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Dr. Isis is a physiologist at a major research university working on some terribly impressive stuff. She blogs about balancing her research career with the demands of raising small children, how to succeed as a woman in academia, and anything else she finds interesting. Also, she blogs about shoes. In fact, she blogs a lot about shoes.
Isis the Scientist
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- December 15, 2008
- 02:42 AM
- 1,176 views
Classics in Physiology - DuBois and Comroe Calculate Airway Resistance
by Isis the Scientist in On Becoming a Domestic and Laboratory Goddess...
This week not many articles have tickled the fancy of the domestic and laboratory goddess. Still, at the end of last week I remarked that everything in physiology could be distilled down to Ohm's Law. Since nothing new is really exciting me, I've found myself thinking a lot about the classic papers in physiology that first inspired me to pursue a career as a physiologist. Foremost among these papers is Arthur DuBois's article in which he first describes the measurement of airway resistance. Arthur DuBois is now Professor Emeritus of Cellular and Molecular Physiology at the Yale School of Medicine and you can read about him here. He is one of Dr. Isis's heros in physiology. His technique is probably one of the most uncommonly used in respiratory medicine/physiology. But, more importantly, how he made it all work is just a great story.
Now, if you are one of the undergraduates Dr. Isis has taught, when she asks, "So how do you calculate airway resistance?" you cheerfully answer, "That's easy! You just use Ohm's Law. The resistance of the airways is equal to the flow through the airways divided by the change in pressure across the airways." Then I pat you on the head and offer you a cupcake for being so darned smart. But, describing this now, 52 years after DuBois published his paper, is easy. Actually making the measurement (a measurement which is now integral to cardiopulmonary physiology) was a huge challenge for respiratory physiologists of that time.
Figure 1: Calculating airway resistance. Airway resistance is equal to the flow through the airways divided by the change in pressure between the mouth and respiratory (ie, gas exchanging) region of the lung. Here, Ra is airway resistance, F is flow through the airway, and deltaPa is the change in airway pressure between the mouth and alveoli. But, how do you measure airway pressure? This is the coolest but unfunniest caption I have ever written.
First, when you make measurements of inspired and expired gas volumes, these volumes change as they either become warmed and humidified by the lung or cooled and dried by exposure to the environment (remember Charles's Law and the ideal gas equation?), as the composition of the gas changes, and as the measurement equipment becomes warmed by body heat. This was a huge source of confounding error for every investigator that tried to make measurements of airway dynamics before DuBois. DuBois's solution? He found that either panting (thereby limiting the warming and humidification of the air by the lung) or warming and humidifying his test equipment corrected the issue. A seemingly simply set of solutions, but this problem had stumped all those before him. I love the image of Arthur DuBois sitting in his lab, doing old school physiology, and panting into his equipment to see if he could get it to work. There is not enough panting in physiology in general.
Second, no one really knew how to measure changes in alveolar (and, thus, airway) pressure noninvasively during breathing. Dr. Isis loves science, but she is unwilling to allow anyone to shove a catheter through her chest wall and wedge it into her lung. So were most other people at the time. Dr. DuBois's mentor Julius Comroe had been working on the problem for years before DuBois joined the lab. Comroe had attemped to make measurements of alveolar pressure using a technique known as plethysmography In this technique a person sits in an airtight box and whole lung volume changes are determined by measuring the change in pressure inside the box and applying Boyle's Law (at least, this is how it is used currently for diagnostic purposes. Comroe used it slightly differently). DuBois describes Comroe's previous failings thusly:
Undaunted, Comroe and [his colleague, Stella] Botelho built a two-chambered steel box with which they hoped to measure alveolar pressure during breathing. The subject sat in one chamber and breathed into the other one. By measuring the change in chest volume in the chamber where the subject sat, and the volume of the air he expired into the second chamber, they hoped to calculate the alveolar pressure that compressed or expanded air in the chest during the breathing.
[The] volume artifacts were much larger than the desired volume signal, and the body box sat in a corner gathering dust for the next two years...In December, 1953, the last research fellow to try to make the body box behave as it should gave up and left. Comroe moved it into room 825 in the Gates Pavilion of the Hospital of the University of Pennsylvania, and put me in with it just in case I wanted to try my hand.
Try his hand he did. DuBois reoutfitted the box, applied his correction techniques, and solved the problem. He describes his solution:
The solution was almost self-evident once one knew what it was. If I measured airflow during breathing and related it to plethysmograph pressure change, and if I then measured alveolar pressure with airflow stopped and related it to the plethysmograph pressure change, then the plethysmograph pressure change would be the common denominator to relate alveolar pressure to airfloweven though alveolar pressure had not been measured during airflow!
