Configure an SAEM model by generating an input list to the SAEM model function
configsaem(
model,
data,
inits,
mcmc = list(niter = c(200, 300), nmc = 3, nu = c(2, 2, 2)),
ODEopt = list(atol = 1e-06, rtol = 1e-04, method = "lsoda", transitAbs = FALSE,
maxeval = 1e+05),
distribution = c("normal", "poisson", "binomial"),
addProp = c("combined2", "combined1"),
seed = 99,
fixed = NULL,
DEBUG = 0,
tol = 1e-04,
itmax = 100L,
type = c("nelder-mead", "newuoa"),
lambdaRange = 3,
powRange = 10,
odeRecalcFactor = 10^(0.5),
maxOdeRecalc = 5L
)a compiled saem model by gen_saem_user_fn()
input data
initial values
a list of various mcmc options
optional ODE solving options
one of c("normal","poisson","binomial")
one of "combined1" and "combined2"; These are the two forms of additive+proportional errors supported by monolix/nonmem:
combined1: transform(y)=transform(f)+(a+b*f^c)*eps
combined2: transform(y)=transform(f)+(a^2+b^2*f^(2c))*eps
seed for random number generator
a character vector of fixed effect only parameters (no random effects attached) to be fixed
Integer determining if debugging is enabled
This is the tolerance for the regression models used for complex residual errors (ie add+prop etc)
This is the maximum number of iterations for the regression models used for complex residual errors. The number of iterations is itmax*number of parameters
indicates the type of optimization for the residuals; Can be one of c("nelder-mead", "newuoa")
This indicates the range that Box-Cox and Yeo-Johnson parameters are constrained to be; The default is 3 indicating the range (-3,3)
This indicates the range that powers can take for residual errors; By default this is 10 indicating the range is c(1/10, 10) or c(0.1,10)
The factor to increase the rtol/atol with bad ODE solving.
Maximum number of times to reduce the ODE tolerances and try to resolve the system if there was a bad ODE solve.
Returns a list neede for the saem fit procedure
Fit a generalized nonlinear mixed-effect model by he Stochastic Approximation Expectation-Maximization (SAEM) algorithm
# \donttest{
# In this ODE system we simply specify the ODEs
ode <- "d/dt(depot) =-KA*depot;
d/dt(centr) = KA*depot - KE*centr;"
m1 <- RxODE(ode)
#>
# In this ode System, we also specify the concentration as C2 = centr/V
ode <- "C2 = centr/V;
d/dt(depot) =-KA*depot;
d/dt(centr) = KA*depot - KE*centr;"
m2 = RxODE(ode)
#>
PKpars <- function() {
CL <- exp(lCL)
V <- exp(lV)
KA <- exp(lKA)
KE <- CL / V
}
PRED <- function() centr / V
PRED2 <- function() C2
saem_fit <- gen_saem_user_fn(model = m1, PKpars, pred = PRED)
#>
#> Warning: this was not generated from nlmixr, loading into symengine
#> → creating SAEM model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
# Can also use PRED2
saem_fit <- gen_saem_user_fn(model=m2, PKpars, pred=PRED2)
#>
#> Warning: this was not generated from nlmixr, loading into symengine
#> → creating SAEM model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
# You can also use the nlmixr UI to run this model and call the lower level functions
one.compartment <- function() {
ini({
tka <- 0.45 # Log Ka
tcl <- 1 # Log Cl
tv <- 3.45 # Log V
eta.ka ~ 0.6
eta.cl ~ 0.3
eta.v ~ 0.1
add.sd <- 0.7
wt.est <- 0.0
})
model({
ka <- exp(tka + eta.ka)
cl <- exp(tcl + eta.cl)
v <- exp(tv + eta.v + wt.est * WT)
d/dt(depot) = -ka * depot
d/dt(center) = ka * depot - cl / v * center
cp = center / v
cp ~ add(add.sd)
})
}
fit <- nlmixr(one.compartment, theo_sd, "saem")
#> ℹ parameter labels from comments will be replaced by 'label()'
#>
#> → generate SAEM model
#> ✔ done
#> 1: 0.2288 0.9677 3.0859 0.0056 0.5700 0.2850 0.0950 4.5245
#> 2: 0.3511 0.9707 3.2955 0.0034 0.5415 0.2707 0.0902 1.8178
#> 3: 0.5238 0.9353 3.2970 0.0027 0.5144 0.2572 0.0857 0.9123
#> 4: 0.4607 0.9651 3.2319 0.0036 0.4887 0.2444 0.0815 0.7016
#> 5: 0.4891 0.9815 3.0947 0.0054 0.4643 0.2321 0.0774 0.6063
#> 6: 0.5061 0.9684 3.0698 0.0058 0.4411 0.2205 0.0735 0.5068
#> 7: 0.5023 0.9883 2.9614 0.0074 0.4414 0.2095 0.0698 0.5062
#> 8: 0.4468 0.9980 2.9028 0.0080 0.4193 0.1990 0.0663 0.5032
#> 9: 0.4153 0.9773 2.9886 0.0067 0.3983 0.1891 0.0630 0.5190
#> 10: 0.4430 0.9780 2.7978 0.0094 0.4423 0.1796 0.0599 0.4963
#> 11: 0.4818 0.9891 2.7850 0.0097 0.4328 0.1706 0.0569 0.4746
#> 12: 0.4665 1.0258 2.8853 0.0082 0.4111 0.1621 0.0540 0.4743
#> 13: 0.4232 1.0326 2.8661 0.0082 0.3906 0.1540 0.0513 0.5009
#> 14: 0.4645 1.0229 2.7932 0.0095 0.4726 0.1463 0.0488 0.4809
#> 15: 0.5062 1.0085 2.8418 0.0090 0.4489 0.1390 0.0463 0.4652
#> 16: 0.5111 1.0073 2.8482 0.0091 0.4265 0.1320 0.0440 0.4645
#> 17: 0.5158 1.0003 2.8472 0.0091 0.4344 0.1254 0.0418 0.4466
#> 18: 0.5092 0.9948 2.8562 0.0089 0.4127 0.1192 0.0397 0.4793
