263086 0.327637 -5.634331 3.234640 2.755069 -1.510695 0.550426 2.217312 0.979119 0.322320 0.176250 0.662333
#> 068: -6.292892 0.362669 -5.612425 3.180375 2.701803 -1.509967 0.559493 2.262292 0.930163 0.306204 0.209163 0.659376
#> 069: -6.406907 0.311112 -5.588864 2.947345 2.659620 -1.506976 0.586969 2.254385 1.083297 0.321730 0.198705 0.665014
#> 070: -6.314687 0.246440 -5.595287 2.908022 2.630289 -1.497341 0.549582 2.261500 1.029132 0.314350 0.206450 0.657920
#> 071: -6.217709 0.265446 -5.567675 2.798543 2.600281 -1.531825 0.566408 2.206204 0.977676 0.298633 0.196128 0.659110
#> 072: -6.157095 0.238023 -5.754847 2.756068 2.610835 -1.545311 0.590166 2.188482 0.928792 0.302674 0.215475 0.656766
#> 073: -6.287617 0.255763 -5.782974 2.668018 2.562220 -1.547860 0.620664 2.168260 0.961688 0.313501 0.204701 0.659373
#> 074: -6.509203 0.260687 -5.652472 2.846293 2.500960 -1.562527 0.515292 2.121736 1.267267 0.297826 0.194466 0.668704
#> 075: -6.416412 0.278495 -5.663658 2.889233 2.531158 -1.575245 0.563700 2.156104 1.203903 0.282935 0.184743 0.660703
#> 076: -6.372197 0.258099 -5.726064 2.809855 2.497007 -1.585770 0.554655 2.130951 1.143708 0.268788 0.175506 0.656914
#> 077: -6.345672 0.278881 -5.670182 2.647593 2.595867 -1.575106 0.604909 2.152797 1.189868 0.296868 0.166730 0.657233
#> 078: -6.348930 0.262330 -5.658917 2.462042 2.552281 -1.543080 0.649866 2.176722 1.130374 0.282025 0.158394 0.658202
#> 079: -6.182329 0.305910 -5.622486 2.681155 2.576799 -1.530473 0.609340 2.235116 1.073856 0.267924 0.151881 0.666624
#> 080: -6.278351 0.247696 -5.611191 2.640099 2.540012 -1.529954 0.613512 2.216091 1.020163 0.254528 0.152491 0.665660
#> 081: -6.161229 0.308140 -5.648894 2.746375 2.584527 -1.542349 0.612081 2.185029 0.969155 0.251895 0.144867 0.658389
#> 082: -6.134250 0.290519 -5.697368 2.861817 2.573103 -1.554697 0.594581 2.126595 0.920697 0.239300 0.137623 0.654481
#> 083: -6.157780 0.293400 -5.674551 2.596083 2.552749 -1.554927 0.613874 2.102997 0.874662 0.227335 0.130742 0.649084
#> 084: -6.043718 0.270041 -5.524905 2.548757 2.544325 -1.547110 0.572517 2.204878 0.830929 0.215968 0.132570 0.649058
#> 085: -6.035218 0.203893 -5.464928 2.517038 2.519986 -1.562535 0.583354 2.289152 0.809167 0.205170 0.125942 0.659515
#> 086: -6.155169 0.188440 -5.358699 2.760529 2.498737 -1.578073 0.580119 2.283462 0.904021 0.194911 0.120566 0.652512
#> 087: -6.115400 0.156386 -5.284803 2.778030 2.502999 -1.590966 0.603655 2.235995 0.858820 0.185166 0.114538 0.654176
#> 088: -6.158905 0.168182 -5.450443 2.449863 2.516668 -1.578885 0.565575 2.174054 0.887651 0.235742 0.113189 0.672454
#> 089: -6.264660 0.164214 -5.592644 2.405672 2.533449 -1.562987 0.581745 2.165362 1.141834 0.228379 0.107530 0.663633
#> 090: -6.279971 0.227163 -5.563073 2.419175 2.545061 -1.556209 0.595420 2.181293 1.239181 0.235747 0.102153 0.659207
#> 091: -6.211909 0.182332 -5.561700 2.445815 2.572867 -1.544233 0.596836 2.182525 1.177222 0.223959 0.128134 0.653343
#> 092: -6.054699 0.227844 -5.661706 2.325238 2.516278 -1.536466 0.568745 2.156513 1.118361 0.212761 0.122333 0.654642
#> 093: -6.060565 0.272713 -5.729856 2.462729 2.511964 -1.535758 0.574684 2.156639 1.062443 0.212576 0.116217 0.657862
#> 094: -6.246009 0.287082 -5.862449 2.551871 2.478441 -1.539652 0.606569 2.199354 1.234343 0.247500 0.110406 0.654755
#> 095: -6.430293 0.274664 -5.696054 2.580877 2.460005 -1.534625 0.608098 2.271460 1.691609 0.236875 0.104886 0.658308
#> 096: -6.235785 0.261008 -5.573622 2.627211 2.484236 -1.537258 0.653057 2.253702 1.607029 0.225031 0.099641 0.659037
#> 097: -6.424872 0.273861 -5.622372 2.356470 2.528754 -1.536887 0.689467 2.268328 1.556114 0.213780 0.094659 0.654865
#> 098: -6.292736 0.285177 -5.715682 2.226018 2.579253 -1.531399 0.684539 2.272246 1.600298 0.203091 0.089926 0.662134
#> 099: -6.272271 0.291946 -5.757178 2.435993 2.512930 -1.534143 0.677665 2.285231 1.520283 0.224477 0.095242 0.661521
#> 100: -6.212044 0.249385 -5.898241 2.320787 2.509986 -1.546925 0.700892 2.320300 1.444269 0.213253 0.123807 0.664829
#> 101: -6.145608 0.204983 -5.761245 2.475931 2.517424 -1.559297 0.720140 2.349080 1.372055 0.202590 0.117616 0.663993
#> 102: -6.088134 0.202131 -5.798948 2.318193 2.482019 -1.557104 0.714314 2.330478 1.303453 0.192461 0.111736 0.656278
#> 103: -6.155875 0.197593 -5.842397 2.162408 2.429311 -1.566786 0.730617 2.305273 1.238280 0.182838 0.106149 0.656881
#> 104: -6.087011 0.207827 -5.953135 2.118611 2.511587 -1.562439 0.767974 2.280894 1.176366 0.188620 0.100841 0.666994
#> 105: -6.039989 0.251439 -5.966304 2.123777 2.549131 -1.557299 0.757149 2.254959 1.117548 0.253200 0.095799 0.666102
#> 106: -6.290345 0.268955 -5.975043 2.145418 2.573836 -1.550764 0.743828 2.239197 1.151869 0.245265 0.091009 0.659745
#> 107: -6.286730 0.287510 -5.955899 2.111745 2.594305 -1.561735 0.747215 2.250038 1.094275 0.248733 0.086459 0.659499
#> 108: -6.273823 0.297585 -6.016208 2.113022 2.595285 -1.566934 0.734420 2.258948 1.039562 0.277755 0.082136 0.660153
#> 109: -6.267443 0.316282 -6.038765 2.197108 2.609124 -1.577313 0.734572 2.255037 1.005796 0.315716 0.078029 0.661130
#> 110: -6.157332 0.269255 -6.051623 2.140537 2.550621 -1.569779 0.731601 2.273520 0.955506 0.299930 0.074935 0.659734
#> 111: -6.076713 0.269728 -5.953031 2.187567 2.523093 -1.573527 0.738749 2.270180 0.907731 0.284934 0.078932 0.655210
#> 112: -5.964195 0.169871 -5.815473 2.113463 2.501764 -1.570052 0.722121 2.274298 0.931897 0.270687 0.079653 0.658917
#> 113: -6.037903 0.193654 -5.686140 2.183916 2.521836 -1.569770 0.686944 2.272125 0.885302 0.257152 0.075670 0.656216
#> 114: -6.212603 0.207454 -5.578621 2.227185 2.468546 -1.572799 0.704449 2.289144 0.852730 0.244295 0.071886 0.659052
#> 115: -6.087506 0.159465 -5.562266 2.362240 2.467027 -1.569250 0.703103 2.295304 0.810094 0.232080 0.068292 0.659037
#> 116: -6.271836 0.207026 -5.771661 2.317987 2.466562 -1.567764 0.735192 2.279674 1.040933 0.220476 0.074169 0.661909
#> 117: -6.181938 0.247848 -5.916636 2.197798 2.461699 -1.577292 0.724590 2.285703 0.988886 0.221815 0.073582 0.656724
#> 118: -6.105514 0.259773 -6.031286 2.199732 2.433550 -1.573767 0.713413 2.310808 0.939442 0.227781 0.077772 0.662981
#> 119: -6.139682 0.230993 -5.775459 2.245673 2.475944 -1.576630 0.720349 2.319870 1.079576 0.255713 0.092191 0.660103
#> 120: -6.222458 0.265085 -5.780395 2.238269 2.407321 -1.563498 0.717967 2.312104 1.343394 0.242927 0.087581 0.662831
#> 121: -6.205576 0.292690 -5.818731 2.215492 2.353619 -1.568312 0.708781 2.332225 1.276224 0.237629 0.083202 0.658801
#> 122: -6.340574 0.248690 -5.792620 2.186040 2.336950 -1.568947 0.751458 2.336919 1.327683 0.225748 0.079042 0.664029
#> 123: -6.240619 0.286918 -5.922783 2.151440 2.385952 -1.578815 0.739304 2.315010 1.261299 0.239872 0.075090 0.665589
