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: -6.914482 0.016474 -5.493299 3.953329 2.781526 -1.308564 -0.246181 2.169817 1.900000 1.900000 2.449522 1.484619
#> 002: -6.819436 0.343715 -5.470699 3.814344 3.002895 -1.190431 -0.374498 2.301739 1.805000 1.805000 2.327046 0.802331
#> 003: -6.582867 0.353952 -5.512010 3.801872 2.952968 -1.306888 -0.245627 2.338586 1.714750 1.714750 2.210693 0.705040
#> 004: -6.728009 0.289825 -5.339309 3.975293 2.845173 -1.626509 -0.332403 2.301086 1.629012 1.629012 2.100159 0.680643
#> 005: -6.618628 0.356340 -5.324386 4.103812 2.871893 -1.504798 -0.291670 2.145594 1.547562 1.547562 1.995151 0.664037
#> 006: -6.837136 0.348125 -5.241727 4.200836 2.748498 -1.585960 -0.238234 2.176533 1.470184 1.470184 1.896834 0.667170
#> 007: -6.741281 0.250508 -5.291013 4.178116 2.849688 -1.532423 -0.410910 2.207508 1.396675 1.396675 1.801992 0.666620
#> 008: -6.855104 0.287385 -5.320877 4.114158 2.710457 -1.625941 -0.286789 2.223673 1.395116 1.326841 2.001486 0.660569
#> 009: -6.530282 0.273822 -5.378142 3.913521 2.831565 -1.567159 -0.132779 2.117732 1.325360 1.260499 1.901411 0.656455
#> 010: -6.661594 0.384447 -5.403747 3.816714 2.854113 -1.538320 -0.103166 2.217243 1.259092 1.197474 1.806341 0.657697
#> 011: -6.684598 0.329975 -5.399798 3.828264 2.940350 -1.545483 -0.010219 2.314174 1.234165 1.137600 1.716024 0.667492
#> 012: -6.588625 0.359245 -5.300847 3.793875 3.044952 -1.562746 0.085883 2.391274 1.330653 1.080720 1.933127 0.662020
#> 013: -6.704110 0.345852 -5.394675 3.804468 3.060335 -1.523339 0.102024 2.370731 1.264121 1.026684 1.861993 0.661558
#> 014: -6.729996 0.284292 -5.364095 3.860207 3.111585 -1.396802 0.073807 2.215396 1.412781 0.975350 1.768893 0.661614
#> 015: -6.818633 0.240150 -5.369279 4.035203 2.996029 -1.467952 0.132409 2.283729 1.463639 0.926582 1.680449 0.655655
#> 016: -6.918713 0.299213 -5.383584 4.082332 3.067859 -1.324230 0.040918 2.200035 1.487904 0.880253 1.596426 0.669805
#> 017: -6.809761 0.295317 -5.401558 3.844066 3.095869 -1.344422 0.145221 2.127343 1.413509 0.836241 1.516605 0.673400
#> 018: -6.865311 0.313463 -5.334817 3.819778 3.101805 -1.390841 0.141473 2.149978 1.342833 0.794429 1.440775 0.671659
#> 019: -6.846406 0.281306 -5.340926 3.669133 3.084536 -1.300504 0.133551 2.168557 1.275691 0.754707 1.368736 0.667459
#> 020: -6.849124 0.279594 -5.308830 3.736926 2.957913 -1.358374 0.232499 2.182700 1.211907 0.716972 1.300299 0.668514
#> 021: -7.061192 0.267195 -5.320240 3.698222 2.790875 -1.370177 0.266964 2.322090 1.151312 0.681123 1.235284 0.662466
#> 022: -7.224031 0.321864 -5.240993 3.794683 2.804530 -1.469822 0.278856 2.373900 1.475546 0.647067 1.173520 0.668582
#> 023: -7.233900 0.270104 -5.218276 3.744525 2.791887 -1.434262 0.254848 2.335459 1.401768 0.614714 1.114844 0.663759
#> 024: -7.229964 0.250526 -5.269407 3.706237 2.799937 -1.386859 0.185029 2.287496 1.433516 0.583978 1.113109 0.664701
#> 025: -7.105193 0.275289 -5.160335 3.861715 2.756977 -1.501375 0.174402 2.288972 1.361840 0.554779 1.057454 0.664838
#> 026: -7.191734 0.289017 -5.213754 3.837710 2.768048 -1.482197 0.143706 2.250098 1.293748 0.527040 1.004581 0.663593
#> 027: -7.111995 0.247283 -5.234289 3.863042 2.690533 -1.534585 0.189780 2.255539 1.229061 0.500688 0.954352 0.660438
#> 028: -7.137182 0.317031 -5.326907 3.936494 2.643802 -1.498281 0.162903 2.221112 1.287245 0.475654 0.906634 0.664100
#> 029: -7.065910 0.298181 -5.301461 4.129367 2.651502 -1.496702 0.176391 2.258657 1.531178 0.451871 1.142894 0.671430
#> 030: -7.081589 0.279400 -5.288630 4.041575 2.540978 -1.538153 0.189543 2.301692 1.454619 0.429278 1.085750 0.664394
#> 031: -7.345401 0.280522 -5.285089 3.856727 2.501656 -1.456653 0.123601 2.244742 1.582745 0.407814 1.031462 0.671167
#> 032: -7.330787 0.284799 -5.293881 3.732114 2.417886 -1.400980 0.205017 2.229669 1.503608 0.387423 0.979889 0.669425
#> 033: -7.224964 0.302803 -5.350354 3.672262 2.441714 -1.393232 0.313490 2.257816 1.601775 0.368052 0.930895 0.666949
#> 034: -7.175344 0.301502 -5.313417 3.580642 2.559157 -1.516492 0.285321 2.163593 1.755554 0.349649 0.884350 0.665502
#> 035: -7.150417 0.329565 -5.314110 3.578594 2.628034 -1.546253 0.243321 2.176913 1.667776 0.332167 0.908735 0.671639
#> 036: -6.918253 0.249159 -5.254137 3.631880 2.710284 -1.549101 0.187823 2.175748 1.584387 0.315558 0.863298 0.666407
#> 037: -7.091180 0.228291 -5.209337 3.554362 2.798050 -1.540088 0.209591 2.169958 1.634782 0.299781 0.820133 0.662823
#> 038: -7.095036 0.286148 -5.251850 3.586294 2.735655 -1.446276 0.232623 2.153432 2.053092 0.284791 0.779127 0.658274
#> 039: -7.113119 0.287339 -5.261290 3.558021 2.655369 -1.407257 0.179161 2.172111 1.950437 0.302287 0.740170 0.663073
#> 040: -7.162952 0.364008 -5.230255 3.576343 2.719708 -1.466499 0.182905 2.165589 2.269271 0.305775 0.703162 0.666826
#> 041: -7.263707 0.292009 -5.220779 3.531752 2.622960 -1.437846 0.181075 2.176548 2.348641 0.290487 0.668004 0.671097
#> 042: -7.226501 0.264484 -5.260884 3.476615 2.652070 -1.398807 0.179380 2.088141 2.231209 0.275962 0.634604 0.671719
#> 043: -7.087759 0.305624 -5.306365 3.514786 2.589153 -1.334986 0.134143 1.989949 2.119648 0.262164 0.602873 0.658616
#> 044: -7.231224 0.289672 -5.357232 3.461051 2.533159 -1.312052 0.158429 1.982562 2.013666 0.249056 0.572730 0.656291
#> 045: -7.163111 0.315924 -5.325022 3.542982 2.582322 -1.294601 0.104496 1.906099 1.912982 0.236603 0.643810 0.666197
#> 046: -7.313343 0.268235 -5.292604 3.483319 2.565969 -1.161746 0.059350 1.872730 1.817333 0.227179 0.766983 0.662443
#> 047: -7.071555 0.286481 -5.319568 3.441684 2.789278 -1.148521 0.052185 1.815530 1.726467 0.215820 0.959460 0.661594
#> 048: -7.047720 0.310923 -5.363941 3.501217 2.836546 -1.044215 -0.000468 1.805442 1.640143 0.205029 1.013723 0.666942
#> 049: -7.044512 0.377444 -5.325346 3.480065 2.918906 -1.071962 0.049540 1.814141 1.826520 0.213857 0.963037 0.666954
#> 050: -6.997297 0.340865 -5.245277 3.542043 3.078940 -1.216829 0.022206 1.830944 1.854632 0.251955 1.011387 0.663225
#> 051: -7.043409 0.305549 -5.211207 3.557447 3.007410 -1.268743 0.040444 1.803441 1.761900 0.239358 0.960818 0.667913
#> 052: -7.073907 0.360382 -5.306185 3.688925 3.090221 -1.319321 0.083892 1.758843 1.864628 0.227390 0.960415 0.674531
#> 053: -7.240278 0.299172 -5.321606 3.731697 2.993008 -1.428530 0.124909 1.801623 2.038873 0.237377 0.947057 0.672320
#> 054: -7.172902 0.356635 -5.317032 3.715849 3.064195 -1.367736 0.113503 1.749145 1.936930 0.283826 0.899704 0.662308
#> 055: -7.172379 0.359853 -5.341980 3.784723 3.012051 -1.438815 0.149270 1.758675 1.840083 0.300613 0.854719 0.660637
#> 056: -7.219676 0.382484 -5.307379 3.856501 2.987322 -1.424209 0.114850 1.725127 1.796002 0.285583 0.811983 0.662091
#> 057: -7.588019 0.382999 -5.380854 3.879877 2.942696 -1.423378 0.117995 1.712175 2.008233 0.271303 0.771384 0.662284
#> 058: -7.639869 0.414939 -5.299922 3.810096 2.966009 -1.439728 0.101300 1.685914 2.088644 0.271681 0.732815 0.663788
#> 059: -7.839156 0.381269 -5.459183 3.773137 2.834983 -1.381692 0.119364 1.644283 2.152469 0.280777 0.696174 0.657387
#> 060: -7.655245 0.345142 -5.601210 3.727992 2.873847 -1.254458 0.131665 1.596283 2.044846 0.266738 0.661365 0.667663
#> 061: -7.707903 0.406734 -5.624838 3.773104 2.937255 -1.271140 0.117227 1.606912 2.000826 0.253648 0.643277 0.672645
#> 062: -7.675870 0.346736 -5.500956 3.814468 2.895095 -1.250650 0.132157 1.670900 2.132835 0.240966 0.634200 0.669149
#> 063: -7.670482 0.318380 -5.440615 3.818260 2.866578 -1.296139 0.138641 1.699365 2.026193 0.228917 0.607845 0.665058
