Monday, August 24, 2015

China Down Another 5.5%

Shanghai is down 5.5% and dropping. This AM in US markets we saw an almost 1100 point drop. It was like watching the White Ford on the LA Freeway. Deer in the headlights.

Tuesday will be another round, possibly not as bad. We are going from a "Correction" to a massive down turn. And where are our glorious leaders? On the golf course, of course.

The key question is a two part question; (i) our exports are low as compared to imports so who cares, and if China drops values we get cheaper imports, (ii) what about the debt on the fracking companies now that oil is in the tank? The China issue may be secondary to another financial collapse hidden in low cost but un-payable debt, close to a trillion.

I guess that pipeline can wait?
But then again for China look at the past ten years. They collapsed in 2008-2009 but what we see is really a bubble bursting. So we are still on good growth if we take out the bubble. So possibly China is not a problem. Debt is however.

More on Windows 10 and Bluetooth

Drivers can be the bane of any user. When I first did an OS some 40+ years ago the interfaces to external devices were through various drivers. Nothing much has changed.

Except there seems to be a mass of defective Bluetooth devices, due it appears to drivers.

An interesting tale can be put together by Googling w10 and Bluetooth. One of the better one is on SuperSite.

Could you imagine what may have happened if one were inclined to update from W7 to W10 and now you have dozens of dead drivers!

Welcome to Microsoft! Thanks to Google!

A Current Mindset: Terrifying

It is always interesting to read comments on the Web, especially those in prominent sites. In a Science article discussing President Carter's illness a commentator writes:

You are wrong. The meaning of existence of private/public company/corporation is to serve critical needs of society at large and that's why it is allowed by the society to make reasonable, limited, profits for future investments and not for opulent spending. If company cease to serve the public interest is must be dismantled. And because of that monopolistic Big Pharma must be dismantled for the good of patients. But those principles have been corrupted and now so-called US company serves their management and also foreign oligarch ownership, not public.

The English is atrocious but the thought is terrifying. This goes beyond socialism, communism, into some communitarian extreme. 

What drive this person to write in such a highly regarded journal. Well it was this paragraph:

Still, researchers have a lot to learn about pembrolizumab and other PD-1 therapies in development. Keytruda is also extremely expensive, at about $150,000 a year. In clinical trials, PD-1 blockers generally work in less than half the participants. Research published earlier this year suggested PD-1 inhibitors may work best on tumors with lots of mutations, and a small clinical trial of pembrolizumab backed this up.  It found that people with advanced cancer were far more likely to respond if they had so-called mismatch repair mutations in their tumors. This could also help explain why, so far, PD-1 inhibitors have produced the best outcomes in people with lung cancer and melanoma—both are often mutation-heavy tumors.

 PD-1 inhibitors are the next step in immune therapy with MABs. There has been decades of R&D and hundreds of billions spent, not to mention trials which have exposed many patients to false hopes. But as we have written before this is now one of several paths to treaing cancers.

But that is no excuse for the vitriolic comments by some of these readers. This same commenter states:

There is some other aspect of it however. President J. Carter recently stated that US is run by Oligarchic cabal and that democracy is no more. An that includes Big Pharma that grows like a cancer within the bodies of cancer patients and that's the problem in America. The Big Pharma is offering nothing but more pain, suffering, household financial collapse and plenty of false hopes. Mr. President I suggests you look seriously into massive, up to million mg intravenously a day dose of ascorbic acid aka Vitamin C in appropriate form, that has shown good results in clinical therapy but is dismissed by Big Pharma brainwashed medical professionals.

Perhaps this individual is some hidden genius we have just missed as a society. Perhaps not!

Sunday, August 23, 2015

China Down 7.5% at the Start

There seems to be a total collapse in China. This was not fully expected but the ripples will be significant. Remember the China Sovereign Fund holds several trillion US Debt. This will be a very very bumpy week!

Why Windows 10 is Like a California Ham Sandwich

Now a few years ago I wrote about my saga of getting a ham on rye sandwich in California. Some how in California no one listens to the customers, they all want to add something. I noticed Panera also acts that way but not as bad as California. You ask for a "ham on rye" and they ask if you want sprouts or onions, peppers or tomatoes, "you want chips or fries".

All I wanted was ham on rye! I then did the Jack Nicholson thing; hold the tomatoes, hold the peppers, hold the fries!

Then I found someone who had experience. He said; "You from New York?" "Yeah!" then he said: "Two pieces of rye with ham in between, nothing else, yeas!" I answered, "got it!"

Now W10 is like a California sandwich. Instead of getting the computer you get their graphics, their placements, their way of doing things which when you try do not work.

Why not try like  ham on rye. Let me decide what to add, lay out the condiments. Don't force me to figure out how to scrape off the avocado stuff, I hate avocados. I also hate mayonnaise on ham! I like mustard and I want to put on my own amount!

