The Corpus Callosum

Corpus Callosum Has Gone To Seed

2006-06-09T12:00:00.000-04:00

As of now, Corpus Callosum will no longer be published on blogspot. The new location is at ScienceBlogs, sponsored by Seed Media Group, publishers of Seed Magazine.

Photo by Tennessee-Gator
Licence: Creative Commons, Attribution-NonCommercial-NoDerivs 2.0

Today's Lesson?

2006-06-08T14:45:00.000-04:00

The two big news items today are : 1) the killing of Abu Musab al-Zarqawi, and 2) the sharp decline in stock markets around the world. The two are not particularly related.

The juxtaposition of these two events creates an interesting perspective. While it is good news that Zarqawi is out of action, it is bad news that the stock markets around the world are struggling. The thing is, the good news does not have any direct effect on the quality of life here in the USA, while the bad news does have a direct domestic effect. How bad the negative effect will be remains to be seen. I'm not arguing that the economic news is dire; rather, I am saying that this juxtaposition of events may highlight the relative importance of the two. It is going to be hard for people to care about an incremental improvement in Iraq, when their own retirement funds are going in the tank.

"They Must Actually Take Their Medication"

2006-06-08T02:10:00.000-04:00

A new report indicates that treatment with calcium and vitamin D might actually reduce the incidence of hip fractures. This appears to contradict some other studies that were reported widely in the popular media.

Dr. Boonen presented results of a meta-analysis of major randomized placebo-controlled trials that analyzed the effects of vitamin D alone or in combination with calcium. The meta-analysis found that in patients getting 800 units of vitamin D and more than 1,000 mg of calcium a day, there was a 21% reduction in risk of fracture compared to placebo.

The new report was a meta-analysis, meaning that the authors pooled the results of several studies. As seen in Wikipedia:

In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. The first meta-analysis was performed by Karl Pearson in 1904, in an attempt to overcome the problem of reduced statistical power in studies with small sample sizes; analyzing the results from a group of studies can allow more accurate data analysis.

To give an idea of why the meta-analysis might be more valid than the other studies, the authors point out:

For one thing, he said, neither study had enough statistical power to find an effect. For instance, he said, the RECORD trial, looking at hip fractures, had 2,649 participants and only 93 events. By contrast, Dr. Boonen said, he and his colleagues had a patient pool of 16,978 individuals and 812 fractures.

I'm not sophisticated enough with statistics to be able to give an opinion of the validity of this particular analysis, and the report I am citing here has not yet been subjected to peer review. Therefore, the results are to be considered to be preliminary.

What is interesting is the list of reasons given, for why the meta-analysis gives results that are different than the previously-reported studies. It turns out that the positive effect is seen only in those patients who actually had a deficiency of either calcium or vitamin D. If the patient's regular diet provides enough of those nutrients, there is no effect from supplements. Some patients in the studies did not take doses that were high enough. Some did not take both the calcium and the vitamin D. Also, the prior reports included in the analysis patients who did not actually take the supplements at all:

Dr. Boonen told reporters after his presentation that clinicians need to pay attention to four factors. They must prescribe a combination of calcium and vitamin D, the doses must be high enough, the patients must be in need of the supplements, and finally they must actually take their medication.

It seems kind of obvious to say that the patients actually have to take the supplements in order to see an effect, but in daily practice, noncompliance turns out to be a common problem. Sometimes the factors that seem too obvious to even consider, are the ones that turn out to be important.

Is This One For Real?

2006-06-05T01:09:00.000-04:00

The LA Times (free registration required) has an article on the possibility of a shortage of physicians in the USA:

Physician Shortage Looms, Risking a Crisis, as Demand for Care Explodes
An aging America needs more doctors, but supply isn't keeping up. Experts fear worsening quality and dangerously long waits for appointments.
By Lisa Girion, Times Staff Writer
June 4, 2006

A looming doctor shortage threatens to create a national healthcare crisis by further limiting access to physicians, jeopardizing quality and accelerating cost increases.