#> 124: -6.062197 0.188491 -5.671910 2.065987 2.407938 -1.575661 0.754348 2.354000 1.198234 0.258650 0.071335 0.655621
#> 125: -5.938171 0.133588 -5.669819 2.098894 2.394591 -1.567429 0.766950 2.346589 1.138322 0.245718 0.067769 0.647558
#> 126: -6.050836 0.159536 -5.575193 2.028379 2.321413 -1.567408 0.759598 2.356169 1.081406 0.233432 0.064380 0.646938
#> 127: -6.043550 0.162555 -5.630182 2.028261 2.279293 -1.565329 0.757574 2.375814 1.027336 0.221760 0.063550 0.652070
#> 128: -6.163815 0.156006 -5.713401 2.082449 2.292989 -1.567436 0.783207 2.368118 0.994222 0.210672 0.060373 0.652423
#> 129: -6.026360 0.134431 -5.730523 2.080405 2.279718 -1.560976 0.774327 2.367867 0.944511 0.207261 0.057354 0.646028
#> 130: -6.182462 0.182418 -5.854656 2.108885 2.282749 -1.562019 0.772143 2.336400 1.141696 0.206348 0.054486 0.651123
#> 131: -6.123334 0.226231 -5.956765 2.269243 2.261948 -1.562097 0.764782 2.345229 1.084611 0.203200 0.063076 0.646223
#> 132: -6.157793 0.253613 -5.899925 2.213909 2.231974 -1.566266 0.763625 2.348024 1.030380 0.193040 0.072373 0.646635
#> 133: -6.160282 0.176399 -5.600395 2.237008 2.202996 -1.566850 0.759821 2.343707 0.978861 0.200522 0.068755 0.643980
#> 134: -6.091373 0.214783 -5.522203 2.174087 2.204914 -1.567717 0.766791 2.351139 0.929918 0.190496 0.065317 0.639176
#> 135: -6.223544 0.196752 -5.619198 2.134648 2.148990 -1.569439 0.762407 2.354880 1.029688 0.189921 0.062051 0.638897
#> 136: -6.351980 0.222879 -5.619590 1.940290 2.136948 -1.569182 0.777299 2.362702 0.978204 0.180425 0.060331 0.638686
#> 137: -6.254703 0.238560 -5.325081 1.962909 2.156771 -1.567986 0.778301 2.386634 0.929294 0.197500 0.060935 0.642611
#> 138: -6.325032 0.223826 -5.596957 1.927149 2.119538 -1.568227 0.777141 2.401026 0.882829 0.208409 0.057888 0.645660
#> 139: -6.327387 0.252262 -5.794480 1.837559 2.130708 -1.571525 0.771579 2.385050 0.849735 0.205737 0.054994 0.648003
#> 140: -6.315469 0.252960 -5.515650 1.918284 2.087438 -1.569570 0.765491 2.393909 1.066001 0.200785 0.052244 0.650808
#> 141: -6.259260 0.196768 -5.359083 1.898649 2.102203 -1.572031 0.760099 2.389715 1.012701 0.190746 0.054229 0.650098
#> 142: -6.286116 0.207886 -5.429603 1.828356 2.113582 -1.568979 0.760490 2.398108 1.040263 0.210455 0.051517 0.644076
#> 143: -6.277863 0.144409 -5.400326 1.798129 2.124122 -1.568783 0.766750 2.390298 1.135030 0.199932 0.083070 0.640880
#> 144: -6.097191 0.152707 -5.265616 1.784166 2.067682 -1.569320 0.775770 2.387152 1.078278 0.189935 0.081843 0.640220
#> 145: -6.030562 0.169422 -5.372859 1.638945 2.042808 -1.571701 0.782241 2.388795 1.024364 0.182802 0.079024 0.646379
#> 146: -5.929208 0.183166 -5.215155 1.582296 2.124695 -1.572587 0.799206 2.384018 0.973146 0.173661 0.080349 0.649840
#> 147: -6.091094 0.148861 -5.413417 1.518910 2.117711 -1.577794 0.803974 2.390770 1.018066 0.189119 0.076332 0.651413
#> 148: -6.038322 0.163040 -5.364643 1.405403 2.060034 -1.580065 0.800919 2.394011 0.967163 0.199397 0.075860 0.643081
#> 149: -6.144971 0.162795 -5.434824 1.639964 2.046322 -1.578302 0.788771 2.397330 0.918804 0.189427 0.100187 0.642488
#> 150: -6.158308 0.153766 -5.322483 1.715597 2.019627 -1.577785 0.777469 2.393026 0.872864 0.179956 0.095178 0.642393
#> 151: -6.325919 0.162711 -5.333445 1.774397 1.980282 -1.576951 0.764681 2.393685 0.924791 0.177011 0.090419 0.640315
#> 152: -6.275873 0.140045 -5.434571 1.728362 1.946403 -1.579603 0.779750 2.395632 0.947999 0.177398 0.074118 0.640285
#> 153: -6.388154 0.204051 -5.674642 1.587373 1.920670 -1.577911 0.790669 2.395030 0.973367 0.198067 0.059956 0.633047
#> 154: -6.392683 0.185443 -5.801330 1.582848 1.964034 -1.578287 0.793954 2.392946 1.015318 0.204812 0.070121 0.631243
#> 155: -6.318437 0.228441 -5.918381 1.503735 1.936745 -1.577975 0.794713 2.391426 0.593669 0.212431 0.062457 0.635381
#> 156: -6.244482 0.191055 -5.744870 1.600130 1.955168 -1.577474 0.795110 2.391378 0.654095 0.239660 0.058790 0.636975
#> 157: -6.280873 0.176652 -5.640207 1.532814 1.973167 -1.579682 0.792470 2.391740 0.693335 0.222825 0.054457 0.642161
#> 158: -6.347095 0.192369 -5.639766 1.674537 1.995592 -1.580147 0.791439 2.396190 0.803920 0.212944 0.051899 0.642383
#> 159: -6.316945 0.133937 -5.675075 1.639609 1.976042 -1.579965 0.785751 2.394868 0.984798 0.193061 0.052124 0.642193
#> 160: -6.196957 0.133609 -5.674684 1.679991 1.981697 -1.580074 0.785797 2.393723 0.826229 0.196067 0.071522 0.636361
#> 161: -6.158592 0.155390 -5.689167 1.712191 2.025802 -1.580988 0.784514 2.392092 0.581564 0.166288 0.073511 0.634819
#> 162: -6.137448 0.154718 -5.678096 1.699526 2.025256 -1.580696 0.782306 2.393472 0.572338 0.162702 0.065574 0.636686
#> 163: -6.100945 0.148876 -5.661370 1.590237 2.003860 -1.582737 0.776825 2.392300 0.717984 0.148697 0.056941 0.645844
#> 164: -6.169722 0.144153 -5.675152 1.588790 2.007761 -1.583089 0.780865 2.393946 0.791595 0.180963 0.062668 0.639522
#> 165: -6.165415 0.136011 -5.468960 1.626551 2.036934 -1.584196 0.776216 2.391671 0.953662 0.223472 0.055287 0.653602
#> 166: -6.168184 0.169013 -5.549479 1.658533 2.018651 -1.584383 0.776294 2.390741 1.047761 0.222250 0.050838 0.653822
#> 167: -6.228627 0.220283 -5.594599 1.565492 2.028183 -1.583950 0.781883 2.391679 1.008091 0.206021 0.035260 0.641002
#> 168: -6.313146 0.222538 -5.916894 1.534677 2.032115 -1.584270 0.784079 2.390755 1.151038 0.223107 0.030725 0.645640
#> 169: -6.245363 0.215022 -5.951179 1.528584 2.022510 -1.584000 0.785383 2.389286 0.970954 0.219767 0.032126 0.647806
#> 170: -6.147276 0.130025 -5.557288 1.601452 2.020010 -1.584146 0.787341 2.386905 0.940890 0.185054 0.031372 0.650503
#> 171: -6.189950 0.113086 -5.714958 1.737105 2.031047 -1.584089 0.782702 2.386961 1.128114 0.135486 0.036217 0.647351
#> 172: -6.221322 0.102054 -5.701951 1.781948 2.055567 -1.583864 0.781344 2.387267 1.214306 0.128140 0.033982 0.652524
#> 173: -6.375344 0.146202 -5.820274 1.867366 2.078362 -1.583308 0.788934 2.388403 1.604321 0.132159 0.027481 0.653632
#> 174: -6.317145 0.145986 -5.704583 1.950026 2.081375 -1.583737 0.794455 2.389226 1.069156 0.151687 0.024780 0.645972
#> 175: -6.354248 0.193550 -5.778465 1.889422 2.079067 -1.583930 0.799495 2.388396 1.196044 0.158432 0.027334 0.655684
#> 176: -6.474609 0.164674 -5.288514 1.896971 2.095629 -1.584153 0.802286 2.389881 1.636644 0.176902 0.025370 0.642049
#> 177: -6.481511 0.194558 -5.409854 1.920877 2.108349 -1.583950 0.800018 2.388218 1.798048 0.155473 0.027795 0.651002
#> 178: -6.236869 0.174708 -5.611176 1.800213 2.116938 -1.583644 0.802930 2.386063 1.219576 0.140254 0.032773 0.649996
#> 179: -6.402773 0.160141 -5.504130 1.821194 2.150982 -1.583531 0.807279 2.384348 1.661895 0.128963 0.034756 0.648968
