More evidence that schizophrenia is an evolutionary disorders

A year ago I coined the term "evolutionary disorders" for diseases arising from malfunctions of rapidly evolving organs -- like the human brain.

Today comes news that the vast spectrum of disorders we lump together as "schizophrenia" arise from a very diverse array of unrelated mutations.

Sounds like a disorder of evolution.

See also:

•  What is schizophrenia? Not what we though
  
•  Is schizophrenia the price we pay for an evolving brain?
  

Sometimes a criminal can do you a favor

File this one under ‘life is best drunk black’.

We know phishing scams are getting more sophisticated. It’s the age old story – target the vulnerable. Mostly the vulnerable are the cognitively disabled, including the ever growing population of once sophisticated adults with new pre-dementia. (Emerging trend: children filtering their parent’s email.)

There are other vulnerables though. People facing medical or financial crises, where desperation trumps judgment. Or people with a missing loved one.

Recently I received a phishing email promising information on my brother. It wasn’t all that well done (no, I won’t point out how the scum could improve); I presume it was an amateurish attack from some online registry.

Coincidentally it came in around the 6th anniversary of my return to Saint Paul from Whistler Canada. Nice timing!

Ironically, the crooks did me a favor. They made me check the old domain I setup years ago. I was shocked to find it pointing to my hosting service – Lunarpages. Turns out a credit card had expired, and the registration had lapsed. Lunarpages still held the domain, so once I fixed the card they restored the service. (Now I have to figure out what happened to their missing notifications, and whether I want a different host.)

So here’s a thanks to the scum-sucking lice running phishing scams against the families of disappeared persons. You did me a good turn. Tell me where you live, and I’ll return the favor …

Challenges to medicine and science – medication invention hits a brick wall

Pharma has a problem – they’re not coming up with any great ideas…

Health Blog : Hey, Drug Researchers, Lotsa Luck!

Name a drugmaker that isn’t struggling to come up with breakthrough medicines. Research costs have ballooned while output at many companies has slowed to a trickle. Technology that was supposed to make drug research more predictable seems to have instead made it easier to come up with more drug failures faster.

“The molecular revolution was supposed to enable drug discovery to evolve from chance observation into rational design, yet dwindling pipelines threaten the survival of the pharmaceutical industry,” say consultant David Shaywitz and Nassim Nicholas Taleb, author of “The Black Swan: The Impact of the Highly Improbable.”

“What went wrong?” they ask in the opinion pages of the Financial Times. “The answer, we suggest, is the mismeasure of uncertainty, as academic researchers underestimated the fragility of their scientific knowledge while pharmaceuticals executives overestimated their ability to domesticate scientific research.”

When you get right down to it, Shaywitz and Taleb say, we still don’t understand the causes of most disease. Even when we think we do, because someone found a relevant gene, we’re not very good at turning the knowledge into a treatment. “Spreadsheets are easy; science is hard,” they tell Big Pharma…

I can vouch for the lack of progress. I’m wrapping up a review of roughly the last 7 years of changes in medical practice.

To put it delicately, progress has sucked. If you put a good physician to sleep 7 years ago, and woke her up today, she’d be reasonable competent on day one. A week later she’d be fully up to speed.

My med review conclusions are:

1. Lots of new combinations of old drugs, maybe due to co-pay schemes
2. Many new drugs have suicidal ideation as a side-effect.
3. Lots of failed immune related drugs re-purposed with limited focal impact on a few disorders.
4. Probably some improvements in seizure meds. Lots of new Parkinson’s and diabetes meds, but they’ve had limited value. (metformin was a home run, but that was more than 7 years ago).
5. Really lousy progress in antibiotics; there are fewer useful therapies now than 7 years ago. Actually, fewer every year.

Every so often I read stories about how physicians are demoralized by financial pressures or lack of social support. I can see that, but maybe we should start asking real physicians (not industry types like me) if they’re feeling discouraged by the lack of medical progress.

It’s a lot more fun to practice medicine when you’re able to do new things to help people, not so much fun when there’s no more magic in the hat …

Amazon Payments and Simple Pay - will be big (and a bug)

PayPal, about a hundred years late, has established a signed email infrastructure. I don't see PayPal/eBay phishing scams on Gmail any more, because anything unsigned is instantly deleted.