So W10 comes as Seattle would like you to consume it. I guess that is also why I hate Starbucks. Try and get a small regular black coffee!

Saturday, August 22, 2015

Making Windows 10 Look Like XP

Microsoft is not very user friendly. Really not friendly. Well welcome to Windows 10. Just got a pad to use and it comes with 10. Now Dell makes a fantastic product. Then on to W10.

First thing I do is get rid of all the junk that some marketing guru, a true oxymoron for Microsoft, wants me to have. Change screen to classic blue and layout the files folders like my other 7 machines. That way no visual dissonance.

Then go to start and get rid of all the junk. Tons of junk, none of which I will ever use!

Then make a Recovery stub. No wait, it seems that no one has been able to do this yet. You have to Google this since Microsoft tells you they have too many questions and yours is not important.

But, there is a back door, a Windows 7 restore to a 1TB disk. Got that done.

Then try and get Bluetooth working! It connects, then drops, and then, well I have no idea what then. To see how bad Microsoft is one need look no further than the "Support" pages. The Company in my opinion must really despise its customers. The poor customer had the same issues I did. Now bluetooth is really simple. I have it in my car, my GPS, dozens of other computers. But for Microsoft, taking a simple need and turning it into massive neuro surgery in the dark is common place!

Then there is your WiFi. For various reasons it drops you, sending you to Airplane mode. This happens randomly.

Yes, it can be made to look and almost act like XP. But given a clean install and the mess so far I could see no rational human upgrading from W7 to W10! Why upgrade to a system which the users have not shaken down yet. Yes, that is Microsoft. Thank God Google still works, but I suspect they will also soon be going the way of Seattle. Pity.

Friday, August 21, 2015

Obesity and Genes; Redux

There seems to be a continuing search for the genes which "cause" obesity. To reiterate, independent of any gene;

Input - Output = Net Accumulation

Thus eat too much means you get fat. Of course the problem with the above is; how does one measure input and output. The classic manner is in food and Kcal. Thus:

3500 Kcal = 1 pound

That is for every 3500 Kcal one consumes above a Basal Metabolism burn rate one gains a pound.

However not all food is equal and not all people burn calories at the same rate. Thus perhaps there is a genetic factor on burn rates. That does not negate the above argument.

Into this fray is a new article in NEJM. They state:

Our results point to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-obesity effects.

 This is 3 genes and a single SNV. But we must always ask; what is the cause? Again it appears that with these genes fat cells burn at a lower rate. Thus if a normal person, whatever that means, can deal with 1800 Kcal per day and not gain weight then a gene encumbered person may only burn 1200 Kcal per day and eating the same amount will thus gain weight. So eat less! The cause of obesity is consumption. If one has a lower set point then eat less.

Now in the MIT write up of this article the authors state:

But there may now be a new approach to prevent and even cure obesity, thanks to a study led by researchers at MIT and Harvard Medical School and published today in the New England Journal of Medicine. By analyzing the cellular circuitry underlying the strongest genetic association with obesity, the researchers have unveiled a new pathway that controls human metabolism by prompting our adipocytes, or fat cells, to store fat or burn it away. “Obesity has traditionally been seen as the result of an imbalance between the amount of food we eat and how much we exercise, but this view ignores the contribution of genetics to each individual’s metabolism,” says senior author Manolis Kellis, a professor of computer science and a member of MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) and of the Broad Institute.

 Well frankly the CSAIL reference is wrong. It does not relate to exercise bu cell burn rates. We always knew that. We further know that some people's cells burn at different rates and that obese people burn at a lower rate. The classic case is the Southwest Indian Tribes who most likely after generations have adapted to low caloric input due to the nature of their environment and thus have a lower conserving burn rate. We see this in many immigrants from countries where food was no readily available. The Irish and many Hispanics have a similar characteristic. (Also some early epigenetic studies demonstrated inheritable traits from WW II starvation in the Low Countries).They can maintain lower weight by not eating our high calorie foods. Don't blame the genes, in fact the genes have adapted to the harsh limited food environment which may be beneficial.

The NEJM article concludes:

Last, we found that direct manipulation of the ARID5B–rs1421085–IRX3/IRX5 regulatory axis in primary cell cultures of adipocytes from patients reversed the signatures of obesity. This indicates that in addition to changes in physical activity and nutrition, manipulation of mitochondrial thermogenesis offers a potential third pathway for shifting between energy storage and expenditure in a brain-independent and tissue-autonomous way in humans. In summary, our work elucidates a mechanistic basis for the strongest genetic association with obesity. Our results indicate that the SNV rs1421085 underlies the genetic association between the FTO locus and obesity. The SNV disrupts an evolutionarily conserved motif for the ARID5B repressor, which leads to loss of binding, derepression of a potent preadipocyte superenhancer, and activation of downstream targets IRX3 and IRX5 during early differentiation of mesenchymal progenitors into adipocyte subtypes. This results in a cell-autonomous shift from white adipocyte browning to lipid-storage gene expression programs and to repression of basal mitochondrial respiration, a decrease in thermogenesis in response to stimulus, and an increase in adipocyte size. Manipulation of the uncovered pathway, including knockdown or overexpression of the upstream regulator ARID5B, genome editing of the predicted causal variant rs1421085, and knockdown or overexpression of target genes IRX3 and IRX5, had a significant effect on obesity phenotypes.

