FutureGen

Somewhere, I ran across a reference to "clean coal" technology, and thought I would blog about it later.  For the past few days, I've been looking at some of the available information.  The US Government has some ideas about this.  Investigating this subject leads to some interesting findings about the possibilities for improved energy production.  It also shows something about the priorities of those in power in Washington DC.   Read the rest at The Rest of the Story. 

Cassini-Huygens Update...Sort Of

I checked at the NASA and JPL sites to see if the Huygens probe had sent back any information yet.  If so, it has not been announced yet.  So instead, here is an image from Cassini:

Cassini has found Titan's upper atmosphere to consist of a surprising number of layers of haze, as shown in this ultraviolet image of Titan's night side limb, colorized to look like true color. The many fine haze layers extend several hundred kilometers above the surface. Although this is a night side view, with only a thin crescent receiving direct sunlight, the haze layers are bright from light scattered through the atmosphere.

Here's Some Help For You!

Here's Some Help For You!

The Third Bush-Kerry Presidential Debate
October 13, 2004
THIRD PRESIDENTIAL CANDIDATES' DEBATE
ARIZONA STATE UNIVERSITY, TEMPE, ARIZONA

SCHIEFFER: Let's go to a new question, Mr. President. Two minutes. And let's continue on jobs.

You know, there are all kind of statistics out there, but I want to bring it down to an individual.

Mr. President, what do you say to someone in this country who has lost his job to someone overseas who's being paid a fraction of what that job paid here in the United States?

BUSH: I'd say, Bob, I've got policies to continue to grow our economy and create the jobs of the 21st century. And here's some help for you to go get an education. Here's some help for you to go to a community college. [...]

And Merry Christmas, Too!

College aid formula ends some low-income grants
By Dan Morgan
The Washington Post
Published December 26, 2004

WASHINGTON -- The Department of Education has announced a new formula for calculating eligibility for college financial aid, a move that will eliminate federal Pell Grant scholarships for an estimated 80,000 to 90,000 low-income students. It also will force a modest scaling back of other types of state and federal assistance to broader categories of undergraduates.

Tyranny of the Should

Karen Horney (pronounced Horn-eye, please) was a brilliant German psychoanalyst, born in 1885 near Hamburg.  In 1906, she began her studies in medical school, in Berlin.  In 1932, she became a member of the Chicago Institute for Psychoanalysis.  She published some fairly easy-to-read books on the subject of neurosis.  Possible the most influential was Neurosis and Human Growth: The Struggle Toward Self-Realization (Amazon link).  Psychoanalysis has waned in popularity these days.   Despite that, her books are still in print.  This says something about the validity of her work. 

Dr. Horney coined the phrase, 'the tyranny of the should.'  For my purposes today, I will ignore the remainder of her biography, and pretend that all of the controversies pertaining to psychoanalysis don't exist.  (Both topics are moderately interesting, but others on the 'net have covered them in greater depth than I ever would.)

Consider the word, 'should.'  It is one of the true gemstones of the English language, because it can mean so many different things.  As a consequence of its inherent ambiguity, it is a favored word among preachers and politicians.  To illustrate, here is a usage note from the American Heritage Dictionary:

Usage Note: Like the rules governing the use of shall and will on which they are based, the traditional rules governing the use of should and would are largely ignored in modern American practice. Either should or would can now be used in the first person to express conditional futurity: If I had known that, I would (or somewhat more formally, should) have answered differently. But in the second and third persons only would is used: If he had known that, he would (not should) have answered differently.Would cannot always be substituted for should, however. Should is used in all three persons in a conditional clause: if I (or you or he) should decide to go. Should is also used in all three persons to express duty or obligation (the equivalent of ought to): I (or you or he) should go. On the other hand, would is used to express volition or promise: I agreed that I would do it. Either would or should is possible as an auxiliary with like, be inclined, be glad, prefer, and related verbs: I would (or should) like to call your attention to an oversight. Here would was acceptable on all levels to a large majority of the Usage Panel in an earlier survey and is more common in American usage than should. Should have is sometimes incorrectly written should of by writers who have mistaken the source of the spoken contraction should've. See Usage Note at if. See Usage Note at rather. See Usage Note at shall.

As far as I am concerned, what I "should do" depends upon the goals I have set for myself.  Not that this is entirely hedonistic; often one of my goals is to be considerate of my conspecifics, and to a lesser extent, to other creatures on this planet. 

If my primary goal is to impress others, then certainly I should  avoid spelling errors; if my goal is to relax and have a little fun, I shood not spend a lot of time proffreading. 

In order to avoid being tyrannized by a delightfully disingenuous six-letter word, I find it helpful to edit out the little beast from my inner dialog, and substitute the decidedly ungainly, but psychologically less damaging,phrase: "in consideration of my personal priorities, with due respect for the rights of others, I will consider..."

Example: 'I should wash the dishes tonight,' becomes 'I, in consideration of my personal priorities, with due respect for the rights of others, will consider washing the dishes tonight.'  Substitutions of this sort do require the burning of a bit more acetylcholine, but it pays off in the long run. 

Maybe instead of washing the dishes tonight, I might consider rereading Dr. Horney's book.  Although, in fact, I think someone else has it right now. 

Rumsfeld Does the Right Thing

No snark today; it's almost Christmas.  Donald Rumsfeld visited the troops in Iraq, served a holiday meal, and consoled injured service personnel.  He also met with the interim government.  This is big news, apparently.  Google News lists 1,112 related articles on the subject. 

Cassini-Huygens Leads to Discovery;Difference Between Fonks and Gonks

The Cassini space probe is set to release a daughter probe, Huygens, sometime today.  Cassini is the craft that has been providing us with pictures of Saturn, its rings, and moons.  Cassini was named after an astronomer, although I am not sure which one; Wikipedia informs us that there were four astronomers named Cassini.  The elder Cassini seems to have been the most influential, so I suspect that the probe was named after him.

