The Effect of Caffeine on Web Design

From Wikipedia:

Caffeine has a significant effect on spiders,
which is reflected in their web construction.

The question is, does this apply to humans as well?  After all, humans engage in web design, so it should be possible to do a direct comparison.

Here is the structure of a web site designed by a person who is not impaired at all.  Here's the information about it:

Image: created by Websites as Graphics.

KEY: What do these colored dots mean?
blue: for links (the A tag)
red: for tables (TABLE, TR and TD tags)
green: for the DIV tag
violet: for images (the IMG tag)
yellow: for forms (FORM, INPUT, TEXTAREA, SELECT and OPTION tags)
orange: for linebreaks and blockquotes (BR, P, and BLOCKQUOTE tags)
black: the HTML tag, the root node
gray: all other tags

Now, what happens if a person makes a web site while drinking too much Starbucks?

Again, from Wikipedia:

Too much caffeine, especially over an extended period of time, can lead to a number of physical and mental conditions. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) states: "The 4 caffeine-induced psychiatric disorders include caffeine intoxication, caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeine-related disorder not otherwise specified (NOS)."

An overdose of caffeine can result in a state termed caffeine intoxication or caffeine poisoning. Its symptoms are both physiological and psychological. Symptoms of caffeine intoxication include: restlessness, nervousness, excitement, insomnia, flushed face, diuresis, muscle twitching, rambling flow of thought and speech, paranoia, cardiac arrhythmia or tachycardia, and psychomotor agitation, gastrointestinal complaints, increased blood pressure, rapid pulse, vasoconstriction (tightening or constricting of superficial blood vessels) sometimes resulting in cold hands or fingers, increased amounts of fatty acids in the blood, and an increased production of gastric acid. In extreme cases mania, depression, lapses in judgment, disorientation, loss of social inhibition, delusions, hallucinations and psychosis may occur.^[13]

When DSM-V is published, it will expand the list of symptoms of caffeine intoxication:

• Excessive use of unordered lists and bullet points
• Gross failure to comply with social norms of HTML coding
• Implusive, pointless linking from one post to another
• Pathological refusal to use tags only for their intended purpose

This is a good illustration of an important point reagrding the categorization of medical conditions (nosology).  When the expectations and demands of society change, we have to revise our system of diagnosing mental illness.

HT: Hedwig the Owl, et alia.

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Update: there are over 400 websites-as-graphs on Flickr.

Generic Escitalopram

This is not really big news, but it makes me stop and think.  Escitalopram has been approved in generic form (5, 10, 20mg tabs, 5mg/5ml solution).  Previously, it could only be obtained as the branded product, Lexapro.  As of today, that leaves only one selective serotonin reuptake inhibitor (SSRI) with patent protection: Zoloft (sertraline).  Zoloft is going off patent in June 2006.  

I'm still not entirely sure when generic sertraline will be available.  There has been a lot of convoluted legal wrangling over the subject, a discussed in this court ruling (82 KB PDF).  When it does occur, though, there will be no SSRIs under patent protection.  Effexor (venlafaxine) and Cymbalta (duloxetine) will be the only popular antidepressants that are patented.  (The Emsam (selegiline) patch was approved recently, but it remains to be seen how popular it will turn out to be.)

For many years, antidepressants have been a major contributor to the cost of prescription drug insurance coverage.  Clearly, that is changing.  

I suppose we can all expect our insurance to get cheaper now.

On the Recursive Nature of Pride

Pride is one of the seven deadly sins.  The others are greed and sloth and a few others I can't remember.  Pride is the one I remember best, because of its curious mathematical properties.  Things with unexpected properties are easier to remember than ordinary things like greed and sloth and so forth.


The thing about pride is this: once a person becomes aware of it, he or she tends to recognize that it is a sin.  That person then takes steps to banish the pride.  Then the person is proud for having banished the sin, thus becoming a paragon of virtue.  Rather naturally, the person then realizes that excessive pride in one's own virtue is itself a sin.  Then the whole thing starts over again.

Some people do manage to get little bit wiser with each iteration.  Others do not.

I have never been able to figure out what makes the difference.  Nor have I been able to find an objective way to determine if I am one of the ones who is getting wiser.

New Banner

Getting ready for the transition to ScienceBlogs, I've gone ahead an designed a new banner.  (I had help with the techincal aspects, but the design was my idea.)  I'm a little worried that they are redesigning the layout, so it is possible that the size will be wrong or the colors won't match, but I decided to do it anyway.  It should be simple enough to change, if that turns out to be necessary.

The image on the left is a macro photo of an Intel 486-DX2 processor; the image on the right is an illustration from the 1918 edition of Gray's Anatomy.  Both are in the public domain.  I found the images on Wikipedia.  The text is in a font known as Ringbearer, which I downloaded from a free font site.  I suppose I should mention the site, but I can't recall the name of the site.  If you search for "Ringbearer font" you will find several sites that have it.

The banner was made using GIMP, the Gnu Image Processor, which is an open-source program.  Although it started as a Linux program, there are version for Mac and Windows.

Using GIMP on a Mac, image from the GIMP.org site.

Knoppix Screenshots

These are pictures of Knoppix, a kind of Linux, in use.  See the previous post for the context.  The images are from the O'Reilly site, OSDir.com.  

Knoppix, showing the browser.  Firefox is also available, but not shown here.


With Knoppix, you click on the lower-left icon to open the main menu, as shown.

Accelerated Knoppix

I know I've written about this before, so if you've read one of my prior posts on the topic, or if you already are familiar with the concept of a live CD, just skip to the bottom line for the info that is specific to Accelerated Knoppix.  

    We affirm that the world's magnificence
    has been enriched by a new beauty:
    the beauty of speed.

Filippo Tommaso Marinetti - Manifesto of Futurism -

That quote is on the homepage for the Accelerated Knoppix project.  What that means is that computer users can boot from the CD and get a complete operating system and a complex set of applications, ready to use.   It boots if the hard drive has crashed.  It even boots if there is no hard drive in the computer at all.  

There are several uses for a live CD.  Probably the most obvious is that it enables a user to try an operating system or an application without having to install the application on the hard drive.  So if you've never used Linux before, and want to give it a try, you can use alive CD to try it out, with minimal effort, and with no risk of messing anything up.  Or, if you've heard about OpenOffice -- the free alternative to Microsoft Office -- and want to see if it really will open your Word documents, and see if it really is as easy to use as Microsoft Word, you can do so easily.  

Another use for a live CD is for emergency use.  If your computer crashes and you HAVE TO check your email, you can do it quickly with a live CD. (It can't configure a dial-up connection automatically, but it can and will recognize and use a broadband or ethernet connection without specific user intervention.)  Likewise, if your system won't boot, you might be able to recover data using a live CD.  

A more obscure use of a live CD could be to use it for anonymous browsing.  lxnay dEsigN is planning to develop a live CD (actually a DVD) that uses TOR servers to obscure your internet usage.  Plus, being on an unwritable medium, there would be no cookies, no browsing history, or other traces that could be recovered later.

Finally, some folks have used Knoppix to figure out how to configure their Linux systems.  I've done that myself.  When I was first learning to do intermediate-level configuration, I somehow messed up my XF86Config file (one of the files that says "Please do not edit this file" at the top.)  I booted from Knoppix and saw how Knoppix autoconfigured the file, saved it to a USB flash drive, and fixed the problem that way.