Now the last things we need is a new medication to control genetic pathways when the answer is just lower food consumption. That is free!

As an aside I found that the paper relied on murine samples. In addition they state:

To translate the results of genomewide association studies into mechanistic insights, we combined public resources (epigenomic annotations, chromosome conformation, and regulatory motif conservation), targeted experiments for risk and nonrisk haplotypes (enhancer tiling, gene expression, and cellular profiling), and directed perturbations in human primary cells and mouse models (regulator–target knockdown and overexpression and CRISPR–Cas9 genome editing). 

 Let's just hope we don't do CRISPR Cas9 editing on humans for obesity! Just a concern.

Oh and by the way, there is a very effective tool already in use. It is called the Scale. Cheap, lots of them around, and it provides a set point feedback loop. You get on it once a day and if it gets higher you stop eating, if it gets too low, then see a Doc!

And yes, one last thing, the MIT Stata Center where CSAIL is located has a "food court" I used to frequent, albeit carefully. The food there is carb rich, and more than likely will be the cause of later obesity issues. So one must always examine their own sand box, and not blame the genes for everything!

Thursday, August 20, 2015

Iran, the French Revolution and Manchuria

In 1967 Noam Chomsky wrote a piece for Liberation entitled On the Backgrounds of the Pacific War.  This was what would become classic Chomsky. In my opinion is is excellent Sophistry, having a conclusion and fitting the facts to support the conclusion. Lawyers do it all the time and even some historians do so. Simply stated Chomsky rewrote his view of Japan' taking of China as driven by US Foreign Policy and then went on to link it to Viet Nam. It was my first time reading a powerful piece on the Viet Nam War. It too me almost 30 years to come back and understand it, and fifty years almost to counter it. I was then a strong supporter of Chomsky, even seeing his way as the only way. It took those 50 years of seeing the world up close to understand it.

Then there is the Kennan Telegram. Kennan saw Russia up close, as a diplomat. It would take me to the late 70s to see the Soviets up close in treaty negotiations and then from the mid 90s to mod 2000s to have them as business partners. The one thing I saw even in the 70s was that we and the Russians at core have the same values, our children. I recall talking with some Russians and we went to our children, we both wanted them to see a future, we both saw nuclear weapons as devastating. The RISOP scenarios I recalled lead to the elimination of not only humanity but nature. Kennan saw a middle way, that of delimiting Soviet reach, containment.

Now on the one hand we have the Chomsky view of seeing the US as the source of all international upheaval and the Kennan view of Soviet imperialism, a view which the US had to deal with, and was not the cause.

Now we have Iran, Persia to those of us who have long memories. Persia has for almost 3000 years tried to gain territory to the West, Xerxes, Darius, and the list goes on. Today they are not as strong, except through the power of a nuclear weapon. Do it leaders share the love of their children that we and the Russians do? That may be the only question worth asking. Nuclear weapons are not sending a plane into the World Trade Center. A nuclear event is devastating.

Now along comes some "expert" in The Syndicate to tells us what we should believe. He states:

Forget the French Revolution as a model: the so-called Thermidorian Reaction, when moderates ended Robespierre’s Reign of Terror, was an exception to the pattern of modern revolutions. The typical pattern during our living memory is that the hardliners come after the moderates. In the Soviet Union, for example, it was hardliners after World War II who strove to export Marxist-Leninist revolution, condemning the world to decades of cold war.

Somehow Revolutions are not all the same. Many have studied the French Revolution and the rise of a Robespierre is a complex issue. The generalization the author makes in my opinion is totally without merit.
The author continues:
Worse was to follow for those hoping for better US-Iran relations. First, there was Bush’s “axis of evil” speech in 2002. Then, in February 2005, just as the hardline Ahmadinejad was about to begin his first term as president, Bush formally rejected a nuclear deal that had been painstakingly negotiated by Rouhani (then Khamenei’s representative in Iran’s Supreme National Security Council) and signed in late 2004 by France, Germany, and Britain. As Iran scanned the strategic horizon, it seemed obvious that the US had invaded Iraq because Saddam did not have any weapons of mass destruction. This made Ahmadinejad’s insistence on Iran’s nuclear “rights” popular with the Iranian masses and the middle class alike.