The eldest, Giovanni Domenico (Jean-Dominique) Cassini, discovered the Great Red Spot.  He also figured out how to use the eclipses of the moons of Jupiter as an -- admittedly unwieldy -- kind of clock. 

Huygens also was an astronomer.  (He was mentioned in Neal Stephenson's inspiring novel, Quicksilver, which is what drew my attention to this whole thing.)  If you want to look him up, be advised that his surname also can be spelled Hugens, or Huyghens.  Cristian Huygens discovered the mathematical properties of the rings of Saturn, and observed the moons of Saturn.  Like Cassini, he was interested in timekeeping.  Among his many important works was Horologium Oscillatorium, a book in which he described the motion of the pendulum.  This led to the development of the first clock that was accurate enough, and sufficiently precise, for scientific work. 

The development of a clock that was accurate, precise, and practical, was necessary for the progress of Science.  Politics, as we shall see, still has a way to go.  Read the rest at The Rest of the Story.

"We [the United States of America] are the only nation in the world where all our poor people are fat."
--former Senator, Phil Gram

"We are not, however, the only nation where the politicians are fat."
--blogger, Joseph j7uy5

The Intestine Bone is Connected to the Nose Bone

I love reports such as this one.  Researchers at the University of Michigan Medical Center have demonstrated a link between alterations in the microflora of the intestinal tract and symptoms of allergic rhinitis.  They speculate:

Noverr and Huffnagle suspect that changes in gut microflora caused by widespread use of antibiotics anda modern high-fat, high-sugar, low-fiber diet could be responsible for a major increase, over the last 40 years, in cases of chronic asthma and allergies in Western industrialized countries.

The press release is based upon two studies, one published in August 2004 in Infection & Immunity; the second to be published in the January 2005 issue of the same journal.  The studies were done on mice, not humans, so it remains to be seen if there will be an clinical utility to the findings.  Even if there is not, the studies are interesting, because they show that two seemingly unrelated aspects of animal physiology are in fact related. 

Normally, the intestinal tract contains a variety of microorganisms.  Some are helpful, by facilitating digestion.  Others seem to serve no purpose for the host; they merely may be along for the ride, and a free lunch.  However, it is possible, also, that those organisms that seem to provide no benefit actually do us a lot of good. 

Keep that in mind, next time you are tempted to think of something -- or someone -- as a mere parasite.  Things are not always what they seem.  Ecology is full of surprises. 

And no, there is not really a bone in the intestines.

Don't Just Read the News -- Read It and Think

Excerpt One:

Nicotine as Therapy
November 2004
 
[...] Although the analgesic effect of drugs that mimic acetylcholine were originally attributed to a different class of receptors, it is now clear that nAChRs play an important role in the control of pain. For instance, epibatidine, a drug that is extracted from the skin of an Ecuadorian frog and that acts at nAChRs, has been shown to be 200 times more potent than morphine at blocking pain in animals. Current animal research is aimed at discovering just where, how, and which classes of nAChRs work against pain, with the aim of developing more selective drugs. [...]

Excerpt Two:

Teen Drug Use Declines 2003-2004 - But Concerns Remain About Inhalants and Painkillers
December 21, 2004

[...] The survey noted some areas that raise concern. For example, while the rates of Vicodin abuse did not change significantly from 2003 to 2004, Vicodin was used by 9.3% of 12th graders, 6.2% of 10th graders and 2.5% of 8th graders in the past year. OxyContin was used in the past year by 5% of 12th graders, 3.5% of 10th graders and 1.7% of 8th graders in 2004. These rates were not significantly different from the rates in 2003; however, when all three grades were combined, there was a significant increase in past year OxyContin use between 2002 and 2004. [...]

Excerpt Three:

NEW BUSH ADMINISTRATION REGULATIONS UNDERMINE DECADES OF SOUND FOREST MANAGEMENT
Dec 22, 2004

WASHINGTON, DC – The Bush Administration today finalized new forest policy regulations that potentially open millions of acres of national forests to logging and mining projects with little or no attention given to the effect those projects would have on wildlife and the environment. The regulations reverse decades of progress toward responsible forest management and represent another serious blow, along with the Bush Administration’s “Healthy Forests Initiative,” to sound management of the public’s 191 million acre national forest system.

“The President’s forest regulations are an early Christmas gift to the timber industry masquerading as a government streamlining measure,” said Rodger Schlickeisen, President of Defenders of Wildlife. “This is all about opening more and more forested lands to unsustainable logging with no regard for environmental impact.”

“The new regulations jeopardize important wildlife habitat and put more species at risk of endangerment and extinction. They toss aside decades of bipartisan consensus on forest protection and fly in the face of the recommendations of hundreds of scientists and expert policy makers,” continued Schlickeisen. [emphasis added] [...]

What kind of bootscraper would call legislation the "Healthy Forest Initiative," when it obviously has nothing to do with healthy anything.  A damn liar -- the same liar we just reelected.  But that is a rant tangent. 

The real point of this post is this: obscure species are extremely valuable resources.  An Ecuadorian frog has provided us with a molecule that may help with the problem of drug abuse, not to mention the problem of chronic pain.  Any policy that erodes the protection of endangered species is foolish and short-sighted. 

Sitemeter Reveals...

I used to get a lot of hits by people looking for a picture of Robocop, but I haven't gotten any of those for a while.  Many of the hits came from South America, or Europe. 

For the last several months, just about every day, I have gotten one or two hits by people looking for a picture of Gottfried Leibniz.  I also tend to get one or two from people looking for pictures of a toilet.  That seems too unlikely to be a mere coincidence.  It must mean something. 

Robocop	Leibniz	Toilet

The pictures are linked to the original posts. I am fairly sure that the posts have nothing to do with whatever the googlers are looking for.  If anyone using the Google image search finds these pictures, I would appreciate it if they would leave comments explaining why these topics are so fascinating.

