Monday, April 30, 2012

Lambertville, April 2012

One of my periodic updates on Lambertville, on the banks of the Delaware. This is the old canal which rode along side the Delaware River, and in parts still remains. Down the road a piece is where Washington crossed over that famous Christmas night and kicked off a set of positive moves on his part. The Delaware is wide and was filled with ice that night. No small stream this river.

I am always amazed that most folks fail to realize how much of the Revolution was fought in our back yards. Unlike the Civil War, the remnants are few, but the consequences are important.

College Education: Goals, Objectives and Costs

Unlike many pure libertarians, I believe that the Government can provide for positive incentives that will benefit all. Take College education. The US needs more engineers and scientists, and not to mention physicians.

In contrast to the all negative bantering of Krugman, the Petulant Princeton Professor, I believe that the Government can be a positive contributor. In fact it has shown in the past how to do this. In the later 1950s after Sputnik the US had a great demand for scientists and engineers, and it created undergraduate and graduate scholarships for those who could achieve at the higher levels. Namely it rewarded success, and in a sense punished failure, if the Draft could be called such, by providing scholarships to US citizens who majored in the engineering and science areas. You also got a Draft deferment.

Now the inimitable Krugman states:

College graduates, then, are taking it on the chin thanks to the weak economy. And research tells us that the price isn’t temporary: students who graduate into a bad economy never recover the lost ground. Instead, their earnings are depressed for life. 

What the young need most of all, then, is a better job market. People like Mr. Romney claim that they have the recipe for job creation: slash taxes on corporations and the rich, slash spending on public services and the poor. But we now have plenty of evidence on how these policies actually work in a depressed economy — and they clearly destroy jobs rather than create them. 

 Perhaps what the young need more than anything else is a dose of reality. Getting a BA in Fine Arts is perfectly fine if you have a billion dollar trust fund and you want to prepare for your Grand Tour. Or a degree in Ancient History is great if you also have that Trust Fund. But if you want a job then perhaps you do what anyone else would or should do, look at who is hiring, look at the costs and see if you will ever get a return on your investment, Just going to college often does not help. I have hired many High School grads over the years because they can work. The MBA type may very well have excessive expectations and no competence.

At eighteen, and it really has changed little in sixty plus years, one must make a decision based upon facts and reality. If you really do not like math, and you really just want to coast through an easy college, think of all those Hispanic immigrants I see at 6 AM on a January morning on the corner in Morristown seeking some pay for the day ... for they are your competition, not some Chinese laborer in Harbin.

Thus perhaps it would be helpful for the Government to renew those Science and Engineering scholarships, national tests, best performers win, no other requirement, no sex, no race, just how well one does. Just smart motivated US citizens. And yes, there is no funding for the arts or any other area not strategic to our national success, including economics. The Chinese and Indians do this, we should do it as well. Bring back the fifties!

Sunday, April 29, 2012

Type 2 Diabetes, Children, and the Cause

The NY Times has a piece bemoaning the rise of Type 2 Diabetes in children. We have been concerned with that to the extreme. In our book, Obesity and Type 2 Diabetes, we argued that this epidemic would become a pandemic. There have been almost 100 downloads per week of the DRAFT. On the other hand people like Harvard economists have dismissed the issue, and they would rather focus on taxing gasoline. The pandemic will collapse our health care system, since Type 2 Diabetes patients just will not die quickly! They can be kept alive at enormous costs. However the early cure is simple, stop eating!

But the cause, the US Department of Agriculture and its exploding budget of fat foods! The solution, twofold, stop all in school meals, let parents send kinds with brow bags or have them shed some weight, and second disband the Department of Agriculture. We prime the  pumps at school and then watch as the fat munchkins go to fast food outlets after they get dropped off from the school bus.

As the Times notes:

... a college senior from ... learned that she had type 2 diabetes when she was 16. Her grandfather had had both legs amputated as a result of the disease, and one of the first questions she asked was when she would lose her legs and her eyesight. A doctor scolded her for being fat and told her she had to lose weight and could never eat sugar again. She left the office in tears and did not go back; soon after, she joined the study at Columbia. Like many of the children in the program, she did not even know how to swallow a pill. 

She believes that the disease “is not a death sentence,” she said, if she is careful about controlling her blood sugar. But it has been a struggle. Her family tends to be overweight, she sometimes craves sweets and she has orthopedic problems that have required surgery and have made it hard for her to exercise. She is also being treated for high blood pressure. 

A few weeks ago, because her blood sugar shot up despite the diabetes pills she was taking, she began using insulin. 

And in a few months she will be having kidney, nerve, and eye problems, then heart problems. And we will be paying. Thank God the physician at least said she was fat! Tears were not the answer, self-control was, and it requires a family effort. The problem is we consider her a victim when in reality she is a self inflicted burden on society. The child with leukemia is not at fault, while the obese teen is. And the solution is so simple, stop eating!

Recession Statistics: Q1 2012

As before we use the St Louis FED data showing the min, max and average metrics for the GDP and its components. The GDP above, the total metric, lags the average recovery but does exceed the worst. Yet there is a major concern that even the worse is nearing where we are now. Growth is consistently slow. There now is a clear concern that the recovery may be so weak as to fall below the min curve.

Consumer consumption is a problem since it now defines the bottom at this point as shown above. This has been the aggregate demand argument but it is a combination of fear and reduced credit as well as unemployment, real not the DoL type. The consumption number is a major concern since at one level fewer taxpayers means less revenue and more unemployed means higher benefits and thus expenditures.

Government consumption is now lowest. I find this amazing given the deficit and its continued explosion. This is shown below. The real issue is what are  we truly measuring here. It must also be made clear that min, max and avg are not necessarily the same recession recovery so the data may be highly mixed.

The following are the stats on Imports and Exports. First Exports have exceeded the average recovery which is good.

Imports have met average. This is most likely due to reduced consumer demands. However imports reduce GDP and since imports have been several multiples of exports even a flat number may still create a negative effect.
Bottom line, things seem to be getting worse not better.

Herbert Spencer: A Review

I wrote this a couple of years ago in reviewing the book by Francis. It is worth restating.

The biography of Spencer entitled "Herbert Spencer and the Invention of Modern Life" by Mark Francis is a recent addition to the body of works of an interesting 19th century polymath. Spencer was both a philosopher and advocate of Darwin's evolutionary ideas as well as one who opined frequently on matters of political import. In many ways Spencer was a true polymath, one who wrote seminal works on psychology and sociology and wrote extensively on biology and integrated that with the new ideas promulgated by Darwin. Spencer was praised by many of his contemporaries and was also in many ways the typical Victorian, hardened in that period but also having his views shaped by it also.

Overall the book addresses Spencer, his life and his views. However, the author, in my opinion, is more interested in detailing how Spencer fits his personal view of Spencer than Spencer truly was as a person and as an influence on his world. Spencer, in his most lasting work, The Man Versus The State, clearly is an individualist and as such in many ways has become a major cornerstone for many libertarians. Yet Francis seems to reject this view and, for the most part, this book is a tirade against that position of individualism which Spencer clearly took.

Spencer was well known for his views on psychology, sociology, biology, and especially the views on Darwinism and individualism. For Spencer all of life, all of existence was a continually evolving process. The author continually returns to that fact in all of its aspects.