By the way, there are live CD's for operating systems other than Linux.  I've never used any of them, though.  

The bottom line: one disadvantage of a live CD is that it can take a couple of minutes to boot.  Accelerated Knoppix uses a new technology to speed up the boot process.  I did not time it, but it seemed to boot in less than a minute.  

In the spirit of open-source software, the developers of Acclerated Linux have made available their "LCAT" (Live CD Acceleration Toolkit).  If you want to convert your favorite Live CD distro to an accelerated version.  

The one trick to this distribution is that the default language is Japanese.  In order to get English menus, you have to type  Knoppix lang=US  when it first starts.

So, I will now keep a copy of this at home and at my various offices, just for emergency recovery.

No New Taxes...

...except on people who are not very influential.

It was publicized pretty well, when the Administration increased taxes on teenagers.  This has been discussed elsewhere, so I won't go into it very much.  I just learned, however, that there has been another tax increase, again affecting Americans who have little influence.  And like the one that affects teenagers saving for college, this one could have serious negative consequences.

U.S. tax law sends expatriates reeling
By Keith Bradsher and David Cay Johnston
The New York Times

FRIDAY, MAY 26, 2006

HONG KONG The sudden, and retroactive, imposition by the U.S. Congress last week of much higher taxes on Americans living abroad has left individuals and companies scrambling to regroup, while many executives and entrepreneurs assert that the move could backfire by hurting U.S. business interests at home and abroad.
 
The $69 billion tax cut signed into law May 17 raises taxes on Americans living overseas by $2.1 billion over the coming decade. [...]

To put this in perspective, consider that the additional revenue represents the cost of only a two weeks of fighting the war in Iraq (which does not include reconstruction costs).  If it hurts international trade, it obviously wouldn't be worth it.  

Note that this increase is not only a violation of one of Bush's campaign pledges, but it also increases the complexity of the tax code:

Last year the law allowed most overseas Americans to exclude $80,000 of foreign earned income from income taxed in the United States. The new law adjusts the exclusion for inflation to $82,400, but it raises taxes by adding complex new provisions on how the exclusion is calculated. 

Oddly, this article shows up on the International Herald Tribune site, but not on the New York Times website, despite the fact that it was written by NYT reporters.

War On Science Update

I can't tell you how glad I am to see this:

In Speech to Medical Graduates, Bloomberg Diverges From G.O.P. Line
By DIANE CARDWELL
Published: May 26, 2006

Distancing himself from national Republicans and the Bush administration, Mayor Michael R. Bloomberg yesterday urged an end to the political manipulation of science, which he said had been used to discredit the threat of global warming and undermine medical advancements in areas like stem-cell research.

In a speech to graduating students of Johns Hopkins University School of Medicine in Baltimore, Mr. Bloomberg railed against what he sees as ideologically motivated arguments that have fueled debate over hot-button issues like teaching evolution in public schools and the Terri Schiavo case.

"Today, we are seeing hundreds of years of scientific discovery being challenged by people who simply disregard facts that don't happen to agree with their agenda," Mr. Bloomberg said. "Some call it pseudoscience, others call it faith-based science, but when you notice where this negligence tends to take place, you might as well call it 'political science.' " [...]

Bloomberg only cited global warming, stem cells, Terri Schiavo, and Intelligent Design.  There is a lot more that he could have mentioned, but I am sure the new graduates appreciate the fact that he didn't go on at encyclopedic length.

In his speech, Bloomberg clearly acknowledged the systematic nature of the war on science.  

From time to time, I have wondered, momentarily, if scientists are defensive about their field, imagining they are under attack, much as a subset of conservative Christians feel there is a war on Christmas.  I never think that for more than a few seconds, though.  

At other times, I wonder why scientists worry about the war on science.  After all, science will endure.  Presidents come and go, religions come and go, but science marches on.  Surely scientists can find other things to work on, at those times that petty power struggles give rise to temporary impediments.  Then, when the heat dies down, they can get back to whatever it was that the politicians or theocrats were meddling in.

But then I remember that science is actually important, now.

Nature is Full of Surprises

From Nature News, we hear of another twist in the story of inheritance:

Mutant mice challenge rules of genetic inheritance
DNA's cousin, RNA, may also pass information down the generations.

Helen Pearson

In a discovery that rips up the rulebook of genetics, researchers in France have shown that RNA, rather than its more famous cousin DNA, might be able to ferry information from one generation of mice to the next.

DNA has long been credited with the job of passing traits from parent to child. Sperm and egg deliver that DNA to the embryo, where it ultimately decides much of our looks and personality.

The new study in Nature1 thrusts RNA, DNA's sidekick, into the limelight. It suggests that sperm and eggs of mammals, perhaps including humans, can carry a cargo of RNA molecules into the embryo - and that these can change that generation and subsequent ones.

"It's a very exciting possibility," says Emma Whitelaw who studies patterns of inheritance at Queensland Institute of Medical Research in Brisbane, Australia. "DNA is certainly not all you inherit from your parents." [...]

We already knew that mitochondrial DNA could play a role, albeit a small
role, in the process of inheritance.  

Spotty mice flout genetics laws, on the BBC site, is another article on the same topic.  The Washington Post has a version, here.  

When I hear of things like this, I am reminded of how little we know about the details of the functioning of even fairly simple processes in biology.  Think about inheritance, which is the transfer of a defined set of information.  Then think about the operation of the human brain, which has something like 10¹⁵ synaptic connections.  

Now, I am going to write something very un-scientific.  

Proponents of Intelligent Design might look at the subtleties of inheritance, or the vast complexity of the brain, and take those observations as evidence for their proposition.  As far as I can tell, though, their only argument is that the origin of species via evolution just doesn't seem right; it doesn't mesh with their intuition.  My intuition apparently works differently.  What I see is that scientists start out with a bunch of complex, seemingly-inexplicable phenomena, then one by one, make discoveries that explain more and more of what previously was inexplicable.  What my intuition tells me is that, eventually, science will come up with mundane (complex, perhaps, but still mundane) explanations for an ever-increasing percentage of things that formerly were awe-inspiring.  From that, I conclude that the mere existence of seemingly-miraculous things can only be taken as evidence of limitation in our knowledge and understanding.  It does not mean anything more.

Nice Picture

This is a smoke plume from a volcano in the Aleutian Islands, as photographed from the International Space Station; it's from the NASA Earth Observatory site.

Astronaut photograph ISS013-E-24184 was acquired May 23, 2006, with a Kodak 760C digital camera using an 800 mm lens, and is provided by the ISS Crew Earth Observations experiment and the Image Science & Analysis Group, Johnson Space Center. The image in this article has been cropped and enhanced to improve contrast. Lens artifacts have been removed. The International Space Station Program supports the laboratory to help astronauts take pictures of Earth that will be of the greatest value to scientists and the public, and to make those images freely available on the Internet. Additional images taken by astronauts and cosmonauts can be viewed at the NASA/JSC Gateway to Astronaut Photography of Earth.