#> 19: 0.4526 0.9930 2.8934 0.0081 0.3974 0.1132 0.0377 0.4742
#> 20: 0.4593 1.0190 2.9236 0.0076 0.4383 0.1075 0.0358 0.4910
#> 21: 0.4705 0.9978 2.9321 0.0077 0.4420 0.1022 0.0341 0.4647
#> 22: 0.4778 1.0054 2.9304 0.0077 0.4458 0.0971 0.0324 0.4556
#> 23: 0.5338 1.0089 2.9851 0.0070 0.5067 0.0922 0.0307 0.4845
#> 24: 0.4738 1.0230 2.9628 0.0071 0.4814 0.0876 0.0292 0.4673
#> 25: 0.4489 1.0101 2.8713 0.0083 0.4573 0.0915 0.0277 0.4668
#> 26: 0.4073 1.0336 2.8700 0.0080 0.4344 0.0869 0.0264 0.4755
#> 27: 0.3808 1.0525 2.8990 0.0076 0.4127 0.0825 0.0250 0.4971
#> 28: 0.4344 1.0355 2.9030 0.0078 0.3980 0.0784 0.0238 0.4465
#> 29: 0.4449 1.0333 2.9591 0.0068 0.3781 0.0745 0.0226 0.4823
#> 30: 0.4594 1.0127 2.9503 0.0072 0.3956 0.0708 0.0215 0.4810
#> 31: 0.4110 1.0045 2.9568 0.0071 0.3758 0.0724 0.0204 0.4825
#> 32: 0.4334 0.9960 2.9692 0.0071 0.4048 0.0688 0.0194 0.4654
#> 33: 0.4543 1.0036 2.9884 0.0068 0.4051 0.0654 0.0184 0.4750
#> 34: 0.4781 1.0037 2.9265 0.0076 0.3849 0.0700 0.0175 0.4857
#> 35: 0.4588 1.0011 2.9969 0.0066 0.3656 0.0716 0.0166 0.4759
#> 36: 0.4455 1.0307 3.0652 0.0055 0.3474 0.0773 0.0158 0.4665
#> 37: 0.4349 1.0312 2.9285 0.0076 0.3354 0.0839 0.0150 0.4916
#> 38: 0.4869 1.0158 2.9028 0.0078 0.4736 0.0797 0.0142 0.4837
#> 39: 0.4968 0.9977 2.8434 0.0090 0.4499 0.0815 0.0140 0.4578
#> 40: 0.5032 0.9914 2.7436 0.0106 0.4274 0.0774 0.0134 0.4765
#> 41: 0.4678 0.9660 2.8057 0.0096 0.4060 0.0735 0.0132 0.4977
#> 42: 0.4708 0.9883 2.8399 0.0090 0.4092 0.0701 0.0126 0.4429
#> 43: 0.4380 1.0116 2.8828 0.0081 0.3887 0.0768 0.0128 0.4403
#> 44: 0.4164 1.0246 2.8060 0.0091 0.4065 0.0730 0.0126 0.4442
#> 45: 0.3910 1.0598 2.7412 0.0098 0.3862 0.0781 0.0119 0.4632
#> 46: 0.3975 1.0336 2.9049 0.0076 0.3669 0.0865 0.0113 0.4583
#> 47: 0.4134 1.0289 2.9616 0.0067 0.3818 0.0858 0.0108 0.4664
#> 48: 0.4256 1.0193 2.8668 0.0081 0.4218 0.0815 0.0106 0.4875
#> 49: 0.4285 1.0266 2.9383 0.0073 0.4007 0.0853 0.0101 0.4973
#> 50: 0.4991 0.9878 2.9406 0.0073 0.4039 0.0929 0.0096 0.5091
#> 51: 0.4606 0.9888 2.9466 0.0072 0.4161 0.0917 0.0094 0.4993
#> 52: 0.5027 1.0133 3.0064 0.0065 0.4647 0.0871 0.0089 0.4759
#> 53: 0.4773 1.0112 2.9368 0.0075 0.4500 0.0827 0.0085 0.4720
#> 54: 0.4237 0.9982 2.9494 0.0072 0.4275 0.0830 0.0080 0.4867
#> 55: 0.4425 1.0135 2.9529 0.0071 0.4061 0.0789 0.0077 0.5019
#> 56: 0.4366 0.9921 2.9077 0.0077 0.3858 0.0749 0.0086 0.4981
#> 57: 0.4427 0.9931 2.8733 0.0083 0.3991 0.0725 0.0086 0.5088
#> 58: 0.4913 0.9949 2.9670 0.0069 0.4044 0.0791 0.0081 0.4903
#> 59: 0.4631 0.9812 3.0400 0.0058 0.4732 0.1079 0.0077 0.5167
#> 60: 0.4629 0.9885 3.0546 0.0057 0.4875 0.1025 0.0099 0.5172
#> 61: 0.5446 0.9957 3.0156 0.0064 0.5543 0.0974 0.0116 0.5103
#> 62: 0.4900 1.0253 2.9865 0.0069 0.5266 0.1013 0.0130 0.5280
#> 63: 0.4927 0.9962 3.0938 0.0053 0.5003 0.1023 0.0152 0.5047
#> 64: 0.4871 1.0171 3.0618 0.0057 0.4753 0.0972 0.0144 0.4929
#> 65: 0.4838 1.0020 3.0185 0.0062 0.4644 0.0923 0.0137 0.4628
#> 66: 0.4921 1.0017 3.0340 0.0062 0.4412 0.0877 0.0135 0.4587
#> 67: 0.4716 0.9783 3.0422 0.0060 0.4796 0.0833 0.0151 0.4604
#> 68: 0.4366 0.9940 3.0199 0.0064 0.4556 0.0791 0.0143 0.5108
#> 69: 0.4385 0.9982 2.9486 0.0072 0.4328 0.0752 0.0136 0.5002
#> 70: 0.4221 1.0189 2.9937 0.0066 0.4860 0.0757 0.0129 0.5009
#> 71: 0.4016 1.0347 2.9678 0.0065 0.4617 0.0758 0.0142 0.5264
#> 72: 0.4151 0.9912 3.0228 0.0060 0.4386 0.0824 0.0135 0.5032
#> 73: 0.4749 1.0136 3.0081 0.0066 0.4167 0.0783 0.0128 0.5045
#> 74: 0.4607 0.9816 2.9735 0.0071 0.3959 0.0743 0.0121 0.4821
#> 75: 0.4948 0.9853 2.9088 0.0083 0.4011 0.0833 0.0122 0.4848
#> 76: 0.5378 0.9899 2.9698 0.0076 0.3811 0.0792 0.0122 0.5201
#> 77: 0.5506 0.9519 2.8874 0.0086 0.3806 0.0752 0.0131 0.5408
#> 78: 0.4911 0.9855 2.7746 0.0101 0.4157 0.0795 0.0144 0.5161
#> 79: 0.5034 1.0018 2.7222 0.0109 0.4490 0.0755 0.0137 0.5172
#> 80: 0.5105 0.9842 2.7954 0.0096 0.4817 0.0755 0.0130 0.5032
#> 81: 0.5110 0.9991 2.8877 0.0083 0.4607 0.0717 0.0141 0.5045
#> 82: 0.4897 0.9758 2.8211 0.0094 0.4761 0.0682 0.0163 0.4973
#> 83: 0.4645 0.9945 2.8349 0.0091 0.4523 0.0685 0.0167 0.4678
#> 84: 0.4845 0.9784 2.9136 0.0079 0.4509 0.0661 0.0180 0.4708
#> 85: 0.4779 1.0076 2.9204 0.0079 0.4445 0.0642 0.0171 0.4917
#> 86: 0.4861 0.9979 2.8459 0.0090 0.4222 0.0753 0.0169 0.4880
#> 87: 0.5066 0.9855 2.9493 0.0075 0.4011 0.0743 0.0160 0.4859
#> 88: 0.4139 0.9689 2.8814 0.0084 0.3964 0.0729 0.0152 0.5056
#> 89: 0.4880 0.9880 3.0100 0.0064 0.3976 0.0715 0.0146 0.4985
#> 90: 0.4508 1.0008 2.9872 0.0066 0.4187 0.0699 0.0154 0.5140
#> 91: 0.4260 1.0124 2.9353 0.0070 0.4915 0.0721 0.0170 0.4828
#> 92: 0.4507 1.0310 2.9768 0.0065 0.5508 0.0821 0.0186 0.4849