Spencer was well read from the time he started to write through the 1930s. Then he was attacked unjustly by the left wing in American academia, centered at the time at Columbia University, a hotbed of Communists and Marxists. For it was in the mid 1940s that Spencer was vilified by the one-time Communist history professor at Columbia University, one Richard Hofstadter.

Hofstadter in his book Social Darwinism uses Spencer's ideas on Darwin in a somewhat self serving and twisted manner to attack both Spencer and the free market capitalism as it evolved over the century from 1850 to 1950. Hofstadter was well known in leftist circles as one who could readily take a few apparently disconnected points and with what could be at best described as shabby research methods produce polemics against the conservatives and right wing advocates in the body politic.

Hofstadter was also well know to write "soft" history, what we would expect in a New Republic piece, rather than hard academic history. Hofstadter was polemical in his style and greatly deficient in primary sources. He was all too often just a recorder of old press clippings using these as the window to the world he wanted the reader to see rather than addressing the reality via primary sources.

In a recent work by Prof. T. Leonard at Princeton University (See Origins of the Myth of Social Darwinism: The Ambiguous Legacy of Richard Hofstadter's Social Darwinism in American Thought ) Prof. Leonard states about Hofstadter and Spencer the following, while reviewing the issues in "Social Darwinism in American Thought", also called "SDAT":

"Richard Hofstadter, like many New York intellectuals in the 1930s, embraced radical reform. He joined Columbia University's Communist Party unit for a brief period in 1938. The more mature Hofstadter grew disenchanted with radical politics, indeed came to see it as hostile to scholarship. But SDAT, which revised his doctoral dissertation published in 1939, preserves Hofstadter's earlier world view, that of a precocious scholar, still much influenced by his mentors, Merle Curti and Charles Beard, who could say to close friends, "I hate capitalism and everything that goes with it" ... SDAT also bears the historiographic imprint of Beard's "rule" that historical interpretation must assume that "changes in the structure of social ideas wait on general changes in economic and social life" ... SDAT is thus sprinkled with unadorned Beardian claims, such as "Herbert Spencer and his philosophy were products of English Industrialism"..."

But let me return to Francis and his book. He sets his tone for the entire biography on p. 2 when he writes:

"...the greatest source of popular confusion about Spencer does not arise from national prejudice, but from writers who have explained his theories by reference to those of Charles Darwin as if the former were a simple version of the latter. This misidentification has been so common that its correction would be an obligatory as well as unpleasant task for any Spencerian scholar. There are two reasons why it is painful. First it forces me to write about Darwin....also, it is slightly obtuse to explain an intellectual phenomenon such as Spencer' reference to something it is not."

This statement clearly lays forth the attitude of the author going forward, cumbersome as the use of the language is. First, there is the almost arrogant exposition of Spencerian evolution not being akin to Darwin and then the outcry of having to endure the unpleasant task of education of the reader, specifically what appears to be the less well educated readers who, frankly as per the author, should know better. Francis seems to bemoan the fact that he must tell the readers things that they should have know ab initio about Spencer. As such one wonders what audience Francis had in mind for his book. Perhaps it is meant for the small cadre of fellow Spencerian academics.

The last phrase in the above quote is at best condescending and at worst insulting to the readers since it implies that each reader should be approaching the biography already well educated in Spencer as well as in Darwin. This shrill tone of the author's style continues to resonate throughout the book.

The next interesting comment is on p 3 which frankly refutes the entire basis of the Hofstadter diatribe on Social Darwinists. In Hofstadter SDAT, he accuses Spencer of being a pure Darwinian and as such lacking in any human emotions. However Francis states:

"...First there was Graham him Spencer was merely an early and hasty generalize on the subject of evolution....secondly, there was Richard Leakey...he possessed the same information as Wallas except ...he was praising not condemning Spencer....After Darwin had explained his theory...Spencer quipped that it might as well be called "survival of the fittest"....if either Wallas or Leakey had read Spencer...(he) was unsympathetic to Darwin's theory..."

Thus Spencer was not a pure Darwinian. As Leonard states:

"Darwinian defenses of laissez-faire among scholars, who were more likely to have read Darwin, are not much easier to find. Bannister and other revisionists point out that even Hofstadter's social Darwinist exemplars, Herbert Spencer and William Graham Sumner, were not especially Darwinist. Spencer certainly invoked the evolutionary advantages of competition among men. And, Spencer's extraordinary intellectual prominence in the last third of the 19th century also made him a large target for reform scholars. But Spencer would have rejected the label of "Darwinist," in part because his own theory of evolution differed from and was published before Darwin's On the Origin of Species. The catch-phrase "survival of the fittest" was Spencer's and Darwin did not adopt it as a synonym for "natural selection" until Alfred Russell Wallace convinced him to do so in the fifth edition of the Origin (1869).

Importantly, Spencer was a Lamarckian with respect to human inheritance. He imagined that competition induced human beings to actively adapt themselves to their environments, improving their mental and physical skills - improved traits that would then be inherited by their descendants. Spencer's view was that, in the struggle for existence, self-improvement came from conscious, planned exertion, not from the chance variation and natural selection that are the heart of Darwinism. As a result, evolution is progressive in Spencer, whereas, for Darwin, at least the early Darwin, evolution means only non-teleological change. Spencer's fundamental belief in human progress via Lamarckian bootstrapping was at odds with Darwinian natural selection's randomness and its openness to non-progressive change.

Spencer, in fact, was not just a Lamarckian, he was a leading Lamarckian, taking up cudgels against the neo-Darwinians such as biologist August Weismann, whose watershed finding in 1889--that mice with their tails cut off do not bear short-tailed progeny--was seen by many as a crucial-experiment refutation of Lamarckism. Spencer's status as a defender of Lamarckism in the 1890s was such that that progressive Lamarckians, such as Lester Frank Ward, often found themselves in the awkward position defending Spencer, a man whose individualism and laissez-faire economics they loathed, and dedicated their lives to opposing."

Thus the fundamental basis of the Hofstadter argument against Spencer has no merit. Francis begins by throwing the cudgel down early on in the biography as to his apparent dislike of free markets and then continues to pound the cause home.

On p. 13 the author begins to position Spencer as a non-individualist, by redefining what he believed Spencer meant by his individualism. The author commences what appears to be his personal repositioning of Spencer as not the one lauded by many 21st century libertarians but as a mainstream 21st century liberal. Although he defines "individualist" as the "natural antonym" of the term "state" the author commences the rehabilitation of Spencer from his point of view.

The most published work of Spencer, his small but compelling book, "The Man Versus the State", is a well read treatise which clearly and unambiguously states the position of the individual against the state. Unfortunately the positioning by the author at this stage to marginalize this work of Spencer presages his attempt to reconstruct Spencer as a man who may not even have written that book.

Chapter 3 depicts Spencer and the problems he allegedly had with women. One of his alleged lovers was the writer George Eliot with whom he had an affair which lasted a brief while. The chapter is less a discussion of Spencer's problems with women than it is a presentation of conflicted Victorians in England.

Chapter 6 discuses Spencer's rather common eccentricities starting with his hypochondria. The author states:

"Spencer combined hypochondria with radical political opinions."

It appears that this was a common British trait not unique to Spencer. For if one looks at Lord Russell one see that he suffered from exactly the same set of problems. One may conjecture that such a set of common characteristics were both common to the Victorian British as well as those holding extreme views.