So they're trying to clean up a bit. Too late for me. They played a dirty game too long - I want 'em gone.

I thought Google Checkout would do the trick. Much as I like Checkout though, Google hasn't done that much with it. (Given a choice, I usually choose a Google Checkout vendor.) In particular Checkout never went person-to-person, and it never went international.

Maybe Amazon will do better with Simple Pay and Amazon Payments.

Simple Pay is very much like Google Checkout (confusingly, Amazon Checkout is more like a store front service). It's business oriented, but I went through part of the signup and it's trivial -- any individual proprietor could easily use Simple Pay.

Simple Pay is also available for non-profit donations (so is Google Checkout, but we couldn't get that to work for MN Special Hockey). Here's their cut:

For Transactions >= $10:

• 2.9% + $0.30 for all transactions

For Transactions < $10:

• 5.0% + $0.05 for all transactions

Amazon payments is even more interesting. It allows phone-to-phone cash transfers and online cash transfers to any person.

I signed up. I can now send money to "anyone's" (I suspect they really mean "anyone in the US") email or phone, it goes against my regular credit card.

Update: You might want to wait a bit before using Amazon Payments. I, of course, found a bug. Amazon Payment has assigned me the name of a corporate admin who's card was a available for my use in my Amazon account. That card was never my primary payment card, and it's not been used for ages, but it was there. Extremely annoying. I've deleted it and remove the name from my address book, but the identity assignment remains. I'll update this note with Amazon's response.

Update 8/8/08: Yeah, it's a bug -- though Amazon thinks it's only a cosmetic problem.

It took me quite a few emails until Amazon stopped sending me automated, useless, support responses. Sadly, I had to resort to one of those upper case, exclamation point, adjective infested "YOU HAVE A BUG!!!!" emails. Modern email decision support systems treat these the same way voice recognition systems treat obscenities -- they route to a human.

That's so sad.

This is what Amazon finally responded with:

I have reviewed our previous correspondence with you, and I offer my sincere apologies for any misunderstanding thus far.

I'm sorry to hear about the difficulty you experienced with the name on your Amazon Payments account.

At this time, I do see that the name listed for your Amazon.com account is John G Faughnan, and your Flexible payments account may be showing as xxxxx.

We are aware that the Payments website may greet you by the name associated with a credit card rather than the name on your Amazon.com account. I have passed this feedback along to our developers. We are always happy to get this type of feedback from our members.

We will update the display name for your Amazon Payments account for you. This change should be completed within 1-2 weeks.

Please be assured that in the meantime your Payments account will operate correctly in spite of the name difference...

The problem arose because one of the credit cards on my Amazon account belonged to a corporate admin, that happened to be the name Payments randomly picked for a "greeting name".

Update 8/19/08: Amazon has some support issues. Either that, or their outsourced support organization is suffering from very high levels of turnover.

Today's episode:

I reviewed your Payments account and saw that the name associated with credit card on the account is "xxxxxxxxxxxxx" and the one associated with Amazon Payment is "yyyyyyyyyyyyyy". Please advise which one needs to be changed/updated on the account.

As always, please feel free to contact us should you have future questions or comments. If you need to contact us back, you can do so by using the secure form at the following specialized link to assure we receive your message:

Of course all my prior correspondence was clear on which was the correct name, and, as noted above, there's no way to respond to the message.

I tried the "specialized link". The saga continues.

11/1/08: The bug remains. Clearly, they can't fix it.

Odd note in a story on a national artificial joint registry

The NYT joins a call for a national joint registry to find problems sooner.

Makes sense, if the FDA had not been gutted by Bush it would probably have done this years ago.

The interesting bit, however, is the article unconsciously suggests an alternative approach:

The Evidence Gap - Experts Seek a Data Safety Net for Joint Replacements - NYTimes.com

.... The use of joint registries has proven beneficial abroad. In Australia, regulators use such data to force manufacturers to justify why poorly performing hips or knees should remain available, and products have been withdrawn as a result. In Sweden several years ago, surgeons alerted by their national registry stopped using a badly flawed hip long before their American counterparts did. A few medical organizations here, like Kaiser Permanente, operate their own registries to good effect and the Hospital for Special Surgery in New York has recently set up a registry....

