Defining a disease: how often are atypical presentations due to multiple agents?

It's been a long time since I was a real doctor, but occasionally I play one when the kids are sick (my wife is still a real doctor). In the latest episode our six year old had a week of vomiting, persistent fevers, hand and foot complaints and rashes that, to tired and worried parents, looked a bit like Kawaski's Disease. Happily a set of bloodlettings cured him and he never made the diagnostic criteria.

So what did he "really" have? "Bad adenovirus" is the story our most excellent pediatrican gave, though he admits he really doesn't know. In reality, of course, there's no reason why he had to have just one virus. There's nothing about being infected with, say, an enterovirus, that makes one immune to infection with an adenovirus. Likewise a strep infection, for example, does not prevent coronavirus infection. They're all around us in Minnesota at this time of year.

We're used to thinking about multi-organism infections in the context of HIV and ICUs, but they must happen reasonably often in the ambulatory setting. How many unusual presentations, including some with persistent injury or even death, are really the result of coincidental simultaneous viral (or bacterial) infections that together produce far more disease than each would alone? How often does a pathogen cause a commensal to become pathogenic? Our models of disease are, like all models in science, only approximations. We haven't had the instruments to further refine these models, and thus to reconsider the nature and definition of infectious diseases. It will be interesting to see how these things change as we get cheaper and better rapid tests for viral and bacterial infections.

Of course I'm sure all of these speculations are old hat in the infectious disease and microbiology communities, but my background is in primary care. I think changing from a simplified model of disease to a multifactorial and 'emergent' model, will have some interesting consequences in many domains. (I've omitted mention of additional genetic and environmental interactions because that's kind of obvious ...)

PS. Incidentally, when reading about KD both my wife and I were struck yet again about how feeble the descriptions of disease are in the biomedical literature. Most of the descriptions are a list of uncorrelated and unsequenced complaints and findings, as though combinations and temporal evolution were irrelevant -- when in fact those are often the key 'signatures' of a disease. If I didn't know better I'd say our medical writers are encrypting their knowledge, but in fact this I know there's no conspiracy here. It's simply that the audience doesn't demand better.

By comparison layperson stories are often much richer; one parent's website featured a terrific slideshow and description of the evolution of their daughter's successful treatment that shamed every medical text we reviewed. Osler's descriptions of disease in the early 20th century are far better than what we read nowadays.

Some curmudgeon needs to write a paper about this!

PPS. And then there's the remarkable paucity of data in most reviews and articles on the prevalence of cardiac aneurysms in treated Kawasaki's Disease. Come on gang! Applied biomedicine could use a kick in the old pants ...

What's really going on with the "Port" story?

Google has about 2380 articles about the port story. That's a heck of a lot of noise. None of it makes much sense. There isn't enough there to justify all the fuss. Sure, US port security sucks. Sure this is an incredible sign of incompetence five years after 9/11. That's the fault of the GOP and the Bush administratiion, not the port management company. Dubai is as good an ally as the near-friendless US has these days. The friendless part is also the fault of the GOP and the Bush administration. Sure foreigners are buying up fundamental US assets, but that's because our governmental finances are a complete mess. That's also the fault of the GOP and the Bush administration.

No news here.

So what's really going on that so many Senators have their knickers in knot? It has to be something that no-one is ready to talk about. I have two suggestions:

1. Sure Dubai is an ally. So was Iran under the Shah. Dubai is not a democracy. Maybe security analysts suspect it's ripe for revolution. Maybe Senators know that. It's a rather impolitic thing to say. This is one way in which Duba is not the UK.

2. Follow the money. (This one comes via Emily.) No deal of any size is done in the US today without a kickback to the GOP. They got a percentage, somehow, womewhere. The deal was done pre-Abramoff, and now the GOP is afraid this one might get attention.

Or maybe the answer is #1 and #2 and something else. The one thing I'm betting on is that it isn't anything that's being talked about.

Google to PayPal: your days are numbered

Google's official blog features a remarkably bland post on payment systems that includes a remarkably coy phrase:

Official Google Blog: An update on payments:

... We expect to add payment functionality to Google services where our users need a way to buy online....