#> 93: 0.4156 1.0215 2.9663 0.0067 0.5232 0.0818 0.0176 0.4967
#> 94: 0.4253 1.0309 2.9672 0.0067 0.4971 0.0927 0.0168 0.4940
#> 95: 0.4293 1.0402 2.9557 0.0069 0.5670 0.0880 0.0159 0.5130
#> 96: 0.4091 1.0215 2.7608 0.0095 0.6011 0.0836 0.0179 0.4914
#> 97: 0.4148 1.0283 2.7167 0.0103 0.5710 0.0795 0.0182 0.4873
#> 98: 0.4568 1.0388 2.7550 0.0099 0.5425 0.0755 0.0173 0.4683
#> 99: 0.4516 1.0081 2.8131 0.0090 0.5154 0.0717 0.0164 0.4685
#> 100: 0.4161 1.0146 2.7195 0.0104 0.4896 0.0681 0.0156 0.4648
#> 101: 0.4124 0.9984 2.7309 0.0100 0.4862 0.0774 0.0148 0.4674
#> 102: 0.4114 1.0021 2.7699 0.0094 0.4965 0.0735 0.0141 0.4836
#> 103: 0.4631 1.0080 2.7506 0.0099 0.5232 0.0699 0.0144 0.4663
#> 104: 0.4380 0.9986 2.8772 0.0083 0.5338 0.0694 0.0141 0.5044
#> 105: 0.4544 1.0045 2.8444 0.0085 0.5273 0.0803 0.0134 0.5151
#> 106: 0.4545 0.9904 2.8583 0.0086 0.5009 0.0840 0.0128 0.4922
#> 107: 0.4684 1.0089 2.8140 0.0091 0.5415 0.0892 0.0121 0.4703
#> 108: 0.4306 0.9987 2.9950 0.0065 0.5144 0.0847 0.0118 0.4906
#> 109: 0.4180 1.0095 2.9333 0.0075 0.4887 0.0968 0.0114 0.4718
#> 110: 0.4760 1.0181 2.9466 0.0071 0.4643 0.0919 0.0117 0.4844
#> 111: 0.4700 1.0164 2.9324 0.0075 0.4411 0.0976 0.0113 0.4680
#> 112: 0.4558 1.0036 2.9026 0.0077 0.4766 0.0927 0.0108 0.4614
#> 113: 0.4388 1.0328 2.8671 0.0083 0.5079 0.0881 0.0102 0.4698
#> 114: 0.4567 1.0134 2.9205 0.0075 0.4825 0.0971 0.0098 0.4603
#> 115: 0.4423 1.0116 2.9967 0.0064 0.4583 0.1005 0.0095 0.4718
#> 116: 0.4732 1.0196 2.9908 0.0066 0.4465 0.0955 0.0093 0.4558
#> 117: 0.4275 1.0510 2.9419 0.0072 0.4242 0.0907 0.0089 0.4711
#> 118: 0.4356 1.0201 2.8569 0.0084 0.4142 0.0894 0.0090 0.4577
#> 119: 0.4511 1.0283 2.8167 0.0090 0.4283 0.0931 0.0112 0.4782
#> 120: 0.4049 1.0045 2.8063 0.0092 0.4234 0.0885 0.0107 0.4742
#> 121: 0.4341 1.0186 2.8541 0.0084 0.4063 0.0840 0.0111 0.4768
#> 122: 0.4254 0.9997 2.7958 0.0094 0.4185 0.0798 0.0141 0.4655
#> 123: 0.4609 1.0209 2.8832 0.0081 0.4395 0.0758 0.0141 0.4529
#> 124: 0.4608 1.0518 2.8655 0.0082 0.4666 0.0720 0.0134 0.4620
#> 125: 0.4488 1.0380 2.9991 0.0062 0.4433 0.0787 0.0127 0.4632
#> 126: 0.4332 1.0575 2.8804 0.0078 0.4494 0.0855 0.0121 0.4689
#> 127: 0.4617 1.0350 2.8689 0.0080 0.4269 0.0942 0.0115 0.4848
#> 128: 0.3910 1.0242 2.8530 0.0083 0.4511 0.0895 0.0133 0.4976
#> 129: 0.4243 1.0408 2.8930 0.0078 0.4872 0.0891 0.0127 0.4864
#> 130: 0.4753 1.0640 2.8764 0.0080 0.5144 0.0846 0.0120 0.4768
#> 131: 0.4224 1.0240 2.9354 0.0070 0.4886 0.0816 0.0114 0.4668
#> 132: 0.3935 1.0262 2.9957 0.0061 0.4642 0.0886 0.0108 0.5029
#> 133: 0.4031 1.0150 3.0069 0.0060 0.4410 0.0842 0.0103 0.5101
#> 134: 0.4223 0.9989 3.0363 0.0059 0.4189 0.0800 0.0131 0.4907
#> 135: 0.4447 1.0099 3.0033 0.0065 0.3980 0.0760 0.0125 0.4672
#> 136: 0.4646 1.0001 2.9817 0.0068 0.3854 0.0722 0.0118 0.4583
#> 137: 0.4921 0.9963 3.0924 0.0054 0.4607 0.0686 0.0134 0.4840
#> 138: 0.4692 1.0106 3.0587 0.0058 0.4377 0.0651 0.0131 0.4779
#> 139: 0.4420 1.0132 3.0325 0.0062 0.4158 0.0675 0.0140 0.4725
#> 140: 0.4556 1.0254 2.9416 0.0075 0.4146 0.0690 0.0133 0.4819
#> 141: 0.4540 0.9972 2.9206 0.0078 0.4090 0.0714 0.0127 0.4595
#> 142: 0.5174 0.9817 2.9641 0.0073 0.4369 0.0819 0.0120 0.4643
#> 143: 0.5016 1.0166 2.8976 0.0082 0.4396 0.0778 0.0124 0.4634
#> 144: 0.5336 1.0114 2.9333 0.0078 0.4176 0.0740 0.0118 0.4726
#> 145: 0.4565 1.0076 2.8688 0.0083 0.3968 0.0802 0.0116 0.4578
#> 146: 0.4438 1.0191 2.9896 0.0067 0.4003 0.0762 0.0125 0.4758
#> 147: 0.4326 0.9820 2.8972 0.0079 0.3803 0.0729 0.0119 0.4618
#> 148: 0.4267 1.0131 2.8369 0.0088 0.3648 0.0693 0.0113 0.4653
#> 149: 0.4456 1.0167 2.9018 0.0079 0.3466 0.0727 0.0121 0.4622
#> 150: 0.4858 0.9967 2.8976 0.0080 0.3817 0.0715 0.0115 0.4682
#> 151: 0.4110 1.0269 2.8744 0.0082 0.3701 0.0679 0.0117 0.4809
#> 152: 0.4328 1.0276 2.8772 0.0082 0.3669 0.0755 0.0112 0.4811
#> 153: 0.4322 1.0284 2.8966 0.0079 0.3996 0.0801 0.0138 0.4670
#> 154: 0.4750 1.0416 2.9668 0.0070 0.4104 0.0841 0.0138 0.4819
#> 155: 0.4535 0.9959 2.9690 0.0069 0.4584 0.0740 0.0171 0.4693
#> 156: 0.4958 1.0126 3.0649 0.0057 0.4047 0.0805 0.0188 0.4825
#> 157: 0.4477 0.9991 3.0897 0.0054 0.3324 0.0704 0.0200 0.5065
#> 158: 0.5050 1.0234 3.1133 0.0051 0.3720 0.0596 0.0229 0.4760
#> 159: 0.4442 1.0203 3.0917 0.0054 0.3527 0.0514 0.0198 0.4889
#> 160: 0.4549 0.9931 3.0166 0.0064 0.4168 0.0570 0.0158 0.4968
#> 161: 0.4608 1.0038 3.0785 0.0055 0.3741 0.0534 0.0188 0.4789
#> 162: 0.4568 1.0266 2.9913 0.0066 0.4522 0.0527 0.0190 0.4742
#> 163: 0.4874 1.0062 3.0151 0.0062 0.4967 0.0417 0.0170 0.4633
#> 164: 0.4707 1.0040 2.8950 0.0080 0.4550 0.0453 0.0198 0.4505
#> 165: 0.4828 1.0009 2.8603 0.0086 0.4469 0.0505 0.0182 0.4531
#> 166: 0.5274 1.0169 2.8670 0.0086 0.4745 0.0496 0.0178 0.4634