The concept of the pervasiveness of evolution for Spencer is detailed by the author on p. 193 where he states:

"A constant refrain in Spencer's early scientific writings was that all phenomenon of the universe...were subject to evolution."

Further Francis states:

"Spencer's initial conception of life was not a cold and objective; he saw life as the general impulse towards goodness and perfection, evidenced everywhere one looked."

This is a teleological outlook towards evolution, the goal being the goodness and perfection as stated by Spencer. But was that indeed his view, and if so what drove this end point, since Spencer was not a truly religious man. Francis states that the intelligence was science in and of itself.

Spencer was a prolific writer and there are a continuing set of streams of an evolving set of views. Yet Francis states that the paper "A theory of Population" written in 1852 was the singular key to his early views. Francis argues on p 194 for Spencer's views, views which aligned with the expanding presence of Great Britain. Francis states:

"...Spencer perceived his own experience and that of nature generally as "the inherent tendency of things going towards good..." He called this vis medicatrix naturae...the progressive quality of nature even justified...suffering...necessary for benign progress...each conquered race or nation could acquire a liking for new modes of the future Spencer saw new modes of evolution...(and) maintain a perfect and long lived existence for each individual."

In Chapter 15 Francis appears to get annoyed by the seminal work of Spencer, "The Man versus the State". He speaks of Spencer's anti-utilitarianism and his hostility towards Bentham like hedonism (see pp 248-249). Francis states:

"In "The Proper Sphere of Government" he (Spencer) wrote as a Christian utilitarian opposed to individualism and thus was hostile to those who construed happiness as if the collective did not matter."

On p. 249 he attacks "The Man versus the State" as being inconsistent with the true meaning of Spencer's views. This is a wandering and almost incoherent presentation in the text and Francis continually tries to say that "The Man versus The State" was an aberration of an old man rather than a culminating view developed by Spencer. In fact this was one of Spencer's clearest texts and the one which has had lasting influence. Moreover it is a text devoid of the Darwin and reflects an evolving and mature view of the individual versus the expanding nature of the State.

Francis on pp 250-251 then goes into the current position we find in Rawls with direct reference to him. Francis speaks of the confusion Rawls has between liberalism and communitarianism, but no matter, both are counter individualism which is where Spencer had allegedly evolved to. Francis gets quiet complex and confusing as he attempts to draw together what he sees a conflicting views of Spencer while at the same time attempting to keep Spencer in what we would see today as a truly "liberal" player and not one dedicated to true individualism. He ends the discussion with the statement:

"For Spencer it was not that the individual and society operated in different spheres as they had for ...Mill. That distinction would have allowed for a principled discussion of when interference with the former was justified. Spencer's conceptualization of the individual and society places them on separate planes making it illegitimate to permit some restrictions on freedom while forbidding others."

This sentence makes little sense to me. On the one hand they are not in different spheres but on the other hand they are on different planes. Now the metaphor is not just weak it makes no sense. This chapter is rant with such non sequiturs!

Now Francis continues his attack against "The Man Versus the State" on pp 258-259. Here is states:

"Spencer's liberalism in particular is not usefully glossed over as a "bourgeois" individualistic ideology that was forged in opposition to the collective."

Indeed it was not. It was carefully thought out and predicated on the events that allowed him to detail fact by fact with the resulting impacts on individual freedom equally detailed. Also individualism had and continues to have evolving and complex expressions, from the one extreme of current day libertarian views to those which are socially more open.

In Chapter 18 Francis discusses Spencer's work on Sociology in political systems. On pp 304-305 he detailed the nexus between these topics and evolution. It is seen that Spencer continually winds the evolutionary elements into his work. To Spencer everything was continually in an ever changing evolutionary milieu. It was for him Lamarckian where the Darwinian step changes were Lamarck's slow changes which were absorbed.

In the Conclusion on p 334 he again returns to what seems to be the major conflict that Francis sees, that is that Spencer was at heart in his maturity a true individualist yet Francis does not seem to want to accept that. He states:

"When it is realized that Spencer was a corporate thinker rather than an individualist, then his argument for the need to give a paramount place for the emotions becomes more easily explicable."

This is apparently a total rejection by Francis of the facts that are evident in "The Man Versus the State". Francis fails to discuss the contents of this book in the slightest degree, he discusses in detail the early works but merely shouts against the latter. This book does provide valuable insight into Spencer and especially in view of the later invective by Hofstadter it would seem most appropriate to have devoted some care an attention to it.

Thus this book is a good contribution to Spencer since it forces the reader to go back and read in detail what he said and see how all too often is counters Francis. Yet Francis knows Spencer and Spencer had and potentially continues to have made contributions to our thinking. Thus I recommend this book strongly for those interested in Spencer and just as importantly those interested in individualism as say a view in contrast to neo-progressivism.

Saturday, April 28, 2012

Will This Happen Here?

The Guardian has an interesting piece on denial of health care under their socializes system.

They state:

A majority of doctors support measures to deny treatment to smokers and the obese, according to a survey that has sparked a row over the NHS's growing use of "lifestyle rationing".

Some 54% of doctors who took part said the NHS should have the right to withhold non-emergency treatment from patients who do not lose weight or stop smoking. Some medics believe unhealthy behaviour can make procedures less likely to work, and that the service is not obliged to devote scarce resources to them.

I can see this happening here. One just need look at the current crop of pols in DC and start to see who we can deny service to. A smoking Chief Executive, a morbidly obese Surgeon General, how about half of Congress, the SCOTUS, a few on the overweight side there I'd say. Think how much that would save!

Just a thought.

A Calculator: A Sign of American Intellect in Decline

Now one may wonder why I have spent more than a few seconds on this issue. The reason is that it is a metaphor for what is wrong with a few things. Here is the issue. Back in 1978 I believe I got the calculator on the left, a TI which may have been close to $100 at the time, a steep sum in today's world. Well designed, keys were colored to correspond to actions. Good human factors engineering. Bad packaging since it has not lasted this almost 30 years, neither did my first PC.

In the middle is a second unit about 10 years ago. Still good design, holds up, and the human factors is weakening, the blue keys should be of a more contrasting color.

Now today, I got the one on the right. The keys are all silver on silver and one cannot see them when using it in say a lab. Bad human factors design,

Now what makes the Apple products great are great human factors. I remember meeting Jobs back in the early 80's when I was at Warner, we had Atari and he had Apple, we had games and he had a dream. I always thought his idea was better and time tells out.

Now I bought one of these on the right and found it almost impossible to use. Bad human factors. So when I saw a comment on Amazon stating as such I just left my comment, using my real name which I believe is ethical and necessary to judge the remark, and then ZigZagJoe, whoever that may be, remarks:

"Fine tip black sharpie - problem solved."

 Now that is when I asked what would Steve Jobs say to that remark? I suspect the good ZigZag would be leaving the parking lot for good before I finished this sentence!

But, and this is the observation, who is ZigZag and why should I listen to him. He has no real name, no bona fides, he lacks any engineering sense, just a snarky sense of humor, if that is what I sense. But more importantly the design flow is more critical, from a 1970s great design to something which is unusable. Perhaps that is one of the problems with American industry, people like ZigZag who may very well have been the designer!

The issue truly is as follows:

1. Form follows Function: This is a calculator, and using plus, minus, multiply and divide, are key functions, hidden by the form. This is by definition a design failure.