I Give In

I had been tryign to resist, but I can'r do it any longer. Maybe another week, I could make a New Year's resolution. But no. I am going to do it. In public. I am going to boast about my son. He got perfect scores on all three sections ofthe SAT II. 800 to the third power is 512,000,000. Great job Kevin!!! There. It is done. All I have to do is click on "Publish Post."

Biggest News of the Week...Maybe

What is the biggest news of the week?  More dead in Iraq?  Hardly, except that Rumsfeld gets to make good on his promise to sign the letters to the families of the dead soldiers.  Bush is the Person of the Year?  Hardly.  Yes, he joins luminaries such as FDR, Eisenhower, and The Computer, but also Hitler, Gingrich, Stalin, and Khrushchev.  New version (0.9.1) of Damn Small Linux released.  No, although the GIMP 2.2 comes close.  The Castro-Chavez trade pact?  Maybe.  That could turn out to be really important.  My nomination for Biggest News of the Week is reported in Science Magazine, echoed by news@Nature.com and The-Scientist.com.

Authored by Solomon Snyder, et. al., Phosphorylation of Proteins by Inositol Pyrophosphates appears in Science (17 December 2004: 2101-2105.)  Dr. Snyder is a neuroscientist, sometimes referred to as "the father of synaptic chemistry."   From the review at The-Scientist:

Phosphorylation without ATP
IP7 offers a nonenzymatic alternative for adding phosphate to proteins
By Charles Q Choi

For the first time, scientists have described in this week's Science a way for cells to add phosphate groups to proteins that doesn't involve using adenosine triphosphate (ATP) as a donor.

"Nobody had ever dreamt you could phosphorylate with a donor other than ATP," said senior author Solomon Snyder at Johns Hopkins University in Baltimore, who, along with colleagues, suggested a decade ago that inositol pyrophosphates such as diphosphoinositol pentakisphosphate (IP7) might serve as phosphorylating agents due to their highly energetic pyrophosphate bonds.

"ATP phosphorylation has heretofore been regarded as the primary mode of all cellular signaling in biology," Snyder told The Scientist. "IP7 phosphorylation may be of comparable importance, with similarities but major differences—for instance, it is nonenzymatic. It may represent a new form of intracellular signaling." [...]

For decades, phosphorylation of proteins by ATP has been thought to be the central means of controlling the behavior of intracellular proteins.  The discovery of an alternative pathway could have profound implications.  It could even have therapeutic implications, for a wide range of diseases.  

Lately, I've been critical of science reporters who oversell the implications of the studies upon which they base their articles.  So I guess I better not do the same thing.  The fact is, there is a lot of research to be done, to figure out how important this mechanism really is, and how to control it, assuming that it turns out to be important.  To their credit, the reporters at news@Nature.com and The-Scientist.com were cautious about their interpretation.  From Nature: 

[...]Snyder speculates that interfering with IP7 might, one day, be used to treat certain diseases. If, for example, IP7 normally fires up a protein that triggers cancer, then blocking that activation could help fight the disease.

York counters that this is "a huge stretch". He and others in the field say they would like to see much more evidence before they are convinced that IP7 is as crucial in cell biology as ATP.

For example, scientists need to prove that IP7 adds phosphates to many more proteins than those demonstrated, and that this actually alters what they do in the cell. The IP7 discovery is not yet as big a deal as the ATP find, says York, "but maybe it'll just take time to figure out." [...]

Forget Bush, Rumsfeld, Iraq, and Castro.  I vote for nonenzymatic phosphorylation as the big news of the week. 

Big News of the Week...Maybe

Human Chimeras, Continued

Andrew Huff, from Monkey McGee's Wild Ride, left a comment about my post pertaining to three-parent babies.  It is one of the longer, more thoughtful comments I have had in a while.   He raises a point that I had overlooked.  In addition to the moral issues pertaining to chimeras that contain human cells, he points out that there are safety issues involved with the creation of such new creatures.  This is analogous to the issues surrounding genetically-modified crops.  Specifically, there can be definite benefits, but there also are risks that come with the insertion of foreign genetic material into crops.  So far, no one has demonstrated a serious ecological harm, but the potential is there, and it is very difficult to predict ahead of time what sort of unintended consequences might ensue. 

I'm not sure that anyone has explored this issue in detail.  For example, would the creation of chimeras that contain human cells make it easier for viruses to mutate such that they could inhabit human cells?  That is pure speculation on my part, but it is the sort of thing that ought to be considered before going ahead with such research. 

When I first thought about the issue, I was assuming that any chimeras that would be created would be contained in a laboratory environment, not released into the wild.  That probably is true.   But microorganisms are not so easily contained, especially if the chimeras are used to generate products that are intended for use outside the laboratory. 

Not that we don't have enough to worry about already, but it is something to think about.

Holiday Tip # 1.41421356

...Don't invest a large sum of money in diamonds...

This synthetic brilliant-cut single-crystal diamond, grown by chemical vapor deposition (CVD), is 2.5 mm high and was made in about one day at Carnegie.

Alternatives to Judicial Activism

The Bush Administration has been complaining about "activist judges" for a long time, but mostly these complaints have gone unheeded.  That is because they did not have a good alternative to offer. Now, they do. According to The Washington Post, judges now are permitted greater latitude in accepting lavish junkets paid for by large corporations. After all, we can't have judges making important decisions based upon their personal beliefs.  No, instead we will have them making important decisions based upon the beliefs of corporate donors. Now that's progress!

New Rules For Judges Are Weaker, Critics Say
Guidelines Address Sponsored Trips

By Carol D. Leonnig
Washington Post Staff Writer
Friday, December 17, 2004; Page A31

A judicial conduct committee has rewritten the ethics guidelines for federal judges in a way that legal experts and critics said allow judges to take more corporate-funded trips and avoid disclosing their attendance.