#> 064: -7.431745 0.337815 -5.453761 3.865966 2.897381 -1.360831 0.124382 1.651176 1.924884 0.233984 0.577453 0.663534
#> 065: -7.529399 0.323797 -5.471688 3.798697 2.843363 -1.428387 0.116370 1.643224 2.041775 0.222285 0.548580 0.654007
#> 066: -7.325511 0.344051 -5.386737 3.778785 2.789880 -1.460946 0.096865 1.679771 2.006639 0.233688 0.521151 0.660227
#> 067: -7.330396 0.387743 -5.378663 3.769411 2.868637 -1.481350 0.083651 1.654957 1.906307 0.231272 0.510413 0.660347
#> 068: -7.339606 0.278427 -5.283691 3.753403 2.838913 -1.543627 0.084818 1.639113 1.810992 0.219708 0.484892 0.659440
#> 069: -7.285998 0.325719 -5.328522 3.748840 2.835668 -1.557553 0.092835 1.609421 1.720442 0.235109 0.499206 0.662063
#> 070: -7.232980 0.208826 -5.433208 3.663195 2.783737 -1.543189 0.085950 1.547160 1.634420 0.231917 0.474246 0.660770
#> 071: -7.381829 0.257745 -5.397206 3.643190 2.659883 -1.498516 0.069657 1.533203 1.552699 0.232615 0.450534 0.661169
#> 072: -7.266482 0.244138 -5.375615 3.676924 2.712292 -1.517724 0.042189 1.522265 1.695883 0.220984 0.428007 0.667300
#> 073: -7.145767 0.288511 -5.284307 3.658542 2.744943 -1.525432 0.095375 1.516115 1.842879 0.220219 0.406607 0.661996
#> 074: -7.188289 0.299592 -5.319425 3.681416 2.834873 -1.519843 0.137359 1.530411 1.907210 0.209208 0.400598 0.666512
#> 075: -7.243984 0.311252 -5.368692 3.691760 2.917381 -1.481587 0.149748 1.544855 1.856001 0.231087 0.416226 0.667799
#> 076: -7.103642 0.339213 -5.362342 3.635621 2.887099 -1.462164 0.122680 1.518757 1.763201 0.248580 0.395415 0.658367
#> 077: -7.112888 0.314604 -5.350759 3.688364 2.854637 -1.459558 0.154870 1.554377 1.675041 0.236151 0.380255 0.670290
#> 078: -7.209884 0.305611 -5.477977 3.704058 2.907212 -1.499042 0.165185 1.517499 1.962122 0.258664 0.361243 0.665738
#> 079: -7.093237 0.353882 -5.426122 3.657542 2.915020 -1.506303 0.159974 1.553805 1.864016 0.267238 0.386769 0.660540
#> 080: -6.912129 0.327524 -5.510560 3.691050 2.931850 -1.474556 0.135650 1.570071 1.770815 0.253876 0.373227 0.665780
#> 081: -7.011220 0.303175 -5.423123 3.804970 2.858132 -1.509481 0.145057 1.575275 1.682274 0.247051 0.444266 0.663041
#> 082: -7.207427 0.343244 -5.526908 3.750491 2.801898 -1.550669 0.182372 1.527566 1.598161 0.234698 0.422053 0.668174
#> 083: -7.120697 0.355271 -5.609807 3.825232 2.778279 -1.510526 0.133588 1.552264 1.518253 0.222963 0.478913 0.668248
#> 084: -7.183620 0.330008 -5.556814 3.883674 2.645653 -1.520276 0.133748 1.566389 1.442340 0.215284 0.454967 0.672353
#> 085: -7.574003 0.354428 -5.486883 3.912608 2.566221 -1.548326 0.177366 1.591621 1.370223 0.221744 0.432219 0.663256
#> 086: -7.613886 0.283195 -5.450051 3.792734 2.523406 -1.573365 0.212699 1.645456 1.301712 0.210657 0.528409 0.659078
#> 087: -7.580677 0.265828 -5.484501 3.909558 2.472463 -1.589409 0.200232 1.617358 1.236626 0.200124 0.501988 0.669928
#> 088: -7.658087 0.265950 -5.563201 3.922337 2.549615 -1.590849 0.227490 1.584981 1.376016 0.202271 0.509928 0.675766
#> 089: -7.615280 0.336141 -5.577240 4.002995 2.644322 -1.600905 0.219738 1.585023 1.307216 0.210631 0.593184 0.660534
#> 090: -7.556934 0.334487 -5.543477 4.068602 2.615642 -1.624460 0.218679 1.581273 1.241855 0.276291 0.563525 0.663667
#> 091: -7.544171 0.396360 -5.526697 4.013822 2.618521 -1.656577 0.224565 1.561843 1.179762 0.311947 0.569798 0.666616
#> 092: -7.577851 0.386912 -5.481723 3.992882 2.631167 -1.651791 0.169301 1.552511 1.120774 0.360128 0.742735 0.663697
#> 093: -7.635376 0.340918 -5.465015 3.903458 2.671358 -1.619445 0.125568 1.543128 1.064735 0.342122 0.948491 0.669139
#> 094: -7.753070 0.377136 -5.467659 3.770711 2.587448 -1.625564 0.130815 1.548841 1.011499 0.335252 0.901067 0.663105
#> 095: -7.864931 0.360429 -5.433170 3.760934 2.509518 -1.657168 0.095246 1.550648 1.030129 0.318489 0.856014 0.665222
#> 096: -7.780223 0.314070 -5.417875 3.725360 2.446114 -1.666749 0.103289 1.572967 1.033704 0.302565 0.813213 0.666981
#> 097: -7.621180 0.313678 -5.511474 3.738421 2.461147 -1.671815 0.071346 1.530011 0.982019 0.304409 0.772552 0.651483
#> 098: -7.753332 0.402724 -5.496057 3.773790 2.406169 -1.686588 0.063194 1.552017 0.932918 0.302956 0.733925 0.662169
#> 099: -7.730195 0.420811 -5.309360 3.803750 2.523807 -1.709883 0.047775 1.572759 0.886272 0.303144 0.697228 0.668703
#> 100: -7.673505 0.347550 -5.297369 3.804835 2.594129 -1.687138 0.069714 1.543184 0.841958 0.296905 0.685734 0.668012
#> 101: -7.590033 0.336415 -5.340594 3.843439 2.595867 -1.732812 0.070029 1.510660 0.799860 0.282059 0.729189 0.666109
#> 102: -7.536486 0.324112 -5.350863 3.857390 2.561865 -1.748387 0.084014 1.487371 0.759867 0.267957 0.847870 0.661980
#> 103: -7.519646 0.269210 -5.300323 3.883000 2.544636 -1.733365 0.069103 1.536515 0.721874 0.254559 1.126673 0.667395
#> 104: -7.715542 0.261755 -5.264686 3.810420 2.517687 -1.715137 0.090898 1.499392 0.685780 0.241831 1.070339 0.666428
#> 105: -7.561154 0.307131 -5.250161 3.820197 2.700990 -1.753600 0.079310 1.507287 0.651491 0.245273 1.155401 0.672682
#> 106: -7.605518 0.269108 -5.233835 3.775668 2.800074 -1.664324 0.043972 1.502847 0.618917 0.271829 1.310986 0.669825
#> 107: -7.518702 0.254964 -5.292088 3.905229 2.664754 -1.666309 0.030991 1.499479 0.619284 0.258238 1.245436 0.672548
#> 108: -7.493037 0.327960 -5.309814 3.927044 2.640432 -1.668852 0.009886 1.483506 0.588320 0.245326 1.292697 0.668058
#> 109: -7.361666 0.299332 -5.246063 3.928822 2.838836 -1.665274 -0.015314 1.497702 0.558904 0.233060 1.742785 0.661541
#> 110: -7.295420 0.324685 -5.250351 3.891413 2.851265 -1.692870 0.000274 1.486403 0.530959 0.263463 1.655646 0.664391
#> 111: -7.388781 0.327422 -5.276343 3.876659 2.827125 -1.662853 -0.002417 1.451375 0.504411 0.266527 1.572864 0.660158
#> 112: -7.315082 0.287329 -5.329679 3.822851 2.796913 -1.621366 0.002984 1.450101 0.535833 0.283879 1.494220 0.652598
#> 113: -7.210165 0.325424 -5.250378 3.767372 2.797469 -1.646338 0.015555 1.483660 0.513687 0.269685 1.419509 0.658716
#> 114: -7.229060 0.311440 -5.283707 3.828202 2.701979 -1.638494 0.030416 1.496578 0.705375 0.256201 1.348534 0.660667
#> 115: -7.182975 0.278153 -5.209097 3.775709 2.774494 -1.642455 0.045452 1.501060 0.670106 0.254576 1.286011 0.667253
#> 116: -7.202891 0.198060 -5.190446 3.794787 2.846953 -1.666827 0.038917 1.495475 0.636601 0.243178 1.501925 0.666128
#> 117: -7.329950 0.242328 -5.235329 3.839577 2.723103 -1.670512 0.017016 1.499066 0.604771 0.297675 1.426829 0.672605
#> 118: -7.368418 0.292244 -5.219909 3.744965 2.557378 -1.618824 0.033437 1.502116 0.574532 0.282791 1.355487 0.663629
#> 119: -7.214748 0.319861 -5.259522 3.693077 2.567002 -1.654345 0.053655 1.520610 0.545806 0.268652 1.287713 0.667974
#> 120: -7.356994 0.350210 -5.309903 3.714522 2.674943 -1.668949 0.032518 1.520104 0.536936 0.255219 1.223327 0.674938
#> 121: -7.310281 0.325514 -5.336143 3.782335 2.730752 -1.681865 0.072384 1.521064 0.510090 0.242458 1.368272 0.675528
#> 122: -7.343814 0.299105 -5.464185 3.798791 2.580431 -1.638865 0.034002 1.513645 0.537844 0.230335 1.422966 0.673910
#> 123: -7.297533 0.309766 -5.395394 3.860489 2.618419 -1.626384 0.030686 1.514271 0.510952 0.233347 1.351817 0.671054
#> 124: -7.193157 0.364008 -5.390127 3.826152 2.522587 -1.648797 0.031153 1.519168 0.485404 0.251616 1.464952 0.665486
#> 125: -7.218728 0.314165 -5.297563 3.791521 2.509877 -1.683403 0.002274 1.563709 0.461134 0.239035 1.481559 0.676300
#> 126: -7.160883 0.315493 -5.263577 3.832437 2.672681 -1.673098 -0.012239 1.539009 0.568150 0.227083 1.407481 0.663111