Penguin Power

After messing around with XGL -- the most advanced graphical user interface there is for a computer operating system, I've now been using a much older and simpler interface: FVWM.  What is FVWM?  The answer, from their FAQ:

1.1 What does FVWM stand for?

A: "Fill_in_the_blank_with_whatever_f_word_you_like_
 at_the_time Virtual Window Manager". Rob Nation 
 (the original Author of FVWM, doesn't really remember 
 what the F stood for originally ...

I suppose that one tires of all the fancy do-dads after a while.  Or maybe it is just a desire for something different.  After all, different things always have a certain appeal.

Speaking of that appeal, it has been determined that we now have a "new" species of penguin:

The eyebrows have it for new penguin species
By John Lichfield in Paris
Published: 24 May 2006

In a world full of disappearing or threatened species, here is some good news at last. The planet is about to welcome a new species of penguin.

The birds - a few thousand small penguins on the French islands of Amsterdam and St Paul in the southern Indian Ocean - resemble millions of rockhopper penguins found all around the northern fringe of the Antarctic.

And thanks to the stubborn research of a French ornithologist, they have been declared a species in their own right.

Pierre Jouventin, scientist and film-maker and one of the world's foremost experts on penguins, first claimed that the Amsterdam and St Paul rockhoppers were a separate species 25 years ago. [...]

His claims were dismissed by other ornithologists. Now, two years before his retirement, Mr Jouventin, 63, has been vindicated. In a forthcoming article in the magazine Molecular Ecology he will reveal DNA tests which show that the Amsterdam and St Paul rockhoppers are a distinct species. [...]

Eudyptes moseleyi

This is a nice illustration of the power of close observation, combined with a little intuition, and a lot of perseverance.

Grand Rounds 2:35 is Up

Dr. Emer has posted the latest Grand Rounds.  He even came up with a nifty logo for it.  As always, he has a nice layout/design.  

At first, I was going to list a few posts that I found particularly interesting, but that proved to be too difficult.  I will say that it is good to see nonmedical persons participating.

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Update: shortly after posting this, I realized that Coturnix has the new Tangled Bank up.  

This is an astonishing array of science writing; I find it inspiring.  In fact, it is almost enough to make me wish I had become a real scientist.

XGL Eyecandy

I do think that XGL has promise, but it needs a few things.  First, it has to be more stable.  With it, I cannot run Firefox in KDE, unless I run it as root, which I am loathe to do; or, unless I open another session and use Gnome or FVWM.  Also, ideally, it would be possible to customize mouse gestures, so that awkward keyboard commands are not necessary.  

I must say that the performance is decent.  I expected the system to be more sluggish, but any decrement is not noticeable.  

Some of the commands really are useless, such as the "rain" command:

I suppose there is a use: it shows a potential that somebody, some day, might find a real use for.  But why would I want the effect of raindrops splashing on the screen?  

Also, I cannot resist this comment.  Everyone keeps referring to the "cube."  It is not a cube. (Unless you have a square monitor.)  It is a square cuboid: The top and bottom are square, but the sides are non-square rectangles.

Huh? Botox for Depression?

Medscape News has an interesting item: Botox Injections May Be Useful for Major Depression (free registration required).

Botox Injections May Be Useful for Major Depression
Laurie Barclay, MD

May 16, 2006 — Botulinum toxin A injections can treat major depression, according to the results of a small case series reported in the May issue of Dermatologic Surgery.

"Major depression is a common and serious disease that may be resistant to routine pharmacologic and psychotherapeutic treatment approaches," write Eric Finzi, MD, PhD, and Erik A. Wasserman, PhD, from Dermatology and Cosmetic Surgery Associates in Greenbelt, Maryland, and Chevy Chase Cosmetic Center in Maryland. "There is a body of evidence that suggests that the facial expression of emotion may play a causal role in the subjective experience of emotion. We initiated a small open pilot trial to determine whether inhibiting the expression of facial frowning commonly associated with depression could help ameliorate depressive symptoms."

This was an extremely small study, involving only ten patients, without, and with double- or single-blind condition.  That means that it is not possible to draw any valid conclusions, other that to say that a larger, double-blind, placebo-controlled study might be worthwhile.  

The idea is not without precedent.  It is known that people with anxiety tend to be overly vigilant concerning somatic symptoms that are correlated with anxiety.  When they notice such symptoms, it tends to increase their anxiety, which increases the symptoms: a classic positive feedback loop.  Sometimes, patients with anxiety disorders can learn to interrupt the feedback loop, resulting in clinical improvement.  As far as I know, nobody has tried anything like that with mood disorders, until now.

A total of 10 patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for ongoing major depression refractory to pharmacologic or psychotherapeutic treatment were evaluated with the Beck Depression Inventory II (BDI-II) before receiving botulinum toxin A to their glabellar frown lines.

Two months later, all patients were reevaluated clinically and with the BDI-II. Nine of 10 patients were no longer depressed, and the 10th patient had an improvement in mood.

"These findings are very promising and show that Botox has the ability to work in ways we don't expect," Alastair Carruthers, MD, president-elect of the American Society for Dermatologic Surgery and head of Carruthers Dermatology in Vancouver, British Columbia, Canada, says in a news release.

Personally, I would be astonished if this turned out to work in a large, randomized, double-blind, placebo-controlled study.  On the other hand, it would be pretty neat if it did work.  What is more likely is that it either will not pan out at all; or it will turn out to be of great benefit to a few people, partial benefit to a few more, and no benefit to everyone else.  Even so, stranger things have happened.  The first discovery of antidepressant medication occurred when an antitubercular antibiotic, iproniazid, was found to relieve melancholia in patients being treated for tuberculosis.  

None of this indicates that Botox is likely to work for treatment of depression, but it shows that it is, at least, remotely possible.

Update: The Washington Post picked up the story, and has a testimonial from one patient.  From a scientific standpoint, one testimonial is meaningless.  What it does do, though, is give you an idea of what the experience is like from the patient's point of view.

Serotonin and Depression: A Disconnect

This is sort of  a follow-up to a recent post, in which I discussed the correlation between administration of fluoxetine, and neurogenesis in the hippocampus.  In that post, I mentioned that skeptics of psychopharmacology are fond of pointing out the lack of a well-defined connection between the inhibition of serotonin reuptake, and the clinical effects of the serotonin reuptake inhibitors.  

The hypothesis that there is a connection between serotonin and depression is a refinement of the monoamine hypothesis of depression.  That hypothesis states that there may be a connection between relative underactivity of brain monoamines (serotonin, norepinepherine, dopamine) and depression.  It is an old idea, derived in part from studies such as this one:  Antagonism to reserpine induced depression by imipramine, related psychoactive drugs, and some autonomic agents.  Sigg EB, Gyermek L, Hill RT. Psychopharmacologia. 1965 Feb 15;7(2):144-9.

Obviously, we have learned a lot since 1965, so the monoamine hypothesis is significant mainly as an historical relic.  Even the refinement -- the serotonin hypothesis -- is ancient.  Since then, ample evidence has been found, showing that the serotonin hypothesis is, at best, a gross oversimplification.  There is no strict correlation between serotonin activity and any defined mental illness.