Enough already with the Bush bashing. It is a poor Chomsky like way to blame others for Iran's actions. Even the Soviets did not chant "death to America". Should we take such chants seriously? If one would in my opinion follow Chomsky we must ask ourselves "what have WE done to make them do this?". If were were to follow Kennan we would seek "containment". 

The author concludes:

For Iran, what counts now is no longer ideology but national interest and realpolitik. That is why it finds itself currently backing the opponents of revolutionary Islam: Bashar al-Assad against the Islamists in Syria and the Houthis against al-Qaeda in Yemen. And it is why it finds itself not only signing a nuclear accord with the Great Satan but also tacitly cooperating with it against the Islamic State, their common enemy. Now that the revolution is over, cooperation in other areas is likely to become equally appealing.

 The conclusions in my opinion lacks any touch of reality. Iran backs the Syrian regime for religious reasons. It does so for the other mentioned enemies. There is no realpolitik. There is a collection of funds and sellers of arms, Russia and China. 

Thus how should the US react. Again I would go back to Kennan. We can bemoan whatever Chomskieque actions taken but that will not control the future. What will and only will is a strong policy of containment. There is an inevitability of them attaining nuclear weapons, a clear and present danger to humanity. Yet Pakistan and India are in the same club. The US strategic nuclear policy covers only China and Russia. We somehow neglect Pakistan and India. We must add all three to this containment strategy and pray that they like the Russians value their children.

Wednesday, August 19, 2015

Text Books, Tuition and Harvard

In an interesting post Mankiw has a bit on the ratio of text book prices to annual tuition. Now there is quite a bit of apples and oranges here. But it is worth the study.

1. Text books have expanded in complexity and useless fill in the last 150+ years. For example I gave my granddaughter an 1880 algebra book, she is going into 7th grade and completing that course. You see algebra has not changed a great deal. In fact current texts contain more confusing extraneous materials that a good old 1880 version is just fine. I used an 1895 Geometry one for grandsons and that was sufficient. And yes they all cost less than $5.00.

2. The production of text books, on the printer's side have dropped dramatically. The promotion costs have expanded. Getting someone to use the latest version of Calculus, and yes Macroeconomics, just pushes up the price, and the cost falls on sales not production. Nothing is new in Calculus, at least for the past 100 years. So get an old book for a couple of dollars and you are set.

3. Tuition reflects a lost more over head now than 150 years ago. Just think, there was no Title IX, and all the other mandated Government stuff. Text books did not do that.

4. Production efficiency in pedagogy seems to have been negative, less teaching student-hours and more other stuff.

It is a worthwhile observation but worthy of a great deal more insight.

Monday, August 17, 2015

An Alternative Tunnel

The NY Times is advocating for a new tunnel under the Hudson. As they state:

The only long-term solution is the construction of a new tunnel complex, as proposed by Amtrak in its Gateway Program. Without a new tunnel and new rail tracks, a massive storm or some other disaster could sever a critical link in the Northeast rail corridor that serves more than 750,000 people a day on 2,000 intercity and commuter trains. For commuters and rail passengers crossing the Hudson River who are already complaining about delays, it can only get worse.

That is giving Amtrak from the Feds and States the money to build the tunnel. But I remember the first time I took a cab from the new Hong Kong airport through the new tunnel, a privately owned and financed tunnel. It was built in a very short time period, cost the Hong Kong taxpayers nothing, and was paid by those who used it.

Why not try that one. I use the train to Penn Station whenever I get to the city. The old facilities are rally falling apart and need replacement. But Government does not seem to work, especially Amtrak. So why not emulate the Chinese, it works.

More Thoughts of Kennan: Russia and/or Iran

George Kennan in his lecture on American Diplomacy articulated a path to dealing with the USSR, in fact Russia. The following summarizes his view: 

But we have seen that the Kremlin is under no ideological compulsion to accomplish its purposes in a hurry. Like the Church, it is dealing in ideological concepts which are of long­ term validity, and it can afford to be patient. It has no right to risk the existing achievements of the ·revolution for the sake of vain baubles of the future. The very teachings of Lenin himself require great caution and flexibility in the pursuit of Communist purposes. Again, these precepts are fortified by the ·lessons of Russian history: of centuries of obscure battles between nomadic forces over the stretches of a vast unfortified plan. Here caution, circumspection, flexibility and deception are the valuable qualms; and their value finds natural appreciation in the Russian or the oriental mind. Thus the Kremlin has no compunction about retreating in the face of superior force. And being under the compulsion of no timetable, it-does not get panicky under the necessity for such retreat. Its political action is a fluid stream which moves constantly, wherever it is permitted to move, toward a given goal. Its main concern is to make sure that it has filled every nook and cranny available to it in the basin of world power. But if it finds unassailable barriers in its path, it accepts these philosophically and accommodates itself to them. The main thing is that there_ should always be pressure, increasing constant pressure, toward the desired goal. There is no trace of any feeling in Soviet psychology that that goal must be reached at any given time. 