There's no mention of when this will be released. My bet would be that we'll see the announcement within 3 weeks.

[note: in the original version of this post I wrote 'eBay' instead of 'PayPal'. I meant the latter.]

Another update on America 1984

Hilzoy of obsidian wings has extensive commentary on a recent New Yorker Article on America's torture program. The torment of the "20th hijacker" is truly impressive. Stalin would have approved.

What I want now is an international panel of wise women and men, trustworthy group of outsider, to pronounce judgment on America. Is it "happening here"?

Air America: On Groundhog Day

I'm a bit behind on my email. I just found this in my inbox (thanks K.):

This year, Groundhog Day and the State of the Union Address fall within two days of each other. As Air America Radio pointed out, "It is an ironic juxtaposition: one involves a meaningless ritual in which we look to a creature of little intelligence for prognostication, and the other involves a groundhog."

Newsweek shreds Bush, but is he incompetent or delusional?

Shrillblog sent me to this massacre of the Bush administration by Bill Hirsch, a senior editor at Newsweek:

Hirsh: Bush’s Poor Leadership in Terror War - Newsweek Politics - MSNBC.com

... What a contrast to four years ago, when the rapid collapse of the Taliban caught bin Laden by surprise as he sought to escape the Afghan mountains of Tora Bora. It was probably the last time, we must now conclude, that the terror impresario was surprised at all. As Gary Berntsen, the CIA officer in charge of the operation, records in his new book 'Jawbreaker,' (Crown, 2005) bin Laden told his followers, 'Forgive me,' and apologized for getting them pinned down by the Americans (Berntsen's men were listening on radio). Bin Laden then asked them to pray. And, lo, a miracle occurred. As Berntsen stewed in frustration over the Pentagon’s refusal to rush in more troops to encircle the trapped “sheikh,’ bin Laden was allowed to flee. And not only did Bush stop talking about the man he wanted “dead or alive,” the president began to shift U.S. Special Forces (in particular the Arabic-speaking 5th Group, which had built close relations with its Afghan allies) and Predator drones to the Iraq theater.

It is time to have an accounting of just how badly run, and conceived, this 'war on terror' has been...

...Al-Qaeda’s leaders worried about a military response from the United States, but in such a response they spied opportunity: they had fought the Soviet Union in Afghanistan, and they fondly remembered that war as a galvanizing experience, an event that roused the indifferent of the Arab world to fight and win against a technologically superior Western infidel. The jihadis expected the United States, like the Soviet Union, to be a clumsy opponent."

Not in their fondest dreams did they realize how clumsy...

... How then did we arrive at this day, with anti-American Islamist governments rising in the Mideast, bin Laden sneering at us, Qaeda lieutenants escaping from prison, Iran brazenly enriching uranium, and America as hated and mistrusted as it ever has been? The answer, in a word, is incompetence ... So catastrophic was Bush's decision to shift his attention and resources to Iraq, when bin Laden was panting at Tora Bora, that one is tempted to rank it with Adolf Hitler's decision to invade the Soviet Union in June 1941...

... bin Laden and Zawahiri have been fortunate in their enemies. Had the Bush administration been more competent, these two would have long since been bloody pulp, perhaps largely forgotten. Luckily for the rest of us, the Al Qaeda revolutionary program is so abhorrent that most of the world still has no choice but to stick with us, through thick and thin—and dumb and dumber. How long we can test the world’s patience is another matter. Alan Cullison’s 2004 article based on Zawahiri’s private thoughts is again instructive here. "Al Qaeda understood that its attacks would not lead to a quick collapse of the great powers,” he wrote. “Rather, its aim was to tempt the powers to strike back in a way that would create sympathy for the terrorists. ... One wonders if the United States is indeed playing the role written for it on the computer." What I wonder is, how many more years will we have to wait for Rumsfeld to figure that one out?

Hirsch led the 9/11 coverage for Newsweek. He takes this story seriously.

I'm not sure incompetence is the correct charge however. I think the problem is deeper. Bush is very competent at getting what he wants, but he's delusional. He gets what he wants, but it doesn't produce the results he expects.

We are led by the a faith-based delusional regime. It wouldn't be so bad if God seemed to favor them, but based on how things are going the evidence suggests God doesn't like GWB very much ...