The lack of a strict correlation means that the action of antidepressant medication is not fully understood; nobody I know will dispute that. But the thing is, harping on that string is pointless.  It is like pointing out that there is not a strict correlation between the noise of an automobile engine, and the motion of he automobile.  It is true that sometimes an automobile moves without the engine making noise; and sometimes the engine makes noise without moving.  Sometimes there is a significant lag between the time the engine starts making noise, and the time the automobile starts to move.  With the correct instruments, it would even be possible to show that none of the energy that goes into the production of noise has anything to do with the movement of the automobile.  True, all of it.  But can we conclude that there is no connection between the noise of the automobile, and the motion?  

Perhaps the serotonin boost is not at all related to the clinical effect.  It could be an epiphenomenon.  Physicians generally know about epiphenomena, and are cautious about overinterpreting them.  Pointing out the fact, that there is not necessarily a causal connection, is tiresome.  Thus, when a skeptic takes pains to point it out, it merely shows that the skeptic is not aware of how obvious it is to medically-educated people.

As an aside, it occurs to me that epiphenomena are roughly analogous to spandrels.  If I felt like getting tediously philosophical, I could write a post outlining that analogy.  Another time, perhaps.  (A hint: just as a feature that evolves as a spandrel can turn out to be useful, sometimes side effects of mediation can be useful.)

Sometimes it is difficult to avoid getting tediously philosophical.  Oh well.  It occurs to me also that this is an example of how a good understanding of evolutionary theory can be helpful in understanding medicine, as Orac is fond of pointing out.  (As is my former residency director, Randy Nesse.)  This is true regardless of whether you believe that evolution is responsible for the origin of species.

Putting that aside aside, and getting back to the point: Because it is tiresome to hear skeptics harp on that string (the lack of a fully-delineated connection between serotonin and depression) I was surprised to see this article in a well-regarded journal:
Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature, by Jeffrey R. Lacasse and Jonathan Leo.

Illustration: Margaret Shear, Public Library of Science

I was surprised to see this, because it is, to me, a new twist on the old theme.  The authors do not imply that antidepressant medication does not work; nor do they argue that psychopharmacology is suspect.  

To equate the impressive recent achievements of neuroscience with support for the serotonin hypothesis is a mistake.

Rather, they argue that it is inappropriate for pharmaceutical companies to base advertising campaigns upon the presumed link between serotonin and depression.  

In the US, the FDA monitors and regulates DTCA. The FDA requires that advertisements “cannot be false or misleading” and “must present information that is not inconsistent with the product label” [27]. Pharmaceutical companies that disseminate advertising incompatible with these requirements can receive warning letters and can be sanctioned. The Irish equivalent of the FDA, the Irish Medical Board, recently banned GlaxoSmithKline from claiming that paroxetine corrects a chemical imbalance even in their patient information leaflets [29]. Should the FDA take similar action against consumer advertisements of SSRIs?

Curiously, the authors devote several paragraphs to debunking the serotonin hypothesis, even though, in my opinion, their purpose could have been served with one or two citations.  What is even more curious is that they do not go on to draw a specific conclusion that answers the question they pose: they never answer directly the question about whether the FDA should take action against the pharmaceutical companies that refer to the serotonin hypothesis in their advertisements.  

In fact, they do make a good case against the pharmaceutical companies, and I happen to agree.  It appears to be true, based upon their argument, that pharmaceutical companies are not following FDA regulations regarding DTC advertisements.  Moreover, the authors make several other good points, such as this one:

Patients who are convinced they are suffering from a neurotransmitter defect are likely to request a prescription for antidepressants, and may be skeptical of physicians who suggest other interventions, such as cognitive-behavioral therapy [48], evidence-based or not.

I personally have spent a lot of time in the office, with patients, trying to undo the misinformation contained in DTCA.  It bothers me that I have to do that.  I would much rather spend the time providing good education, not undoing bad education.  I would prefer to not have to deal with direct-to-consumer advertising at all; but if we have to have it, companies really ought to be held to the standards that exist to ensure balance and accuracy.

Impeachment Update

Howard Kurtz, writing on the Washington Post column, Media Notes, has an update on the brewing impeachment issue.  It turns out that some Republican strategists have been hyping the threat of impeachment.  Apparently, they believe that the possibility of impeachment of the President might motivate some voters to go to the polls and vote for Republican congressional candidates.

Personally, I do not see the problem with impeachment hearings, even looking at it from the Republican perspective.  After all, with regard to the domestic spying operations, the Administration keeps telling us that if we haven't done anything wrong, we have nothing to fear.  Certainly, the same principle applies to the Administration itself.

Neurogenesis Promoted By Fluoxetine

Browsing on the Scientific American site, I came across a reference to a new study: Fluoxetine targets early progenitor cells in the adult brain.  In was written by Juan M. Encinas, Anne Vaahtokari, and Grigori Enikolopov; it was published online ahead of print in PNAS on May 15, 2006.  The abstract is here; the PDF (2.8MB), which is freely available, is here.

Fluoxetine targets early progenitor cells in the adult brain
Juan M. Encinas, Anne Vaahtokari, and Grigori Enikolopov
Published online before print May 15, 2006
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0601992103

Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neurogenic agents in these distinct subclasses of neuronal precursors. We use this line to demonstrate that the selective serotonin reuptake inhibitor antidepressant fluoxetine does not affect division of stem-like cells in the dentate gyrus but increases symmetric divisions of an early progenitor cell class. We further demonstrate that these cells are the sole class of neuronal progenitors targeted by fluoxetine in the adult brain and suggest that the fluoxetine-induced increase in new neurons arises as a result of the expansion of this cell class. This finding defines a cellular target for antidepressant drug therapies.

This particular study is interesting to neuroscientists, mainly because it outlines a technique for studying what happens in the brain when certain medications are given.  For nonspecialists, there are several points of interest.  The Scientific American article points out one:

By isolating the step in neuron development that fluoxetine influences, the scientists have identified a new target for antidepressants that may have fewer side effects. The research also unveils the links in the chain leading from stem cells to new neurons as well as provides an animal tailor-made to investigate the mechanisms of other medicines and treatments, permitting a ray of hope into the darker regions of brain dysfunction.

I suppose that is true; we might someday develop a new treatment, based upon this research.  That is not guaranteed, though; even if it does turn out to be the case, it would take decades to get a marketable product out of it.  Perhaps what is more interesting is what is tells us about the mechanism of action of antidepressant medication, and how the reality of what these drugs do compares with popular misconceptions.

Fluoxetine is the generic name for Prozac, the first selective serotonin reuptake inhibitor marketed in the USA.  Much has been made of the fact that fluoxetine boosts the amount of serotonin in the neuronal synapse.  That effect is commonly thought of as the mechanism of action of the drug.  Skeptics of psychopharmacology are fond of pointing out a problem with this hypothesis.  The problem is that the serotonin boost occurs within hours of taking the medication, but the therapeutic effect takes weeks to develop.  The article by Encinas et. al. shows that the time course for the development of new neurons takes about a month (in mice).  (On page 3 of the PDF file, there is an illustration showing the progression from quiescent neural progenitor cells to mature granule cells.)  

The thing is, one often starts to see clinical improvement about two weeks after the drug is started.  That is well after the serotonin boost, but before any new neurons are fully developed.  This makes it seem unlikely that neurogenesis is, by itself, responsible for the therapeutic effect.  Of course, the validity of that line of reasoning is based upon the assumption that neurogenesis in humans is no faster than that in mice.  