These considerations make Soviet diplomacy at once easier and more difficult to deal with than the diplomacy of individual aggressive leaders like Napoleon and Hitler. On the one hand it is more sensitive to contrary force, more ready to yield on individual sectors of the diplomatic front when that force is felt to be too strong, and thus more rational in the logic and rhetoric of power. On the other hand it cannot be easily defeated or discouraged by a single victory on the part of its opponents. And the patient persistence by which it is animated means that it can be effectively countered not by sporadic acts which represent the momentary whims of democratic opinion but only by intelligent long-range policies on the part of Russia’s adversaries policies no less steady in their purpose, and no less variegated and resourceful in their application, than those of the Soviet Union itself. 

In these circumstances it is clear that the main element of any United States policy toward the Soviet Union must be that of a long-term, patient but firm and 'vigilant containment of Russian expansive tendencies. It is important to note, however, that such a policy has nothing to do with' outward histrionics: with threats or blustering or superfluous gestures of outward "toughness." While the Kremlin is basically flexible in its reaction to political realities, it is by no means unamenable to considerations of prestige. Like almost any other government, it can be placed by tactless and threatening gestures in a position where it cannot afford to yield even though this might be dictated by its sense of realism. The Russian leaders are keen judges of human psychology, and as such they are highly conscious that loss of temper and of self-control is never a source of strength in political affairs. They are quick to exploit such evidences of weakness. For these reasons, it is a sine qua non of successful dealing with Russia that the foreign government in question should remain at all times cool and collected and that its demands on Russian policy should be put forward in such a manner as to leave the way open for compliance not too detrimental to Russian prestige.

 The key elements are that the Russians have a different view of time and we must let them preserve their prestige. Nothing has changed. Yet does this in any way apply to Iran, Persia in a historical context. The true issue is; does the United States today have a diplomatic core capable of having this discussion or have we politicized the extreme political tendencies of the State Department even further.

The US State Department has not always been the bastion of clever strategic thinking. Hay and the Open Door policy may have very well set the stage for Pearl Harbor. The State Department closed the doors to the Jews in the 30s. The list goes on. The problem now is that Executive Agreements can be cut that are not Treaties yet have significant influence. One wonders if we have any more Kennans.

Ockham versus the Scholastics

Friedman’s book, Medieval Trinitarian Thought, is an exceptionally accessible work discussing the complex issue of the Christian concept of the Trinity. Many of the early heresies in the Christian Church dealt with what was interpreted as false views on what the Trinity was. The complexity of the Trinity is driven by the acceptance of Jesus as God but also man and the incorporation of the Holy Spirit as a separate manifestation of God. The former was a result of the acceptance of the four Gospels, especially that of John and the latter the acceptance of the Acts of Paul. The complexity was further complicated by the inclusion of Greek philosophical thought and terms of philosophical understanding that became the tools to make this interpretation.

It was left to Augustine to lay for the Western Church a foundation that lasted almost a millennium until Aquinas delved into the process again in the 13th Century. To some degree the development ends as so many of these pursuits with Ockham. Ockham rejects the Academics and states that one can accept the Trinity sola fide, on faith alone. It is Ockham who introduces the concepts of Nominalism, the importance and criticality of the individual, the ability to rely on faith, and of course his accusation of heresy to the Pope in Avignon.

The Aquinas versus Ockham debate is first framed as the Dominican versus Franciscan debate. In Chapter 1 the author in the clearest of terms describes the debate. Here we have the Dominicans trying to rely on Aristotelean constructs and speak of the Trinity as a familiar set of relationships. The Franciscans take a more ethereal approach and lay out the emanation approach. It is Ockham, a Franciscan, who takes the ultimate extreme of rejecting both and stating that faith alone carries the day. This is a brilliantly written Chapter, one of the best I have seen addressing this debate. It may have been improved if it has a preface discussing Augustine a bit more and also the early Church debates, but that in no way detracts from the presentation.

Chapter 2 discusses the Psychological Model, or as the author states on pp 50-51 that the Son is literally the Concept of the Father and the Holy Spirit is the Love produced by the will shared by the Father and the Son. The author clearly explains the evolution of this approach via John’s Gospel and the use of the term logos. In Latin the term is verbum and yet there may be a slight but material difference between the two terms. There is a brief integration of the Augustine thought on this approach.

Chapter 3 discusses the Trinity and Metaphysical thought. Chapter 4 is a key chapter; it introduces Ockham and sola fide. This is an especially clear and well written presentation. The author examines Gilson, the French Neo-Scholastic, and presents a well-structured Gilsonian analysis and contrasts it to Ockham. Whereas Gilson is a Thomist, and Thomism has persevered in classic Catholicism, the Ockham school does lend itself to a bifurcation of Scholastic approach into one that faith exists and can play a vital role to that attempt to use reason to explain all the nuances introduced in the New Testament.