The committee said it revised the rules in response to public and congressional criticism of judges taking all-expenses-paid trips to "judicial education" seminars. These events were often held in luxury hunting lodges and in Arizona golfing resorts, and paid for at least in part by petroleum, chemical and manufacturing companies whose interests often come before federal courts, records show.

But critics said the new rules actually weaken the attendance and disclosure guidelines.

"This effectively clears the path for federal judges to take lavish, corporate-funded trips," Douglas T. Kendall, executive director of Community Rights Counsel, a group that has opposed the free trips, wrote in a letter yesterday to U.S. District Judge William L. Osteen, chairman of the judicial committee. [...]

The real beauty of this is that the new regulations were written in response to complaints about the possibility that such trips could influence judges. So they write new rules, which actually make the situation worse!  All in the name of judicial education!  No Judge Left Behind!

Scientists Seek To Create 'three-parent' Babies

This is old news by now, but it is something I sort of kept in reserve, to blog about when I got a round tuit. 

In October of this year (2004), New Scientist et. al. reported that researchers in the UK were developing plans to create human embryos with genetic material from three persons.  Furthermore, recent news reports indicate that scientists are going about creating chimeras, creatures that contain cells from both humans are other animals.  These developments highlight certain moral issues.  Read the rest at The Rest of the Story.

Reading Psychiatric News

Today's NYT contains an article about a study, originally published in Molecular Psychiatry.   The original study report  is here; the NYT article is here (permanent link).   Sometimes, when I see that something I know about has been reported in the newspaper, I wonder what it was about the topic that drew the attention of the reporter who wrote the news article.  After all, there are hundreds of medical journals, some are published every week.  Thus, there are thousands of journal articles to choose from.  Yet, only a few are deemed newsworthy. 

One would hope that reading the news article would answer the most important question: Why should I care about this?  After all, if I am going to take time away from reading blogs, and actually read a newspaper, I was to have some assurance that what I am reading is important. 

So let's give it a try, and see if this particular news article answers the question.  While we're at it, let's see if the study cited here has any other significance, perhaps something other that what the news reporter picked up on.  Read the rest at The Rest of the Story. 

Lunesta Receives Final FDA ApprovalInitial Comments on New Insomnia Drug

As reported in CCN Money, among other sources, a pharmaceutical company called Sepracor had obtained FDA approval for its new drug, Lunesta (eszopiclone).  Their stock went up by 15% immediately.  Looking through the news reports, most of them focus upon the financial implications of the impending release of this new product.  Patients, however, probably don't care much about that.  They want to know about the drug itself.

It turns out that technical information is hard to come by.  For a short, general discussion of insomnia, see this Medscape CME article (free registration required.)  For the package insert, see this PDF file.  A list of references can be found at the Sepracor site, here.  A Medline search reveals only one article with relevant information.  Read the rest at The Rest of the Story.

I Now Support the Theory of Intelligent DesignAND I Insist That It Should be Taught in Schools

I used to think that proponents of Intelligent Design were Damn Liars.  Now I've changed my mind. 

For years, schoolchildren have been taught that the American Government "just evolved."  Some rich old white guys sat around and just made it up.  They came up with the ideas of "government of the people, for the people, by the people", "all men are created equal", etc. out of thin air.  Some even referred to it as a "primordial soup" of ideas.  What do they think our Founding Fathers had for lunch, Alpha-Bits soup?  Do they think that the noodles just formed themselve into sentences via brownian motion?  They say that fundamental ideas, such as the notion of balance of powers, evolved from earlier ideas, such as those contained in the Magna Carta.  However, a scientific anaylsis of the American Government shows that this simply is not possible.

For example, what is the probability that all of the Senators and Representatives would be honest servants of the people, if it "just happened?" How likely is it that the President would always tell the truth, if his election were merely a product of random events?  Clearly, these things could not happen by chance alone.  Therefore, there must have been some kind of intelligent Higher Power that designed our fine government.  How else could it have turned out to be infallible?

Now, we have a system of public so-called "education" that is teaching our kids that there is only one theory for the origin of the US Government.  They fail to include the competing view that a growing number of scholars are developing: Intelligent Design.  I have heard lately that a few students are even GRADUATING FROM HIGH SCHOOL, believing that POLITICIANS SOMETIMES LIE, and that GOVERNMENT SOMETIMES MAKES MISTAKES!!!!  The vast conspiracy of freethinkers must not be allowed to brainwash our children any longer!!!!!!!

Holiday Tip # 3.14159265 and so forth

If you celebrate, or at least attend, a holiday during which gifts, especially electronic gifts, are likely to be given, then do yourself, and everyone else, or at least some others, a favor, by bringing a Sharpie fine-point, not extra-fine, but regular-fine-point marker, and when anyone, including yourself, opens a present that includes one of those little plug-in chargers, take out the Sharpie, with a flourish, not a major ostentatious flourish, but a modest flourish, and LABEL the charger with the name of the thing it is supposed to plug in to. 

No one will thank you right away. 

In fact, they will think you are strange. 

But years later, when they have a drawer full of those little charger things, and can't figure out what any of them goes to, but they don't dare throw them away, in case they need one of them, someday, and it goes to something really important, but they can't figure out what, or something like that, they will remember you and then they will understand, and although they still will not thank you, the world will be a little bit nicer, or at least a bit more tidy, because of what you did.

And if there are any industry moguls out there who are in charge of making those damn little boxes, get a clue and start labeling them with the make and model number of the thing that the charger goes to.

Metyrapone as Additive Treatment in Major Depression

I've written before about the potential for modulation of the glucocorticoid system for the treatment of depression. Mifepristone (RU-486) is a drug that blocks cortisol receptors. It is being tested to see if it can be used to treat psychotic depression and bipolar depression. Now there is a study that shows benefit from treatment with metyrapone (Metopirone).

