Monday, September 28, 2015

On the Right to Self Determination

In 2014 a Scottish independence vote lost 55%-45%. It probably seemed a little odd to most people that such a thing could happen in a stable, first world nation. However, yesterday the pro-independence parties of Catalonia won the majority of seats in their legislature. They have stated that they will move toward independence from Spain. However, the rhetoric holds no force, since the Spanish Supreme Court ruled that it would be illegal for Catalonia to secede from Spain. Yet, there it will be - nearly 8 million Catalonians have formally, if not legally, declared that they don't want to be part of Spain.
This is not ourt of the ordinary, actually. Abkhazia and South Ossetia don't want to be part of Georgia. Transnistria doesn't want to be part of Moldova. The Donbass doesn't want to be part of Ukraine. Chechnya doesn't want to be part of Russia.  The Kybelians don't want to be part of Algeria. The Sahrawians don't want to be part of Morroco. The Tamil do not want to be part of Sri Lanka. The Kurds don't want to be part of Turkey, Syria, Iraq and Iran. This is just the tip of the iceberg when it comes to separatist movements. We don't know much about them because the press won't give them oxygen. The Catalonia vote may change that.
Thirteen British North American colonies, in their declaration stated 'The history of the present King of Great Britain is a history of repeated injuries and usurpations, all having in direct object the establishment of an absolute Tyranny over these States.' Anyone who is familiar with the history will likely conclude that this was hyperbole in the support of what they wanted to do. However, in retrospect, the secession generally has been granted legitimacy.
It seems that a right to secession won't be viewed as legitimate without some justification. In other words, a people can't just decide one day, 'Hey, you guys are nice and all, but we really have decided that we want to be us, not a part of you.' I'm not sure why, but that seems to be universally frowned upon.  
We readily confess, however, that at some point subjugation of a region reaches a level of severity where secession is morally justified. However, there has been no formally stated set of criteria that delineates when that point is reached and we have ample evidence that the severity of usurpations is in the eyes of a, usually, not unbiased observer.
The secession of the Balkan states from a Serbian dominated Yugoslavia was generally assessed to be legitimate by the EUNA, but not by Russia. The secessation of Crimea was assessed as legitimate by Russa, but not by EUNA. In a just world, the criteria for legitimate secession would be clear, allowing for objective adjudication.  
I, for one, would be inclined to institute a relatively low hurdle. I have stated that, in my opinion, the first principle of Information Age political philosophy will be that no person should be required to live under a body of laws, programs and policies that they consider to be fundamentally unjust. That is not to say that political disagreement constitutes justification for secession. However, morality informs us as to what constitutes just laws and if we can't agree on basic moral questions, we can't very well craft a nation ruled by law that seems just to all. It assertion seems quite reasonable if, to many, impractical. If shown to be practical, I do not think there is will great resistance, at least in principle.
From a practical standpoint, I think that any region that can demonstrate that their will is consistently thwarted by the will of the national majority is in a strong position to say that their right to self-determination has been sufficiently abridged. I realize that this would probably allow much of the South to secede from the U.S. even today. However, I would argue that it is well justified.  
The South, in a majority, doesn't want abortion on demand, gay marriage, the current level of adjudicated separation of church and state, etc. The, in the main, believe in less Federal control of local affairs. In other words, they are, generally, not living under a body of laws, programs and policies that they consider to be morally correct. While they would not vote in favor of any of these, the majority of Americans do not live in the South and in its entirety, these laws have support. However, the notion that the people of New York and California, by virtue of their very large populations may impose their will upon the people of Alabama and Mississippi is sharp, to say the least. I am having this problem right now with the Ukraine. The Donbass was OK, if not thrilled, with being part of Ukraine until a government came to power that stated without equivocation that it intended to pursue EU membership. The ruling party has a history of disenfranchising the Russian language, the majority language of the Donbass. These are what is causing this violence in the Donbass, not Russia. The Donbass, by a rather wide margin, does not want to be in the EU, given the hostility that the EU has demonstrated in word and deed toward Russia. Kiev is attempting, through force, to enforce a continued sovereignty over the Donbass to do so.
The International community of nations has 'international law' that prohibits self-determination for the Donbass. Most countries have national laws that forbid secession (the USSR was an exception). So, it is claimed by the people of Brussels, Washington, or Kiev that Donbass secession (and Catalonian secession if it comes) is illegal. Isn't this properly an issue between and among the people of the Donbass? We can, improperly I think, get it all lost in issues of Russia-EUNA relations which may mean little or nothing to the people of Eastern Ukraine who are just looking for some right of self determination.
However, now the Catalonians will present the problem again without the International political intrigues. In other words, EUNA vs Russia is not going to cloud the issue. And the Catalonians will hardly be the last. This statement of Catalonian national identity will likely embolden the Kurds, for example, to their desire for an independent Kurdistan. Sooner or later, the community of nations with transcend the 'our friends can secede, but our enemy's friends cannot' approach and develop consistent, objective and fair criteria. Mostly, I hope that EUNA, Russia and China will develop a attitude of neutrality and allow local peoples to resolve local issues.  
When we draw a clear line between International law and the rights of a regional population, the world will become a kinder, gentler place.

