Wednesday, March 17, 2004

BBC NEWS | Health | How vCJD proteins trigger disease - deeply weird

BBC NEWS | Health | How vCJD proteins trigger disease
Researchers had assumed this must only be possible if these proteins - prions - had some form of genetic content.

But US researchers have shown that they are made up solely of protein, and that new 'strains' result simply from prions twisting into new shapes...

It suggests that the ability of prions to misfold into new formations - or strains - accounts for their ability to trigger different diseases...

The researchers, from the University of California at San Francisco and Florida State University, believe that once a prion has folded into a new shape, it acts as template for others.

This produces a chain reaction that allows infection to spread.

This is much weirder than it sounds. Information processing actions, including replication and mutation, are occurring based on the ability of proteins to create multiple conformations ... the resulting "code" is then executed in the cellular interpreter. Prions are the spam of the body.

How do creationists think students will be able to understand ANYTHING without understanding how natural selection and emergent complexity works? Complex adaptive systems tend towards self-sustaining information processing cycles because natural selection drives towards persistent signals. Again, the ancient pattern of recursive complexity.

Where does it all end?

(PS. Yes, I know the above doesn't quite make sense, but trust me that there's something big here ...)

Tuesday, March 16, 2004

The Center for Public Integrity: Corruption in America

The Center for Public Integrity

I heard a Cleveland Club address from Charles Lewis via NPR today. Per the NPR blurg:
Investigative journalist and author, Charles Lewis, speaking recently at the City Club of Cleveland. Lewis is the founder and executive director of the Washington-based Center for Public Integrity, a non-profit, non-partisan watchdog group that tracks the links between monied interests and American elected leaders. His books include The Buying of the President 2000, and The Buying of the President 2004: Who's Really Bankrolling Bush and His Democratic Challengers--and What They Expect in Return.
The bit I heard was every bit as bad as I've long feared. The intense corruption is as expected, what surprises me is that Charles Lewis continues to struggle against this. There is far more idealism left out there than most of us would expect -- even in an era where people like Ralph Nader have trashed their reputation.

I will have to send them some money.

BBC Iraqi survey: it's good to have data, esp. positive data

BBC NEWS | Middle East | Survey finds hope in occupied Iraq
... of the 2,500 people questioned, 85% said the restoration of public security must be a major priority.

Opinion was split about who should be responsible, with an Iraqi government scoring highest.

Creating job opportunities was rated more likely to improve security effectively than hiring more police.

Seventy percent of people said that things were going well or quite well in their lives, while only 29% felt things were bad.

And 56% said that things were better now than they were before the war.

On a quick reading this BBC survey sounds like it might be better done than most surveys. It may actually say something useful. I don't think 70% of Americans feel things are going well or quite well in their lives, this fits with happiness research which emphasizes the effect of relativity. Prosperity is not as important to happiness as is exceeding expectations and feeling improvement. More than half thought their lives were getting better compared to before the start of the war (the sanctions period). Security was felt to be the responsibility of the Iraqi government.

This has to boost the morale of our soldiers.

Monday, March 15, 2004

Al Qaeda: retreat is an option for some

Following Attacks, Spain’s Governing Party Is Beaten: "26-year-old window frame maker, who identified himself only as David, said he had changed his vote from Popular Party to Socialist because of the bombings and the war in Iraq. 'Maybe the Socialists will get our troops out of Iraq, and Al Qaeda will forget about Spain, so we will be less frightened,' he said. 'A bit of us died in the train.'

The hope of this man is that al Qaeda will leave Spain alone if Spain appears to accede to its demands.

One problem is that one of al Qaeda's demands is for operating bases to attack their enemies. Since Spain is an ideal forward platform, al Qaeda won't be satisfied with retreat from Iraq, they will want an end to investigations and arrests. I doubt the new Spanish government will stop arresting al Qaeda operatives. On the other hand al Qaeda does have a lot to worry about right now, and they may now shift their focus from Spain.

Sunday, March 14, 2004

Complex adaptive systems spawn al Qaeda as an agent of progress?

United Press International: Commentary: Al-Qaida in Africa
... a new insurgency erupted in the west -- the Chad-based Darfar rebellion.