 2. Yet the ZigZag character suggests a fix, use a marker, color in the key so that one can see them better, redesign the calculator. Only ZigZag misses the point, it is not the users role to design but to use. ZigZag is reflective of all that is wrong, he may suggest a suboptimal solution, if even that, but it is not the user but the designer who has the obligation. And TI clearly showed that decades ago, almost 40 years ago!

3. ZigZag has become a universal model for how not to act, his snarky attitude, his failure to understand the issue, his lack of appreciation of quality is an embodiment of what is wrong. Would a Japanese designer do this, doubtful.

4. The customer is key. One should never ask the customer to assemble the product, any moron should know that. I recall having this discussion in NYNEX (now Verizon) back in the 1980s when they were just getting out of being a monopoly. The customer, given a choice, will go with the provider who respects them, who anticipates their needs. ZigZag was and is clueless on this issue. He just seems to say that the customer should improvise and fix the fault, as if he has some divine insight.

5. ZigZag is thus a representation for what I see more and more of in the US. Young arrogant people who have a modicum of knowledge and will push their arrogance on the customer. This is NOT Jobs, it is however much of what we see from the young developers. It is truly intellect in decline, it is the taking of the easy way out, namely they thought of this so it must be correct and you should use their simple idea or you are stupid. This is a product of our state run education systems.

6. The problem then is with TI and ZigZagJoe, each in their own way. TI, for no longer designing properly, it is truly a design flaw, and for that as an American company, a diminution of intellect. As for ZigZagJoe, he is unknown, and other than what appears to be youthful ignorance and arrogance, often telltale signs of American youth, he could frankly just be generationally representative.

It is a shame we do not have an overabundance of the perfectionists like Jobs, but we have all too many of the snarks like ZigZag!

Bandwidth and the Negroponte Switch

About 20 years ago Prof Negroponte published his switch concept: simply TV would go from wireless broadcast to fiber and telephony would go from copper wires to wireless. We show the idea above.

But what has happened. Twenty years ago I also proposed in an FCC Pioneer Preference Filing the extensive use of multi beam base station antennas, a technique I had worked on for thirty years by that time. Too early. Marty Cooper also started a company just after that which also was too early.

But what has happened since. The above graphic details some of the issues:

1. QPSK/CDMA led to OFDM, which is why Qualcomm bought Farinon, and we saw BPS/Hz gone from 1 to 10.

2. Video codecs have brought down HDTV from 200 Mbps to 2 Mbps.

3. Multi beam antennas have allowed beam pointing per subscriber.

The result, the number of instantaneous, yes I mean instantaneous, video channels per user can explode. How:
Stick fiber in the backbone and wireless at the edge, all IP. The we have the re-switch as below:

This shows the Negroponte switch goes back on video, namely video for the "last mile" can be all wireless, and yes with the same or even less spectrum.

So why are the incumbent wireless carriers demanding more spectrum? Ever heard of monopoly? And the DoJ/FTC is chasing Google, while the foxes run rampant! Lawyers.

Friday, April 27, 2012

Some GDP Details Q1 2012

We have added some details on the recent GDP results. Above shows a close up of the unchained.
The above details the amounts by sector.
The above shows Government spending. Note the drop in non-defense. Defense still is half the amount! Frankly one could halve Defense and still have a strong base.
 The above are the HH breakouts. There is a rise as we shall see below.
The above is the percent changes. Note the rise in all elements except housing. The spending seems to indicate some assurance that we will be better but not just yet.

GDP Update

The GDP is still dragging as seen in the above based on latest release. There is slow growth in core numbers and only slow growth based on limited inflation which is controlled by the FED.
M2 is still increasing but slowly and thus limited risk of inflation if one looks at this classic measure. However:
The FED still has massive amounts of currency stored in banks who still are holding onto the cash making substantial spreads. With an all Democrat FOMC we do not expect a change for at least five years in this plan unless the current Chairman is replaced by a very strong and astute monetarist.
Current calculated inflation is still quite low and trending downward. This is monetary inflation as contrasted to real inflation at the consumer level which we estimate to be in excess of 10%. What drives this down is the housing collapse and the current Administrations pressure to allow stagnant foreclosable properties to become walking dead.

Non surprises in the above chart for inflation components.

Wednesday, April 25, 2012

Subsidize Student Loans? Not the Problem

University Administrators are a class unto themselves. If they ran US corporations we would now be paying $5,000 for a gallon of milk. Why? Because they would have raised great amounts to construct massive barns for the cows, and massive cow support systems, but failed to figure in the life cycle costs or removing the cow manure. That is what would drive the costs of milk.

Now to the NY Times and Congress. Students have gotten hooked on ever escalating tuition. Part their fault. If you pay $250,000 for a BA in Roman Art or Byzantine History, then you have set yourself for a tragic economic crisis, unless you are a Trust Fund baby. If you are middle class you have demonstrated your total lack of understanding of our economy. And perhaps you are doomed to fail.

When I started tuition was about $1,200 per year, a small fraction of the average middle class salary, one may say 10%. Thus one could have parents pay, but equally one could work in summers and save and get by paying one's own tuition. Now tuition is $60,000 and it has become a multiple of average middle class salaries and unpayable by any summer job other than selling drugs or arms.

Why? Professors just do not get paid that much more and offices really are no better. Labs got more complex but alas the Administrative overhead has exploded and the buildings have life cycle costs that have exploded. Namely University Presidents have expanded plants with no thought to their life cycle costs. Then as they costs kick in, yes buildings age, and need upgrading, the weakest link is fixed and the others go to disrepair. And as Administrators grow they suck up more buildings, more costs, and drive students and faculty away.

It is a deadly cycle. More Government subsidies will not solve the problem. Revolt against Administrators is the only solution.

Pleckstrin Homology: A Spy Novel or a New Target for Melanoma

There has been some recent work (see DeSemir et al) on the targeting of the Pleckstrin Homology, “PH”, as an additional target for controlling melanomas. As DeSemir et al state regarding the Pleckstrin Homology Domain-Interacting Protein (PHIP) (slightly edited):

Given the important role of Akt in the IGF (Insulin Growth Factor) axis, we then assessed whether Phip was involved in Akt activation. …

Because of the uncharacterized role of PHIP in cancer, we performed cDNA microarray analysis to identify the global patterns of gene expression after suppression of Phip expression. Significance analysis of microarrays identified 51 down-regulated genes (including Igf2 and Tln1) and 184 overexpressed genes … Thus, PHIP can regulate the expression of upstream mediators of the IGF axis and downstream mediators of tumor cell invasion.

 Having demonstrated Phips functional role in promoting murine melanoma metastasis, we examined its impact on human melanoma progression.

We performed immunohistochemical analysis of PHIP expression on a tissue microarray cohort of 345 patients with primary cutaneous melanoma …

High levels of PHIP expression were found in each histological subtype of melanoma and accounted for almost one-third of the melanomas in this cohort.

High PHIP expression correlated significantly with the presence of ulceration, an adverse prognostic factor incorporated into the staging classification for melanoma whose biologic basis is poorly understood…

PHIP overexpression was significantly predictive of reduced distant metastasis-free survival … and disease-specific survival …

PHIP overexpression was an independent predictor of DMFS  and DSS…

PHIP overexpression directly correlated with the progression of distant metastases, and with reduced survival, in both murine and human melanoma.

