Monday, December 28, 2015

A Good Idea Does Not a Business Make

The NY Times has an article on Universities spending tuition money to "support" start up.

They state:

Ten years ago, it may have sufficed for colleges and universities like Rice to offer a few entrepreneurship courses, start-up workshops and clubs. But now hundreds of thousands of undergraduates, driven by a sullen job market and inspired by billion-dollar success narratives from Silicon Valley, expect universities to teach them how to convert their ideas into big businesses or nonprofit ventures. As a result, colleges across the United States — and elite institutions in particular — have become engaged in an innovation arms race. Universities are expanding academic programs at a breakneck pace and constructing start-up centers. Harvard opened an Innovation Lab in 2011 that has helped start more than 75 companies; last year, New York University founded a campus entrepreneurs’ lab; this year, Northwestern University opened a student start-up center, The Garage.

Now I have been involved in 34 start ups in some way shape or form. I have created them, managed them, turned them around, bought them, sold them, and whatever one can do with them. Every time some new wanna be comes along I hear the same tale as to how this will be a success. After a half dozen questions that easy tasks starts to mold, to fall apart.

I have seen many of these dreamers at places like MIT where post-docs are one the one hand supported in their entrepreneurial ventures but at the same time burdened by their low paid post-doc efforts.

I did my first start up in 1969, when in Grad school, and I was just a part time consultant. I saw it go up and then collapse in just a few months. Good idea but poor execution. Also poor management.

Of the 34 that actually made it airborne, all had their challenges. Some with management, some with strategy, some with execution, some just with the market collapsing.

But perhaps Universities should do what we pay them to do. Train young people in skills that subsequently can be monetized. Academics for the most part, I have seen a few, very few exceptions, have no idea how to run anything, not even their own research efforts. So we expect that same group to "lead" students? This is literally the blind leading the blind. More tuition money down the drain. I see Universities having people teach entrepreneurial courses who have never even held a job!

To be an entrepreneur is to be the ultimate risk taker. You have no Plan B, you have burned all your boats and move forward based on your abject belief that you are right. You have no cozy University supported location. 

I recall travelling the world with my Passport and credit card, country after country, building a global network. I was a dream merchant but I knew what I could do. We really do not need another App, really. We need better infrastructure, we need improved Health Care, we need a variety of real stuff, including improved environmental controls, whatever that may mean.

To get there we need educated entrepreneurs. We do not need Freshman with another App. We also do not need increased tuition driven by some Administrative vision of what entrepreneurs do. Frankly they are clueless, and worse, self serving!

Friday, December 25, 2015

Merry Christmas

1 And it came to pass in those days that a decree went out from Caesar Augustus that all the world should be registered.
2 This census first took place while Quirinius was governing Syria.
3 So all went to be registered, everyone to his own city.
4 Joseph also went up from Galilee, out of the city of Nazareth, into Judea, to the city of David, which is called Bethlehem, because he was of the house and lineage of David,
5 to be registered with Mary, his betrothed wife, who was with child.
6 So it was, that while they were there, the days were completed for her to be delivered.
7 And she brought forth her firstborn Son, and wrapped Him in swaddling cloths, and laid Him in a manger, because there was no room for them in the inn.
8 Now there were in the same country shepherds living out in the fields, keeping watch over their flock by night.
9 And behold, an angel of the Lord stood before them, and the glory of the Lord shone around them, and they were greatly afraid.
10 Then the angel said to them, “Do not be afraid, for behold, I bring you good tidings of great joy which will be to all people.
11 For there is born to you this day in the city of David a Savior, who is Christ the Lord.
12 And this will be the sign to you: You will find a Babe wrapped in swaddling cloths, lying in a manger.”
13 And suddenly there was with the angel a multitude of the heavenly host praising God and saying:
14 “ Glory to God in the highest, And on earth peace, goodwill toward men!
15 So it was, when the angels had gone away from them into heaven, that the shepherds said to one another, “Let us now go to Bethlehem and see this thing that has come to pass, which the Lord has made known to us.”
16 And they came with haste and found Mary and Joseph, and the Babe lying in a manger.
17 Now when they had seen Him, they made widely[d] known the saying which was told them concerning this Child.
18 And all those who heard it marveled at those things which were told them by the shepherds.
19 But Mary kept all these things and pondered them in her heart.
20 Then the shepherds returned, glorifying and praising God for all the things that they had heard and seen, as it was told them.

Tuesday, December 22, 2015

Amazon Reviewers

I started writing reviews on Amazon some eight years ago. I have done 235 at this point, not a massive number, but reasonable. I generally write reviews of books, professional ones, not novels, and always do so in my own name. I generally discount anonymous reviews, especially ones with less than rational name tags. I also use the reviews to see what may be wrong with a product. What breaks, what is poorly designed. Many negative reviews are just folks with a chip on their shoulder but who cares.

Now reviews have value and when Amazon decided to change their format I decided to follow the comments of those feeling I thought in a right minded manner. I am not a trained Psychiatrist but I can at times fell the chill of reading some of these comments. They appear to be folks who have no other life, who take minutia quite seriously and can be overly aggressive about small issues. Perhaps DHS and NSA should be watching these discussion groups.

Are Reviews useful? I believe so. If they are honest and present positive and negative factors then they can help the consumer. Frankly if I know who the Reviewer is then I have mush more reliance on the Review. But it appears that Amazon may have an out of control process here. There are people writing thousands of reviews by getting tons of free stuff. The IRS aside, how can anyone do a credible review of so many items? It may take me a couple of weeks at least to prepare a book review. And then only if I have the time!

Thus this Review process has many flaws. Especially the anonymous elements and in addition the element of what appears to be "gift" reviews. Add to that what seems to be less than well balanced folks, well, you can see where that leads.

I have seen over the years that if you give a book a credible but bad review, the Collective which may form around the writer, such as those in the Net Neutrality space, go mad and drive your review away. A key to detecting that is  a bimodal set of Reviews, five and one star, with may positive on the five and many negative on the one. That is an example of the Collective at work.