#> 180: -6.200352 0.201573 -5.379617 1.622757 2.098665 -1.583212 0.808068 2.384942 1.291450 0.136027 0.034760 0.648252
#> 181: -6.154629 0.134022 -5.703647 1.517957 2.097937 -1.583226 0.808596 2.384396 1.267142 0.109287 0.038464 0.653541
#> 182: -6.017586 0.152084 -5.621212 1.590407 2.115783 -1.582320 0.809266 2.382520 0.877975 0.112818 0.049803 0.646612
#> 183: -6.035195 0.155852 -5.613930 1.541263 2.122084 -1.582177 0.812211 2.383690 1.082328 0.138553 0.063931 0.643363
#> 184: -6.030149 0.160561 -5.707476 1.547401 2.114630 -1.581728 0.814090 2.381816 0.915867 0.133825 0.054102 0.644635
#> 185: -6.104584 0.163207 -5.560511 1.570250 2.105220 -1.582416 0.815267 2.381782 0.914228 0.115981 0.058587 0.651400
#> 186: -6.083656 0.135009 -5.726392 1.448787 2.091375 -1.582231 0.812878 2.382702 1.109141 0.121905 0.049311 0.642818
#> 187: -6.043931 0.169513 -5.764281 1.324844 2.099793 -1.581689 0.812464 2.383573 1.185721 0.131987 0.028303 0.653317
#> 188: -6.248159 0.200303 -5.876567 1.222233 2.095785 -1.580985 0.814765 2.382389 1.274920 0.189190 0.025971 0.654679
#> 189: -6.216796 0.232604 -6.068976 1.185167 2.121533 -1.581243 0.814869 2.380470 0.890098 0.128944 0.026408 0.657332
#> 190: -6.051454 0.196362 -5.889591 1.267705 2.123353 -1.581451 0.813807 2.380939 0.935833 0.110422 0.029227 0.662972
#> 191: -5.991635 0.211124 -5.881368 1.313101 2.106945 -1.580983 0.816506 2.382569 0.892656 0.156577 0.024955 0.654841
#> 192: -6.047691 0.215289 -5.768730 1.315070 2.103683 -1.580539 0.820562 2.383456 0.727932 0.177825 0.023876 0.651624
#> 193: -6.053332 0.208433 -5.776476 1.347489 2.108651 -1.579734 0.820091 2.383674 0.700510 0.190835 0.022941 0.649058
#> 194: -6.123540 0.202063 -5.700192 1.444472 2.111670 -1.579863 0.821033 2.384423 1.008728 0.164231 0.017636 0.642233
#> 195: -6.218184 0.192921 -5.639303 1.445180 2.068593 -1.579882 0.822934 2.383242 0.897313 0.191179 0.011468 0.639504
#> 196: -6.285609 0.167080 -5.523271 1.453079 2.058030 -1.580034 0.821900 2.384355 0.759962 0.198764 0.011644 0.647291
#> 197: -6.134340 0.224728 -5.594996 1.423208 2.062669 -1.580017 0.821988 2.384156 0.772882 0.154793 0.011072 0.653979
#> 198: -6.155253 0.218676 -5.762134 1.424059 2.085973 -1.579790 0.821053 2.384384 0.731096 0.143189 0.009429 0.652154
#> 199: -6.045881 0.177204 -5.636785 1.439550 2.070981 -1.579288 0.830498 2.386089 0.639387 0.124564 0.009880 0.655914
#> 200: -6.055478 0.209543 -6.063878 1.199574 2.077961 -1.579419 0.833684 2.386815 0.575297 0.143785 0.011720 0.659664
#> 201: -6.037418 0.198611 -6.093451 1.217432 2.074870 -1.579223 0.832098 2.386906 0.532374 0.144897 0.011077 0.660308
#> 202: -6.074725 0.210894 -5.998796 1.214613 2.063287 -1.579066 0.830320 2.387384 0.564264 0.154532 0.011140 0.659082
#> 203: -6.091109 0.218927 -5.960044 1.201478 2.055370 -1.579145 0.830100 2.387662 0.601134 0.159588 0.011460 0.658665
#> 204: -6.105597 0.219126 -5.964669 1.231455 2.048827 -1.579183 0.831098 2.387578 0.603384 0.161013 0.010930 0.658939
#> 205: -6.096807 0.214335 -5.952901 1.238991 2.046068 -1.579252 0.831319 2.387162 0.609380 0.163230 0.010500 0.657699
#> 206: -6.087488 0.207680 -5.923162 1.228464 2.045265 -1.579303 0.831680 2.386755 0.621802 0.166719 0.010294 0.657861
#> 207: -6.071840 0.200371 -5.899969 1.216463 2.046658 -1.579275 0.832070 2.386550 0.614502 0.170331 0.010192 0.657761
#> 208: -6.065574 0.201665 -5.848686 1.206129 2.047026 -1.579319 0.831664 2.386522 0.619872 0.171661 0.010531 0.656912
#> 209: -6.063189 0.201077 -5.839097 1.202585 2.046578 -1.579385 0.831411 2.386416 0.622716 0.174177 0.010417 0.655942
#> 210: -6.063305 0.197269 -5.836365 1.198254 2.047620 -1.579384 0.831114 2.386404 0.630926 0.176023 0.010390 0.655562
#> 211: -6.067943 0.197980 -5.847309 1.190643 2.047523 -1.579372 0.831228 2.386387 0.634219 0.179484 0.010593 0.654887
#> 212: -6.056753 0.196640 -5.871002 1.184433 2.047436 -1.579335 0.831147 2.386499 0.632418 0.180047 0.010865 0.655014
#> 213: -6.049761 0.196915 -5.864488 1.193781 2.047104 -1.579357 0.830967 2.386601 0.635111 0.178485 0.011130 0.654298
#> 214: -6.051699 0.195731 -5.857607 1.200313 2.046627 -1.579373 0.830825 2.386797 0.654442 0.175970 0.011481 0.654196
#> 215: -6.046734 0.196397 -5.847588 1.194736 2.046321 -1.579405 0.831030 2.386905 0.661428 0.173087 0.011493 0.653840
#> 216: -6.044855 0.192708 -5.836508 1.194547 2.046263 -1.579366 0.830665 2.386951 0.667204 0.171216 0.011635 0.653311
#> 217: -6.041256 0.189992 -5.833164 1.195505 2.046501 -1.579332 0.830390 2.386961 0.669282 0.171713 0.011667 0.653050
#> 218: -6.040552 0.188114 -5.825899 1.195071 2.046500 -1.579332 0.830343 2.386879 0.667698 0.172848 0.011602 0.652917
#> 219: -6.041706 0.187935 -5.827650 1.193297 2.046167 -1.579337 0.830204 2.386839 0.673168 0.172418 0.011582 0.652717
#> 220: -6.040923 0.187858 -5.826091 1.191068 2.046317 -1.579322 0.829879 2.386898 0.677496 0.172795 0.011446 0.652684
#> 221: -6.031841 0.184546 -5.818764 1.185344 2.046799 -1.579308 0.829943 2.386914 0.679127 0.172090 0.011317 0.652913
#> 222: -6.027131 0.183334 -5.813323 1.185231 2.047118 -1.579318 0.830009 2.386954 0.681745 0.172352 0.011277 0.652750
#> 223: -6.028836 0.183496 -5.811891 1.187753 2.045743 -1.579332 0.830173 2.386971 0.681366 0.172628 0.011470 0.652661
#> 224: -6.029598 0.182832 -5.807053 1.189294 2.044740 -1.579336 0.830326 2.386992 0.682544 0.172985 0.011507 0.652776
#> 225: -6.030101 0.181380 -5.803794 1.192640 2.043908 -1.579338 0.830447 2.387027 0.680371 0.172376 0.011501 0.652624
#> 226: -6.031507 0.182399 -5.810773 1.196079 2.044494 -1.579355 0.830324 2.387071 0.675101 0.173093 0.011642 0.652537
#> 227: -6.032667 0.182962 -5.806224 1.198234 2.044621 -1.579363 0.830503 2.387154 0.670883 0.173915 0.011571 0.652498
#> 228: -6.032264 0.184453 -5.796634 1.199624 2.044230 -1.579407 0.830594 2.387187 0.670582 0.174462 0.011569 0.652353
#> 229: -6.028916 0.183285 -5.793965 1.196713 2.044632 -1.579414 0.830643 2.387209 0.674898 0.174125 0.011463 0.652093
#> 230: -6.028921 0.183653 -5.791007 1.195125 2.044342 -1.579420 0.830701 2.387286 0.677747 0.174179 0.011419 0.651960
#> 231: -6.027478 0.182719 -5.794337 1.190773 2.044201 -1.579421 0.830904 2.387342 0.678057 0.173973 0.011386 0.652007
#> 232: -6.028107 0.182883 -5.793973 1.189968 2.044126 -1.579446 0.831017 2.387354 0.679718 0.174387 0.011371 0.652116
#> 233: -6.026146 0.181489 -5.796603 1.188469 2.044252 -1.579462 0.831025 2.387376 0.679750 0.175606 0.011344 0.651899
#> 234: -6.027695 0.182845 -5.797839 1.191645 2.044907 -1.579465 0.830893 2.387288 0.678211 0.176828 0.011369 0.651612
#> 235: -6.030135 0.182271 -5.798147 1.189381 2.045080 -1.579475 0.830877 2.387263 0.688212 0.177701 0.011318 0.651636