#> 127: -7.163772 0.277754 -5.209825 3.873475 2.705128 -1.636695 -0.104885 1.533586 0.551445 0.218256 1.733728 0.671953
#> 128: -7.112813 0.239777 -5.211748 3.915861 2.608392 -1.662354 -0.130458 1.536360 0.523873 0.228442 1.647042 0.666048
#> 129: -7.180114 0.306451 -5.180583 3.881843 2.689900 -1.674028 -0.158249 1.526649 0.497679 0.270581 1.798513 0.662745
#> 130: -7.111239 0.366745 -5.187334 3.749547 2.804547 -1.691692 -0.155969 1.543169 0.549222 0.257052 1.814970 0.660076
#> 131: -7.017072 0.293180 -5.150603 3.854051 2.779081 -1.735148 -0.150071 1.549946 0.524854 0.244199 1.934384 0.659852
#> 132: -7.134799 0.329736 -5.153560 3.886799 2.648047 -1.775115 -0.145195 1.523241 0.498612 0.231989 1.845650 0.667284
#> 133: -6.995189 0.258434 -5.148432 3.816437 2.698910 -1.766222 -0.157406 1.519524 0.473681 0.220390 1.753367 0.663261
#> 134: -6.919090 0.253737 -5.284208 3.900886 2.684117 -1.652343 -0.149895 1.525732 0.449997 0.209370 1.665699 0.671709
#> 135: -6.986639 0.287619 -5.279714 3.878806 2.567078 -1.604463 -0.147210 1.536112 0.427497 0.229619 1.582414 0.662533
#> 136: -7.066493 0.325394 -5.293950 4.040700 2.614074 -1.625336 -0.167162 1.530326 0.406122 0.268301 1.503293 0.665947
#> 137: -6.951282 0.362174 -5.239351 3.973070 2.757953 -1.649086 -0.184241 1.498994 0.385816 0.254886 1.428129 0.660269
#> 138: -6.963707 0.354554 -5.209773 4.032075 2.818874 -1.588612 -0.186842 1.496276 0.366525 0.294496 1.356722 0.663401
#> 139: -6.921696 0.388580 -5.185394 3.955198 2.890466 -1.609874 -0.203804 1.504212 0.348199 0.312621 1.288886 0.666278
#> 140: -6.908138 0.380675 -5.266751 4.014870 2.953004 -1.583420 -0.189735 1.509598 0.330789 0.296990 1.243818 0.663811
#> 141: -6.754225 0.350511 -5.208675 4.051000 2.926469 -1.609166 -0.186481 1.517137 0.328475 0.282140 1.181627 0.657867
#> 142: -6.789293 0.307814 -5.297207 4.118640 2.932774 -1.635073 -0.188538 1.544762 0.312052 0.268033 1.185930 0.664649
#> 143: -6.823577 0.301436 -5.377798 4.018783 2.867539 -1.636593 -0.190189 1.517159 0.296449 0.321428 1.141547 0.658433
#> 144: -6.745211 0.387494 -5.313900 3.967272 2.824354 -1.610766 -0.185932 1.544770 0.281627 0.305356 1.105945 0.663428
#> 145: -6.528921 0.375596 -5.290895 4.080892 3.029239 -1.572953 -0.185804 1.535426 0.267545 0.311453 1.050648 0.667253
#> 146: -6.515166 0.342967 -5.354908 4.079100 3.063869 -1.573064 -0.197223 1.528802 0.303318 0.295881 1.095246 0.666587
#> 147: -6.482191 0.395980 -5.352293 4.144348 2.950902 -1.626264 -0.196328 1.555241 0.288152 0.305804 1.054109 0.667759
#> 148: -6.436935 0.348233 -5.322893 4.248489 2.843411 -1.626107 -0.200522 1.542432 0.273744 0.290514 1.001403 0.670078
#> 149: -6.464610 0.331942 -5.320880 3.911816 2.861399 -1.602902 -0.194779 1.546269 0.260057 0.275988 0.951333 0.665687
#> 150: -6.382175 0.298856 -5.367868 3.837603 2.938831 -1.610288 -0.204386 1.559655 0.271703 0.283664 0.903766 0.662113
#> 151: -6.471131 0.271042 -5.329659 3.788960 2.830587 -1.636315 -0.201760 1.585338 0.258118 0.297515 0.858578 0.659265
#> 152: -6.451226 0.273419 -5.268870 3.843862 2.761992 -1.644630 -0.194039 1.600684 0.208256 0.257844 0.716671 0.666523
#> 153: -6.486853 0.259362 -5.382011 3.904397 2.665264 -1.649768 -0.190338 1.597332 0.200105 0.232628 0.622717 0.665571
#> 154: -6.513257 0.217444 -5.289794 3.902728 2.585772 -1.669724 -0.196120 1.558978 0.203347 0.173057 0.401597 0.672208
#> 155: -6.463513 0.288071 -5.296245 3.853401 2.685523 -1.677810 -0.197416 1.578774 0.206721 0.191569 0.511092 0.658010
#> 156: -6.424735 0.289768 -5.227929 4.060901 2.595856 -1.691553 -0.195858 1.626379 0.212120 0.199707 0.437943 0.661257
#> 157: -6.437111 0.264291 -5.115213 4.084077 2.650002 -1.685681 -0.196643 1.615329 0.220888 0.202089 0.310153 0.654699
#> 158: -6.396430 0.298569 -5.230836 4.100050 2.767698 -1.677785 -0.190106 1.638621 0.139703 0.192802 0.333109 0.662221
#> 159: -6.394523 0.331959 -5.232099 4.274840 2.752179 -1.680634 -0.186828 1.638169 0.143472 0.215945 0.295831 0.662181
#> 160: -6.508765 0.310173 -5.344182 4.317062 2.748192 -1.660713 -0.176451 1.659913 0.146772 0.223736 0.317652 0.669867
#> 161: -6.451146 0.363151 -5.439934 4.379403 2.721551 -1.666758 -0.174653 1.677718 0.229344 0.219357 0.351610 0.663298
#> 162: -6.377784 0.372434 -5.432603 4.451006 2.549236 -1.654461 -0.183114 1.717399 0.157320 0.258113 0.238191 0.666623
#> 163: -6.399764 0.381543 -5.499056 4.303776 2.616415 -1.648346 -0.164355 1.701312 0.175666 0.304777 0.212564 0.660202
#> 164: -6.406619 0.357397 -5.495576 4.431315 2.579277 -1.620666 -0.156906 1.757044 0.118229 0.307628 0.203972 0.659701
#> 165: -6.484943 0.348162 -5.525846 4.416562 2.467224 -1.618712 -0.162456 1.756178 0.086671 0.267052 0.130309 0.661004
#> 166: -6.556071 0.331029 -5.448923 4.660439 2.467413 -1.643719 -0.152967 1.751351 0.055035 0.281619 0.122698 0.657432
#> 167: -6.510775 0.345007 -5.441888 4.452343 2.573625 -1.628949 -0.161399 1.733079 0.041860 0.293787 0.092062 0.656586
#> 168: -6.522450 0.340553 -5.354491 4.620076 2.613483 -1.631543 -0.161768 1.768930 0.048816 0.282325 0.072310 0.665195
#> 169: -6.527803 0.349010 -5.383653 4.475012 2.565853 -1.638452 -0.160631 1.759506 0.052307 0.261481 0.076797 0.657038
#> 170: -6.484452 0.394860 -5.470141 4.450725 2.585146 -1.644711 -0.160295 1.733670 0.051129 0.296564 0.099696 0.676826
#> 171: -6.486887 0.428320 -5.412454 4.452697 2.557947 -1.661730 -0.178167 1.717609 0.052950 0.258495 0.084811 0.672577
#> 172: -6.482485 0.375314 -5.364526 4.443782 2.585896 -1.652037 -0.177625 1.732403 0.055128 0.205859 0.063388 0.667217
#> 173: -6.484679 0.406833 -5.404183 4.364709 2.578668 -1.636775 -0.181969 1.709207 0.046732 0.250733 0.036453 0.662388
#> 174: -6.452953 0.327174 -5.351084 4.444720 2.562729 -1.641378 -0.183554 1.742271 0.033274 0.266571 0.031857 0.661032
#> 175: -6.456781 0.331127 -5.416462 4.426139 2.558285 -1.631932 -0.179660 1.723142 0.032631 0.208434 0.035224 0.674741
#> 176: -6.440788 0.327817 -5.394946 4.414572 2.530989 -1.631237 -0.186095 1.721659 0.023839 0.204685 0.028189 0.670957
#> 177: -6.430808 0.338601 -5.420462 4.207963 2.532735 -1.621996 -0.188031 1.708998 0.021225 0.204696 0.028626 0.668456
#> 178: -6.438010 0.392721 -5.409678 4.333538 2.530739 -1.641908 -0.186101 1.719044 0.026114 0.208537 0.034478 0.656813
#> 179: -6.453589 0.388826 -5.510601 4.389954 2.510959 -1.626200 -0.187146 1.725966 0.028723 0.267332 0.032805 0.667802
#> 180: -6.466918 0.387044 -5.556213 4.500530 2.521761 -1.625161 -0.186853 1.703181 0.019897 0.230582 0.027512 0.667226
#> 181: -6.447777 0.432952 -5.641951 4.590872 2.520678 -1.616208 -0.190165 1.720373 0.012911 0.250081 0.023688 0.675736
#> 182: -6.449494 0.353734 -5.556372 4.534662 2.520332 -1.622270 -0.192615 1.714721 0.011477 0.255926 0.024488 0.663313
#> 183: -6.447030 0.372219 -5.477240 4.439340 2.454365 -1.624966 -0.193174 1.736848 0.013578 0.218204 0.021151 0.662898
#> 184: -6.447970 0.357647 -5.553752 4.564937 2.425948 -1.623617 -0.190866 1.757958 0.014635 0.232893 0.019499 0.666803
#> 185: -6.421707 0.352109 -5.440262 4.628208 2.419503 -1.624096 -0.190055 1.768205 0.015169 0.209310 0.021165 0.672594
#> 186: -6.411722 0.373495 -5.516977 4.602970 2.435219 -1.623640 -0.186917 1.769615 0.016854 0.211137 0.023895 0.669643
#> 187: -6.382424 0.377623 -5.603715 4.517060 2.440059 -1.625806 -0.188581 1.793693 0.007631 0.230118 0.024120 0.669154
#> 188: -6.425327 0.381864 -5.568906 4.678167 2.434221 -1.624738 -0.191030 1.815674 0.006623 0.192654 0.020066 0.666758