Monday, December 21, 2015

In Case You Missed This

Every once in a while I recall something that is of note. Back in January Modern Healthcare reported:

The Obama administration wants 30% of payments for traditional Medicare benefits to be tied to alternative payment models such as accountable care organizations by the end of 2016. The administration also has set a goal of hitting 50% by the end of 2018. The administration wants even larger portions of hospital payments to be tied to quality- or value-based payment models. HHS indicated that it wants 85% of Medicare's hospital payments made through programs such as the Hospital Value-Based Purchasing Program or the Hospital Readmissions Reduction Program by the end of 2016. That threshold kicks up to 90% two years later. It is the first time that the federal agency has set specific goals for overhauling the payment system for standard Medicare beneficiaries, which has traditionally relied on a fee-for-service model. That system has long been criticized for providing economic incentives for providers to offer a greater volume of care regardless of outcomes. Currently, 20% of Medicare payments for traditional beneficiaries are made through alternative payments models, which also include bundled payment arrangements, according to HHS.

This is the first time we have seen specific targets. The current Administration wants to push all on Medicare to the equivalent of HMOs. Take them off what they have and slam them into an HMO or rationing type system. If you are too old, albeit healthy, if you get ill, perhaps you die. Too bad! You no longer have any choice.

Hopefully this madness will be gone in another year. Then all we have to worry about is the Terrorists that don't exist. "Keep moving, nothing to see here!"

Sunday, December 20, 2015

Seven Years Old

After seven years, some 157,000 visitors, from 150 countries and over 3 million words, I thought I would try to summarize where we are. Now more than 10% of my life has gone into this idiosyncratic presentation of thoughts. The original intent was to follow the actions by many to the financial collapse of 2008 as well as the new leadership of the country. I was especially motivated by the prognostications of left wing macro-economists who believed all that they espoused. Namely all that was required was a trillion plus in Government money and in months things would be right again. So how did that work out Mrs. Romer?

Overall we have addressed the following issues:

1. Macro Economics: It is clear that these folks oftentimes do not even agree with themselves! What became clear to me is that macroeconomics is really just political theory. I examined Keynes, and then followed these characters for eight years. They all seem to have keen insight into nothing. One of my favorite piques is the Pigou vs Coase controversy. Here we have allegedly Republican macro economists, rare as unicorns, espousing taxes to reduce carbon. They seem totally ignorant of solving the problem technically.

2. Health Care. My timing was good here as well. Yes, the ACA, the most massive attempt by Progressives to “tell” the rest of us how to deal with our health. So what happened? Personally I am paying 5 times more now than in 2008 and still taking no advantage of the system. God has been good so far. But who gets the money. The Millennials without jobs! You can’t make this up! Some morbidly obese 20 year old having no job but collecting for their early stage Type 2 Diabetes! Say what’s with that?

3. Russia and China. After seven years we still see nothing from Russia in Walmart. It is still China. Oil has collapsed so that Russia as an extraction economy may be hurting. China is trying to expand, but it should take a careful dance forward. It still depends on customers.

4. Cancer. We have examined cancer and its progress in understanding and care. In seven years we have seen massive changes. We have ways to deal with advanced melanoma, and even many hematological diseases. However we still have the prostate cancer problems; over 100 target genes. Moreover we have a collection of people without any basis saying to abandon any tests on men. All too frequently these cries are from women, and women who do not even practice or do clinical research in the field.

5. MOOCs. I initially thought MOOCS may have some value. Except for Prof Lander’s course the rest have been marginal at best and some outright useless. What I did examine was the tendency of anonymous participants making the most incendiary remarks on the MOOC’S discussion groups. This seems to be a pandemic characteristic of Millennials. Every opinion is valid yet they do not want to tell anyone who they are.

6. CRISPRS. Eric Lander mentioned these offhandedly in a talk a few months after they came out and I dove into them. I told my grandkids 6th Grade class to follow CRISPRs. These could be the most powerful tool yet. Also they have deadly consequences.

7. The Academy. Here I examined the Academy over seven years. It is becoming a mess. Costs are uncontrolled, student sensitivities rule, political correctness is pandemic, and our Government thinks a degree has value. What a person can “do” has value, not what “everyone gets a prize” degree.

It will be interesting to see what the coming year brings. Thanks for those who visited here. Hope I have not annoyed too many, and feel free to drop a note from time to time.

Saturday, December 19, 2015

Indentured Servitude

I just noted the following in the NY Times by Mankiw:

Another approach is to find better private mechanisms to finance higher education. Senator Marco Rubio, who is seeking the Republican nomination, wants to establish a legal framework in which private investors help pay for a student’s education in exchange for a share of the student’s earnings after college. In essence, the student would finance college less with debt and more with equity. The Rubio plan does not let the student get away without paying, but it does help spread the risk from the educational investment.

This is not Mankiw but is Rubio. This is a classic example of being totally blind to the problem. Higher  Ed costs more for a variety of correctable reasons. They are:

1. Government mandated overhead has exploded. Namely Deans for this and Deans for that and policies here and there just add to costs.

2. Buildings costs lots to build and even more to maintain. College Presidents like to build stuff, it meets their self perceived mandate. Yet I have never met a College President who fully understood life cycle costs.

3. Services to students and staff have exploded. From new gyms, swimming pools and yes the sacred cows of football. MIT once had sports for sports sake. Now, alas, they are going Varsity.

4. Student Support has also exploded. The well coddled student has one type of support for this and one for that. Guess what? That costs, lots!

So creating Indentured Servitude is wrong, and frankly it demonstrates some terribly shallow understanding of the problem and perhaps we should ask what the leading candidate wants? Oops, you're fired! Yep, that cuts costs.