The human PHIP gene resides on the 6q14.1 locus. Deletions of the 6q arm have been shown in melanoma  and have been suggested as a possible diagnostic marker. …

FISH analysis revealed that the PHIP locus was still present in all 78 melanomas examined.

Importantly, there was a significant correlation between PHIP copy number (assessed as a percentage of cells with three or more copies) and the corresponding PHIP immunohistochemical scores …

 Melanomas with immunohistochemical scores of 13 had a significantly higher percentage of cells with increased copy number compared with melanomas with a PHIP score of 0 .. In addition, 80.6% of PHIP 3 melanomas had three or more copies of the PHIP locus.

Although we found no evidence of amplification, because PHIP copy number remains comparable with chromosome 6 centromeric copy number increased copy number of the PHIP melanomas for β-catenin mutations at six different sites (previously described in melanoma; COSMIC database) and found no mutations at any of these sites.

These results show that PHIP levels can be activated in a unique molecular subset of melanoma independent of mutations in these other four genes.

This brief summary of the work makes PHIP an interesting and attractive target. It presents a pathway element which is more a facilitator rather than a major participant (see Weinberg). As we shall note later from DeSemir et al, they contend that the PHIP target presents a more universal target especially for those melanomas which do not have well defined mutations in BRAF, NRAS or PTEN. As we have discussed previously, for example, PTEN mutations, loss of control in the Akt pathway, is often an end game in cancer progression, for example in prostate cancer and many others.

We will attempt to assemble some of the literature and present a brief summary of this area. In many ways it is distinct from the pathway targets themselves since the PH targets are smaller and often are found in many of the pathway elements. The PHD. Pleckstrin Homology Domain, has received significant interest by other researchers especially regarding its pathway control effects. For example Hirano et al have examined it in CML and Miyamoto et al in cardiology and the Akt pathway.

Pleckstrin and the Homology

We first examine Pleckstrin then its homology and its function. We begin first with Pleckstrin. Pleckstrin is a specific protein which is found in blood platelets. The name is derived using the concatenation of the phrases: Platelet and LEukocyte C Kinase substrate and the KSTR string of amino acids. It is located on 2p13.3.

Now the Pleckstrin Homology is defined as:

Pleckstrin homology domain (PH domain) is a protein domain which consists of approximately 120 amino acids. The PH domain is present in various proteins which are key elements of intracellular signaling as well  as constituents of the cytoskeleton.

This domain can bind phosphatidylinositol lipids within biological membranes (such as phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate. PIP3 and PIP2), and proteins such as the βγ-subunits of heterotrimeric G proteins, and protein kinase C.

Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways.

PH domains can be found in many different proteins, such as ARF. Recruitment to the Golgi in this case is dependent on both PtdIns and ARF. A large number of PH domains have poor affinity for phosphoinositides and are hypothesized to function as protein binding domains. Proteins reported to contain PH domains belong to the following families:

  • ·       Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. Pleckstrin is one of the rare proteins to contain two PH domains.
  • ·       Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family.
  • ·       Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily.
  • ·       Insulin Receptor Substrate 1 (IRS-1).
  • ·       Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and S. cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr.
  • ·       Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) isoforms gamma

Discussion of PH in cancer is somewhat sparse and limited in detail. Bunz has a short reference (p 191) and Weinberg also has passing comments in several locations, and Schulz on p. 120.
PH and Pathways

The following is from Marks et al and shows how the PH domain can act as a binding and activating substrate in the overall pathway cascade process. It can unwrap from the complex protein of which it is a part, and then it can attach to a membrane protein and this allows activation, in the case below, by phosphorylating the resulting domain substrate. This simple model offers also a mechanism to block pathway activation as well.

 As Huang and Oliff state regarding the PH domain:

There are three members of the AKT (PKB) family. They are widely expressed and implicated in apoptosis, insulin signalling and growth regulation. All three contain a pleckstrin lipid-binding domain (PH Domain)and are activated at the membrane by upstream kinases. Candidates for this upstream regulatory activity include integrin-linked kinase, PDK-1, and possibly AKT itself. In addition, AKT activity is regulated indirectly through modulation of lipid metabolism.

The loss of PTEN (a protein and lipid phosphatase) activity and the gain of PI3K (a protein and lipid kinase) activity correlate with AKT activity and binding of AKT to the membrane lipid, PI(3)P. The PI3K inhibitor wortmannin has already been shown to inhibit AKT signalling. Some proteins that have been shown to be substrates of AKT and relevant to apoptosis are listed. Antagonists of AKT kinase activity should inhibit signalling through these downstream effectors.

We demonstrate this pathway selectivity and control below. Here we have modified a Figure from Huang and Oliff to make the point that loss of PTEN control or over-activation of the Akt pathway can result in excess of proliferation and suppression of apoptosis. This is generalized below:

 PTEN is a major control protein in pathway management. As Chow and Baker had stated in an earlier description of the effects of PTEN:

Soon after the discovery of its PIP3 phosphatase activity, PTEN was found to negatively regulate the PI3K/AKT pathway . Generation of PIP3 by growth factor-stimulated PI3K activity results in membrane recruitment of the serine–threonine kinase AKT via its pleckstrin homology (PH) domain, and activation by phosphoinositide-dependent kinases (PDK1 and 2) . Numerous AKT substrates have been identified affecting a broad range of cellular activities .

A few that have been implicated in oncogenic transformation include the Forkhead family of transcription factors (FOXO), p27KIP1, MDM2, GSK3, BAD, IKK-b, and tuberin (TSC2), a negative regulator of mTOR. The specific targets phosphorylated by AKT vary with physiological stimuli and cell context and the mechanism for this selection is unclear. The complexity of this pathway is further underscored by the recent finding that mTOR can act both upstream and downstream of AKT activation. The raptor–mTOR complex can phosphorylate and activate AKT while the raptor–mTOR complex, which regulates growth and protein translation, can be activated downstream of AKT .

PTEN-mediated regulation of the PI3K/AKT pathway results in cell context-dependent effects on cell size, proliferation and survival. A dominant-negative form of AKT rescues the lethality caused by PTEN deficiency in flies.  This strongly suggests that AKT is the major critical downstream target of PTEN activity ..

The impact of Akt has been understood now for quite a while and the BRAF facilitation when mutated has become a focal element of the control mechanism. However PH also plays a significant role and this too has been understood. As Dehaia states:

PI3-kinase triggers signaling through multiple pathways, many of which are thought to associate with cell growth and survival. PTEN, working in opposition to PI3-kinase, is therefore associated with cell death or arrest signals. Phospholipid residues such as PtdIns(3,4,5)P3 are present in cells upon stimulation by several growth factors, such as platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), and epidermal growth factor (EGF).

Upon activation by growth factor, proteins containing a pleckstrin-homology (PH) domain are recruited to the membrane 3 where they associate with phospholipids. One of the PH domain-containing proteins relevant in this pathway is the serine-threonine kinase, AKT, also known as PKB or RAC1. AKT, in turn, and as a consequence of lipid binding, alters its conformation to allow two of its residues, threonine 308 and serine 473, to be phosphorylated and therefore become active.

The kinase responsible for phosphorylation of threonine 308 is phosphonositide-dependent kinase 1 (PDK1), an enzyme which also contains a PH domain and is therefore dependent on lipid binding for its full activity. There is some preliminary evidence, predominantly from in vitro studies, that a second lipid-dependent, PH domain-containing enzyme, ILK (integrin-linked kinase), is responsible for phosphorylation of the serine 473.