Sunday, September 20, 2015

The Future of Prostate Cancer Treatment

On July 17, 2015 I was diagnosed with high risk but localized prostate cancer.  In the subsequent two months I have learned just about everything there is to know about the treatment and prognosis of prostate cancer  Prostate cancer is an adenocarcinoma which forms from mucous producing tissue.  It is a common form of cancer, in addition to the prostate, of the lungs, pancreas, colon, and others.  Consequently, though I am specifically studying prostate cancer, the advances in treatment will have importance over a broader range of cancers, among which are some of the most deadly.

We are probably closing in on very high 'cure' rates for many of the more stubborn cancers by utilizing multimodal approaches.  For example  the treatment that I have chosen begins with four to six months of multi-drug neoadjuvant treatment.  The three drugs I will be taking are Lupron, Cassodex and Metformin.  This will be followed by Intensity Modulated Radiation Therapy (IMRT).  This will take between 6 and 8 weeks.  Then we will use the same drugs for adjuvant treatment, except we will add a statin.

Here is the logic.  Lupron and Cassodex, in combination, lower available testosterone to nearly zero.  Prostate cancer needs testosterone to survive and grow.  Lupron stops the 90% to 95% of the testosterone made by the testicles and Cassodex interferes with the availability of the remaining 5% to 10%.  The result is that the prostate cancer cells have no access to testosterone.  

These drugs do not constitute a cure because over about three years, the cancer evolves into one that survives despite the absence of testosterone.  However, the two in the short term shrinks the tumor by as much as 50%.  This allows the largest radiation dose to be focused on a smaller volume.

Lupron, Metformin and, perhaps, a very low carbohydrate diet, weaken the cancer cells more than normal cells.  Consequently, after four to six months treatment radiation therapy is much more successful.  This may partially be due to prostate cancer's relative inability to metabolize ketone bodies.  Both Metformin and a ketogenic diet lower glucose availability which doesn't much affect normal cells but starves cancer cells.  

Lastly, both Lupron and Metformin through metabolic modifications of reactive oxygen species, make the cancer cells more susceptible to radiation damage.

After the radiation therapy the vast majority of cancer cells have died.  However, even a few escapes can eventually grow into a new, more resistant cancer.  So, after the radiation therapy, we want to make the body's environment as hostile to the cancer as possible.  This is done first with a continued testosterone starvation using Lupron and Cassodex.  Between the two 99% of testosterone is either turned off or unavailable to the cancer

However, we also want to continue with the combination of Metformin and a statin.  In one study, Metformin use reduced risk of disease specific mortality (DSM) by 24% for every six months of use.  Another study found that combining Metformin and statins result in a 40% reduction in DSM.

The key to this is that Casodex, Metformin and statins attack the cancer in different ways. While Metformin weakens the cancer cells to radiation in the neoadjuvant phase, it has a different role in the adjuvant phase.  There is a cellular mechanism called apoptosis by which a cell recognizes that it is not well and commits suicide.  Clearly, because cancer cells are not well, in order to survive apoptosis must be turned off.  Metformin appears to turn it back on again.

What this means is that the cells that are not susceptible to Casodex are susceptible to Metformin and may be susceptible to statins.  In addition to these three drugs, I will continue to use a ketogenic diet to control my diabetes.  Consequently, cancer cells that survive the radiation therapy will need to survive testosterone starvation, glucose starvation and an assault of apoptosis.  That is a really hostile environment for the cancer.

There is no literature on this four pronged approach.  I may be the first patient to try it.  Also, most of the research, especially on combined Casodex and Metformin, has been on patients with metastatic prostate cancer, where the objective is not a cure but to slow the march toward mortality.  Such a broad spectrum assault on just a handful of PCa 'escapes' may be unique.

A promising fifth assault is a vaccine Provenge which sensitizes the body's immune system to PCa cells.  It is approved for use when there is pathological evidence of metastasis and is not intended as a cure, but rather to extend life.  It does so, on average by four months and costs $100,000.  It is generally, therefore, not being used.  However, it is not being tested as a normal adjuvant treatment designed not to attack a massive body wide cancer but to eradicate any escaped cancer cells after radiation or radical prostatectomy.  There, because it does not work like the other adjuvant treatments, it may be the straw that breask the cancer's back.