#> 167: 0.4898 1.0285 2.9447 0.0075 0.4278 0.0585 0.0218 0.4708
#> 168: 0.4873 1.0282 2.9624 0.0074 0.3973 0.0578 0.0207 0.4528
#> 169: 0.4812 1.0384 2.9701 0.0070 0.3871 0.0667 0.0179 0.4842
#> 170: 0.4844 1.0288 2.9239 0.0076 0.4184 0.0556 0.0184 0.4802
#> 171: 0.4471 1.0276 2.8019 0.0093 0.4141 0.0578 0.0188 0.4546
#> 172: 0.4315 1.0385 2.8005 0.0093 0.4145 0.0571 0.0204 0.4507
#> 173: 0.4244 1.0388 2.6534 0.0112 0.3821 0.0610 0.0226 0.4576
#> 174: 0.4490 1.0203 2.7964 0.0094 0.3334 0.0550 0.0223 0.4525
#> 175: 0.4491 1.0067 2.7608 0.0099 0.3644 0.0637 0.0239 0.4566
#> 176: 0.4285 1.0386 2.8126 0.0093 0.3820 0.0631 0.0199 0.4672
#> 177: 0.4596 1.0290 2.6672 0.0114 0.4707 0.0672 0.0222 0.4599
#> 178: 0.4589 1.0065 2.9180 0.0079 0.3906 0.0752 0.0170 0.4490
#> 179: 0.4890 1.0179 2.9000 0.0080 0.3831 0.0773 0.0150 0.4694
#> 180: 0.4382 1.0205 2.9316 0.0075 0.3146 0.0757 0.0144 0.5138
#> 181: 0.4384 1.0189 2.9433 0.0071 0.3520 0.0731 0.0141 0.4903
#> 182: 0.3792 1.0020 2.8568 0.0082 0.3414 0.0916 0.0118 0.5128
#> 183: 0.4133 1.0272 2.8032 0.0090 0.3523 0.0814 0.0118 0.5067
#> 184: 0.3963 1.0338 2.8254 0.0086 0.4331 0.0696 0.0114 0.4769
#> 185: 0.3783 1.0473 2.6707 0.0108 0.4167 0.0649 0.0124 0.4843
#> 186: 0.4024 1.0594 2.7015 0.0104 0.4177 0.0698 0.0128 0.4901
#> 187: 0.4299 1.0275 2.7684 0.0097 0.4662 0.0519 0.0139 0.4750
#> 188: 0.4289 1.0439 2.8010 0.0091 0.5849 0.0656 0.0138 0.4645
#> 189: 0.4313 1.0321 2.7656 0.0097 0.5111 0.0670 0.0127 0.4678
#> 190: 0.4391 1.0272 2.7202 0.0104 0.4190 0.0535 0.0137 0.4502
#> 191: 0.4100 1.0340 2.7200 0.0101 0.4611 0.0647 0.0137 0.4510
#> 192: 0.4006 1.0357 2.7894 0.0092 0.4084 0.0707 0.0116 0.4706
#> 193: 0.4149 1.0503 2.9093 0.0075 0.4382 0.0688 0.0135 0.4404
#> 194: 0.4167 1.0333 2.9343 0.0071 0.4483 0.0717 0.0096 0.4892
#> 195: 0.3717 1.0380 2.9064 0.0073 0.4141 0.0609 0.0095 0.4875
#> 196: 0.3941 1.0387 2.8818 0.0078 0.4471 0.0775 0.0100 0.4823
#> 197: 0.4041 1.0437 2.8901 0.0080 0.4481 0.0665 0.0129 0.5150
#> 198: 0.4718 1.0247 2.9158 0.0075 0.6110 0.0663 0.0155 0.4890
#> 199: 0.4223 1.0229 2.8925 0.0078 0.4937 0.0727 0.0136 0.4724
#> 200: 0.4234 1.0167 2.8196 0.0089 0.4497 0.0770 0.0145 0.5080
#> 201: 0.4196 1.0146 2.8090 0.0090 0.4285 0.0765 0.0148 0.4862
#> 202: 0.4221 1.0182 2.8035 0.0091 0.4430 0.0730 0.0158 0.4848
#> 203: 0.4311 1.0161 2.7955 0.0092 0.4506 0.0737 0.0166 0.4807
#> 204: 0.4343 1.0121 2.8241 0.0089 0.4525 0.0726 0.0161 0.4817
#> 205: 0.4315 1.0157 2.8386 0.0087 0.4450 0.0744 0.0165 0.4818
#> 206: 0.4339 1.0202 2.8425 0.0086 0.4498 0.0749 0.0163 0.4861
#> 207: 0.4304 1.0213 2.8367 0.0087 0.4450 0.0746 0.0161 0.4830
#> 208: 0.4304 1.0201 2.8441 0.0086 0.4351 0.0733 0.0163 0.4814
#> 209: 0.4358 1.0169 2.8511 0.0085 0.4397 0.0728 0.0163 0.4798
#> 210: 0.4398 1.0141 2.8553 0.0085 0.4401 0.0719 0.0161 0.4777
#> 211: 0.4463 1.0130 2.8558 0.0085 0.4403 0.0719 0.0159 0.4760
#> 212: 0.4530 1.0112 2.8588 0.0085 0.4411 0.0712 0.0156 0.4756
#> 213: 0.4568 1.0080 2.8646 0.0084 0.4404 0.0711 0.0155 0.4780
#> 214: 0.4622 1.0065 2.8773 0.0082 0.4414 0.0719 0.0154 0.4782
#> 215: 0.4638 1.0068 2.8915 0.0081 0.4392 0.0722 0.0156 0.4777
#> 216: 0.4697 1.0057 2.9001 0.0079 0.4454 0.0722 0.0154 0.4800
#> 217: 0.4722 1.0061 2.9040 0.0079 0.4476 0.0720 0.0154 0.4790
#> 218: 0.4743 1.0064 2.9118 0.0078 0.4511 0.0715 0.0155 0.4790
#> 219: 0.4754 1.0059 2.9234 0.0076 0.4527 0.0709 0.0156 0.4799
#> 220: 0.4738 1.0063 2.9283 0.0075 0.4499 0.0706 0.0158 0.4806
#> 221: 0.4727 1.0066 2.9310 0.0075 0.4451 0.0701 0.0159 0.4802
#> 222: 0.4730 1.0072 2.9332 0.0075 0.4459 0.0702 0.0160 0.4798
#> 223: 0.4751 1.0076 2.9349 0.0075 0.4458 0.0698 0.0161 0.4788
#> 224: 0.4777 1.0081 2.9325 0.0075 0.4480 0.0699 0.0162 0.4789
#> 225: 0.4771 1.0068 2.9309 0.0075 0.4474 0.0694 0.0163 0.4794
#> 226: 0.4779 1.0056 2.9263 0.0076 0.4482 0.0690 0.0164 0.4788
#> 227: 0.4773 1.0059 2.9236 0.0076 0.4473 0.0686 0.0164 0.4785
#> 228: 0.4759 1.0069 2.9224 0.0076 0.4456 0.0680 0.0164 0.4781
#> 229: 0.4747 1.0069 2.9185 0.0077 0.4456 0.0679 0.0165 0.4773
#> 230: 0.4741 1.0072 2.9148 0.0077 0.4438 0.0684 0.0165 0.4768
#> 231: 0.4733 1.0082 2.9121 0.0078 0.4412 0.0684 0.0165 0.4765
#> 232: 0.4721 1.0088 2.9114 0.0078 0.4408 0.0685 0.0164 0.4758
#> 233: 0.4707 1.0086 2.9138 0.0078 0.4426 0.0682 0.0165 0.4758
#> 234: 0.4703 1.0088 2.9113 0.0078 0.4413 0.0679 0.0165 0.4761
#> 235: 0.4700 1.0089 2.9091 0.0078 0.4419 0.0677 0.0165 0.4761
#> 236: 0.4691 1.0096 2.9077 0.0078 0.4410 0.0677 0.0166 0.4761
#> 237: 0.4687 1.0096 2.9068 0.0078 0.4405 0.0678 0.0167 0.4766
#> 238: 0.4683 1.0098 2.9069 0.0078 0.4408 0.0677 0.0167 0.4766
#> 239: 0.4678 1.0102 2.9051 0.0079 0.4420 0.0676 0.0167 0.4763