Khartoum hit back ruthlessly with scorched-earth tactics and ethnic cleansing. About 100,000 refugees made it across the border into Chad. Another 600,000 were without shelter and the United Nations and Doctors Without Borders said they were now faced with "the worst humanitarian crisis in the world." No TV footage, no story.

The only sub-Saharan country with a professional army up to Western standards is South Africa, which keeps 75,000 under arms. Forty percent of the force is HIV positive. And only 3,000 men are deployable for peacekeeping duties. Nigeria, Africa's most populous country with 130 million, maintains a 17,000-strong air force, but only one troop transport can fly.

West Africa is a graveyard of failed nation-states. Government writs seldom extend much beyond capital-city shantytowns. In the countryside, bush and savanna, radicalized Islamist clerics and Christian missionaries battle it out in a war of words for desperate African souls.

The Christian missions offer rudimentary medical services, T-shirts and occasional staples. The Muslim clerics get stipends from the Saudi Arabian Wahhabi clergy and train youngsters to become "jihadis," meaning "holy warriors." Hunger stalks most west and equatorial African states. And the Supreme Allied Commander, Gen. James Jones is alarmed. He is responsible for 93 countries, including all of Africa, except the Horn -- Ethiopia, Somalia and Djibouti. And in a recent trip in SACEUR's G-5, from Algeria to South Africa, Jones -- who speaks flawless, unaccented French -- saw first-hand the emerging failed and failing states that contain huge ungoverned areas that now serve as breeding grounds or sanctuary for terrorists.

The 27 "least developed countries" are all African, says the United Nations Development Program. Half of the 25 "worst countries in the world" are West African. The average Sierra Leonean doesn't live beyond 39. Nigeria, supposedly comparatively well off, pumping 2.1 million barrels of oil per day, is now on the verge of becoming a failed state. It is breaking apart along ethnic and religious fault lines. The Muslim north is terra incognita for federal authorities.

Rwandan and Ugandan forces have reinfiltrated the Democratic Republic of Congo. The DRC, formerly Zaire, is the size of the United States east of the Mississippi. Some 11,000 ineffectual U.N. peacekeeping troops are lost in the vastness of Africa's answer to "Darkness at Noon" that is costing the world body $90,000 per blue helmet per year. It is the United Nations' most expensive operation.

DRC is only a country on a map. Nineteenth-century tribalism has displaced the Western notion of a nation state. Gone are a modern highway system, a network of airports with daily air service between major cities, guest houses in national parks, plantations, water and sewage treatment plants -- in short, all the components of the former Belgian colony's infrastructure.

There are 11,000 U.N. troops in Sierra Leone, 15,000 in Liberia, 6,200 in the Ivory Coast, all stovepipe operations with separate commands for each of these mini-states, and 4,200 in Ethiopia and Eritrea. The nations that contribute troops to the United Nations for blue-helmet assignments are now tapped out. So are contributions to peacekeeping from dues-paying U.N. member nations. U.N. stabilization has become unsustainable. No sooner are these troops withdrawn from the civil war they went in to stop than the fighting starts again.

Sierra Leone, Liberia and (former French) Guinea are states in name only. Two generations of young Africans in these countries, from the ages of 10 to their early 20s, have known no other life than shooting and being shot at.

Flat-earth Muslim clerics are quick to exploit opportunities by inculcating their jihadi creed. Northern Nigeria, where the Sharia law of Islam has been imposed in large swaths of the province, armed Islamist thugs descend on a village with the marabou, a sort of religious enforcer and his noisy tintinnabula. Some of the larger towns have been occupied by jihadi militants who demand more volunteers -- and government authorities kindly oblige by staying out of their way.

There has been sufficient al-Qaida input in the thousands of square miles of unpoliced territory in both West and Equatorial Africa for French and U.S. intelligence to draw the conclusion terrorist networks are alive throughout the region. But there is also ample evidence that little of this is controlled by al-Qaida Central.

Osama Bin Laden and his associates haven't been using satellite and cell phones for the past two years. They know the National Security Agency can intercept mobile phone signals in a nano-second and flash global positioning system information back to Special Forces looking for them in the mountain ranges that straddle Pakistan and Afghanistan.

