Thursday, May 28, 2015

Ad Hoc Propiter Hoc

In a recent piece in Vox the authors state:

Compared to other developed countries, the US ranks high on income inequality and low on social mobility. This could be particularly concerning if such a trend is self-perpetuating. In this column, the authors argue that there is a causal relationship between income inequality and high school dropout rates among disadvantaged youth. In particular, moving from a low-inequality to a high-inequality state increases the likelihood that a male student from a low socioeconomic status drops out of high school by 4.1 percentage points. The lack of opportunity for disadvantaged students, therefore, may be self-perpetuating.

Perhaps they have never been to France or the UK. In the UK it is your birth family that all too often defines you. It defines your position in society and your outcome. In France it again is family and school. In Russia, well we all know that one.

In the US anyone has a chance despite the author's contentions. Moreover one should look at their own data to see that DC has the highest drop out rate the the highest income disparity! Why, the Government. Lobbyists get millions and the old time residents wallow in a failing school system, albeit supported by the taxpayers.

In my experience the US has the greatest social mobility of any country. Anyone can start anything and try to make a go of it. Failing to complete High School is all too often a failure of the local Government and its way to educate. One need just look at the Charter Schools and their success.

Sunday, May 24, 2015

A Book on the Genomics of PCa

Prostate Cancer by Stabiano is a recent contribution to the field of literature discussing the genetic underpinnings of this disease. It is a multi-author work by those at the University of Naples and surrounding institutions. It consists of eighteen chapters and the focus is on describing the recent efforts on various elements of the genetic bases of prostate cancer. Each chapter is prepared by one or more of the authors and covers a somewhat specific topic.

Chapter 1 is a well written summary of pathological methods of current use in diagnosing PCa and its related presentations. The materials is well presented and sets the stage for the discussions regarding the genetic elements.

Chapter 2 sets the tone of the remaining Chapters. This Chapter discusses inflammation. Its style is carried through the remainder of the book. Namely the author presents briefly the importance of inflammation and then proceeds through the most recent literature on a topic by topic basis covered in one to two sentences. The presentation is more akin to a literature survey rather than an introduction or even detailed discussion of inflammation in PCa. Inflammation has always been a concern in PCa and its study has been spotty at best. To understand inflammation and its effects one must understand what genes may be affected as well as the impacts on methylation and miRNAs. This becomes a somewhat circular analysis and the authors set up each separately and on a somewhat standalone basis.

Chapter 3 is on apoptosis. This is a key element in almost and cancer. This is a well done chapter and does try to tie together some of the elements. The especially useful addition is the discussion on non-apoptotic elements which is fairly complete and of significant interest to those seeking an expansion of this work.

Chapter 4 discusses the AR, androgen receptor, dynamics and it again follows the style of reviewing and commenting upon the current literature. Chapter 5 does likewise for neuroendocrine issues.

Chapter 6 is an excellent chapter on metastasis. It covers a great deal of the current work including for example that on ALDH1A1 and potentially ALDH1A3. The graphics are generally good and useful. Chapters 7-11 continue the discussion of pathways and their interactions.

Chapter 12 is a discussion of epigenetic factors including methylation and miRNAs. This is a powerful area of research and it would be useful to have expanded the discussion. Whether or not SNP issues fit here as well is an open debate. However, epigenetic factors are becoming significant in understanding many cancers, since they can change expression while leaving DNA in its original form. Epigenetics blocks mRNA from converting into their operative proteins. This may then become a viable path for a therapeutic.

The remaining chapters cover a wide variety of related topics. All are written in the same manner

Overall the books is an excellent source of accessing the literature. It is, however, neither an introduction for those seeking to understand all of the elements, nor is it a standalone text useful for in depth understanding. I would strongly recommend it for those studying the genetic factors associated with PCa. It is an excellent addition and expands understanding the literature. However it is not for the individual seeking a first exposure and it is not a document which attempts to provide unification of the topic.

I would like to have seen some detailed discussion on the issues associated with the loss of cell fixation by the breakdown of the extra-cellular matrix adhesion. I would also have like to see a more detailed discussion of the pathways and their interactions. So much of the book is a single sentence statement of third party work that the sense of cohesion is oftentimes missing.

Overall, however, this is definitely worth having as a reference source for those in the field.

What's in a Name?

Names can mean something, should mean something. So I was surprised when I read a WAPO piece by a University President proposing some "innovative" way to monetize research.

The article states:

To create a new way of supporting the first stage — from idea to investment — a coalition of funders from the public, for-profit and not-for-profit sectors could work together to establish “innovation orchards.” These would provide what universities alone cannot: the physical space, mentorship and bridge-funding for entrepreneurs to turn new science into workable products, up to the point that they meet venture capital’s five-year threshold for the journey from investment to an impact on the market. This would make investing in tangible or tangible-digital hybrid innovations no riskier than investing in the purely digital. 