#> 240: 0.4679 1.0100 2.9038 0.0079 0.4406 0.0677 0.0168 0.4759
#> 241: 0.4688 1.0091 2.9044 0.0079 0.4414 0.0679 0.0168 0.4759
#> 242: 0.4690 1.0084 2.9050 0.0079 0.4399 0.0683 0.0167 0.4762
#> 243: 0.4690 1.0088 2.9050 0.0079 0.4380 0.0688 0.0167 0.4765
#> 244: 0.4681 1.0087 2.9065 0.0079 0.4355 0.0691 0.0167 0.4765
#> 245: 0.4684 1.0084 2.9075 0.0079 0.4330 0.0692 0.0166 0.4772
#> 246: 0.4693 1.0085 2.9071 0.0079 0.4324 0.0694 0.0166 0.4775
#> 247: 0.4699 1.0083 2.9082 0.0079 0.4323 0.0696 0.0166 0.4778
#> 248: 0.4708 1.0083 2.9078 0.0079 0.4328 0.0695 0.0166 0.4775
#> 249: 0.4707 1.0081 2.9090 0.0078 0.4325 0.0695 0.0166 0.4774
#> 250: 0.4712 1.0083 2.9082 0.0079 0.4331 0.0694 0.0167 0.4775
#> 251: 0.4714 1.0087 2.9081 0.0079 0.4352 0.0697 0.0166 0.4775
#> 252: 0.4711 1.0088 2.9086 0.0079 0.4369 0.0696 0.0166 0.4774
#> 253: 0.4705 1.0090 2.9102 0.0078 0.4378 0.0693 0.0167 0.4779
#> 254: 0.4701 1.0094 2.9093 0.0078 0.4380 0.0692 0.0166 0.4776
#> 255: 0.4693 1.0097 2.9071 0.0079 0.4371 0.0690 0.0166 0.4775
#> 256: 0.4696 1.0098 2.9058 0.0079 0.4369 0.0690 0.0167 0.4773
#> 257: 0.4693 1.0093 2.9063 0.0079 0.4363 0.0687 0.0166 0.4774
#> 258: 0.4686 1.0092 2.9042 0.0079 0.4365 0.0687 0.0166 0.4772
#> 259: 0.4679 1.0091 2.9029 0.0079 0.4362 0.0689 0.0165 0.4771
#> 260: 0.4673 1.0095 2.9031 0.0079 0.4359 0.0688 0.0165 0.4769
#> 261: 0.4671 1.0098 2.9037 0.0079 0.4350 0.0687 0.0165 0.4773
#> 262: 0.4669 1.0101 2.9044 0.0079 0.4346 0.0688 0.0165 0.4774
#> 263: 0.4664 1.0106 2.9037 0.0079 0.4338 0.0687 0.0166 0.4777
#> 264: 0.4659 1.0111 2.9039 0.0079 0.4343 0.0687 0.0166 0.4783
#> 265: 0.4658 1.0113 2.9046 0.0079 0.4349 0.0688 0.0166 0.4785
#> 266: 0.4660 1.0112 2.9043 0.0079 0.4364 0.0689 0.0166 0.4784
#> 267: 0.4662 1.0111 2.9043 0.0079 0.4383 0.0689 0.0165 0.4783
#> 268: 0.4663 1.0109 2.9044 0.0079 0.4392 0.0688 0.0165 0.4785
#> 269: 0.4665 1.0108 2.9035 0.0079 0.4391 0.0689 0.0165 0.4786
#> 270: 0.4671 1.0108 2.9040 0.0079 0.4401 0.0691 0.0164 0.4785
#> 271: 0.4677 1.0105 2.9037 0.0079 0.4408 0.0692 0.0164 0.4786
#> 272: 0.4681 1.0102 2.9039 0.0079 0.4408 0.0693 0.0163 0.4792
#> 273: 0.4682 1.0102 2.9040 0.0079 0.4406 0.0697 0.0163 0.4793
#> 274: 0.4686 1.0101 2.9045 0.0079 0.4397 0.0698 0.0163 0.4791
#> 275: 0.4689 1.0102 2.9056 0.0079 0.4393 0.0699 0.0163 0.4789
#> 276: 0.4693 1.0102 2.9068 0.0079 0.4398 0.0699 0.0163 0.4788
#> 277: 0.4694 1.0102 2.9074 0.0079 0.4394 0.0699 0.0162 0.4788
#> 278: 0.4693 1.0101 2.9076 0.0079 0.4389 0.0699 0.0162 0.4788
#> 279: 0.4696 1.0099 2.9078 0.0079 0.4394 0.0698 0.0162 0.4790
#> 280: 0.4696 1.0097 2.9071 0.0079 0.4392 0.0699 0.0162 0.4791
#> 281: 0.4695 1.0097 2.9068 0.0079 0.4395 0.0699 0.0162 0.4787
#> 282: 0.4697 1.0100 2.9068 0.0079 0.4407 0.0700 0.0161 0.4785
#> 283: 0.4699 1.0101 2.9077 0.0079 0.4420 0.0700 0.0160 0.4789
#> 284: 0.4696 1.0101 2.9080 0.0079 0.4431 0.0700 0.0160 0.4788
#> 285: 0.4693 1.0101 2.9076 0.0079 0.4428 0.0700 0.0160 0.4790
#> 286: 0.4691 1.0100 2.9072 0.0079 0.4427 0.0700 0.0160 0.4789
#> 287: 0.4687 1.0101 2.9082 0.0079 0.4425 0.0701 0.0160 0.4790
#> 288: 0.4684 1.0102 2.9064 0.0079 0.4419 0.0700 0.0160 0.4792
#> 289: 0.4682 1.0100 2.9060 0.0079 0.4414 0.0699 0.0160 0.4792
#> 290: 0.4686 1.0100 2.9061 0.0079 0.4412 0.0699 0.0160 0.4792
#> 291: 0.4691 1.0101 2.9061 0.0079 0.4419 0.0699 0.0160 0.4790
#> 292: 0.4693 1.0101 2.9059 0.0079 0.4427 0.0700 0.0160 0.4789
#> 293: 0.4695 1.0100 2.9061 0.0079 0.4434 0.0700 0.0160 0.4791
#> 294: 0.4696 1.0100 2.9066 0.0079 0.4440 0.0700 0.0159 0.4790
#> 295: 0.4697 1.0097 2.9069 0.0079 0.4448 0.0700 0.0159 0.4788
#> 296: 0.4695 1.0099 2.9070 0.0079 0.4440 0.0700 0.0159 0.4789
#> 297: 0.4695 1.0101 2.9076 0.0079 0.4438 0.0700 0.0160 0.4789
#> 298: 0.4695 1.0101 2.9079 0.0079 0.4435 0.0699 0.0159 0.4788
#> 299: 0.4694 1.0102 2.9079 0.0079 0.4436 0.0699 0.0159 0.4787
#> 300: 0.4691 1.0100 2.9075 0.0079 0.4434 0.0698 0.0158 0.4788
#> 301: 0.4689 1.0099 2.9073 0.0079 0.4428 0.0698 0.0158 0.4792
#> 302: 0.4690 1.0099 2.9068 0.0079 0.4427 0.0698 0.0158 0.4790
#> 303: 0.4690 1.0099 2.9063 0.0079 0.4426 0.0697 0.0158 0.4787
#> 304: 0.4693 1.0100 2.9048 0.0079 0.4437 0.0696 0.0158 0.4787
#> 305: 0.4691 1.0099 2.9033 0.0079 0.4440 0.0696 0.0158 0.4787
#> 306: 0.4687 1.0098 2.9016 0.0080 0.4439 0.0697 0.0158 0.4787
#> 307: 0.4683 1.0097 2.9000 0.0080 0.4431 0.0697 0.0158 0.4790
#> 308: 0.4678 1.0098 2.8990 0.0080 0.4430 0.0697 0.0158 0.4792
#> 309: 0.4675 1.0098 2.8987 0.0080 0.4423 0.0697 0.0158 0.4796
#> 310: 0.4680 1.0099 2.8984 0.0080 0.4425 0.0698 0.0158 0.4799
#> 311: 0.4681 1.0099 2.8973 0.0080 0.4427 0.0701 0.0157 0.4799
#> 312: 0.4681 1.0099 2.8954 0.0080 0.4425 0.0703 0.0157 0.4799
