Friday, February 4, 2011
Unemployment: Romer Would be Proud
Wednesday, February 2, 2011
Prostate Cancer and Tests: Is This Progress?
In a recent announcement from Dana Farber in Boston, a paper has been prepared that indicates that testing for four gene products significantly improves the ability to determine an indolent Prostate Cancer from an aggressive form. The results also hit the news including a WSJ release.
The release from DF states:
We show some of the pathway elements above. A more detailed version is below.
The loss of PTEN has been known for years to be a sign that metastasis may very well already started. SMAD4, SPP1 and the Cyclin D1 are in pathways that also control the growth of the cell. PTEN is most often the one pathway element of most concern.
The driving factor in the result is:
The standard measure of prostate cancer's aggressiveness, known as the Gleason score (which is based on cancer cells' appearance under a microscope), is accurate about 60 to 70 percent of the time depending on the skill of the pathologist. The four-gene signature method alone was accurate 83 percent of the time. Combining the markers and Gleason methods produced an accuracy of approximately 90 percent.
Now the above result need some clarification.
1. Gleason scores are score based upon the histological presentation of the cells. Gleason 1 for example is low grade and shows the cells as small gland like structures but lacking gland architecture. Gleason 5 is a mass of undifferentiated cells clustered about the stroma, internal part of the prostate, with no structure. Gleason scores are the sum of the most prevalent cell type plus the next most prevalent so a 7 is a 4+3 or a 3+4. Clearly a 4+3 is more sever than a 3+4. But Gleason alone tells one little about the metastatic potential.
2. Genetic pathway changes are often the sine qua non for determination. But what genes and in what cells. The problem is the existence of the cancer stem cell idea, namely that one of the many cancer like cells is pluripotent and if this is true in prostate cancer then it is that cell we want. So perhaps in a biopsy we missed the killer cell, or it may have already escaped.
3. This procedure statistically takes us a step forward, now we can test to see if we do have some very bad cells. However one may ask if we are finding out when the cow has already left the barn. Namely what we may have is a test which conforms the fact that the patient's cancer is one of those very bad types so nothing much can be done. On the other hand we may have a patient with an aggressive form which is just a threshold below the bad level. Thus one need significant clinical tests.
4. The question then is; are there other pathway constituents that are prognostic enough to have a meaningful result in mortality, namely how well do we know the PCa pathways. What are the pathway dynamics between these four, we know some, and many are available through NCI.
5. The results appear to have quite extensive, but causality and dynamics still need some filling in. What caused the change. In addition one may look at the HGPIN cases and see that we have HGPIN which all too often is considered as pre-malignant, but we know that HGPIN also regresses to a fully benign prostate. What happened..
As the WSJ states:
Indeed one must wait and see. However this will be a challenge to Medicare, since so many of the patients are Medicare patients. How effective is this test? If the genes are all showing aggressive growth then we act? Or is it too late already. If the genes do not show aggressive growth do we deny the patient care even if the patient has strong family history of aggressive PCa? The issue is that all too often the family history dominates. Perhaps this creates more issues than it solves, however it is a step in a good direction, it may or may not be the right one.
Finally the WSJ states:
One wonders what research funds were used in the testing. But notwithstanding welcome to the entrepreneur.
We have written a more detailed analysis that the reader may have interest in in one our White Papers.
The release from DF states:
The four-gene signature — Pten, Smad4, SPP1, and CyclinD1 — showed its effectiveness as a predictive tool for survival when researchers drew on data from the Physicians' Health Study, which has been tracking the health of thousands of U.S. physicians for nearly 30 years. When the investigators screened prostate cancer samples from study participants for the four-gene/protein signature, it was more accurate in predicting the ultimate course of the illness than conventional methods were.
The driving factor in the result is:
The standard measure of prostate cancer's aggressiveness, known as the Gleason score (which is based on cancer cells' appearance under a microscope), is accurate about 60 to 70 percent of the time depending on the skill of the pathologist. The four-gene signature method alone was accurate 83 percent of the time. Combining the markers and Gleason methods produced an accuracy of approximately 90 percent.
Now the above result need some clarification.
1. Gleason scores are score based upon the histological presentation of the cells. Gleason 1 for example is low grade and shows the cells as small gland like structures but lacking gland architecture. Gleason 5 is a mass of undifferentiated cells clustered about the stroma, internal part of the prostate, with no structure. Gleason scores are the sum of the most prevalent cell type plus the next most prevalent so a 7 is a 4+3 or a 3+4. Clearly a 4+3 is more sever than a 3+4. But Gleason alone tells one little about the metastatic potential.
2. Genetic pathway changes are often the sine qua non for determination. But what genes and in what cells. The problem is the existence of the cancer stem cell idea, namely that one of the many cancer like cells is pluripotent and if this is true in prostate cancer then it is that cell we want. So perhaps in a biopsy we missed the killer cell, or it may have already escaped.