Further, a recent paper has proposed that the kinase responsible for Ser 473 phosphorylation might in fact be PDK1, when it associates with certain specific proteins, such as PDK1 interacting fragment (PIF), as seen by in vitro studies. By dephosphorylating D3 residues on PtdIns(3,4,5)P3 and PtdIns(3,4)P2, PTEN works in opposition to the PI3K/AKT pathway and therefore counteracts cell survival mechanisms elicited by this signaling. The mechanisms of cell survival associated with AKT appear to involve multiple pathways, including growth factors, cytokines, c-myc overexpression, UV irradiation, and matrix detachment.

One of the known signals activated by AKT is its phosphorylation of the Bcl-2 family member, BAD: phosphorylation of BAD results in suppression of apoptosis. AKT has also been reported to counteract the apoptotic response of several cellular factors. Recently, the transcription factor NF-kappaB has been implicated in the apoptotic response antagonized by the PI3K/AKT pathway

Thus we have demonstrated that PH activateable proteins such as Akt can be deactivated if it were possible to focus on the PH Domain as a target sector. Recent work has demonstrated that in some detail.

Current Understanding

We now will examine some of the current understanding of PH and its implications in melanoma specifically. We examine the work of two other groups and then readdress that of DeSemir et al.

As Farang Fallah et al state:

As a major substrate of the insulin receptor, insulin receptor substrate 1 (IRS-1) plays a central role in transducing insulin-dependent signals that regulate biological processes such as cell growth and cellular uptake of glucose. IRS-1 is a modular protein comprised of an N-terminal region harboring a pleckstrin homology (PH) domain, followed by a phosphotyrosine binding (PTB) domain that cooperatively ensures selective recognition and efficient substrate phosphorylation by the activated insulin receptor (IR). The C-terminal portion contains multiple tyrosine phosphorylation motifs which serve as docking sites for the recruitment of various SH2 (Src-homology 2) domain containing signaling molecules, such as phosphatidylinositol 3-kinase (PI 3-kinase), Grb-2 adaptor protein, and SHP2 (SH2 containing phosphatase 2) tyrosine phosphatase, which in turn elicit the activation of biochemical cascades that promote the metabolic and growth responses to insulin….

In the present study we demonstrate that overexpression of either PHIP or IRS-1 alone in muscle cells was not sufficient in promoting transport of GLUT4 to plasma membrane surfaces This is consistent with other observations, indicating that activation of IRS-1-associated signaling effectors such as PI 3-kinase, although necessary, is not sufficient for GLUT4 activation.

Notably, growth factors such as platelet-derived growth factor and interleukin-4 can activate PI 3-kinase as efficiently as insulin and yet fail to stimulate glucose transport in insulinsensitive cells (17, 22).

One possible explanation is that additional PHIP/IRS-1/PI 3-kinase-independent pathways are required to coordinate GLUT4 intracellular routing. Indeed, recent evidence points to a novel insulin-responsive pathway that recruits flotillin/CAP/CBL complexes to IR-associated lipid rafts in the plasma membrane, an event which is thought to potentiate GLUT4 docking to the cell surface after IR activation.

Our data, however, provide support for the involvement of PHIP/IRS-1 complexes in glucose transporter GLUT4 translocation in muscle cells. Specifically, the use of DN-PHIP or IRS-1 PH domain constructs known to interfere with efficient IR–IRS-1 protein interaction, and hence productive signal transduction from IRS-1 to PI 3-kinase, blocked the ability of insulin to stimulate GLUT4 mobilization in L6 myoblasts and inhibited insulin-stimulated actin cytoskeletal reorganization, a process required for the productive incorporation of GLUT4 vesicles at the cell surface. Moreover, this inhibition did not coincide with changes in the autophosphorylation status of the IR.

As Barnett et al state:

Akt/PKB (protein kinase B) is a serine/threonine kinase which has a key role in the regulation of survival and proliferation [1–8]. There are three isoforms of human Akt (Akt1, Akt2 and Akt3) and they all have an N-terminal PH (pleckstrin homology) domain and a kinase domain separated by a 39-amino-acid hinge region. The PH domains have approx. 60% identity and the kinase domains are >85% identical.

The hinge region is the least conserved at approx. 28% identity. The Akt active-site residues, described in a recent report on the crystal structure of Akt2 containing an ATP analogue and a peptide substrate , are the same in all three iso-enzymes. Based on the high degree of homology between the AGC protein kinase family members, the identification of specific active-site inhibitors has been predicted to be difficult. The identification of Akt iso-enzyme-specific inhibitors seemed to be an even greater challenge….

Two Akt inhibitors were identified that exhibited isoenzyme specificity. The first compound (Akt-I-1) inhibited only Akt1  while the second compound (Akt-I-1,2) inhibited both Akt1 and Akt2 with IC50 values of 2.7 and 21 μM respectively. Neither compound inhibited Akt3 nor mutants lacking the PH (pleckstrin homology) domain at concentrations up to 250 μM.

These compounds were reversible inhibitors, and exhibited a linear mixed-type inhibition against ATP and peptide substrate. In addition to inhibiting kinase activity of individual Akt isoforms, both inhibitors blocked the phosphorylation and activation of the corresponding Akt isoforms by PDK1 (phosphoinositide-dependent kinase 1).

A model is proposed in which these inhibitors bind to a site formed only in the presence of the PH domain. Binding of the inhibitor is postulated to promote the formation of an inactive conformation. In support of this model, antibodies to the Akt PH domain or hinge region blocked the inhibition of Akt by Akt-I-1 and Akt-I-1,2. These inhibitors were found to be cell-active and to block phosphorylation of Akt at Thr308 and Ser473, reduce the levels of active Akt in cells, block the phosphorylation of known Akt substrates and promote TRAIL (tumour-necrosis-factor-related apoptosis inducing ligand)-induced apoptosis in LNCap prostate cancer cells.

We can now return to the results of DeSemir et al. As they look to the usefulness of PHIP they state:

Although melanomas with mutant v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) can now be effectively targeted, there is no molecular target for most melanomas expressing wildtype BRAF. Here, we show that the activation of Pleckstrin homology domain-interacting protein (PHIP), promotes melanoma metastasis, can be used to classify a subset of primary melanomas, and is a prognostic biomarker for melanoma.

Systemic, plasmid based shRNA targeting of Phip inhibited the metastatic progression of melanoma, whereas stable suppression of Phip in melanoma cell lines suppressed metastatic potential and prolonged the survival of tumor-bearing mice.

The human PHIP gene resides on 6q14.1, and although 6q loss has been observed in melanoma, the PHIP locus was preserved in melanoma cell lines and patient samples, and its overexpression was an independent adverse predictor of survival in melanoma patients. In addition, a high proportion of PHIP-overexpressing melanomas harbored increased PHIP copy number.

PHIP-overexpressing melanomas include tumors with wild-type BRAF, neuroblastoma RAS viral (v-ras) oncogene homolog, and phosphatase and tensin homolog, demonstrating PHIP activation in triple-negative melanoma. These results describe previously unreported roles for PHIP in predicting and promoting melanoma metastasis, and in the molecular classification of melanoma.