#> 189: -6.415336 0.368200 -5.605956 4.713606 2.422571 -1.622508 -0.189720 1.832749 0.004812 0.230723 0.023667 0.668348
#> 190: -6.396817 0.362504 -5.537480 4.669190 2.431311 -1.623135 -0.191433 1.833470 0.002958 0.254784 0.014230 0.667469
#> 191: -6.392082 0.360784 -5.554519 4.612908 2.440379 -1.613707 -0.195155 1.843577 0.003646 0.258025 0.012162 0.668102
#> 192: -6.394138 0.331545 -5.566815 4.767379 2.445511 -1.617182 -0.193432 1.852190 0.003773 0.271631 0.009098 0.664063
#> 193: -6.394095 0.380558 -5.510989 4.681286 2.451408 -1.618481 -0.186117 1.852263 0.003635 0.238607 0.007789 0.667804
#> 194: -6.413286 0.378481 -5.553507 4.798061 2.456020 -1.622644 -0.190219 1.860607 0.001972 0.283666 0.005986 0.662935
#> 195: -6.408714 0.370885 -5.465010 4.716866 2.476702 -1.618193 -0.188990 1.876120 0.002388 0.264024 0.007393 0.664851
#> 196: -6.423714 0.393251 -5.521993 4.740352 2.465591 -1.617569 -0.185371 1.877090 0.002907 0.228429 0.009479 0.675504
#> 197: -6.428140 0.364629 -5.496569 4.839591 2.460793 -1.614526 -0.182789 1.880679 0.001835 0.203282 0.006397 0.679509
#> 198: -6.429530 0.399840 -5.474581 4.822805 2.471945 -1.620334 -0.183558 1.881942 0.002253 0.244028 0.007222 0.676522
#> 199: -6.434473 0.350557 -5.469797 4.801316 2.472902 -1.623762 -0.187629 1.885130 0.002879 0.258548 0.005416 0.670653
#> 200: -6.430604 0.383082 -5.532717 4.796004 2.448012 -1.626301 -0.187943 1.893647 0.003400 0.230326 0.006026 0.672637
#> 201: -6.437248 0.370433 -5.578354 4.825441 2.451251 -1.623698 -0.186235 1.894971 0.003367 0.258401 0.006226 0.671164
#> 202: -6.440638 0.367162 -5.603284 4.857679 2.447033 -1.623645 -0.186648 1.895682 0.003294 0.252550 0.006011 0.670439
#> 203: -6.442864 0.376035 -5.601505 4.867229 2.447171 -1.627403 -0.188145 1.896640 0.003061 0.253329 0.006240 0.669135
#> 204: -6.443855 0.377156 -5.573857 4.854268 2.443600 -1.629239 -0.188987 1.896997 0.003091 0.260229 0.005946 0.669497
#> 205: -6.445700 0.377342 -5.570745 4.846937 2.444662 -1.629125 -0.189146 1.896682 0.003182 0.260635 0.006085 0.669587
#> 206: -6.446937 0.379911 -5.552381 4.834881 2.445045 -1.630331 -0.189313 1.897175 0.003198 0.261490 0.006247 0.668911
#> 207: -6.448153 0.384517 -5.527544 4.820058 2.445899 -1.630802 -0.189180 1.897682 0.003277 0.250903 0.006447 0.670167
#> 208: -6.448576 0.381601 -5.516072 4.805597 2.445238 -1.629017 -0.188457 1.898870 0.003289 0.246816 0.006290 0.670216
#> 209: -6.449902 0.384456 -5.509970 4.794579 2.445166 -1.628770 -0.188026 1.900673 0.003323 0.250423 0.006371 0.669894
#> 210: -6.449155 0.381199 -5.504265 4.787916 2.444586 -1.629680 -0.187735 1.901594 0.003325 0.253049 0.006679 0.670548
#> 211: -6.449966 0.382057 -5.503259 4.789742 2.445405 -1.629791 -0.187227 1.902833 0.003243 0.257804 0.006651 0.670964
#> 212: -6.450701 0.384759 -5.501680 4.798528 2.446681 -1.629566 -0.186936 1.902108 0.003217 0.261061 0.006704 0.671259
#> 213: -6.450748 0.386138 -5.496285 4.806357 2.445858 -1.629122 -0.186967 1.901056 0.003272 0.260095 0.006593 0.671373
#> 214: -6.450525 0.391422 -5.491664 4.812621 2.445991 -1.628782 -0.187464 1.900955 0.003260 0.259614 0.006562 0.671353
#> 215: -6.450908 0.389878 -5.485967 4.819706 2.446525 -1.628838 -0.187963 1.901136 0.003257 0.257340 0.006504 0.671694
#> 216: -6.451822 0.390530 -5.487023 4.812164 2.447790 -1.628442 -0.187925 1.901294 0.003252 0.253989 0.006394 0.671644
#> 217: -6.452763 0.393541 -5.487311 4.810227 2.448452 -1.628358 -0.187873 1.901151 0.003244 0.255292 0.006331 0.671935
#> 218: -6.452877 0.391806 -5.487362 4.811635 2.448756 -1.627842 -0.187902 1.900824 0.003249 0.254091 0.006223 0.672036
#> 219: -6.453165 0.392890 -5.489532 4.811403 2.449214 -1.627629 -0.187985 1.900918 0.003175 0.252036 0.006236 0.671850
#> 220: -6.453727 0.393533 -5.488085 4.814387 2.449073 -1.627302 -0.188197 1.900877 0.003137 0.252414 0.006212 0.671476
#> 221: -6.453694 0.392868 -5.486000 4.812279 2.448642 -1.626700 -0.188470 1.900984 0.003108 0.251692 0.006140 0.671634
#> 222: -6.452772 0.391386 -5.486313 4.814275 2.448341 -1.626421 -0.188661 1.900731 0.003083 0.252614 0.006157 0.671781
#> 223: -6.452701 0.391194 -5.486190 4.819029 2.448409 -1.626492 -0.188757 1.901151 0.003057 0.252717 0.006085 0.671769
#> 224: -6.452647 0.391608 -5.487594 4.820839 2.448220 -1.626338 -0.188675 1.901453 0.003014 0.254276 0.006086 0.671609
#> 225: -6.452782 0.390821 -5.488479 4.819751 2.448573 -1.625988 -0.188610 1.901584 0.002968 0.255998 0.006051 0.671620
#> 226: -6.452747 0.389896 -5.487025 4.819909 2.449390 -1.626181 -0.188577 1.901426 0.002954 0.260275 0.006055 0.671619
#> 227: -6.452932 0.392810 -5.485441 4.818605 2.449450 -1.626274 -0.188686 1.900972 0.002943 0.261653 0.006157 0.671565
#> 228: -6.453100 0.393261 -5.487353 4.820800 2.449317 -1.626555 -0.188772 1.900898 0.002899 0.261927 0.006241 0.671828
#> 229: -6.453259 0.396232 -5.485634 4.827574 2.449449 -1.626655 -0.188857 1.900646 0.002932 0.265119 0.006376 0.671735
#> 230: -6.453119 0.395983 -5.485890 4.830931 2.450215 -1.627001 -0.188859 1.900169 0.002957 0.265726 0.006572 0.671679
#> 231: -6.453454 0.394412 -5.484085 4.827848 2.450491 -1.627125 -0.188892 1.899604 0.002973 0.266005 0.006677 0.671523
#> 232: -6.453868 0.392683 -5.482000 4.829034 2.451377 -1.627149 -0.188884 1.899139 0.002986 0.263513 0.006710 0.671616
#> 233: -6.454248 0.393429 -5.482783 4.823918 2.451914 -1.627317 -0.188848 1.898934 0.003033 0.262438 0.006651 0.671690
#> 234: -6.453962 0.393763 -5.483890 4.821519 2.452362 -1.627600 -0.188893 1.898869 0.003064 0.262477 0.006612 0.671696
#> 235: -6.454010 0.393547 -5.481329 4.822137 2.453060 -1.627767 -0.188819 1.899287 0.003066 0.263215 0.006569 0.671459
#> 236: -6.453765 0.392193 -5.477943 4.820405 2.453443 -1.627854 -0.188639 1.899333 0.003081 0.262647 0.006498 0.671072
#> 237: -6.453721 0.390605 -5.475597 4.817802 2.453754 -1.627699 -0.188633 1.899464 0.003099 0.262054 0.006448 0.671032
#> 238: -6.453407 0.390825 -5.474876 4.821414 2.453206 -1.627505 -0.188702 1.899328 0.003096 0.261497 0.006508 0.670864
#> 239: -6.453490 0.390120 -5.474312 4.824196 2.453070 -1.627129 -0.188904 1.899266 0.003103 0.260635 0.006496 0.670867
#> 240: -6.453465 0.389619 -5.474533 4.825847 2.453264 -1.627117 -0.189086 1.899168 0.003099 0.260548 0.006515 0.670894
#> 241: -6.453249 0.388650 -5.474882 4.822760 2.453123 -1.627493 -0.189148 1.899224 0.003099 0.259819 0.006521 0.670824
#> 242: -6.453054 0.386738 -5.474317 4.821373 2.453654 -1.627539 -0.189129 1.899228 0.003101 0.260590 0.006487 0.670613
#> 243: -6.453128 0.385403 -5.473848 4.824209 2.453706 -1.627700 -0.189207 1.899031 0.003112 0.261660 0.006459 0.670609
#> 244: -6.453271 0.385041 -5.472187 4.823493 2.454426 -1.627884 -0.189261 1.898883 0.003115 0.261422 0.006447 0.670482
#> 245: -6.453366 0.384071 -5.470518 4.820415 2.454450 -1.627996 -0.189196 1.898738 0.003109 0.260287 0.006465 0.670449
#> 246: -6.453457 0.383468 -5.469961 4.819863 2.454663 -1.628113 -0.189193 1.898551 0.003089 0.260094 0.006469 0.670473
#> 247: -6.453426 0.382754 -5.468958 4.818907 2.454954 -1.628251 -0.189181 1.898316 0.003069 0.260885 0.006454 0.670382
#> 248: -6.453324 0.382249 -5.468915 4.819875 2.455489 -1.628157 -0.189232 1.898247 0.003073 0.262072 0.006454 0.670291
#> 249: -6.453146 0.382290 -5.468248 4.821675 2.456018 -1.628027 -0.189273 1.898431 0.003083 0.261771 0.006454 0.670207
#> 250: -6.453123 0.381930 -5.466851 4.821143 2.456222 -1.627932 -0.189297 1.898342 0.003076 0.261892 0.006405 0.670107
#> 251: -6.453454 0.381818 -5.465774 4.820509 2.456557 -1.627962 -0.189393 1.898331 0.003069 0.261430 0.006428 0.670042