Friday, December 18, 2015

Dutch Women and the Death of American Men

For almost a decade now we have been examining the details of prostate cancer, PCa. PSA has its ups and downs but for testing for aggressive PCa it is a tool, albeit one which we have shown has some issues. More tools are coming on line almost monthly, as we have also examined.

Now this week in Nature we have some Dutch woman, it appears, opining on having American men adhere to the USPTF guidelines. Now if an American man said that about breast cancer we would have an uproar! But men, well they have outlived their usefulness after a certain age perhaps.

The author states:

These findings raised two questions. First, is it possible to reduce prostate-cancer mortality if the PSA test is introduced as a screening tool? And second, is it possible to reduce the side-effects of PSA screening, including overdiagnosis? To address these questions, two randomized trials — one in the United States and one in Europe — were initiated. Both trials have reported on the effect of PSA testing on prostate-cancer mortality several times over the years, and have always contradicted each other (although it is generally accepted that within the US trial contamination substantially limited researchers' ability to identify a clinically significant screening benefit). This lack of consensus and the considerable risk of overdiagnosis associated with PSA-based screening are the main reasons that screening for prostate cancer is still highly controversial, and why there are so few population-based government-initiated screening programmes.

 We had argued that both tests were flawed. The reasons; simple, they used a 1990s test metric which we now know needs to be modified and the European tests were spaced too far apart. Thus in some ways the test is akin to monitoring melanoma in such a fashion that you excise the lesion only when it bleeds and if you do that mortality is no different than watchful waiting. I do not think so.

The author concludes:

The time has come to actually implement the evidence-based guidelines into clinical practice. Medical associations should better communicate the best practice around PSA testing and strengthen the education of doctors — particularly general practitioners (GPs) who are usually the first point of contact, but are rarely up to date with the latest publications. GP requests for testing should be actively monitored to ensure the message is understood, rather than waiting for registry data to see if there has been an effect.

 The evidence is quite complex. We examined a case a couple of month back and demonstrated that one test after another gave conflicting results. I would agree that most Primary Care physicians are not attuned to dealing with the results but in the US we then send them to a Urologist to see what to do next. They should be the definitive gatekeepers.

Let's try to keep men alive on an equal footing, please.

And by the way, another woman in Nature seems to bemoan the PSA test. This writer states:

Part of the shift is a result of advances in screening, which are helping doctors to zero in on aggressive cancers that need the most attention. Among the new strategies is a tool called the prostate health index (PHI), which measures three types of PSA. According to some research, the PHI is three times more specific than the standard PSA test, an improvement that reduces the number of unnecessary biopsies. Doctors around the world also now factor in a tumour's Gleason score, which assesses aggressiveness based on the way that cancer cells look under a microscope. And researchers are continually re-examining the level at which the quantity of PSA in the blood should be considered abnormal. Some evidence, for example, supports the idea that the threshold for concern should be raised from its present value of 3–4 nanograms per millilitre to 10 nanograms per millilitre. Beyond PSA, scientists are also using magnetic resonance imaging to guide biopsies making false negatives less likely, as well as genetic tissue tests to screen for biomarkers that signal a cancer's degree of aggressiveness. These tests can be expensive, and health-insurance companies in the United States do not necessarily cover them. Many are so new, Barry adds, that there are insufficient data on outcomes. Rushing to accept newer tests before sound trial evidence arrives, in other words, might bring a repeat of the troubled PSA era all over again.

 In my opinion perhaps these should be written by professionals and not what appears as "a freelance journalist". Afterall this is Nature not Men's Health. Just an opinion.

Thursday, December 17, 2015

Sometimes Smart People Do Stupid Things, Now Amazon

I generally like Amazon. Good quality, good prices and good service. I also like to look at the Reviews, five star and one star. All too often the five star are plants but they are obvious. Sometimes the one star are just annoyed. Also ready to catch.

But now Amazon has done one of the stupidest things ever. The went and totally destroyed the reader feedback function. Some character decided to remove all data from Profile reviews and then sce the reviews, remove responses, remove useful and not useful, in essence remove all feedback. One suspects they did so for mobile users.

But you see, I would never use a mobile device. Moreover they made these changes without ever asking. Reviewers really add value. Disregard the Reviewers and you Destroy Value. Dumb? You bet!

So there must be some Media Manager at Amazon with some Ego driven need to do it their way. Guys, get rid of that person. Remember your customers are your value, not the character who most likely had their Ego in a twit over their way or the highway!

Remember; if all else fails listen to the customer. (Could someone tell Bezos! He gets most other things. Get rid of this person now. Otherwise this person will cost Amazon Millions if no Billions!)

As I had noted:

Profiles, as I see them, have two functions.

1. They provide the reader with some understanding of who the person is reviewing the item.

2. They provide the reviewer with an easy means to track the response to their reviews, to see what is useful and what is not.

I think that the new version provides neither of the two. Change is the result of either correcting or improving. However in this case, change just seems to make things worse and of little use to either the reader or reviewer. Frankly one wonders why this was done and what it was to achieve. If it ain't broke please don't fix it!

Also for those folks in Marketing: Remember, if all else fails, listen to the customer!

Whose Money Is It?

Providing funding for "charitable" work is laudable and is frankly an obligation that comes to those who have done well. What to give to however is the individual's choice. Cancer Research, Academic Research, Social Programs, Public Benefit efforts, soup kitchens, and even individuals who with a little help can leverage their own assets subsequently for the benefit of others.

Americans are somewhat unique in that area. Americans also are unique in that they get to choose and those there is a "free market" for "charitable" work.

I saw piece today in the NY Times, of course, that "tells" us what we should do. It says:

In other words, “giving back” is necessary, but not sufficient. We should seek to bring about lasting, systemic change, even if that change might adversely affect us. We must bend each act of generosity toward justice. We, as foundations and individuals, should fund people, their ideas and organizations that are capable of addressing deep-rooted injustice. We should ensure that the voices of those most affected by injustice — women, racial minorities, the poor, religious and ethnic minorities and L.G.B.T. individuals — help decide where and what philanthropy puts money behind, not in simply receiving whatever philanthropy decides to give them.

