The EU and Cohesion

Prof Sachs has an article on The Syndicate which discusses the EU, the failed Arab Union and the idea of a world of unions. His thesis is that a weakening US, I suspect under the current President, means that other regions must find out how to work amongst themselves. He states:

The Middle East is in a strong position to help itself. There is a high degree of economic complementarity between Egypt and the oil-rich Gulf States. Egypt can supply technology, manpower, and considerable expertise for the Arab region, while the Gulf provides energy and finance, as well as some specialists. The long-delayed vision of Arab economic unity should be returned to the table.

Israel, too, should recognize that its long-term security and prosperity will be enhanced as part of an economically stronger region. For the sake of its own national interests, Israel must come to terms with its neighbors.

Other regions also will find that the decline of US power increases the urgency of stronger cooperation between neighbors. Some of the greatest tensions in the world – say India and Pakistan, or North and South Korea – should be defused as part of region-wide strengthening. As the EU shows, ancient enmities and battle lines can be turned into mutually beneficial cooperation if a region looks forward, to resolving its long-term needs, rather than backward, to its long-standing rivalries and conflicts.

 He uses the EU as am example of regional development. He states:

The EU has created a zone of peace where once there was relentless war. It has provided the institutional framework for reuniting Western and Eastern Europe. It has fostered regional-scale infrastructure. The single market has been crucial to making Europe one of the most prosperous places on the planet. And the EU has been a global leader on environmental sustainability.

 Now having lived in the middle of this region for a decade it was still clear that the Thirty Years War had no yet ended, the dislike of Czechs and Slovaks still was there, the fear of the Germans exists and the Irish never really liked the Poles coming to their lands, the French like only the French, and the English still have a strong class society and still ban Catholics, just look at the recently converted ex PM.

Now frankly in the Middle East we have a situation  that has lasted since 680 AD. Probably before. Egypt has ups and downs since the remnants of Alexander took over Alexandria, Ptolemy was always a problem, and Carthage having been settled by Arabs had prospered but after its fall wheat was good but just for so long. Needless to say Persia has been up and down but the rest has had less to show for itself since the Assyrians.

Is it the fault of the US as Sachs seems to infer? Is it a cultural problem. One should consider what Palestine could have become if it had used the Billions sent there for productive purposes. Thus do we still have remnants of a "Thirty Years War" in the Middle East without end, or is it as Sachs seems to say, we the US are faltering and they must get on with it themselves. Well what are they waiting for?

Medicare, Medicare, Medicare!

The New Republic writes about the Hochul election and the Medicare issue. As they state in the intro to the piece:

Hochul bounded to the stage of a union hall in Amherst, just northeast of Buffalo, late Tuesday as the newly elected congresswoman from the ruby red congressional district that brought us Jack Kemp, Bill Paxon, and Tom Reynolds. After all the requisite hugs and thank yous, she mentioned her plans to fight to close corporate tax loopholes and make millionaires pay their fair share. “We can do all that,” she said, “and not decimate Medicare.” Hearing that single word, the crowd erupted with the mantra of the Hochul campaign. “Medicare! Medicare! Medicare!”

 Now I want to make two points.

First, a tale of Medicare from one there. I watch my blood sugar, just in case, family history and all, diet and exercise, try not to get any of the sequellae that I see and write about. So now Medicare pays for the glucose strips, under the new law. Since that change in January my supplier changed billing from me to Medicare, then because the supplier always used my plain old name, no middle initial and no Jr at the end, never really used that, Medicare denied payment. So I called the supplier, mistake number one, they got Medicare, mistake number 2 and here is the result. Since Medicare pays I am not allowed to. But since the supplier has the wrong spelling, Medicare will not pay, but since the wrong spelling can only be corrected with a new prescription and an re-registration, I must re-apply to my supplier under my new name, wait till they tell Medicare etc, you kind of get the tale, and Oh yes, I am not allowed by law to buy it myself!

So what is the problem of medicare, a bunch of GS5s and idealists as managers who have no idea what the real world i like. Hours patiently getting the cats herded and yes we still have not remedied the problem. I cannot buy it myself! If however my kidneys were to fail, then they will pay!

Now to Medicare. Some facts:

1. It is a train wreck in process. Folks, it will not last and Ryan recognized that.

2. Vouchers and private insurance will not work. Just look at the confusion over Part D, the drug component.Some 70 year old with mild dementia is really going to have a tough time selecting a plan and managing it.

3. The principle of Medicare is a valuable one, it has merit.

4. Medicare is truly inefficient and spends too much. My classic example if $300,000 for an IgG transfusion for Lyme disease, yes they pay for that!

