# Infer() error due to variance-covariance matrix calculating failed

Hello, everyone.
I’m trying to creating and estimating virtual patients from literature values. The authors did calculate asymptotic SE, but I am failing.
The Pumas code is shown below.

``````using Random
using Pumas
using PumasUtilities
using CairoMakie
using AlgebraOfGraphics
using StatsBase
using Colors

###################################################
################### Generation  ###################
################# 1. Define model  #################
model_ = @model begin
desc        = "two compartment model with first-order absorption and Tlag"
end

@param begin
"Absorption Rate Constant (hr⁻¹)"
tvka        ∈ RealDomain(lower=0)
"Volume of Central Compartment (L)"
tvvc        ∈ RealDomain(lower=0)
"Volume of Peripheral Compartment (L)"
tvvp        ∈ RealDomain(lower=0)
"Clearance (L/hr)"
tvcl_other  ∈ RealDomain(lower=0)
tvcl_GF     ∈ RealDomain(lower=0)
"Intercompartmental Clearance (L/hr)"
tvq         ∈ RealDomain(lower=0)
"Lagtime (hr)"
tvlag       ∈ RealDomain(lower=0)
"BSV and BOV"
Ω_1          ∈ PSDDomain(2)
Ω_2          ∈ PSDDomain(2)
ω²η      ∈ RealDomain(lower=0)
"Proportional RUV"
σ²_prop   ∈ RealDomain(lower=0)
end

@random begin
η_1         ~ MvNormal(Ω_1)
η_2         ~ MvNormal(Ω_2)
η_BOV       ~ MvNormal(2, sqrt(ω²η))
end

@covariates CrCL LBM OCC

@pre begin
CL          = (tvcl_other + (tvcl_GF * (CrCL/90))) * exp(η_1[1])
Vc          = tvvc * ((LBM/55)^0.92) * exp(η_1[2])
Q           = tvq
Vp          = tvvp
Ka          = tvka * exp(η_2[1]) * exp(η_BOV[OCC])
end

@dosecontrol begin
lags = (Depot = tvlag * exp(η_2[2]),)
end

@dynamics Depots1Central1Periph1

@derived begin
cp = @. (Central/Vc)
dv ~ @. Normal(cp, sqrt((cp^2) * (σ²_prop)))
end
end

################# 2. Define model parameters   #################
@doc "cv(%) convert to sd" ->
function cv_to_sd(x)
SD_val = sqrt(log((x/100)^2+1))
return SD_val
end

BSV_CL_Var     = cv_to_sd(34.7)^2
BSV_Vc_Var     = cv_to_sd(29.0)^2
BSV_Ka_Var     = cv_to_sd(21.9)^2
BSV_Tlag_Var   = cv_to_sd(7.47)^2
BOV_Ka_Var     = cv_to_sd(131.53)^2
WSV_Pro_Var    = cv_to_sd(26)^2
Cov_CL_Vc      = 0.83 * sqrt(BSV_CL_Var * BSV_Vc_Var)
Cov_Ka_Tlag    = -0.79 * sqrt(BSV_Ka_Var * BSV_Tlag_Var)

param = ( tvcl_other  = 7.97,
tvcl_GF     = 8.52,
tvvc        = 122.7,
tvq         = 10.1,
tvvp        = 97.91,
tvka        = 2.15,
tvlag       = 0.22,
Ω_1        = ([BSV_CL_Var Cov_CL_Vc
Cov_CL_Vc BSV_Vc_Var]),
Ω_2        = ([BSV_Ka_Var Cov_Ka_Tlag
Cov_Ka_Tlag BSV_Tlag_Var]),
ω²η      = BOV_Ka_Var,
σ²_prop   = WSV_Pro_Var)

################# 3. Define subject   #################
# Group
Group = [27, 13, 5, 37, 4, 4]
Dose = [10, 20, 40, 80, 90, 100]

# CrCL
CrCL_mean = [91.8, 90.4, 103.4, 90.5, 111.5, 80.5]
CrCL_sd = [20.9, 22.9, 15.7, 23.9, 15.6, 11.9]
CrCL_ll = [55.4, 55.0, 86.9, 32.1, 88.2, 66.1]
CrCL_ul = [120, 120, 120, 120, 120, 93.4]
CrCL = rand.(truncated.(Normal.(CrCL_mean, CrCL_sd), CrCL_ll, CrCL_ul), Group)

# LBM
LBM_mean = [55.9, 56.5, 59.8, 53.6, 58.6, 50.6]
LBM_sd = [11.9, 11.0, 12.1, 10.5, 3.3, 19.1]
LBM_ll = [38.0, 43.7, 48.2, 33.67, 54.5, 35.7]
LBM_ul = [88.3, 75.1, 75.3, 78.5, 62.1, 78.6]
LBM = rand.(truncated.(Normal.(LBM_mean, LBM_sd), LBM_ll, LBM_ul), Group)

# Dose Regimem
ev  = DosageRegimen.(Dose, ii=12, addl = 7, cmt = 1)

# Time
occ = [fill(1,8); fill(2,8)] # 1 = day1, 2 = day4
time_obs_d1 = [0.0, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0]