Now where is the Cancer Research, the funding of up and coming high performance students, public spaces, etc? Not there.  

Charitable Giving by individuals should be individual choices not dicta from on high.

Now Who Wrote That?

It is easy to see what Einstein wrote. His name was on the paper and the only name. Back some 50 years or so when tenure came up one looked at a pile of publications of the faculty member and that had 40-50 papers with their name on them, and only their name.

Now we have the "everyone is a winner" game where there are dozens if not thousands of names. Now really, at most maybe 2 or 3 people wrote the paper. Thousands is nonsense.

In PLOS they state:

...we still don’t have solid norms for the process of deciding authorship, and it’s pretty much team-dependent. Decision structure problems arise “because one or more of the authors, usually the most senior one, assumes tacit agreement and consensus when there is none and then decides on co-authoring with little or no discussion” – as well as suppression of dissent, groupthink, squeaky wheels, and what they call “the jackass factor”. Power dynamics are central, and until we understand and tackle that, some people will continue to “exploit their friends and also those who are in less powerful positions than themselves”. Authorship practice remains astonishingly murky. All science’s incentive problems converge in it and feed from it. It deserves more care.

Well is the process murky because of what? One could argue that it is the process of Government funding that drives this chaos.

Now in BioMedCentral they articulate a "new" way to attribute contribution. Specifically:

Today in GigaScience we launch a project to spearhead this through our Author Contributorship Badges. The badges are based on a taxonomy around contributorship developed by  the Wellcome Trust, MIT, Digital Science, and others  in partnership with CASRAI (Consortia Advancing Standards in Research Administration), National Information Standards Organization (NISO), and the research community...These contributorship badges, in conjunction with other badges around open practices, put credit back into the hands of researchers and offer funders and universities alternative data to obscure author lists and Impact Factors.

 I really have difficulty with this process. There is a "badge" movement afoot, I think kind of like Boy Scout Merit Badges but not as good. This "badge" movement will add more contention and confusion. Again, back to Albert, how would that work again?

Saturday, December 12, 2015

The Downside of Award Galas

Hollywood for decades has celebrated itself over and over. There now are close to a dozen major award events for movies, television and the like and many times that for popular music. The folks get all dressed up, sit in some California type room, laud themselves, and get significant media coverage, the ultimate selfies.

Now we see this in Science. The moneyed folk in California, it appears part to "celebrate" themselves, are now hosting an event to award prizes in a similar social environment. This is no Nobel Prize, no King, no tux type attire. It is Hollywood on El Camino.

Nature has an interesting piece on this. They state about the photo:

From left, former Twitter CEO Dick Costolo, Emmanuelle Charpentier, Jennifer Doudna and Cameron Diaz.

Yep, a full fledged Hollywood star, right there in the Valley! You can bet this will continue. Now I can see awards, professional societies give them out all the time. They are "peer" awards. The White House has been getting in the act as well, and of course there is a lot of Hollywood there as well.

Perhaps "Science" should think twice about what could be pure commercialism. The existing structures work quite well, or at least they seem to. Science is unlike Hollywood, usually no agents. But watch out folks, that too may change. Beware the hubris!

But wait! MIT has a Hollywood movie person for Commencement Speaker! Now this you really can't make up. In 1971 at my PhD Commencement I had no idea who spoke. Who cared! But now a Hollywood social advocate!

As MIT says:

This is an exciting choice of speaker,” says Chancellor for Academic Advancement ..., the longstanding chair of MIT’s Commencement Committee. “..... couples a passion for his art with a passion for making the world a better place, much as our students couple a passion for science and technology with a passion to improve the world. I am sure his message will inspire our students to follow that passion and tackle some of the world’s great challenges, such as in water, health, or education.”

How about getting a job, curing cancer, developing new seems this Hollywood thing is getting a bit out of control......

The Politics of Cancer

The book by DeVita, The Death of Cancer, is a well told tale of one in the fight against the disease. DeVita is well known and well accomplished in the field. His book tells the tale of dealing with many of the characters, especially in Washington, whose actions all too often is just not only counterproductive but can cause true harm. He tells the tale with keen insight and a wonderful turn of the phrase.

I recall seeing my first cancer patient while working in a medical center in the late 1950s. I was learning the basics when the Lab head asked me to come in and look at a blood slide of an eight year old. I think I knew something but this slide was filled with lymphocytes, a Leukemia.  At the time this was a death sentence. In fact unbeknownst to all one could not then identify the type of leukemia, just that this eight year old would not make nine.

DeVita comes to the stage at the same period. Not only could it not be diagnosed but the cure was beyond reach. He becomes one to lead the fight.

However in a New Yorker Review the author, not a physician as best as I can tell, nor even related to the field, takes some strong shots at the author[1]. The author states:

For the past half century, he has been at the forefront of the fight against one of the world’s most feared diseases, and in “The Death of Cancer” he has written an extraordinary chronicle. DeVita’s book is nothing like Siddhartha Mukherjee’s magisterial “The Emperor of All Maladies.” Mukherjee wrote a social and scientific biography of the disease. DeVita, as befits someone who spent a career at the helm of various medical bureaucracies, has written an institutional history of the war on cancer. His interest is in how the various factions and constituencies involved in that effort work together—and his conclusions are deeply unsettling.

DeVita has his career well established with a half century record of achievement and success. The book recounts the hurdles he had to jump and the intense difficulty of working in Washington. I am reminded of a friend’s spouse who went to DC as an Assistant Secretary. A mighty position. I warned her to beware of the professional “back stabbers”. Washington, unlike any other location seems to have a professional corps of “back stabbers”, nothing personal, it is just their job.