Al-Qaida cells operate autonomously with sleeper agents among Muslim communities in most western, eastern and African countries. Bin Laden's capture -- dead or alive -- won't change the correlation of forces between terrorists and counter-terrorists. The growing wretchedness of West Africa's populations -- over a million a year die of malaria in Nigeria alone -- greatly facilitates the marabou's mission of recruiting Islamist desperadoes.

The toughest among them survive the desert trek to Morocco and Algeria and from there take small craft to Spain. Their bodies wash up on Spanish beaches every day. Those who make it alive into Spain have also made it into the European Union.

This is an astounding cry of warning. An anonymous UPI scribe calls out to the empty dark. Well written.

I've written earlier about "emergent intelligence"-- a fundamental property of complex adaptives systems -- such as humanity.

Perhaps we can think of al Qaeda, the avowed enemy of modernity, as the mechanism by which a complex adaptive system maintains itself. We rich nations can, and have, ignored the misery and poverty of much of the world. Now, however, that misery is a threat to our lives and wealth, and the lives and wealth of our children.

We are now forced to pay attention -- not by virtue of any nobility of character, but rather from the far more reliable incentive of base survival. The attention of the Pentagon, and belatedly of the fools of the Bush regime, now turns to Africa. Complex adaptive systems, as in the ecosystems that drive evolution, are not kind or compassionate. They merely perpetuate themselves by virtue of that famous pseudo-tautology: them that do not perpetuate do not long exist. In this case, they spawn a foul spot of evil -- al Qaeda. The system cares not a whit, but we will be forced to act.

As I wrote 3 years ago, al Qaeda may yet be a gift to humanity.

Saturday, March 13, 2004

Better brains born on choline (this is your brain on drugs ..)

Science Blog - Prenatal choline supplements make baby's brain cells bigger, faster
From Duke University:

Prenatal Choline Supplements Make Brain Cells Larger, Faster

The important nutrient choline "super-charged" the brains of animals that received supplements in utero, making their cells larger and faster at firing electrical "signals" that release memory-forming chemicals, according to a new study.

These marked brain changes could explain earlier behavioral studies in which choline improved learning and memory in animals, say the researchers from the departments of pharmacology and psychiatry at Duke University Medical Center and from the Durham VA Medical Center.

The implications for humans are profound, said the researchers, because the collective data on choline suggests that simply augmenting the diets of pregnant women with this one nutrient could affect their children's lifelong learning and memory. In theory, choline could boost cognitive function, diminish age-related memory decline, and reduce the brain's vulnerability toxic insults.

The Duke group is part of a national team of scientists who are exploring the benefits of prenatal choline supplementation on learning and memory. This ongoing research has been instrumental in the Institute of Medicine's decision to elevate choline to the status of an essential nutrient for humans -- particularly pregnant and nursing women, the scientists said.

Results of their study, led by Qiang Li, M.D., of Duke and the Durham VAMC, will be published in the April issue of Journal of Neurophysiology.

"Previous studies at Duke have shown that choline-supplemented animals are smarter and have a greater learning capacity, but we hadn't known until now whether the cells that make up memory-relevant brain circuits are changed by choline" said Li. "Choline didn't just change the general environment of the brain, it changed the fundamental building blocks of brain circuits -- the cells themselves."

Choline is a naturally occurring nutrient found in egg yolks, milk, nuts, fish, liver and other meats as well as in human breast milk. It is the essential building block for a memory-forming brain chemical called acetylcholine, and it plays a vital role in the formation of cell membranes throughout the body.

In the current study, the researchers explored the effects of choline on neurons in the hippocampus, a brain region that is critical for learning and memory. They fed pregnant rats extra amounts of choline during a brief but critical window of pregnancy, then studied how their hippocampal neurons differed from those of control rats.

The researchers found that hippocampal neurons were larger, and they possessed more tentacle-like "dendrites" that reach out and receive signals from neighboring neurons.