Twelve states — including California, Texas and Florida — report some physician shortages now or expect them within a few years. Across the country, patients are experiencing or soon will face shortages in at least a dozen physician specialties, including cardiology and radiology and several pediatric and surgical subspecialties.

The shortages are putting pressure on medical schools to boost enrollment, and on lawmakers to lift a cap on funding for physician training and to ease limits on immigration of foreign physicians, who already constitute 25% of the white-coated workforce.

But it may be too late to head off havoc for at least the next decade, experts say, given the long lead time to train surgeons and other specialists. [...]

The biggest issue there is the funding for medical training. It is incredibly expensive to train physicians. I recall that when I was in medical school, and students were complaining about double-digit increases in tuition, one of the administrators told us that our tuition only covered about one-third of the actual cost of training. As an historical aside:

When the Medical School first opened in 1850, students paid only a $10 registration or matriculation fee.

By 1891, the matriculation fee was $10 for Michigan residents and $25 for students from out of state. Over the next 50 years, tuition rose slowly until it was $250 in 1940. In the early part of the twentieth century, students were required to pay laboratory and demonstration fees totaling $136 over the four years. None of this takes into account room and board. The average cost of room and board in 1893 was $3-$5 a week; 1931: $12-15 a week. In 2003, tuition and fees for Michigan residents were $20,526 (out of state, $31,526) and estimated living expenses were $20,300 a year. Currently, the average student debt for someone receiving an M.D. degree from the University of Michigan is close to $100,000.

Medical schools are allowed to charge more for services, based upon the recognition of the fact that training costs are high. But the federal government has balked at these higher fees, so there have been caps. This debatable policy has made it more difficult for medical schools to expand enrollment.

There have been dire warnings of physician shortages before, but this time it seems more credible to me. The key factor is the fact that the average age of the US population is increasing. Obviously, older people require more doctoring than younger people. But there is another factor:

At the same time, younger male physicians and women — who constitute half of all medical students — are less inclined to work the slavish hours that long typified the profession. As a result, the next generation of physicians is expected to be 10% less productive, Edward Salsberg, director of the Assn. of American Medical Colleges' Center for Workforce Studies, told a congressional committee in May.

I expect that the trend toward fewer work hours will bring up some controversy, and possibly some resentment. Some physicians will be negatively judgmental about those who choose to work fewer hours. Others will face pressures to delay their retirement. At the same time, it will be increasingly difficult for physicians to keep up-to-date with their skills and knowledge base. Every hour spent on continuing education is an hour that is not devoted to patient care. There is a risk that the demand for more patient-care hours could lead to doctors devoting less time to continuing education, which obviously would have a detrimental effect on quality.

It seems likely that the prediction of a shortage of physicians is accurate. That will pose new challenges for physicians, in terms of managing stress. It occurs to me as I write this, that it may be desirable to make a point of educating medical students about these pressures, and how to deal with them. As soon as I figure out how to deal with them, I will post that information here.

What To Do On 6/6/6

2006-06-04T17:01:00.000-04:00

There is still time to make your plans:

Hell plans devil of a time on 6/6/06

June 4, 2006

HELL, Mich. -- They're planning a hot time in Hell on Tuesday.

The day bears the date 6/6/06 -- abbreviated as 666, it is the "number of the beast" according to the Bible's Book of Revelation, often linked to the devil or the Antichrist.

And there's not a snowball's chance in Hell the day will go unnoticed in the unincorporated hamlet 60 miles west of Detroit.

Nobody seems more fired up than John Colone, the town's self-styled mayor and owner of a souvenir shop.

''I've got '666' T-shirts and mugs. I'm only ordering 666 so once they're gone, that's it,'' said Colone, also known as Odum Plenty. ''Everyone who comes will get a letter of authenticity saying you've celebrated June 6, 2006, in Hell.''

Not all 'Hell-billies' happy

Most of Colone's wares will sell for $6.66, including deeds to one square inch of Hell.