Overall I would highly recommend this exceptional book. Although it deals with a highly complex and specialized issued, it does so fairly and in a quite readable manner. It is not a classic heavy tome of Scholastic formalism but a clearly articulated discussion of a core principle of Christin belief.

Sunday, August 16, 2015

Let the Sales Begin!

China Daily reports that it is negotiating sales of an F 16 knockoff to Iran in anticipation of the deal.

As they state:

The China-made J-10 multi-role fighter jet is a suitable choice for Iran if the Middle East power decides to upgrade its aging military aircraft fleet, Chinese aviation experts said. "Once the sanctions against Iran are completely lifted, the country will definitely renovate its civilian and military aircraft fleets. The J-10 is a good option for the Iranians because it can fulfill all operations they want to conduct," said Wang Ya'nan, deputy editor-in-chief of Aerospace Knowledge magazine. "In addition to air combat, our J-10 is also capable of performing air-to-surface strikes and anti-ship operations," he added. "Moreover, the Iranians must have known that China, among other major weapon exporters, is the most reliable supplier when it comes to arms deals. China is also very flexible in payment issues."

Thus the immediacy to see the market opportunity and arm Iran is at the top of the list of advantages of this deal. The idea of unintended consequences may not have been fully appreciated!

One should read and re-read Kennan's short work, American Diplomacy, and better understand all the mistakes the US has made over the years.

Having been a small part of the CTBT during the Carter period, verification of compliance is essential. Second is consequences to violations. Verification here appears to be near zero, since one could not tell until after an explosion.

Russia, The Telegram, Kennan: Then and Now

From time to time it is worth re-reading Kennan's "Telegram" on Russia, then it was the Soviet Union, and ask what has changed; players or roles, or nothing?

On February 22, 1946 Kennan wrote: 

At bottom of Kremlin's neurotic view of world affairs is traditional and instinctive Russian sense of insecurity. Originally, this was insecurity of a peaceful agricultural people trying to live on vast exposed plain in neighborhood of fierce nomadic peoples. To this was added, as Russia came into contact with economically advanced West, fear of more competent, more powerful, more highly organized societies in that area. But this latter type of insecurity was one which afflicted rather Russian rulers than Russian people; for Russian rulers have invariably sensed that their rule was relatively archaic in form fragile and artificial in its psychological foundation, unable to stand comparison or contact with political systems of Western countries. For this reason they have always feared foreign penetration, feared direct contact between Western world and their own, feared what would happen if Russians learned truth about world without or if foreigners learned truth about world within. And they have learned to seek security only in patient but deadly struggle for total destruction of rival power, never in compacts and compromises with it.

Perhaps this applies quite well today.  Russia today, albeit becoming more main stream, is still stuck in a Czarist state of strong rulers and limited outwardness.

He continues: 

 In international economic matters, Soviet policy will really be dominated by pursuit of autarchy for Soviet Union and Soviet-dominated adjacent areas taken together. That, however, will be underlying policy. As far as official line is concerned, position is not yet clear. Soviet Government has shown strange reticence since termination hostilities on subject foreign trade. If large scale long term credits should be forthcoming, I believe Soviet Government may eventually again do lip service, as it did in 1930's to desirability of building up international economic exchanges in general. Otherwise I think it possible Soviet foreign trade may be restricted largely to Soviet's own security sphere, including occupied areas in Germany, and that a cold official shoulder may be turned to principle of general economic collaboration among nations.
Russia  in order to prosper and move from a pure extraction economy must seek to open up and allow for the creation of a full entrepreneurial society. It can adhere to many of its past ways but as to its relationship with the West it must seek trade related development.

The Kennan conclusion was: 

 In summary, we have here a political force committed fanatically to the belief that with US there can be no permanent modus vivendi that it is desirable and necessary that the internal harmony of our society be disrupted, our traditional way of life be destroyed, the international authority of our state be broken, if Soviet power is to be secure. This political force has complete power of disposition over energies of one of world's greatest peoples and resources of world's richest national territory, and is borne along by deep and powerful currents of Russian nationalism. In addition, it has an elaborate and far flung apparatus for exertion of its influence in other countries, an apparatus of amazing flexibility and versatility, managed by people whose experience and skill in underground methods are presumably without parallel in history. Finally, it is seemingly inaccessible to considerations of reality in its basic reactions.

 Thus one wonders if Russia is going backwards or whether it will seek accommodations with the rest of the economic world. Perhaps we will only know when we see "Made in Russia" in Walmart.

A Measure of the Economy

From time to time it is worth looking at some metrics to see if we are going anywhere. The above is the totality of Real Estate Loans. They are coming back to where we were at the time of the collapse. Also the annualized growth rate has been positive for quite a while but not too big, as compared to before the crash. This may be a good sign of returning stability. It is also amazing to see how bad we were before the crash!