5. Every system is scammed, and there is fraud and waste, but the current system almost encourages that.

6. There should be means testing. There should be a slight Medicare Tax increase, and the age should be pegged to a life expectancy number, not a specific date.

Ryan should have approached this incrementally, I suspect he has a tin ear. The problem now is that the Democrats will push back, nothing will happen and we go down the financial tubes.

Poor, poor politicians.

A New View of Cancer Cell Growth

In a recent paper by Hanahan and Weinberg ( Hallmarks ofCancer: The Next Generation, Cell, 2011) has some interesting observations on what has been developed in the area of cancer research. As they state at the outset:

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list—reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the ‘‘tumor microenvironment.’’

 

Another dimension of complexity is not represented in this simple schematic: both neoplastic cells and the stromal cells around them change progressively during the multistep transformation of normal tissues into high-grade malignancies. This histopathological progression must reflect underlying changes in heterotypic signaling between tumor parenchyma and stroma. Such stepwise progression is likely to depend on back-and forth reciprocal interactions between the neoplastic cells and the supporting stromal cells, …. Thus, incipient neoplasias begin the interplay by recruiting and activating stromal cell types that assemble into an initial preneoplastic stroma, which in turn responds reciprocally by enhancing the neoplastic phenotypes of the nearby cancer cells.

The cancer cells, which may further evolve genetically, again feed signals back to the stroma, continuing the reprogramming of normal stromal cells to serve the budding neoplasm; ultimately signals originating in the tumor stroma enable cancer cells to invade normal adjacent tissues and disseminate. This model of reciprocal heterotypic signaling must be extended to encompass the final stage of multistep tumor progression—metastasis ...

The circulating cancer cells that are released from primary tumors leave a microenvironment created by the supportive stroma of such tumors. However, upon landing in a distant organ, these cancer cells encounter a naive, fully normal, tissue microenvironment. Consequently, many of the heterotypic signals that shaped their phenotype while they resided within primary tumors may be absent in sites of dissemination, constituting a barrier to growth of the seeded cancer cells. Thus, the succession of reciprocal cancer cell to stromal cell interactions that defined multistep progression in the primary tumor now must be repeated anew in distant tissues as disseminated cancer cells proceed to colonize their new found organ sites.

The model presented can be reduced to some simple descriptions, albeit a major change from a decade prior. The model is shown below:

Note that we have two different  steps. The classic first step, the Vogelstein model, takes the normal cell via some genetic change into a cancer cell. The model here requires some genetic change where loss of the control mechanism for growth or death are altered. Understanding normal pathways we can see that if we lose a genetic element associated with some pathway we can lose the control elements which would result in a cancerous cell. However that does not in and of itself lead to a metastatic type of cancer, it may merely lead to a cell which grows more than it should.

When we examine the cancer cell we see a multiple set of pathways and a corresponding multiple set of means in which the pathway control of homeostasis can be degraded to create a cancer cell. We show such a model below which is a modification of what the author’s present. 

This model is an example of the classic pathway models which we have discussed earlier . Each of the pathways are triggered by some external stimulus and one often wondered what happened to do this.

To answer this question is the context of a larger model the authors report on a volume of research which they have been doing every ten years. One of the interesting elements is the development of a multicellular control mechanism after a malignancy has developed. To do this the authors consider first a collection of interacting cells and second the signalling mechanism which are used between the cells.

The authors first consider six cell classes. They are:

1.     Cancer Cells – all the developing cancer cells

2.     Bone Marrow – cells in the bone marrow

3.     Tumor Promoting Inflammatory Cells

4.     Endothelial Cells – thin layer of cells inside the blood vessels

5.     Pericytes – connective tissue cell in blood vessels

6.     Fibroblasts – generates the intercellular fabric

Now the cells communicate via the following signalling proteins, each with its receptor. They are:

1.     EGF- Epidermal Growth Factor attached to EGFR (receptor) and initiates cell growth.

2.     HGF – Hepatocyte Growth Factor acts on endothelial cells and other cells

3.     PDGF – Platelet Derived Growth Factor for blood vessel formation and is also a powerful mitogen.

4.     VEGF – Vascular Endothelial Growth Factor produced by blood vessels and induces growth of new endothelial cells.

5.     TGF-β – Tumor Growth Factor stimulates cell growth and tumor growth.

6.     IL-1βapoptosis.

7.     Ang-1 – Angiopoetin 1 promotes angiogenesis

8.     CXCL-12 – Chemokine Ligand 12, This gene product and its receptor CXCR4 can activate lymphocytes and have been implicated in the metastasis of some cancers such as breast cancer.