Breakthrough in Crohn's disease?

Newspapers announce disease breakthroughs all the time, but this smells different ...

BBC NEWS | Health | Fresh theory on cause of Crohn's

...The UCL team also tested Crohn's patients' response to bacteria by injecting a harmless form of E. coli under their skin.

This resulted in a huge increase in blood flow to the inflamed area in healthy volunteers - but a much smaller increase in the Crohn's patients.

The researchers found this abnormally low blood flow could be corrected by treatment with Viagra.

The researchers believe that, because Crohn's patients have weakened immune systems, they are unable to destroy bacteria that penetrate the intestinal wall.

Thus the bacteria are left to build up in the tissue, stimulating the secretion of inflammatory chemicals that trigger the symptoms of Crohn's...

Wow. A new theory, some supporting evidence, a new therapeutic direction... This doesn't happen too often. Crohn's may be another of those mysterious diseases that were once thought to be infectious, then auto-immune, and are now again considered infectious.

Will ulcerative colitis turn out to have an utterly unrelated mechanism? And what does this do to one of my favorite research programs -- using worms to treat inflammatory bowel disease?

Keeping fingers crossed ...

Ugly people are the under class

The ugly are the natural underclass, often born to the homely and inclined to suffer ...

Economist's View: "I'm too ugly to get a job"

..Not only are physically unattractive teenagers likely to be stay-at-homes on prom night, they're also more likely to grow up to be criminals, say two economists... "We find that unattractive individuals commit more crime in comparison to average-looking ones, and very attractive individuals commit less crime in comparison to those who are average-looking," claim Naci Mocan of the University of Colorado and Erdal Tekin of Georgia State University...

-- comments --

.... Attractiveness in most species is a marker for overall fitness. The beautiful, on average, probably have better genes than homely folk like me. [jf: So do their parents, so they are also typically wealthier ...]

I remember well one summer watching a group of first year Harvard med students entering class. The ugliest among them was prettier than almost all of my McGill med school class. Clearly, physical beauty was a part of their selection process (probably filed under "leadership potential"). Why not?

On the other hand, if I were better looking I'd have been even worse behaved as a young man than I was. There's something to be said for having decidely average looks.

For a more interesting question -- what is the relationship between acne, the appearance of young females, and the probability of being raped? What is the adaptive advantage of female acne?

What can we do about this? If we're around in a hundred years maybe we'll be wise enough to sort this out -- or we'll have engineered homeliness out of the human species.

Michael Brown: more than a cartoon

Michael Brown, former head of FEMA, talks about what it's like to be mocked by a million strangers...

A Conversation With Michael Brown

...You're talking about your turf battles within the Department of Homeland Security. You think you should've left earlier.

Frankly, I should've given up. In hindsight, there were points where I knew I was losing the battle....

I searched my blog, it appears I never said anything about Michael Brown. I think I'll pat myself on the back. I had a hunch there was more going on than the initial media coverage. It's well worth reading for a sense of how suffocating and alienated Washington can be.

All Gore, I miss your reinventing government efforts.

Monbiot on a world without privacy

Monbiot writes for the Guardian. He's a reliably left-wing future-is-scary sort of guy. Mostly I think he's off-base or uninteresting, but I follow his blog postings because every month or two he is interesting and unique. This time he writes about implantable RFID chips and the gradual transformation of society:

George Monbiot: Children of the Machine:

... There will be no dramatic developments. We will not step out of our homes one morning to discover that the state, or our boss, or our insurance company, knows everything about us. But, if the muted response to the ID card is anything to go by, we will gradually submit, in the name of our own protection, to the demands of the machine. And it will not then require a tyrannical new government to deprive us of our freedom. Step by voluntary step, we will have given it up already.

I fought this back in the 1980s and early 1990s. I gave up; even before 9/11 it became clear that either people couldn't understand this topic or didn't really care. We live now in a world that would have shocked citizens of 1980s America, but the transition has mostly gone without remark.

