Alzheimers, inflammation and the endocannabinoids

BBC NEWS | Health | Marijuana may block Alzheimer's

Or not. I read recently that headline writing is a low prestige, low paying job, in journalism. I can believe it.

Some background. The current fashion in Alzheimer's research is that local inflammation plays some role. We don't know why there's inflammation (though some think it's a response to malformed protein -- amyloid), we don't know if it's an isolated or secondary phenomena, we don't know whether (if it's secondary) it's ever an appropriate response, we don't know if stopping the inflammation will help or hurt, etc. Some of the lesions of Alzheimer's dementia or now thought to be part of the brain's appropriate response to injury; so stopping inflammation may help in the short term but be very bad in the longer term.

The microglia seem to play a role in activating this inflammation. Researchers found activating the CR2 receptor seemed to protect against the microglia-initiated inflammation triggered by amyloid protein in rats. The CR1 receptor wasn't protective. Marijuana contains a wide variety of cannabinoids; some of them activate CR1, some activate CR2, some do both, etc. CR1 mediates most of the recreational/toxic effects of marijuana.

So the headline is fun but of course quite misleading. Something in marijuana may play some role someday in something do with Alzheimer's disease. In rats, anyway.

On the other hand there are some things that we can't forget.

1. The Alzheimer's process is a condition that seems to begin quite early in life -- perhaps before age 5. It attacks almost everyone to some extent but has its greatest impact on persons with low IQs (it's very severe in people with Down's syndrome). If we can slow or remediate the onset of Alzheimer's the social impact will be vast. Our 75 yr projections for medicare and social security will look quite a bit better.

2. The discovery of the endocannabinoids and the medications that will act on them may bring a new revolution in psychiatry. Some things we'll learn will have bad effects, but I'm optimistic.

3. The role of inflammatory processes, including infectious processes, in what where thought to be "age-related" degenerative conditions of the stomach, brain and heart is quite startling. I'm quite ready now to believe we'll uncover an infections component to rheumatoid arthritis (a longstanding hypothesis that's been often investigated without success).

So this is exciting stuff, despite my kvetching on the headline.

DMCA abuse -- the courts refuse to roll over

Last July, I wrote about how the DMCA might be applied to lock customers in to custom batteries -- or printer catridges. Vendors wanting to move customer off of old products can just stop selling the batteries -- or the printer cartridges.

I figured this was inevitable, but may be I was wrong:

SiliconValley.com | 02/22/2005 | Lexmark printer running low on legal size paper

Looks like Lexmark's effort to use the Digital Millennium Copyright Act (DMCA) to prevent other companies from making refurbished toner cartridges for its printers has received a potentially fatal blow. The U.S. Court of Appeals for the Sixth Circuit has denied Lexmark's request that it reinstitute an injunction against Static Control Components (SCC), a maker of computer chips that enable recycled toner cartridges to work in Lexmark International printers. Lexmark had argued that SCC's Smartek chip circumvents a copyrighted technological measure that its printers use to verify toner cartridges are original and because of that violates a clause in the DMCA that prohibits the dismantling of devices intended to protect intellectual property rights. It was a worrying use of the DMCA and one that, as SCC pointed out in a legal brief, could cause consumer-unfriendly DMCA-protected chips to appear in many consumer products. Evidently, the court agreed. Now, barring the intervention of the Supreme Court, it looks like Lexmark's case is dead in the water. 'This is a very gratifying decision,' said SCC chief exec Ed Swartz. 'We have asserted from the outset that this is a blatant misuse of the DMCA. The Sixth Circuit's ruling and the court's decision not to hear Lexmark's request for another hearing solidifies and supports our position that the DMCA was not intended to create aftermarket electronic monopolies.'

A test of political mores: fun on the web

Moral Politics - A Morality-Based Political Test

I took both the two question test and the 15 question test. On the two test question I fell in the "Moderate Liberalism" category (as in 19th century Liberalism) and I had a 96% overlap with John Kerry. On the longer test I was "Moderate Socialism" and had a lesser overlap with John Kerry.

I knew I liked Kerry for a good reason.

I think I'm in-between the two axis -- but the two question test was more accurate. Both tests pegged me on "Moral Order" (ideal view of the world) but the longer test was less accurate on "Moral Rules" (rules that point to moral order).