It's not often an investigator feels entitled to shout "Eureka!" but for me, this was one of those rare, heady moments.
But, more importantly, why is this of any interest to you? Because DuBois is such a scrappy genius that he solved these problems after being a trainee in Julius Comroe's lab for only one week, resulting in a publication that has been cited more than 300 times. Almost 50 years later Arthur DuBois related Julius Comroe's reaction to his breakthrough to John West (another father of respiratory physiology), saying:
Julius was pleased it worked, but irritated that it only took a week.
Now don't you feel like a slacker?
The Original Article: Arthur B. DuBois, Stella Y. Botelho, Julius H. Comroe (1956). A NEW METHOD FOR MEASURING AIRWAY RESISTANCE IN MAN USING A BODY PLETHYSMOGRAPH: VALUES IN NORMAL SUBJECTS AND IN PATIENTS WITH RESPIRATORY DISEASE 1 Journal of Clinical Investigation, 35 (3), 327-335 DOI: 10.1172/JCI103282
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Arthur B. DuBois, Stella Y. Botelho, & Julius H. Comroe. (1956) A NEW METHOD FOR MEASURING AIRWAY RESISTANCE IN MAN USING A BODY PLETHYSMOGRAPH: VALUES IN NORMAL SUBJECTS AND IN PATIENTS WITH RESPIRATORY DISEASE 1. Journal of Clinical Investigation, 35(3), 327-335. DOI: 10.1172/JCI103282
- January 2, 2009
- 05:18 PM
- 839 views
Classics in Physiology - Kao's Neural and Humoral Dogs
by Isis the Scientist in On Becoming a Domestic and Laboratory Goddess...
A few days ago I read a great post written by my brother in ScienceBlogging, PhysioProf on the generation of novel scientific ideas. His post stemmed from a post originally written by Zuska, and PhysioProf noted that one of the ways he generates new ideas is through the generation of novel methodologies. This left your humble domestic and laboratory goddess reflecting on the source of her own methods. You see, in the work that I am doing the problem came first and the method evolved as a way to solve the problem. I work in an area where it is usually impossible to buy a kit or a pre-made apparatus. Everything that we are currently using is stuff that I built and I was very fortunate to have trained in labs where we were taught to draw diagrams, to hook together electrical-type gizmos, use awesome things like solenoid valves and transducers, and to just build really cool stuff. That's part of what excites me about science -- the opportunity to look at an organism and at man-made equipment and to figure out how to integrate the two in a way that allows me to make physiological measurements and describe phenomena. That is, the ability to combine electrical, chemical, and mechanical engineering techniques with awesome surgical skills and generate data.
And I remember the paper that first really sparked a desire to develop novel methodolgy in order to solve a problem. In the 1950s Frederick Kao of the State University of New York' College of Medicine was trying to discern the mechanism that causes hyperpnea during exercise -- hyperpnea being a physiologic increase in ventilation in order to meet an O2 delivery or CO2 clearance requirement. At this point is was known that an increase in blood pCO2 or decrease in pO2 (to a lesser extent) was enough to increase ventilation in a resting animal/human through activation of the central and peripheral chemoreceptors, located in the carotid bodies and brain. However, it was recognized by researchers of this period that the time course of the increase in ventilation seen at rest with simple alterations in blood gases was too slow to explain the much more rapid increase in ventilation noted with exercise. This led folks to postulate that there was some direct neural connection between the exercising muscle and the respiratory centers in the brain that would signal the hyperpnea at the start of muscle contraction. So, 70 years pass, a whole slew of scientists take a crack at this chicken and the egg-style problem, and none of them are able to effectively tease apart the potential neural mechanisms from mechanisms related to changes in blood factors (what Kao calls "humoral" factors).
Then, like a shining beacon of science hope, along comes Frederick Kao (who had been keeping his finger on the pulse of the field) to solve the problem. Kao clearly demonstrated that there is no humoral-, (or blood-) related component that is necessary for the increase in ventilation caused by exercise. To do so, Kao used two dogs as research subjects, deeming one the "neural dog" and the other the "humoral dog." He connected the circulatory systems of the two dogs, joining their carotid arteries and jugular veins, so that the head and neck of humoral dog (the head and neck being where the chemoreceptors are located) was perfused by blood exclusively from the other dog (check our Figure 1 from their paper for a pretty cool diagram of the experiment). Thus, Kao could perfuse the chemoreceptors of the humoral dog with blood from the other dog and specifically test whether there was a factor in blood that increased ventilation during exercise. Kao then simulated exercise in the neural dog by stimulating the hind legs to contract and measured ventilation in both dogs. In essence (and how freakin' cool is this???) Kao incorporated great surgical technique, setting up his one little bypass circuit between the two animals, with some basic engineering to answer his question.