Also, it may be overkill in my situation.  We are not even sure that there has been any escape and BCR is assessed in my case at 70% probability.  There is a 30% chance that none of this is necessary.  However, I'm not willing to bet with the odds not in my favor.

Lastly, on average BCR takes place 27 months after treatment and with just some of the adjuvant treatment, that is delayed to 36 months.  Then, on average, it takes about five years before there is clinical evidence of cancer.  That is if it happens.  About 65% percent of the time BCR is not followed by clinical evidence of cancer.  Once the first signs of cancer are found, on average it is 8 years to death.

What that means is that IF BCR happens for me and IF it leads to clinical evidence of cancer, my average life expectancy from the time of treatment is 36+60+96=192 months or 16 years.  There is a very good chance that during that 16 years new treatments will be developed that can extend that even further.

Metformin and statins are some of the most widely prescribed drugs, are very cheap and have benefits for most older men even if there is no benefit for prostate cancer.  I am fortunate that I have a oncologist who is willing to go with me on my rather novel preadjuvant and adjuvant therapy.  My belief is that if the radiation therapy can lower my PSA into normal ranges, the four barreled adjuvant therapy of Lupron (which is standard), Casodex, Metformin and statin will place me in the 75% of men who never develop clinical relapse.

If you find yourself confronted with a diagnosis of prostate cancer and about 15% of all men will, don't let your doctors lead down a conservative treatment road unless you have very low risk prostate cancer.  You have one shot at this.  If you have a radical prostectomy and your PSA doesn't drop to zero, they will likely recommend salvage radiation therapy, but the benefit, while measurable, is not wonderful.  If you go directly to radiation therapy as I am, don't allow them to skimp on neodjuvant or adjuvant therapy.  As I said, you have one shot at it.  If it doesn't work, your options decrease quickly.

Wednesday, September 9, 2015

The Study of Mathematically Precocious Youth and The Inappropriately Excluded

Yesterday I found myself in a kerfuffle over 'The Inappropriately Excluded' on Twitter.  Wow, arguing subtle points of cognitive theory and statistics in 140 character bites - that is insanely frustrating.  So, I'm moving over here to my personal blog where I am not limited and I will link back to the other combatants.

The difference of opinion was over whether is a strong refutation to the inappropriately excluded.  Let me say at the outset that every single scientific conclusion is made in the face of some contradictory evidence.  No theory should explain all the evidence because some of the evidence is wrong.  The research into IQ and careers by Robert Hauser is not completely consistent with my conclusions and I do not dismiss that.  It is possible that the exclusion is less dramatic and those who would want to argue that would quite properly use Hauser as an argument.

However, from the perspective of one of the inappropriately excluded the paper under question is a very poor refutation.  In defense of the paper, it really wasn't trying to make a point about very high IQ and commensurate career success.  Still, it is being used as such in my current argument.

The paper states that the children selected are one in 10,000 which implies a D15IQ of 156 which on the surface, if we also accept that their career performance at 38 is commensurate with their intelligence would be a powerful refutation.  However, to begin with, the calculation is incorrect.  The mean SAT score was 1325, which at the time was about 99%'ile and implies, if, IQ equivalent is meaningful, a mental age of about 23.  At age 13, this implies an R16IQ of 23/13=177 which equals a D15IQ of 156.  So, while the calculation is incorrect, on the surface, the conclusion appears correct.

However, that is probably a substantial overstatement of the mean IQ.  Per the Spearman model differential performance is caused by specific factors and a general factor (g).  The general factor explains about 50% of performance differences when applied to a specific performance item.  Now, as we are all aware, some people have a talent that causes them to perform in a specific area much better than their general performance.  That is clear here where the median SAT-M was 690, a truly extraordinary score for a 13 year old, and the median SAT-V was a more ordinary 545.

Among high scorers as a whole, SAT-V tends to be slightly higher than SAT-M, however, generally very close to each other.  a 145 point difference strongly suggests that something in addition to general intelligence is at work.  If we were to estimate IQ from the SAT-V it would imply a mental age of about 20 and a R16IQ of 154 or a D15IQ of 143.  So, in the absence of other problems, which I will discuss later, a more defensible conclusion would be that these young people have a mean IQ of 143 and, additionally, possess a significant talent in mathematics.