9.     Protease  - involved in angiogenesis

10.  CSF-1 – Colony Stimulating Factor 1 a cytokine that controls the production, differentiation, and function of macrophages

We depict the result below:

Now we can reduce the above graphic to a system model which we show below. Here we show cells and driver stimuli from cell to another cell. We have a very complex network where the start of the process is the genetic change in a normal cell which becomes a cancer cell.

We can now look at the dynamics of this complex process. We can specify for example the concentrations of the products or cells as follows:

Now one must remember that if we have no cancer cells then the process may continue without a malignancy. However if the cancer cell is developed then this model may represent the development of the cancer in the related micro environment.

Thus we can state:

 

The matrix A relates the links which have been described. Inherent in this is also the reaction rate dynamics which we have linearized.

Now the process may go as follows:

1. In a benign state there is no cancer cell so that the system functions with the initial condition being zero for cancer cells.

2. Apart from the cycle, something happens inside a normal cell to alter its internal pathways, say from a genetic change, a methylation, some microRNA or the like.

3. This change then alters, activates, or deactivates a set of pathways which now can thrive in this environment.

4. The environment then becomes a positive feedback factor in the growth and dissemination of the cancer cells.

There are many interesting questions which may arise from this view. First the body itself propagates the cancer cells. Thus rather than just attacking the cancer cells we may consider attacking or modifying this supportive environment.

The authors conclude:

Yet other areas are currently in rapid flux. In recent years, elaborate molecular mechanisms controlling transcription through chromatin modifications have been uncovered, and there are clues that specific shifts in chromatin configuration occur during the acquisition of certain hallmark capabilities …. Functionally significant epigenetic alterations seem likely to be factors not only in the cancer cells but also in the altered cells of the tumor-associated stroma. It is unclear at present whether an elucidation of these epigenetic mechanisms will materially change our overall understanding of the means by which hallmark capabilities are acquired or simply add additional detail to the regulatory circuitry that is already known to govern them.

Similarly, the discovery of hundreds of distinct regulatory microRNAs has already led to profound changes in our understanding of the genetic control mechanisms that operate in health and disease. By now dozens of microRNAs have been implicated in various tumor phenotypes … and yet these only scratch the surface of the real complexity, as the functions of hundreds of microRNAs known to be present in our cells and altered in expression in different forms of cancer remain total mysteries. Here again, we are unclear as to whether future progress will cause fundamental shifts in our understanding of the pathogenetic mechanisms of cancer or only add detail to the elaborate regulatory circuits that have already been mapped out.

Finally, the circuit diagrams of heterotypic interactions between the multiple distinct cell types that assemble and collaborate to produce different forms and progressively malignant stages of cancer are currently rudimentary. In another decade, we anticipate that the signaling circuitry describing the intercommunication between these various cells within tumors will be charted in far greater detail and clarity, eclipsing our current knowledge. And, as before … we continue to foresee cancer research as an increasingly logical science, in which myriad phenotypic complexities are manifestations of a small set of underlying organizing principles.

The three points in their conclusion are worth merit:

1. Epigenetics and the complexity of reactions

2. Micro RNAs and their overall influence

3. Heterogeneous pathway dynamics, as we have outlined, and their complexity.

The major effort to date was to understand intracellular pathways. Now we can combine them with extracellular, or spatial pathways. This reminds us again of the work by Turing, the old zebra stripe issue.

Micro RNA and epigenetics can become an issue akin to adding noise but what type. Their behavior is more akin to randomness at least as is currently understood.

Having these papers provides a wonderful baseline worth reviewing a decade at a time.

Arab Uprisings

One is reminded of the final scenes in Lawrence of Arabia when the tribes arrived in Damascus and total riots resulted and the water and electricity failed. The NY Times reports on this issues. The question is; can a stable outcome result or are we seeing just the beginning of more confusion.

This is not at all unexpected to anyone who has spent time in the region. I have been in and out of this areas for the past forty years. One even stays in mind, when in the late 1970s I had to set up training for what was then ArabSat, a pan Arab satellite system. One could sense the issues then. Whether it is Saudi, Jordan, Egypt, Libya, Morocco, to name a few, stability may not be found easily and "democracy" as Americans know it may never be attained.

So why are we not surprised. After all, Elizabeth II was the first English monarch since 1162 who did not claim Ireland in toto.

Manufacturing: Where's the Beef?