#> 236: -6.030725 0.181940 -5.797892 1.189258 2.045424 -1.579471 0.830745 2.387269 0.694006 0.179197 0.011286 0.651486
#> 237: -6.028246 0.181194 -5.801297 1.188542 2.046052 -1.579464 0.830597 2.387284 0.693111 0.180762 0.011243 0.651516
#> 238: -6.030284 0.182256 -5.795379 1.189480 2.047095 -1.579447 0.830620 2.387264 0.698448 0.181233 0.011208 0.651573
#> 239: -6.032709 0.182134 -5.792755 1.191578 2.047679 -1.579453 0.830634 2.387240 0.702301 0.180944 0.011173 0.651450
#> 240: -6.035075 0.182489 -5.796219 1.190613 2.047291 -1.579452 0.830719 2.387233 0.706047 0.180037 0.011061 0.651368
#> 241: -6.036239 0.183473 -5.794169 1.191153 2.048123 -1.579458 0.830600 2.387230 0.710595 0.179563 0.011009 0.651567
#> 242: -6.036142 0.183188 -5.791239 1.191375 2.047816 -1.579474 0.830709 2.387164 0.711367 0.179810 0.010995 0.651476
#> 243: -6.036491 0.182301 -5.792732 1.192755 2.047771 -1.579484 0.830786 2.387142 0.705716 0.180320 0.010956 0.651351
#> 244: -6.039181 0.181941 -5.790970 1.191967 2.047515 -1.579486 0.830940 2.387124 0.709274 0.179943 0.011039 0.651296
#> 245: -6.039574 0.180886 -5.791047 1.190976 2.047688 -1.579489 0.830977 2.387116 0.713114 0.178660 0.011118 0.651259
#> 246: -6.038403 0.179715 -5.793274 1.187608 2.048261 -1.579489 0.830996 2.387092 0.714676 0.178303 0.011134 0.651292
#> 247: -6.039593 0.179429 -5.797415 1.188356 2.048581 -1.579481 0.830951 2.387094 0.718571 0.177630 0.011179 0.651307
#> 248: -6.040672 0.179452 -5.802954 1.187781 2.048939 -1.579457 0.830912 2.387089 0.724880 0.176294 0.011218 0.651307
#> 249: -6.040283 0.178987 -5.807010 1.188216 2.049590 -1.579461 0.830958 2.387085 0.724918 0.176107 0.011280 0.651359
#> 250: -6.041485 0.178522 -5.803293 1.190114 2.049874 -1.579449 0.830880 2.387080 0.726640 0.175874 0.011356 0.651201
#> 251: -6.044769 0.178673 -5.805846 1.191374 2.050411 -1.579435 0.830828 2.387090 0.730368 0.176722 0.011361 0.651277
#> 252: -6.045081 0.178082 -5.809361 1.191183 2.050640 -1.579438 0.830854 2.387152 0.732381 0.177291 0.011265 0.651080
#> 253: -6.044815 0.178126 -5.812862 1.191434 2.050990 -1.579440 0.830990 2.387163 0.734909 0.177757 0.011268 0.651010
#> 254: -6.045637 0.179179 -5.814103 1.191126 2.050915 -1.579453 0.830950 2.387187 0.735563 0.178208 0.011233 0.650989
#> 255: -6.045281 0.179233 -5.814319 1.189830 2.050672 -1.579463 0.830969 2.387190 0.733706 0.179411 0.011273 0.650873
#> 256: -6.044909 0.179224 -5.813710 1.190693 2.050759 -1.579467 0.830982 2.387201 0.733159 0.179879 0.011269 0.650623
#> 257: -6.045287 0.178914 -5.818396 1.190292 2.051007 -1.579471 0.830974 2.387203 0.731533 0.180913 0.011256 0.650512
#> 258: -6.045196 0.178430 -5.821831 1.190603 2.051099 -1.579476 0.831022 2.387216 0.732036 0.180894 0.011212 0.650486
#> 259: -6.045716 0.178756 -5.823485 1.189669 2.051086 -1.579487 0.831152 2.387190 0.733440 0.180764 0.011144 0.650347
#> 260: -6.045814 0.178353 -5.821948 1.190272 2.051117 -1.579503 0.831276 2.387168 0.732752 0.180759 0.011107 0.650387
#> 261: -6.047894 0.178167 -5.822819 1.190855 2.050962 -1.579511 0.831300 2.387176 0.733017 0.180942 0.011103 0.650581
#> 262: -6.049017 0.178202 -5.823395 1.191791 2.051176 -1.579520 0.831299 2.387200 0.735905 0.181303 0.011110 0.650564
#> 263: -6.050157 0.178619 -5.823480 1.190946 2.051049 -1.579526 0.831260 2.387199 0.735843 0.181910 0.011110 0.650425
#> 264: -6.050288 0.178834 -5.825973 1.190918 2.050871 -1.579530 0.831225 2.387224 0.734832 0.182394 0.011114 0.650400
#> 265: -6.049614 0.178549 -5.828619 1.190333 2.050444 -1.579522 0.831149 2.387231 0.734240 0.182514 0.011028 0.650336
#> 266: -6.051179 0.178318 -5.831555 1.190193 2.050249 -1.579514 0.831109 2.387237 0.734298 0.182429 0.010961 0.650316
#> 267: -6.050425 0.177066 -5.833400 1.190721 2.049922 -1.579507 0.831171 2.387252 0.732616 0.182427 0.010933 0.650268
#> 268: -6.050517 0.176183 -5.831380 1.190695 2.049781 -1.579505 0.831198 2.387254 0.732532 0.182453 0.010932 0.650169
#> 269: -6.050097 0.175902 -5.829630 1.189763 2.049729 -1.579497 0.831162 2.387269 0.731700 0.182682 0.010922 0.650060
#> 270: -6.049825 0.175797 -5.823545 1.189178 2.049524 -1.579492 0.831170 2.387271 0.732611 0.182572 0.010918 0.650064
#> 271: -6.049179 0.176104 -5.823946 1.189330 2.049368 -1.579498 0.831174 2.387277 0.733712 0.182495 0.010938 0.650141
#> 272: -6.050914 0.176881 -5.823622 1.189662 2.049214 -1.579495 0.831185 2.387276 0.735293 0.182319 0.010923 0.650165
#> 273: -6.051903 0.177584 -5.824934 1.189587 2.049346 -1.579491 0.831145 2.387278 0.737204 0.182697 0.010911 0.650197
#> 274: -6.054039 0.177962 -5.827075 1.190329 2.049127 -1.579487 0.831132 2.387283 0.738987 0.183443 0.010909 0.650176
#> 275: -6.054253 0.177643 -5.826051 1.190858 2.049065 -1.579494 0.831081 2.387269 0.738160 0.183491 0.010899 0.650134
#> 276: -6.055671 0.177332 -5.824016 1.192295 2.048812 -1.579492 0.831043 2.387266 0.737716 0.183256 0.010925 0.650044
#> 277: -6.056754 0.177174 -5.824446 1.193013 2.048733 -1.579490 0.831066 2.387272 0.736508 0.183407 0.010936 0.649992
#> 278: -6.057840 0.176963 -5.825816 1.193538 2.048521 -1.579486 0.831095 2.387275 0.735471 0.183743 0.010908 0.649989
#> 279: -6.055365 0.176417 -5.824374 1.193328 2.048459 -1.579485 0.831101 2.387292 0.735699 0.183779 0.010870 0.650075
#> 280: -6.055098 0.176581 -5.823018 1.193775 2.048137 -1.579483 0.831081 2.387310 0.736072 0.183805 0.010852 0.650225
#> 281: -6.054662 0.176355 -5.822090 1.194264 2.048089 -1.579480 0.831059 2.387328 0.738238 0.183691 0.010830 0.650219
#> 282: -6.054954 0.176700 -5.820986 1.195055 2.048092 -1.579480 0.831074 2.387323 0.740086 0.183461 0.010790 0.650207
#> 283: -6.054855 0.176624 -5.820457 1.196077 2.048353 -1.579481 0.831095 2.387329 0.738999 0.183519 0.010794 0.650279
#> 284: -6.053718 0.176310 -5.820577 1.196581 2.048594 -1.579479 0.831112 2.387341 0.738365 0.183706 0.010758 0.650290
#> 285: -6.054837 0.175969 -5.819811 1.197163 2.048717 -1.579476 0.831118 2.387336 0.739086 0.183962 0.010728 0.650329
#> 286: -6.054094 0.175523 -5.819596 1.196997 2.048947 -1.579478 0.831173 2.387337 0.738440 0.184307 0.010750 0.650442
#> 287: -6.053474 0.175279 -5.819974 1.197133 2.049235 -1.579481 0.831241 2.387339 0.737342 0.184158 0.010753 0.650500
#> 288: -6.053648 0.175584 -5.821407 1.196546 2.049334 -1.579485 0.831321 2.387338 0.735954 0.184526 0.010749 0.650507
#> 289: -6.055871 0.176060 -5.822254 1.196799 2.049348 -1.579485 0.831338 2.387334 0.735922 0.184701 0.010738 0.650545
#> 290: -6.057906 0.176692 -5.821673 1.197480 2.049410 -1.579486 0.831326 2.387337 0.736821 0.184767 0.010729 0.650650
#> 291: -6.058278 0.176544 -5.820620 1.197045 2.049350 -1.579486 0.831287 2.387341 0.736845 0.184888 0.010701 0.650768
#> 292: -6.057822 0.176122 -5.820517 1.197091 2.049523 -1.579485 0.831259 2.387342 0.736183 0.185168 0.010660 0.650697
