ch12_mediation.qmd

# Mediation {#mediation}

```{r}
library(conflicted)
library(rsample)
library(dplyr)
library(patchwork)
library(ggdag)
library(ggplot2)
library(fciR)
options(dplyr.summarise.inform = FALSE)
conflicts_prefer(dplyr::filter)
```



```{r}
#| label: ch12_scm_12.1
#| warning: false
scm_12.1 <- list()
scm_12.1 <- within(scm_12.1, {
  the_coords <- list(
    x = c(A = 1, H1 = 1.5, H2 = 2.5, H3 = 1.5, M = 2, Y = 3),
    y = c(A = 2, H1 = 1, H2 = 3, H3 = 3, M = 2, Y = 1))
  the_nodes <- c("A" = "", 
                 "H1" = "", 
                 "H2" = "", 
                 "H3" = "",
                 "M" = "",
                 "Y" = "")
  dag <- dagify(
    A ~ H1 + H3,
    M ~ A + H3 + H2,
    Y ~ A + H1 + H2 + M,
    labels = the_nodes,
    coords = the_coords)
  
  text_labels <- c("A",expression(H[1]), expression(H[2]),
                   expression(H[3]), "M", "Y")
  plot <- fciR::ggp_dag(dag, text_labels = text_labels)
})
```

```{r echo=FALSE, fig.align='center', fig.cap="Causal DAG for Mediation by $M$ of the Effect of $A$ on $Y$", warning=FALSE, out.width="80%"}
#| label: fig-ch12_scm_12.1
#| fig-cap: "Causal DAG for Mediation by $M$ of the Effect of $A$ on $Y$"
#| fig-align: 'center'
#| out-width: "80%"
scm_12.1$plot
```

## Theory

We let

-   $M(a)$ be the potential outcome of the mediator $M$ to assigning treatment $A=a$
-   $Y(a, m)$ be the potential outcome for the outcome $Y$ to assigning treatment $A=a$ and mediator $M=m$
-   $Y(a, M(a^*))$ where we assign tretment $A=a$ and then we assign the mediator $M$ to its potential outcome had we assigned treatment $A=a^*$

The *total effect* $TE$ compares the potential outcome for $Y$ to assigning treatment $A=a$ with that of assigning treatment $A=a$.

$$
TE(a,a^*) = Y(a, M(a)) - Y(a^*, M(a^*))
$$

The *controlled direct effect* $CDE$ compares the potential outcome to assigning treatment $A=a$ with that of assinging treatment $A=a^*$ while controlling the mediator at $M=m$.

$$
CDE(a,a^*,m) = Y(a, m) - Y(a^*, m)
$$ 

and the *controlled indirect effect* $CIE$ is what is left to obtain the total effect $TE$.

$$
CIE(a, a^*,m)=TE(a,a^*) - CDE(a,a^*,m)
$$ 

Also another partition, the *natural direct effect* $NDE$ does not control the mediator and lets it assume the value it would naturally take at a controlled level of $A$.

$$
NDE(a,a^*;a^*) = Y(a, M(a^*)) - Y(a^*, M(a^*))
$$ 

and the *natural indirect effect* $NIE$ compares the potential outcome to assigning $M=M(a)$ with that of assinging $M=M(a^*)$ while assigning $A=a$.

$$
NDE(a,a^*;a) = Y(a, M(a)) - Y(a, M(a^*))
$$ 

and therefore the *total effect* $TE$ can be expressed in two was

$$
TE = CDE + CIE = NDE + NIE
$$

We make the four following assumptins about the confounders

**Assumption 1**: There are no unmeasured treatment confounders given $H$ where $H = \{H_1, H_2, H_3 \}$.

$$
Y(a,m) \perp\!\!\!\perp A \mid H
$$

**Assumption 2**: There are no unmeasured mediator-outcome confounders given $\{H,A\}$

$$
Y(a,m) \perp\!\!\!\perp M \mid H, A
$$

**Assumption 3**: There are no unmeasured treatment-mediator confounders given $H$

$$
M(a) \perp\!\!\!\perp A \mid H
$$ 

**Assumption 4**: There are no mediator-outcome confounder affected by treatment, i.e. no arrow from $A$ to $H_2$.

$$
Y(a,m) \perp\!\!\!\perp M(a^*) \mid H
$$

### Prove $E(TE(a, a^*) \mid H = h)$

Under assumption 1, the total effect conditional on $H$ is

$$
E(TE(a, a^*) \mid H = h) = E(Y \mid A=a, H=h) - E(Y \mid A=a^*, H=h)
$$ 

and the proof is is based on the method of section 3.2, p. 41, with assumption 1 
$Y(a,m) \perp\!\!\!\perp A \mid H$ being the same as the assumption of 
*stratified randomized trial* (3.2).