3. This procedure statistically takes us a step forward, now we can test to see if we do have some very bad cells. However one may ask if we are finding out when the cow has already left the barn. Namely what we may have is a test which conforms the fact that the patient's cancer is one of those very bad types so nothing much can be done. On the other hand we may have a patient with an aggressive form which is just a threshold below the bad level. Thus one need significant clinical tests.
4. The question then is; are there other pathway constituents that are prognostic enough to have a meaningful result in mortality, namely how well do we know the PCa pathways. What are the pathway dynamics between these four, we know some, and many are available through NCI.
5. The results appear to have quite extensive, but causality and dynamics still need some filling in. What caused the change. In addition one may look at the HGPIN cases and see that we have HGPIN which all too often is considered as pre-malignant, but we know that HGPIN also regresses to a fully benign prostate. What happened..
As the WSJ states:
Dr. DePinho said the new study suggests a test based on the four genes, when added to current prediction protocols could improve the accuracy to about 90%....Charles Sawyers, a cancer expert and Howard Hughes Medical Institute Investigator at Memorial Sloan Kettering Cancer Center in New York, said if it turns out that such a test is that effective, "it would have a huge impact." He wasn't involved in this research.
Dr. Sawyers cautioned that such gene signatures have been proposed to predict cancer progression in the past and haven't panned out. He said the genes the new research focuses on appear to have a functional role in regulating cancer development, but that more research will be necessary to validate whether a test would have value for doctors and patients..."We'll have to wait and see," he said.
Indeed one must wait and see. However this will be a challenge to Medicare, since so many of the patients are Medicare patients. How effective is this test? If the genes are all showing aggressive growth then we act? Or is it too late already. If the genes do not show aggressive growth do we deny the patient care even if the patient has strong family history of aggressive PCa? The issue is that all too often the family history dominates. Perhaps this creates more issues than it solves, however it is a step in a good direction, it may or may not be the right one.
Finally the WSJ states:
A test based on the findings is being developed and could be available within a couple of years to help determine how aggressively to treat early-stage cancer, said Ronald DePinho, director of the Belfer Institute of Applied Cancer Science at Dana Farber Cancer Institute, Boston, and senior author of the study...Closely held MetamarkDePinho said he has equity in the company.
One wonders what research funds were used in the testing. But notwithstanding welcome to the entrepreneur.
We have written a more detailed analysis that the reader may have interest in in one our White Papers.
Global Warming and the Three Feet of Snow in My Yard
Well the Guru of Global Warming has made a statement as follows:
Last week on his show Bill O’Reilly asked, “Why has southern New York turned into the tundra?” and then said he had a call into me. I appreciate the question.
As it turns out, the scientific community has been addressing this particular question for some time now and they say that increased heavy snowfalls are completely consistent with what they have been predicting as a consequence of man-made global warming:
“In fact, scientists have been warning for at least two decades that global warming could make snowstorms more severe. Snow has two simple ingredients: cold and moisture. Warmer air collects moisture like a sponge until it hits a patch of cold air. When temperatures dip below freezing, a lot of moisture creates a lot of snow.”
“A rise in global temperature can create all sorts of havoc, ranging from hotter dry spells to colder winters, along with increasingly violent storms, flooding, forest fires and loss of endangered species.”
Now this is one of those, "Do you believe me or your lying eyes" type statement. Let me explain:
1. Snow is frozen water, true fact.
2. Yes warm air collects moisture, which is why there is so little snow in the Arctic. Too dry.
3. Here is where the train leaves the rails. Some how it has to hit a patch of cold air, that is what is happening, the Jet Stream has dipped so low into the US that it is cold in places it has never been cold before. So it that Global Warming or National Cooling or both. Somehow you cannot have it both ways. To get snow you need water and cold. The water can come from anywhere, it moves along fronts, but the cold is cold. Not warming. When the Jet Stream moves so far south as it has this winter then is this weather or climate. To Global Warming purists it is weather, to the Guru it is what it is not.
Or as my squirrel friend has just said, it is just snow stupid. And we throw them another few ears of corn!
Tuesday, February 1, 2011
Another Oxymoron: Government Entrepreneur
The current Administration has announced its intent to spend a few billions more but this time focusing on innovation and the entrepreneur. It is worth looking closely at what they propose as Start up America, the program.
They state:
When signing the Small Business Jobs Act, and again when proclaiming the first-ever National Entrepreneurs’ Day this past fall, (the current President) called on leaders from throughout the business, nonprofit, and university communities to join together with his Administration’s efforts to promote the success of more entrepreneurs across America. The initiatives announced today are the initial response to this “call to action,” uniting a range of public and private commitments to:
Then they state:
The essence of the entrepreneur is their ability to overcome barriers, that is the steeling of the idea, the testing of the metal to see if it can withstand the challenge of the market. What challenge does an entrepreneur face, all of them. Finding money, finding people, executing, competing, and of course dealing with Government regulations. What does anyone who has been down that path think the Government can do, what advice can some career GS 11 provide, how to increase their Government benefits!