Monbiot conflates loss of privacy with loss of freedom. David Brin (Surveillance society) has done a good job of showing that they're not necessarily identical. Privacy loss is necessary, but not sufficient, for a loss of freedom. Practically speaking, however, the falling cost of havoc and the a separate drive to protect economic interests means freedom will likely follow privacy.

Is there anything to do? Sure there is. There are better worlds. Will Americans take another path? No, we re-elected George Bush. Will Europeans? Seems not. Canadians? No. Maybe in New Zealand ...

The Blog of Death: R. Hunter Simpson

Blog of Death does obituaries for those of lesser fame. They do concentrate the mind.

The Blog of Death: R. Hunter Simpson

Humanitarian R. Hunter Simpson died on Dec. 31 of brain cancer. He was 18.

Simpson was the son of Brooks and Anne Simpson, and the grandson of corporate magnate W. Hunter Simpson and Dottie Simpson, who was certified by the Guinness World Records as the oldest woman to experience zero gravity. Although Hunter was born to wealth and privilege, he opted to live a simple and charitable life.

Simpson graduated last June from Bellevue High School in Bellevue, Wash., where he won the Brandy West Award, an honor given annually to a student who exemplifies character and leadership. While he participated in the wrestling and lacrosse teams, Simpson still found the time to prepare and give away hot meals for the homeless. During summers, he built homes for the poor in Tijuana, Mexico.

When he was diagnosed with brain cancer in 2005, The Make-a-Wish Foundation offered Simpson a final wish. Instead of choosing something for himself, however, he gave the wish to New Horizons Ministries, a nonprofit, interdenominational Christian ministry that serves Seattle's street youth. His wish provided the organization with furniture and clothing.

In the last months of his life, Simpson attended Trinity Western University in Langley, British Columbia. He saved up his meal-plan money by subsisting on two cups of soup a day. Last month, he used the remaining credits on the plan to purchase $900 worth of food from the school cafeteria -- which he then gave to homeless children in Seattle.

Gliomas are vile things.

Five stars worth knowing about

Astronomers have identified five stars that they feel are the best candidates for extra-terrestrial intelligence:

BBC NEWS | Science/Nature | Top stars picked in alien search

Beta CVn: a Sun-like star 26 light-years away in the constellation Canes Venatici (the hound dogs)

HD 10307: has almost the same mass, temperature and iron content of the Sun

HD 211 415: has about half the metal content of the Sun and is a bit cooler

18 Sco: a near match for the Sun in the constellation Scorpio

51 Pegasus: a Jupiter-like planet has been found here; may also host planets like Earth

I'm hoping someone will show them on a map of the galaxy soon. Twenty-six light years is awfully close.

IP addresses to run out in 2005 ... oops

When searching for an old post of mine on how to write emails, I came across a link to this 2003 BBC Technology article:

BBC NEWS | Technology | Tackling the net's numbers shortage:

BBC ClickOnline's Ian Hardy investigates what is going to happen when the number of net addresses - Internet Protocol numbers - runs out sometime in 2005.

Ahh. The perils of prediction...

PS. I uncovered yet another nasty Blogger bug this morning (BlogThis! behaves very badly when one switches from a blog that exposes the url field to one that hides it). Lord that service has problems. Google is mortal indeed.

Miscommunication made easy: email

I suspect there are numerous problems with this study of undergraduates, but it is amusing:

Wired News: The Secret Cause of Flame Wars

According to recent research published in the Journal of Personality and Social Psychology, I've only a 50-50 chance of ascertaining the tone of any e-mail message. The study also shows that people think they've correctly interpreted the tone of e-mails they receive 90 percent of the time.

... The researchers took 30 pairs of undergraduate students and gave each one a list of 20 statements about topics like campus food or the weather. Assuming either a serious or sarcastic tone, one member of each pair e-mailed the statements to his or her partner. The partners then guessed the intended tone and indicated how confident they were in their answers.

Those who sent the messages predicted that nearly 80 percent of the time their partners would correctly interpret the tone. In fact the recipients got it right just over 50 percent of the time.

On the one hand undergraduates are notorious about leaping to conclusions and one wonders how incented the writers were to do their job well. Sarcasm and irony are extremely hard to communicate.