The demonstration of the existence of neurogenesis, and the time course, refutes the popular notion that the serotonin boost is the main mechanism of action.  There is little doubt that the serotonin boost is an important part of how the drug works, but it clearly is not the whole story.  The existence of neurogenesis also suggests that the notion, that antidepressants are basically "uppers" or a "quick fix," is misguided.  Unlike the case with stimulants, people who take antidepressants do not notice anything immediately, except for side effects.  Moreover, the action of an antidepressant drug takes place in three phases.  In the first two weeks, we tend to see side effects, but little clinical effect.  After two to eight weeks, there is reduction in symptoms.  Over subsequent months, there is a reduction in the frequency of relapse.  If the drug is stopped during the first several months of treatment, there is a high probability of relapse.  That probability drops with each successive month, out for about nine to twelve months.  It is possible that the relapse-reduction effect has a different neuronal basis than the immediate and intermediate effects.

It will be a while before we have a full understanding of all the effects of antidepressant medication.  It will take even longer for us to map each of those neural effects to the clinical effects.  I am tempted to speculate, at this point, that neurogenesis in not responsible for the clinical improvement that is seen in the first few weeks of treatment.  It may, however, play a role in the reduced frequency of relapses.

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Note: the images are public-domain, from Wikipedia.  Click on them to go to the respective Wikipedia pages.

Video Game Boost?

Extremetech informs us that video games had a big impact on the economy last year:

Video Games Had $18B Impact On U.S. Economy

The video game industry, which supported 144,000 full-time jobs and accounted for more than $8 billion in game sales in 2004, had an $18 billion impact on the U.S. economy that year, according to a new study to be released on Wednesday.

What they don't tell you, is that the economic impact of video games was all negative.

It Has Been A While...

...since I've posted anything satirical. This one isn't even my own idea, but I wish it were:

Bush Demands That Iran Halt Production of Long Letters Posted on May 12, 2006 By Andy Borowitz

Days after receiving an 18-page letter from Iranian president Mahmoud Ahmadinejad, President George W. Bush called the lengthy missive "an act of war" and demanded that Iran halt its production of long letters at once.

At the White House, aides said that writing a letter of such length to President Bush, who is known for his extreme distaste for reading, was the most provocative act Mr. Ahmadinejad could have possibly committed. [...]

In the realm of US popular culture, there are TV shows and movies that contain no good people. All the the characters are unlikeable. It is hard to believe that such shows even exist. But somebody must like them, or else they would just go away.

The current situation with Iran is like that. No good guys. It is hard to believe that our government is acting the way it is, but someone in Washington must like it, or else they would stop. And like popular culture, this is not going to go away.

War on Science, Chapter MMVI

Under the guise of fiscal responsibility, Washington has proposed eliminating $2 million from the budget for maintaining libraries run by the Environmental Protection Agency.  According the the Washington Post:

Budget Cut Would Shutter EPA Libraries
By Christopher Lee
Washington Post Staff Writer
Monday, May 15, 2006; Page A15

Proposed budget cuts could cripple a nationwide system of Environmental Protection Agency libraries that government researchers and others depend on for hard-to-find technical information, library advocates say.

The $2 million cut sought by the White House would reduce the 35-year-old EPA Library Network's budget by 80 percent and force many of its 10 regional libraries to close, according to the advocates and internal agency documents.

That, in turn, would dramatically reduce access to certain EPA reports, guidance and technical documents that are used by the agency's scientific and enforcement staff as well as private businesses and citizens, they say.

In the obligatory fair-and-balanced way, WaPo informs us of the defense offered by an EPA spokesperson:

EPA spokeswoman Jennifer Wood said it was "premature" to talk of mass closings among the regional libraries, although the one in Chicago already is shutting down. Wood said that 15 other EPA libraries, many of them attached to federal laboratories, will not be affected by the budget cuts.

She said the agency plans to save money and operate more efficiently by making EPA materials in the regional libraries available electronically. Many documents that exist only on paper will continue to be available through interlibrary loans, Wood said.

It would seem that if you cut the budget by 80%, there would have to be a serious impact.  Also, it seems that if they really plan to convert to electronically-stored documents, they should do that before they close the libraries that have the hard copies.  Critics point out that it will be much more difficult for environmental advocates to do the research necessary for their efforts.  See the blog post by the Public Employees for Environmental Responsibility (PEER) for additional links on the subject.

The physical collections, many of which are sole source documents, will simply be shuttered up, as the agency has no funds to relocate or digitize these records. The EPA Region 2 library is the principal research resource for regulators, academics and researchers in the New York and New Jersey area.

Environmental advocates point out that this is not the only effort to limit the agency's effectiveness.  Internal budget changes are steering funds away from programs that protect children's health, toward other programs that are dedicated to homeland security.  According to PEER, as reported by YubaNet:

At the same time these new security functions are being expanded, EPA's overall budget is being cut. The budgetary axe is falling on traditional environmental programs, such as those designed to improve water quality. EPA is also closing most of its libraries as a cost-saving measure.

Programs that affect children's health have also been particularly hard-hit. This fall, Johnson announced the elimination of EPA's Office of Children's Health Protection, an entity dedicated to ensure that the special vulnerability of children is safeguarded in environmental standard-setting, enforcement and prevention efforts. The Office of Children's Health Protection was collapsed into the Office of Environmental Education, considered one of EPA's lowest priority programs.

Later in the article, they refer specifically to programs designed to protect children from pesticides.  The efforts were found to be inadequate, but rather than correct the problem, they cut the funding even more:

In January, the EPA Office of Inspector General issued a report criticizing serious inadequacies in the agency's ability to assess the effects of pesticides on fetuses, infants, toddlers, and youngsters. The agency claims that it lacks funding to collect data, conduct cumulative effect analyses and develop standards for determining the developmental neurotoxicity of the pesticides that EPA is approving for commercial use. Significantly, EPA is overdue in producing a plan for corrective actions that address the material weaknesses identified by the Inspector General.

Homeland security is all well and good; we do need to prevent terrorists from poisoning us.  Of course, with these changes, the terrorists don't have to poison us.  Our own industries are doing it for them, and we are letting them get away with it.

Is this post merely a rant?  No, I actually have an idea to offer.  If the government thinks it cannot afford to digitize the EPA library, why not ask Google to do it for them?  They'd probably do it for free.

Corpus Callosum Is Going To SEED

photo of Pusteblume by dyzzy -- some rights reserved

Scales of Flowers

Here are two pictures of flowers.  In case you care, I'll let you know that these flowers can be found on the north side of the Michigan Union, on the University of Michigan campus.  You might also want to know what kind of flowers they are, but you will have to wait.

I studied anthropology and zoology, not botany, so don't ask me the name of the flowers.  I can't answer that question.  So I will move on to a different question.
  
Notice that one picture was taken from about two feet away; the other, from just a few inches.  So which is the better picture? 

I did not study art, so I cannot answer that question.  But I can say what I like...

The closer-up one is more appealing to me, when looking at it on the computer monitor.  However, it occurred to me, that if I were to get one of the pictures printed and framed and hung on the wall, I would rather have the one that shows the whole bunch.  

If I had printed the picture that gave me the best impression at first, I would have ended up with the wrong one on the wall.