If I were the governor of MN, I'd use the Swedish and Kaiser registries. How big a registry do we really need?

The NYT story incidentally illustrates how corrupted we physicians are. The physician profiled received lots of money from the hip replacement vendor. He eventually bit the hand that fed him, but we have lots of experimental data to show that paying "consultants" delays or softens any potential "bites".

In the absence of a national registry, or the use of Swedish and Kaiser data, paying off surgeons is a good investment. Not as great an investment as funding a helpful Senator's reelection, but pretty good.

Three Shtetl-Optimized posts for livening the mind

I really need to study, so I'm noting these for future reading.

These are a set of Aaronson posts, found by tracing back from the latests, that taken together are very good reading in physics and philosophy:

• The relativity of originality
• His review of Wolfram (pdf)
• Newcomb's problem
• PHYS771 Free will

All the essays touch, more or less directly, on the question of whether "free will" (as Scott rigorously defines it) is possible. Note this is distinct from the concept of responsibility -- every reasonable thinker over the past few centuries has understood that "responsibility" is a social construction with no intellectual integrity.

By way of background scientists philosophers have gone back and forth on this since science was more or less born with Francis Bacon. Things looked particularly bad in the 20th century; in the absence of quantum mechanics general relativity seemed to predict a universe frozen in space-time, in which every moment occurred at once and invariably. Maybe this is where Vonnegut's Tralfamadorean determinism came from.

QM seemed to restore free will, but it introduced some disturbing predictions of its own. Physicists attempted to restore the concept of an observer-independent reality through the transactional interpretation, but that did in free will

More recently reality (or realism) seems to be out favor, so maybe free will is back.

Now you're prepped to read Aaronson.

PS. See also - Sean Carroll's favorite posts.

The meaningless beta: Apple and Google

The emerging consensus is that iPhone 2.0 is a big, painful beta program. The real release will be iPhone 2.1.

Truthfully, my main pains with iPhone 2.0 have been the optional MobileMe (even if it worked it would be bad) and missing PDA (Palm) functionality. The rest of it has been good enough, and the apps I've installed have worked. I do reboot nightly.

So I'd say iPhone 2.0 is incomplete, but roadworthy if you're ok with GPS and a faster version of iPhone 1.0 (at a far higher cost for AT&T customers mind you).

MobileMe, on the other hand, reminds me of iMovie '08 and 10.5.0 -- an interesting product born 6 months premature.

By contrast, we have Google. Gmail is still beta (look top left at logo), years after it reached a level of reliability Apple rarely achieves.

I think we need to retire the word "beta". It's become meaningless.

McCain embraces Rove. Of course.

The only surprise is that it took him this long.

Editorial - Low-Road Express - Editorial - NYTimes.com

On July 3, news reports said Senator John McCain, worried that he might lose the election before it truly started, opened his doors to disciples of Karl Rove from the 2004 campaign and the Bush White House. Less than a month later, the results are on full display. The candidate who started out talking about high-minded, civil debate has wholeheartedly adopted Mr. Rove’s low-minded and uncivil playbook...

Obama is a Chicago pol, so this can't be unexpected. We know the low road works on Americans.

I expect the GOP to win. I suppose it's the result of 8 years of Bush -- I really can't imagine a better future.

Doesn't matter, I'll fight for Obama anyway. Miracles happen- at least in politics.

Update: There's a risk to playing this game of course. It legitimizes a strategy of pointing out that McCain may have pre-dementia. This ploy has the advantage of possibly being true.

FailMe: a classy approach to getting even

Apple - FailMe is a spoof of Apple's MobileMess with the perfect combination of humor and angry bitchiness.

We've come a long way from sending snail mail complaints to the CEO.

I love it. They'll have time to build out more content -- it will be months before MobileMe is reliable (assuming Apple can do reliability, which is unclear), and a year before it's a real competitor to Google Apps.

