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library(tidyverse)
library(coxme)
library(brms)
library(tidybayes)
library(ggridges)
library(kableExtra)
library(knitrhooks) # install with devtools::install_github("nathaneastwood/knitrhooks")
library(showtext)
output_max_height() # a knitrhook option
options(stringsAsFactors = FALSE)
# set up nice font for figure
nice_font <- "Lora"
font_add_google(name = nice_font, family = nice_font, regular.wt = 400, bold.wt = 700)
showtext_auto()
# load desiccation resistance data
DesRes <- read.csv("data/2.DesRes.csv") %>%
# add event (all flies died)
mutate(EVENT = 1,
LINE = paste0(Treatment, substr(Replicate, 2, 2)),
ID = paste(LINE, Vial, sep = ''))
# calculate survival times
# paste time and date
DesRes$d <- paste(DesRes$Death_date, DesRes$Death_time, sep = ' ')
# experiment start time
start_timeDes <- "04/02/2017 12:00"
DesRes$survival.time <- as.numeric(strptime(DesRes$d, format = "%d/%m/%Y %H") - strptime(start_timeDes, format = "%d/%m/%Y %H"))
# load starvation resistance data
StaRes <- read.csv("data/2.StarvRes.csv") %>%
# add event (all flies died)
mutate(EVENT = 1,
LINE = paste0(Treatment, substr(Replicate, 2, 2)),
ID = paste(LINE, Vial, sep = ''))
# calculate survival times
# paste time and date
StaRes$d <- paste(StaRes$Death_date, StaRes$Death_time, sep = ' ')
# experiment start time
start_timeSta <- "04/02/2017 10:00"
StaRes$survival.time <- as.numeric(strptime(StaRes$d, format = "%d/%m/%Y %H") - strptime(start_timeSta, format = "%d/%m/%Y %H"))
# 5 individuals have missing survival times which we will right censor at max. survival time
# Two M females (M2) were right censored as survival time not recorded
# Three P females (P2 Vial 6 and P4 vial 9) were right censored as survival time not recorded
StaRes[which(is.na(StaRes$survival.time)), 'EVENT'] <- 0
StaRes[which(is.na(StaRes$survival.time)), 'survival.time'] <- max(na.omit(StaRes$survival.time))
bind_rows(
DesRes %>%
select(Treatment, Sex, survival.time) %>% mutate(var = 'Desiccation'),
StaRes %>% filter(EVENT == 1) %>%
select(Treatment, Sex, survival.time) %>% mutate(var = 'Starvation')
) %>%
mutate(var2 = paste(Treatment, Sex)) %>%
ggplot(aes(x = survival.time, y = Sex, fill = var2)) +
geom_boxplot() +
scale_fill_manual(values = c("pink", "skyblue", "red", "blue"), name = "",
labels = c('Monogamy Females', 'Monogamy Males',
'Polandry Females', 'Polandry Males')) +
labs(x = 'Survival time (hours)') +
facet_wrap(~var, ncol = 2) +
theme_bw() +
NULL
Figure 1: Survival time in hours for flies in each treatment split by sex.
We modeled desiccation and starvation resistance using survival analysis. We measured time in hours until death (EVENT
= 1) for single sex triads of flies housed in vials (n = 7-10 vials per replicate per sex) containing no media and silica gel beads between the cotton and Parafilm enclosing the vial (desiccation resistance) or an agar media providing moisture only (starvation resistance). We monitored vials for deaths every two hours until all flies perished. For the starvation resistance assay five individuals (two M females and three E females) were right censored (EVENT
= 0) at the end of the observation period as death times were not recorded or remained alive.
First we plot Kaplan-Meier survival curves.
