Crash with rxSolve() attempt of simulation

[billdenney]

Related to #442 (in that I'm still trying to make that simulation), the below code crashes R at the rxSolve() call:

library(nlmixr)

linear_twocmt_iiv_growth <- function() {
  ini({
    tcl <- fixed(log(0.01)) ; label("Clearance (L/kg/hr)")
    tq <- fixed(log(0.05)) ; label("Intercompartmental clearance (L/kg/hr)")
    tv <- fixed(log(1.5)) ; label("Volume central (L/kg)")
    tv1 <- fixed(log(2)) ; label("Volume peripheral (L/kg)")
    
    tktr <- log(c(0.00001, 0.03, 3)) ; label("Transit compartment rate (1/hr)")
    slope <- c(-2, -0.02, 2) ; label("Slope on growth rate ((ng/mL)/hr)")
    ltumorgrowth <- log(c(0.0001, 0.01, 1)) ; label("Baseline tumor exponential growth rate (1/hr)")

    iiv_tumorgrowth ~ 0.1 ; label("Inter-individual variability in baseline tumor exponential growth rate")

    prop_sd <- 0.2 ; label("Proportional error for tumor volume (fraction)")
    add_sd <- 100 ; label("Additive error for tumor volume (mm^3)")
  })
  drake::no_deps(model({
    cl <- exp(tcl)
    q <- exp(tq)
    v <- exp(tv)
    v1 <- exp(tv1)
    kcp <- q/v
    kpc <- q/v1
    ktr <- exp(tktr)
    TUMOR(0) <- TUMORBL
    
    d/dt(CENTRAL) = -cl/v * CENTRAL - kcp*CENTRAL + kpc*PERIPH1
    d/dt(PERIPH1) = kcp*CENTRAL - kpc*PERIPH1
    # unit conversion
    cp <- CENTRAL/v*1000
    d/dt(TRANSIT) = ktr*(cp - TRANSIT)
    tumorgrowth <- exp(ltumorgrowth + iiv_tumorgrowth)
    ktumor <- tumorgrowth + slope*TRANSIT
    d/dt(TUMOR) = ktumor*TUMOR
    TUMOR ~ add(add_sd) + prop(prop_sd)
  }))
}

sim_dose <-
  data.frame(
    ID=1:50,
    time=0,
    amt=rep(seq(0, 20, by=5), each=10),
    evid=1,
    cmt="CENTRAL",
    mdv=1,
    TUMORBL=100
  )

sim_obs <-
  expand.grid(
    ID=1:50,
    time=(0:60)*24,
    amt=0,
    evid=0,
    cmt="TUMOR",
    mdv=0,
    TUMORBL=100
  )

sim_data <- rbind(sim_dose, sim_obs)
sim_data <- sim_data[order(sim_data$ID, sim_data$time), ]

model <- nlmixr(linear_twocmt_iiv_growth)
simulation <- rxSolve(model, events=sim_data)

My sessionInfo is:

> sessionInfo()
R version 4.1.0 (2021-05-18)
Platform: x86_64-w64-mingw32/x64 (64-bit)
Running under: Windows 10 x64 (build 19043)

Matrix products: default

locale:
[1] LC_COLLATE=English_United States.1252  LC_CTYPE=English_United States.1252    LC_MONETARY=English_United States.1252 LC_NUMERIC=C                          
[5] LC_TIME=English_United States.1252    

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] nlmixr_2.0.4

loaded via a namespace (and not attached):
 [1] styler_1.5.1        tidyselect_1.1.1    xfun_0.24           purrr_0.3.4         lattice_0.20-44     RxODE_1.0.9         colorspace_2.0-2    vctrs_0.3.8         generics_0.1.0     
[10] htmltools_0.5.1.1   yaml_2.2.1          utf8_1.2.1          rlang_0.4.11        pillar_1.6.1        glue_1.4.2          withr_2.4.2         DBI_1.1.1           lbfgsb3c_2020-3.2  
[19] lifecycle_1.0.0     n1qn1_6.0.1-10      munsell_0.5.0       gtable_0.3.0        stringfish_0.15.1   evaluate_0.14       memoise_2.0.0       RApiSerialize_0.1.0 knitr_1.33         
[28] callr_3.7.0         fastmap_1.1.0       ps_1.6.0            parallel_4.1.0      sys_3.4             fansi_0.5.0         highr_0.9           Rcpp_1.0.7          clipr_0.7.1        
[37] backports_1.2.1     scales_1.1.1        checkmate_2.0.0     cachem_1.0.5        RcppParallel_5.1.4  fs_1.5.0            brew_1.0-6          ggplot2_3.3.5       digest_0.6.27      
[46] lotri_0.3.1         processx_3.5.2      dplyr_1.0.7         qs_0.24.1           grid_4.1.0          cli_3.0.1           tools_4.1.0         magrittr_2.0.1      tibble_3.1.2       
[55] PreciseSums_0.4     crayon_1.4.1        pkgconfig_2.0.3     ellipsis_0.3.2      data.table_1.14.0   reprex_2.0.0        assertthat_0.2.1    rmarkdown_2.9       rstudioapi_0.13    
[64] R6_2.5.0            nlme_3.1-152        units_0.7-2         compiler_4.1.0     