What Kao found was that ventilation in the neural dog, whose blood was perfusing the chemoreceptors of the humoral dog, increased as he expected it would with the onset of muscle contraction. The ventilation of the humoral dog, however, did not change. Thus, Kao was able to conclude that there was no factor in the blood of the exercising neural dog that could explain the increase in ventilation. Since Kao's paper was published, investigators have gone on to describe the presence of C-fibers and metaboreceptors in skeletal muscle and to scrap like mad fiends about which is important in determining the exercise hyperpnea response in health and disease.
But still, 2 dogs 1 circulation. How cool an idea is that?
Kao FF (1956). Regulation of respiration during muscular activity. Am J Physiol, 185 (1), 145-151 This article is available here.
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Kao FF. (1956) Regulation of respiration during muscular activity. Am J Physiol, 185(1), 145-151. DOI: http://ajplegacy.physiology.org/cgi/reprint/185/1/145
- March 14, 2010
- 11:50 PM
- 821 views
Science blogs and public engagement with science: practices, challenges, and talking out of your ass
by Isis the Scientist in On Becoming a Domestic and Laboratory Goddess...
This week a couple of my Sciblings have been abuzz about an article published in some journal I'd never heard of... a minor impact journal...the Journal of Who Gives a Fuck Science Communication. Bora has a great break down of some of the major criticisms. Drugmonkey, one of the subjects of the "analysis" in this article, is also displeased and critical of the author's conclusions.I've
since read the offending article and can only tell you this - I have no
idea what the balls the author is talking about. Seriously, this
article is about as informative as this: Video 1: A current favorite at the Isis house. When emailed this video, PhysioProf
replied, " Couldn't they afford to animate some fucking legs on those
fuckers?" I have always wondered why Mr. Lunt has no eyes.But, for those of you who are still interested, here's the run down...Inna Kouper,
a graduate student in Library and Information Science at Indiana
University, somehow magically chose 11 blogs to study, one of which was
Pharyngula. Now, I'm not hating on Pharyngula. PZ plays an important role in the blogosphere and, while I think that sometimes his commenters get out of control,
he's got a unique voice and an uncanny ability to rally the troops. No
one can deny that the climate at Pharyngula is not necessarily
reflective of the entire blogosphere. Still, the fact is that Inna
Krouper sampled 11 blogs. There are 80 blogs currently at
ScienceBlogs, 8 more at Discover Blogs, and a bazillion independent and
network blogs indexed by the Nature Network. Yet, somehow Inna chose
these 11 blogs as representative of the genre and one of them was
motherfucking Pharyngula. Then, she did this:A
combination of quantitative and qualitative techniques of content
analysis has been used in this study. The qualitative analysis
involved iterative close reading of posts and comments with the purpose
of identifying common types of statements and activities
conceptualized as modes of participation. This conceptualization was
informed by the speech act theory and the pragmatics perspective yet it
was purposefully left rather loose and open to allow for the categories
to emerge from the data. Each time a mode of participation was
identified, it was entered into a catalog, and then a post or a comment
was assigned a corresponding code. Along with the modes of
participation, the posts were coded for topics and sources of the post;
the comments were coded for the reader's identification elements (e.g.,
a nickname, first name, full name, link to blog, or blog author).