#> 252: -6.453459 0.380762 -5.465077 4.817491 2.456882 -1.627758 -0.189438 1.898657 0.003050 0.260794 0.006426 0.669993
#> 253: -6.453575 0.379697 -5.464628 4.816332 2.457320 -1.627443 -0.189434 1.898982 0.003031 0.260966 0.006419 0.670004
#> 254: -6.453531 0.379104 -5.463281 4.819653 2.457690 -1.627311 -0.189492 1.899214 0.003010 0.260941 0.006362 0.669887
#> 255: -6.453713 0.377789 -5.463365 4.821095 2.457972 -1.627065 -0.189526 1.899367 0.003001 0.260600 0.006325 0.669971
#> 256: -6.453813 0.378261 -5.463368 4.822094 2.458207 -1.626938 -0.189525 1.899498 0.003004 0.260164 0.006341 0.669948
#> 257: -6.453871 0.377576 -5.462824 4.821333 2.458531 -1.626844 -0.189575 1.899648 0.002992 0.259696 0.006344 0.669921
#> 258: -6.453960 0.376948 -5.462248 4.820660 2.458998 -1.626746 -0.189557 1.899767 0.002991 0.259270 0.006343 0.669990
#> 259: -6.453846 0.376655 -5.461804 4.819189 2.458864 -1.626668 -0.189517 1.899751 0.002974 0.259076 0.006318 0.669849
#> 260: -6.453866 0.376205 -5.461381 4.819075 2.459045 -1.626668 -0.189464 1.899833 0.002970 0.259003 0.006316 0.669919
#> 261: -6.453893 0.376614 -5.460523 4.818795 2.459217 -1.626778 -0.189423 1.899748 0.002961 0.258838 0.006328 0.669886
#> 262: -6.453926 0.376004 -5.460755 4.819219 2.459108 -1.626788 -0.189405 1.899708 0.002969 0.258389 0.006348 0.669887
#> 263: -6.453935 0.376521 -5.460458 4.820808 2.459221 -1.626832 -0.189348 1.899619 0.002958 0.258355 0.006367 0.669931
#> 264: -6.453984 0.375349 -5.459605 4.821178 2.459593 -1.626924 -0.189282 1.899668 0.002945 0.257307 0.006376 0.669950
#> 265: -6.453995 0.374518 -5.458437 4.822198 2.460027 -1.626967 -0.189186 1.899723 0.002941 0.257079 0.006372 0.669945
#> 266: -6.454124 0.374922 -5.457953 4.822108 2.460163 -1.626976 -0.189051 1.899763 0.002927 0.257437 0.006360 0.669873
#> 267: -6.454073 0.375063 -5.457043 4.821511 2.460384 -1.626799 -0.189075 1.899883 0.002918 0.257073 0.006371 0.669932
#> 268: -6.454113 0.374761 -5.456787 4.820866 2.460362 -1.626790 -0.189067 1.900032 0.002915 0.257515 0.006358 0.669949
#> 269: -6.454173 0.374155 -5.456190 4.820396 2.460256 -1.626855 -0.189063 1.900049 0.002918 0.257242 0.006356 0.670071
#> 270: -6.454211 0.373627 -5.455009 4.820025 2.460300 -1.626923 -0.189056 1.900146 0.002907 0.257175 0.006371 0.670312
#> 271: -6.454244 0.373780 -5.454841 4.818128 2.460576 -1.626980 -0.189013 1.900245 0.002912 0.257886 0.006391 0.670315
#> 272: -6.454146 0.374016 -5.454891 4.817692 2.460584 -1.626948 -0.189006 1.900180 0.002922 0.258388 0.006357 0.670391
#> 273: -6.454097 0.374814 -5.454903 4.817815 2.460625 -1.627017 -0.189021 1.900144 0.002931 0.259021 0.006330 0.670402
#> 274: -6.454262 0.374697 -5.454724 4.818051 2.460648 -1.627101 -0.189021 1.900135 0.002945 0.259302 0.006349 0.670456
#> 275: -6.454373 0.374750 -5.454803 4.817649 2.460630 -1.627248 -0.189024 1.900149 0.002933 0.258989 0.006339 0.670524
#> 276: -6.454648 0.374962 -5.453668 4.817980 2.460356 -1.627384 -0.189000 1.900094 0.002936 0.259205 0.006354 0.670678
#> 277: -6.454651 0.374692 -5.452400 4.818777 2.459884 -1.627463 -0.188980 1.900094 0.002940 0.259168 0.006371 0.670814
#> 278: -6.454614 0.374830 -5.451956 4.819357 2.459555 -1.627512 -0.188966 1.900145 0.002933 0.259283 0.006359 0.670880
#> 279: -6.454631 0.374966 -5.451348 4.818721 2.459413 -1.627472 -0.188944 1.900216 0.002940 0.259009 0.006337 0.670983
#> 280: -6.454483 0.375445 -5.451834 4.818339 2.459374 -1.627495 -0.188929 1.900269 0.002934 0.259209 0.006343 0.671080
#> 281: -6.454412 0.374933 -5.451106 4.819351 2.459361 -1.627487 -0.188903 1.900308 0.002932 0.259493 0.006322 0.671154
#> 282: -6.454392 0.374903 -5.450362 4.820802 2.459521 -1.627463 -0.188893 1.900328 0.002939 0.259923 0.006327 0.671139
#> 283: -6.454289 0.374695 -5.450296 4.821277 2.459660 -1.627529 -0.188904 1.900406 0.002925 0.260622 0.006313 0.671184
#> 284: -6.454195 0.373902 -5.449699 4.821848 2.459756 -1.627524 -0.188897 1.900417 0.002914 0.261228 0.006293 0.671282
#> 285: -6.454117 0.374033 -5.448660 4.822083 2.459689 -1.627532 -0.188913 1.900367 0.002907 0.261194 0.006304 0.671409
#> 286: -6.454031 0.374048 -5.448252 4.821554 2.459717 -1.627481 -0.188924 1.900362 0.002895 0.261210 0.006301 0.671549
#> 287: -6.454078 0.374049 -5.447192 4.820560 2.459887 -1.627460 -0.188907 1.900371 0.002880 0.261254 0.006270 0.671631
#> 288: -6.454033 0.374337 -5.446518 4.820010 2.460007 -1.627518 -0.188929 1.900449 0.002887 0.261136 0.006251 0.671640
#> 289: -6.454002 0.374025 -5.446149 4.820065 2.459983 -1.627551 -0.188940 1.900488 0.002904 0.261191 0.006219 0.671717
#> 290: -6.454025 0.374163 -5.445864 4.820447 2.460192 -1.627522 -0.188918 1.900479 0.002909 0.261396 0.006222 0.671759
#> 291: -6.453893 0.373890 -5.445471 4.819767 2.460435 -1.627524 -0.188914 1.900461 0.002914 0.261371 0.006221 0.671778
#> 292: -6.453826 0.374030 -5.445146 4.819693 2.460476 -1.627562 -0.188909 1.900535 0.002912 0.261212 0.006205 0.671845
#> 293: -6.453698 0.373561 -5.445096 4.819831 2.460517 -1.627522 -0.188900 1.900529 0.002910 0.260962 0.006191 0.671973
#> 294: -6.453628 0.373137 -5.445195 4.819994 2.460605 -1.627482 -0.188885 1.900499 0.002918 0.261377 0.006177 0.672120
#> 295: -6.453626 0.372624 -5.444964 4.820436 2.460486 -1.627487 -0.188889 1.900459 0.002922 0.261844 0.006174 0.672171
#> 296: -6.453586 0.372507 -5.444405 4.820567 2.460459 -1.627497 -0.188897 1.900420 0.002914 0.261827 0.006172 0.672217
#> 297: -6.453729 0.372526 -5.444571 4.820229 2.460251 -1.627508 -0.188915 1.900371 0.002909 0.262530 0.006190 0.672265
#> 298: -6.453774 0.372464 -5.444841 4.820105 2.460237 -1.627481 -0.188916 1.900318 0.002904 0.262903 0.006191 0.672413
#> 299: -6.453744 0.372588 -5.445109 4.820411 2.460174 -1.627484 -0.188928 1.900327 0.002893 0.262972 0.006178 0.672443
#> 300: -6.453719 0.372364 -5.444684 4.820420 2.460025 -1.627484 -0.188915 1.900294 0.002902 0.262751 0.006175 0.672633
#> 301: -6.453708 0.372212 -5.443329 4.820761 2.460126 -1.627529 -0.188905 1.900265 0.002898 0.262537 0.006163 0.672777
#> 302: -6.453619 0.371957 -5.442192 4.820849 2.460243 -1.627567 -0.188923 1.900288 0.002896 0.262281 0.006140 0.672966
#> 303: -6.453609 0.371601 -5.441533 4.821137 2.460244 -1.627599 -0.188941 1.900316 0.002893 0.262181 0.006110 0.673064
#> 304: -6.453675 0.371506 -5.441140 4.820675 2.460078 -1.627544 -0.188951 1.900329 0.002897 0.262270 0.006103 0.673139
#> 305: -6.453514 0.371620 -5.441057 4.820399 2.460073 -1.627566 -0.188968 1.900333 0.002888 0.262437 0.006117 0.673233
#> 306: -6.453404 0.371759 -5.440890 4.820808 2.460382 -1.627582 -0.188974 1.900343 0.002890 0.262787 0.006121 0.673339
#> 307: -6.453446 0.372048 -5.440703 4.821513 2.460527 -1.627563 -0.188965 1.900329 0.002888 0.262926 0.006117 0.673542
#> 308: -6.453591 0.371803 -5.440762 4.821594 2.460441 -1.627531 -0.188972 1.900343 0.002880 0.262855 0.006135 0.673709
#> 309: -6.453645 0.371437 -5.440495 4.821744 2.460405 -1.627539 -0.188972 1.900350 0.002878 0.263349 0.006151 0.673886
#> 310: -6.453788 0.371219 -5.440159 4.822121 2.460237 -1.627527 -0.188975 1.900332 0.002887 0.263622 0.006149 0.673924
#> 311: -6.453846 0.370806 -5.439689 4.822263 2.460097 -1.627506 -0.188968 1.900318 0.002885 0.263857 0.006146 0.674049
#> 312: -6.453807 0.370560 -5.438883 4.822480 2.460043 -1.627491 -0.188961 1.900291 0.002886 0.263962 0.006136 0.674185
#> 313: -6.453897 0.370443 -5.438516 4.822993 2.459990 -1.627485 -0.188958 1.900268 0.002887 0.264044 0.006121 0.674370
#> 314: -6.454035 0.370735 -5.438480 4.823194 2.460027 -1.627500 -0.188957 1.900240 0.002903 0.264209 0.006135 0.674497