Two years later the individual informed me after they had moved on that at first I was the only one with such bad news, all others said good luck and take the hill. But alas the professional “back stabber” came out and did their job. DeVita brilliantly recounts them, including the antics of Senator Kennedy. The problem is that it is these very institutional barriers which are more critical than a sociological understanding of cancer.

The author in the New Yorker further recounts:

Later, when DeVita and his fellow N.C.I. researcher George Canellos wanted to test a promising combination-chemotherapy treatment for advanced breast cancer, they had to do their trial overseas, because they couldn’t win the co√∂peration of surgeons at either of the major American cancer centers, Memorial Sloan Kettering or M. D. Anderson. When the cancer researcher Bernard Fisher did a study showing that there was no difference in outcome between radical mastectomies and the far less invasive lumpectomies, he called DeVita in distress. He couldn’t get the study published. “Breast surgeons made their living doing radical or total mastectomies, and they did not want to hear that that was no longer necessary,” DeVita writes. “Fisher had found it difficult to get patients referred to his study, in fact, because of this resistance.” The surgeons at Memorial Sloan Kettering Cancer Center were so stubborn that they went on disfiguring their patients with radical mastectomies for years after Fisher’s data had shown the procedure to be unnecessary.

The fact is that surgeons for decades brought hospital the big money and thus they ruled. Threatening their purse could be problematic at best. DeVita was right, and he pushed forward. Then the author notes:

But here “The Death of Cancer” takes an unexpected turn. DeVita doesn’t think his experience with the stubborn physicians at Memorial Sloan Kettering or at Yale justifies greater standardization. He is wary of too many scripts and guidelines. What made the extraordinary progress against cancer at the N.C.I. during the nineteen-sixties and seventies possible, in his view, was the absence of rules. A good illustration was Freireich’s decision to treat Pseudomonas meningitis by injecting an antibiotic directly into the spinal fluid.

This is where the argument takes a brisk turn indeed. This is the beginning of the battle with the FDA and complexity of Clinical Trials. Anyone who has any proximity to Clinical Trials knows their cost and complexity. Each new therapeutic goes through some variation and a 3 Phase human trial with enormous costs and time. Safety first and then efficacy. Typically the trial patients are the sickest.

Take for example the new therapeutics in melanoma. Using combined therapies on Level 2 patients may be even more productive but the cost and time is extraordinary. Can this be changed, should it be changed? DeVita gives an experiential and emotional argument for why it can and should.

The author ends with:

When DeVita returned to Memorial Sloan Kettering years later, as the physician-in-chief, the hospital got better. But DeVita didn’t last, which will scarcely come as a surprise to anyone who has read his book. “The problem with Vince,” the hospital’s president reportedly said, in announcing his departure, “is that he wants to cure cancer.”

I do not know how best to read this remark. You want a physician to seek to cure your disease. Often patients are willing to commit to that step. I have even recently seen patients, close friends, take that “petri dish” approach, and yes, get cured. So perhaps we need more DeVitas.

Monday, December 7, 2015

Return of the Scribe

Augustine of Hippo allegedly "wrote" all of his massive works by means of scribes. That was in the 4th and 5th century. Scribes were employed extensively throughout the Roman world and managed to survive at least halfway through what we know as the Middle Ages.

It appears as if they are returning with a vengeance thanks to the ACA! All hail the Scribe!

As noted by Kaiser:

A national campaign for electronic health records is driving business for at least 20 companies with thousands of workers ready to help stressed doctors log the details of their patients’ care — for a price. Nearly 1 in 5 physicians now employ medical scribes, many provided by a vendor, who join doctors and patients in examination rooms. They enter relevant information about patients’ ailments and doctors’ advice into a computer, the preferred successor to jotting notes on a clipboard as doctors universally once did. The U.S. has 15,000 scribes today and their numbers will reach 100,000 by 2020, estimates ScribeAmerica, the largest competitor in the business. After buying three rivals this year, it employs 10,000 scribes working in 1,200 locations.

Another source for an increase in health care costs! They accompany a physician into the office with a patient and as the physician examines the patient the Scribe records all that happens.

Now we do see some major issues:

1. Scribes are unregulated and are privy to highly sensitive information. What I may tell my physician I may not want some minimum wage typist to be privy to.

2. Scribes may copy the wrong thing, or too much. Watch out for the lawyers. Once it is written it cannot be unwritten, easily!

3. Scribes cost money. Not only do they get paid for their rime but the physician should review and remark on what they wrote. That just adds costs if you will.

The list of Scribe issues continues. But as that Congressperson said; " have to pass it in order to see what is in it...".

Welcome to America! Oh yes, perhaps we can get those buggy whips back again when we go all green.

Security, Privacy and Data Gathering

Back in 1977 I went to an IEEE meeting at Cornell where there was a big flap by NSA and others over the release of the Rivest et al crypto schemes. At the time I had the opportunity to watch over some Eastern Europeans who were in DC but in Ithaca, there they were. Surprise, no.

Out of those meetings came a way to combine the then crypto scheme approved by NIST and the new RSA scheme. Namely one could use DES as a shared key system but use RSA to send the keys in a secure manner and then cycle through various DES keys using RSA. Works fairly well and even then was doable whereas today it is dirt cheap.

The second issue was authentication. Namely the problem of assuring from whom the message came from. Today we use certificates but then and I assume still now we use complex systems as we had developed then. Our application in the late 70 was the deployment of sensors using seismometers to check for Soviet nuclear testing. We wanted to have authenticated data and not Soviet spoofs.

Today we look for patterns as to who is talking to whom. Assuming people do not try to confuse others then this may be possible over big data systems. However for a couple of decades now we have seen the development of anonymizers. Now MIT researchers announced their latest scheme.