There is a piece in the NY Times by Krugman bemoaning the loss of manufacturing and looking forward to its return in the US. I believe it misses a critical fact. If one looks down the streets aside MIT one sees dozens of multi-story building housing various bio-tech buildings, the replacement for the manufacturing buildings there a century ago. So should we tear them down so we can replace them with dc motor building plants? Doubtful, for the value created per person or per square foot is orders of magnitude greater than ever before.

The issue is that we are facing a society where fewer people create true value than ever before. That means that the old paradigms of the economists must change. Manufacturing may not have that great a value, but it did employ people who had little other than hands and a trainable brain to the table. Clearly our educational system is not up to the challenge. In fact the Dewey system we suffer under, one structured to deliver trainable but limited workers, must be abandoned, and people must face a reality that just getting by may not be enough.

As Krugman states:

First, what’s driving the turnaround in our manufacturing trade? The main answer is that the U.S. dollar has fallen against other currencies, helping give U.S.-based manufacturing a cost advantage. A weaker dollar, it turns out, was just what U.S. industry needed...So while we still have a deeply troubled economy, one piece of good news is that Americans are, once again, starting to actually make things. And we’re doing that thanks, in large part, to the fact that the Fed and the Obama administration ignored very bad advice from right-wingers — ideologues who still, in the face of all the evidence, claim to know something about creating prosperity.

Just making autos may not make the future. One need just look at the names and affiliations on the many papers in bio tech and one sees a trend to the growth from China. That may be the canary in the mine shaft, a tell tale omen that the value creating jobs in that area are not safe here.  I remember Russia and Poland ten years ago, with the lasting remnants of manufacturing and re-manufacturing. Old building where people were employed doing repetitive tasks remaking a DC motor or the like. Little value created.

Now in a strange way this also ties in with some comments on Brooks in the Guardian. They have reviewed his recent work. They state:

But what's important about Brooks is not so much that he acts British, but that he thinks British. His new book, The Social Animal: A Story of How Success Happens, is steeped in the anti-rationalist philosophical reflections of the British Enlightenment. And this is no ordinary book: even before publication this week it has become, according to Times columnist Rachel Sylvester, "the must-read text for politicians searching for a new prism through which to examine the apparently intractable challenges of social immobility, school dropout rates, welfare dependency and crime". Education secretary Michael Gove believes it contains vital clues for turning around failing schools; universities minister David Willetts reckons it may help define modern Conservatism...Brooks hails British rather than French Enlightenment thinkers as the guys who really understood what makes the social animal tick. While Voltaire, Condorcet and Descartes used reason to confront superstition and feudalism, thinkers across the Channel – Brooks cites Burke, Hume and Adam Smith – thought it unwise to trust reason. Rather, and here Brooks quotes Hume with approval: "Reason is and ought to be the slave of the passions."

 Brooks most powerful comment is:

Perhaps the fact that you're a self-described socialist will appeal to Ed Miliband, I suggest to Brooks. "Yes, but my socialism doesn't value state over society. It favours a more communitarian style of politics. The point is to ensure that people from different classes feel united in a common enterprise. 

 You see Brooks is Canadian by birth, which explains everything. The communitarian comment above is the most telling. It is the antithesis of the individualism of the Founders, the rejection of many of the class based structures of a British society. The statement of lack of faith in the rationalism of the French is a Burkean statement of the rejection of the French Revolution. This has been a continual battle as to what the cause of the French Revolution was, a Marxian cause due to the oppression of the workers, or otherwise.

De Tocqueville has written a brilliant piece worth re-looking on the issue, and Rationalism has its merits. Hume and friends always had their heads somewhat in the clouds. Reason has merit, substantial merit, and it is what drives us as humans. Remember if all else fails, look at the facts.

The English cannot really learn anything from the Americans, the cultures are diverging, for England is a class based society where class is based upon a blood line. Even France rid itself of that plague. The US has some semblance of class, but it is diffuse and can be lost or attained. Whether through money or fame, education or politics, there are classes in the US but as such they are all too often ephemeral. 

So what is the connection between Krugman and Brooks, other than the Times? The connection seems to be a total disjointed understanding of the American reality. That Americans will invent, create, evolve, and as a result the need for manufacturing is akin to the need for small farms, or the need for ditch diggers. In the latter case the Irish and Chinese who built the railroad and who were equally despised by the existing class of English, have somehow become the elements of what has moved upward. Again just look at the names on so many of the papers in genomics. That is the future of the United States, and that is what we should be supporting, not fender benders in Detroit.