#> 313: 0.4678 1.0096 2.8948 0.0080 0.4423 0.0704 0.0156 0.4803
#> 314: 0.4675 1.0095 2.8943 0.0081 0.4420 0.0703 0.0156 0.4803
#> 315: 0.4674 1.0096 2.8938 0.0081 0.4422 0.0703 0.0156 0.4802
#> 316: 0.4674 1.0097 2.8937 0.0081 0.4424 0.0703 0.0155 0.4801
#> 317: 0.4675 1.0098 2.8938 0.0081 0.4418 0.0703 0.0155 0.4802
#> 318: 0.4676 1.0098 2.8938 0.0081 0.4411 0.0702 0.0155 0.4801
#> 319: 0.4675 1.0098 2.8930 0.0081 0.4404 0.0702 0.0155 0.4802
#> 320: 0.4672 1.0096 2.8925 0.0081 0.4410 0.0702 0.0155 0.4803
#> 321: 0.4667 1.0097 2.8911 0.0081 0.4410 0.0700 0.0155 0.4804
#> 322: 0.4664 1.0098 2.8907 0.0081 0.4416 0.0699 0.0155 0.4804
#> 323: 0.4662 1.0098 2.8907 0.0081 0.4418 0.0699 0.0155 0.4801
#> 324: 0.4659 1.0099 2.8908 0.0081 0.4419 0.0699 0.0154 0.4798
#> 325: 0.4658 1.0102 2.8903 0.0081 0.4419 0.0698 0.0154 0.4796
#> 326: 0.4653 1.0103 2.8902 0.0081 0.4417 0.0698 0.0154 0.4795
#> 327: 0.4654 1.0104 2.8897 0.0081 0.4425 0.0698 0.0155 0.4793
#> 328: 0.4655 1.0106 2.8900 0.0081 0.4431 0.0697 0.0155 0.4793
#> 329: 0.4654 1.0106 2.8897 0.0081 0.4431 0.0697 0.0154 0.4793
#> 330: 0.4651 1.0107 2.8895 0.0081 0.4430 0.0697 0.0154 0.4795
#> 331: 0.4649 1.0109 2.8894 0.0081 0.4429 0.0697 0.0154 0.4793
#> 332: 0.4651 1.0109 2.8895 0.0081 0.4432 0.0698 0.0154 0.4794
#> 333: 0.4651 1.0110 2.8891 0.0081 0.4435 0.0698 0.0154 0.4794
#> 334: 0.4648 1.0110 2.8882 0.0081 0.4432 0.0698 0.0154 0.4795
#> 335: 0.4645 1.0109 2.8882 0.0081 0.4433 0.0698 0.0154 0.4795
#> 336: 0.4638 1.0112 2.8876 0.0081 0.4432 0.0699 0.0154 0.4796
#> 337: 0.4635 1.0115 2.8871 0.0081 0.4433 0.0700 0.0154 0.4797
#> 338: 0.4635 1.0115 2.8860 0.0081 0.4435 0.0701 0.0154 0.4796
#> 339: 0.4633 1.0116 2.8859 0.0081 0.4434 0.0700 0.0154 0.4795
#> 340: 0.4632 1.0116 2.8856 0.0082 0.4436 0.0701 0.0154 0.4795
#> 341: 0.4631 1.0117 2.8850 0.0082 0.4438 0.0702 0.0154 0.4795
#> 342: 0.4627 1.0116 2.8844 0.0082 0.4436 0.0702 0.0154 0.4795
#> 343: 0.4623 1.0116 2.8839 0.0082 0.4431 0.0703 0.0154 0.4796
#> 344: 0.4623 1.0116 2.8837 0.0082 0.4431 0.0702 0.0154 0.4796
#> 345: 0.4621 1.0115 2.8832 0.0082 0.4430 0.0702 0.0153 0.4797
#> 346: 0.4619 1.0117 2.8831 0.0082 0.4428 0.0701 0.0153 0.4797
#> 347: 0.4615 1.0118 2.8832 0.0082 0.4425 0.0702 0.0153 0.4797
#> 348: 0.4611 1.0119 2.8828 0.0082 0.4424 0.0702 0.0153 0.4799
#> 349: 0.4605 1.0120 2.8828 0.0082 0.4424 0.0702 0.0153 0.4799
#> 350: 0.4602 1.0120 2.8825 0.0082 0.4428 0.0702 0.0153 0.4799
#> 351: 0.4601 1.0122 2.8822 0.0082 0.4429 0.0702 0.0153 0.4799
#> 352: 0.4597 1.0122 2.8823 0.0082 0.4429 0.0702 0.0154 0.4802
#> 353: 0.4596 1.0124 2.8816 0.0082 0.4428 0.0702 0.0154 0.4803
#> 354: 0.4594 1.0125 2.8818 0.0082 0.4429 0.0702 0.0154 0.4804
#> 355: 0.4594 1.0126 2.8826 0.0082 0.4428 0.0702 0.0154 0.4804
#> 356: 0.4592 1.0125 2.8824 0.0082 0.4427 0.0702 0.0154 0.4806
#> 357: 0.4595 1.0127 2.8831 0.0082 0.4428 0.0701 0.0153 0.4805
#> 358: 0.4593 1.0127 2.8836 0.0082 0.4426 0.0701 0.0153 0.4806
#> 359: 0.4591 1.0129 2.8842 0.0082 0.4424 0.0701 0.0153 0.4805
#> 360: 0.4590 1.0129 2.8846 0.0081 0.4423 0.0701 0.0153 0.4804
#> 361: 0.4588 1.0130 2.8851 0.0081 0.4420 0.0701 0.0153 0.4804
#> 362: 0.4588 1.0131 2.8851 0.0081 0.4417 0.0701 0.0153 0.4802
#> 363: 0.4587 1.0130 2.8849 0.0081 0.4417 0.0700 0.0153 0.4798
#> 364: 0.4589 1.0129 2.8850 0.0081 0.4422 0.0699 0.0153 0.4798
#> 365: 0.4588 1.0128 2.8842 0.0081 0.4422 0.0699 0.0153 0.4798
#> 366: 0.4587 1.0128 2.8838 0.0082 0.4417 0.0699 0.0153 0.4801
#> 367: 0.4586 1.0128 2.8836 0.0082 0.4414 0.0699 0.0153 0.4801
#> 368: 0.4588 1.0128 2.8830 0.0082 0.4414 0.0699 0.0153 0.4799
#> 369: 0.4588 1.0128 2.8830 0.0082 0.4418 0.0699 0.0153 0.4799
#> 370: 0.4587 1.0128 2.8825 0.0082 0.4417 0.0699 0.0153 0.4800
#> 371: 0.4585 1.0130 2.8820 0.0082 0.4413 0.0699 0.0153 0.4800
#> 372: 0.4580 1.0132 2.8812 0.0082 0.4410 0.0699 0.0153 0.4800
#> 373: 0.4574 1.0135 2.8805 0.0082 0.4407 0.0700 0.0152 0.4801
#> 374: 0.4569 1.0137 2.8797 0.0082 0.4407 0.0700 0.0152 0.4802
#> 375: 0.4566 1.0138 2.8792 0.0082 0.4406 0.0700 0.0152 0.4803
#> 376: 0.4563 1.0139 2.8787 0.0082 0.4403 0.0701 0.0152 0.4802
#> 377: 0.4561 1.0140 2.8783 0.0082 0.4401 0.0701 0.0152 0.4801
#> 378: 0.4557 1.0140 2.8788 0.0082 0.4399 0.0701 0.0152 0.4802
#> 379: 0.4556 1.0139 2.8791 0.0082 0.4398 0.0701 0.0152 0.4802
#> 380: 0.4554 1.0139 2.8790 0.0082 0.4395 0.0702 0.0152 0.4801
#> 381: 0.4551 1.0140 2.8789 0.0082 0.4393 0.0703 0.0152 0.4801
#> 382: 0.4550 1.0140 2.8793 0.0082 0.4390 0.0703 0.0151 0.4802
#> 383: 0.4550 1.0140 2.8793 0.0082 0.4387 0.0702 0.0152 0.4800
#> 384: 0.4548 1.0140 2.8790 0.0082 0.4383 0.0702 0.0152 0.4800
#> 385: 0.4549 1.0139 2.8784 0.0082 0.4383 0.0702 0.0152 0.4799
#> 386: 0.4551 1.0140 2.8777 0.0082 0.4385 0.0702 0.0152 0.4798