Metyrapone currently is used in a test to assess the functioning of the pituitary gland. It inhibits an enzyme, steroid 11-beta hydroxylase, which is necessary for the production of cortisol. If the pituitary gland is functioning properly, it should produce a greater amount of adrenocorticotropic hormone (ACTH) when metyrapone is given. This is because the pituitary detects a drop in the amount of available cortisol, and responds by secreting ACTH, in an effort to coax the adrenal glands to produce more cortisol. The study cited here was intended to see if metyrapone might have a therapeutic effect for treatment of major depression, it addition to its established use as a test agent.

Metyrapone as Additive Treatment in Major Depression
A Double-blind and Placebo-Controlled Trial
Holger Jahn, MD; Mildred Schick, MD; Falk Kiefer, MD; Michael Kellner, MD; Alexander Yassouridis, PhD; Klaus Wiedemann, MD
Arch Gen Psychiatry. 2004;61:1235-1244.

Background Inhibitors of steroid synthesis have been reported to exert antidepressive effects, according to preliminary findings.

Objective To test whether the addition of metyrapone to standard antidepressants induces a more rapid, more efficacious, and sustained treatment response in patients with major depression.

Design Double-blind, randomized, placebo-controlled trial.

Setting Hospitalized care.

Patients Sixty-three inpatients with a DSM-IV diagnosis of major depression and a baseline score 18 points or higher on the Hamilton Rating Scale for Depression.

Interventions Random allocation to 2 treatment groups receiving either placebo or metyrapone (1 g/d) for the first 3 weeks during a 5-week treatment with standard serotonergic antidepressants (nefazodone or fluvoxamine).

Main Outcome Measures Primary outcome criteria were the number of responders and the time to onset of action. Responder rates were considered twice after 3 and 5 weeks with a definition of treatment response as 30% and 50% reduction, respectively, of baseline Hamilton Rating Scale for Depression scores. Onset of action was defined as the time point at which at least a 20% reduction of baseline Hamilton Rating Scale for Depression scores occurred.

Results Using intention-to-treat analysis, we found that a higher proportion of patients receiving metyrapone showed a positive treatment response at day 21 (23 of 33 patients) and at day 35 (19 of 33 patients) compared with placebo patients (day 21: 13 of 30 patients; Fisher exact P = .031; day 35: 10 of 30 patients; Fisher exact P = .047). The clinical course of patients treated with metyrapone showed an earlier onset of action (Kaplan-Meier analysis; log-rank test P<.006) beginning in the first week. The plasma concentrations of corticotropin and deoxycortisol were significantly higher during metyrapone treatment (multivariate analysis of covariance, P<.05), whereas cortisol remained largely unchanged. Metyrapone treatment was well tolerated without serious adverse effects.

Conclusions Metyrapone is an effective adjunct in the treatment of major depression, accelerating the onset of antidepressant action. A better treatment outcome compared with standard treatment and a sustained antidepressive effect were observed.

This study is a small, preliminary investigation; it is way too early to think of it as having any clinical significance. Despite that, there are two reasons to care about it. One, it confirms that new approaches to treatment of depression are possible; two, it shows that it may be possible to treat depression by manipulating the hypothalamic-pituitary-adrenal axis without causing a major disruption in the balance of circulating hormones.

Notice that, in the study cited above, cortisol levels did not change much. This was a short-term finding; it remains to be seen if long-term use of metyrapone would have the same result. If so, it would tend to alleviate some concerns about the safety of the treatment.

What is the most serious threat to national security?

The current political apparatus has not been very productive lately.  Even though the Republicans control the House, Senate, and White House, they have shown signs of degenerating into a quagmire of infighting, barely able to pass the 9/11 reforms. 

Perhaps they should take on something that ought to be easy to pass, and is just as important.  In the first debate, both major Presidential candidates agreed on the answer to the question: What is the most serious threat to national security?

In this post, I review the recent news reports to see what Bush has done to address the issue.  I also look at the controversy that has come up over recent allegations that the Bush Administration distorted and misrepresented the intelligence data that indicated a looming nuclear threat in North Korea, and how well that situation has been handled.  Read the rest at The Rest of the Story. 

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What We Need, What We've Got, What We Get, and Why

What we need:
1. Armor for trucks
2. Jobs for citizens

What We've Got
1. Thousands of unemployed factory workers
2. Many idle factories
3. Lots of steel

What We Get
1. Hundreds of troops dead, unnecessarily

Why is that?

This guy gives a tax cut to oil companies, saying it will create jobs, which it won't, while oil companies make record profits, charging record prices, thus putting even more American people out of work, while emptying government coffers under the guise of giving money "back to the people."

"After all it's your money," he said. 

If it's my money, why are you giving it to your buddies?


Thanks to Middle Earth Journal for the photo link

Why Today's Post is Vapid

Science News Top Stories

Experts Urge People to Unplug Occasionally
Katie Achille grew up with the Internet. She was 9 when she first tapped into it - and quickly became an avid e-mailer, Web surfer and sender of instant messages. But when recent computer troubles left her without regular Web access, something unexpected happened: To her surprise, she suddenly felt free. ``I find the break from the Internet somewhat refreshing,'' says Achille, now 19 and a junior at Rutgers University in New Jersey. ``After spending a good portion of my freshman and sophomore years holed up here in my dorm room typing away to friends, I feel like I missed just sitting outside and enjoying the weather or going for a walk, just because.'' More »

Holiday Idea in the Ann Arbor Area

The UM Health System has teamed up with the Chelsea Teddy Bear Company to help send pediatric burn patients to camp. 

“We choose the Trauma Burn Center and the Kids Burn Camp  because it specifically involved children, and especially children that have suffered from an extremely painful and traumatic event,” says Bob Turner, president of the Chelsea Teddy Bear Company. “Our goal is to send as many kids to burn camp as possible, and we can see the direct result from our efforts, which are different then when you give to a large charitable organization. Here we know that with about every $500 dollars we raise, another kid gets to go to camp. It's very rewarding.”