#> 315: -6.454161 0.371162 -5.438325 4.823326 2.460017 -1.627507 -0.188958 1.900224 0.002907 0.264171 0.006149 0.674748
#> 316: -6.454148 0.370973 -5.437996 4.823757 2.459963 -1.627503 -0.188980 1.900232 0.002915 0.263913 0.006169 0.674982
#> 317: -6.454094 0.370805 -5.437838 4.823628 2.459990 -1.627510 -0.188992 1.900238 0.002911 0.263901 0.006171 0.675194
#> 318: -6.454057 0.370987 -5.437595 4.823649 2.460096 -1.627548 -0.188996 1.900267 0.002907 0.263657 0.006171 0.675400
#> 319: -6.454033 0.371173 -5.436826 4.823622 2.460081 -1.627554 -0.189000 1.900281 0.002919 0.263354 0.006164 0.675605
#> 320: -6.454041 0.371082 -5.436413 4.823999 2.460145 -1.627587 -0.188995 1.900282 0.002916 0.263276 0.006167 0.675721
#> 321: -6.454101 0.370982 -5.436109 4.824184 2.460003 -1.627598 -0.188995 1.900297 0.002917 0.263368 0.006158 0.675836
#> 322: -6.454296 0.370845 -5.435325 4.824529 2.460101 -1.627587 -0.188990 1.900307 0.002920 0.263237 0.006147 0.675930
#> 323: -6.454365 0.370550 -5.434561 4.824851 2.459935 -1.627602 -0.188999 1.900305 0.002922 0.262770 0.006162 0.676038
#> 324: -6.454444 0.370072 -5.434181 4.825143 2.459837 -1.627596 -0.189001 1.900323 0.002927 0.262541 0.006168 0.676188
#> 325: -6.454532 0.369658 -5.433911 4.825232 2.459788 -1.627613 -0.189003 1.900307 0.002926 0.262440 0.006152 0.676441
#> 326: -6.454580 0.369660 -5.433132 4.825334 2.459811 -1.627634 -0.189013 1.900286 0.002923 0.262587 0.006135 0.676727
#> 327: -6.454610 0.369471 -5.432617 4.825533 2.459896 -1.627635 -0.189015 1.900266 0.002928 0.262553 0.006131 0.677011
#> 328: -6.454625 0.369576 -5.432086 4.825236 2.459984 -1.627610 -0.189029 1.900249 0.002933 0.263180 0.006132 0.677252
#> 329: -6.454702 0.369111 -5.431560 4.824933 2.460045 -1.627584 -0.189040 1.900270 0.002941 0.264020 0.006130 0.677477
#> 330: -6.454813 0.368692 -5.431209 4.824655 2.459994 -1.627572 -0.189044 1.900278 0.002935 0.264028 0.006128 0.677665
#> 331: -6.454905 0.368476 -5.431129 4.824770 2.460004 -1.627561 -0.189055 1.900282 0.002929 0.264393 0.006125 0.677876
#> 332: -6.454940 0.368317 -5.430856 4.824854 2.460015 -1.627564 -0.189049 1.900299 0.002923 0.264581 0.006127 0.678100
#> 333: -6.454941 0.368233 -5.430662 4.824653 2.460218 -1.627560 -0.189050 1.900302 0.002917 0.265183 0.006141 0.678402
#> 334: -6.454858 0.368293 -5.430361 4.824638 2.460410 -1.627564 -0.189052 1.900300 0.002929 0.265979 0.006138 0.678728
#> 335: -6.454817 0.368498 -5.429841 4.825147 2.460580 -1.627571 -0.189054 1.900317 0.002933 0.266512 0.006162 0.679089
#> 336: -6.454803 0.368166 -5.429464 4.825337 2.460694 -1.627575 -0.189056 1.900310 0.002930 0.266667 0.006192 0.679453
#> 337: -6.454810 0.368147 -5.429169 4.825355 2.460772 -1.627584 -0.189064 1.900306 0.002929 0.266970 0.006202 0.679712
#> 338: -6.454880 0.368053 -5.429126 4.825295 2.460586 -1.627584 -0.189072 1.900305 0.002936 0.267414 0.006205 0.680013
#> 339: -6.454817 0.367873 -5.428806 4.825461 2.460631 -1.627575 -0.189073 1.900305 0.002942 0.267815 0.006223 0.680331
#> 340: -6.454796 0.367790 -5.428382 4.825400 2.460535 -1.627560 -0.189066 1.900307 0.002944 0.268215 0.006232 0.680719
#> 341: -6.454921 0.367611 -5.427949 4.825662 2.460564 -1.627552 -0.189058 1.900301 0.002960 0.268332 0.006228 0.681086
#> 342: -6.454959 0.367276 -5.427664 4.825694 2.460540 -1.627541 -0.189052 1.900295 0.002964 0.268480 0.006241 0.681431
#> 343: -6.455010 0.367138 -5.427372 4.825842 2.460522 -1.627529 -0.189048 1.900280 0.002966 0.269049 0.006255 0.681730
#> 344: -6.455099 0.367383 -5.427025 4.825975 2.460562 -1.627539 -0.189049 1.900281 0.002967 0.269326 0.006259 0.682073
#> 345: -6.455158 0.367278 -5.426737 4.826004 2.460626 -1.627550 -0.189048 1.900263 0.002964 0.269561 0.006277 0.682437
#> 346: -6.455166 0.367369 -5.426712 4.826073 2.460659 -1.627551 -0.189049 1.900251 0.002962 0.270266 0.006278 0.682814
#> 347: -6.455246 0.367425 -5.426678 4.826056 2.460553 -1.627561 -0.189052 1.900253 0.002955 0.270915 0.006291 0.683227
#> 348: -6.455348 0.367800 -5.426419 4.826059 2.460524 -1.627561 -0.189056 1.900241 0.002949 0.271788 0.006299 0.683579
#> 349: -6.455418 0.368103 -5.426331 4.826193 2.460459 -1.627557 -0.189061 1.900244 0.002940 0.272606 0.006309 0.683928
#> 350: -6.455396 0.368507 -5.426257 4.826189 2.460437 -1.627554 -0.189063 1.900250 0.002938 0.273378 0.006319 0.684299
#> 351: -6.455378 0.368907 -5.426091 4.826348 2.460502 -1.627563 -0.189065 1.900238 0.002935 0.273964 0.006334 0.684681
#> 352: -6.455399 0.369210 -5.426078 4.826405 2.460615 -1.627556 -0.189069 1.900236 0.002930 0.274451 0.006360 0.685110
#> 353: -6.455488 0.369116 -5.425984 4.826308 2.460522 -1.627565 -0.189069 1.900232 0.002928 0.275419 0.006382 0.685514
#> 354: -6.455459 0.369105 -5.426022 4.826283 2.460427 -1.627570 -0.189072 1.900233 0.002921 0.275933 0.006386 0.685976
#> 355: -6.455537 0.369442 -5.425977 4.826074 2.460326 -1.627575 -0.189067 1.900233 0.002920 0.276769 0.006412 0.686411
#> 356: -6.455517 0.369666 -5.426102 4.825913 2.460279 -1.627562 -0.189070 1.900237 0.002913 0.277400 0.006426 0.686848
#> 357: -6.455505 0.369749 -5.425900 4.825760 2.460175 -1.627558 -0.189070 1.900233 0.002910 0.278289 0.006445 0.687321
#> 358: -6.455444 0.369942 -5.425705 4.825718 2.460183 -1.627564 -0.189067 1.900227 0.002909 0.278879 0.006460 0.687767
#> 359: -6.455465 0.370093 -5.425762 4.825665 2.460160 -1.627564 -0.189065 1.900227 0.002909 0.279903 0.006477 0.688197
#> 360: -6.455521 0.370045 -5.426011 4.825467 2.460206 -1.627565 -0.189065 1.900222 0.002911 0.280318 0.006486 0.688709
#> 361: -6.455508 0.369982 -5.426092 4.825345 2.460260 -1.627565 -0.189068 1.900219 0.002911 0.281228 0.006493 0.689184
#> 362: -6.455489 0.369727 -5.426074 4.825399 2.460329 -1.627572 -0.189069 1.900215 0.002914 0.282202 0.006496 0.689670
#> 363: -6.455486 0.369961 -5.426003 4.825451 2.460327 -1.627574 -0.189074 1.900218 0.002916 0.282929 0.006502 0.690109
#> 364: -6.455466 0.370037 -5.426151 4.825563 2.460319 -1.627571 -0.189074 1.900220 0.002914 0.283826 0.006527 0.690574
#> 365: -6.455449 0.370220 -5.426068 4.825549 2.460363 -1.627578 -0.189080 1.900219 0.002915 0.284345 0.006550 0.690982
#> 366: -6.455419 0.370745 -5.425872 4.825549 2.460429 -1.627574 -0.189079 1.900223 0.002916 0.285284 0.006560 0.691409
#> 367: -6.455353 0.371128 -5.425744 4.825639 2.460265 -1.627577 -0.189082 1.900228 0.002915 0.286158 0.006565 0.691827
#> 368: -6.455296 0.371416 -5.425679 4.825658 2.460124 -1.627574 -0.189081 1.900228 0.002916 0.287194 0.006565 0.692235
#> 369: -6.455271 0.371737 -5.425622 4.825739 2.459990 -1.627582 -0.189080 1.900228 0.002918 0.288199 0.006582 0.692629
#> 370: -6.455304 0.371862 -5.425614 4.825839 2.459876 -1.627588 -0.189083 1.900229 0.002915 0.289186 0.006596 0.693033
#> 371: -6.455306 0.372186 -5.425592 4.826001 2.459834 -1.627591 -0.189082 1.900232 0.002916 0.290155 0.006617 0.693437
#> 372: -6.455296 0.372540 -5.425648 4.826123 2.459834 -1.627584 -0.189083 1.900230 0.002925 0.290785 0.006622 0.693828
#> 373: -6.455335 0.372927 -5.425489 4.826169 2.459880 -1.627589 -0.189086 1.900228 0.002926 0.291830 0.006630 0.694222
#> 374: -6.455413 0.373214 -5.425445 4.826133 2.459921 -1.627584 -0.189088 1.900227 0.002928 0.292620 0.006629 0.694655
#> 375: -6.455460 0.373587 -5.425446 4.826196 2.460005 -1.627584 -0.189088 1.900231 0.002929 0.293386 0.006629 0.695124
#> 376: -6.455508 0.373716 -5.425383 4.826127 2.460074 -1.627585 -0.189088 1.900233 0.002934 0.294056 0.006622 0.695666