[mattfidler]

I will look into this. I will likely transfer this to RxODE when I figure out what the issue is.

[mattfidler]

C based back-trace:

Thread 1 "R" received signal SIGSEGV, Segmentation fault.
0x00007ffff3022317 in Rcpp::Rcpp_precious_preserve (object=0x5555580bc7f0) at barrier.cpp:107
107	barrier.cpp: No such file or directory.
(gdb) bt
#0  0x00007ffff3022317 in Rcpp::Rcpp_precious_preserve (object=0x5555580bc7f0) at barrier.cpp:107
nlmixrdevelopment/nlmixr#1  0x00007ffff27f19e8 in Rcpp::Rcpp_precious_preserve (object=0x5555580bc7f0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/Rcpp/routines.h:155
nlmixrdevelopment/nlmixr#2  0x00007ffff27f1782 in Rcpp::Rcpp_PreciousPreserve (object=0x5555580bc7f0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/RcppCommon.h:116
nlmixrdevelopment/nlmixr#3  0x00007ffff281c6e3 in Rcpp::PreserveStorage<Rcpp::Vector<16, Rcpp::PreserveStorage> >::set__ (this=0x7fffff670110, x=0x5555580bc7f0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/Rcpp/storage/PreserveStorage.h:43
nlmixrdevelopment/nlmixr#4  0x00007ffff281d200 in Rcpp::Vector<16, Rcpp::PreserveStorage>::Vector (this=0x7fffff670110, x=0x5555580bc7f0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/Rcpp/vector/Vector.h:74
nlmixrdevelopment/nlmixr#5  0x00007ffff282a593 in Rcpp::traits::Exporter<Rcpp::Vector<16, Rcpp::PreserveStorage> >::Exporter (this=0x7fffff670110, x=0x5555580bc7f0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/Rcpp/internal/Exporter.h:31
nlmixrdevelopment/nlmixr#6  0x00007ffff281dade in Rcpp::internal::as<Rcpp::Vector<16, Rcpp::PreserveStorage> > (x=0x5555580bc7f0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/Rcpp/as.h:87
nlmixrdevelopment/nlmixr#7  0x00007ffff2816fe3 in Rcpp::as<Rcpp::Vector<16, Rcpp::PreserveStorage> > (x=0x5555580bc7f0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/Rcpp/as.h:152
nlmixrdevelopment/nlmixr#8  0x00007ffff28d643d in Rcpp::AttributeProxyPolicy<Rcpp::RObject_Impl<Rcpp::PreserveStorage> >::const_AttributeProxy::operator Rcpp::Vector<16, Rcpp::PreserveStorage><Rcpp::Vector<16, Rcpp::PreserveStorage> >() const (this=0x7fffff6702a0)
    at /home/matt/R/x86_64-pc-linux-gnu-library/4.1/Rcpp/include/Rcpp/api/meat/proxy.h:51
nlmixrdevelopment/nlmixr#9  0x00007ffff288bbef in rxIs_list (obj=..., cls="rxModelVars") at rxData.cpp:176
nlmixrdevelopment/nlmixr#10 0x00007ffff288e064 in rxIs (obj=..., cls="rxModelVars") at rxData.cpp:397
nlmixrdevelopment/nlmixr#11 0x00007ffff2894706 in rxModelVars_ (obj=...) at rxData.cpp:817
nlmixrdevelopment/nlmixr#12 0x00007ffff28cc966 in rxRxODEenv (obj=...) at rxData.cpp:5504
nlmixrdevelopment/nlmixr#13 0x00007ffff28cc999 in rxRxODEenv (obj=...) at rxData.cpp:5504

[mattfidler]

An even smaller reprex is:

rxSolve(list(a=3), events=et(0))

[billdenney]

That is a lot smaller... (Thanks for looking into this one.)

[mattfidler]

This no longer crashes R, but says the model is unsupported (at least for now)

[billdenney]

An "Unsupported" error makes sense to me.