survminer::ggsurvplot(survfit(Surv(survival.time, EVENT) ~ Treatment + Sex, data = DesRes),
conf.int = TRUE,
risk.table = FALSE,
linetype = "Sex",
palette = c("pink", "skyblue", "red", "blue"),
xlab = "Time (hours)",
legend = 'right',
legend.title = "",
legend.labs = c("M \u2640","M \u2642",
'E \u2640','E \u2642'),
break.time.by = 12,
ggtheme = theme_bw())
#ggsave(filename = 'figures/desiccation.pdf', width = 5.5, height = 5, dpi = 600, useDingbats = FALSE)
survminer::ggsurvplot(survfit(Surv(survival.time, EVENT) ~ Treatment + Sex, data = StaRes),
conf.int = TRUE,
risk.table = FALSE,
linetype = "Sex",
palette = c("pink", "skyblue", "red", "blue"),
xlab = "Time (hours)",
legend = 'right',
legend.title = "",
legend.labs = c("M \u2640","M \u2642",
'E \u2640','E \u2642'),
break.time.by = 12,
ggtheme = theme_bw())
#ggsave(filename = 'figures/starvation.pdf', width = 5.5, height = 5, dpi = 600, useDingbats = FALSE)
Figure 2: Kaplan-Meier survival curves for flies in each treatment split by sex. + indicates censored individuals (n = 5).
bind_rows(
summary(survfit(Surv(survival.time, EVENT) ~ Treatment + Sex, data = DesRes))$table %>%
as_tibble() %>%
mutate(Treatment = c('M', 'M', 'E', 'E'),
Sex = c('Female', 'Male', 'Female', 'Male')),
summary(survfit(Surv(survival.time, EVENT) ~ Treatment + Sex, data = StaRes))$table %>%
as_tibble() %>%
mutate(Treatment = c('M', 'M', 'E', 'E'),
Sex = c('Female', 'Male', 'Female', 'Male'))) %>%
mutate(`Median (± 95% CI)` = paste0(median, ' (', `0.95LCL`, '-', `0.95UCL`, ')')) %>%
dplyr::select(Treatment, Sex, N = records, `N events` = events, `Median (± 95% CI)`) %>%
#write_csv('output/stress_medians.csv')
kable() %>%
kable_styling(full_width = FALSE) %>%
group_rows("Desiccation", 1, 4) %>%
group_rows("Starvation", 5, 8)
Treatment | Sex | N | N events | Median (± 95% CI) |
---|---|---|---|---|
Desiccation | ||||
M | Female | 108 | 108 | 38 (38-42) |
M | Male | 111 | 111 | 32 (32-34) |
E | Female | 114 | 114 | 40 (38-42) |
E | Male | 105 | 105 | 32 (32-34) |
Starvation | ||||
M | Female | 120 | 118 | 59 (54-64) |
M | Male | 120 | 120 | 42 (40-46) |
E | Female | 120 | 117 | 68 (64-72) |
E | Male | 120 | 120 | 44 (42-44) |
Next we need to check that the proportional hazards assumption is not violated before fitting the model, where crossing hazards (lines) indicate violation of the proportional hazards assumption. For both desiccation and starvation we see crossing hazards for the male survival curves. We therefore fit accelerated failure time (AFT) models with a Weibull distribution (see here).
# assess proportional hazards assumption
par(mar = c(2, 2, 2, 2), mfrow = c(1, 2))
plot(survfit(Surv(survival.time, EVENT) ~ Treatment + Sex, data = DesRes),
lty = 1:2, lwd = 2,
col = c("pink", "skyblue", "red", "blue"),
main = 'Desiccation',
fun = "cloglog")
legend("topleft", c("M \u2640","M \u2642",'E \u2640','E \u2642'),
col = c("pink", "skyblue", "red", "blue"),
lty = 1:2,
lwd = 2,
bty = 'n'
)
plot(survfit(Surv(survival.time, EVENT) ~ Treatment + Sex, data = StaRes),
lty = 1:2, lwd = 2,
col = c("pink", "skyblue", "red", "blue"),
main = 'Starvation',
fun = "cloglog")
par(mfrow = c(1, 1))
We fit an accelerated failure time model in brms
using family = weibull()
, with time (hours) to event (death) as the response and sexual selection treatment (Treatment
; Monogamy or Elevated polyandry), Sex
(female or male) and their interaction as predictors. See here for a helpful explanation on fitting survival models in brms
. We also include replicate treatment as a random intercept term for each of the 8 lines and a random slope term to allow the effect of selection treatment to vary across replicate lines. We also include vial ID
as a random intercept term as individuals housed in the same vial may show a correlated response.