I suspect what the longer test misses is the gap between how I'd like the world to be and what I believe humanity is capable of. So I'd like a world that was more of the "moderate socialist" order, but I don't believe humanity can really manage that degree of enlightened self-interest. The best humanity can sustain is "moderate liberalism".

Now if we make a few changes to the genome ...

Jon Stewart is completely hilarious -- the Gannon show

Jon Stewart's Daily Show on Bloggers 02/16/05

This site is hosting a John Stewart's Gannon show as a QuickTime video. It's hilarious. It almost makes me want to watch TV.

Is Stewart the only real journalist left?

I wonder if he'll do the "Bush tapes". Perhaps not, neither Bush's allies nor his "enemies" really like the tapes. To Bush's allies the tapes are disturbing and upsetting. To his "enemies" (who wish him well in retirement) the tapes portray him as too much like one of us.

Obituary for a Grammarian

The New Yorker: The Talk of the Town

To one correspondent she sent a beautiful letter, frank and kind, needlessly grateful, which ended with the sentence “Please forget about me.” Of course, we never could and we never will.

The Grammarian of the New Yorker dies at age 87, five years after a stroke forced her out of her office. All die, few have such a fine obituary.

Friends don't let friends buy HP

Boing Boing: HP faces lawsuit for inkjet cartridges with expiration chip

The allegation:

H-P ink cartridges use a chip technology to sense when they are low on ink and advise the user to make a change. But, the suit claims, those chips also shut down the cartridges at a predetermined date regardless of whether they are empty. 'The smart chip is dually engineered to prematurely register ink depletion and to render a cartridge unusable through the use of a built-in expiration date that is not revealed to the consumer,' the suit said.

I soured on HP after buying some of their sheet feeder scanners that doubled as paper shredders. They seemed to be making poor quality devices and punishing anyone foolish enough to buy from them.

Now this. If it's true then:

1. Does everyone do this? (I've got a Canon printer, I liked the separate ink wells.)
2. I won't be buying anything from HP. (Ok, so I wasn't going to anyway

More things I did wrong in my practice

Another day, another thing I did wrong when I practiced medicine:

TheMilwaukeeChannel.com - Health - Study: Hormone Therapy Makes Incontinence Worse, Not Better

By some estimates, up to half of all women over 50 will suffer from urinary incontinence. Many women take hormone replacement therapy because doctors believe it can reduce the risk of urinary leakage, but according to a new study, the opposite is true.

... Hendrix and her colleagues tracked the health of more than 27,000 post-menopausal women for one year to see if hormones reduced incontinence.

The study, published in Wednesday's issue of the Journal of the American Medical Association, showed that women who hadn't had leakage before taking the hormones were more likely to become incontinent, and women who were already incontinent were more likely to see their condition get worse...

... Women taking estrogen pills for one year were 53 percent more likely to develop urinary incontinence than women who took dummy pills. Women taking pills containing both estrogen and progestin faced a 39 percent higher risk.

I stopped doing clinical practice about 4-5 years ago, and it's been more years than that since I saw women for incontinence. Back then, however, a 50 yo woman with incontinence was a great candidate for estrogen therapy (w/ progestins usually): build up bones, reduce incontinence, reduce fracture risk, reduce heart disease risk, less dementia ...

Except none of those things, except the fracture, are felt to be true nowadays. Maybe this study is wrong (the design doesn't sound very robust), but I gather it's not the only study with similar results. It seems unlikely that estrogens are a great treatment for incontinence, and given their other issues I wouldn't use them for urinary incontinence today.

Sigh. Things wouldn't be so bad if I were confident that the newer therapies will hold up significantly better than the nostrums I was taught eons ago ...

Child atheletes in America - a bit crazy

The New York Times > Sports > Other Sports > Doctors See a Big Rise in Injuries for Young Athletes

High school students apply the technology and methodologies of the 1990 olympics. Grade schoolers are applying the technology and methodologies of the 1970 olympics. The NYT reports on one outcome -- exotic injuries:

A competitive swimmer since she was 7, Alex Glashow of Barrington, R.I., logged 8,000 yards a day in the pool, until her arms ached. She learned to dislocate one shoulder intentionally to ease the pain in the water, but after shoulder surgery and a year of physical therapy, Glashow quit competitive swimming forever when she was 15.