What this demonstrates, is that one picture is better for one particular purpose, while the other is better for a different purpose.  Yet is is almost automatic, to ask ourselves: "which one is better?"  We conclude that something is good or bad, better or worse; then, we base our subsequent decisions on that conclusion.  In the process, we forget what observations led us to the conclusion in the first place.

That is one way that we end up making the wrong choices.  We base our decisions on intermediate conclusions; then we forget the original observations.

Often, when we consider a bunch of observations, then draw some kind of conclusion, we think we have gained new information.  That is not the case. Conclusions tend to obscure information, not generate new information.

---

Politicians know this.  That is why they so often try to get us to draw conclusions prematurely.  They try to get us to form a positive impression of them, based on vague niceties.  We draw a conclusion, and feel good about ourselves, thinking we have figured something out.  We often don't bother to notice when subsequent observations don't fit with our nice little conclusion.  After we form that initial impression, we tend to disregard the little details.  After all, why go through the effort of noticing and/or remembering all those little details, when you already know what your conclusion is?

Well, the reason is this: you might end up with the wrong picture on the wall.

Chantix (varenicline tartrate) For Smoking Cessation

Both the New York Times (link) and the Washington Post (link) carried an article about the new smoking-cessation pill from Pfizer.  The brand name for the product is Chantix; the generic name is varenicline tartrate.  

Varenicline tartrate was the Prous Scientific Molecule of the Month for March 2006.

Chantix (varenicline tartrate)

Chantix is a partial agonist for a particular type of nicotine receptor.  The term partial agonist refers to a chemical that activates the receptor, but is not able activate the receptor to its full extent.  

In the case of Chantix, it acts on a subtype of nicotine receptor called the α4β2 (alpha4beta2 nicotinic receptors).  Chantix activates these receptors, providing an effect similar to that of a low to medium amount of nicotine.  However, because it is a partial agonist, it is not possible to get as strong an effect as one would get with a high dose of nicotine.  In fact, the presence of Chantix would make it impossible for the receptors to be activated fully, even in the presence of a high dose of nicotine.

As a result, the patient gets relief from nicotine craving, but only to a certain extent.  Smoking a cigarette while taking Chantix would not result in increased activation of the receptors.  

The behavioral theory here, is that it will be much easier to quit smoking, once the behavior of smoking is not coupled with a reward.  That is, it is no longer positively reinforced.  

Likewise, the negative reinforcement is eliminated.  Once the behavior of smoking no longer results in a relief from craving, there is not so much of a reason to keep doing it.

Note that the mechanism of action of Chantix is analogous to that of Subutex and Suboxone (buprenorphine).  

One of the reasons that addiction is such a nasty problem, is that the addictive behavior is reinforced both positively and negatively.  Not only does the behavior lead to something positive, but it also avoids a negative consequence.  In the case of addiction, the negative consequence is the withdrawal syndrome.  See this e-Medicine page for on overview of the problem of nicotine addiction.

Of course, addiction is a complex phenomenon.  Simple behavioral models are not perfect.  It follows, then, that the results of the treatment are less than perfect.  According to the Washington Post:

Several studies conducted in Europe on about 2,000 smokers and presented in November at an American Heart Association conference showed that a year after initial treatment with varenicline, abstinence rates were 22 percent, versus 16 percent among those given Zyban. Just 8 percent of those given dummy medicines had stopped after a year.

A success rate of 22% may not sound impressive.  However, smoking is so prevalent and so damaging, that even a small success rate could have a large impact on public health.  

Another thing to keep in mind, when interpreting the success rate, is this: many people have already quit smoking.  Presumably, the ones who continue to smoke are those who have the greatest difficulty in quitting.  It is likely that most of the people who participated in the studies were people who already had tried to quit several times.  Therefore, any improvement seen with the drug is all the more impressive.

Tenkile Conservation Alliance

Papua New Guinea (PNG) is home to a number of threatened and endangered species; one of these is the tenkile (Dendrolagus scottae; Scott's Tree Kangaroo).  According to the Tenkile Conservation Alliance:

The Tenkile Conservation Alliance (TCA) aims to save the critically endangered Tenkile, or Scott's Tree Kangaroo (Dendrolagus scottae), from becoming extinct.

The Tenkile is one of the most endangered mammal species in the world with as few as one hundred individuals remaining. So it is really now or never to save the Tenkile. TCA works in the Torricelli Mountains of Papua New Guinea researching the animal, providing education to the schools and helping the community.

Tenkile are tree kangaroos; they are marsupials, typically about 10kg (22 pounds).  They are vegetarian, with a diurnal activity pattern.  Most sightings these days are of single individuals.  Historically, they have been observed to live in families of four.  There are listed as "critically endangered," having about 100 surviving individuals, and a range of only 50 square kilometers.  

What is interesting about the TCA's effort is the way they are helping to reduce predation of tenkiles.  The local humans traditionally have hunted the tenkile.  The TCA has introduced rabbits to breed, and is teaching the people to raise the rabbits and make use of them. The idea is that people can eat rabbit meat, instead of hunting tenkiles.

The environment in Papua New Guinea is not conducive to rabbit breeding; consequently, there is little concern about the possibility of rabbits escaping and causing environmental damage.  

TCA does not limit its activities to conservation of tenkiles.  The have started a local educational radio program.  They conduct educational programs in local schools.

Students learn about the discovery of Tenkile, the establishment of a hunting moratorium and Tenkile Conservation Alliance.

They also teach children about zoology, ecology, and general conservation principles.  (Perhaps in their spare time, they could come to the US and teach our adults a few of these things, too.)

There are adult education courses in the local villages.  Local people learn about nutrition.  They also participate in a drama program that has a educational purpose, as well as being a form of entertainment and community-building.

The clever aspect to the TCA's operation, is the way in which the workers have integrated themselves into the community.  This gives them credibility among the people.  Moreover, they do not merely go in and tell people what not to do; rather, they provide a practical alternative.

this photo by Paul Downey; others courtesy of Jim and Jean

If you are so inclined, you can contribute to the Tenkile Conservation Alliance here.

In Case You Were Wondering...

...about my bumper sticker, this explains it:

PROSPECT for Survivial

The NIMH sposored a study, called the Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT).  PROSPECT ran from 1999 to 2005, and has resulted in three papers, plus one abstract.

Bruce ML, Ten Have TR, Reynolds CF 3rd, Katz II, Schulberg HC, Mulsant BH, Brown GK, McAvay GJ, Pearson JL, Alexopoulos GS. Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial. JAMA. 2004 Mar 3;291(9):1081-91.

Alexopoulos GS, Katz IR, Bruce ML, Heo M, Ten Have T, Raue P, Bogner HR, Schulberg HC, Mulsant BH, Reynolds CF 3rd; PROSPECT Group. Remission in depressed geriatric primary care patients: a report from the PROSPECT study. Am J Psychiatry. 2005 Apr;162(4):718-24.

Gallo JJ, Bogner HR, Morales KH, Post EP, Ten Have T, Bruce ML. Depression, cardiovascular disease, diabetes, and two-year mortality among older, primary-care patients. Am J Geriatr Psychiatry. 2005 Sep;13(9):748-55.