On the other hand, I admit to having written many emails that were misconstrued. And those are only the ones I heard about. The researchers may be about right. Some general guidelines for corporate email:

1. Assume anything sent by email will be read by the entire world.
2. Don't do irony, don't do sarcasm. They're hard to do. Mark Twain was misunderstood.
3. Keep email short. As a rule if it's more than three paragraphs send a document attachment. (People read documents differently from email, in particular they often print them. Seems to help.)
   
4. You can try emoticons, but remember #2. Humor doesn't work well either!
5. If you ever pause for to wonder if your email is impolitic, it is probably lethal. Delete it at once and burn the hard drive.
6. If it takes too long to craft the email, phone instead.
7. Configure your email program so that mail is not sent immediately, but is instead queued for sending. There've been quite a few times I edited something I'd sent to that queue.
8. Assume your email will go to the wrong person and that they'll misinterpret it. This is commonplace with Outlook thanks to its braindead systems of at least 3 (4 I think) completely distinct and inconsistent methods for autocompleting email addresses.
   

I have more email "best practices" at work. I'm going to try and dig up my references and add them here.

Update 2/20/06:

Steve Robbins wrote an excellent article on 'email best practices' for the Harvard Business Review. The key takeways are very clear subject lines (revise them!) and being very careful about using the CC option. The person who should take action should be the primary subject, key interested parties the CC line. (If there's no action required, why the heck are you sending the email?). Prune the CC line on longer messages.

When in doubt use forwarding rather than CC. Never BCC unless it's to yourself.

Better decisions without the prefrontal cortex

Ok, I thought all this business about snap judgment decisions was nonsense. I regret to state that maybe I was wrong about that. This research study is seriously interesting:

BBC NEWS | Health | Sleep on it, decision-makers told

A Dutch study suggests complex decisions like buying a car can be better made when the unconscious mind is left to churn through the options.

This is because people can only focus on a limited amount of information, the study in the journal Science suggests.

The conscious brain should be reserved for simple choices like picking between towels and shampoos, the team said.

Psychologists from the University of Amsterdam in the Netherlands divided their participants into two groups and devised a series of experiments to test a theory on "deliberation without attention".

One group was given four minutes to pick a favourite car from a list having weighed up four attributes including fuel consumption and legroom.

The other group was given a series of puzzles to keep their conscious selves busy before making a decision.

The conscious thought group managed to pick the best car based on four aspects around 55% of the time, while the unconscious thought group only chose the right one 40% of the time.

But when the experiment was made more complex by bringing in 12 attributes to weigh up, the conscious thought group's success rate fell to around 23% as opposed to nearly 60% for the unconscious thought group. [jf: so they did better with more attributes? That sounds flaky.]

... the study found that people can think unconsciously and that for complex decisions unconscious thought is actually superior.

The team argued the problem with conscious thought is that the brain can only focus on a few things at the same time, which can lead to some aspects being given undue importance.

Lead researcher Dr Ap Dijksterhuis said: "The take-home message is that when you have to make a decision, the first step should be to get all the information necessary for the decision.

"Once you have the information, you have to decide, and this is best done with conscious thought for simple decisions, but left to unconscious thought - to 'sleep on it' - when the decision is complex."

Jonathan Schooler of the University of British Columbia in Vancouver told Science the study built on evidence that too much reflection could be detrimental in some situations.

"What may be really critical is to engage in [conscious] reflection but not make decision," he added.

Well, there are a few things that seem flaky. The success rate with 12 variables seems unnaturally high. Still this is not entirely implausible. The seat of the conscious mind is roughly the prefrontal cortex, and the human PF is a massive bio-hack with a kludged connection to the rest of the brain. In particular the PF has real problems with multi-variable analysis. On the other hand, the older brain solves these problems all the time (social dynamics, hunting, etc). So it might make sense that it could this well.

In retrospect, smart test takers use techniques consistent with this theory. We read the whole test and scan the hard problems, then go work the easy problems. When you get to the hard problems, the answers may have already come to mind.

I wonder if this goes some way to explaining why some children and adults with poor prefrontal cortex functions (low measured IQ, severe ADHD) may make surprisingly correct decisions given complex problems. If their unconscious reason is less impaired than their PF cortex ...