The Chelsea Teddy Bear Company is offering red felt hearts that individuals can purchase for $1 at its stores. The hearts will then be “stuffed” into the World's Largest Real Teddy Bear, with the proceeds benefiting Kids Burn Camp. Not only will participants help children gain the ability to cope with life after being burned, but also be part of breaking a world's record.

This reminds me of another medical school story.  When I was in my fourth year, I spent a month on pediatric ENT.  We were doing rounds at the end of the day, when the senior resident got a stat page.  One of the kids had developed respiratory distress.  He had had a tracheostomy, such that he could breath only through a tube that had been inserted into a surgical opening in his trachea.  The tube itself fit into a little flange that kept the tube from going into his lungs.  The tube was supposed to be glued to the flange.  Unfortunately, the device had been shipped without having been glued together. 

There was a very real risk that the kid was going to die, so we were in a hurry.  We wheeled the patient, on his hospital bed, down the hall and into the elevator.  There were two well-dressed persons there, who looked like ladies but did not act like ladies.  The resident informed them that this was an emergency, and instructed them to get off the elevator. They were indignant.  The resident cursed at them after the elevator door closed.  We got to the OR area where bronchoscopies are done.  Within minutes, the resident had used the bronchoscope to remove the tube, and the kid was fine.

Later, when we went to visit the kid, someone had taken his teddy bear down to X-ray and had an X-ray of the bear up on his window.  The kid's mother went up to the resident and said, "I was SO glad to see you come in, I knew you would save my son."

There was no need to tell her that a good outcome had not been a sure thing.  Anyway, I'll never forget that teddy bear.

Via DistroWatch.com

2004-12-06

Distribution Release: Games Knoppix 3.7

Games Knoppix, a special edition of the upcoming Knoppix 3.7, has been released: "Finally, the first release of the Games Knoppix (St. Nicholas Day Release) is ready for download. The following games have been lately added: Castle-Combat, Globulation 2, Hatman, Kobodeluxe, Miniracer, Pingus, Rafkill, lots of small games. If there is a graphics card with possible acceleration detected, you will be asked whether you want to use the NVIDIA or ATI drivers. To use this option, you need at least 400MB RAM. The joystick configuration tool is started via 'joystick-config' inside the console. We'll add a small HOWTO about how to turn your Linux box into a game console soon." Here is the full release announcement with additional details. Currently, the ISO image is only available for download via BitTorrent: GamesKnoppix-3.7-0.1.torrent (683MB). Happy gaming!

Looking for a present that doesn't cost much, for someone with a PC, who likes games?  Knoppix my be the easiest-to-use Linux around.  It runs right from the CD, so you do not have to install it and take up hard drive space.  Rather than spend 30-50 dollars on a single game for a console, get several games for the cost of a blank CD. 

The download will take hours, even on a fairly fast network.  First, you have to get a bittorrent program; there are several available, even for Windows.  (TorrentStorm - Windows Bittorrent Client).  Start the download and let it run all night. 

If you're curious about Linux, this would be a decent introduction.

Apropos of Pearl Harbor Day

A vulnerability known as "cross-site scripting vulnerability," has been used to get some Internet banking users to divulge their account information.  Details here.  The significance of this is that the vulnerability overlays fake web page elements onto a real banking site, so it appears authentic.  In order for it to work, though, the user must follow a link that is sent in an e-mail, asking users to "verify their account information."  That, by now, should be a tipoff to anyone. 

If money is involved, don't follow links in e-mail.  Close the e-mail, and navigate to the site as you normally would.  And use a better browser. 

"Save us from the FDA"

A quick update to my last post:  There is an inspiring editorial in The Berkshire Eagle, from Pittsfield MA. 

Save us from the FDA
[...] The Bush political hacks who run the FDA are having fits. Dr. Graham has been told he may be "reassigned" to what he says would be a do-nothing job in the commissioner's office, where he would be far removed from research and analysis. His lawyer says Dr. Graham has received threatening anonymous calls from within the agency. Dr. Graham is trying to withstand the pressure and keep on with his life's work, which is reviewing the safety of drugs on the market.

In addition to fixing inadequate whistle-blower laws, congressional reformers should attempt to remove the monitoring of problematic drugs from FDA jurisdiction. This month the Journal of the American Medical Association urged just such a move. Drug safety involves life-and-death decisions for millions of Americans and has no place in a process that has been so thoroughly politicized. [...]

The editorial is worded more strongly than I would have put in a newspaper, although it is fine for a blog.  I found the editorial after doing a Waypath search; the reference was in a Livejournal post on Stranger than Fiction.  I mention this to give the author credit, but don't bother reading her post.  It's mostly about the author's social life; she mentions the editorial as an aside.  The JAMA articles that are mentioned in the editorial are available, open access:

Strom discusses the current US spontaneous reporting system and its limitations, concluding that while asking industry to monitor its own drugs is a conflict of interest, there is no need for additional duplicative regulatory oversight. Rather, more funding is needed to support programs that could complement the role of FDA in postmarketing surveillance. FREE ARTICLE
MORE >

In an editorial, Fontanarosa, Rennie, and DeAngelis discuss recent drug withdrawals from the marketplace and the limitations of the FDA's postmarketing surveillance. They recommend that the drug approval process be decoupled from the postmarketing safety and surveillance system, including the establishment of a new drug safety monitoring agency, completely independent of influence from the pharmaceutical industry. FREE ARTICLE
MORE >

The articles themselves are highly technical, but the first one mentions this gem about a Massachusetts Liberal:

The Joint Commission on Prescription Drug Use, triggered by Senator Edward Kennedy, called for creating a private nonprofit Center for Drug Surveillance to address these gaps; that call came in 1980. Twenty-four years later, I join Psaty et al in renewing that call. This could be accomplished by vastly increasing the number of CERTs and the funding of each. It also could be accomplished by forming a new organization. Regardless, such investment is critical to optimizing the health outcomes resulting from the substantial sums spent in the United States on therapeutics.