By definition we have that $TE(a, a^*) = Y(a, M(a)) - Y(a^*, M(a^*)$, hence

$$
\begin{align*}
E(TE(a, a^*) \mid H = h) &= E(Y(a, M(a)) - Y(a^*, M(a^*)) \mid H = h) \\
&= E(Y(a, M(a)) \mid H = h) - E(Y(a^*, M(a^*)) \mid H = h)
\end{align*}
$$

and by assumption 1

$$
\begin{align*}
=E(Y(a, M(a)) \mid A = a, H = h) - E(Y(a^*, M(a^*)) \mid A = a^*, H = h) \\
\end{align*}
$$ 

and by the assumption of consistency which implies that 
$E(Y(a, M(a)) \mid A = a, H = h)= E(Y \mid H = h, A = a)$ and 
$E(Y(a, M(a)) \mid A = a^*, H = h)= E(Y \mid H = h, A = a^*)$ we obtain

By definition we have that $TE(a, a^*) = Y(a, M(a)) - Y(a^*, M(a^*)$, hence

$$
\begin{align*}
=E(Y \mid A = a, H = h) - E(Y \mid A = a^*, H = h) \\
\end{align*}
$$

### Prove $E(CDE(a, a^*;m) \mid H = h)$

By definition $CDE(a, a^*;m) = Y(a,m) - Y(a^*, m)$ therefore

$$
\begin{align*}
E(CDE(a, a^*;m) \mid H = h) = E(Y(a,m) \mid H = h) - E(Y(a^*, m) \mid H = h)
\end{align*}
$$ 

and by assumption 1

$$
\begin{align*}
= E(Y(a,m) \mid A = a, H = h) - E(Y(a^*, m) \mid A = a^* H = h)
\end{align*}
$$ 

by assumption 2

$$
\begin{align*}
= E(Y(a,m) \mid A = a, M = m, H = h) - E(Y(a^*, m) \mid A = a^*, M = m, H = h)
\end{align*}
$$

by assumption of consistency

$$
\begin{align*}
= E(Y \mid A = a, M = m, H = h) - E(Y \mid A = a^*, M = m, H = h)
\end{align*}
$$

### Prove $E(NDE(a, a^* ; a^*) \mid H = h)$

By definition $NDE(a, a^*;a^*) = Y(a,M(a^*) - Y(a^*, M(a^*)$ so

$$
\begin{align*}
E(NDE(a, a^*;a^*) \mid H = h) = E(Y(a,M(a^*)) \mid H = h) - E(Y(a^*, M(a^*)) \mid H = h)
\end{align*}
$$

now for the part $E(Y(a,M(a^*)) \mid H = h)$ we have

$$
\begin{align*}
\text{by the law of total expectations} \\
E(Y(a,M(a^*)) \mid H = h) &= \sum_m{E(Y(a,M(a^*))\mid M(a^*)=m, H)P(M(a^*)=m \mid H)} \\
\text{by consistency} \\
&= \sum_m{E(Y(a,m)\mid M(a^*)=m, H)P(M(a^*)=m \mid H)} \\
\text{by assumption 3} \\
&= \sum_m{E(Y(a,m)\mid M(a^*)=m, H)P(M(a^*)=m \mid A = a^*, H)} \\
\text{by assumption 4} \\
&= \sum_m{E(Y(a,m)\mid H)P(M(a^*)=m \mid A = a^*, H)} \\
\text{by assumption 1} \\
&= \sum_m{E(Y(a,m)\mid A=a, H)P(M(a^*)=m \mid A = a^*, H)} \\
\text{by consistency} \\
&= \sum_m{E(Y(a,m)\mid A=a, H)P(M=m \mid A = a^*, H)} \\
\text{by assumption 2} \\
&= \sum_m{E(Y(a,m)\mid A=a, M=m, H)P(M=m \mid A = a^*, H)} \\
\text{by consistency} \\
&= \sum_m{E(Y \mid A=a, M=m, H)P(M=m \mid A = a^*, H)} \\
\end{align*}
$$ 

and we can do the same for the part $E(Y(a^*,M(a^*)) \mid H = h)$.