They state:

If an adversary has infiltrated the server, however, he or she can see which users are accessing which memory addresses. If Charlie’s message is routed to one address, but both Alice’s and Bob’s messages are routed to another, the adversary, again, knows who’s been talking. So instead of using a single server, Vuvuzela uses three. Corresponding to the three servers, every message sent through the system is wrapped in three layers of encryption. The first server peels off the first layer of encryption before passing messages on to the second server. But it also randomly permutes their order. So if, for example, Alice’s message arrived at the first server before Bob’s, and Bob’s arrived before Charlie’s, the first server will pass them to the second in the order Bob, Alice, Charlie, or Charlie, Bob, Alice, or the like. The second server peels off the second layer of encryption and permutes the message order yet again. Only the third server sees which messages are bound for which memory addresses. But even if it’s been infiltrated, and even if the adversary observed the order in which the messages arrived at the first server, he or she can’t tell whose message ended up where. The adversary does, however, know that two users whose messages reached the first server within some window of time have been talking. And even that is more information than Vuvuzela’s designers want to give away.

Namely they flush everything they have across the net and confuse any adversary. Cute, but I suspect this is but one of many such schemes. Hiding in plain sight, hiding in noise, etc all follow a similar path.

Thus the questions which this poses are:

1.  In encryption, any junior engineer could implement an AES/RSA system which would be quite difficult to break. In fact a "whack a mole" feature one could argue would make it unbreakable. In fact such a system would be outside the transmission path, and thus one could care less about iPhone encryption, you do not rely upon it.

2. Authentication is critical. If two adversaries desire to speak then they must be certain as to whom each is. This is an authentication problem and one cannot expect to use Certificates here. Yet there also a large collections of options.

3. Patterning is the means of looking at data flows and trying to see what they infer as to the actions of parties. Systems like the one above demonstrate that the complexity of this can be increased exponentially. In fact it can be made almost fool proof.

Thus the screams and moans as to making all systems open is just that; scream and moans. Any adversary already has a wealth of tools, many most likely funded by Government contracts and in the public literature.

Remember 1977! When RSA came out you could guess who was in the audience. Today, different faces but same result.

Pearl Harbor: Then and Now

Above is my father's ship, USS Albert W Grant, in Manus for repairs, after the Battle of Leyte Gulf in October 1944. This was the beginning of the end for Japan. Its fleet destroyed but Okinawa was still ahead, thousands of Japanese aircraft dive bombing in suicide manner the ships in the landing force. Some felt that Japan was on the brink of surrender, I am assured that none at Okinawa thought the slightest as such.

But on December 7th in 1941 the US was attacked and we went to War, total and devastating war. Millions died as a result of the actions of Japan. But Japan attacked military sites. Our recent "war" was precipitated by an even more deadlier attack on civilians while the only defense were unarmed National Guard Fighters from several hundreds of miles distant.

Now we have been attacked again, and again, and again, most recently in California. The response is tepid at best. Perhaps we need better history lessons.

Saturday, December 5, 2015

Some Thoughts on Plant Evolution in The Urban Jungle

Plants evolve, often more rapidly that animals. We may not notice it since we don't look closely at them. But they do. In a recent paper on plant evolution in The American Journal of Botany the authors remark:

Why might urbanization infl uence plant evolution? Clearly, urban development changes both the biotic and abiotic environment in ways that could alter natural selection and adaptive evolution within plant populations. Urbanization may also infl uence nonadaptive evolution due to altered gene fl ow, genetic drift, or nonrandom mating. For example, urban development causes habitat fragmentation given that buildings and roads are a common feature to every city, where extensive pavement, concrete, and alteration of natural habitats is the rule rather than the exception. Th is fragmentation can limit dispersal and gene fl ow,  leading to greater genetic diff erentiation between populations. It can also infl uence the size of populations and thus the importance of neutral evolution because genetic drift will be greater in  smaller populations. Finally, urban areas can alter mating patterns (e.g., increased selfing) through changes in pollinator communities...

 The authors then make several predictions:
  1. Urban and non-urban populations will diff er in the amount of genetic diversity
  2. Urbanization will alter natural selection on populations
  3. Neutral evolution will be greater in urban areas
  4. Genetic divergence between urban and non-urban populations will be proportional to the size of urban areas
  5. Insect-pollinated plants will evolve greater selfpollination or clonal growth in urban areas
Now I would argue a bit differently. The primary influence on urban diversity will be driven by humans. Humans select plants that they like, like the triploid Hemerocallis. They become invasive via human attraction. They are sterile but aggressive growers pushing out other plants. They are a typical invasive species. Also the introduction of foreign species may very well lead to cross breeding that would have been impossible otherwise. Yet successful growth may be inhibited. Also the use of pesticides and similar plant control biotics will cause a shift in classic evolutionary manners.

Thus the five predictions above I believe are at most a small part of the complexity of urban development. For example I have more than twice the tree species on my small acreage than indigenous plants would provide. Some of the trees are quite hardy and aggressive such as Ginkgo and Metasequoia.

I believe that a more details analysis and monitoring would be quite useful, and that what the authors propose may be quite limited.

Employment December 2015

We have been following employment for seven years now and the pattern is clear; there is a large systemic gap in permanently unemployed and the ratio of those employed outside Government to inside Government is decreasing to almost 1:1. Perhaps at some time some folks will take notice.
First our standard curve. Unemployment per the Government is down but the unemployment using 2006 participation rates is still in excess of 7%.
Population continues to increase and the employment continues to grow keeping the gap at the point with a lower participation rate. There is no way we can recover to 2006.

This shows the participation rate bottoming out with no movement forward.
The above details the gap between actual increase and target increases.
Finally the above details the systemic unemployed, now about 3.5 million. Had we recovered these numbers we would have a much healthier economy with less money going to these people and more tax revenue generated.

It should also be noted that starting in 2016 we will see the ACA taxes increase significantly and this should be a throttle on any consumer growth.

Friday, December 4, 2015

The PhD: Value and Use

Nature has a small piece on the growth of PhDs and their alleged mis-direction. My observations are based upon 50 years of doctoral/post-doctoral involvement with time spent in and out of academia.