And oh by the way, why did they not include Boston and 128 area? Strange since it is all Democrats!
They state:
When signing the Small Business Jobs Act, and again when proclaiming the first-ever National Entrepreneurs’ Day this past fall, (the current President) called on leaders from throughout the business, nonprofit, and university communities to join together with his Administration’s efforts to promote the success of more entrepreneurs across America. The initiatives announced today are the initial response to this “call to action,” uniting a range of public and private commitments to:
- Expand access to capital for high-growth startups throughout the country;
- Expand entrepreneurship education and mentorship programs that empower more Americans not just to get a job, but to create jobs;
- Strengthen commercialization of the about $148 billion in annual federally-funded research and development, which can generate innovative startups and entirely new industries;
- Identify and remove unnecessary barriers to high-growth startups; and
- Expand collaborations between large companies and startups.
Then they state:
Top Administration Leaders Announce National Tour to Support Public Participation in Removing Barriers to Entrepreneurship: The President has issued an Executive Order and accompanying memorandums to federal agencies to identify and take steps to eliminate or reduce processes that are outdated or overly burdensome to entrepreneurs. As part of this effort to receive feedback from entrepreneurs on the front lines, the Administration will launch online suggestion tools for the public and go on the road to innovation centers like Silicon Valley and North Carolina’s Research Triangle Park to hear from entrepreneurs about the challenges they face, share current Administration efforts to support entrepreneurship, and to streamline or eliminate the biggest barriers to startup growth.
The essence of the entrepreneur is their ability to overcome barriers, that is the steeling of the idea, the testing of the metal to see if it can withstand the challenge of the market. What challenge does an entrepreneur face, all of them. Finding money, finding people, executing, competing, and of course dealing with Government regulations. What does anyone who has been down that path think the Government can do, what advice can some career GS 11 provide, how to increase their Government benefits!
And oh by the way, why did they not include Boston and 128 area? Strange since it is all Democrats!
Monetary Policy and The Bernak.
A bit long in the tooth but gets the point.
1. FED pumps money to Banks
2. Banks "invest" in Government, btw another meaning of investing
3. Interest rates are zero so the old folks on fixed incomes will burn out soon if the cuts in health care do not get them first
4. Investment Bankers make bundles on free money.
5. And guess who gets re-elected! Guess!
China is Not Japan
China is not Japan. In the 1930s Japan was driven by military forces and there was still the strong mercantile interests that controlled the industrial elements. However Japan was short on natural resources, thus its expansion. Ultimately they aggressively expanded to south east Asia.
China is not Japan. They have a strong military, they have if you will a quasi mercantile industrial base, mercantile in the sense that there is strong state support, yet unlike a Japanese industry, and they are short many natural resources that they find amongst all places, Africa.
There is an interesting piece in Project Syndicate worth the read on China and Africa. As the author states:
Africa is rich in natural resources yet is all too often unstable. That is the risk the Chinese face as they build their interests. The win-lose issue is one of real concern. China may very well further deplete existing weak countries and create even more instability.
China is not Japan. They have a strong military, they have if you will a quasi mercantile industrial base, mercantile in the sense that there is strong state support, yet unlike a Japanese industry, and they are short many natural resources that they find amongst all places, Africa.
There is an interesting piece in Project Syndicate worth the read on China and Africa. As the author states:
Astutely, China has sought to place its African investments and diplomacy within the context of the old non-aligned movement and “Bandung spirit,” an era when many Africans viewed China as a brotherly oppressed nation, and thus supported efforts by the People’s Republic to gain a permanent seat on the United Nations Security Council, to replace Taiwan. And, of course, China offered firm backing for Africa’s anti-colonial struggles and efforts to end apartheid.
In trying to depict its current dealings with Africa as “win-win” cooperation, China deliberately seeks to portray Africa’s current relations with the West as exploitative. Unlike China, its leaders claim, the West continues to hold African countries hostage through a combination of unequal trade deals, lack of access to capital markets, aid dependency, financial deregulation and economic liberalization, budget austerity, crippling debt, political meddling, and military intervention.
What the Chinese are silent about is that their country’s growing engagement in Africa has created both opportunities and risks for African development. Although China’s trade, foreign direct investment (FDI), and aid may broaden Africa’s growth options, they also promote what can only be called a win-lose situation. For, excluding oil, Africa has a negative trade balance with China.
Africa is rich in natural resources yet is all too often unstable. That is the risk the Chinese face as they build their interests. The win-lose issue is one of real concern. China may very well further deplete existing weak countries and create even more instability.
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