This demonstrates the extended ability of PHIP to enhance the usefulness of other markers. They continue as follows:

As a result, triple-negative melanomapatients, whose tumors harbor wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), neuroblastoma RAS viral (vras) oncogene homolog (NRAS), and phosphatase and tensin homolog (PTEN) (the most common mutations observed in melanoma), are not candidates for most targeted therapies developed to date.

This as we have noted before is one of the most significant findings. We know that BRAF mutations are currently targeted with some beneficial albeit temporally limited results. Perhaps PHIP may add an additional targeting.

They conclude:

Overexpression or mutation of genes that play important roles in tumor progression. A high proportion of melanomas are characterized by BRAF, NRAS, or PTEN mutations. However, the molecular basis of triple-negative melanomas lacking these mutations is poorly characterized. Our results suggest that PHIP levels may be used to classify some melanomas that lack these three mutations. It is likely that additional molecular aberrations will be identified to further characterize triple-negative melanomas.

Along with recent studies demonstrating that the IGF axis is activated in melanomas with acquired resistance to BRAF inhibition (23), these studies have identified IGF signaling as an important alternative pathway to promote melanoma progression. Overall, our studies identify PHIP as a molecular mediator of melanoma progression that also appears to function in the setting of a subset of triple-negative melanomas.

Clearly BRAF, NRAS and PTEN mutations are well defined targets, BRAF especially for melanoma and PTEN seems to span a wide number of cancers. However if they are not changed the PHIP mutation seems more in line with wit an reasonable target.

1.     Barnett, S., et al, Identification and characterization of pleckstrin-homology-domain dependent and isoenzyme-specific Akt inhibitors, Biochem. J. (2005) 385, 399–408 (Printed in Great Britain) p 399.
2.     Biro, A., Class III Phosphoinositide 3-kinase in Melanoma, Thesis, Univ Basel, 2011.
3.     Bunz, F., Principles of Cancer Genetics, Springer (New York) 2008.
4.     Chow, L., S. Baker, PTEN function in normal and neoplastic growth, Cancer Letters 241 (2006) 184–196.
5.     Dehaia, P, PTEN, a unique tumor suppressor gene , Endocrine-Related Cancer (2000) 7 115–129,
7.     Farhang-Fallah, J., et al, The Pleckstrin Homology (PH) Domain-Interacting Protein Couples the Insulin Receptor  substrate 1 PH Domain to Insulin Signaling Pathways Leading to Mitogenesis and GLUT4 Translocation, MOLECULAR AND CELLULAR BIOLOGY, Oct. 2002, p. 7325–7336.
8.     Hirano, I., et al, Depletion of Pleckstrin Homology Domain Leucine rich Repeat Phosphatases 1 and 2 by Bcr-Abl Promotes Chronic Myelogenous Leukemia Cell Proliferation through Continuous Phosphorylation of Akt Isoforms, Jrl Bio Chem V 284, 2009.
9.     Huang,P., A.  Oliff, Signaling pathways in apoptosis as potential targets for cancer therapy, TRENDS in Cell Biology Vol.11 No.8 August 2001.
10.  Marks, F., Cellular Signal Processing, Garland (NY, NY) 2009.
11.  McGarty, T., Prostate Cancer Genomics: A Systems Approach, DRAFT , 2012.
12.  Miyamoto, S., et al, PHLPP-1 Negatively Regulates Akt Activity and Survival in the Heart, Cir Res, 2010.
13.  Schulz, W., Molecular Biology of Human Cancers, Springer (New York) 2007.
14.  Weinberg, R., Biology of Cancer, Garland (New York) 2008.

Monday, April 23, 2012

Medicare Report

CMS has released the Medicare Trustee Report and we shall be looking into details.

Saturday, April 21, 2012

Some Thoughts on Bandwidth

The NY Times has recently reported on wireless that the carriers are seeking more bandwidth. They state:

The wireless carriers say that in the next few years they may not have enough of it to meet the exploding demands for mobile data. The result, they ominously warn, may be slower or spotty connections on smartphones and tablets. They imply in carefully couched language that, given the laws of supply and demand, the price of cellphone service will soar. 

I would suggest several observations:

1. With the change from QPSK to OFDM we have gone from 1 bps/Hz to almost 10 bps/Hz.

2. With smart antennas we will go from 10 bps/Hz to over 100 bps/Hz.

3. At the same time data rates for video using MPEG X, 4 to 5, we see rates for HDTV dropping from 20 Mbps to 4 Mbps to 2 Mbps.

So as capacity increases and as demand decreases where is the gap?

Somehow this set of simple facts was missing from the article, and from the carriers as well.

Fairness: And Others Words

What really is fairness. In today's political debate it is about outcomes. In most other contexts it is about the rules. Fairness means following the rules, not what the winner or loser gets. In a NY Times piece there is a post hoc description of fairness.

The author states:

Economics, by contrast, hasn’t traditionally been much concerned with fairness. Instead, economists have based their analysis on “Homo economicus,” a model human being who is perfectly rational and perfectly guided by self-interest. 

The financial crisis of 2008 made it hard to believe in a world of perfectly rational actors, even when they earn million-dollar salaries and have advanced degrees. Now, a growing body of research is challenging the second part of the definition of Homo economicus — that he is guided purely by self-interest.  

The alternate view was advanced by Armin Falk, a Bonn University economist, at a recent economics conference in Berlin organized by the Institute for New Economic Thinking. It emphasizes the importance of fairness and trust to human behavior. This approach takes as its starting point the idea that we are social animals, driven powerfully by how we fit into our community. 

The definition that they seem to be bringing out is fairness of outcomes and loss of individuality, and communalism. In contrast what has built a competitive entrepreneurial America is a fairness in rules, namely that one cannot steal or bribe to achieve a goal, one cannot steal or kill likewise, that there are rules and then let the players follow them to the end. The end may be quite disparate in results. That is the true nature of fairness.

Fairness is NOT ensuring that no matter how one functions that the end point is the same, that the community is more important than the individual. For it is the individual who takes the risk, who goes out bare into the playing field and attempts to seek a return. If Government will punish that efforts by redistributing what has been gained then why work at all, we should just sit back and watch the system collapse.

She continues:

Some of Dr. Falk’s most recent work takes the question of fairness back into the medical laboratory. He and a team of colleagues asked what the physical impact of unfair pay was, this time as measured by our heart rate rather than brain waves. Experimental subjects who felt they were being unfairly paid showed higher heart rate variability, an indicator of stress that has been shown to predict heart disease. 

Faulty tires and failing hearts are the grim consequences of unfairness suggested by Dr. Falk’s talk. But the new vision he and like-minded researchers are developing of how human beings operate in the economy is actually rather uplifting. We aren’t driven solely by self-interest; fairness and decency matter, too. Kindness and justice turn out to be useful concepts not just at the pulpit or among philosophers, but also as essential tools in the workplace. 

 If you feel you are poorly compensated, then quit and start your own company, this is America not Germany. You can readily do that, at least for a while. Life does not work in some 19th century Utopian commune, they are all failures. Success is driven by many factors and the ability to deal with risk is key. If you cannot do that then go work for the Government, it appears that it is impossible to get fired no matter how incompetent.

Medicare: A Release to Watch

 According to Medpage:

On Monday, the Medicare Board of Trustees releases its annual report, which will offer a long-term assessment of the solvency of Medicare.

This will be followed closely.