#> 293: -6.057357 0.175553 -5.821762 1.197110 2.049732 -1.579484 0.831253 2.387343 0.735810 0.184962 0.010631 0.650755
#> 294: -6.058023 0.175377 -5.821405 1.197762 2.049804 -1.579485 0.831267 2.387356 0.737845 0.184838 0.010635 0.650799
#> 295: -6.058442 0.175248 -5.823396 1.198525 2.049947 -1.579484 0.831256 2.387360 0.739066 0.184722 0.010664 0.650915
#> 296: -6.059286 0.174834 -5.825005 1.198886 2.050122 -1.579482 0.831226 2.387370 0.740183 0.184920 0.010669 0.650925
#> 297: -6.059679 0.174972 -5.825805 1.198811 2.050331 -1.579480 0.831227 2.387365 0.740264 0.184991 0.010708 0.650969
#> 298: -6.060177 0.175088 -5.825383 1.199166 2.050227 -1.579482 0.831244 2.387356 0.740962 0.185339 0.010679 0.651082
#> 299: -6.060598 0.174778 -5.825341 1.198994 2.050309 -1.579484 0.831244 2.387352 0.740977 0.185802 0.010683 0.651035
#> 300: -6.060052 0.174512 -5.825305 1.198753 2.050484 -1.579484 0.831227 2.387349 0.741640 0.185463 0.010666 0.651102
#> 301: -6.060990 0.174045 -5.825185 1.198931 2.050461 -1.579485 0.831202 2.387341 0.743479 0.185307 0.010666 0.651133
#> 302: -6.061123 0.173578 -5.825024 1.198703 2.050519 -1.579485 0.831190 2.387343 0.744186 0.185525 0.010692 0.651138
#> 303: -6.062172 0.173710 -5.825630 1.198391 2.050641 -1.579485 0.831158 2.387343 0.745380 0.186279 0.010691 0.651083
#> 304: -6.062943 0.174174 -5.825900 1.197886 2.050731 -1.579486 0.831146 2.387339 0.744729 0.186364 0.010699 0.651161
#> 305: -6.063397 0.174121 -5.825873 1.198074 2.050573 -1.579484 0.831143 2.387343 0.743725 0.186452 0.010696 0.651202
#> 306: -6.063236 0.174450 -5.824594 1.198339 2.050636 -1.579487 0.831123 2.387347 0.743346 0.186166 0.010709 0.651292
#> 307: -6.063155 0.174318 -5.823954 1.198566 2.050603 -1.579486 0.831095 2.387357 0.745145 0.185630 0.010710 0.651424
#> 308: -6.064193 0.174445 -5.824002 1.198658 2.050624 -1.579485 0.831068 2.387360 0.746479 0.185443 0.010742 0.651509
#> 309: -6.065370 0.174331 -5.823644 1.198970 2.050646 -1.579486 0.831060 2.387358 0.748181 0.185297 0.010729 0.651622
#> 310: -6.066001 0.174270 -5.824979 1.199296 2.050607 -1.579485 0.831079 2.387355 0.749151 0.185172 0.010717 0.651714
#> 311: -6.067609 0.174125 -5.825373 1.199660 2.050663 -1.579483 0.831072 2.387354 0.750689 0.185528 0.010748 0.651771
#> 312: -6.071300 0.174434 -5.825806 1.199826 2.050639 -1.579481 0.831065 2.387353 0.754733 0.185676 0.010753 0.651906
#> 313: -6.073328 0.174242 -5.826462 1.200030 2.050550 -1.579477 0.831051 2.387351 0.758623 0.185347 0.010773 0.652156
#> 314: -6.074236 0.174438 -5.826614 1.199945 2.050432 -1.579477 0.831044 2.387354 0.759999 0.185253 0.010778 0.652295
#> 315: -6.075277 0.174369 -5.827435 1.200099 2.050080 -1.579477 0.831028 2.387350 0.760421 0.185119 0.010787 0.652371
#> 316: -6.075647 0.174016 -5.828365 1.200212 2.050149 -1.579476 0.831018 2.387348 0.760800 0.185141 0.010790 0.652442
#> 317: -6.074873 0.173835 -5.828380 1.200333 2.050222 -1.579476 0.830997 2.387347 0.760485 0.185101 0.010753 0.652577
#> 318: -6.075851 0.173957 -5.829418 1.200677 2.050228 -1.579476 0.830993 2.387348 0.761798 0.185264 0.010733 0.652754
#> 319: -6.075915 0.173401 -5.829284 1.200996 2.050462 -1.579478 0.830988 2.387348 0.762057 0.185444 0.010714 0.652877
#> 320: -6.075997 0.173114 -5.829800 1.201027 2.050773 -1.579480 0.830988 2.387350 0.761478 0.185361 0.010702 0.653019
#> 321: -6.075930 0.173000 -5.830617 1.200902 2.050928 -1.579479 0.830980 2.387349 0.761883 0.185541 0.010683 0.653162
#> 322: -6.077828 0.173042 -5.831770 1.200676 2.050945 -1.579479 0.830958 2.387351 0.766041 0.185550 0.010671 0.653282
#> 323: -6.078748 0.172915 -5.832968 1.200245 2.051014 -1.579481 0.830948 2.387351 0.769077 0.185684 0.010683 0.653455
#> 324: -6.079321 0.172885 -5.834469 1.200035 2.051120 -1.579480 0.830943 2.387346 0.769822 0.185896 0.010701 0.653571
#> 325: -6.080297 0.172576 -5.836348 1.199924 2.051170 -1.579482 0.830943 2.387344 0.771948 0.185953 0.010742 0.653657
#> 326: -6.080651 0.172461 -5.837793 1.199693 2.051454 -1.579483 0.830935 2.387341 0.772924 0.185870 0.010741 0.653799
#> 327: -6.081379 0.172525 -5.838636 1.199408 2.051669 -1.579486 0.830925 2.387341 0.774039 0.185826 0.010761 0.653943
#> 328: -6.081670 0.172427 -5.840043 1.199288 2.051975 -1.579487 0.830922 2.387339 0.774594 0.185418 0.010752 0.654123
#> 329: -6.082429 0.172425 -5.840843 1.199231 2.052101 -1.579487 0.830900 2.387340 0.775743 0.185199 0.010750 0.654282
#> 330: -6.082947 0.172312 -5.842195 1.199262 2.052251 -1.579488 0.830885 2.387336 0.776030 0.185112 0.010741 0.654427
#> 331: -6.083433 0.172684 -5.843093 1.199334 2.052353 -1.579489 0.830881 2.387332 0.776828 0.185032 0.010732 0.654529
#> 332: -6.083493 0.172271 -5.844282 1.199648 2.052243 -1.579491 0.830882 2.387330 0.777095 0.184981 0.010724 0.654643
#> 333: -6.084202 0.172084 -5.845606 1.200024 2.052181 -1.579492 0.830886 2.387329 0.776676 0.185011 0.010759 0.654706
#> 334: -6.084942 0.171817 -5.846207 1.200270 2.052270 -1.579493 0.830885 2.387326 0.776477 0.185388 0.010794 0.654819
#> 335: -6.085331 0.171894 -5.846656 1.200446 2.052652 -1.579492 0.830885 2.387324 0.777063 0.185533 0.010843 0.654949
#> 336: -6.085309 0.171901 -5.847335 1.200577 2.052865 -1.579492 0.830883 2.387322 0.776956 0.185380 0.010878 0.655144
#> 337: -6.086467 0.172122 -5.848304 1.200479 2.053080 -1.579493 0.830868 2.387319 0.776274 0.185741 0.010870 0.655347
#> 338: -6.087671 0.172313 -5.848983 1.200450 2.053392 -1.579493 0.830861 2.387319 0.777639 0.185993 0.010876 0.655504
#> 339: -6.088606 0.172482 -5.849853 1.200451 2.053614 -1.579493 0.830866 2.387318 0.778066 0.186131 0.010902 0.655722
#> 340: -6.089364 0.172539 -5.850417 1.200644 2.053538 -1.579493 0.830872 2.387320 0.779755 0.186105 0.010910 0.655955
#> 341: -6.091562 0.172456 -5.851590 1.200644 2.053376 -1.579494 0.830873 2.387321 0.784532 0.185802 0.010928 0.656095
#> 342: -6.093540 0.172430 -5.852885 1.200566 2.053274 -1.579494 0.830875 2.387323 0.788421 0.185717 0.010922 0.656309
#> 343: -6.094680 0.172450 -5.853537 1.200493 2.053127 -1.579494 0.830881 2.387325 0.790456 0.185500 0.010923 0.656542
#> 344: -6.096284 0.172698 -5.854322 1.200415 2.052872 -1.579494 0.830884 2.387325 0.792268 0.185385 0.010934 0.656716
#> 345: -6.098183 0.172696 -5.854925 1.200458 2.052617 -1.579494 0.830883 2.387323 0.793947 0.185386 0.010932 0.656867
#> 346: -6.099082 0.172904 -5.855826 1.200441 2.052588 -1.579494 0.830876 2.387324 0.795260 0.185244 0.010936 0.657042
#> 347: -6.099537 0.172904 -5.856673 1.200342 2.052692 -1.579495 0.830873 2.387322 0.795728 0.185312 0.010935 0.657232
#> 348: -6.100042 0.172659 -5.857234 1.200362 2.052736 -1.579495 0.830872 2.387321 0.797461 0.185395 0.010914 0.657431