It seems to propose that some group or groups "fund" the process of going from pure research to implementation with this "Orchard" concept. Frankly funding of all types seeks a return. The VC or similar funding entity has a lifetime associated with it. It does not go on forever and its returns have a discount factor. You can promise billions of dollars but if it is thousands of years from now one will have little to no interest.

One can suggest something but perhaps more meat on the bones would have been useful. There once was a time when University Presidents could suggest with some detail. This is throwing a name on the wall and hoping that others will fill in the gaps, there being many.

In my experience I a reminded by a comment made by a colleague, oft repeated, "A good idea does not a business make" It is quite unfair to researchers to let them think that the idea alone, even if it is embodied, has any merit other than its very existence. University research is a process of training, teaching a student how to accomplish a task. True research is just that, exploring the future. However one should not expect that every research result is productizeable. They are not.

The real issue is that in our current research the biotech world is soon to dominate. Unlike our past high tech adventures this world will be controlled by the Government, the FDA. It is that process which will delimit what we can accomplish and it is that world which needs modification.

Thursday, May 21, 2015

Dig a Bit Deeper!

In a recent Nutrition and Diabetes journal article the authors conclude:

Most studies examining the relationship of body mass index (BMI) with mortality in diabetic persons suggest a paradox: the BMI category with lowest associated mortality risk (overweight or obese) is higher than it is in non-diabetic persons (normal weight)

Let's try this in English. They seem to state that Type 2 Diabetics with lower BMI have higher mortality.

They continue:

In conclusion, in comparing physical and mental health status by BMI category in concurrent national samples of diabetic and non-diabetic persons, we found evidence of a physical (but not mental) health status paradox in diabetes. Physical health status was most optimal in the overweight category among diabetic persons, versus in the normal-weight category among non-diabetic persons. Given that physical health status influences mortality risk, the findings suggest possible pathways to a BMI mortality paradox in diabetes.

Now this article leaves several questions. They seem to mix Type 1 and Type 2 Diabetes. It is not really clear in reading.

Second, perhaps if one has Diabetes and has low BMI then one may have a totally different form of Diabetes.

Third, in examining anything like this one needs the history of each patient. Not just a single time sample. How heavy were they when the Diabetes started? Just to begin with.

The Tables state Diabetes, but what type?

Type 2 Diabetes with BMI under 20? I find that amazing. One is on the verge of ketosis and yet they have Type 2 Diabetes. It makes no sense. Unless of course it is something else.

Perhaps we should have seen a picture of the authors? Just a thought.

Tuesday, May 19, 2015

Yield Curves May 2015

The Treasury Yield curves are shown above. They seem to have clumped and are now spreading out again
The above is an example show today's curves and lows and highs. The question is: what do these really reflect?
Finally the spreads, starting up again but not a great deal. In many ways this is still very artificial.

Free Tuition

There is a movement to have free tuition at state universities funded by the Feds, aka the taxpayers. Is this a good idea?

Frankly if students who perform well and demonstrate their abilities, then in state tuition at their state schools is great. West Virginia already has it for high performers and New York used to have Regents scholarships before they did away with Regents. It makes sense for those who are doing well but not MIT or Harvard yet.

But one must beware of several factors:

1. It should be performance based. What performance? Class ranking, grades, even a competitive exam. There must be some clear demonstrable level of performance. It must also be blind to anything else. Otherwise it will be gamed.

2. The Feds must be hands off. We all know what the Feds up costs. How can this be done, block grants perhaps.

3. Avoid social engineering. If one wants people to perform then make the rules clear and play the game. We do not social engineer football, basketball, etc.

4. Promote productive studies. We really do not need too many fine art majors or French literature majors. We do need engineers. We don't need more lawyers, we do need competent physicians.

5. Reward performance and punish failure. Yes, if they fail then drop them. Give a second chance but do not let them linger.

6. Set standards, real standards for real life. The goal of education is to be productive. Productive in society. One can always study philosophy later. Or at the same time if one can fit it in.

Just some thoughts.