Subsequently all codes were counted and the analysis proceeded with the
examination of the most frequent and rare patterns and their groupings.Translation?Figure 1: Inna sat down one night, read some blogs, and then wrote some shit. She must really be itching to finish the ole thesis.I
mean, I truly am baffled by these methods, especially when the author
brags that "it is necessary to analyze current practices of science
blogging. To date no attempts have been made to do that. The present
study is the first step in this direction." This article is a step
alright...Figure 2: Problem is, none of realize where that step is taking us until it is too late to unlearn the stupid.I'm
just plain ole disappointed by the "methodology." This author could
have taken the opportunity to perform a carefully controlled study with
randomly-selected non-scientists. She could have shown them blinded
content and administered questionnaires. Instead she wrote 10 pages of
opinion and passed it off as science.After pages upon pages of presenting cherry-picked content, Inna concludes this:Science
blogs examined in this study are very heterogeneous. They provide
information and explain complicated matters, but their evaluations are
often trivial and they rarely provide extensive critique or articulate
positions on controversial issues... It appears that science blogging
can also be characterized as relying on reductive analysis and
dependent reporting and drawing caustic and petty commentary. These
characteristics may as well be applied to the newspaper and magazine
science communication, but with the newer science communication outlet
such as blogging they indicate that the potential of blogging to do
something differently, e.g., to provide informed expert and citizen
commentary, is not realized. In their current multiplicity of forms and
contents science blogs present a challenge rather than an opportunity
for public engagement with science. Lack of genre conventions, which
for the audience translates into broken expectations and uncertainty,
impedes the development of stable readership and participation from the
larger public, which may also be very heterogeneous. The "neighborhood
bar" or "water cooler" commentary creates a sense of community with
shared context and culture, but at the same time it creates a barrier
that prevents strangers and outsiders from joining the conversation. As
a community of scientists or individuals close to science, the
existing readers may enjoy the entertaining nature of science blogs and
not need science blogs to serve as a place for discussion and rational
debate. Relying on such community of readers, bloggers may reduce their
interpretive activities and resort to copying, re-distributing, and
re-packaging of the existing information, which is still quite
rewarding given the background of the majority of current readers and
yet requires much less time and effort. This study provides further
evidence that blogging as a web tool has no magic properties on its
own. Without a concerted effort of different social actors involved it
will not solve any problems...Reading this, I
realize that I did my PhD in the wrong damned field. I would be a much
more prolific publisher if I had entered a field where I could have
written whatever bullshit moved me on any given day and called it
"research." I also wonder how many of you feel like you
simply add "caustic and petty commentary"? I question how Inna can
conclude that blogs pose a barrier to the conversation. That's a
difficult statement to take seriously, knowing that Inna had no access
to traffic data for any of the blogs she read. For me, I know that a
single blog will be read by 1000s more non-scientists than any original
scientific article I publish in a peer-reviewed journal. And, she
certainly wouldn't have found the analysis trivial if she had read some
of Ed Yong or Carl Zimmer's work, not that I find any of the blogs she included trivial. Then again, I think it is the diversity of voice is what makes the blogosphere so beautiful. My
sample size = 1 is probably no better than Inna's sample size = 11, but
I can at least offer my experience to the data set. I get many letters
a week from young people interested in science careers and soliciting
advice on graduate school, fields of study, and professional
development. The number of people who have come to my office in person
to have these conversations is trivial in comparison. Thus, these data
would lead me to conclude that my blog presence has lowered the barrier
to engagement with this audience.I'll also never forget one of the occasions,
quite a while ago, that I wrote about some novel research. It was a
topic semi-related to my expertise.&nb... Read more »
Inna Kouper. (2010) Science blogs and public engagement with science: practices, challenges, and opportunities. Journal of Science Communication, 9(1). info:/
- April 18, 2010
- 02:51 PM
- 531 views
If You're Going to Taser a Sheep, at Least Do It Right!
by Isis the Scientist in On Becoming a Domestic and Laboratory Goddess...
On Friday I read with interest a post written by my dear SciBling DrugMonkey conducted by the folks at TASER International on the effects of the TASER on anesthetized, methamphetamine-intoxicated sheep. The TASER is a device used by law enforcement agents that uses an electrical shock to disrupt neuromuscular function and immobilize suspects.
Figure 1: The multi-shot TASER X3.According to Dr. Monkey, in this study (1), The study was conducted in Dorset sheep who were [isoflurane] anesthetized,
and administered 0, 0.5, 1.0 or 1.5 mg/kg of methamphetamine HCl
(curiously from dissolved Desoxyn, the approved pharmaceutical product)
in an IV infusion. The drug treatment was a between subjects factor (N=4
per group) and animals were monitored for "continuous blood
pressure, heart rhythm (one-lead), pulse oximetry, and capnography...
Arterial blood sampling was performed at baseline, 30 minutes after the
administration of the methamphetamine, and after each exposure from a
TASER X26".The authors looked at the number of sheep that developed abnormal heart rhythms from exposure to the TASER both with and without pre-intoxication with methamphetamine. They conclude that in small animals TASER exposure worsens the cardiac irritability induced by methamphetamine intoxication, but
that this is not seen in adult animals. DrugMonkey points out the need for these types of studies. Indeed, an article in the International Journal of Cardiology states: Read the rest of this post... | Read the comments on this post...... Read more »
Cevik, C., Otahbachi, M., Miller, E., Bagdure, S., & Nugent, K. (2009) Acute stress cardiomyopathy and deaths associated with electronic weapons. International Journal of Cardiology, 132(3), 312-317. DOI: 10.1016/j.ijcard.2008.12.006
Dawes, D., Ho, J., Cole, J., Reardon, R., Lundin, E., Terwey, K., Falvey, D., & Miner, J. (2010) Effect of an Electronic Control Device Exposure on a Methamphetamine-intoxicated Animal Model. Academic Emergency Medicine, 17(4), 436-443. DOI: 10.1111/j.1553-2712.2010.00708.x
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