if(!file.exists("output/des_brm.rds")){ # if the model doesn't exist fit it, else load it
des_brm <- brm(survival.time | cens(1 - EVENT) ~ Treatment * Sex + (Treatment|LINE) + (1|ID),
prior = c(set_prior("normal(0,0.5)", class = "b"),
set_prior("cauchy(0,0.1)", class = "sd")),
iter = 5000, chains = 4, cores = 4,
control = list(max_treedepth = 20,
adapt_delta = 0.999),
data = DesRes, family = weibull())
#saveRDS(des_brm, "output/des_brm_noslope.rds") # save with no random slope term
saveRDS(des_brm, "output/des_brm.rds")
} else {
des_brm <- readRDS('output/des_brm_noslope.rds')
}
if(!file.exists("output/sta_brm.rds")){ # if the model doesn't exist fit it, else load it
sta_brm <- brm(survival.time | cens(EVENT) ~ Treatment * Sex + (Treatment|LINE) + (1|ID),
prior = c(set_prior("normal(0,0.5)", class = "b"),
set_prior("cauchy(0,0.1)", class = "sd")),
iter = 5000, chains = 4, cores = 4,
control = list(max_treedepth = 20,
adapt_delta = 0.999),
# brm uses 0 = event, 1 = censor so need to recode
data = StaRes %>% mutate(EVENT = if_else(EVENT == 1, 0, 1)),
family = weibull())
#saveRDS(sta_brm, "output/sta_brm_noslope.rds") # save with no random slope term
saveRDS(sta_brm, "output/sta_brm.rds")
} else {
sta_brm <- readRDS('output/sta_brm_noslope.rds')
}
Taking the exponent of the coefficients gives an estimate of the multiplicative effect of the time to event compared to baseline (Monogamy females) (see here). For instance, for desiccation resistance, being male accelerates time to event by a factor of exp(-0.167) = 0.847 (95% confidence intervals = 0.795 - 0.902), i.e. Monogamy males live 0.847 times as long as Monogamy females.
des_test <- bind_rows(
hypothesis(des_brm, 'TreatmentP = 0')$hypothesis,
hypothesis(des_brm, 'Sexm = 0')$hypothesis,
hypothesis(des_brm, 'TreatmentP:Sexm = 0')$hypothesis
) %>%
mutate(Parameter = c('Treatment (E)', 'Sex (M)', 'Treatment (E) x Sex (M)'),
across(2:5, round, 3)) %>%
relocate(Parameter, Estimate, Est.Error, CI.Lower, CI.Upper, Star)
sta_test <- bind_rows(
hypothesis(sta_brm, 'TreatmentP = 0')$hypothesis,
hypothesis(sta_brm, 'Sexm = 0')$hypothesis,
hypothesis(sta_brm, 'TreatmentP:Sexm = 0')$hypothesis
) %>%
mutate(Parameter = c('Treatment (E)', 'Sex (M)', 'Treatment (E) x Sex (M)'),
across(2:5, round, 3)) %>%
relocate(Parameter, Estimate, Est.Error, CI.Lower, CI.Upper, Star)
des_pvals <- bayestestR::p_direction(des_brm) %>%
as.data.frame() %>%
mutate(vars = map_chr(str_split(Parameter, "_"), ~ .x[2]),
p_val = 1 - pd,
star = ifelse(p_val < 0.05, "\\*", "")) %>%
select(vars, p_val, star)
sta_pvals <- bayestestR::p_direction(sta_brm) %>%
as.data.frame() %>%
mutate(vars = map_chr(str_split(Parameter, "_"), ~ .x[2]),
p_val = 1 - pd,
star = ifelse(p_val < 0.05, "\\*", "")) %>%
select(vars, p_val, star)
bind_rows(
des_test %>%
mutate(vars = c('TreatmentP', 'Sexm', 'TreatmentP:Sexm')) %>%
left_join(des_pvals %>% filter(vars != 'Intercept'),
by = c("vars")) %>%
select(Parameter, Estimate, Est.Error, CI.Lower, CI.Upper, `p` = p_val, star),
sta_test %>%
mutate(vars = c('TreatmentP', 'Sexm', 'TreatmentP:Sexm')) %>%
left_join(sta_pvals %>% filter(vars != 'Intercept'),
by = c("vars")) %>%
select(Parameter, Estimate, Est.Error, CI.Lower, CI.Upper, `p` = p_val, star)