#> 349: -6.100642 0.172609 -5.857718 1.200399 2.052712 -1.579496 0.830863 2.387320 0.798307 0.185370 0.010927 0.657626
#> 350: -6.101860 0.172633 -5.858544 1.200430 2.052648 -1.579495 0.830851 2.387319 0.799734 0.185548 0.010951 0.657856
#> 351: -6.103918 0.172859 -5.858844 1.200464 2.052596 -1.579495 0.830836 2.387318 0.803448 0.185595 0.010983 0.658014
#> 352: -6.105158 0.173134 -5.858920 1.200477 2.052470 -1.579495 0.830838 2.387320 0.804163 0.185583 0.010974 0.658184
#> 353: -6.105837 0.172938 -5.859399 1.200442 2.052480 -1.579495 0.830843 2.387321 0.804381 0.185805 0.010989 0.658342
#> 354: -6.106663 0.173158 -5.860199 1.200477 2.052586 -1.579495 0.830843 2.387322 0.804435 0.186123 0.010987 0.658531
#> 355: -6.107458 0.173359 -5.860599 1.200587 2.052676 -1.579495 0.830845 2.387319 0.805566 0.186047 0.011001 0.658732
#> 356: -6.108082 0.173548 -5.861304 1.200674 2.052785 -1.579495 0.830849 2.387317 0.805610 0.185767 0.011033 0.658897
#> 357: -6.108975 0.173619 -5.861657 1.200694 2.052846 -1.579495 0.830846 2.387319 0.805788 0.185562 0.011051 0.659064
#> 358: -6.109106 0.173552 -5.862635 1.200608 2.052991 -1.579495 0.830845 2.387319 0.805696 0.185240 0.011049 0.659252
#> 359: -6.109321 0.173639 -5.863246 1.200674 2.053066 -1.579495 0.830849 2.387318 0.806739 0.185044 0.011046 0.659500
#> 360: -6.110853 0.173896 -5.863655 1.200690 2.053195 -1.579495 0.830853 2.387318 0.808761 0.184909 0.011035 0.659719
#> 361: -6.112543 0.174398 -5.864353 1.200597 2.053260 -1.579494 0.830855 2.387318 0.809947 0.184901 0.011027 0.659947
#> 362: -6.114088 0.174626 -5.864966 1.200577 2.053323 -1.579494 0.830859 2.387318 0.811580 0.184808 0.011020 0.660197
#> 363: -6.115910 0.174883 -5.865428 1.200614 2.053315 -1.579494 0.830856 2.387318 0.812852 0.184579 0.011024 0.660397
#> 364: -6.116765 0.174920 -5.866058 1.200594 2.053277 -1.579494 0.830859 2.387319 0.811850 0.184545 0.011038 0.660573
#> 365: -6.117887 0.175090 -5.867099 1.200717 2.053234 -1.579494 0.830859 2.387320 0.811690 0.184789 0.011044 0.660805
#> 366: -6.118970 0.175091 -5.867961 1.200721 2.053226 -1.579494 0.830867 2.387320 0.811123 0.184616 0.011059 0.661085
#> 367: -6.120330 0.175222 -5.868353 1.200678 2.053238 -1.579493 0.830871 2.387319 0.811369 0.184610 0.011072 0.661340
#> 368: -6.121938 0.175654 -5.868754 1.200593 2.053271 -1.579493 0.830870 2.387319 0.813320 0.184731 0.011057 0.661592
#> 369: -6.123707 0.176155 -5.868783 1.200562 2.053298 -1.579493 0.830867 2.387320 0.815323 0.184851 0.011035 0.661785
#> 370: -6.124142 0.176149 -5.869339 1.200552 2.053470 -1.579493 0.830867 2.387319 0.814998 0.184863 0.011041 0.661986
#> 371: -6.124759 0.176197 -5.869777 1.200532 2.053488 -1.579493 0.830867 2.387319 0.814701 0.184877 0.011032 0.662209
#> 372: -6.125487 0.176021 -5.870028 1.200501 2.053566 -1.579493 0.830868 2.387318 0.815465 0.184993 0.011027 0.662482
#> 373: -6.127186 0.176094 -5.870440 1.200507 2.053509 -1.579493 0.830871 2.387317 0.818744 0.185056 0.011047 0.662697
#> 374: -6.128353 0.176209 -5.870915 1.200477 2.053593 -1.579493 0.830872 2.387317 0.821513 0.184967 0.011062 0.662914
#> 375: -6.129919 0.176660 -5.871212 1.200515 2.053568 -1.579492 0.830874 2.387316 0.823749 0.184903 0.011088 0.663129
#> 376: -6.131644 0.177069 -5.871792 1.200499 2.053542 -1.579492 0.830875 2.387315 0.825639 0.184875 0.011109 0.663331
#> 377: -6.133236 0.177334 -5.872170 1.200535 2.053501 -1.579492 0.830876 2.387315 0.828080 0.184585 0.011122 0.663511
#> 378: -6.134394 0.177449 -5.872585 1.200585 2.053472 -1.579492 0.830876 2.387315 0.829454 0.184372 0.011167 0.663695
#> 379: -6.135371 0.177561 -5.872993 1.200658 2.053565 -1.579492 0.830874 2.387314 0.831185 0.184153 0.011184 0.663879
#> 380: -6.135824 0.177504 -5.873049 1.200697 2.053696 -1.579492 0.830871 2.387314 0.833535 0.183849 0.011181 0.664071
#> 381: -6.136943 0.177686 -5.873157 1.200617 2.053800 -1.579492 0.830867 2.387314 0.836649 0.183591 0.011173 0.664252
#> 382: -6.137785 0.177882 -5.873422 1.200563 2.053831 -1.579492 0.830865 2.387313 0.838287 0.183622 0.011184 0.664481
#> 383: -6.138789 0.177967 -5.873855 1.200572 2.053865 -1.579492 0.830865 2.387312 0.840525 0.183683 0.011181 0.664709
#> 384: -6.138867 0.177920 -5.874240 1.200600 2.054025 -1.579492 0.830865 2.387313 0.841091 0.183711 0.011187 0.664947
#> 385: -6.139536 0.178197 -5.874486 1.200595 2.054168 -1.579492 0.830862 2.387313 0.841759 0.183732 0.011170 0.665189
#> 386: -6.140125 0.178050 -5.874679 1.200620 2.054333 -1.579492 0.830861 2.387314 0.842507 0.183569 0.011167 0.665436
#> 387: -6.140221 0.178157 -5.874843 1.200584 2.054489 -1.579492 0.830860 2.387315 0.842648 0.183411 0.011162 0.665675
#> 388: -6.140366 0.178246 -5.875190 1.200606 2.054653 -1.579492 0.830858 2.387314 0.843840 0.183192 0.011190 0.665911
#> 389: -6.140925 0.178421 -5.875596 1.200651 2.054784 -1.579492 0.830859 2.387314 0.845008 0.183062 0.011190 0.666167
#> 390: -6.141427 0.178460 -5.876042 1.200704 2.054883 -1.579492 0.830859 2.387313 0.845693 0.182972 0.011203 0.666403
#> 391: -6.142777 0.178517 -5.876421 1.200701 2.055008 -1.579492 0.830858 2.387313 0.847730 0.182746 0.011233 0.666633
#> 392: -6.143989 0.178695 -5.876533 1.200701 2.055110 -1.579492 0.830858 2.387312 0.849540 0.182784 0.011235 0.666884
#> 393: -6.144962 0.178799 -5.876644 1.200715 2.055177 -1.579492 0.830858 2.387312 0.851905 0.182668 0.011245 0.667118
#> 394: -6.145093 0.178740 -5.876876 1.200684 2.055127 -1.579492 0.830856 2.387312 0.852005 0.182574 0.011260 0.667358
#> 395: -6.145696 0.178815 -5.876935 1.200657 2.055027 -1.579492 0.830854 2.387312 0.851843 0.182437 0.011268 0.667623
#> 396: -6.146140 0.178854 -5.876986 1.200661 2.055009 -1.579492 0.830857 2.387312 0.851916 0.182127 0.011276 0.667868
#> 397: -6.145810 0.178809 -5.877216 1.200669 2.054994 -1.579492 0.830858 2.387312 0.851486 0.181902 0.011284 0.668138
#> 398: -6.145360 0.178693 -5.877324 1.200648 2.055019 -1.579491 0.830858 2.387312 0.850883 0.181810 0.011272 0.668398
#> 399: -6.145428 0.178777 -5.877387 1.200627 2.055165 -1.579492 0.830858 2.387313 0.850639 0.181604 0.011275 0.668654
#> 400: -6.145031 0.178821 -5.877388 1.200609 2.055248 -1.579492 0.830857 2.387313 0.850573 0.181696 0.011289 0.668889
#> 401: -6.145925 0.179186 -5.877371 1.200609 2.055244 -1.579491 0.830856 2.387312 0.851643 0.181645 0.011307 0.669119
#> 402: -6.146838 0.179335 -5.877534 1.200624 2.055286 -1.579492 0.830856 2.387312 0.852291 0.181441 0.011313 0.669322
#> 403: -6.147098 0.179393 -5.877518 1.200607 2.055194 -1.579491 0.830856 2.387313 0.852506 0.181296 0.011311 0.669538
#> 404: -6.147371 0.179546 -5.877577 1.200576 2.055164 -1.579491 0.830857 2.387312 0.852174 0.181091 0.011307 0.669768
#> 405: -6.148736 0.179702 -5.877568 1.200570 2.055261 -1.579491 0.830857 2.387312 0.853850 0.180990 0.011297 0.669992