Did Anyone Ever Take Geography?

New Guinea was a major front during WW II. MacArthur landed on the northern side, I recalled from the exploits of my father's Destroyer records at the time. Today New Guinea is split down the middle. The West is Indonesia and the East is Papua. The interior is impenetrable. Abot 2 to 3 meters from the waterline one can no longer see the fingers on an out stretched hand, the growth of vegetation is so great.

Yet in all the news channels they indicate Papua as the West! Just check Google maps, please, someone! I am totally amazed at the general incompetence of the news media. Really guys! It is just Grammar School geography!

This is reflective of the general competence or lack thereof of both our media and our education system. I had this in the 5th grade with Sister Rosita. As did the Public School colleagues.

Why not try this one out on the Candidates, even the former Secretary of State!

Friday, August 14, 2015

Reinterpreting Pearl Harbor

I have to admit that being alive during WW II and with a father in the Pacific the position taken by Japan still rings loudly. Thus in reading Abe's somewhat self serving piece in The Syndicate I was a bit taken aback.

For example he states:

With the Manchurian Incident, followed by withdrawal from the League of Nations, Japan gradually transformed itself into a challenger to the new global order that the international community sought to establish after such tremendous sacrifices. Japan took the wrong course and advanced along the road to war.  

The Manchurian Incident was a massive invasion and occupation by Japan of China's territory resulting in the massacre of thousands in Nanking. 

Then he states:

More than one hundred years ago, vast colonies, possessed mainly by the Western powers, stretched across the world. With their overwhelming supremacy in technology, waves of Western colonial forces surged toward Asia in the nineteenth century. There is no doubt that the resulting sense of crisis drove Japan to pursue modernization. Japan established a constitutional government earlier than any other country in Asia, and preserved its independence throughout. The Japan-Russia War gave encouragement to many people under colonial rule from Asia to Africa. 

But was that an excuse for the assault on Pearl Harbor, for the Death Marches, for the abject slaughter?
Abe, in my opinion, writes a classic "on the one hand and on the other hand" piece. Japan had defeated Russia. Japan then occupied land mass after land mass, gathering up natural resources it needed in its attempt to defeat the United States.

Abe continues:

We will engrave in our hearts the past, when Japan attempted to break the deadlock it faced with force. Upon this reflection, Japan will continue to uphold firmly the principle that any disputes must be settled peacefully and diplomatically, based on respect for the rule of law, and to reach out to other countries in the world to do the same. As the only country to have ever suffered the devastation of atomic bombings during war, Japan will fulfill its responsibility within the international community, aiming at the non-proliferation and ultimate abolition of nuclear weapons. 

I recall the writing from my father's shipmate which recorded today, as they prepared in the Aleutians for an invasion of Japan and sure death, that the men who had survived Japanese attack after Japanese attack and seen hundreds of their shipmates dismembered by Japanese shells, just sit in tears on the deck of their Destroyer, knowing that the end of the horror was near. Regrettably it was Hiroshima, and Nagasaki, but the end was quick, and the lives lost significantly attenuated.

Perhaps Japan may someday come to the point of recognizing that it really was not on the one hand and on the other, but that they made a terrible error. Yet it is this understanding that should be understood by all, for such errors, as can be self justified, can be repeated. The consequences of nuclear weapons are a horror mankind must avoid, and that means an acceptance of consequences, not an attempt to justify, no matter how slightly.

Thursday, August 13, 2015

Interesting Work on Mabs

Monoclonal antibodies are a class of antibodies which on the one hand reflect a response to a specific antigen and on the other hand can activate the immune system to respond to the cells presenting to that antigen and have them eliminated if possible.

Back in the mid-1960s when I first came across the clinical use of antibodies what was frequently employed was gamma globulin, a massive amount of mixed IgG, immunoglobulin G, from many people and it was somewhat tried as another treatment for a variety of disorders including some cases of mumps. However the specificity of IgGs and the other immunoglobulins had not yet been ascertained.

As this identification progressed it became apparent that specificity of the antibodies could perhaps be a tool to attack certain disorders, including cancers. This then led to many examinations of ways to produce large volumes of specific antibodies. The result was the development of monoclonal antibodies. Simply this is the chimeric combination of antibodies developed to attack a specific target and a vehicle cell that had immortality to bind this product to so it became a small factory for production. From this came, after a significant amount of effort, the monoclonal antibody, and in turn the new therapeutics ending in –mab.

The work of Marks, The Lock and Key of Medicine, is an effort to tell this story. It starts with some of the early researchers in the UK who persevered to get some of the initial samples available and the ever changing dynamic of researchers and clinicians. As with so many efforts of this type, there is an ever challenging set of steps that the researchers and the clinicians go through, some winning and some losing. The early days of the late 1960s, when in the practice of medicine little was truly understood but the tools for the researchers were coming on quickly.