The abstract I mentioned was just presented at the annual meeting of the American Geriatrics Society, and is reported on Medscape News (free registration required).  None of the papers mention that they were successful in reducing the risk of suicide, although the later reports indicate that suicidal thinking was reduced.  

The interesting thing is that the patients in the intervention group tended to live longer, as reported in the AGS abstract.

"We found that depressed older adults in the intervention practices were less likely to die over a 4-year follow-up period compared to not-depressed older adults in the usual-care practices," Dr. Bogner said. She noted that her findings reached statistical significance.

The intervention was simple.  They assigned patients randomly to receive either usual care, or to receive intervention by primary care physicians who were assisted by a "masters level depression specialist."

The study method involved deploying a masters level depression specialist to collaborate with the patient's primary care physician (PCP) with the goal of improving patient adherence to medical therapy for depression. The specialist also educated both the PCP and the patient's family about the issues involved. A "depression care manager" provided general treatment recommendations for all study patients. The manager did not make specific recommendations for individual patients.

Notice that the intervention is the sort of thing that could be done easily almost anywhere, at little cost.  However, notice also that it would be difficult to find someone to pay for the intervention.

Eye Candy From the Deep

News@Nature has a collection of six photographs from the Census of Marine Zooplankton, illustrating odd creatures from the deep sea.

This intricately formed tunicate seems to be curled around its young.

Evolution and Drug Development

After reading this article about the antibiotic drug-development pipeline, I had a thought.  

The Antibiotic Pipeline — Challenges, Costs, and Values
Richard P. Wenzel, M.D.
NEJM 351:523-526

In 2004, there are few antibacterial agents in the pipeline. Recall that in the 1930s and 1940s, four new classes of antibiotics were approved, each with novel antibacterial targets: sulfonamides, beta-lactams, aminoglycosides, and chloramphenicol. In the 1950s and 1960s, six more new classes became available (tetracycline, macrolides, glycopeptides, rifamycins, quinolones, and trimethoprim). In the 1970s, 1980s, and 1990s, however, no novel classes were licensed, and all the new drugs that became available were derivatives of existing classes. Since 2000, two new classes of antibiotics have been approved for the treatment of gram-positive bacteria: the oxazolidinones (linezolid) and the cyclic lipopeptides (daptomycin).

A relatively unfavorable return on investment is apparently deterring large pharmaceutical companies from engaging in antibiotic-drug discovery [...]

Drug companies generate candidates for drug development in a variety of ways.  Some of the candidates are developed by making random changes to existing drugs, then testing them.  As the candidates proceed through the pipeline, various economic models are used to determine which ones are worthy of additional investment.  

What occurred to me is something that might already be obvious to others; but for me, it is a new idea.  The idea is that the process of drug development could be modeled using evolutionary principles: mutation, founder effect, natural selection, and the probable mutation effect.  

The NEJM article (cited above) contains a discussion of the way in which economic models influence drug development.  This is kind of obvious: if the anticipated return on investment is low, then the incentive for developing new classes of drugs is going to be low.  However, this does not always fit with health policy priorities.  For example, we need new classes of antibiotics a lot more than we need new classes of insomnia drugs, but we currently are seeing a lot more new drugs for insomnia than for serious infections.

From the perspective of public health, it would be desirable to rearrange the incentives in drug development.  

I am wondering if a really sophisticated analysis of the drug pipeline, using evolutionary principles, could lead to some modifications of health policy.  The goal would be to modify the incentives for drug development in a way that would promote the development of drugs to meet high public-heath priorities.

New Use For Old Drug

I always like to see this kind of a thing:

Aspirin shows promise in combating a common, antibiotic-induced hearing loss

University of Michigan, Chinese hospital find high success rate at preserving hearing when aspirin is paired with widely used antibiotic

ANN ARBOR, MI –Around the world, inexpensive antibiotics known as aminoglycosides have been used for the past 60 years in the battles against acute infections and tuberculosis, as antibacterial prophylaxis in cystic fibrosis patients, and other conditions. But for all of the good they do, the drugs also have been widely linked to irreversible hearing loss. [...]

The researchers studied [link to extract] 195 patients in China who received 80 to 160 milligrams of gentamicin (a type of aminoglycoside) intravenously twice daily, typically for five to seven days. Of those, 89 patients were given aspirin along with the antibiotic, and 106 were given placebos along with the antibiotic. The results were dramatic: The incidence of hearing loss in the group that was given placebos was 13 percent, while in the aspirin group it was just 3 percent, or 75 percent lower.

“We would like to see the word get around to the medical community around the world that you can take some precautions to minimize the risk to your patients. Aspirin is available everywhere, and it’s cheap,” says senior author Schacht, professor of biological chemistry in otolaryngology at the University of Michigan Medical School and director of the U-M Health System’s Kresge Hearing Research Institute. Gentamicin is not commonly used in the United States. [...]

This is a nice bit of work that could have significant implications for health in developing countries.  Even in the US, aminoglycosides are used often enough that the findings could be important here, too.

Feeding Time

Chicago Tribute Sports Pix of the Week
Brother Derek tries to get hold of the helmet of Angel Rangel as groomer Rafael Martinez washes him down following Kentucky Derby workouts at Churchill Downs on Monday in Louisville, Ky.
(Lexington Herald-Leader photo by Mark Cornelison) May. 1, 2006

I don't know why, but I felt like posting this photo.

Junk Science Revealed, and Other Stories

Scienceblog.com has a nice little post about the war on science.  There are a couple of particularly good links.  One link goes to an article that gives examples of the use of the term "sound science" as a propaganda ploy.

"Sound science is whatever somebody likes," Kennedy said. "It's essentially a politically useful term, but it doesn't have any normative meaning whatsoever. My science is sound science, and the science of my enemies is junk science."

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In other science news, CIDRAP reports on the federal plan for management of a bird flu epidemic:

The White House today released a lengthy new plan describing how the government intends to cope with an influenza pandemic, but officials continued to stress their standard message that states and communities will have to rely mainly on themselves in that situation, with the federal government in an advisory role.

I don't think many people in the post-Katrina USA ever thought otherwise.  

"Local communities will have to address the medical and non-medical effects of the pandemic with available resources," the document says. "This means that it is essential for communities, tribes, states, and regions to have plans in place to support the full spectrum of their needs over the course of weeks or months, and for the Federal Government to provide clear guidance on the manner in which these needs can be met."

I am happy that they notice that tribes, in particular will have to be self-sufficient.  At least the federal government has not totally forgotten how badly Native Americans were affected by the diseases brought by settlers.  On the other hand (LA Times; free registration required)...

But in a budget-cutting proposal that has set off protests and indignation among Indians from Los Angeles to New York and several smaller cities in between, the Bush administration has proposed eliminating funds for these clinics, which served about 106,000 Indians last year.

I guess that just proves their point about self-reliance.

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Speaking of threatened populations, National Geographic has a photo gallery of some of the species that have been added to the list of threatened species.  The list includes polar bears and hippos, for the first time.

XGL on Linux

XGL on Linux is pretty flashy.  After I finally got it working, I found out that I did not know the commands to use.  In the event that someone is trying to find them, I just made it a little easier to find them.  