However, there are other problems.  If you were to give IQ tests to 100,000 people and select the top 100, you would have selected people with D15IQs over 146.  However, not really.  The reason is that people have good days and bad days and their tested IQ will vary based upon which they were having when they took the test.  Test makers give a margin of error of 4 or 5 points.  Well, when you do the above process, you are selecting high IQ people to be sure.  But you also are introducing a selection bias toward people who were having a good day and would probably not score as well if they took an IQ test again.  It is generally not significant, but when you are selecting one in 10,000 it does become significant and means that the computed IQ of 143 is probably high by 2 or 3 points.

There is a second selection bias.  The SAT is not an IQ test, however, during the time the test was administered, it had a correlation of about 80% with IQ.  So, one can think of the SAT as .8IQ+.2?.  In normal situations, that would probably not be significant.  However, in situations where you are selecting high SAT performers, you are also selecting high ? performers and, therefore, a conversion will tend to overstate IQ, again probably by 2 or 3 points.

Lastly, as all girls do not reach menarche at precisely the same age, not all children reach intellectual maturity at the age 16 that is assumed in calculating IQ tests.  Consequently, when you select high IQ children, you are differentially selecting early maturers.  That is important because their apparent intellectual superiority disappears when they mature early and by age 16 or 17 the other kids have caught up.  Again, in most circumstances this is not very important, but when you choose the very highest performers at age 13, you are, again, introducing a 2 or 3 point selection bias.

So, in total, this group of high SAT performers, if they had their IQs measured at age 38 would probably average between about 134 and 137.  However, because their math talent would cause them to max out their quantitative part scores, they may score as high as 140.  This places them at an IQ range where we would expect the exclusion to be moderate and a significant percentage of them would be expected to have solid careers commensurate with their IQs.

Leta Hollingworth placed an upper limit on the range of success at 155 R16IQor 144 D15IQ.  While that is the point where the exclusion reaches a relative 50%, I would set it higher, since about half of Nobelists have IQs higher than that.  So, we see that based upon the 'one in 10,000' statement, this group would appear to be outside Hollingworth's 'success sweet spot' (and mine as well), but based upon the likely actual IQ, they are comfortably within it.  And, with a pronounced talent, high performance especially in STEM is to be expected.

However, in truth, the performance of the group is not particularly impressive.  They achieved 107 graduate degrees out of 320, which, while good, is not impressive.  11% or 35 became tenured professors, but between them, they only published 60 papers by age 38.  Many individual academics manage that by themselves.  Arthur Jensen published over 400 peer reviewed papers, for example.  They are responsible, as a group, for 49 patents.  There are 37 currently active inventors who have individually created more than 500 patent families (a patent family is all the patents registered with regard to one invention).

To reiterate, there are always research data that are at odds with a conclusion.   Robert Hauser's research, while not eliminating the exclusion, is the most contradictory.  I don't place as much weight on his work as I would if he reported IQs above 133.  A few STEM luminaries have taken a few high IQ tests, notably the LAIT and Mega, and have done very well on them.  This, in addition to some theoretical considerations, explains why I have a caveat about Math and Physics in the article.

We need a comprehensive 150+ IQ study similar to the Minnesota Twin Study on the heritability of intelligence.  Without it, my conclusions, while well supported and generally consistent with a preponderance of the evidence, are not as strongly supported as I would like.

Yesterday's kerfuffle is a good example of how confirmation bias interferes with the thought processes of the highly intelligent.  Those who argued with me don't want the inappropriate exclusion to be true and they went out to find evidence that it wasn't.

Friday, September 4, 2015

Either I Am Insanely Brilliant or Steve Hsu is Wrong Again

Steve Hsu made the claim that if parents have a mean IQ of n, their children will have a mean IQ of .6n.  Ok, my children have a mean IQ of 2.5 sigma.  That means that their mother and I have a mean IQ of 4.2 sigma.  Their mother has an IQ of 1.8 sigma, so my IQ must be 6.6 sigma.  Of course, that would statistically make me the smartest person in the world.  I think that there may be a different explanation.

The answer is that regression to the mean isn't 40%.  In fact making that assumption leads to other curious conclusions.  The Terman subjects had a mean IQ of 3.25 sigma.  Their children had a mean IQ of 2 sigma.  So, from this we can calculate the mean IQ of the spouses.  It is 3.4 sigma.  In other words, despite the difficulty of finding spouses in the same intellectual range for people with IQs above 2 sigma, the Terman subject managed to find spouses that were even smarter than themselves.

Let's take a more reasonable assumption.  Suppose the Terman subjects managed to find spouses at 2.5 sigma.  That is high and, actually, not very likely.  Still, from this we can conclude that regression to the mean would be about 30%.  This would calculate my IQ at 4.65 sigma.  High but at least not outrageous.

What astonishes me is that we don't KNOW the answer to the regression to the mean.  It is not a hard piece of research.