time_obs_d4 = [0.0, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0] + fill(24*3, length(time_obs_d1))
time_obs = reduce(vcat,(time_obs_d1,time_obs_d4))

# Population covariates
pop_with_covariates = 0
for ii in 1:length(Group)
pop_with_covariates = map(
i -> Subject(;
id=i,
events = ev[ii],
time = time_obs,
covariates_time = time_obs,
covariates=(
LBM = fill(LBM[ii][i-sum(Group[1:(ii-1)])], length(time_obs)),
CrCL = fill(CrCL[ii][i-sum(Group[1:(ii-1)])], length(time_obs)),
OCC = occ
),
observations = (; dv=nothing),
),
(1+sum(Group[1:(ii-1)])):sum(Group[1:(ii)]),
)
assignment = Meta.parse("pop_\$(ii) = pop_with_covariates")
eval(assignment)
end

pop = vcat(pop_1, pop_2, pop_3, pop_4, pop_5, pop_6)

################# 4. Simulate #################
Random.seed!(123)
sim_sub = simobs(model_, pop, param, obstimes=time_obs)

################# 5. Postprocessing #################
generated = Pumas.postprocess(sim_sub)

# Concentration
temp_dv = (generated[1])[:dv]*1000
temp_cp = (generated[1])[:cp]*1000
temp_CrCL = (generated[1])[:CrCL]
temp_LBM = (generated[1])[:LBM]

for ii in 2:sum(Group)
temp_dv = vcat(temp_dv, (generated[ii])[:dv]*1000) # Unit change
temp_cp = vcat(temp_cp, (generated[ii])[:cp]*1000) # Unit change
temp_CrCL = vcat(temp_CrCL, (generated[ii])[:CrCL])
temp_LBM = vcat(temp_LBM, (generated[ii])[:LBM])
end

# id
id_vector = fill.(1:sum(Group), length(time_obs))
id_scalar = reduce(vcat, id_vector)

# time
time_scalar = reduce(vcat, fill(time_obs, 90))

# amt
temp_amt = (
reduce(vcat, [[Dose[1]], fill(missing, length(time_obs)-1)]),
reduce(vcat, [[Dose[2]], fill(missing, length(time_obs)-1)]),
reduce(vcat, [[Dose[3]], fill(missing, length(time_obs)-1)]),
reduce(vcat, [[Dose[4]], fill(missing, length(time_obs)-1)]),
reduce(vcat, [[Dose[5]], fill(missing, length(time_obs)-1)]),
reduce(vcat, [[Dose[6]], fill(missing, length(time_obs)-1)])
)
amt_vector_1 = fill.(temp_amt, Group)
amt_vector_2 = reduce(vcat, amt_vector_1)
amt_scalar = reduce(vcat, amt_vector_2)

temp_addl = reduce(vcat, [[7], fill(missing, length(time_obs)-1)])

# ii
temp_ii = reduce(vcat, [[12], fill(missing, length(time_obs)-1)])
ii_scalar = reduce(vcat, fill(temp_ii, sum(Group)))

# evid
temp_evid = reduce(vcat, [[1], fill(0, length(time_obs)-1)])
evid_scalar = reduce(vcat, fill(temp_evid, sum(Group)))

# cmt
temp_cmt = reduce(vcat, [[1], fill(2, length(time_obs)-1)])
cmt_scalar = reduce(vcat, fill(temp_cmt, sum(Group)))

# occ
occ_scalar = reduce(vcat, fill(occ, sum(Group)))

# merge
conc_table = hcat(id_scalar, time_scalar, amt_scalar, addl_scalar, ii_scalar, temp_dv, temp_cp,
evid_scalar, cmt_scalar, occ_scalar, temp_CrCL, temp_LBM)
df_conc = DataFrame(conc_table,:auto)

rename!(df_conc, ["ID", "TIME", "AMT", "ADDL", "II", "DV", "CP", "EVID", "CMT", "OCC", "CrCL", "LBM"])

df_conc.DV = @. ifelse(df_conc.EVID == 1, missing , df_conc.DV)
df_conc.CP = @. ifelse(df_conc.EVID == 1, missing , df_conc.CP)

###################################################
################### Estimation  ###################
pkdata = df_conc

pkdata[!,:AMT].= pkdata[!,:AMT].*1000 # DV: ug/L (ng/mL), AMT: mg -> ug
pkdata[!,[:ID,:CMT,:EVID,:OCC]] = convert.(Int64, pkdata[:,[:ID,:CMT,:EVID,:OCC]])
rename!(pkdata, :DV => :dv)
replace!(pkdata.dv, 0 => missing)

## map data
id = :ID,
time = :TIME,
amt = :AMT,
ii = :II,
evid = :EVID,
cmt = :CMT,
observations = [:dv],
covariates = [:CrCL, :LBM, :OCC])

################# 2. Fit the model #################
fit_pkdata = fit(
model_,
pop_est,
param,
FOCE()
)
infer(fit_pkdata)
``````