These instructions are for SuSE 10.1, which is still at the release-candidate stage.  I am using XGL on RR4, and I find that there are some differences.  For example, I cannot rotate the cube by moving the cursor to the edge of the screen;  I have to use the keyboard shortcuts.  I also find that it is the F-12 key, not the F-11 key, that actuates the scale mode for switching windows.  

Is any of this really useful?  It is hard to say, because sometimes utility is not obvious at first.  I do like the scale mode, and find it useful when I have a lot of open windows.  I also think the zoom mode will turn out to be useful.  Some of the other features might just be eye candy.  On the other hand, different user interfaces are good for different people.  If a particular interface is a good fit for your particular style of intuition, then it will be easy for you to use.

The following table is from SuSE's site, here.

XGL Shortcuts

Some of the features of XGL are executed when you perform certain functions. Mostly, this is some kind of key combination on your keyboard in addition to some button press and/or movement of your mouse. Below, I have provided a table with the different XGL options and how to execute each one.

Window Operations
Move Window	ALT + Left-Click and Drag
Move Window - Snap to screen	CTRL + ALT + Left-Click and Drag
Resize Window	ALT + Right-Click and Drag
Switch Windows	ALT + TAB
Switch Windows (Scale Mode)	F11
Wobbly Windows	Left-Click Window and Drag
Translucency	ALT + Mouse Up / Mouse Down
Cube
Rotate Cube - Next Desktop	CTRL + ALT + Left or Right Arrow
Rotate Cube - Next Desktop	Move Mouse cursor to extreme edge of desktop
Rotate Cube - Take Active Window	CTRL + SHIFT + ALT + Left or Right Arrow
Manually Rotate Cube	CTRL + SHIFT + Left-Click on Desktop and Drag
Zoom
Zoom Once	Super-Key (Windows Key)
Zoom In Manually	Mouse Wheel Scroll Up + Super-Key (Windows Key)
Zoom Out Manually	Mouse Wheel Scroll Down + Super-Key (Windows Key)

Addendum: it turns out that on my instance of Suse 10.1, the scale mode is not activated by pressing F11. Instead, it is activated by moving the mouse cursor to the upper right-hand corner of the screen. That is actually a better arrangement, in my opinion. Also, I noticed that pressing control-alt down-arrow shows a triptych with a minature version of the current cube facet, flanked by minature versions of the two flanking facets.

Also, if you simply move the mouse cursor to the edge of the screen, nothing happens. You do not get the cube to rotate that way. But if you click on a window and drag it toward either the left or right edge, the cube rotates, and the window you are dragging slides over the next facet.

Please leave a comment if you know of any other XGL function that is not listed here.

How the US Drug Safety System Should Be Changed

The Journal of the American Medical Association has published a commentary article about proposed changes to the FDA.  The author is Brian L. Strom, MD, MPH, a professor at the University of Pennsylvania School of Medicine.  The article itself is subscription-only, but Penn's website has an article about the article:

Commentary on How the US Drug Safety System Should Be Changed
MAY 2, 2006

In the May 3 issue of the Journal of the American Medical Association, Brian L. Strom, MD, MPH, Professor of Public Health and Preventive Medicine and Chair of the Department of Biostatistics and Epidemiology at the University of Pennsylvania School of Medicine, analyzes the limitations of the current system of drug-safety monitoring and proposes a solution that addresses overly aggressive early marketing practices; an absence of incentives to complete post-marketing safety studies; direct-to-consumer (DTC) advertising that can promote non-critical use of "blockbuster" drugs; the current trend toward delaying drug approval; and public misunderstanding about the safety of drugs. [...]

Strom proposes an alternative approach with three elements: conditional approval, an empowered US Food and Drug Administration (FDA), and a complementary nongovernmental organization.  [...]

Dr. Strom explains that any new drug should have a two-step approval.  When it is first released on the market, it would be sold under a conditional approval.  This would be like a probationary period.  During this period, the drug would carry extra warnings, and direct-to-consumer (DTC) advertising would be limited.  In order to get rid of the extra warnings, the pharmaceutical company would have to comply with required post-marketing safety studies.  

His other two recommendations are good ideas, but they have been promoted before by others, and I won't discuss them now.  It is the first recommendation that caught my interest.  

It would seem that pharmaceutical companies would resist the notice of a two-tiered approval, at least at first.  After investing all that money on a new drug, they want to recoup their investment as quickly as possible.  Advocates of small government might oppose the idea, because it would generate a new level of regulation and an awful lot of paperwork, and a small army of government employees to handle all that paperwork.

However, the fact is, pharmaceutical companies have not been doing as much post-marketing safety testing as they are supposed to do.  The FDA does not really have any way of compelling them to do so.  By using a two-tiered approval process, they would have some incentive to offer.  

Another possible benefit to the two-tiered process, could be a reduction in liability exposure for the company.  

Regarding the potential objection over increasing the size of government, it would seem that there are times when a bigger government is called for.  The issues regarding drug safety are getting more complex, as exotic new medications are developed.  At the second stage of approval, it should be possible to get input from a wider variety of professionals, who actually have experience prescribing and studying the drug.  It would allow for a more detailed assessment of the product.  During the first stage of approval, it may be difficult for the agency to know what questions they should be asking.  After the drug has been on the market for a while, there would be more specific hypotheses to be tested.  

Overhaul of the FDA is overdue.  Getting it to actually happen in today's political climate will not be easy.

Speaking Truth to Teflon®

This is pure armchair musing.  There has been a lot of talk lately about the brazen performance by Stephen Colbert at the White House Correspondent's Dinner's a couple of days ago (YouTube video here).  

This got me to thinking, again, about the willingness of the media to print, broadcast, or otherwise acknowledge criticism of the President.  Back in the 1980's liberal persons were amazed by the "Teflon President," Ronald Reagan.  He did all kinds of terrible things, it seemed, and nothing ever stuck.  I am sure that conservatives thought the same about Clinton.  

During Bush 43's first term, the same thing seemed to be happening.  Abu Ghraib is perhaps the best example, but there are many.  More recently, things definitely have changed.

Joseph Lowery
Harry Taylor
Harry Reid
John Murtha
John Conyers
Cindy Sheehan
Stephen Colbert

I am sure there have been more, but those are the names that come to mind, of people whose criticisms of the President have been taken seriously by the media.

All of these persons have been outspoken in opposition to Mr. Bush and his policies.  I have not done any real research into this, other than just thinking about it, but it seems to me that the first person on that list to get any respect in the media was Cindy Sheehan.  Once the media covered her and her story, it became acceptable for the media in the USA to report on criticisms of the President.

It strikes me that this is a significant development.  I would like to understand more about what happened to crack the Teflon coating of the Presidency.   I know it was not just Sheehan who caused this.  The Downing Street Memo, Katrina, and the indictment of Scooter Libby all caused spikes in the mention of the word "impeachment," according to Blogpulse.  Unfortunately, their system only allows tracking back for six months, so right now the only spike you can see is the one caused by the Libby indictment; but I have been following this.  Since then, there has been a steady simmer, but no big spike.  Still, it is clear that it now is acceptable for the media to report on criticism of the President.   Something has changed.  The Teflon is gone.

Perhaps some historian will be able to go back someday, and look at the blogs, and the data collected by services such as Blogpulse and Technorati, and figure out exactly what happened to scrub away the Teflon.