The author takes the reader through the many individuals and the many crises and victories as they progressed. The book focuses on the many individuals and their steps in developing MABs and the ultimate commercialization of them and their application to human therapeutics.

As we progress we have seen basically four classes of Mabs. They are: murine or mouse versions with therapeutics ending in –omab, chimeric murine and human Mabs with the ending –ximab, the humanized Mabs ending in –zumab, and finally all human Mabs ending in –umab. Mabs are now one of the arms in treating a variety of diseases from cancer to arthritis and colitis. At the same time they have become “big pharma” and the author takes the reader through this process in some detail.

Overall, the book and an excellent articulation of the people, the conflicts, the achievement, and the institutional progress. From that perspective is an excellent contribution.

On the other side it would have been more helpful to have provided some simpler introductions to Mabs and the immune system. For a well-educated reader this is an interesting tale of scientific and clinical development. It does lack a feeling of personal involvement. The description of the individuals is in my opinion quite arm’s length and unlike other works of similar genre this is a discussion of facts and events and dates.

What I especially missed was the recent explosion of applications. For example in advanced melanoma there is the use of Mabs and pathway control therapeutics such as BRAF inhibitors and MEK inhibitors. This raises the issue of how does one see a blending of these two or are they not so complementary. On the other hand there are certain cancers such a prostate cancer which may be so complex and changing at such a rapid rate that Mabs would just not work. It would have been useful for the author to have contributed some substance to the debate.

Overall, again, this is an excellent book albeit for possibly a smaller community of engaged readers.

More on PCORI

PCORI has now exceeded $1 B in funding as a result of the ACA. One should examine the projects. Its head recently stated in an email:

We've just marked a major milestone here at PCORI - topping $1 billion in funding approved for research projects and other initiatives that will help patients and those who care for them make better-informed healthcare choices. 
We're proud of these investments, all of which support our mandate to advance comparative clinical effectiveness research (CER), studies of what works best for whom under which circumstances. All of our awards are approved by our Board of Governors and reflect ongoing input from patients, family caregivers, clinicians, and other stakeholders from across the healthcare community. All directly fulfill our mission to both improve the quality and relevance of evidence available to clinical decision makers and the methods used to see that this evidence is reliable. And all ensure that we live up to our name by supporting research addressing the questions and concerns of patients and other stakeholders.Two-thirds of our awards to date, nearly $680 million, support studies of the effectiveness of two or more approaches to care focusing on outcomes that matter to patients
However when one tries to examine what may actually have been accomplished it seems in my opinion to be fairly empty.  Needless to say they will continue to burn $500 M or more each year, a sum which frankly could be much better spent elsewhere.

Calories are Calories?

In a recent NIH study there was an attempt to demonstrate that fat calories were more effective in adding body fact than carbohydrate calories.

The procedure was as follows:

The researchers studied 19 non-diabetic men and women with obesity in the Metabolic Clinical Research Unit at the NIH ..... Participants stayed in the unit 24 hours per day for two extended visits, eating the same food and doing the same activities. For the first five days of each visit they ate a baseline balanced diet. Then for six days, they were fed diets containing 30 percent fewer calories, achieved by cutting either only total carbs or total fat from the baseline diet, while eating the same amount of protein. They switched diets during the second visit. 

They conclude:

“Our data tell us that when it comes to body fat loss, not all diet calories are exactly equal,” .....“But the real world is more complicated than a research lab, and if you have obesity and want to lose weight, it may be more important to consider which type of diet you’ll be most likely to stick to over time.”  

Now there are several issues here:

1. The sample is much too small

2. The duration time is much too short

3. The switching is in the middle of a metabolic change which takes possibly weeks, not hours to adapt.

4. The key issue is the definition of a calorie. Namely if we measure 3500 Kcal = 1 pound, then how do we differentiate at all?

This is not in my opinion a study of any value for the above and many other reasons.

Wednesday, August 5, 2015

Ginkgo and Hiroshima

Seventy years ago Hiroshima was bombed. Some nearly 20KT yield uranium device fell some 30,000 feet and exploded several thousand feet above the city. The result was a massive ring of destruction. Surviving that was a few century old Ginkgo trees, tress which themselves had survived some 250 million years[1]. As a symbol of survival the Ginkgo has great standing. As we look backwards and then again look forward one thinks of these Ginkgos.

Some twenty five years ago I took a handful of Ginkgo nuts from the trees at the New York Botanical Garden. I placed them in my pocket, stink and all, and let them sit in my refrigerator to cold stratify over the winter and then planted them in my seed beds. Up they came and now twenty five years later I have one female tree filled with Ginkgo nuts. The legacy of 250 million years goes on. The hardy tree may survive us all, in some way shape or form, since its seeds will be transplanted elsewhere, to grow again.