The problem with my 'brain and mind' tag - the mind is not in the brain

Blogger supports tagging of posts, though they're called "labels". One of the tags for this blog is Brain and mind.

There's a problem with that tag. No, not the boring old "mind/body" duality stuff. I'm a pragmatic materialist 2.0 (ie reality + emergence), for me the "mind" more or less runs on the body [1].

The problem came to me as I thought about a post I wrote a week or two ago on current models of chronic pain syndromes ...

Gordon's Notes: The pain is all in your head

... The ideas aren't quite as novel as Gawande suggests. I recall fifteen years ago veteran physicians, with lots of experience with intractable pain and chronic fatigue, had begun to think the problems were 'all in the patient's head'. By which we meant, with intentional irony, that the problem was 'malwiring' of the brain.

The good news is, the brain is plastic. We can't easily alter it directly, but we can slowly reprogram it through the mind. That's how the mirror-box therapies Gawande describes work, and presumably that's how exercise therapy works for chronic fatigue syndrome (albeit both imperfectly)...

Ok, I have to also thank my son, who has an extremely tight connection between psyche and soma. I watched a recent shoulder problem wax and wane in proportion to psychic stress, and I realized what's wrong with both my tag and my prior post.

I have too strong a division in my own head between the central and peripheral nervous system. Yeah, sure, everything is connected to everything else so we do need to draw lines, but I think for the purposes of modeling disorders of sensation and perception, including pain, the line should be drawn around the peripheral nervous system -- not around the central nervous system (and not around the body -- that's too broad to be conceptually useful).

Perception and sensation are core functions of mind, and we physicians may err in ascribing them primarily to the periphery or the core.

Yes, I know this seems self-evident when I put it this way. Maybe it is, but I think there's something here. If we truly believed in this model, I think we would approach all management of sensation, whether arising in a broken leg (peripheral nervous system), or my son's sore shoulder (central and peripheral) or intractable itching (central) with an eye to techniques applied both peripherally (set the leg) and centrally (??).

There's something here ... I just need to think about it a bit more.

[1] More or less, without the "oxygen" of social interaction and coherent sensory input it won't run well for long.

Why Apple can't do the Cloud: secrecy is the enemy

I've been forced to stare deep into the bowels of Apple's MobileMess, Outlook synchronization, and oddball .Mac conversion disasters.

This stuff is extremely hard, but Apple has brains and money. What in their culture caused such a massive screw-up?

The problem, I think, is secrecy -- an obsession with surprises that comes partly from their CEO (though if I read one more article claiming Jobs is Apple my brain will explode), partly from their history, and largely from an insanely successful marketing strategy.

The complexity of changing a densely interconnected system like .Mac to a very different system like MobileMe requires months of public beta before launch. There can't be any surprises, there has to be high reliability.

Google gets this. Microsoft gets this.

Apple doesn't.

Apple won't be able to compete in the (cursed) Cloud if they can't kill their secrecy demon.

Apple begins the MobileMe recovery

It only took the NYT and the squeaking of thousands of customer mice, but Apple has launched @ daily MobileMe status reports:

Apple - MobileMe - Status

... One issue we encountered was a mail outage affecting 1% of our members. Last Friday a serious problem with one of our mail servers blocked those members’ access to their MobileMe mail accounts. As of today a team was able to restore limited web access to those accounts so the affected members can use their browsers to read mail that has arrived since last Friday (though not before) as well as send and receive new mail. The team has already begun rolling out restoration of full access for all the accounts and expect to finish by the end of next week. We particularly regret to report the loss in the affected accounts of approximately 10% of the messages received between July 16 and July 18.

.... fixed over 70 bugs including one that was preventing MobileMe IMAP mail folders from syncing correctly between the web app and Mac OS X Mail or Outlook, plus others correcting display issues in Calendar and in general enhancing the performance of our web apps...

Software-as-service and DRM mean you don't own. You rent. Everything. Another lesson from Yahoo.

This would be the third time I recall that a major vendor has shut down a DRM service and stripped customers of all their products.