) %>%
mutate(p = ifelse(p > 0.001, round(p, 3), '< 0.001')) %>%
rename(` ` = star) %>%
kable() %>%
kable_styling(full_width = FALSE) %>%
group_rows("Desiccation", 1, 3) %>%
group_rows("Starvation", 4, 6)
Parameter | Estimate | Est.Error | CI.Lower | CI.Upper | p | |
---|---|---|---|---|---|---|
Desiccation | ||||||
Treatment (E) | 0.054 | 0.085 | -0.117 | 0.224 | 0.24 | |
Sex (M) | -0.167 | 0.032 | -0.229 | -0.103 | < 0.001 | * |
Treatment (E) x Sex (M) | -0.097 | 0.046 | -0.188 | -0.007 | 0.018 | * |
Starvation | ||||||
Treatment (E) | 0.083 | 0.097 | -0.112 | 0.273 | 0.181 | |
Sex (M) | -0.322 | 0.035 | -0.391 | -0.256 | < 0.001 | * |
Treatment (E) x Sex (M) | -0.126 | 0.049 | -0.222 | -0.029 | 0.005 | * |
summary.brmsfit()
The shape parameter (\(1/\)scale parameter; see here) describes the change in hazard over time where:
des_brm
Family: weibull Links: mu = log; shape = identity Formula: survival.time | cens(1 - EVENT) ~ Treatment * Sex + (1 | LINE) + (1 | ID) Data: DesRes (Number of observations: 438) Draws: 4 chains, each with iter = 5000; warmup = 2500; thin = 1; total post-warmup draws = 10000 Group-Level Effects: ~ID (Number of levels: 146) Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS sd(Intercept) 0.11 0.01 0.09 0.13 1.00 3552 5532 ~LINE (Number of levels: 8) Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS sd(Intercept) 0.11 0.04 0.06 0.20 1.00 3911 5251 Population-Level Effects: Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS Intercept 3.66 0.06 3.54 3.78 1.00 4601 5308 TreatmentP 0.05 0.09 -0.12 0.22 1.00 4334 6055 Sexm -0.17 0.03 -0.23 -0.10 1.00 5200 6875 TreatmentP:Sexm -0.10 0.05 -0.19 -0.01 1.00 4810 6616 Family Specific Parameters: Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS shape 7.56 0.36 6.89 8.28 1.00 6108 7957 Draws were sampled using sampling(NUTS). For each parameter, Bulk_ESS and Tail_ESS are effective sample size measures, and Rhat is the potential scale reduction factor on split chains (at convergence, Rhat = 1).
sta_brm
Family: weibull Links: mu = log; shape = identity Formula: survival.time | cens(EVENT) ~ Treatment * Sex + (1 | LINE) + (1 | ID) Data: StaRes %>% mutate(EVENT = if_else(EVENT == 1, 0, 1 (Number of observations: 480) Draws: 4 chains, each with iter = 5000; warmup = 2500; thin = 1; total post-warmup draws = 10000 Group-Level Effects: ~ID (Number of levels: 160) Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS sd(Intercept) 0.12 0.01 0.09 0.14 1.00 4057 6009 ~LINE (Number of levels: 8) Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS sd(Intercept) 0.13 0.04 0.07 0.23 1.00 3677 5482 Population-Level Effects: Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS Intercept 4.11 0.07 3.97 4.25 1.00 3511 4489 TreatmentP 0.08 0.10 -0.11 0.27 1.00 3727 4908 Sexm -0.32 0.03 -0.39 -0.26 1.00 4942 5685 TreatmentP:Sexm -0.13 0.05 -0.22 -0.03 1.00 4874 6607 Family Specific Parameters: Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS shape 5.96 0.27 5.45 6.49 1.00 6453 7484 Draws were sampled using sampling(NUTS). For each parameter, Bulk_ESS and Tail_ESS are effective sample size measures, and Rhat is the potential scale reduction factor on split chains (at convergence, Rhat = 1).
