Monday, August 31, 2009

Monday meetings, more than oversight.

The Monday Meeting(tm), or weekly meetings on another day, is one of the fundaments of labs and research groups everywhere. It can take on any number of guises. Here I will outline how we organize our Monday meetings now and how we arrived there.

When Our Enlightened Despot spent his first sabbatical in the US he came home with the idea of the Monday meeting.

It basically consisted of the Peons reporting what they did last week, and planned to do the coming week. People showed up when they had time and our Illustrious Clinicians never had that time. Mostly because 9.00am Monday morning is a busy time in the clinic. Every now and then someone was assigned to present some data. This was usually done in the form of graphs on paper, with the intro of: "In the 2004-03 project the expression of pro-col-n-pep was increased... as you see here." Obviously no one understood why this might be important or even interesting, but it was done anyway.

Three (or four) years ago the scientific presentations and discussions were moved to Fridays, and there was a series of very interesting Friday seminars. However, with two meetings per week, attendance was down and there were still no clinicians to be seen.

Two years ago we set a schedule with fifteen minute long scientific presentations every monday. These were supposed to be either brief reports of recent results, or a review presentation of a relevant area. In either case they should be properly prepared and formatted presentation, with proper introduction, hypothesis, methods and results. With this more strict setup we have managed to keep everyone in the loop, the lab rats can understand the archaic ways of epidemiological research and the clinicians get the background needed to understand the importance of the genetic expression of the Gene of the Day(tm).

Meeting at nine in the morning still did not work great for our clinicians, so last year we moved the meeting to Mondays at 14.00 (2.00pm). It is a fairly low intensity time for clinicians, but it does destroy the afternoons lab work for those so inclined. We have a short progress report where everyone says what they are working with, and we have one fifteen minute scientific presentation every Monday.

We have managed to keep attendance high and are well on the way to creating a common knowledge base in the whole group, so that the discussion can focus more on the science than on the peculiarities of the different fields.

How do you do it at your lab?

Does it work well or...?



Saturday, August 29, 2009

The lady tasting tea

Statistics is one of the cornerstones of modern science, the other three being Blood, Sweat and Tears.

First, it is important to distinguish between the different things that are called statistics. There is mathematical statistics, or so I have heard, and there is applied statistics, which is what we are generally talking about. In applied statistics there is descriptive statistics, which we call plotting, and finally inferential statistics.

Inferential statistics is the area that most (junior) scientists mean when they say that they hate statistics. It is the area of hypothesis testing or finding of significant differences, and what people hate about it is that it is never clear which test you should use.

You will have learnt that you should predefine the tests you are looking for and design the experiment after that. The problem lies in having a too theoretical understanding of statistics and not having enough experience with what ever kind of data you possess. This means that you have not been able to predict what kind of analysis gives the most power with the data you end up with.

In the end, the first time you handle any type of dataset has to be considered an exploratory investigation. And, it is important to accept that and really get to know how the data responds to analysis and what kind of results you can get out of it. Then, next time, you can predetermine the correct type of analysis, and feel like you are on higher ground, theoretically.

So, how do you get to understand statistics, or at least start to understand it?

I have found no statistics text books that are worth while in the beginning. None. Many are useful once you have understood something.

The same goes for statistics courses. They are just not useful, especially not for understanding statistics. The most useful courses I have had in statistics were those that focused on a specific problem and a specific approach, i.e. "Using R and Bioconductor for the analysis of mRNA expression micro arrays". Even with those, the real help with understanding comes from working with your own data.

I suggest two things:

  1. Read the wonderful book "The lady tasting tea" by David Salsburg describes the development of statistics as a science in a most delightful way. He manages to present many of the basic ideas of statistics without being technical. I can only recommend it, especially if you like the history of science.
  2. Start using a statistics program that can help you understand what you do. I suggest R. It's free, it's what all the statisticians use (so you can ask them how to do something), it includes a manual, and it includes original references to many of the methods.

Michael Hultström

Failed experiment depression

How depressed should you get when an experiment fails?

I have a tendency to get a bit blue whenever an experiment goes south. This generally takes the form of an immediate re-run and a panic-like reading of lab journals to find any possible error. If it doesn't resolve directly, I usually come up with a plausible explanation and try to confirm it with my colleagues. When I have a decent plan for how to continue I generally feel better, but not happy by any measure. I will often continue my ruminations for days, often until the experiment has finally succeded and sometimes even after it is done, finished and published.

Maybe this is a Good Thing(TM). As recently reported on Slashdot from an article in Scientific American, and an original article in Evolutionary Psychology in 2007, depression may serve to focus attention at the causative incident. From an evolutionary perspective this would potentially allow for the quick resolution of otherwise intractable problems.

So, when my western blot failed (no discernerable bands at al) on friday I immediatly went into a panic. Tried another ECL, tried an extremely sensitive ECL. Re-washed and re-applied the secondary antibody etc. It still didn't work. The problem is probably that the secondary antibody is dead. It was an all new batch, and it was stuck in transit, at room temperature, for almost a week.

Anyway the failed western blot soundly destroyed my Friday and my week end. Not to mention that I can't think about anything else and that I therefore have to write this blog instead of working on my thesis introduction or the other parts of the paper where the western blot will be included once it works.