#> 377: -6.455519 0.373882 -5.425255 4.826018 2.460123 -1.627577 -0.189089 1.900234 0.002940 0.294898 0.006632 0.696176
#> 378: -6.455513 0.373714 -5.425232 4.826041 2.460193 -1.627569 -0.189090 1.900233 0.002937 0.295543 0.006636 0.696701
#> 379: -6.455508 0.373726 -5.425381 4.825966 2.460161 -1.627569 -0.189091 1.900239 0.002934 0.296362 0.006636 0.697262
#> 380: -6.455542 0.373454 -5.425396 4.825987 2.460120 -1.627566 -0.189090 1.900241 0.002935 0.297041 0.006638 0.697830
#> 381: -6.455526 0.373323 -5.425341 4.826053 2.460135 -1.627568 -0.189094 1.900239 0.002933 0.297804 0.006647 0.698367
#> 382: -6.455518 0.373245 -5.425248 4.826144 2.459987 -1.627569 -0.189093 1.900236 0.002932 0.298701 0.006661 0.698889
#> 383: -6.455554 0.373239 -5.425358 4.826152 2.459870 -1.627574 -0.189095 1.900232 0.002931 0.299575 0.006674 0.699407
#> 384: -6.455597 0.373275 -5.425348 4.826187 2.459918 -1.627575 -0.189099 1.900228 0.002933 0.300542 0.006685 0.699908
#> 385: -6.455617 0.373361 -5.425303 4.826240 2.459960 -1.627575 -0.189099 1.900225 0.002935 0.301869 0.006676 0.700431
#> 386: -6.455649 0.373320 -5.425369 4.826303 2.460003 -1.627580 -0.189098 1.900232 0.002931 0.303042 0.006662 0.700921
#> 387: -6.455654 0.373487 -5.425413 4.826324 2.459945 -1.627579 -0.189098 1.900229 0.002928 0.304074 0.006650 0.701401
#> 388: -6.455759 0.373532 -5.425535 4.826262 2.459951 -1.627579 -0.189099 1.900228 0.002931 0.305078 0.006649 0.701906
#> 389: -6.455745 0.373710 -5.425573 4.826292 2.459927 -1.627580 -0.189097 1.900229 0.002932 0.306581 0.006648 0.702400
#> 390: -6.455845 0.373744 -5.425565 4.826249 2.459823 -1.627582 -0.189097 1.900230 0.002932 0.308039 0.006657 0.702865
#> 391: -6.455950 0.373495 -5.425550 4.826185 2.459727 -1.627587 -0.189096 1.900230 0.002933 0.309070 0.006654 0.703348
#> 392: -6.456020 0.373734 -5.425613 4.826155 2.459687 -1.627585 -0.189096 1.900228 0.002931 0.310421 0.006656 0.703825
#> 393: -6.456050 0.373693 -5.425584 4.826121 2.459656 -1.627582 -0.189095 1.900231 0.002929 0.311610 0.006654 0.704316
#> 394: -6.456052 0.373604 -5.425540 4.826096 2.459514 -1.627584 -0.189095 1.900227 0.002933 0.312736 0.006675 0.704783
#> 395: -6.456098 0.373792 -5.425517 4.826167 2.459432 -1.627585 -0.189094 1.900221 0.002925 0.313766 0.006673 0.705283
#> 396: -6.456171 0.373871 -5.425561 4.826194 2.459330 -1.627586 -0.189090 1.900224 0.002927 0.314845 0.006678 0.705715
#> 397: -6.456150 0.373963 -5.425492 4.826161 2.459296 -1.627592 -0.189090 1.900227 0.002927 0.315836 0.006693 0.706184
#> 398: -6.456165 0.374076 -5.425526 4.826186 2.459264 -1.627588 -0.189091 1.900222 0.002930 0.316870 0.006699 0.706627
#> 399: -6.456154 0.374251 -5.425554 4.826210 2.459271 -1.627586 -0.189092 1.900224 0.002937 0.318087 0.006704 0.707070
#> 400: -6.456247 0.374233 -5.425556 4.826204 2.459255 -1.627586 -0.189091 1.900227 0.002935 0.319043 0.006706 0.707543
#> 401: -6.456301 0.374073 -5.425531 4.826238 2.459367 -1.627586 -0.189091 1.900231 0.002935 0.319828 0.006708 0.707998
#> 402: -6.456359 0.373963 -5.425574 4.826232 2.459417 -1.627588 -0.189091 1.900232 0.002944 0.320626 0.006704 0.708464
#> 403: -6.456419 0.374021 -5.425506 4.826239 2.459494 -1.627587 -0.189089 1.900234 0.002952 0.321493 0.006698 0.708951
#> 404: -6.456486 0.374130 -5.425518 4.826244 2.459550 -1.627588 -0.189088 1.900235 0.002948 0.322628 0.006694 0.709423
#> 405: -6.456476 0.373852 -5.425506 4.826239 2.459548 -1.627587 -0.189088 1.900236 0.002945 0.323629 0.006693 0.709915
#> 406: -6.456438 0.374091 -5.425518 4.826241 2.459578 -1.627590 -0.189088 1.900235 0.002947 0.324582 0.006697 0.710376
#> 407: -6.456424 0.374340 -5.425495 4.826221 2.459548 -1.627593 -0.189089 1.900236 0.002947 0.325660 0.006695 0.710852
#> 408: -6.456415 0.374410 -5.425518 4.826221 2.459574 -1.627593 -0.189090 1.900237 0.002948 0.326674 0.006703 0.711356
#> 409: -6.456444 0.374173 -5.425545 4.826260 2.459615 -1.627597 -0.189091 1.900233 0.002948 0.327462 0.006705 0.711846
#> 410: -6.456461 0.374151 -5.425589 4.826291 2.459631 -1.627599 -0.189091 1.900232 0.002949 0.328703 0.006703 0.712304
#> 411: -6.456502 0.374097 -5.425567 4.826283 2.459707 -1.627597 -0.189090 1.900232 0.002948 0.329411 0.006718 0.712742
#> 412: -6.456585 0.374018 -5.425627 4.826272 2.459746 -1.627597 -0.189089 1.900234 0.002951 0.330691 0.006724 0.713175
#> 413: -6.456633 0.374405 -5.425645 4.826295 2.459737 -1.627596 -0.189091 1.900236 0.002951 0.331780 0.006737 0.713616
#> 414: -6.456703 0.374604 -5.425666 4.826265 2.459833 -1.627596 -0.189091 1.900235 0.002955 0.332865 0.006762 0.714030
#> 415: -6.456814 0.374641 -5.425672 4.826266 2.459846 -1.627597 -0.189090 1.900237 0.002954 0.334128 0.006792 0.714461
#> 416: -6.456802 0.374767 -5.425673 4.826214 2.459856 -1.627600 -0.189090 1.900237 0.002951 0.335294 0.006808 0.714849
#> 417: -6.456760 0.375136 -5.425714 4.826255 2.459839 -1.627603 -0.189089 1.900236 0.002954 0.336458 0.006812 0.715268
#> 418: -6.456733 0.374941 -5.425704 4.826302 2.459920 -1.627603 -0.189089 1.900237 0.002953 0.337322 0.006814 0.715684
#> 419: -6.456717 0.375075 -5.425727 4.826316 2.459987 -1.627605 -0.189088 1.900241 0.002952 0.338301 0.006815 0.716097
#> 420: -6.456763 0.374758 -5.425701 4.826293 2.459999 -1.627607 -0.189087 1.900240 0.002952 0.339477 0.006818 0.716477
#> 421: -6.456793 0.374787 -5.425666 4.826301 2.460010 -1.627606 -0.189087 1.900241 0.002952 0.340374 0.006826 0.716903
#> 422: -6.456816 0.374765 -5.425651 4.826305 2.460015 -1.627609 -0.189087 1.900241 0.002955 0.341133 0.006820 0.717308
#> 423: -6.456840 0.374818 -5.425657 4.826305 2.460115 -1.627608 -0.189086 1.900240 0.002957 0.341834 0.006816 0.717724
#> 424: -6.456824 0.374690 -5.425654 4.826321 2.460227 -1.627609 -0.189086 1.900240 0.002964 0.342838 0.006825 0.718118
#> 425: -6.456863 0.374777 -5.425691 4.826310 2.460296 -1.627613 -0.189086 1.900240 0.002968 0.343383 0.006840 0.718560
#> 426: -6.456930 0.374850 -5.425690 4.826337 2.460277 -1.627613 -0.189088 1.900239 0.002969 0.344115 0.006834 0.718956
#> 427: -6.456993 0.374771 -5.425722 4.826354 2.460249 -1.627614 -0.189087 1.900240 0.002970 0.345215 0.006844 0.719330
#> 428: -6.456991 0.374628 -5.425765 4.826366 2.460228 -1.627614 -0.189087 1.900239 0.002972 0.346099 0.006852 0.719699
#> 429: -6.456998 0.374575 -5.425762 4.826351 2.460278 -1.627614 -0.189088 1.900241 0.002973 0.347003 0.006850 0.720060
#> 430: -6.457038 0.374759 -5.425735 4.826348 2.460333 -1.627613 -0.189088 1.900239 0.002976 0.347725 0.006847 0.720435
#> 431: -6.457083 0.374586 -5.425756 4.826369 2.460385 -1.627614 -0.189087 1.900239 0.002975 0.348466 0.006852 0.720803
#> 432: -6.457100 0.374682 -5.425765 4.826390 2.460366 -1.627615 -0.189088 1.900239 0.002975 0.349439 0.006870 0.721160
#> 433: -6.457153 0.374640 -5.425776 4.826355 2.460286 -1.627615 -0.189087 1.900238 0.002975 0.350401 0.006876 0.721523
#> 434: -6.457120 0.374515 -5.425797 4.826358 2.460236 -1.627616 -0.189087 1.900238 0.002974 0.351188 0.006883 0.721889
#> 435: -6.457105 0.374629 -5.425809 4.826340 2.460267 -1.627616 -0.189087 1.900237 0.002972 0.352173 0.006881 0.722253
#> 436: -6.457048 0.374579 -5.425816 4.826340 2.460223 -1.627615 -0.189088 1.900236 0.002974 0.352827 0.006880 0.722611
#> 437: -6.457042 0.374731 -5.425800 4.826352 2.460195 -1.627617 -0.189088 1.900237 0.002975 0.353845 0.006882 0.722971
#> 438: -6.457056 0.374684 -5.425805 4.826344 2.460171 -1.627616 -0.189089 1.900237 0.002975 0.354744 0.006891 0.723352
#> 439: -6.457067 0.374596 -5.425835 4.826348 2.460198 -1.627616 -0.189088 1.900236 0.002978 0.355937 0.006892 0.723728