# get posterior predictions
post_des <- posterior_samples(des_brm) %>%
as_tibble() %>%
select(contains("b_"), -contains("Intercept")) %>%
mutate(draw = 1:n()) %>%
pivot_longer(-draw) %>%
mutate(key = str_remove_all(name, "b_"))
post_sta <- posterior_samples(sta_brm) %>%
as_tibble() %>%
select(contains("b_"), -contains("Intercept")) %>%
mutate(draw = 1:n()) %>%
pivot_longer(-draw) %>%
mutate(key = str_remove_all(name, "b_"))
bind_rows(post_des %>% mutate(var = 'Desiccation'),
post_sta %>% mutate(var = 'Starvation')) %>%
mutate(key = recode(key, TreatmentP = "Treatment (E)", Sexm = 'Sex (M)', `TreatmentP:Sexm` = 'Treatment (E) x Sex (M)')) %>%
ggplot(aes(x = value, y = key, fill = key)) +
geom_vline(xintercept = 0, linetype = 2) +
stat_halfeye(alpha = .8) +
scale_fill_brewer(palette = "Spectral") +
coord_cartesian(xlim = c(-0.4, 0.4)) +
labs(x = "Effect size", y = "Model parameter") +
facet_wrap(~var) +
theme_ridges() +
theme(legend.position = 'none',
legend.title = element_blank()) +
NULL
Here, we use the model to predict the mean survival coefficient in each treatment and sex (averaged across the eight replicate selection lines). We then calculate the effect size of treatment by subtracting the (sex-specific) mean for the M treatment from the mean for the E treatment. We see that there is no overall effect of treatment in males or females.
new_data_stress <- expand_grid(Sex = c("m", "f"),
Treatment = c("M", "P"),
LINE = NA) %>%
mutate(type = 1:4)
fitted_des <- posterior_epred(
des_brm, newdata = new_data_stress, re_formula = NA,
summary = FALSE) %>%
reshape2::melt() %>% rename(draw = Var1, type = Var2) %>%
as_tibble() %>%
left_join(new_data_stress, by = "type") %>%
select(draw, value, Sex, Treatment)
treat_diff_des <- fitted_des %>%
spread(Treatment, value) %>%
mutate(`Difference in means (Poly - Mono)` = P - M)
fitted_sta <- posterior_epred(
sta_brm, newdata = new_data_stress, re_formula = NA,
summary = FALSE) %>%
reshape2::melt() %>% rename(draw = Var1, type = Var2) %>%
as_tibble() %>%
left_join(new_data_stress, by = "type") %>%
select(draw, value, Sex, Treatment)
treat_diff_sta <- fitted_sta %>%
spread(Treatment, value) %>%
mutate(`Difference in means (Poly - Mono)` = P - M)
treat_diff_des %>%
mutate(Sex = factor(ifelse(Sex == "m", "Males", "Females"))) %>%
ggplot(aes(x = `Difference in means (Poly - Mono)`, y = Sex, fill = Sex)) +
geom_vline(xintercept = 0, linetype = 2) +
stat_halfeye() +
scale_fill_brewer(palette = 'Pastel1', direction = 1, name = "") +
scale_colour_brewer(palette = 'Pastel1', direction = 1, name = "") +
labs(x = 'Difference in means between\nselection treatments (E - M)', y = 'Sex') +
theme_bw() +
theme(legend.position = 'none',
strip.background = element_blank(),
panel.grid.major.x = element_blank()) +
NULL
treat_diff_sta %>%
mutate(Sex = factor(ifelse(Sex == "m", "Males", "Females"))) %>%
ggplot(aes(x = `Difference in means (Poly - Mono)`, y = Sex, fill = Sex)) +
geom_vline(xintercept = 0, linetype = 2) +
stat_halfeye() +
scale_fill_brewer(palette = 'Pastel1', direction = 1, name = "") +
scale_colour_brewer(palette = 'Pastel1', direction = 1, name = "") +
labs(x = 'Difference in means between\nselection treatments (E - M)', y = 'Sex') +
theme_bw() +
theme(legend.position = 'none',
strip.background = element_blank(),
panel.grid.major.x = element_blank()) +
NULL
This section examines the treatment \(\times\) sex interaction term, by calculating the difference in the effect size of the E/M treatment between sexes. We find evidence for a treatment \(\times\) sex interaction, i.e. the difference in survival time between the sexes was greater in the E treatment than the M treatment.