The error message from infer is as follows.

``````julia> infer(fit_pkdata)
[ Info: Calculating: variance-covariance matrix.
┌ Error: Failed.
└ @ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/inference.jl:70
``````

Could anyone let me know what to do when the following error message occurs in infer?

Welcome to the community @Sooyoung.Lee !
Two points:

1. you have a correlation between `Ka` and `tlag`, is that correct?
2. can you try `infer(fitobj, sandwich_estimator=false)`

I am glad to meet you @vijay.
However, my problem is still not solved.

1. For the first answers below,

Could you please check if there is any miscalculation?

The article values are as follows:
`Ka` BSV (CV%): 21.9
`tlag` BSV (CV%): 7.47
Correlation between random effects for Tlag and Ka: -0.79

So I calculated and constructed the variance-covariance matrix, Ω_2, as follows codes:

``````function cv_to_sd(x)
SD_val = sqrt(log((x/100)^2+1))
return SD_val
end

BSV_Ka_Var     = cv_to_sd(21.9)^2
BSV_Tlag_Var   = cv_to_sd(7.47)^2
Cov_Ka_Tlag    = -0.79 * sqrt(BSV_Ka_Var * BSV_Tlag_Var)

Ω_2        = ([BSV_Ka_Var Cov_Ka_Tlag
Cov_Ka_Tlag BSV_Tlag_Var])
``````

I can’t see the problem with only my view, so I would like to ask for the check.