#> 406: -6.149501 0.179860 -5.877500 1.200580 2.055391 -1.579491 0.830857 2.387312 0.855034 0.181020 0.011293 0.670204
#> 407: -6.150580 0.179928 -5.877568 1.200637 2.055403 -1.579491 0.830856 2.387313 0.857183 0.181121 0.011273 0.670440
#> 408: -6.151903 0.180081 -5.877606 1.200674 2.055463 -1.579490 0.830855 2.387313 0.858199 0.181315 0.011255 0.670697
#> 409: -6.152836 0.180278 -5.877658 1.200679 2.055485 -1.579490 0.830855 2.387313 0.859181 0.181246 0.011274 0.670917
#> 410: -6.153281 0.180395 -5.877715 1.200682 2.055382 -1.579490 0.830855 2.387314 0.859627 0.181090 0.011284 0.671197
#> 411: -6.153972 0.180533 -5.877792 1.200664 2.055304 -1.579490 0.830854 2.387314 0.859758 0.180878 0.011271 0.671425
#> 412: -6.154445 0.180514 -5.877945 1.200668 2.055214 -1.579490 0.830854 2.387314 0.859553 0.180738 0.011250 0.671675
#> 413: -6.155711 0.180615 -5.878066 1.200693 2.055146 -1.579490 0.830852 2.387314 0.861316 0.180602 0.011266 0.671878
#> 414: -6.156575 0.180837 -5.878085 1.200703 2.055187 -1.579490 0.830853 2.387314 0.862491 0.180647 0.011286 0.672087
#> 415: -6.157931 0.180947 -5.878088 1.200709 2.055241 -1.579490 0.830854 2.387314 0.863377 0.180856 0.011294 0.672270
#> 416: -6.158198 0.181204 -5.878116 1.200714 2.055297 -1.579490 0.830854 2.387314 0.863566 0.181034 0.011297 0.672484
#> 417: -6.159327 0.181374 -5.878110 1.200708 2.055298 -1.579490 0.830855 2.387314 0.863950 0.180901 0.011313 0.672723
#> 418: -6.160794 0.181616 -5.878291 1.200733 2.055318 -1.579490 0.830854 2.387314 0.865153 0.181069 0.011292 0.672911
#> 419: -6.162256 0.181726 -5.878452 1.200749 2.055451 -1.579491 0.830854 2.387314 0.866759 0.181001 0.011282 0.673143
#> 420: -6.163162 0.181932 -5.878477 1.200738 2.055514 -1.579490 0.830855 2.387314 0.867608 0.180865 0.011265 0.673350
#> 421: -6.163450 0.182135 -5.878474 1.200725 2.055650 -1.579490 0.830855 2.387314 0.867744 0.180763 0.011267 0.673591
#> 422: -6.163795 0.182280 -5.878439 1.200749 2.055812 -1.579490 0.830855 2.387314 0.867700 0.180682 0.011265 0.673803
#> 423: -6.164692 0.182347 -5.878637 1.200760 2.055883 -1.579490 0.830856 2.387314 0.868826 0.180556 0.011257 0.674022
#> 424: -6.164858 0.182136 -5.878807 1.200779 2.055841 -1.579490 0.830858 2.387314 0.869351 0.180367 0.011265 0.674235
#> 425: -6.165271 0.182228 -5.878899 1.200826 2.055865 -1.579490 0.830858 2.387314 0.870201 0.180083 0.011255 0.674456
#> 426: -6.165668 0.182418 -5.878929 1.200851 2.055866 -1.579490 0.830858 2.387314 0.870429 0.179998 0.011243 0.674677
#> 427: -6.166103 0.182539 -5.878918 1.200880 2.055903 -1.579490 0.830857 2.387314 0.870426 0.179795 0.011233 0.674967
#> 428: -6.166646 0.183016 -5.878941 1.200887 2.055998 -1.579490 0.830855 2.387314 0.871483 0.179534 0.011240 0.675203
#> 429: -6.167115 0.183133 -5.879023 1.200871 2.056047 -1.579490 0.830855 2.387313 0.871724 0.179406 0.011246 0.675391
#> 430: -6.167605 0.183201 -5.879113 1.200868 2.056031 -1.579490 0.830855 2.387313 0.871642 0.179330 0.011262 0.675579
#> 431: -6.168522 0.183336 -5.879092 1.200855 2.056111 -1.579490 0.830855 2.387313 0.872489 0.179261 0.011274 0.675761
#> 432: -6.168937 0.183313 -5.879121 1.200846 2.056208 -1.579490 0.830856 2.387313 0.873366 0.179304 0.011283 0.675944
#> 433: -6.170052 0.183358 -5.879173 1.200848 2.056169 -1.579490 0.830855 2.387313 0.875655 0.179130 0.011287 0.676118
#> 434: -6.170614 0.183206 -5.879279 1.200846 2.056123 -1.579490 0.830855 2.387313 0.877458 0.178922 0.011286 0.676295
#> 435: -6.171766 0.183320 -5.879239 1.200866 2.056135 -1.579490 0.830856 2.387313 0.879293 0.178757 0.011272 0.676482
#> 436: -6.172472 0.183375 -5.879317 1.200848 2.056191 -1.579490 0.830855 2.387313 0.880316 0.178580 0.011268 0.676648
#> 437: -6.173349 0.183520 -5.879396 1.200855 2.056230 -1.579490 0.830855 2.387313 0.881096 0.178468 0.011275 0.676831
#> 438: -6.174284 0.183871 -5.879396 1.200841 2.056375 -1.579490 0.830855 2.387313 0.882702 0.178449 0.011276 0.677038
#> 439: -6.174683 0.184041 -5.879447 1.200846 2.056609 -1.579490 0.830855 2.387313 0.883002 0.178545 0.011299 0.677195
#> 440: -6.175346 0.184352 -5.879375 1.200834 2.056633 -1.579490 0.830855 2.387314 0.883707 0.178527 0.011302 0.677364
#> 441: -6.175870 0.184456 -5.879349 1.200819 2.056671 -1.579490 0.830855 2.387314 0.883608 0.178619 0.011299 0.677563
#> 442: -6.176289 0.184580 -5.879366 1.200806 2.056744 -1.579490 0.830855 2.387314 0.883310 0.178538 0.011294 0.677756
#> 443: -6.176523 0.184700 -5.879410 1.200811 2.056720 -1.579490 0.830855 2.387314 0.883064 0.178535 0.011274 0.677941
#> 444: -6.177131 0.184865 -5.879399 1.200832 2.056783 -1.579490 0.830855 2.387314 0.884506 0.178447 0.011252 0.678119
#> 445: -6.178670 0.184912 -5.879441 1.200847 2.056757 -1.579490 0.830854 2.387314 0.885996 0.178483 0.011240 0.678274
#> 446: -6.180276 0.185141 -5.879503 1.200849 2.056778 -1.579490 0.830854 2.387314 0.887537 0.178447 0.011233 0.678445
#> 447: -6.181375 0.185433 -5.879506 1.200830 2.056767 -1.579490 0.830855 2.387314 0.888009 0.178287 0.011236 0.678629
#> 448: -6.182060 0.185640 -5.879499 1.200832 2.056797 -1.579490 0.830855 2.387314 0.888496 0.178187 0.011228 0.678789
#> 449: -6.182388 0.185733 -5.879460 1.200831 2.056906 -1.579490 0.830854 2.387314 0.889697 0.178059 0.011231 0.678986
#> 450: -6.182682 0.185817 -5.879522 1.200841 2.057031 -1.579490 0.830855 2.387314 0.889598 0.177962 0.011249 0.679156
#> 451: -6.182457 0.185871 -5.879552 1.200847 2.057237 -1.579490 0.830855 2.387314 0.889303 0.177825 0.011270 0.679344
#> 452: -6.183075 0.186100 -5.879636 1.200846 2.057353 -1.579490 0.830855 2.387314 0.889293 0.177835 0.011286 0.679526
#> 453: -6.183884 0.186359 -5.879632 1.200838 2.057438 -1.579490 0.830856 2.387314 0.889883 0.177755 0.011281 0.679691
#> 454: -6.184640 0.186508 -5.879677 1.200857 2.057524 -1.579490 0.830855 2.387314 0.889447 0.177802 0.011269 0.679846
#> 455: -6.185347 0.186704 -5.879688 1.200853 2.057537 -1.579490 0.830855 2.387314 0.889752 0.177786 0.011253 0.680029
#> 456: -6.186170 0.186979 -5.879702 1.200847 2.057559 -1.579490 0.830855 2.387314 0.890002 0.177677 0.011248 0.680197
#> 457: -6.186798 0.187114 -5.879713 1.200851 2.057633 -1.579490 0.830856 2.387314 0.890504 0.177843 0.011247 0.680359
#> 458: -6.187041 0.187211 -5.879694 1.200857 2.057790 -1.579490 0.830856 2.387314 0.891333 0.177818 0.011236 0.680504
#> 459: -6.187394 0.187298 -5.879688 1.200865 2.057871 -1.579490 0.830856 2.387314 0.892181 0.177778 0.011219 0.680667
#> 460: -6.188005 0.187404 -5.879720 1.200860 2.057906 -1.579490 0.830857 2.387314 0.892554 0.177796 0.011207 0.680812
#> 461: -6.188131 0.187614 -5.879743 1.200851 2.057962 -1.579490 0.830857 2.387315 0.892711 0.177648 0.011209 0.680981