### Prove $E(NIE(a, a^* ; a^*) \mid H = h)$

By definition $NIE(a, a^*;a^*) = Y(a,M(a)) - Y(a, M(a^*))$ therefore

$$
\begin{align*}
E(NIE(a, a^*;a^*) \mid H = h) &= E(Y(a,M(a)) \mid H = h) - E(Y(a, M(a^*)) \mid H = h)
\end{align*}
$$ 

and we can use the same method as for $NDE(a, a^*;a^*)$ on each of the 2 right-hand side parts to prove the result.

Using $CDE$ and $CIE$ partition, we can estimate the proportion of the effect that would be eliminated if we fixed the mediator to a level $M=m$.

$$
PE = \frac{TE-CDE(m)}{TE}
$$

and using $NDE$ and $NIE$ partition we can estimate the proportion mediated as

$$
PM =\frac{NIE}{TE}
$$

The dimension of $H$ will often require parametric methods. The parametric models in that case can be

$$
\begin{align*}
E(Y \mid A=a, M = m, H=h) &= \beta_0 + \beta_1 a+ \beta_2 m + \beta_3 a m + \beta_4^T h \\
E(M \mid A = a, H = h) &= \alpha_0 + \alpha_1 a + \alpha_2^T h
\end{align*}
$$ 

and with assumptions 1 through 4 we combine the estimate to obtain

$$
\begin{align*}
CDE(a, a^*;m) &= (\beta_1 + \beta_3 m)(a-a^*) \\
NDE(a, a^*;a^*) &= (\beta_1 + \beta_3 (\alpha_0 + \alpha_1 a + \alpha_2^T E(H)))(a-a^*) \\
NIE(a, a^*;a) &= (\beta_2 \alpha_1 + \beta_3 \alpha_1 a)(a-a^*)
\end{align*}
$$

## Traditional Parametric Methods

Two traditional parametric methods assume the parametric models from above 
*but without the interaction term*, that is $\beta_3=0$.

### Product method

Letting $a=1$ and $a^*=0$, the $NIE$ is estimated by $\hat{\beta_2} \hat{\alpha_1}$.

### Difference method

Estimate $NIE$ by comparing the coefficient of $a$ in

$$
\begin{align*}
E(Y \mid A=a, H=h) = \beta_0 + \beta_1 a+ \beta_2 (\alpha_0 +\alpha_1 a + \alpha_2^T h) + \beta_4^T h
\end{align*}
$$ 

which equals $\beta_1 + \beta_2 \alpha_1$ to the coeficient of $a$ in

$$
\begin{align*}
E(Y \mid A=a, M=m, H=h) = \beta_0 + \beta_1 a + \beta_2 m + \beta_4^T h
\end{align*}
$$ 

which equals $\beta_1$.

The idea is to see if the coefficient $\beta_1 + \beta_2 \alpha_1$ is significantly reduced by adding $M$ to the regression.

### Example

```{r}
#| label: ch12_gss
data("gss", package = "fciR")
gssmed <- gss |>
  dplyr::select(c("trump", "gthsedu", "magthsedu", "white", "female", "gt65",
                  "conservative")) |>
  tidyr::drop_na()
assertthat::assert_that(nrow(gssmed) == 2084)
```