2. For the second answers below,

This is the result I got when I ran the code you mentioned `infer(fitobj, sandwich_estimator=false)`.

``````julia> infer(fit_pkdata, sandwich_estimator=false)
[ Info: Calculating: variance-covariance matrix.
┌ Error: Failed.
└ @ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/inference.jl:70
``````

I also tried `infer(fit_pkdata, rethrow_error=true)`.

``````julia> infer(fit_pkdata, rethrow_error=true)
[ Info: Calculating: variance-covariance matrix.
ERROR: Pumas.PumasFailedCovariance(PosDefException(2))
Stacktrace:
[1] checkpositivedefinite
@ /opt/julia-1.7.3/share/julia/stdlib/v1.7/LinearAlgebra/src/factorization.jl:18 [inlined]
[2] cholesky!(A::Hermitian{Float64, Matrix{Float64}}, ::Val{false}; check::Bool)
@ LinearAlgebra /opt/julia-1.7.3/share/julia/stdlib/v1.7/LinearAlgebra/src/cholesky.jl:266
[3] cholesky!(A::Matrix{Float64}, ::Val{false}; check::Bool)
@ LinearAlgebra /opt/julia-1.7.3/share/julia/stdlib/v1.7/LinearAlgebra/src/cholesky.jl:298
[4] #cholesky#143
@ /opt/julia-1.7.3/share/julia/stdlib/v1.7/LinearAlgebra/src/cholesky.jl:394 [inlined]
[5] cholesky (repeats 2 times)
@ /opt/julia-1.7.3/share/julia/stdlib/v1.7/LinearAlgebra/src/cholesky.jl:394 [inlined]
[6] PDMat
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/PDMats/ZW0lN/src/pdmat.jl:19 [inlined]
[7] MvNormal(μ::FillArrays.Zeros{Float64, 1, Tuple{Base.OneTo{Int64}}}, Σ::Matrix{Float64})
@ Distributions /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Distributions/7iOJp/src/multivariate/mvnormal.jl:201
[8] MvNormal
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Distributions/7iOJp/src/multivariate/mvnormal.jl:218 [inlined]
[9] #25
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/dsl/model_macro.jl:334 [inlined]
[10] _orth_empirical_bayes(m::PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, subject::Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, param::NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, Matrix{Float64}, Matrix{Float64}, Float64, Float64}}, approx::FOCE, diffeq_options::NamedTuple{(:reltol,), Tuple{Float64}})
@ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/likelihoods.jl:936
[11] (::Pumas.var"#641#644"{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, NamedTuple{(:reltol,), Tuple{Float64}}, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}})(_vparam::Vector{Float64}, _fdrelstep::Float64)
@ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/likelihoods.jl:4741
[12] (::Pumas.var"#642#645"{Pumas.var"#641#644"{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, NamedTuple{(:reltol,), Tuple{Float64}}, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}, Float64})(_vparam::Vector{Float64})
@ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/likelihoods.jl:4770
[13] (::FiniteDiff.var"#calculate_Ji_central#36"{Float64, Float64, Bool, Pumas.var"#642#645"{Pumas.var"#641#644"{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, NamedTuple{(:reltol,), Tuple{Float64}}, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}, Float64}, Vector{Float64}, Vector{Float64}, Vector{Float64}})(i::Int64)
@ FiniteDiff /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/FiniteDiff/zdZSa/src/jacobians.jl:234
[14] _mapreduce(f::FiniteDiff.var"#calculate_Ji_central#36"{Float64, Float64, Bool, Pumas.var"#642#645"{Pumas.var"#641#644"{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, NamedTuple{(:reltol,), Tuple{Float64}}, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}, Float64}, Vector{Float64}, Vector{Float64}, Vector{Float64}}, op::typeof(hcat), #unused#::IndexLinear, A::UnitRange{Int64})
@ Base ./reduce.jl:413
[15] _mapreduce_dim
@ ./reducedim.jl:330 [inlined]
[16] #mapreduce#731
@ ./reducedim.jl:322 [inlined]
[17] mapreduce
@ ./reducedim.jl:322 [inlined]