treat_diff_des %>%
rename(d = `Difference in means (Poly - Mono)`) %>%
select(draw, Sex, d) %>%
group_by(draw) %>%
summarise(`Difference in effect size between sexes (male - female)` = d[2] - d[1],
.groups = "drop") %>%
ggplot(aes(x = `Difference in effect size between sexes (male - female)`, y = 1, fill = stat(x < 0))) +
geom_vline(xintercept = 0, linetype = 2) +
stat_halfeye() +
scale_fill_brewer(palette = 'Pastel2', direction = 1, name = "") +
theme_bw() +
theme(legend.position = 'none',
text = element_text(family = nice_font),
strip.background = element_blank()) +
ylab("Posterior density") +
#ggsave("figures/des_interaction_plot.pdf", height=4, width=4) +
NULL
treat_diff_sta %>%
rename(d = `Difference in means (Poly - Mono)`) %>%
select(draw, Sex, d) %>%
group_by(draw) %>%
summarise(`Difference in effect size between sexes (male - female)` = d[2] - d[1],
.groups = "drop") %>%
ggplot(aes(x = `Difference in effect size between sexes (male - female)`, y = 1, fill = stat(x < 0))) +
geom_vline(xintercept = 0, linetype = 2) +
stat_halfeye() +
scale_fill_brewer(palette = 'Pastel2', direction = 1, name = "") +
theme_bw() +
theme(legend.position = 'none',
text = element_text(family = nice_font),
strip.background = element_blank()) +
ylab("Posterior density") +
#ggsave("figures/sta_interaction_plot.pdf", height=4, width=4) +
NULL
treatsex_interaction_des <- treat_diff_des %>%
select(draw, Sex, d = `Difference in means (Poly - Mono)`) %>%
arrange(draw, Sex) %>%
group_by(draw) %>%
summarise(`Difference in effect size between sexes (male - female)` = d[2] - d[1],
.groups = "drop") # males - females
treatsex_interaction_sta <- treat_diff_sta %>%
select(draw, Sex, d = `Difference in means (Poly - Mono)`) %>%
arrange(draw, Sex) %>%
group_by(draw) %>%
summarise(`Difference in effect size between sexes (male - female)` = d[2] - d[1],
.groups = "drop") # males - females
bind_rows(treatsex_interaction_des %>% mutate(variable = 'Dessication'),
treatsex_interaction_sta %>% mutate(variable = 'Starvation')) %>%
rename(x = `Difference in effect size between sexes (male - female)`) %>%
group_by(variable) %>%
summarise(`Difference in effect size between sexes (male - female)` = median(x),
`Lower 95% CI` = quantile(x, probs = 0.025),
`Upper 95% CI` = quantile(x, probs = 0.975),
p = 1 - as.numeric(bayestestR::p_direction(x)),
` ` = ifelse(p < 0.05, "\\*", ""),
.groups = "drop") %>%
kable(digits=3) %>%
kable_styling(full_width = FALSE)
variable | Difference in effect size between sexes (male - female) | Lower 95% CI | Upper 95% CI | p | |
---|---|---|---|---|---|
Dessication | -3.562 | -7.090 | -0.065 | 0.023 | * |
Starvation | -7.111 | -13.423 | -0.573 | 0.016 | * |
sessionInfo()