Tuesday, April 17, 2012

Mathematics, Models, Reality and Gnostics

Using mathematical models to understand and predict physical phenomenon has been around for a few centuries. The physical sciences is based upon them and engineering cannot function without them. However, there are other applications where we find that certain limitations may exist. Let me first start with a quote from Cassirer, The Philosophy of the Enlightenment, pp 108-109:

A survey of the special problems of eighteenth century epistemology and psychology shows that in all their variety and inner diversity they are grouped around a common center. The investigation of individual problems in all their abundance and apparent dispersion comes back again and again to a general theoretical problem in which all the threads of the study unite This is the problem which Molyneux  first formulated in his Optics, and which soon awakened the greatest philosophical interest. 

Is the experience derived from one field of sense perception a sufficient basis on which to construct another field of perception that is of qualitatively different content and of a specifically different structure? Is there an inner connection which permits us to make a direct    transition from one such field to another, from the world of touch, for instance to that of vision? Will a person born blind, who has acquired an exact knowledge of certain corporeal forms by means of experience and so can distinguish accurately among them, have the same power to distinguish objects if, as a result of a successful operation, he gains possession of his visual faculties, and is required to judge concerning these forms on the basis of purely optical data without the aid of the sense of touch?

The point, perhaps one should be cautious in employing techniques which work well in one field but may have limits in others. Let me consider two recent efforts.

In Science  there is a recent article on the use of models in understanding the operation of genetic pathways. Working in the field at this time I can fully understand the attraction. Yet I also understand the complexity and potential for misuse. The author states:

Four hundred years ago, Galileo observed that “Nature’s great book is written in mathematical language.” Since that time, physical phenomena have been described by mathematical equations, yet biology has remained qualitative. A possible explanation is that complex behavior in physics emerges from relatively simple interactions between many copies of few elements, whereas biological complexity results from nonlinear interactions of many heterogeneous species. In this sense, biological systems are similar to engineered machines: Inventories of both airplane parts and animal cell proteins consist of tens of thousands entries; cell interactomes look similar to machine blueprints; and performances of both engineering and biological structures are characterized by robustness and noise resistance. This analogy has limitations: Biological systems are built from stochastic and unreliable parts; are evolved rather than designed; and are subject to reverse, not direct, engineering. Nevertheless, in the last two decades, the mathematics usually applied to engineering and physics has been often used in cell biological studies where quantitative models serve as a guide for failing intuition.

Here I would agree and disagree. Mathematical models are embodiments of intuition, of understanding, not surrogates for them. The problem is that this is a very difficult problem. In addition there is “noise” in these systems which create uncertainty. Do we model the noise as random or is it necessary to understand its dynamics as well and push the noise level lower. Thus is miRNA a noise element or an element we must account for in detail.

The author continues:

The foundation for this surge was laid by two seminal papers that appeared 60 years ago. One was the biologically abstract and mathematically simple manuscript by Alan Turing proposing that a pattern can emerge in an initially homogeneous mixture of two chemicals. Turing used two linear partial differential equations (PDEs) with few parameters to demonstrate that two chemicals, a slowly diffusing “activator” and a rapidly diffusing “inhibitor,” could concentrate in different regions of space. Untested and unsubstantiated at the time, this conceptual model has served as a basis for many studies of polarity, chemotaxis, and development. Another work by Hodgkin and Huxley was mathematically complex, grounded in experimental data and very detailed: Many ordinary differential equations (ODEs) with many parameters and nonlinearities were used to describe ion currents through voltage-gated channels in the axon membrane. The parameters and nonlinearities were measured, and the model reproduced the observed electric bursts in nerve cells, which revolutionized our understanding of excitable systems.

Here I have a true concern. The Turing paper is a true classic. It was intuition to the extreme. I have used it in modeling plant color patterning, and I am currently using it as a means to understand stem cells in melanoma. The problem is that despite the metaphor provided by Turing it may or may not be the correct one and the understanding to assure ourselves is still a bit distant. Let me consider cancer at a high level. It is characterized by:

1. Loss of control of the cell cycle. Namely we have ligands, then receptors, then pathways and then promoters, the cyclins, and then the cycle, and on and on. Control of the cell cycle will stop the multiplication of the malignant cell.

2. Loss of Location: Loss of E-cadherin attachment capacity results in melanocytes going where they should not. Why and is this a Turing effect?

3. Stem Cells: Are there some collection of control cells, the stem cells, which send out in a Turing like fashion in space control signals. If one removes the stem cell do the others die off? I have observed some of this in prostate neoplasia but it is at best anecdotal.

4. Mutations:How do they occur and why?

The authors continue:

These two papers symbolize the opposite ends of “modeling space”. It is tempting to pronounce that we will be describing cells in ever more accurate terms and minute detail, moving from focused and conceptual (like ODEs describing three-node motifs in regulatory networks) to accurate and broad models, perhaps ending with a “whole-cell model” that completely recapitulates cell behavior on a computer, substitutes for wet laboratory experiments and makes personalized medicine possible. This is an appealing, if distant, goal. Meanwhile, this view subtly puts broad models above focused ones and suggests that there is a modeling “Road to Valhalla.”

I doubt that we are near that “Road” yet but there is much superb work being done. If I had to bet I would bet on Turing. I have seen it function in plant patterning with secondary pathways, perhaps in cancer cells as well.

But the key question is: Are these models and methods reliable for this domain of knowledge. Have we managed to challenge the Cassirer model? I think they are worthwhile. I think they will function quite well but not as simply as many think. After all the control system for a B-2 bomber may be as complex as the pathways of a single cell organism, we just do not yet know enough. But it is worth a try.

Now to the other extreme, macroeconomics. A recent book, The Assumptions Economists Make, by Schlefer, is an interesting contribution to understanding the world of macroeconomists, from the perspective of an outsider. It also demonstrates the use and gross misuse of models, unlike the discussion above.

Let me start by commenting on a paper by Mankiw and Weinzierl, An Exploration of Optimal Stabilization Policy, which states in an opening set of assumptions (modified):

The economy is populated by a large number of identical households. The representative household has the following objective function:


where C, is consumption in period t, G is government purchases, and b is the discount factor. Households choose consumption but take government purchases as given.

Households derive all their income from their ownership of firms. Each household's consumption choices are limited by a present-value budget constraint:

P1(I1-T1-C1)+ P2(I2-T2-C2)/(1+i1)=0

where P is the price level, I is profits of the firm, T is tax payments, and i is the nominal interest rate between the first and second periods. Implicit in this budget constraint is the assumption of a bond market in which house­holds can borrow or lend at the market interest rate.

Just what does this model have to do with reality? Why are households identical, is it not the real issue that they differ, and that their difference changes in time. and what objective function, is there not a psychological element as well and that often the choices are not logical or consistent. And what household owes its income from owning firms, very few. Thus, this statement, typical of almost all, assumes a world not in evidence. In contrast to my biological pathways, which we struggle so hard to understand with facts, the economists can easily say, "assume a spherical elephant". Yet none exists.

Unlike the problems in the world of genomics where we do not assume but base our models on facts, like science and engineering in general, this paper and this statement is the typical example of what Schlefer discusses, namely macroeconomists using equations to justify the total lack of reality. Schlefer goes through many of the absurd assumptions made by economists in their models and then he correctly articulates the arrogance many have in stating that they have knowledge that others lack. They have become the Gnostics of the twenty first century.