Licensing of Economists

Frances Woolley always has some thought provoking posts on my favorite economics blog, Worthwhile Canadian Initiatives. My general means of replying is done here because at times the responses are somewhat askew of the intelligent post.

She raises an issue of licensing. I have a few and they vary from one extreme to another. I have been through the professional side and I also had to get a Pesticide License in New Jersey, just to handle my genetically modified plants. That was an interesting exam but alas a tale for another day. I even have an FCC radio license, and yes it did take some reviewing. Come to think of it there are medical licenses, car licenses, gun licenses, no I do not have a gun but New Jersey requires them if you ever bring a BB rifle through the state so just in case got that one too. Never got a Professional Engineer license however, it required learning stuff that I would never use, like surveying, advanced bridge design, strength of materials, and the like.

I remember taking the PhD qualifying exam when I spent a year at Northwestern. They asked questions about transmission lines, vacuum tubes, and dc motors. I went back to MIT, and never looked back to Illinois.

But back to Woolley and her argument. She argues, possibly somewhat tongue in cheek:

First, licensing might serve the public interest. In order to obtain a license, an individual must demonstrate competence in his or her field. In order to keep and maintain their licence, an individual must continue to act competently and ethically. Hence licensing guarantees consumers some basic level of competence and integrity.

Second, licensing might increase wages. Kleiner and Krueger (2008) estimate that, all else being equal, licensing increases wages by 15 percent, about the same as unionization. A licensing body can increase wages either by restricting the supply of licensed professionals, or by setting price guidelines, say, $85 for a dental examination.

Third, the process of licensing might provide opportunities for rent-seeking. For example, if economics bloggers were licensed, then license fee revenue could be used to fund honoraria for directors of the Canadian College of Economics Bloggers or jobs for Economics Blog Inspectors.

 The first issue may have some merit. In medicine we really do not want incompetents operating on someone's brain. In fact we do not want someone even diagnosing a disease unless they have been educated and demonstrated proficiency. Same for the engineer and bridges. But alas these two science based professions demonstrate consequences, and a generally agreed to and provable base of knowledge. Yes Medicine is still part art, but today we have a lot of science in it as well. Even Law has an defined and agreed to body of knowledge. Thus the Bar exams test that agreed to set of knowledge and of process.

However economics lacks almost any of the qualities of the above. There is Keynes, there Hayek, there is well a whole mass of schools and believers. Probably more than there are religions in the world. Which is true, they fight amongst each other calling each other names, specifically those down here in the States, and in addition they seem never to get things right. I think of Ms. Romer and her infamous document of January 11, 2009 where she predicted the results of the Stimulus to the month. Did not happen! My guesses were better.

Thus how can one conceive of a license to such a group if the core beliefs are so disparate.

The second concern is that given the lack of structure in economics, namely core beliefs, I really discount all the math as want to be engineers who want to be mathematicians type of stuff, I went through part of that phase when I started out so I know, the core beliefs are so disparate.

My third point is a bit more serious. Namely by creating some license for an area of study which is still in its infancy it may create a chilling effect on those who may desire to comment and contribute. Would the license be such that any commentary would be controlled similarly to that of a physician who is diagnosing a patient. In this case the patient is the economy in large and thus putatively any comment on the economy would be diagnosing a patient, namely the economy, and thus may be allowed only to those who are licensed.

Fourth, as any medical student knows in their fourth year, what they have learned will most likely be invalidated by the time they are at the peak of their profession, so expect the change. Yet as the students know for their licensing exams they must recite back what the standard is at the time at which they take the exam! Namely licensing exams reflect what the assembly of minds believe at a specific point in time, and God forbid you have a different insight, do not exhibit that in the exam, recite what has been agreed to mantra. In medicine that may get worse as the new health laws require the following not of the professional wisdom but of the Governments CME directives. So as a summary of the fourth observation, licensing means compliance with the past. Economics just does not work that way.

She continues:

The other way of establishing competence is through examinations, such as law societies' bar exams, or the chartered accounting profession's uniform final exam.

Done well, accreditation could raise the quality of economic debate. How many times have you read a newspaper, or turned on the TV, and heard someone claiming to be an economist who demonstrated absolutely no knowledge of basic economic principles? Accreditation could - perhaps - flush out these charlatans.

Done poorly, accreditation could institutionalize a rigid orthodoxy, a particular approach to the economics discipline.

Economics as a profession, or more importantly as a field of study, needs many commentators and providers of insight. There has been no Newton to establish ground rules, there still is a cacophony of voices all with opinions. Woolley raises many interesting points and is a well deserved discussion.