[18] finite_difference_jacobian(f::Pumas.var"#642#645"{Pumas.var"#641#644"{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, NamedTuple{(:reltol,), Tuple{Float64}}, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}, Float64}, x::Vector{Float64}, cache::FiniteDiff.JacobianCache{Vector{Float64}, Vector{Float64}, Vector{Float64}, Vector{Float64}, UnitRange{Int64}, Nothing, Val{:central}(), Float64}, f_in::Vector{Float64}; relstep::Float64, absstep::Float64, colorvec::UnitRange{Int64}, sparsity::Nothing, jac_prototype::Nothing, dir::Bool)
@ FiniteDiff /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/FiniteDiff/zdZSa/src/jacobians.jl:240
[19] #finite_difference_jacobian#29
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/FiniteDiff/zdZSa/src/jacobians.jl:152 [inlined]
[20] (::Pumas.var"#640#643"{PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, Bool, NamedTuple{(:reltol,), Tuple{Float64}}, ProgressMeter.Progress, Float64, Float64, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}})(subject::Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}})
@ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/likelihoods.jl:4769
[21] next
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/library.jl:54 [inlined]
[22] next
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/core.jl:785 [inlined]
[23] next
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/simd.jl:8 [inlined]
[24] macro expansion
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/core.jl:181 [inlined]
[25] _foldl_array
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/processes.jl:187 [inlined]
[26] __foldl__
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/processes.jl:182 [inlined]
[27] foldl_basecase
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/processes.jl:365 [inlined]
``````
`````` [28] _reduce_basecase(rf::Transducers.Reduction{Transducers.UseSIMD{false}, Transducers.Reduction{Transducers.Map{Pumas.var"#640#643"{PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, Bool, NamedTuple{(:reltol,), Tuple{Float64}}, ProgressMeter.Progress, Float64, Float64, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}}, Transducers.BottomRF{Transducers.Completing{typeof(Base.add_sum)}}}}, init::InitialValues.InitialValueOf{typeof(Base.add_sum)}, reducible::Transducers.SizedReducible{SubArray{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, 1, Vector{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, Tuple{UnitRange{Int64}}, true}, Int64})
[29] _reduce(ctx::Transducers.CancellableDACContext, rf::Transducers.Reduction{Transducers.UseSIMD{false}, Transducers.Reduction{Transducers.Map{Pumas.var"#640#643"{PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, Bool, NamedTuple{(:reltol,), Tuple{Float64}}, ProgressMeter.Progress, Float64, Float64, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}}, Transducers.BottomRF{Transducers.Completing{typeof(Base.add_sum)}}}}, init::InitialValues.InitialValueOf{typeof(Base.add_sum)}, reducible::Transducers.SizedReducible{SubArray{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, 1, Vector{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, Tuple{UnitRange{Int64}}, true}, Int64})
@ Transducers /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/reduce.jl:150
[30] _reduce(ctx::Transducers.CancellableDACContext, rf::Transducers.Reduction{Transducers.UseSIMD{false}, Transducers.Reduction{Transducers.Map{Pumas.var"#640#643"{PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, Bool, NamedTuple{(:reltol,), Tuple{Float64}}, ProgressMeter.Progress, Float64, Float64, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}}, Transducers.BottomRF{Transducers.Completing{typeof(Base.add_sum)}}}}, init::InitialValues.InitialValueOf{typeof(Base.add_sum)}, reducible::Transducers.SizedReducible{SubArray{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, 1, Vector{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, Tuple{UnitRange{Int64}}, true}, Int64}) (repeats 6 times)
@ Transducers /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/reduce.jl:159
[31] _transduce_assoc_nocomplete
@ /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/reduce.jl:139 [inlined]