#> 387: 0.4554 1.0140 2.8772 0.0082 0.4385 0.0701 0.0152 0.4798
#> 388: 0.4556 1.0140 2.8764 0.0082 0.4387 0.0702 0.0152 0.4797
#> 389: 0.4556 1.0138 2.8762 0.0082 0.4387 0.0702 0.0152 0.4797
#> 390: 0.4555 1.0137 2.8765 0.0082 0.4388 0.0702 0.0152 0.4797
#> 391: 0.4557 1.0136 2.8770 0.0082 0.4389 0.0703 0.0152 0.4796
#> 392: 0.4558 1.0136 2.8771 0.0082 0.4393 0.0702 0.0152 0.4797
#> 393: 0.4560 1.0135 2.8775 0.0082 0.4399 0.0702 0.0152 0.4798
#> 394: 0.4561 1.0134 2.8779 0.0082 0.4403 0.0702 0.0152 0.4799
#> 395: 0.4562 1.0134 2.8782 0.0082 0.4402 0.0701 0.0152 0.4799
#> 396: 0.4563 1.0134 2.8785 0.0082 0.4404 0.0701 0.0152 0.4799
#> 397: 0.4565 1.0133 2.8785 0.0082 0.4405 0.0702 0.0152 0.4799
#> 398: 0.4567 1.0132 2.8783 0.0082 0.4403 0.0702 0.0152 0.4800
#> 399: 0.4567 1.0132 2.8779 0.0082 0.4403 0.0703 0.0152 0.4800
#> 400: 0.4567 1.0133 2.8773 0.0082 0.4403 0.0703 0.0152 0.4800
#> 401: 0.4564 1.0133 2.8761 0.0083 0.4402 0.0703 0.0152 0.4802
#> 402: 0.4564 1.0134 2.8752 0.0083 0.4399 0.0703 0.0152 0.4801
#> 403: 0.4564 1.0135 2.8749 0.0083 0.4400 0.0703 0.0152 0.4800
#> 404: 0.4563 1.0135 2.8743 0.0083 0.4398 0.0703 0.0152 0.4799
#> 405: 0.4561 1.0136 2.8739 0.0083 0.4400 0.0703 0.0152 0.4799
#> 406: 0.4560 1.0136 2.8737 0.0083 0.4399 0.0703 0.0152 0.4800
#> 407: 0.4559 1.0136 2.8738 0.0083 0.4399 0.0704 0.0152 0.4799
#> 408: 0.4561 1.0136 2.8740 0.0083 0.4399 0.0704 0.0152 0.4800
#> 409: 0.4560 1.0137 2.8744 0.0083 0.4395 0.0704 0.0152 0.4799
#> 410: 0.4560 1.0137 2.8748 0.0083 0.4395 0.0704 0.0152 0.4800
#> 411: 0.4562 1.0136 2.8751 0.0083 0.4397 0.0704 0.0152 0.4800
#> 412: 0.4560 1.0138 2.8758 0.0083 0.4391 0.0704 0.0152 0.4800
#> 413: 0.4558 1.0138 2.8760 0.0082 0.4385 0.0704 0.0152 0.4801
#> 414: 0.4556 1.0139 2.8758 0.0083 0.4387 0.0704 0.0152 0.4800
#> 415: 0.4558 1.0139 2.8757 0.0083 0.4391 0.0704 0.0152 0.4799
#> 416: 0.4558 1.0139 2.8753 0.0083 0.4392 0.0704 0.0152 0.4799
#> 417: 0.4559 1.0139 2.8750 0.0083 0.4394 0.0704 0.0152 0.4798
#> 418: 0.4558 1.0138 2.8748 0.0083 0.4393 0.0704 0.0152 0.4796
#> 419: 0.4559 1.0139 2.8746 0.0083 0.4390 0.0704 0.0152 0.4796
#> 420: 0.4559 1.0139 2.8748 0.0083 0.4388 0.0705 0.0151 0.4794
#> 421: 0.4557 1.0139 2.8747 0.0083 0.4385 0.0704 0.0151 0.4794
#> 422: 0.4558 1.0139 2.8748 0.0083 0.4387 0.0704 0.0151 0.4793
#> 423: 0.4557 1.0139 2.8749 0.0083 0.4387 0.0704 0.0151 0.4792
#> 424: 0.4555 1.0140 2.8747 0.0083 0.4387 0.0705 0.0151 0.4791
#> 425: 0.4555 1.0140 2.8745 0.0083 0.4388 0.0705 0.0151 0.4790
#> 426: 0.4555 1.0141 2.8744 0.0083 0.4389 0.0705 0.0151 0.4789
#> 427: 0.4554 1.0142 2.8748 0.0083 0.4391 0.0705 0.0151 0.4788
#> 428: 0.4554 1.0142 2.8753 0.0083 0.4390 0.0705 0.0151 0.4789
#> 429: 0.4555 1.0142 2.8753 0.0083 0.4390 0.0705 0.0151 0.4788
#> 430: 0.4554 1.0143 2.8758 0.0083 0.4390 0.0705 0.0151 0.4788
#> 431: 0.4554 1.0143 2.8762 0.0082 0.4387 0.0705 0.0151 0.4787
#> 432: 0.4555 1.0144 2.8767 0.0082 0.4387 0.0705 0.0151 0.4785
#> 433: 0.4555 1.0145 2.8765 0.0082 0.4389 0.0706 0.0152 0.4784
#> 434: 0.4555 1.0144 2.8766 0.0082 0.4389 0.0706 0.0152 0.4783
#> 435: 0.4555 1.0144 2.8768 0.0082 0.4388 0.0706 0.0152 0.4782
#> 436: 0.4555 1.0144 2.8777 0.0082 0.4386 0.0706 0.0152 0.4783
#> 437: 0.4555 1.0144 2.8781 0.0082 0.4384 0.0706 0.0152 0.4783
#> 438: 0.4555 1.0145 2.8779 0.0082 0.4383 0.0706 0.0151 0.4782
#> 439: 0.4556 1.0146 2.8780 0.0082 0.4384 0.0706 0.0151 0.4781
#> 440: 0.4556 1.0147 2.8782 0.0082 0.4382 0.0706 0.0151 0.4781
#> 441: 0.4557 1.0146 2.8784 0.0082 0.4383 0.0705 0.0151 0.4781
#> 442: 0.4558 1.0146 2.8784 0.0082 0.4383 0.0705 0.0151 0.4779
#> 443: 0.4559 1.0147 2.8785 0.0082 0.4385 0.0705 0.0151 0.4778
#> 444: 0.4558 1.0148 2.8790 0.0082 0.4385 0.0706 0.0151 0.4777
#> 445: 0.4558 1.0149 2.8788 0.0082 0.4389 0.0706 0.0151 0.4777
#> 446: 0.4557 1.0149 2.8788 0.0082 0.4392 0.0706 0.0150 0.4777
#> 447: 0.4559 1.0149 2.8789 0.0082 0.4393 0.0706 0.0150 0.4776
#> 448: 0.4560 1.0148 2.8793 0.0082 0.4391 0.0706 0.0150 0.4776
#> 449: 0.4562 1.0148 2.8795 0.0082 0.4387 0.0706 0.0150 0.4776
#> 450: 0.4563 1.0147 2.8796 0.0082 0.4385 0.0705 0.0150 0.4777
#> 451: 0.4566 1.0146 2.8795 0.0082 0.4388 0.0705 0.0151 0.4777
#> 452: 0.4567 1.0146 2.8798 0.0082 0.4390 0.0705 0.0150 0.4777
#> 453: 0.4567 1.0146 2.8799 0.0082 0.4390 0.0705 0.0150 0.4776
#> 454: 0.4567 1.0147 2.8801 0.0082 0.4389 0.0705 0.0150 0.4775
#> 455: 0.4567 1.0147 2.8801 0.0082 0.4391 0.0705 0.0150 0.4775
#> 456: 0.4566 1.0147 2.8801 0.0082 0.4391 0.0705 0.0150 0.4775
#> 457: 0.4564 1.0147 2.8801 0.0082 0.4392 0.0704 0.0150 0.4775
#> 458: 0.4564 1.0148 2.8803 0.0082 0.4393 0.0704 0.0150 0.4773
#> 459: 0.4562 1.0150 2.8804 0.0082 0.4392 0.0704 0.0150 0.4773