What is a PhD good for? Perhaps a good question. It takes time, money, dedication, delayed gratification. It produces a highly trained and filtered individual. It is an individual who has intellectually achieved as well as having demonstrated an ability to dedicate great resources with limited returns for a longer term benefit. What is the benefit? The ability to see and produce what the less well trained individual does, perhaps. It should not be a training ground for Lab Tech replacements, low cost, well trained worker bees who when they are burned out are replaced by new worker bees, an endless supply.

In Germany many PhDs go into industry. There must be more Doctors of some specialty in Germany per sq km than any other species. I think I even seen some Dr so and so at the Munich ticket counter service passengers. So the education per se is not the issue. The issue is; how is it used.

The Nature article states:  

The numbers show newly minted PhD students flooding out of the academic pipeline. In 2003, 21,343 science graduate students in the United States received a doctorate. By 2013, this had increased by almost 41% — and the life sciences showed the greatest growth. That trend is mirrored elsewhere. According to a 2014 report looking at the 34 countries that make up the Organisation for Economic Co-operation and Development, the proportion of people who leave tertiary education with a doctorate has doubled from 0.8% to 1.6% over the past 17 years.

So in the US we are producing them at a great rate. But they can and should find places in industry. The Academy does not need them, cannot use them, other than as cheap labor, and their use is maximized monetizing those skills, not trying to hang on. They should be aware of that from the get go. Back in the 60sw at MIT I knew of few of my classmates finishing PhDs trying to find teaching spots. They wanted jobs, and for a while there were a few, then Nixon collapsed the country in 1971, and none were around. At least we could become electricians!

Now here Nature states the crux:

One reason is that there is little institutional incentive to turn them away. Faculty members rely on cheap PhD students and postdocs because they are trying to get the most science out of stretched grants. Universities, in turn, know that PhD students help faculty members to produce the world-class research on which their reputations rest. “The biomedical research system is structured around a large workforce of graduate students and postdocs,” says Michael Teitelbaum, a labour economist at Harvard Law School in Cambridge, Massachusetts. “Many find it awkward to talk about change.”

 Yes, cheap labor, in hope of some dream. In fact they would be better off in industry, and industry would be better for using them and the assets they bring. All too often industry, especially MBA type managers, view PhDs as "head in the cloud types" or "single focus" types. In reality the PhD can do more than any MBA, they can create value not just transfer or worse destroy value. The PhD should be viewed as a peer, one who can add as much value to an establishment as any other and at times more. The PhD should also understand that value statement as well. The PhD should not be held captive as cheap labor.

Nature concludes:

But there are signs that the issue is becoming less taboo. In September, a group of high-profile US scientists (Harold Varmus, Marc Kirschner, Shirley Tilghman and Bruce Alberts, colloquially known as 'the Quartet') launched Rescuing Biomedical Research, a website where scientists can make recommendations on how to 'fix' different aspects of the broken biomedical research system in the United States — the PhD among them. “How can we improve graduate education so as to produce a more effective scientific workforce, while also reducing the ever-expanding PhD workforce in search of biomedical research careers?” the site asks.

The change is simple. Let the PhDs know from the get go that they should, can, and must seek to "market" their talents, and not just their PhD research, and they they should seek jobs not short term low paid and low return task work. This is not just a problem in the bio area, it is quickly becoming a pandemic across many fields, engineering included. Why should any PhD in engineering do a post-doc? Get a job, use your skills, make something, and get out of the dream world of academia.     

DeVita, Cancer, and a Must Read

DeVita’s book, The Death of Cancer, is a personal recollection of one of the most well-known cancer specialists in the world. In a sense it is an Odyssey tale of a highly competent and prolific person who flows with his times and manages the Scylla and Charybdis of Government work. The book is well written and reflective of the man and his times. DeVita started out during the Vietnam era when any male graduating from Med School found themselves, unless otherwise excused, ready for immediate assignment to some military unit. Many of the top students were fortunate to get to go to NIH which was DeVita’s fate, and it was this flow of talent in the late 60s which made NIH and NCI one of the best institutions in the world. Thus the tale of DeVita and cancer starts here with NCI and a flow of excellent talent.

DeVita describes his work on the use of multiple chemotherapy regimens and the resistance from the likes of Farber in Boston, hardly an uncommon occurrence especially in Medicine. This was the MOPP therapy that most now know as a major breakthrough in Hodgkin’s. The discussion on how he and the team managed to persist and managed to go through the then significant administrative a bureaucratic complexities is amazing.

The discussion on his involvement in the “War on Cancer” and the political games is quite interesting especially for anyone who has not spent a tour of duty in Washington. There were games within games and DeVita was at times a willing participant but as see in the book and excellent observer. His description of the political gamesmanship is worth the read if nothing else. It is also worth the while for anyone seeking to grasp how Washington functions, and why it may work at times and often falls into total disarray.

On p. 159 I was interested to see the interlocutory between Benno Schmidt and Jim Watson while Watson was I gather performing one of his classic poses. This also is worth the read. I have had my students return from a talk by Watson and ask me: “Does he really think Physicians and Engineers are useless?” But I gather that is Watson, a scientist at heart.

On p 219 there is a great discussion of his time at MSKCC, a world renowned institution but at times falling behind in certain areas. DeVita states: “MSKCC had the potential to be the best cancer center in the world, it wasn’t” is a powerful statement and at times quite true. MSKCC has powerful backers and Board members and although it may try from time to time to be at the lead there is always the chance that it becomes insular. The lesson DeVita brings out here should be a warning for many such institutions.

On p 247 DeVita discusses the recent Hanahan and Weinberg paper on Cancer, a follow on to what the two authors had written in 2000. This is a paper on the hallmarks of cancer and is looked upon as a sine qua non in the literature. DeVita lauds it at length and rightly so. Yet what this paper also shows is that we have learned a great deal but the “War on Cancer” is just getting harder the more we learn. One could argue that the recent Hanahan and Weinberg paper albeit prescient and insightful lacks the depth on epigenetic factors which we are seeing more and more in cancers. The more that is learned the more complex the disease.

