AI/ML in PMx

Artificial intelligence (AI) and machine learning (ML) are revolutionizing the field of pharmacokinetics and pharmacodynamics (PK/PD). These advanced technologies offer the potential to personalize drug treatment, optimize dosing regimens, and predict drug behavior with unprecedented accuracy. By leveraging AI/ML models, researchers can analyze vast amounts of PK/PD data, identify complex relationships between drug exposure and response, and develop more effective and individualized therapies. This emerging field holds immense promise for improving drug development, enhancing patient care, and ultimately advancing the future of medicine.

---
title: "An Example Using the Scientific Style"
author: "John Smith"
output:
  scientific::html
---

Example plot using ploty!

data(airquality)
library(dplyr)

## 
## Attaching package: 'dplyr'

## The following objects are masked from 'package:stats':
## 
##     filter, lag

## The following objects are masked from 'package:base':
## 
##     intersect, setdiff, setequal, union

library(plotly)

## Loading required package: ggplot2

## 
## Attaching package: 'plotly'

## The following object is masked from 'package:ggplot2':
## 
##     last_plot

## The following object is masked from 'package:stats':
## 
##     filter

## The following object is masked from 'package:graphics':
## 
##     layout

# designing the first 3-dimensional plot
tm <- plot_ly(airquality,x=~Month, y=~Temp, z=~Ozone,color=~Month, mode= "markers",type = "scatter3d") %>% layout(title = "Ozone, Temperature correlation by Month")
tm

## Warning: Ignoring 37 observations

Margin Figures

Images and graphics play an integral role in Scientific’s work. To place figures in the margin you can use the knitr chunk option fig.margin = TRUE. For example:

MPG vs horsepower, colored by transmission.

library(ggplot2)
mtcars2 <- mtcars
mtcars2$am <- factor(
  mtcars$am, labels = c('automatic', 'manual')
)
ggplot(mtcars2, aes(hp, mpg, color = am)) +
  geom_point() + geom_smooth() +
  theme(legend.position = 'bottom')

Note the use of the fig.cap chunk option to provide a figure caption. You can adjust the proportions of figures using the fig.width and fig.height chunk options. These are specified in inches, and will be automatically scaled down to fit within the handout margin.

Arbitrary Margin Content

In fact, you can include anything in the margin using the knitr engine named marginfigure. Unlike R code chunks ```{r}, you write a chunk starting with ```{marginfigure} instead, then put the content in the chunk. See an example on the right about the first fundamental theorem of calculus.

⊕We know from the first fundamental theorem of calculus that for \(x\) in \([a, b]\): \[\frac{d}{dx}\left( \int_{a}^{x} f(u)\,du\right)=f(x).\]

\[\frac{d}{dx}\left( \int_{b}^{x} f(x)\,du\right)=f(x).\] For the sake of portability between LaTeX and HTML, you should keep the margin content as simple as possible (syntax-wise) in the marginefigure blocks. You may use simple Markdown syntax like **bold** and _italic_ text, but please refrain from using footnotes, citations, or block-level elements (e.g. blockquotes and lists) there.

Note: if you set echo = FALSE in your global chunk options, you will have to add echo = TRUE to the chunk to display a margin figure, for example ```{marginfigure, echo = TRUE}.

Full Width Figures

You can arrange for figures to span across the entire page by using the chunk option fig.fullwidth = TRUE.

ggplot(diamonds, aes(carat, price)) + geom_smooth() +
  facet_grid(~ cut)

A full width figure.

Other chunk options related to figures can still be used, such as fig.width, fig.cap, out.width, and so on. For full width figures, usually fig.width is large and fig.height is small. In the above example, the plot size is \(10 \times 2\).

Arbitrary Full Width Content

Any content can span to the full width of the page. This feature requires Pandoc 2.0 or above. All you need is to put your content in a fenced Div with the class fullwidth, e.g.,

::: {.fullwidth}
Any _full width_ content here.
:::

Main Column Figures

Besides margin and full width figures, you can of course also include figures constrained to the main column. This is the default type of figures in the LaTeX/HTML output.

ggplot(diamonds, aes(cut, price)) + geom_boxplot()

A figure in the main column.

Sidenotes

One of the most prominent and distinctive features of this style is the extensive use of sidenotes. There is a wide margin to provide ample room for sidenotes and small figures. Any use of a footnote will automatically be converted to a sidenote. ¹

If you’d like to place ancillary information in the margin without the sidenote mark (the superscript number), you can use the margin_note() function from tufte in an inline R expression. ⊕This is a margin note. Notice that there is no number preceding the note. This function does not process the text with Pandoc, so Markdown syntax will not work here. If you need to write anything in Markdown syntax, please use the marginfigure block described previously.

If your version of pandoc-citeproc is too low, or you did not set link-citations: yes in YAML, references in the HTML output will be placed at the end of the output document.