"Having more dendrites means that a neuron has more surface area to receive incoming signals," said Scott Swartzwelder, Ph.D., senior author of the study and a neuropsychologist at Duke and the Durham VA Medical Center. "This could make it easier to push the neuron to the threshold for firing its signal to another neuron." When a neuron fires a signal, it releases brain chemicals called "neurotransmitters" that trigger neighboring neurons to react. As neurons successively fire, one to the next, they create a neural circuit that can process new information, he said.

Not only were neurons structured with more dendrites, they also "fired" electrical signals more rapidly and sustained their firing for longer periods of time, the study showed. The neurons also rebounded more easily from their resting phase in between firing signals. These findings complement a previous study by this group showing that neurons from supplemented animals were less susceptible to insults from toxic drugs that are known to kill neurons.

Collectively, these behaviors should heighten the neurons' capacity to accept, transmit and integrate incoming information, said Swartzwelder.

"We've seen before that the brains of choline-supplemented rats have a greater plasticity -- or an ability to change and react to stimuli more readily than normal rats -- and now we are beginning to understand why," he said...

"Overall, we found that neurons in choline-exposed rats were more excitable, more robust in their physiologic response," said Wilkie Wilson, Ph.D., a Duke pharmacologist and member of the team at the Durham VAMC. "We've demonstrated a measurable change in brain cells prompted by moderate amounts of choline given during a narrow window of prenatal development."

Biochemical studies on the brain effects of choline at the University of North Carolina at Chapel Hill and Boston University have complemented the Duke findings, Wilson said.

Steven Zeisel, M.D.,at the University of North Carolina at Chapel Hill, has demonstrated that choline alters a gene called CDKN-3 by adding a "methyl group" of atoms to the gene. The methyl group switches off the gene and, in doing so, uninhibits the cell division process in the memory centers of the brain.

Tiffany Mellott and Jan Krzysztof Blusztajn, Ph.D., at Boston University -- in collaboration with Christina Williams, Ph.D., and Warren Meck, Ph.D., at Duke, -- recently found that two hippocampal proteins known to participate in learning and memory, called MAPK and CREB, are activated to a greater extent in the animals prenatally supplemented with choline. These studies provide biochemical correlates to the new data reported by the Swartzwelder group.

More fascinating and disturbing information from the neuroscience world. One near term implication may be a focus on maternal vitamins and nutritional supplement in low income groups and low income nations. There are usually unforseen consequences though. Since schizophrenia seems to be associated at some stage in its evolution with excessive and inappropriate neuronal interconnections, would choline supplementation predispose to schizophrenia in vulnerable groups?

It's a long way from rats to humans.

The story of the Bush drug benefit package -- standard operating procedure

KR Washington Bureau
The Bush drug benefits bill is quite an interesting tale. This is one take on it.

Friday, March 12, 2004

Structural causes of healthcare inflation


The cost of healthcare is rising much faster than general inflation. In the US a chunk of that is the collapse of managed care. There are fundamental structural causes however; aging population, new technology, etc.

Today I ran into a structural example I'd not thought of for a while. My son needed an antibiotic for a strep throat and co-occurring ear infection. Ten years ago that would have cost about $10. Instead today it's $120. A tenfold cost increase, because of antimicrobial resistance.

We expect antimicrobial resistance to worsen. Eventually many old favorites, such as augmentin, will bite the dust. Their replacements will cost even more.

Will a strep infection eventually cost $1000 to treat with antibiotics? Talk about health care inflation ...

Productivity and Demographics: Was the boom from the boomers?


In the past decade we've had nice year on year productivity increases. Productivity increases grow the pie -- they're generally a good thing. I'm hoping much of it comes from the application of IT, globalization, etc.

I wonder about demographics though. Over past 10 years the number of workers between the ages of 32 and 47 must have peaked, following the boomer's age path. Now the oldest boomers are almost 60. For knowledge workers productivity probably peaks, for most people, between the ages of 36 and 50. As we boomers move out of that range, will productivity decline?

Unintended consequences: DVRs & the death of broadcast tv, HDTV and massive hard drives

Mercury News | 03/10/2004 | Hitachi unveils massive drive for digital media
Digital media hogs can celebrate.