and we use this function to compute the $NIE$

```{r}
#| label: ch12_func_mediation_NIE
func_mediation_NIE <- function(data, formula, exposure.name, mediator.name, confound.names) {
  outcome.name <- all.vars(formula[[2]])
  
  # reduced formula, without exposure in input
  exposure.confound.names <- c(exposure.name, confound.names)
  formula_red <- as.formula(paste(outcome.name, 
                                  paste(exposure.confound.names, collapse = "+"), 
                                  sep = "~"))
  # mediator formula
  formula_med <- as.formula(paste(mediator.name,
                                  paste(exposure.confound.names, collapse = "+"), 
                                  sep = "~"))
  
  # the models
  the_models <- list(
    "full" = formula,
    "reduced" = formula_red,
    "mediator" = formula_med)
  
  # the coefficients
  the_coefs <- lapply(the_models, function(x) {
    glm(formula = x, data = data) |>
      coef()
  }) |>
    setNames(names(the_models))
  
  
  NIE_prod <- the_coefs$full[mediator.name] * the_coefs$mediator[exposure.name]
  
  NIE_diff <- the_coefs$reduced[exposure.name] - the_coefs$full[exposure.name]

  msg <- sprintf("NIE_prod of %f != NIE_diff of %f", NIE_prod, NIE_diff)
  assertthat::assert_that(dplyr::near(NIE_prod, NIE_diff), msg = msg)
  
  # output compatible with boostrap function
  data.frame(
    term = c("NIE_prod", "NIE_diff"),
    estimate = unname(c(NIE_prod, NIE_diff)),
    std.err = NA_real_
  )
}
```

```{r}
#| label: ch12_gssmed.mediate_effect
gssmed.mediate_effect <- func_mediation_NIE(gssmed, 
                                            formula = 
                                              trump ~ magthsedu + conservative,
                                            exposure.name = "magthsedu", 
                                            mediator.name  = "conservative",
                                            confound.names = NULL)
gssmed.mediate_effect
```

and we evaluate the intervals with bootstrapping

```{r}
#| label: ch12_gssmed_boot
#| cache: true
gssmed.mediate_effect <- boot_est(data = gssmed, func = func_mediation_NIE,
           times = 250, alpha = 0.05,
           formula = trump ~ magthsedu + conservative, 
           exposure.name = "magthsedu", 
           mediator.name  = "conservative",
           confound.names = NULL)
gssmed.mediate_effect
```

## More Examples

This function is used to compute the final results by the `func_mediation_np` and `func_mediation` below.

```{r}
#| label: ch12_func_mediation_calc
func_mediation_calc <- function(NDE, NIE, CDE0, CDE1) {
  # estimate the total effect
  TE <- NDE + NIE
  assertthat::assert_that(!dplyr::near(TE, 0),
                          msg = "Total effect must not be zero.")
  # estimate the proportion mediated
  PM <- NIE / TE
  # estimate the proportion eliminated setting M=1
  PE1 <- (TE - CDE1) / TE
  # estimate the proportion eliminated setting M=0
  PE0 <- (TE - CDE0) / TE
  
  # output format can be used with bootstrap
  data.frame(
    term = c("TE", "PM", "PE(0)", "PE(1)"),
    estimate = c(TE, PM, PE0, PE1),
    std.err = NA_real_
  )
}
```