#> 462: -6.188725 0.187779 -5.879719 1.200855 2.057923 -1.579490 0.830857 2.387315 0.893415 0.177511 0.011217 0.681145
#> 463: -6.189685 0.187898 -5.879719 1.200857 2.057915 -1.579490 0.830857 2.387315 0.894260 0.177459 0.011215 0.681281
#> 464: -6.190744 0.188007 -5.879703 1.200852 2.057937 -1.579490 0.830858 2.387314 0.895977 0.177360 0.011228 0.681427
#> 465: -6.191259 0.188020 -5.879724 1.200856 2.057910 -1.579489 0.830858 2.387314 0.896649 0.177185 0.011241 0.681603
#> 466: -6.191545 0.188207 -5.879742 1.200860 2.058006 -1.579490 0.830858 2.387315 0.896558 0.177017 0.011260 0.681758
#> 467: -6.191373 0.188286 -5.879739 1.200854 2.058021 -1.579490 0.830858 2.387315 0.897293 0.176865 0.011273 0.681952
#> 468: -6.191634 0.188443 -5.879753 1.200857 2.058119 -1.579490 0.830858 2.387315 0.898326 0.176726 0.011285 0.682123
#> 469: -6.192186 0.188437 -5.879743 1.200852 2.058278 -1.579490 0.830859 2.387315 0.899635 0.176512 0.011303 0.682297
#> 470: -6.192971 0.188718 -5.879724 1.200862 2.058366 -1.579490 0.830859 2.387315 0.900616 0.176479 0.011320 0.682441
#> 471: -6.193860 0.188904 -5.879756 1.200866 2.058428 -1.579490 0.830858 2.387315 0.901429 0.176393 0.011322 0.682586
#> 472: -6.194394 0.189112 -5.879751 1.200867 2.058512 -1.579490 0.830858 2.387315 0.901913 0.176267 0.011336 0.682724
#> 473: -6.194880 0.189203 -5.879779 1.200865 2.058530 -1.579490 0.830858 2.387315 0.902779 0.176116 0.011348 0.682863
#> 474: -6.195162 0.189273 -5.879789 1.200862 2.058520 -1.579490 0.830858 2.387314 0.903560 0.175994 0.011358 0.683025
#> 475: -6.195068 0.189251 -5.879811 1.200874 2.058607 -1.579490 0.830858 2.387314 0.903593 0.176087 0.011375 0.683166
#> 476: -6.195441 0.189389 -5.879799 1.200874 2.058682 -1.579490 0.830858 2.387314 0.903494 0.176200 0.011377 0.683306
#> 477: -6.195697 0.189586 -5.879792 1.200875 2.058734 -1.579490 0.830859 2.387314 0.903958 0.176198 0.011371 0.683463
#> 478: -6.196177 0.189769 -5.879784 1.200883 2.058860 -1.579490 0.830859 2.387314 0.904497 0.176180 0.011381 0.683607
#> 479: -6.196587 0.189817 -5.879786 1.200890 2.058826 -1.579490 0.830859 2.387314 0.905260 0.175991 0.011377 0.683735
#> 480: -6.196811 0.189934 -5.879794 1.200889 2.058989 -1.579490 0.830859 2.387314 0.906125 0.175830 0.011400 0.683872
#> 481: -6.196594 0.189908 -5.879829 1.200891 2.059043 -1.579490 0.830859 2.387314 0.905836 0.175600 0.011407 0.684019
#> 482: -6.196842 0.189647 -5.879847 1.200890 2.059069 -1.579490 0.830859 2.387314 0.905986 0.175579 0.011407 0.684176
#> 483: -6.197460 0.189626 -5.879854 1.200888 2.059084 -1.579490 0.830859 2.387314 0.906125 0.175455 0.011418 0.684327
#> 484: -6.197804 0.189899 -5.879826 1.200892 2.059137 -1.579490 0.830859 2.387314 0.906452 0.175295 0.011429 0.684467
#> 485: -6.198453 0.190083 -5.879826 1.200894 2.059129 -1.579490 0.830859 2.387314 0.907069 0.175111 0.011430 0.684621
#> 486: -6.198856 0.190081 -5.879843 1.200900 2.059068 -1.579490 0.830859 2.387314 0.906844 0.174968 0.011431 0.684746
#> 487: -6.199473 0.190138 -5.879849 1.200903 2.059011 -1.579490 0.830859 2.387314 0.906948 0.174815 0.011440 0.684882
#> 488: -6.199854 0.190322 -5.879834 1.200903 2.058928 -1.579490 0.830859 2.387314 0.907097 0.174644 0.011455 0.685011
#> 489: -6.200131 0.190539 -5.879852 1.200900 2.058997 -1.579490 0.830859 2.387314 0.907821 0.174548 0.011457 0.685137
#> 490: -6.200349 0.190702 -5.879879 1.200905 2.059038 -1.579490 0.830859 2.387314 0.908038 0.174420 0.011470 0.685282
#> 491: -6.201074 0.190752 -5.879894 1.200905 2.059042 -1.579490 0.830860 2.387314 0.909186 0.174281 0.011480 0.685406
#> 492: -6.201215 0.190804 -5.879886 1.200901 2.059043 -1.579490 0.830860 2.387314 0.908662 0.174201 0.011505 0.685535
#> 493: -6.201787 0.190948 -5.879898 1.200904 2.058984 -1.579490 0.830860 2.387314 0.908998 0.174062 0.011514 0.685661
#> 494: -6.202129 0.191016 -5.879918 1.200907 2.059039 -1.579490 0.830860 2.387314 0.909021 0.174020 0.011517 0.685766
#> 495: -6.202744 0.191175 -5.879915 1.200911 2.059126 -1.579490 0.830860 2.387314 0.909702 0.174028 0.011519 0.685903
#> 496: -6.203025 0.191428 -5.879908 1.200903 2.059216 -1.579490 0.830860 2.387314 0.909762 0.174049 0.011513 0.686040
#> 497: -6.203383 0.191487 -5.879919 1.200903 2.059258 -1.579490 0.830860 2.387314 0.909814 0.174040 0.011509 0.686174
#> 498: -6.203699 0.191535 -5.879915 1.200896 2.059282 -1.579490 0.830860 2.387314 0.909695 0.173908 0.011511 0.686304
#> 499: -6.203989 0.191612 -5.879893 1.200889 2.059334 -1.579490 0.830860 2.387314 0.909469 0.173669 0.011505 0.686468
#> 500: -6.204474 0.191575 -5.879888 1.200884 2.059361 -1.579490 0.830860 2.387314 0.910054 0.173555 0.011493 0.686604
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## Add cwres/npde after fit
fit <- fit %>% addCwres() %>% addNpde()
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plot(fit) ## Standard nlmixr plots
################################################################################
## Xpose plots; Need to print otherwise running a script won't
## show xpose plots
################################################################################
xpdb <- xpose_data_nlmixr(fit) ## first convert to nlmixr object
print(dv_vs_pred(xpdb) +
ylab("Observed Nimotuzumab Concentrations (ug/mL)") +
xlab("Population Predicted Nimotuzumab Concentrations (ug/mL)"))
print(dv_vs_ipred(xpdb) +
ylab("Observed Nimotuzumab Concentrations (ug/mL)") +
xlab("Individual Predicted Nimotuzumab Concentrations (ug/mL)"))
print(res_vs_pred(xpdb) +
ylab("Conditional Weighted Residuals") +
xlab("Population Predicted Nimotuzumab Concentrations (ug/mL)"))
print(res_vs_idv(xpdb) +
ylab("Conditional Weighted Residuals") +
xlab("Time (h)"))
print(prm_vs_iteration(xpdb))
print(absval_res_vs_idv(xpdb, res = 'IWRES') +
ylab("Individual Weighted Residuals") +
xlab("Time (h)"))
print(absval_res_vs_pred(xpdb, res = 'IWRES') +
ylab("Individual Weighted Residuals") +
xlab("Population Predicted Nimotuzumab Concentrations (ug/mL)"))
print(ind_plots(xpdb, nrow=3, ncol=4) +
ylab("Predicted and Observed Nimotuzumab concentrations (ug/mL)") +
xlab("Time (h)"))
print(res_distrib(xpdb) +
ylab("Density") +
xlab("Conditional Weighted Residuals"))
################################################################################
##Visual Predictive Checks
################################################################################
vpcPlot(fit,n=500,stratify=c("DOS"), show=list(obs_dv=T),
bins = c(-0.5,0,25,75,100,200,400,600,750,900,1100,1200,1400,1600,1900,2150,2300),
ylab = "Nimotuzumab Concentrations (ug/mL)", xlab = "Time (h)")
vpcPlot(fit,n=500, show=list(obs_dv=T),
bins = c(-0.5,0,25,75,100,200,400,600,750,900,1100,1200,1400,1600,1900,2150,2300),
ylab = "Nimotuzumab Concentrations (ug/mL)", xlab = "Time (h)")