Tables

You can use the kable() function from the knitr package to format tables that integrate well with the rest of the Scientific handout style. The table captions are placed in the margin like figures in the HTML output.

knitr::kable(
  mtcars[1:6, 1:6], caption = 'A subset of mtcars.'
)

Block Quotes

We know from the Markdown syntax that paragraphs that start with > are converted to block quotes. If you want to add a right-aligned footer for the quote, you may use the function quote_footer() from tufte in an inline R expression. Here is an example:

“If it weren’t for my lawyer, I’d still be in prison. It went a lot faster with two people digging.”

Without using quote_footer(), it looks like this (the second line is just a normal paragraph):

“Great people talk about ideas, average people talk about things, and small people talk about wine.”

— Fran Lebowitz

Responsiveness

The HTML page is responsive in the sense that when the page width is smaller than 760px, sidenotes and margin notes will be hidden by default. For sidenotes, you can click their numbers (the superscripts) to toggle their visibility. For margin notes, you may click the circled plus signs to toggle visibility.

More Examples

The rest of this document consists of a few test cases to make sure everything still works well in slightly more complicated scenarios. First we generate two plots in one figure environment with the chunk option fig.show = 'hold':

p <- ggplot(mtcars2, aes(hp, mpg, color = am)) +
  geom_point()
p
p + geom_smooth()

Two plots in one figure environment.

Then two plots in separate figure environments (the code is identical to the previous code chunk, but the chunk option is the default fig.show = 'asis' now):

p <- ggplot(mtcars2, aes(hp, mpg, color = am)) +
  geom_point()
p

Two plots in separate figure environments (the first plot).

p + geom_smooth()

Two plots in separate figure environments (the second plot).

You may have noticed that the two figures have different captions, and that is because we used a character vector of length 2 for the chunk option fig.cap (something like fig.cap = c('first plot', 'second plot')).

Next we show multiple plots in margin figures. Similarly, two plots in the same figure environment in the margin:

Two plots in one figure environment in the margin.

p
p + geom_smooth(method = 'lm')

## `geom_smooth()` using formula = 'y ~ x'

Then two plots from the same code chunk placed in different figure environments:

knitr::kable(head(iris, 15))

Two plots in separate figure environments in the margin (the first plot).

p

knitr::kable(head(iris, 12))

Two plots in separate figure environments in the margin (the second plot).

p + geom_smooth(method = 'lm')

## `geom_smooth()` using formula = 'y ~ x'

knitr::kable(head(iris, 5))

We blended some tables in the above code chunk only as placeholders to make sure there is enough vertical space among the margin figures, otherwise they will be stacked tightly together. For a practical document, you should not insert too many margin figures consecutively and make the margin crowded.

You do not have to assign captions to figures. We show three figures with no captions below in the margin, in the main column, and in full width, respectively.

# a boxplot of weight vs transmission; this figure
# will be placed in the margin
ggplot(mtcars2, aes(am, wt)) + geom_boxplot() +
  coord_flip()

# a figure in the main column
p <- ggplot(mtcars, aes(wt, hp)) + geom_point()
p

# a fullwidth figure
p + geom_smooth(method = 'lm') + facet_grid(~ gear)

## `geom_smooth()` using formula = 'y ~ x'

Some Notes on Scientific CSS

There are a few other things in Scientific CSS that we have not mentioned so far. If you prefer sans-serif fonts, use the function sans_serif() in tufte. For epigraphs, you may use a pair of underscores to make the paragraph italic in a block quote, e.g.

I can win an argument on any topic, against any opponent. People know this, and steer clear of me at parties. Often, as a sign of their great respect, they don’t even invite me.

We hope you will enjoy the simplicity of R Markdown and this R package, and we sincerely thank the authors of the Scientific-CSS and Scientific-LaTeX projects for developing the beautiful CSS and LaTeX classes. Our tufte package would not have been possible without their heavy lifting.

You can turn on/off some features of the Scientific style in HTML output. The default features enabled are:

output:
  scientific::html:
    tufte_features: ["fonts", "background", "italics"]

If you do not want the page background to be lightyellow, you can remove background from tufte_features. You can also customize the style of the HTML page via a CSS file. For example, if you do not want the subtitle to be italic, you can define

h3.subtitle em {
  font-style: normal;
}

in, say, a CSS file my_style.css (under the same directory of your Rmd document), and apply it to your HTML output via the css option, e.g.,

output:
  scientific::html:
    tufte_features: ["fonts", "background"]
    css: "my_style.css"

There is also a variant of the Scientific style in HTML/CSS named “Envisoned CSS”. This style can be used by specifying the argument tufte_variant = 'envisioned' in html()², e.g.

output:
  scientific::html:
    tufte_variant: "envisioned"

This document is also available in Chinese, and its envisioned style can be found here.