### Mediation nonparametric

```{r}
#| label: ch12_func_mediation_np
func_mediation_np <- function(data, formula, exposure.name, mediator.name,
                           confound.names) {
  # character vectors of names used below
  outcome.name <- all.vars(formula[[2]])
  exposure.confound.names <- c(exposure.name, confound.names)
  mediator.confound.names <- c(mediator.name, confound.names)
  input.names <- c(exposure.name, mediator.name, confound.names)
  all.names <- c(outcome.name, exposure.name, mediator.name, confound.names)
  
  # P(H)
  probH <- data |>
    fciR::calc_prob(var.name = confound.names, prob.name = "probH")
  assertthat::assert_that(sum(probH$probH) == 1,
                          msg = "Sum of prob. H must equal 1.")
  
  # P(M = m | A, H)
  probMcondAH <- data |>
    fciR::calc_prob_cond(condition.names = exposure.confound.names, 
                        var.name = mediator.name, 
                        prob.name = "probM") |>
    tidyr::pivot_wider(names_from = exposure.name, values_from = "probM",
                       names_prefix = "probMA") |>
    # add P(H) to th data, it will be used later for standardization by H
    dplyr::inner_join(y = probH, by = confound.names)
  
  # E(Y | A, M, H)
  expYcondAMH <- data |>
    group_by(across(all_of(input.names))) |>
    summarize(expYcondAMH = mean(.data[[outcome.name]])) |>
    tidyr::pivot_wider(names_from = exposure.name, values_from = expYcondAMH,
                       names_prefix = "EYA")
  
  # NOTE: This is the final dataframe used to make all computations
  #       It is an important dataframe when debuging
  processed_data <- inner_join(x = expYcondAMH, y = probMcondAH,
                    by = mediator.confound.names) |>
    ungroup()
  
  NDE <- processed_data |>
    mutate(NDEH = (EYA1 - EYA0) * probMA0) |>
    # standardize over H
    summarize(NDE = sum(NDEH * probH)) |>
    pull()

  NIE <- processed_data |>
    mutate(NIEH = EYA1 * (probMA1 - probMA0)) |>
    # standardize over H
    summarize(NIE = sum(NIEH * probH)) |>
    pull()

  CDE <- processed_data |>
    group_by(across(all_of(mediator.name))) |>
    summarize(CDE = sum((EYA1 - EYA0) * probH)) |>
    mutate(term = paste0("CDE(", .data[[mediator.name]], ")"))
  
  # calculated variables
  calc <- func_mediation_calc(NDE = NDE, NIE = NIE, 
                              CDE0 = CDE$CDE[CDE$term == "CDE(0)"], 
                              CDE1 = CDE$CDE[CDE$term == "CDE(1)"])
  
  # output format can be used with bootstrap
  out <- data.frame(
    term = c("NDE", "NIE", CDE$term),
    estimate = c(NDE, NIE, CDE$CDE),
    std.err = NA_real_) |>
    dplyr::bind_rows(calc)
  # relocate the columns
  the_terms <- c("TE", "CDE(0)", "CDE(1)", "NDE", "NIE", "PE(0)", "PE(1)", "PM")
  pos <- match(the_terms, out$term)
  out <- out[pos, ]
  out
}
```

```{r}
#| label: ch12_doublewhatifdat
data("doublewhatifdat", package = "fciR")
```

```{r}
#| label: ch12_dwhatif.med.np
dwhatif.med.np <- func_mediation_np(doublewhatifdat,
                                formula = VL1 ~ `T` + A + AD0,
                                exposure.name = "T", 
                                mediator.name = "A",
                                confound.names = c("AD0"))
# relocate the columns
dwhatif.med.np
```

### Mediation parametric

```{r}
#| label: ch12_func_mediation
# estimate natural direct effect (NDE) and natural indirect effect (NIE)
func_mediation <- function(data, formula, exposure.name, mediator.name,
                           confound.names) {
  # character vectors of names used below
  outcome.name <- all.vars(formula[[2]])
  exposure.confound.names <- c(exposure.name, confound.names)
  input.names <- c(exposure.name, mediator.name, confound.names)

  # fit a saturated model including the mediator
  formula_out <- paste(outcome.name, paste(input.names, collapse = "*"), 
                       sep = "~")
  fit_out <- glm(formula = formula_out, family = "binomial", data = data)
  # fit a saturated model for the mediator
  formula_med <- paste(mediator.name, paste(exposure.confound.names, collapse = "*"), 
                       sep = "~")
  fit_med <- glm(formula = formula_med, family = "binomial", data = data)
  
  # create new data sets
  newdat <- list()
  newdat$A0M0 <- data |>
    mutate(
      !!exposure.name := 0L,
      !!mediator.name := 0L)
  newdat$A1M0 <- data |>
    mutate(
      !!exposure.name := 1L,
      !!mediator.name := 0L)
  newdat$A0M1 <- data |>
    mutate(
      !!exposure.name := 0L,
      !!mediator.name := 1L)
  newdat$A1M1 <- data |>
    mutate(
      !!exposure.name := 1L,
      !!mediator.name := 1L)
  
  # estimate the first term  of equation (1) as a funciton of H
  EY1M0H <- 
    predict(fit_out, newdata = newdat$A1M0, type = "response") *
    (1 - predict(fit_med, newdata = newdat$A0M0, type = "response")) +
    predict(fit_out, newdata = newdat$A1M1, type = "response") *
    predict(fit_med, newdata = newdat$A0M1, type = "response")
  # standardize with respect to marginal distribution of H
  EY1M0 <- mean(EY1M0H)
  # estimate the second term  of equation (1) as a funciton of H
  EY0M0H <- 
    predict(fit_out, newdata = newdat$A0M0, type = "response") *
    (1 - predict(fit_med, newdata = newdat$A0M0, type = "response")) +
    predict(fit_out, newdata = newdat$A0M1, type = "response") *
    predict(fit_med, newdata = newdat$A0M1, type = "response")
  # standardize with respect to marginal distribution of H
  EY0M0 <- mean(EY0M0H)
    # estimate the first term  of equation (2) as a funciton of H
  EY1M1H <- 
    predict(fit_out, newdata = newdat$A1M0, type = "response") *
    (1 - predict(fit_med, newdata = newdat$A1M0, type = "response")) +
    predict(fit_out, newdata = newdat$A1M1, type = "response") *
    predict(fit_med, newdata = newdat$A1M1, type = "response")
  # standardize with respect to marginal distribution of H
  EY1M1 <- mean(EY1M1H)
  
  NDE <- EY1M0 - EY0M0
  NIE <- EY1M1 - EY1M0
  
  # estimate the controlled direct effects
  CDE1H <- predict(fit_out, newdata = newdat$A1M1, type = "response") -
    predict(fit_out, newdata = newdat$A0M1, type = "response")
  # standardize with respect to marginal distribution of H
  CDE1 <- mean(CDE1H)
  
  # estimate the controlled direct effects
  CDE0H <- predict(fit_out, newdata = newdat$A1M0, type = "response") -
    predict(fit_out, newdata = newdat$A0M0, type = "response")
  # standardize with respect to marginal distribution of H
  CDE0 <- mean(CDE0H)
  
    # calculated variables
  calc <- func_mediation_calc(NDE = NDE, NIE = NIE, CDE0 = CDE0, CDE1 = CDE1)
  
  # output format can be used with bootstrap
  out <- data.frame(
    term = c("NDE", "NIE", "CDE(0)", "CDE(1)"),
    estimate = c(NDE, NIE, CDE0, CDE1),
    std.err = NA_real_) |>
    dplyr::bind_rows(calc)
  # relocate the columns
  the_terms <- c("TE", "CDE(0)", "CDE(1)", "NDE", "NIE", "PE(0)", "PE(1)", "PM")
  pos <- match(the_terms, out$term)
  out <- out[pos, ]
  out
}
```

```{r}
#| label: ch12_dwhatif.med
# estimate controlled direct effect
dwhatif.med <- func_mediation(doublewhatifdat,
                                formula = VL1 ~ `T` + A + AD0,
                                exposure.name = "T", 
                                mediator.name = "A",
                                confound.names = c("AD0"))
dwhatif.med
```