#> 460: 0.4560 1.0150 2.8808 0.0082 0.4390 0.0704 0.0150 0.4773
#> 461: 0.4560 1.0151 2.8813 0.0082 0.4388 0.0703 0.0150 0.4774
#> 462: 0.4557 1.0152 2.8815 0.0082 0.4386 0.0703 0.0150 0.4774
#> 463: 0.4557 1.0153 2.8819 0.0082 0.4384 0.0703 0.0150 0.4774
#> 464: 0.4557 1.0153 2.8824 0.0082 0.4384 0.0703 0.0150 0.4774
#> 465: 0.4557 1.0152 2.8827 0.0082 0.4382 0.0703 0.0150 0.4774
#> 466: 0.4557 1.0152 2.8829 0.0082 0.4379 0.0703 0.0150 0.4775
#> 467: 0.4555 1.0151 2.8833 0.0081 0.4376 0.0703 0.0150 0.4774
#> 468: 0.4556 1.0151 2.8837 0.0081 0.4374 0.0703 0.0150 0.4774
#> 469: 0.4557 1.0152 2.8842 0.0081 0.4374 0.0704 0.0149 0.4773
#> 470: 0.4557 1.0152 2.8843 0.0081 0.4374 0.0704 0.0149 0.4774
#> 471: 0.4557 1.0152 2.8844 0.0081 0.4374 0.0705 0.0149 0.4775
#> 472: 0.4557 1.0151 2.8842 0.0081 0.4374 0.0705 0.0149 0.4776
#> 473: 0.4557 1.0150 2.8845 0.0081 0.4372 0.0705 0.0149 0.4776
#> 474: 0.4557 1.0149 2.8844 0.0081 0.4370 0.0705 0.0149 0.4777
#> 475: 0.4558 1.0151 2.8848 0.0081 0.4368 0.0705 0.0149 0.4777
#> 476: 0.4558 1.0151 2.8847 0.0081 0.4367 0.0705 0.0149 0.4777
#> 477: 0.4557 1.0151 2.8845 0.0081 0.4365 0.0705 0.0149 0.4777
#> 478: 0.4555 1.0150 2.8840 0.0081 0.4363 0.0705 0.0149 0.4777
#> 479: 0.4556 1.0150 2.8838 0.0081 0.4362 0.0705 0.0149 0.4777
#> 480: 0.4555 1.0151 2.8841 0.0081 0.4359 0.0706 0.0149 0.4778
#> 481: 0.4553 1.0151 2.8842 0.0081 0.4356 0.0706 0.0149 0.4779
#> 482: 0.4553 1.0152 2.8842 0.0081 0.4355 0.0705 0.0149 0.4779
#> 483: 0.4552 1.0152 2.8844 0.0081 0.4357 0.0705 0.0149 0.4779
#> 484: 0.4550 1.0151 2.8844 0.0081 0.4359 0.0705 0.0149 0.4779
#> 485: 0.4551 1.0152 2.8844 0.0081 0.4361 0.0705 0.0149 0.4779
#> 486: 0.4550 1.0153 2.8844 0.0081 0.4360 0.0705 0.0149 0.4779
#> 487: 0.4552 1.0153 2.8848 0.0081 0.4359 0.0705 0.0149 0.4779
#> 488: 0.4553 1.0154 2.8851 0.0081 0.4358 0.0706 0.0149 0.4778
#> 489: 0.4554 1.0153 2.8851 0.0081 0.4358 0.0705 0.0149 0.4778
#> 490: 0.4555 1.0153 2.8852 0.0081 0.4358 0.0705 0.0149 0.4777
#> 491: 0.4554 1.0153 2.8851 0.0081 0.4357 0.0705 0.0149 0.4775
#> 492: 0.4554 1.0154 2.8850 0.0081 0.4356 0.0704 0.0149 0.4775
#> 493: 0.4553 1.0154 2.8850 0.0081 0.4354 0.0704 0.0149 0.4775
#> 494: 0.4553 1.0154 2.8848 0.0081 0.4353 0.0704 0.0149 0.4775
#> 495: 0.4554 1.0154 2.8847 0.0081 0.4352 0.0703 0.0149 0.4775
#> 496: 0.4555 1.0155 2.8845 0.0081 0.4351 0.0703 0.0149 0.4775
#> 497: 0.4555 1.0154 2.8843 0.0081 0.4352 0.0702 0.0149 0.4775
#> 498: 0.4555 1.0154 2.8840 0.0081 0.4351 0.0702 0.0149 0.4775
#> 499: 0.4556 1.0155 2.8838 0.0081 0.4354 0.0702 0.0149 0.4774
#> 500: 0.4557 1.0155 2.8839 0.0081 0.4356 0.0702 0.0148 0.4773
#> Calculating covariance matrix
#>
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → compiling EBE model...
#>
#> ✔ done
#> Needed Covariates:
#> [1] "WT"
#> Calculating residuals/tables
#> done
fit
#> ── nlmixr SAEM(ODE); OBJF not calculated fit ───────────────────────────────────
#>
#> Gaussian/Laplacian Likelihoods: AIC() or $objf etc.
#> FOCEi CWRES & Likelihoods: addCwres()
#>
#> ── Time (sec $time): ───────────────────────────────────────────────────────────
#>
#> saem setup table covariance other
#> elapsed 6.14 2.014173 0.013 0.012 0.623827
#>
#> ── Population Parameters ($parFixed or $parFixedDf): ───────────────────────────
#>
#> Parameter Est. SE %RSE Back-transformed(95%CI) BSV(CV%)
#> tka Log Ka 0.456 0.201 44 1.58 (1.06, 2.34) 73.9
#> tcl Log Cl 1.02 0.0837 8.24 2.76 (2.34, 3.25) 27.0
#> tv Log V 2.88 0.316 11 17.9 (9.62, 33.2) 12.2
#> add.sd 0.691 0.691
#> wt.est 0.00814 0.00449 55.2 0.00814 (-0.000659, 0.0169)
#> Shrink(SD)%
#> tka -0.309%
#> tcl 3.49%
#> tv 14.2%
#> add.sd
#> wt.est
#>
#> Covariance Type ($covMethod): linFim
#> Some strong fixed parameter correlations exist ($cor) :
#> cor:tcl,tka cor:tv,tka cor:wt.est,tka cor:tv,tcl cor:wt.est,tcl
#> -0.0542 0.0174 -0.000404 -0.0261 0.00832
#> cor:wt.est,tv
#> -0.991
#>
#>
#> No correlations in between subject variability (BSV) matrix
#> Full BSV covariance ($omega) or correlation ($omegaR; diagonals=SDs)
#> Distribution stats (mean/skewness/kurtosis/p-value) available in $shrink
#>
#> ── Fit Data (object is a modified tibble): ─────────────────────────────────────
#> # A tibble: 132 × 20
#> ID TIME DV PRED RES IPRED IRES IWRES eta.ka eta.cl eta.v cp
#> <fct> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 1 0 0.74 0 0.74 0 0.74 1.07 0.120 -0.498 -0.150 0
#> 2 1 0.25 2.84 3.02 -0.179 3.87 -1.03 -1.50 0.120 -0.498 -0.150 3.87
#> 3 1 0.57 6.57 5.41 1.16 6.80 -0.229 -0.332 0.120 -0.498 -0.150 6.80
#> # … with 129 more rows, and 8 more variables: depot <dbl>, center <dbl>,
#> # ka <dbl>, cl <dbl>, v <dbl>, tad <dbl>, dosenum <dbl>, WT <dbl>
# }