R version 4.0.3 (2020-10-10) Platform: x86_64-apple-darwin17.0 (64-bit) Running under: macOS Big Sur 10.16 Matrix products: default BLAS: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRblas.dylib LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib locale: [1] en_GB.UTF-8/en_GB.UTF-8/en_GB.UTF-8/C/en_GB.UTF-8/en_GB.UTF-8 attached base packages: [1] stats graphics grDevices utils datasets methods base other attached packages: [1] showtext_0.9-4 showtextdb_3.0 sysfonts_0.8.5 knitrhooks_0.0.4 [5] knitr_1.33 kableExtra_1.3.4 ggridges_0.5.3 tidybayes_3.0.1 [9] brms_2.16.1 Rcpp_1.0.7 coxme_2.2-16 bdsmatrix_1.3-4 [13] survival_3.2-12 forcats_0.5.1 stringr_1.4.0 dplyr_1.0.7 [17] purrr_0.3.4 readr_2.0.1 tidyr_1.1.3 tibble_3.1.3 [21] ggplot2_3.3.5 tidyverse_1.3.1 workflowr_1.6.2 loaded via a namespace (and not attached): [1] utf8_1.2.2 tidyselect_1.1.1 lme4_1.1-27.1 [4] htmlwidgets_1.5.3 grid_4.0.3 munsell_0.5.0 [7] codetools_0.2-18 DT_0.18 miniUI_0.1.1.1 [10] withr_2.4.2 Brobdingnag_1.2-6 colorspace_2.0-2 [13] highr_0.9 rstudioapi_0.13 stats4_4.0.3 [16] ggsignif_0.6.2 bayesplot_1.8.1 labeling_0.4.2 [19] git2r_0.28.0 rstan_2.21.1 KMsurv_0.1-5 [22] farver_2.1.0 datawizard_0.2.0 bridgesampling_1.1-2 [25] rprojroot_2.0.2 coda_0.19-4 vctrs_0.3.8 [28] generics_0.1.0 xfun_0.25 R6_2.5.1 [31] markdown_1.1 gamm4_0.2-6 projpred_2.0.2 [34] assertthat_0.2.1 promises_1.2.0.1 scales_1.1.1 [37] gtable_0.3.0 processx_3.5.2 rlang_0.4.11 [40] systemfonts_1.0.2 splines_4.0.3 rstatix_0.7.0 [43] broom_0.7.9 checkmate_2.0.0 inline_0.3.19 [46] yaml_2.2.1 reshape2_1.4.4 abind_1.4-5 [49] modelr_0.1.8 threejs_0.3.3 crosstalk_1.1.1 [52] backports_1.2.1 httpuv_1.6.2 rsconnect_0.8.24 [55] tensorA_0.36.2 tools_4.0.3 ellipsis_0.3.2 [58] RColorBrewer_1.1-2 jquerylib_0.1.4 posterior_1.0.1 [61] plyr_1.8.6 base64enc_0.1-3 ps_1.6.0 [64] prettyunits_1.1.1 ggpubr_0.4.0 zoo_1.8-9 [67] haven_2.4.3 fs_1.5.0 magrittr_2.0.1 [70] data.table_1.14.0 ggdist_3.0.0 openxlsx_4.2.4 [73] colourpicker_1.1.0 reprex_2.0.1 survminer_0.4.9 [76] mvtnorm_1.1-2 whisker_0.4 matrixStats_0.60.0 [79] hms_1.1.0 shinyjs_2.0.0 mime_0.11 [82] evaluate_0.14 arrayhelpers_1.1-0 xtable_1.8-4 [85] shinystan_2.5.0 rio_0.5.27 readxl_1.3.1 [88] gridExtra_2.3 rstantools_2.1.1 compiler_4.0.3 [91] V8_3.4.2 crayon_1.4.1 minqa_1.2.4 [94] StanHeaders_2.21.0-7 htmltools_0.5.1.1 mgcv_1.8-36 [97] later_1.3.0 tzdb_0.1.2 RcppParallel_5.1.4 [100] lubridate_1.7.10 DBI_1.1.1 dbplyr_2.1.1 [103] MASS_7.3-54 boot_1.3-28 Matrix_1.3-4 [106] car_3.0-11 cli_3.0.1 parallel_4.0.3 [109] insight_0.14.3 igraph_1.2.6 pkgconfig_2.0.3 [112] km.ci_0.5-2 foreign_0.8-81 xml2_1.3.2 [115] svUnit_1.0.6 dygraphs_1.1.1.6 svglite_2.0.0 [118] bslib_0.2.5.1 webshot_0.5.2 rvest_1.0.1 [121] distributional_0.2.2 callr_3.7.0 digest_0.6.27 [124] rmarkdown_2.10 cellranger_1.1.0 survMisc_0.5.5 [127] curl_4.3.2 shiny_1.6.0 gtools_3.9.2 [130] nloptr_1.2.2.2 lifecycle_1.0.0 nlme_3.1-152 [133] jsonlite_1.7.2 carData_3.0-4 viridisLite_0.4.0 [136] fansi_0.5.0 pillar_1.6.2 lattice_0.20-44 [139] loo_2.4.1 fastmap_1.1.0 httr_1.4.2 [142] pkgbuild_1.2.0 glue_1.4.2 xts_0.12.1 [145] bayestestR_0.10.5 zip_2.2.0 shinythemes_1.2.0 [148] stringi_1.7.3 sass_0.4.0