### simulation `simmed`

```{r}
#| label: ch12_simmed
simmed <- function(n = 1000, seed = 44444) {
  set.seed(seed)
  A <- rbinom(n, size = 1, prob = 0.5)
  H <- rbinom(n, size = 1, prob = 0.5)
  # let the mediator increase with A and/or H
  tmppm <- A + H
  pm <- exp(tmppm) / (1 + exp(tmppm))
  M <- rbinom(n, size = 1, prob = pm)
  # let the outcome increase with A and/or H but dcrease with M
  tmppy <- H - M + A
  py <- exp(tmppy) / (1 + exp(tmppy))
  Y <- rbinom(n, size = 1, prob = py)
  data.frame(
    "H" = H,
    "A" = A,
    "M" = M,
    "Y" = Y
  )
}
```

```{r }
#| label: ch12_simmeddat
#| cache: true
simmeddat <- simmed()
```

```{r}
#| label: ch12_simmed.np
# estimate controlled direct effect
simmed.np <- func_mediation_np(simmeddat,
                                formula = Y ~ A + M + H,
                                exposure.name = "A", 
                                mediator.name = "M",
                                confound.names = "H")
simmed.np
```

```{r }
#| label: ch12_simmed_np_boot
#| cache: true
the_terms <- c("TE", "CDE(0)", "CDE(1)", "NDE", "NIE", "PE(0)", "PE(1)", "PM")
simmed.np.boot <- boot_est(data = simmeddat, func = func_mediation_np,
           times = 500, alpha = 0.05,
           terms = the_terms,
           formula = Y ~ A + M + H, 
           exposure.name = "A",
           mediator.name = "M",
           confound.names = "H")
```

```{r}
#| label: tbl-ch12_03
#| tbl-cap: "Table 12.3"
#| fig-align: 'center'
#| out-width: '100%'
fciR::gt_measures(simmed.np.boot,
                  title = "Table 12.3",
                  subtitle = paste("Nonparametric Mediation Analysis of the",
                                   "data generated by <em>simmed.r</em>",
                                   sep = "<br>"))
```