A new, whopping 400-gigabyte hard drive from Hitachi Global Storage Technologies can store up to 400 hours of standard television programming, 45 hours of high-definition programming or more than 6,500 hours of digital music...

San Jose-based Hitachi said it designed the monster drive, the Deskstar 7K400, for audio/video products such as digital video recorders.

So many fascinating aspects it's hard to figure where to start. Quickly:

1. The storage industry has moved to Hitachi and Toshiba. Quite a shift from a few years ago. I think the movement of mass storage from dedicated computers to consumer devices has transformed that industry. The iPod and the DVR are the leading edge. Massive hard drives in cellphones, video cameras and still cameras are obvious additions, but where else will they appear. Ten years ago we thought ubiquitious networking would make hard drives less important -- but we were way wrong. Weird. I remember when CDs first came out, and Bill Gates had his name an a MASSIVE tome about the glorious age of cheaply replicated mass read-only devices. I wrote a letter to a Canadian aid agency waxing enthusiastic about the potential of cheaply distributing educational and reference materials via CD. Then came Gopher came along and that "fork in history" was forgotten with some embarrassment. (Yes, Gopher came before the web -- and it alone demoted the CD as a reference source.)

Now storage is back, as limits to network traffic have become apparent. The world now seems to be converging on a combination of local storage, network traffic, and the critical new world of local caching of massive amounts of data.

Very neat.

2. We thought HDTV would drive the creation of cheap hi resolution display technology. It will, but the conjunction of HDTV and DVRs is driving the creation of massive storage. Unexpected.

3. DVRs, even though they are used by relatively few people, have destroyed broadcast tv. We watched the Simpsons the other day, for the first time in 10 years (we don't watch much tv). The density of commercials was stunning for one unaccustomed to commercial tv. It was unwatchable without a DVR to zip past the commercials. DVRs make standard commercials less effective, also mortal. The natural reaction of a dying industry is to redouble their efforts. But that makes tv less watchable, so it accelerates the move to DVRs (and cable). End result -- an accelerated technology transition. This feedback phenomenon also hit with pay phones and mobile phones. As mobile phone use grew pay phones became worth less and were less reliable and less available. That meant one could not rely on a pay phone, so one needed a cell phone. Feedback is interesting.

Tuesday, March 09, 2004

The Endocannabanoids - medicine does move on

Entrez-PubMed
After the discovery, in the early 1990s, of specific G-protein-coupled receptors for marijuana's psychoactive principle Delta(9)-tetrahydrocannabinol, the cannabinoid receptors, and of their endogenous agonists, the endocannabinoids, a decade of investigations has greatly enlarged our understanding of this altogether new signalling system.

I finished medical school in 1986, so my core medical sciences ended in 1983, about 21 years ago. The endocannabanoids, endogenous (natural) agents that act on the same neuro receptors as cannabis, feel like the most dramatic new discovery since that time. Researchers long suspected that, just as we have endogneous opioids, we must have endogenous cannabinoids. It just took a while to find them.

True, we did sequence the genome -- and that's been amazing. But, oddly enough, it felt like a continuation of what we new or guessed in the early 80s. New physiology feels more "real" and proximal to a physician. For example, I went to this research article because of hype about an endocannabinoid derived medication that allegedly helps with weight loss and smoking cessation. Talk about near term impact.

This feels new, and exceptionally interesting. I know nothing at all of the basic science, but I'll be looking for a "popular" (eg. physician oriented review) in JAMA or NEJM.

This probably also provides some insight as to why cannabis sativa manufactures its namesake product in the first place.

MSNBC - Avoiding attacking suspected terrorist mastermind

MSNBC - Avoiding attacking suspected terrorist mastermind
In June 2002, U.S. officials say intelligence had revealed that Zarqawi and members of al-Qaida had set up a weapons lab at Kirma, in northern Iraq, producing deadly ricin and cyanide.

The Pentagon quickly drafted plans to attack the camp with cruise missiles and airstrikes and sent it to the White House, where, according to U.S. government sources, the plan was debated to death in the National Security Council...

Four months later, intelligence showed Zarqawi was planning to use ricin in terrorist attacks in Europe.

The Pentagon drew up a second strike plan, and the White House again killed it.  By then the administration had set its course for war with Iraq...