Jeret Adair, a top young pitching prospect from Atlanta who started 64 games in one summer for his traveling baseball team, last year had Tommy John surgery, an elbow reconstruction once reserved for aging major leaguers.

Ana Sani of Scarsdale, N.Y., a 13-year-old budding soccer star, practiced daily until she tore the anterior cruciate ligament in her knee...

...Dr. Lyle Micheli, a pioneer in the field of treating youth sports injuries and director of the sports medicine division of Boston Children's Hospital, said that 25 years ago, only 10 percent of the patients he treated came to him for injuries caused by overuse. Back then, most childhood injuries were fractures and sprains. Dr. Micheli said overuse injuries now represented 70 percent of the cases he sees...

... "It's not enough that they play on a school team, two travel teams and go to four camps for their sport in the summer," said Dr. Eric Small, who has a family sports-medicine practice in Westchester County. "They have private instructors for that one sport that they see twice a week. Then their parents get them out to practice in the backyard at night."

... It is not uncommon for the damage done by an overuse injury to be irrevocable, and the doctor's advice is to quit the sport.

"That's usually not received too well," said Dr. Michael Busch, an Atlanta orthopedic surgeon. "The parents will ask if there isn't some kind of surgery that can be done, so their child can keep doing the things that brought this injury on in the first place...

"To tell you the truth, the kids usually take it better than the parents. Many kids are relieved. They can be kids again."...

This is seriously crazy. Some of those parents seem to qualify as an odd variant of child abuser. The real problem, however, is not misplaced parental pride. It's a society that's become obsessed with excellence. Get over it guys. There's always someone faster, someone smarter, someone better. There are maybe 6 billion people on earth; 6,000 of them are "one in a million".

More importantly, the most significant injury is not to these child atheletes. It's their inactive peers who are really hurt and hurting. If the standard for sports participation is an elite athletic ideal, then 95% of children can't even imagine participating. We aren't going to do anything about obesity if 95% of kids are sidelined from first grade onwards.

Sports is important. For some people it will be the most important thing in their lives. (I make no value judgment, for all I know God is a quarterback. If I'd had the talent to attract girls by athletic display I'd have fully exploited that opportunity!) But like everything else in America, we carry it to absurd extremes.

We need to slow things down, and we need to broaden the experience to include all children -- including the slow and clumsy. Get a grip America!

How I use Gmail and why it really is so great

Gmail - Inbox

Gmail is getting ready to go public. I have about 50 "invitations" to handout. Good time to mention how my use has evolved.

1. My desktop email has become a repository and backup store. I do most of my work in Gmail. Messages go out with a return address to my public (spamcop) account but my Gmail account is well known to spammers so this is not critical.

2. I don't use the "labels" much. I thought I'd use 'em more. I'm very post-hierarchy these days. (Labels are an attribute that can be used to emulate a non-hierarchical folder with multiple inheritance.)

3. I "fork" my mailstream. (Relatively few people can do this, I control my mail domain.) Mail to my primary address is replicated to my POP box and to Gmail. So there are two copies everywhere. Works very well with two downsides:
- I have to remember to cc myself if want my replies or messages to be in both repositories. (I wish auto-cc was a Gmail feature, it's not.)
- I have to deal with spam twice, fortunately the filtering I use works pretty well. Gmail keeps a steady level of about 6000 spams in my spam box -- about 30 days worth.

4. Gmail is also a repository for files of less than 10MB that I want to quickly backup or pass around.

5. I use the "star" feature quite a bit.

6. My Inbox is emptied on reading. If I want to come back to a message I "star" it.

Things I really like about Gmail:

1. speed, speed, speed.
2. did i mention search speed?
3. no filing
4. keyboard shortcuts (see speed)
5. smart address book and adress completion
6. elegance
7. reliability
8. useful and interesting ad links

Things I want:

1. auto-bcc feature so I can copy replies to my personal repository
2. IMAP support (I'd pay)
3. more capacity -- 1GB will last me about another 2 years. (I'd pay)

Udell on screencasting

InfoWorld: Let's hear it for screencasting: February 11, 2005: By Jon Udell : APPLICATION_DEVELOPMENT : APPLICATIONS : BUSINESS : DATA_MANAGEMENT

Udell (uber guru) writes about screencasting:

I’m now using screencasts — that is, narrated movies of software in action — to showcase application tips, capture and publish product demonstrations, and even make short documentaries. And I’m seeing others around the Net starting to do the same. Now’s a good time to explain why I think this mode of communication matters and will flourish.