#> 440: -6.457091 0.374610 -5.425836 4.826364 2.460188 -1.627614 -0.189087 1.900237 0.002983 0.356725 0.006887 0.724092
#> 441: -6.457118 0.374779 -5.425836 4.826366 2.460170 -1.627614 -0.189087 1.900235 0.002987 0.357522 0.006887 0.724439
#> 442: -6.457150 0.374634 -5.425856 4.826359 2.460148 -1.627615 -0.189088 1.900235 0.002990 0.358132 0.006887 0.724787
#> 443: -6.457117 0.374762 -5.425840 4.826364 2.460169 -1.627614 -0.189089 1.900235 0.002990 0.358834 0.006892 0.725138
#> 444: -6.457091 0.374827 -5.425849 4.826377 2.460208 -1.627616 -0.189089 1.900235 0.002992 0.359644 0.006904 0.725477
#> 445: -6.457068 0.375004 -5.425863 4.826377 2.460246 -1.627615 -0.189088 1.900237 0.002999 0.360393 0.006908 0.725802
#> 446: -6.457054 0.374966 -5.425887 4.826368 2.460237 -1.627614 -0.189088 1.900238 0.003004 0.361349 0.006906 0.726145
#> 447: -6.457078 0.375102 -5.425902 4.826361 2.460159 -1.627613 -0.189087 1.900239 0.003004 0.362229 0.006903 0.726484
#> 448: -6.457056 0.374932 -5.425923 4.826348 2.460041 -1.627612 -0.189088 1.900238 0.003006 0.363076 0.006914 0.726823
#> 449: -6.457072 0.374770 -5.425940 4.826349 2.459955 -1.627613 -0.189088 1.900240 0.003004 0.363979 0.006925 0.727168
#> 450: -6.457037 0.375014 -5.425942 4.826369 2.459841 -1.627614 -0.189088 1.900239 0.003007 0.364652 0.006930 0.727540
#> 451: -6.457031 0.375386 -5.425939 4.826376 2.459797 -1.627614 -0.189087 1.900239 0.003008 0.365409 0.006937 0.727922
#> 452: -6.457035 0.375748 -5.425946 4.826369 2.459825 -1.627614 -0.189087 1.900239 0.003005 0.366122 0.006936 0.728282
#> 453: -6.457054 0.376025 -5.425942 4.826360 2.459778 -1.627614 -0.189087 1.900239 0.003004 0.366831 0.006938 0.728642
#> 454: -6.457066 0.376233 -5.425954 4.826371 2.459834 -1.627615 -0.189087 1.900239 0.003005 0.367433 0.006941 0.728999
#> 455: -6.457067 0.376797 -5.425963 4.826367 2.459882 -1.627615 -0.189087 1.900239 0.003011 0.368242 0.006941 0.729353
#> 456: -6.457081 0.376992 -5.425953 4.826362 2.459820 -1.627614 -0.189087 1.900238 0.003013 0.368595 0.006950 0.729669
#> 457: -6.457112 0.377080 -5.425943 4.826334 2.459793 -1.627615 -0.189087 1.900238 0.003012 0.369188 0.006948 0.730019
#> 458: -6.457119 0.377428 -5.425926 4.826335 2.459789 -1.627616 -0.189087 1.900237 0.003008 0.369810 0.006945 0.730359
#> 459: -6.457159 0.377944 -5.425922 4.826353 2.459765 -1.627617 -0.189087 1.900237 0.003009 0.370529 0.006940 0.730688
#> 460: -6.457121 0.378541 -5.425919 4.826362 2.459806 -1.627617 -0.189087 1.900237 0.003005 0.371227 0.006942 0.731040
#> 461: -6.457114 0.378790 -5.425930 4.826349 2.459853 -1.627618 -0.189087 1.900238 0.003002 0.371980 0.006949 0.731365
#> 462: -6.457117 0.379238 -5.425933 4.826345 2.459880 -1.627618 -0.189087 1.900239 0.003003 0.372842 0.006951 0.731675
#> 463: -6.457105 0.379646 -5.425921 4.826347 2.459898 -1.627619 -0.189087 1.900240 0.003004 0.373379 0.006959 0.731994
#> 464: -6.457074 0.379857 -5.425935 4.826360 2.459940 -1.627619 -0.189087 1.900240 0.003004 0.374330 0.006965 0.732317
#> 465: -6.457074 0.380175 -5.425944 4.826376 2.460027 -1.627619 -0.189088 1.900239 0.003005 0.375014 0.006968 0.732639
#> 466: -6.457069 0.380628 -5.425930 4.826369 2.460028 -1.627618 -0.189088 1.900240 0.003008 0.375572 0.006976 0.732956
#> 467: -6.457078 0.381052 -5.425925 4.826373 2.460038 -1.627618 -0.189088 1.900240 0.003006 0.376312 0.006982 0.733262
#> 468: -6.457074 0.381350 -5.425939 4.826387 2.459992 -1.627618 -0.189088 1.900240 0.003003 0.376891 0.006995 0.733558
#> 469: -6.457075 0.381655 -5.425943 4.826389 2.459975 -1.627618 -0.189088 1.900241 0.002999 0.377341 0.007016 0.733871
#> 470: -6.457071 0.381922 -5.425947 4.826394 2.459991 -1.627618 -0.189088 1.900240 0.003000 0.378069 0.007022 0.734169
#> 471: -6.457076 0.382277 -5.425943 4.826398 2.459992 -1.627617 -0.189088 1.900241 0.003002 0.378685 0.007023 0.734464
#> 472: -6.457091 0.382305 -5.425940 4.826402 2.459952 -1.627617 -0.189088 1.900241 0.003004 0.379340 0.007027 0.734770
#> 473: -6.457146 0.382282 -5.425945 4.826406 2.459952 -1.627618 -0.189087 1.900241 0.003007 0.380362 0.007023 0.735106
#> 474: -6.457138 0.382250 -5.425935 4.826398 2.459968 -1.627618 -0.189087 1.900240 0.003005 0.381073 0.007029 0.735394
#> 475: -6.457129 0.382405 -5.425942 4.826405 2.460070 -1.627618 -0.189087 1.900241 0.003006 0.381689 0.007040 0.735667
#> 476: -6.457105 0.382441 -5.425950 4.826412 2.460127 -1.627618 -0.189087 1.900241 0.003005 0.382523 0.007050 0.735943
#> 477: -6.457084 0.382635 -5.425956 4.826420 2.460179 -1.627618 -0.189087 1.900241 0.003009 0.383076 0.007053 0.736209
#> 478: -6.457070 0.382655 -5.425959 4.826414 2.460299 -1.627618 -0.189087 1.900241 0.003012 0.383899 0.007068 0.736495
#> 479: -6.457057 0.382621 -5.425965 4.826417 2.460280 -1.627618 -0.189087 1.900241 0.003012 0.384429 0.007083 0.736772
#> 480: -6.457019 0.382540 -5.425969 4.826416 2.460197 -1.627619 -0.189086 1.900240 0.003014 0.384924 0.007090 0.737021
#> 481: -6.456942 0.382330 -5.425966 4.826424 2.460137 -1.627619 -0.189087 1.900240 0.003018 0.385381 0.007099 0.737271
#> 482: -6.456869 0.382137 -5.425963 4.826432 2.460125 -1.627619 -0.189087 1.900240 0.003022 0.385870 0.007114 0.737545
#> 483: -6.456812 0.382198 -5.425959 4.826435 2.460163 -1.627619 -0.189087 1.900240 0.003025 0.386609 0.007113 0.737807
#> 484: -6.456753 0.382143 -5.425956 4.826447 2.460126 -1.627619 -0.189087 1.900240 0.003026 0.387297 0.007115 0.738082
#> 485: -6.456733 0.382269 -5.425958 4.826448 2.460152 -1.627619 -0.189087 1.900240 0.003024 0.387864 0.007119 0.738326
#> 486: -6.456714 0.382357 -5.425961 4.826456 2.460197 -1.627619 -0.189087 1.900241 0.003023 0.388465 0.007117 0.738589
#> 487: -6.456704 0.382377 -5.425964 4.826453 2.460207 -1.627619 -0.189087 1.900241 0.003019 0.388944 0.007132 0.738853
#> 488: -6.456661 0.382147 -5.425961 4.826463 2.460209 -1.627619 -0.189087 1.900241 0.003019 0.389434 0.007133 0.739117
#> 489: -6.456724 0.381833 -5.425960 4.826469 2.460159 -1.627619 -0.189086 1.900241 0.003021 0.390031 0.007148 0.739359
#> 490: -6.456708 0.381878 -5.425966 4.826474 2.460160 -1.627619 -0.189086 1.900241 0.003024 0.390670 0.007147 0.739636
#> 491: -6.456702 0.381831 -5.425962 4.826479 2.460132 -1.627620 -0.189086 1.900241 0.003025 0.391154 0.007151 0.739869
#> 492: -6.456706 0.381853 -5.425959 4.826480 2.460078 -1.627620 -0.189087 1.900241 0.003029 0.391731 0.007161 0.740110
#> 493: -6.456689 0.381802 -5.425949 4.826488 2.460073 -1.627619 -0.189087 1.900241 0.003030 0.392218 0.007168 0.740354
#> 494: -6.456660 0.381838 -5.425945 4.826488 2.460048 -1.627619 -0.189086 1.900241 0.003030 0.392761 0.007177 0.740592
#> 495: -6.456607 0.381818 -5.425946 4.826483 2.460063 -1.627619 -0.189086 1.900242 0.003028 0.393506 0.007188 0.740817
#> 496: -6.456579 0.381877 -5.425946 4.826488 2.460026 -1.627619 -0.189086 1.900242 0.003030 0.394137 0.007194 0.741047
#> 497: -6.456601 0.381936 -5.425946 4.826491 2.460012 -1.627619 -0.189086 1.900242 0.003030 0.394665 0.007203 0.741292
#> 498: -6.456583 0.381874 -5.425948 4.826491 2.459960 -1.627619 -0.189086 1.900242 0.003030 0.395317 0.007202 0.741535
#> 499: -6.456536 0.381987 -5.425953 4.826490 2.459901 -1.627619 -0.189086 1.900242 0.003030 0.396084 0.007207 0.741780
#> 500: -6.456511 0.382125 -5.425956 4.826490 2.459841 -1.627620 -0.189086 1.900243 0.003029 0.396818 0.007208 0.742012
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#> [====|====|====|====|====|====|====|====|====|====] 0:00:00Goodness of fit Plots
## 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)")