[32] transduce_assoc(xform::Transducers.Map{Pumas.var"#640#643"{PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, Bool, NamedTuple{(:reltol,), Tuple{Float64}}, ProgressMeter.Progress, Float64, Float64, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}}, step::Transducers.Completing{typeof(Base.add_sum)}, init::InitialValues.InitialValueOf{typeof(Base.add_sum)}, coll0::Vector{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}; simd::Val{true}, basesize::Int64, stoppable::Nothing, nestlevel::Nothing)
@ Transducers /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/reduce.jl:108
[33] foldxt(step::typeof(Base.add_sum), xform::Transducers.Map{Pumas.var"#640#643"{PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, FOCE, Bool, NamedTuple{(:reltol,), Tuple{Float64}}, ProgressMeter.Progress, Float64, Float64, Vector{Float64}, TransformVariables.TransformTuple{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.VechTransform{Nothing}, Pumas.VechTransform{Nothing}, TransformVariables.Identity, TransformVariables.Identity}}}}}, itr::Vector{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}; init::InitialValues.InitialValueOf{typeof(Base.add_sum)}, kwargs::Base.Pairs{Symbol, Any, Tuple{Symbol, Symbol}, NamedTuple{(:basesize, :simd), Tuple{Int64, Val{true}}}})
@ Transducers /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Transducers/DSfBv/src/reduce.jl:246
[34] #mapreduce#11
[35] #sum#14
[36] sum
[37] __observed_information_threads(model::PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, fixedparamset::ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, data::Vector{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, param::NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDMat{Float64, Matrix{Float64}}, PDMats.PDMat{Float64, Matrix{Float64}}, Float64, Float64}}, approx::FOCE, score::Bool, diffeq_options::NamedTuple{(:reltol,), Tuple{Float64}})
@ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/likelihoods.jl:4728
[38] _observed_information_threads(f::Pumas.FittedPumasModel{PumasModel{(tvka = 1, tvvc = 1, tvvp = 1, tvcl_other = 1, tvcl_GF = 1, tvq = 1, tvlag = 1, Ω_1 = 3, Ω_2 = 3, ω²η = 1, σ²_prop = 1), 6, (:Depot, :Central, :Peripheral), ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}, var"#25#34", Pumas.TimeDispatcher{var"#26#35", var"#27#36"}, Pumas.TimeDispatcher{var"#29#38", var"#30#39"}, var"#31#40", Depots1Central1Periph1, var"#32#41", var"#33#42", Nothing}, Vector{Subject{NamedTuple{(:dv,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantInterpolationStructArray{Vector{Float64}, NamedTuple{(:CrCL, :LBM, :OCC, :Dose), Tuple{Vector{Float64}, Vector{Float64}, Vector{Int64}, Vector{Int64}}}, Symbol}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, Optim.MultivariateOptimizationResults{Optim.BFGS{LineSearches.InitialStatic{Float64}, LineSearches.BackTracking{Float64, Int64}, Nothing, Float64, Optim.Flat}, Vector{Float64}, Float64, Float64, Vector{Optim.OptimizationState{Float64, Optim.BFGS{LineSearches.InitialStatic{Float64}, LineSearches.BackTracking{Float64, Int64}, Nothing, Float64, Optim.Flat}}}, Bool, NamedTuple{(:f_limit_reached, :g_limit_reached, :h_limit_reached, :time_limit, :callback, :f_increased), NTuple{6, Bool}}}, FOCE, Vector{Vector{Float64}}, NamedTuple{(:optimize_fn, :constantcoef, :omegas, :ensemblealg, :diffeq_options), Tuple{Pumas.DefaultOptimizeFN{Nothing, NamedTuple{(:show_trace, :store_trace, :extended_trace, :g_tol, :allow_f_increases), Tuple{Bool, Bool, Bool, Float64, Bool}}}, NamedTuple{(), Tuple{}}, Tuple{}, EnsembleThreads, NamedTuple{(), Tuple{}}}}, ParamSet{NamedTuple{(:tvka, :tvvc, :tvvp, :tvcl_other, :tvcl_GF, :tvq, :tvlag, :Ω_1, :Ω_2, :ω²η, :σ²_prop), Tuple{RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, PSDDomain{Matrix{Float64}}, PSDDomain{Matrix{Float64}}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}, RealDomain{Int64, TransformVariables.Infinity{true}, Int64}}}}}, score::Bool; reltol::Float64)
@ Pumas /build/_work/PumasSystemImages/PumasSystemImages/julia_depot/packages/Pumas/Td3Jp/src/estimation/likelihoods.jl:4664