Mike ''Smitty'' Hickey, owner of Dam Site Inn, wasn't sure what kind of clientele would show up Tuesday.

''I don't think we're going to get the cult crowd, the devil worshippers or anything like that,'' Hickey said.

Jason LeTeff, one of the town's 72 year-round residents -- or, as the mayor calls them, Hellions or Hell-billies, wasn't enthused.

''Now, here I am living in Hell, taking my kids to church and trying to teach them the right things and the town where we live is having a 6-6-6 party,'' he said.

More information on Hell, here.

War on Science Update

2006-06-04T12:51:00.000-04:00

Seed Magazine, the originator of the web's largest conversation about science, has an editorial: The American War on Science. There have been many such articles lately, but this one is different. It examines the logistical aspect of the war. By that, I mean that the author, Christopher Mims, discusses the complex issues involved in the supply of scientists, mathematicians, and engineers in the USA.

It is possible that American students' accelerating disinterest in science and engineering, coupled with a dwindling supply of foreign replacements, would set up a Peak Oil-type scenario in the US, where demand for these workers continues to grow while supply plateaus and then dwindles.

There is another issue that is peripherally related to this: The Undercover Activist Blog, a blog that allows public employees to post anonymous criticisms of their agencies and governmental activities, has posted some new information (1 2) about the industry push to get controversial pesticides approved by the FDA.

EPA scientists protest pending pesticide approvals

In a PEER-released May 24th letter to the U.S. Environmental Protection Agency, leaders from three unions representing 9,000 scientists, risk managers and other specialists are publicly objecting to imminent agency approval for a score of powerful, controversial pesticides.

The letter is in reference to an August 3, 2006 deadline for the EPA to issue final tolerance approval for 20 organophosphate and carbamate pesticides. The scientists cite “compelling evidence” which EPA leadership is choosing to ignore that these “pesticides damage the developing nervous systems of fetuses, infants and children.”

Today’s Wall Street Journal article (subscription) broke the story and cites political pressure by agency managers and pesticide-industry officials to allow the continued use of a family of pesticides that might be harmful to children, infants and fetuses. The letter asks EPA Administrator Stephen Johnson to either adopt maximum exposure protections for these agents or take them off the market.

It seems ironic that persons who advocate for a "culture of life" would want to make it legal to poison fetuses. Of course, no one is saying that these pesticides actually kill fetuses, just that they damage their brains. The real irony is that it is going to be a lot harder to keep up the supply of scientists and science teachers, if we poison their developing brains.

Cheslea Painters Art Show

2006-06-03T17:52:00.000-04:00

In Chelsea, Michigan, the Chelsea Painters are having their annual art fair. It is closed for today, but will be up again tomorrow from 10 AM to 5 PM.

It's on the grounds of Chelsea Community Hospital (map), about 20 miles west of Ann Arbor.

A Skeptic's View of "Viagra for Diabetic Women"

2006-06-02T01:34:00.000-04:00

OK, this synopsis does not contain much actual information; certainly, not enough to be useful as a basis for medical decisions. But it does provide an example to illustrate the process of skeptical thinking. It's from Medscape News (free registration required -- but it's worth the hassle).

Sildenafil May Improve Sexual Functioning in Diabetic Women

NEW YORK (Reuters Health) May 31 - Premenopausal women with type 1 diabetes with sexual dysfunction may find that sildenafil improves arousal, orgasm and sexual enjoyment and decreases pain during intercourse, results of a small pilot study suggest. [...]

To test their theory, they recruited 32 women with type 1 diabetes who in the past had experienced normal sexual desire within their heterosexual relationship, but currently experienced sexual dysfunction -- for 3.5 years on average. [...]

Sildenafil was associated with significantly improved arousal, orgasm, and enjoyment compared with baseline (p < 0.001 for each). Compared with placebo, the experience of arousal (p < 0.01) and orgasm (p < 0.05) were better during active treatment. Only desire and frequency did not change significantly in either group. [...]