Maybe people should listen to Kennedy more often.

The second article contains specific recommendations for correcting the problems with the monitoring of drug safety. I won't repeat the recommendations here, since JAMA kindly made the entire text freely available.  However, I would like to add my own recommendation. 

Currently, the FDA does not have the authority to mandate specific postmarketing studies.  Yet, the current political climate is such that there is a lot of concern about expanding government, and about the role of legal liability in driving up drug costs.  In addition, there is concern about the propriety of spending a lot of public funds for additional safety testing.  After all, it is the drug company that stands to profit, so it would make sense for them to bear the brunt of the cost. 

In order to address these three concerns simultaneously, I suggest what I might call the Autobahn method.  There was a time that there was no speed limit of the expressways in West Germany.  There were posted speed recommendations, but here was no penalty for driving faster that recommended -- unless you caused an accident.  Then, you faced mush greater liability if you were driving above the recommended speed. 

What I suggest is that a new organization be set up, independent from the FDA, that has the power to recommend specific postmarketing safety studies.  The pharmaceutical company could choose to follow, or to ignore, the recommendations.  If they follow the recommendations, and find a problem, they would be exempt from punitive damages (assuming no actual malfeasance was involved).  Perhaps other liability limits could be set, although I am less sure about the appropriateness of that.  If the company chooses to ignore the recommendation, then they would have no special protection in the courts. 

The advantages are that the company pays for all the studies, so public funds are not used; the government does not take over additional regulatory functions, merely taking an advisory role; and there would be limits to liability, so long as everyone plays by the rules.  I'm not very good at thinking like a Republican, but I should think that this sort of compromise would be acceptable to them.  The drug companies might not like it, but they would go along with it more readily than they would a more intrusive system, and consumers get more protection. 

Liberal activists might argue that it does not go far enough.  Realistically, though, whatever is proposed has to be some kind of compromise.  Congress is close to a stalemate even on the 9/11 Commission reforms, even though just about everyone agrees that reform is necessary.  The Medicare drug benefit almost did not pass, even though the Party in Power (the PIP) hailed it as one of the most important advances put forth by the current administration.  Clearly, something needs to be done, quickly.  And given the near-paralysis of the PIP, there will have to be some serious compromise in order to get anything done. 

FDA Under the Microscope

Sunday's New York Times has long article about the problems at the US Food and Drug Administration. Although some of the problems mentioned have been reported elsewhere, before -- including this blog -- there are some things I did not know.

For example, I did not know that Newt Gingrich et. al. (part of the Contract on America) once proposed that drug companies be allowed to market their products without FDA approval!

In 1996, Republicans lawmakers led by Newt Gingrich, the house speaker, proposed legislation that would have allowed companies to market their products without agency review, gutting its oversight authority.

Everyone who thought that was a good idea ought to have to take Vioxx until they die. The main point of the article, though, is not that pro-business politicians are misguided. Rather, their main point is that incessant budget cutbacks have had unintended consequences. They point out that the FDA is responsible for oversight of about a quarter of the US economy (food, drugs, and cosmetics), yet it is a small agency by federal government standards: only 10,800 employees, with an annual budget of 1.9 billion dollars.

It turns out that the resources dedicated to monitoring drug safety have declined significantly since 1992. In part, this change resulted from the AIDS pandemic. It became apparent that something had to be done to speed up the drug approval process. Following a mostly-good idea, they decided to collect fees from the pharmaceutical industry, and use that money to speed up the approvals. That's fine, obviously. But the Industry was concerned that the amount of government money that was already going to the process would shrink. Therefore, they lobbied -- successfully -- to have the funding structured such that that could not happen:

The 1992 agreement provided that the F.D.A. could collect fees from industry only if government financing of new drug reviews, adjusted for inflation, never fell below 1992 levels (later revised to 1997 levels). This stipulation was intended by industry to ensure that its money was used to hire new drug reviewers and not simply substitute for government support of those already on staff.

But Congressional financing has lagged the agency's escalating payroll costs. To meet the "trigger" and keep fees flowing, agency officials have been forced to shift dollars from other programs into new drug reviews. This shifting has increased the agency's focus on the reviews even beyond what the drug industry had negotiated.

In 1992, the agency's drug center spent 53 percent of its budget on new drug reviews. The rest went to survey programs, laboratories and other efforts that in part helped ensure that drugs already on the market were safe. In 2003, 79 percent of the agency's drug center budget went to new drug reviews. Everything else has gotten squeezed. [...]

Since the 1992 agreement, agency officials have eliminated half of the scientists in the drug center's laboratories and starved them of new equipment. They have ended many of the agency's collaborations with academic groups that scrutinize the problems of marketed drugs. To pay for a modest in-house effort to catalog some information on drug side effects, a system called the Adverse Event Reporting System, the agency has raided furniture and travel budgets.

The article goes on to review the case of Seldane, a prescription antihistamine that was taken off the market. The FDA did testing that revealed safety problems. Now, the FDA does not have the capacity to do that kind of testing. The FDA also cannot require companies to do testing on drugs that already have been approved. They then turn to the Vioxx story:

Realizing this weakness, Dr. Graham of the agency's office of drug safety collaborated with Kaiser Permanente, a huge health maintenance organization, to check its computer records to see if those taking Vioxx had had more heart attacks. The study took nearly four years to complete. Its results became known in August [2004] and demonstrated Vioxx's dangers.

Dr. David Campen, medical director of Kaiser's pharmacy operations, said the study would have taken half the time if the agency had had the money to pay for drug monitoring programs with Kaiser or other large managed care organizations. Dr. Graham has estimated that the delay in uncovering Vioxx's dangers cost 55,000 Americans their lives, a number top officials at the F.D.A. have labeled as "junk science."