In January 2003, the threat turned real. Police in London arrested six terror suspects and discovered a ricin lab connected to the camp in Iraq.

The Pentagon drew up still another attack plan, and for the third time, the National Security Council killed it.

Military officials insist their case for attacking Zarqawi’s operation was airtight, but the administration feared destroying the terrorist camp in Iraq could undercut its case for war against Saddam.

If Bush loses the next election the truth may come out; this will be one of the cases to investigate.

Monday, March 08, 2004

Wahhabism and the Saudi Front (NYT Magazine)

Intruders in the House of Saud, Part I: The Jihadi Who Kept Asking Why
Long NYT Magazine article -- Saudi Arabia and Pakistan are the next "front" in the Forever War.

Betting against Bush's America ... Buffet's move.

NYT: Weak Dollar Gains Notice of Buffett
Warren E. Buffett, the billionaire investor, has a $12 billion bet against the United States. Mr. Buffett said over the weekend in an annual letter to shareholders of Berkshire Hathaway Inc., his holding company, that he began investing in foreign currency for the first time in 2002 and expanded his positions in 2003.

By the end of 2003, Berkshire Hathaway held foreign-exchange contracts valued at $12 billion that were spread among five unspecified currencies, he said in the letter, which was released on his company's Web site.

He said Berkshire also owned $1 billion of euro-denominated junk bonds. Mr. Buffett, who still has the bulk of his assets in the United States, bought into the foreign currency as the United States trade deficit swelled and enjoyed large investment gains as the dollar continued to weaken. 'As an American, I hope there is a benign ending to this problem,' Mr. Buffett wrote, referring to the trade deficit and the weaker dollar. He said, however, that the impact could reach 'well beyond currency markets.'

One Berkshire shareholder said the move was an about-face for Mr. Buffett.

'I've attended the annual meeting for well over the past 15 years, and every year until this year when asked about the dollar or foreign currency, Berkshire's basically said, 'You don't make money betting against the United States of America,' said Tom Russo, a partner at Gardner, Russo & Gardner, which owns about 1,000 Berkshire shares. 'Something must have really scared him.'

And so it begins. Seriously, about 1-2 years ago, looking at the Bush budgets, I looked for an easy way for a small investor to bet against the Bush budget. I didn't have the time or expertise to devise a strategy. Buffett is less constrained.

Sunday, March 07, 2004

Evolution in action: why Theocons need to teach natural selection in the schools

Wapo: Dueling Viruses Are Latest Computer Pest (TechNews.com)
The programmers behind the ongoing wave of computer worms and viruses hitting the Internet are starting to take aim at each other, and consumers and businesses around the world are getting caught in the crossfire, security experts said yesterday.

In the space of about three hours early Wednesday morning, five new variants of widespread bugs MyDoom, Bagle and Netsky were spotted roaming the Web...

... Ken Dunham, director of malicious code at Reston-based iDefense, said the authors of Bagle and MyDoom appear, in essence, to be wrestling for remote control over compromised computers, while the Netsky worm attempts to deactivate the other two.

... "We are seeing just variation after variation after variation," said Steven Sundermeier, vice president of products and services at Central Command Inc., a Medina, Ohio-based antivirus company.

If the theocons are able to remove natural selection from our science curriculum, how will students understand the evolution of their spam?

Viruses and worms have one of four agendas:

1. economic and military disruption (allegedly used by US forces prior to GW I and possibley GW II).
2. terrorism (no clear examples known)
3. an unusually ineffective form of display competition between teenage boys
4. seizing control of computing resources (increasingly important).

Natural selection has only a limited role in understanding #1 and #2. In #3, and especially #4, it has a strong role. Theory predicts that computer worm/viruses should increasingly protect the host computer by limiting harm to it while simultaneously fighting off rival code. In time worm/viruses should emerge that are effective antiviral agents while simultaneously causing minimal harm to the host, indeed in time they should theoretically improve performance of the host. (example: more efficient code for particular functions inserted by the virus).

On wonders if this is partly how early multicellular immune systems developed. Were the first immune systems in bacteria constructed by competing viruses?