If Andrews et al is correct this may be a well adapted response. However, I think this demands that one can continue working on the problem until it is solved (damn these week ends). When you have lots of other things to do even the small depression caused by a failed western blot can severly sabotage your schedule.

My vain hope is that now that I know about it I may be able to compensate. At least a little.


Thursday, August 27, 2009

First recorded nephrology experiment?

I like finding original documentation for the facts in science that are generally accepted, and for which experimental evidence is seldom or never given. I hope to write a series of these small notes concerning the history of experimental renal physiology.

One can assume that the association between the kidneys and urine production has been known since the first time pre-historic man, or woman, killed an animal and ate the kidneys. There has however been considerable discussion through the ages what the relative roles of the kidneys, the urethers and the bladder actually are.

Around 360 B.C. Plato wrote in "Timaeus" that:
“The outlet for drink by which liquids pass through the lung under the kidneys and into the bladder, which receives and then by the pressure of the air emits them...” (from the Internet Classics Archive at MIT, translated by Benjamin Jowett.)
He then goes on to describe the use of the actual outlet in sexual intercourse.

Somewhere around the same time Aristotle has a surprisingly correct description in "On the parts of animals":

"A pair of stout ducts, void of blood, run, one from the cavity of each kidney, to the bladder; and other ducts, strong and continuous, lead into the kidneys from the aorta.

The purpose of this arrangement is to allow the superfluous fluid to pass from the blood-vessel into the kidney, and the resulting renal excretion to collect by the percolation of the fluid through the solid substance of the organ, in its center, where as a general rule there is a cavity.

From the central cavity the fluid is discharged into the bladder by the ducts that have been mentioned, having already assumed in great degree the character of excremental residue." (Part 9. Also from the Internet Classics Archive, translated by William Ogle.)
However, even though some dissection must have taken place, neither Plato nor Aristotle describe the methods behind their conclusions. I have read somewhere that it was not fashionable to refer too closely to the real world at the time. The world of ideas (platonic) was thought to exist independently of the real world and all important conclusions could be arrived at through contemplation and deduction.

Quite a bit later Galen or Claudius Galenus describes what I believe is the oldest surviving description of a scientific experiement in renal physiology. Seeking to show that the urine is produced in the kidneys and passed through the urethers to the bladder, Galen writes:
"Now the method of demonstration is as follows. One has to divide the peritoneum in front of the ureters, then secure these with ligatures, and next, having bandaged up the animal, let him go (for he will not continue to urinate). After this one loosens the external bandages and shows the bladder empty and the ureters quite full and distended- in fact almost on the point of rupturing; on removing the ligature from them, one then plainly sees the bladder becoming filled with urine." ("On the Natural Faculties", book 1, chapter 13, from the Internet Classics Archive, translated by Arthur John Brock).
It is ofcourse not a very humane experiment given that anaesthesia was not developed for another 1600 years or so. I have not found any date of publication, but given that he lived from year 129 to year 200 it is the oldest fairly solid experimental description in nephrology I have been able to find.

Do you know of any older records?

Please chime in,


Tuesday, August 25, 2009

Nephrophysiologist, but why?

This was meant to be the first post, but it was much harder to come up with an honest "artist's statement", as Chemiotics calls it, than I thought.

Can there really be an interest for a blog about renal physiology? Any really interesting stuff will be published anyway, and if it is blogged, that may count as prior publication. What is left is to discuss ideas in general terms, published work, methods, and the practice of physiology. However, I believe some interesting discussions may be had in these areas. There are many insights that aren't appropriate for full publication that may be aired in a blog much in the way these kind of things are aired and discussed at conferences and meetings.

My hope is to keep the discussion going between the all to far apart meetings in Real Life(tm). There are some science bloggers out there in not too far away fields. I hope to tie up with these early adopters of this brave new world 2.0, there are many things that different fields of science have in common. Maybe I can even induce a couple of new ones to join in.

So, please, write a comment, start a blog and let's have a discussion.


Michael Hultström

Prevalence of hypertension in Norway

The Norwegian society for hypertension got a surprisingly difficult question: What is the prevalence of hypertension per age group in Norway?

You would certainly think there was a straight forward answer to that question, and that we should know it. You don't even predict the question, because you think it has to be published in an easily accessible form. Any way, it is not. The best current evidence is only published in Norwegian, so in the interest of the hypertension community here is the short story.

2000-2003 the Norwegian institue of public health performed a health survey in selected counties and this was published in the journal of the norwegian medical association(Pubmed: Tidsskr Nor Laegeforen. 2007 Oct 4;127(19):2537-41.). The data is in table 4. What it says is that 17.4 % of men and 3.2 % of women aged 30 had a systolic blood pressure higher than 140 mmHg and/or a diastolic blood pressure higher than 90 mmHg. The number of hypertensives gradually increased to 65.4 % of men and 69% of women at the age of 75 years.

Thanks to my collegues in the Hypertension society for helping me find the data. Especially Randi Selmer at the Norwegian institute of public health who provided (and co-authored) the paper.

In the coming year we can look forward to the publication of the whole population data from the health survey in the county Nord-Trøndelag study number 3 (HUNT-3). There still will not be a definitive answer to the question of the prevalence of hypertension in Norway, but age group coverage will be down to 13 years of age.

So, as far as I can see, I have a 82.6 % chance of not having hypertension (not counting that I am rather stressed at the moment, which would bring it down to -10% somewhere).