I don't know if it is junk science or not, but even if the actual number was only one-tenth of the 55,000, that would mean over five thousand people died unnecessarily over a two-year period. Now all we have to do is calculate how much of a hit those premature deaths caused to the economy, to see if the budget cutbacks were a good investment. Oh, there I go, thinking like Mr. Gingrich again...

I supposed I should go easy on the Republicans.  After all, their Secretary of Health and Human Services, Tommy Thomson, has stated that he favors the formation of a new agency that would monitor drug safety, independently from the FDA.  Too bad he's leaving.

Rumsfeld ReappointedNew Definition of "Bootscraper"

For some reason, there is something that really bugs me about Mr. Rumsfeld.  It isn't that he was reappointed as Secretary of Defense.  No, it's not the fact that he participated in lying to the American people about the rationale for the war in Iraq.  It's not that he has failed to atone for, and may even have endorsed, the atrocities at Abu Ghraib, Guantanamo, and elsewhere.  It isn't even the fact that he pressured the CIA to come up with reports that supported the Administration's policies, regardless of the truth of the matter. 

What bothers me about Rumsfeld is that, prior to the latest invasion of Fallujah, he told the Press that he expected low civilian casualties.  That statements bothers me because it is dishonest.  It is a statement that implies something good about an important matter, but that cannot be verified. 

As I started to write this, I scanned the 'net for reports on the civilian casualties in Fallujah.  There are many such reports, but they cite wildly different numbers, and they all point out that the numbers are not reliable.  The US government steadfastly refuses to provide such figures.  My opinion on this is, if you are not going to provide the numbers to back up your claims, then you should not make the claim in the first place.  To do so is to commit a kind of dishonesty.

You can scrape the boot all you want, but the mud does not go away; you just keep it outside where you don't have to look at it.

Spaces: The First Frontier

No doubt, most of you are aware that Uncle Redmond has gotten into the blogging business.  MSN Spaces is the name of a new free blogging service.  I've looked at some of their blogs.  Nice enough.  But the Terms of Service are repulsive:

2. HOW MICROSOFT MAY MODIFY THIS AGREEMENT

Microsoft reserves the right to change the terms, conditions, and notices under which it offers the MSN Web Sites, including any charges associated with the use of the MSN Web Sites. You are responsible for regularly reviewing these terms, conditions and notices, and any additional terms posted on any MSN Web Site. Your continued use of the MSN Web Sites after the effective date of such changes constitutes your acceptance of and agreement to such changes.

So they can put a change in the terms of service on any MSN site (there must be thousands) and you are responsible for seeing it and adhering to it. 

6. MATERIALS YOU POST OR PROVIDE; COMMUNICATIONS MONITORING

For materials you post or otherwise provide to Microsoft related to the MSN Web Sites (a "Submission"), you grant Microsoft permission to (1) use, copy, distribute, transmit, publicly display, publicly perform, reproduce, edit, modify, translate and reformat your Submission, each in connection with the MSN Web Sites, and (2) sublicense these rights, to the maximum extent permitted by applicable law. Microsoft will not pay you for your Submission. Microsoft may remove your Submission at any time. For each Submission, you represent that you have all rights necessary for you to make the grants in this section. To the maximum extent permitted by applicable law, Microsoft may monitor your e-mail, or other electronic communications and may disclose such information in the event it has a good faith reason to believe it is necessary for purposes of ensuring your compliance with this Agreement, and protecting the rights, property, and interests of the Microsoft Parties or any customer of a Microsoft Party.

Anything you post their becomes their property.  If they want, they can reformat what you write.  They may monitor your e-mail, and disclose its content.  Why would anyone consent to this?

There are other nutty provisions, but those are the most egregious.  They have some clever features.  You can put up a list of your favorite songs.  Your readers can click on the titles and are offered a chance to download the song for 99 cents.  I suspect all the profit goes to Microsoft, though...

Good News and Bad News About Flu Vaccine Shortage;Bush Administration Dodges Pundit's Jab

There are two article's in this week's NEJM that address the issue of the current shortage of influenza vaccine in the USA.  The good news is in one of their Perspective pieces, by Dr. Thomas Lee.  He is glad that citizens have, for the most part, been understanding of the need for rationing.

The second article is a Sounding Board piece, The Fragility of the U.S. Vaccine Supply.  It is written in an apolitical style, which is characteristic for medical journals.  The authors are to be commended for their restraint. 

When I read it, I felt inspired to use it as source material to criticize the Bush Administration.  After all, there was evidence that we had advance notice of the possibility of a vaccine crisis, yet nothing had been done.  Read what I learned, plus a few pointed political comments, at The Rest of the Story.

Dear Government

Dear Government:

Thank you for the tax cut. I plan to use the money I saved to buy cigarettes, which now cost more that five dollars a pack, since the tax was increased.  I heard on the radio last night that you cut taxes for business, too. Thank you. I also heard that when you passed the business tax cut, you did not define exactly what a business had to do to qualify. Now you are asking for our help, to figure this out. As a good citizen who is too old to go into combat and fight for the right of our citizens to pay higher prices for gas on Thanksgiving, I figured I should do my part to help you figure out which businesses should get the tax cut.

What they said on the radio is that businesses have to prove that they are manufacturing businesses, and that their products are made primarily in the USA. I am writing to let you know that I have a business right here. It manufactures a product. The product is not just primarily made in the USA, it is entirely made in the USA. Not only that, but the product is far more useful than anything made in Washington D.C. You see, I have some horses. I put hay in one end, and the manufactured product comes out the other.  Do I get the tax cut?

Conversation in a Nursing Home

(This really happened.)

Social Worker, thinking Ms. H has dementia: OK, can you subtract 7 from 100, and keep counting backward by 7?

Ms. H: Hell no, I can't do that!

Social Worker:  Can you tell me who the president is?

Ms. H: It's that damn fool, Bush!  I can't believe he got reelected! Did you see what what he just did? (Gets up and gets a newspaper, then shakes it in the face of the social worker.)