On p 253 DeVita discusses the inflammation relationship. We often ask what causes cancer and the more we understand inflammation the more we can see the nexus. This is a useful and important discussion as well.

On p 258 DeVita makes an interesting statement:

“In my opinion, when there is less than a 10% chance of the cancer recurring after a patient passes his or her cancer’s critical period, then the patient should be told, in all likelihood, he or she is cured.”

This is a powerful statement and one a physician with extensive clinical experience is wont to utter. However one should parse the statement. First, how does one determine a 10% chance? In prostate cancer we can perform a prostatectomy and monitor PPSA for several years and then see a met occur. When did the 10% level occur? Second, what is a critical period? How do we define it for each cancer? Then the catch phrase of “in all likelihood” is something the patient may or most likely not hear. Cancer patients often has selective hearing.

Overall the book is highly enlightening and a must read for anyone interested in the progression of cancer therapy. Also DeVita’s discussion of his battles with the FDA and Sen. Kennedy’s blatant interference with NCI if it in his opinion interfered with the FDA was quite interesting. DeVita bares the political quagmires of Washington and demonstrates that progress can often be made despite the Government overhead by dedicated and highly competent individuals.

Thursday, December 3, 2015

An Excellent Contribution to the Literature

The book by Mydlo and Godec, Prostate Cancer, is an exceptionally good text for practicing urologists and residents to get an understanding of the current understanding of this disease, prostate cancer (PCa). PCa is a complex disorder, and is unlike many other cancers. On the one hand almost all PCas are indolent, namely the patient will most likely dies of something else, but the small percent that have an aggressive form die very rapidly. The primary tool for detection has been the PSA tests which were virulently attacked by the USPTF. It can be argued that the data they based their opinion on was flawed but we leave that for time to tell, unfortunately at the cost to the patient. The genetics of PCa is also highly complex.

Unlike so many other cancers where we can identify a specific target such as BRAF in melanoma, BRACA in breast cancer and ABL fusion in CML, PCa is a mass of speculative genetic changes. Also the treatment of PCa is becoming more problematic. The options are several; surgery, radiation, implants, and even “watchful waiting” which in a sense is let hope and see what happens. The problem is that PCa metastasis is insidious and unlike breast or melanoma the path is circuitous and uncertain.

This book is introduced at a time when all of these issues are facing the physician. The question is; what does the physician recommend as a course of action to a patient? All too often the patient presents with a diagnosed PCa and based upon the patient’s own investigations finds his path to a recommended therapy. Whether that is the best for this patient is usually uncertain.

On p3 the authors open with a direct assessment of the USPTF, one which I would strongly recommend reading for any practitioner. It is short, well written and on point. This in a sense sets this rest of the work in clear perspective; unlike the USPTF, this is a “what is the best for the patient” work.

The book is structured along standard lines.

The first several chapters deal with a wide variety of current issues such as the genetics, the androgen receptor issues, and fusion. All are done at a reasonably high level for the practitioner. This is clearly not a book on the detailed genetic issues associated with PCa. Chapter 5 is an interesting chapter since it discusses the issues of Gleason 6 and is it even a cancer. This is a compelling question since as we are discovering the genetic makeup is often more telling and that may mean the genetic makeup of the most aggressive cell. Chapter 6 is another significant chapter since it deals with HGPIN. HGPIN has for a decade or more been synonymous with a progression to PCa. However that is not inevitable. The interesting cases are those where there is a HGPIN at initial biopsy and then it disappears and never returns. The question then is; how significant a prognostic issue is HGPIN?

Chapter 11 discusses MRI imaging in localized PCa. MRI imaging is becoming more common and is becoming an element in integrated biopsies with real time ultrasound. This is a useful chapter for the urologist to become familiar with an imaging technique which will become a more integral part of diagnosis and prognosis. However as with all modalities it may add significantly to the costs and also may cause increased biopsy covers for what may not be significant observations.

Chapter 13 is an excellent discussion on PSA screening. PSA is a useful but sometimes problematic measure. PSA increases with prostate volume and age as well as with pathological changes. Differentiating them is complex. The physician must balance reasonableness with the risk of being too insensitive to the changes. Chapter 17 discusses hereditary PCa. This is mostly a discussion of genetic inheritances that result in PCa. However we also know that there is a strong correlation between first degree relative PCa and PCa in the patient. This is correlative and not causative, whereas what in in this chapter seems to be much more causative.

Chapters 26 thru 41 discuss the complexities of surgical treatment and the presentation is clear and up to date. Chapters 42 thru 48 discuss radiation therapies with equal presentation. Chapters 52 thru 57 discuss some advanced issue of PCa therapy. This includes several biologics as well as androgen therapies.

Chapter 66 is an interesting chapter in that it discusses new markers for diagnosis and prognosis. On the diagnosis side there are many ways to enhance PSA and related measures including PCA3. One of the recent tests such as 4K have seemed to be of some use in assessing the chance of there being PCa prior to biopsy. Although I have had experience with this test and positively specifically it is still as I write this not FDA approved. There are also almost a dozen genetic tests used on PCa cells after biopsy to ascertain a prognosis for subsequent aggressive potential. Many of these are still being tested but generally they also provide guidance. However the conundrum is using them for prognosis when the result is poor and there is no significant treatment available.

Overall this is an excellent up to date summary of PCa, its diagnosis, prognosis, treatment and the state of the science that surrounds it. It clearly meets the needs of the practitioner. Its weakness in my view, and that of one involved more deeply on the genetics side, is that it would have been helpful to have delved a bit more deeply in the genetics of PCa. Unlike many other cancers PCa is highly heterogeneous and it seems that each week one sees another several genes putatively involved. Thus one can appreciate perhaps avoiding this area since it may be out of date by publication.

This is an excellent and up to date text and a worthy addition to what is currently available.