Experts use software far more effectively than novices. This knowledge is very rarely communicated in manuals; only a few books are good at providing this information. Sharing brief task-based usage is a valuable tool for building effective users.

Google's one page guide to becoming a Google Guru

Google Help : Cheat Sheet

This is very impressive. It's a single page summary that captures the key high value user interactions with a range of Google services. Memorize it and impress ... ummm ... ok, impress noone. But get more done faster.

The tedious response to having one's identity stolen

Has Your Identity Been Stolen? - What to do if it happens to you. By Daniel Engber

Next: a web business that outsources the response to identity theft. Fill out a form with the specifics, enter your credit card number, and sign stuff in the mail.

Since identity theft is becoming rather prevalent, we might as well automate the response to it.

Ajax: thickening a web client

adaptive path » ajax: a new approach to web applications

It's not easy to make JavaScript do all this stuff, and Safari is missing some of the key pieces (shame on Apple), but it is astounding when it works.

There's a fair bit of history here. Years ago we used to speak of "thin clients" (Citrix) and "thick clients" (conventional apps). Thin clients were easy to deploy but put a lot of processing burden on servers and suffered from communications latency.

Web browsers were thicker than Citrix but still suffered the effects of latency and had a much more limited GUI than a Citrix thin client. Both Sun's Java and Netscape's Javascript/HTML extensions were supposed to address the GUI and latency issues, but Sun and Netscape stupidly fought tooth and claw; two dogs fighting while a tiger chuckled nearby. Once Sun and Netscape had just about done in each other in Microsoft waltzed off with the browser. IE's DHTML framework threatened to finish what Netscape had started, but then the Office/.NET vs IE wars started at Microsoft. Office won and it looked like .NET would be the only path forward. Nonone could trust Microsoft to keep IE/DHTML healthy; it was a platform without a future.

But the vestiges of the old wars survived , in the IE/W3C document object model and in Javascript that was slowly getting less buggy. Different people in different places and times figured out how to get this rickety architecture working. Then came the rise of Firefox. Now even if IE stopped supporting this .NET alternative, it could still work on Firefox.

Of course it might also work even better on gBrowser ...

And now we have Ajax vs .NET for the variable weight browser-client title.

And so it goes.

Update: a colleague mentions the alternative approach to reducing latency - unbelievable server and network performance:

I would point out that several of the techniques Google is using don't require an
elaborate client side DHTML approach. They are, instead, leveraging
their incredible load capacity and low latency server array. Google maps is
a perfect example of relatively low tech client, plus an incredible tech
server architecture. If you look carefully you can sometimes see upwards of
20 GET requests being spun off, each with a latency response that is way way
sub second.

Update Again 2/23: Udell has much more on this topic, including more on how Google got its server latency to unprecedented levels.

Right wing fruitcake's "most unwanted" page

A guide to the political left

I loved the photo of Ted Kennedy. It has to be among the least flattering of the 250,000 pictures taken of him in the past 50 years. Among his many crimes: "Described the 2003 war in Iraq as “a fraud”".

This site hosts a right-wing fruitcake's "most unwanted" list. It has links to the Zawahiri and Betty Friedan. A Java applet is supposed to allow one to browse the network of connections (degrees of separation) but it didn't work on Safari.

I realize I'm just encouraging these folks by linking to this type of page, but it's a good reminder of how many reasonably intelligent people are really quite nuts.

Sheesh.

Dedication: Free Mojtaba and Arash Day

BBC NEWS | Technology | Global blogger action day called

Free Mojtaba and Arash Day.

From the BBC (with link):

The global web blog community is being called into action to lend support to two imprisoned Iranian bloggers.

The month-old Committee to Protect Bloggers is asking those with blogs to dedicate their sites on 22 February to the 'Free Mojtaba and Arash Day'.

Arash Sigarchi and Mojtaba Saminejad are both in prison in Iran.

... The group has a list of actions which it says bloggers can take, including writing to local Iranian embassies...