Note: sildenafil is the generic name for Viagra.

The original study can be found here, but you need subscription-level access or a bunch of money (that you have no other use for) in order to read the text.

There are a couple of points that one needs to consider in interpreting a study such as this. First, as a general rule, one should not make medical decisions based upon small studies that are identified as pilot studies. Doing so, one is likely to expose patients to risks that have not been justified by sufficient research.

Second, it is important to examine critically the outcome measures used in the study. Specifically, it is necessary to look beyond the measures of statistical significance. The statistics in this study look reasonably impressive, at first glance. However, those numbers do not tell you what you really want to know. Remember, statistical significance does not necessarily translate into clinical significance.

So let's look at the numbers:

Sexual activity	Baseline	Sildenafil	Placebo	P^a	P ^b	P ^c
Desire	4 ± 1.3	3.9 ± 0.5	4.1 ± 0.6	NS	NS	NS
Arousal	2.9 ± 1.2	3.7 ± 0.5	3.2 ± 0.3	<.01	NS	<.001
Orgasm	2.8 ± 1.4	3.8 ± 0.8	3.1 ± 0.6	<.05	NS	<.001
Enjoyment	3.5 ± 1.1	4 ± 0.5	3.7 ± 0.6	NS	NS	<.001
Satisfied by frequency	3 ± 1.1	3.2 ± 0.7	3.1 ± 0.4	NS	NS	NS
Frequency of intercourse	1.8 ± 1	2.3 ± 0.5	2.4 ± 0.6	NS	<.05	<.05
Frequency of fantasies	2.1 ± 0.8	2.3 ± 0.4	2.2 ± 0.6	NS	NS	NS
Dyspareunia	2.3 ± 1.1	1.4 ± 0.8	2 ± 0.7	<.05	NS	<.05

a Sildenafil vs. placebo.
b Placebo vs. baseline.
c Sildenafil vs. baseline.

Qualitative items were answered on a 5-point Likert scale, ranging from 1, not at all, to 5, a great deal. Quantitative items were answered as 0, never; 1, less than once a week; 2, once or twice a week; 3, several times a week; 4, once a day/sometimes twice; and 5, several times a day.

To be fair, the authors of the paper are cautious about interpreting the numbers. They include all the appropriate cautions and limitations. My concern is that a newspaper could easily pick up this story and print the high points, leading to a great deal of misinterpretation among the general public.

When I get around to it, I'll put up another post with my interpretation of the numbers. In the meantime medical students and interested readers are encouraged to look at the data and think about what conclusions may be justified by the numbers.

Depending on when I do get around to it, and when the new Seedlings go live, the follow-up post may be here, or it may be at http://www.scienceblogs.com/corpuscallosum (which is not up as of this writing).

Climate Change Affects Blogs

2006-06-01T15:58:00.000-04:00

Due to the unseasonably hot weather, Corpus Callosum will not be going to Seed tomorrow. The ScienceBlog meteoblogologists inform me that they expect the new Seedlings to sprout in 10 days or less. So all those good ideas I've been saving will have to wait.

The Effect of Caffeine on Web Design

2006-05-29T14:58:00.000-04:00

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.

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

Generic Escitalopram

2006-05-28T23:53:00.000-04:00

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

2006-05-28T19:40:00.000-04:00

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

2006-05-28T13:55:00.000-04:00

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

2006-05-27T21:26:00.000-04:00

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

2006-05-27T21:05:00.000-04:00

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...

2006-05-27T14:34:00.000-04:00

...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

2006-05-27T02:09:00.000-04:00

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

2006-05-25T23:45:00.000-04:00

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

2006-05-25T00:44:00.000-04:00

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

2006-05-24T19:46:00.000-04:00

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

2006-05-24T01:04:00.000-04:00

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.

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

2006-05-23T00:21:00.000-04:00

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?

2006-05-21T00:38:00.000-04:00

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

2006-05-20T18:48:00.000-04:00

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

2006-05-20T02:32:00.000-04:00

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.