AppleInsider | Yahoo! Music's death at age 3 warns of DRM's risk

... Yahoo did its best to stage a rival to Apple Inc.'s iTunes, but after three years of lagging results, the Internet icon is putting its Yahoo! Music service to rest and leaving subscribers with copy-protected music libraries that can't be transferred to new computers...

Due the vagaries of computer life, within a year much of that music will be gone. Yahoo is telling users to burn CDs from the music. Anyone who's ever tried to do this will know what an inane idea that is. It's prohibitively time consuming, and future lossy compression of that music will generally produce awful results.

When Microsoft/MSN (? or was it AOL?) did something similar I think they refunded customer money, though that only works for people with current accounts.

They key lesson is that when you buy a used CD for $3 you have access to that material for an unlimited amount of time. When you buy the same CD new on iTunes for $14 you have use until Apple closes its FairPlay servers, or until it changes your iTunes contract.

We live in an age of transience. I suspect a younger generation will simply accept this as the way things are.

Incidentally, there's a cruel surprise slowly being uncovered. A surprise, that is, to the vast majority of people who don't bother thinking about DRM.

Lots of families are going to have multiple iPhones (great phone, fascinating computer, lousy PDA, Outlook sync broken, don't touch MobileMe before November, wait for 2.1 if you can).

They'll expect they can sync all their iPhones to what they think of as the family music and video library.

Cue evil laughter.

They'll discover then that an iPhone is a personal device, and it must sync to an individual user account. They will also discover that Apple's DRMd music and videos are owned by an Apple username, not a family. Lastly, they'll discover that iTunes libraries are personal libraries, not family libraries.

Slowly they'll realize the jaws are closing around them. They need to buy a copy of each video and song for each member of the family. [1] Eventually, they'll see the shape of a BrainLocked future, where we pay to keep access to our own memories...

[1] There used to be a workaround for non-DRMd iTunes media, but I've not tested it on iTunes 7.7. Sooner or later Apple will close the door on this; my transient DRM optimism has faded. I don't think Americans are going to figure this one out. Maybe the EUs will twig to this, and put some serious laws in place.

Update: Recently Apple terminated its .Mac web page authoring tools. All .Mac web pages are now inaccessible. For a scary moment I thought Google had done the same thing with my old Google Pages. Turns out they're only close to gone. Dang, but I sure as shootin' don't trust that cloud.

Strangely met in night: a blog I’ll never read …

A google search took me to a caustic discussion of a Hofstadter book:

The New Skeptic: I Am a Strange Loop: Gödel's Loop

…Continuing my review of I Am a Strange Loop, today I get to tackle metamathematics. Hofstadter tackles it too, and finds it rich in philosophic insight. Strangely rich, actually.

I suppose I ought to explain who Kurt Gödel is and why he is a hero of many, many nerds today (I am among those ranks). And that tale doesn't start with Gödel, so stay patient while I explain the background…

Caustic and opinionated, but interesting. I started to look at the archives. Should I grab this feed?

Then I saw the “links of note”:  national review, weekly standard, rush… savage … beck …

On closer inspection, the stranger in the night wears a necklace of human noses.

Backing slowly away …

Thank heavens for the link list – who knows what horrors I might have been exposed to!

Bayes theorem and the anthropic principle

Years ago I used to teach Bayes theorem to informatics grad students.

I was reassigned to other lectures though. Truth is, I had a hard time focusing on the boring stuff we were doing with Bayes. It just seemed like there was a deep weirdness about the Bayesian model of probability, but I couldn't quite put my finger on it. I was sure someone who understood it deeply would justify my queasiness.

Since then there's been a bit of a renaissance in thinking about Bayes. In Our Time even did a recent programme with a good bit of Bayes. Physicists are all over Bayes these days, and the Bayesian vs. Frequentist combat is out in the open (I knew this stuff was weird).

These days, I could assign students this essay to read:

PHYS771 Lecture 17: Fun With the Anthropic Principle

... So if Bayes' Theorem seems unobjectionable, then I want to make you feel queasy about it. That's my goal. The way to do that is to take the theorem very, very seriously as an account of how we should reason about the state of the world...

Of course that assignment might also shrink the class size ...