PSA, Tax Dollars, and the Government

From time to time one reads about the errors induced in Government programs. The recent report that NCI has removed all of the historical data due to data entry problems, that is about 45 years worth of data, is truly amazing. Here is what NCI states:

The results for this registry-based evaluation in two SEER registries confirmed that the PSA values were often incorrectly reported based on an implied decimal in that data field. Following current reporting guidelines for cancer registry data, PSA is coded in a 3-digit field with an implied decimal between the second and third digits. For example, a PSA of 4.0 ng/ml should be coded as 040. In both the study described above and in the SEER registry’s evaluation of their data, it was noted that some registrars were confused with proper use of the implied decimal. For example, this resulted in coding a PSA of 4.0 ng/ml incorrectly as 004. The error rate for the SEER data was lower than that seen in the original study and was approximately 17%. The likely reason that the error rate was lower was a reflection of the ongoing quality activities that routinely occur at each of the SEER registries as data are submitted.

The core rule in entering data is to avoid ambiguity, yet expect it and check. Now we have many studies which have used this data and then make regulations based upon it. Perhaps the PSA rules mandated by the USPTF should be not only reconsidered but totally abandoned!

They conclude by stating:

We are currently developing a protocol that will be applied by all SEER registries to further assess the error rate and allow the registries to correct PSA values in recent years. As part of that protocol we will determine whether we can use statistical methodology to correct PSA from prior years. Once we have corrected the data, we will repost the PSA corrected values and make those available to researchers. 

Anyone who has ever done a set of questions for a database knows the possibility of mis-interpretation. I see it all the time. Recently I examined a Columbia Medical Center set of questions that not only were ambiguous but flawed. They made no sense. But did that stop anyone, no!

Clearly the 040 or 4.0 could have been avoided by being clear, namely x.y, two fields, with an error check and a feedback in red restating the value. Frankly the required entry is truly confusing, and it probably costs us millions to design!

Monday, May 18, 2015

Now It's 5000+ Authors

In Nature there is a report of a paper having over 5,000 authors. As they state:

A physics paper with 5,154 authors has — as far as anyone knows — broken the record for the largest number of contributors to a single research article. Only the first nine pages in the 33-page article, published on 14 May in Physical Review Letters, describe the research itself — including references. The other 24 pages list the authors and their institutions.

This seems to be the trend.

Sunday, May 17, 2015

Interesting But Worth a Critique

The End of Ancient Christianity by Markus is an enlightening presentation of the Church from Augustine to Gregory I, about 400 to 600. This is the post Constantine period, one where Christianity was no longer persecuted and managed to begin its establishment of elements of control over the lives of most people. At the time of Augustine, say 400, there were clouds on the horizon but not to the extent of those that Gregory had to contend with. Markus argues that there was in the West a change from the secular to the sacred, namely changes from classic Roman control to controls influenced and dominated by the Church.

One of the dominant changes was the move of the capitol city from Rome to Constantinople, Byzantium, and the remnants of control in the west being limited presence in Ravenna. Augustine in Hippo knew the old Rome, while Gregory in Rome saw a totally new reality. Markus presents his interpretation of how this change occurred and what were its elements.

On p 15 the author commences building his presentation of secular and sacred. He states “No one really doubts that in ways such as these Western Europe was being drained of the “secular”…” This in some ways is contradicted by the facts. The Franks, namely the Merovinginians, albeit Christian in calling, were anything but sacred in their actions. Gregory of Tours recounts their blatant brutality and even the letters between Gregory and Brunhilda, the former Queen, lay out the clear continuation of Frankish ways. Moreover the preponderance of Salic law had supplanted Roman law and the Code of Justinian never really made its way to the West. Add to that the Lombards who were Arians, and a continual burden to Gregory. Spain and its Visigoths had a similar situation. Thus the statement made by the author in my opinion is contradicted by both the record and the facts.

On pp 16-17 the author provides an outline. Part I is a discussion of the post Constantine changes. Part II discusses the forces that the author contends led to the changes from secular to sacred. Part III considers the ascetic norms which became part of the way of life going forward.

Chapter 2 is a discussion of the structure of the Christians in the beginning of the 5th century. They had become communities, open and were using the martyrs and their relics as a nexus to their past.

Chapter 4 is a discussion of Pelagius and Augustine. The key to understanding Augustine is his theory of grace and it is predicated on Paul’s letters in Romans. Grace was given, and acts were less important than grace. Pelagius in a simplistic sense saw acts as important if not more so than grace. To this speculation Augustine responded with vitriol. On p 52 is an excellent interpretation of the development of Augustin and his battle on grace. He had sharpened his arguments on what he did with the Donatists. The Donatists position was that if you denied your faith you were not able to return to where you were when the cause for the denial was lifted. Augustine stated that once a priest always a priest and that if one recants one can return. This battle was the driver for sharpening the Augustine dialectic.

On p 55 is an interesting discussion on Augustine and the Pelagian view of sin. Namely the Pelagian view was that man could abstain from sin whereas Augustine saw man in a continually losing battle being saved only by grace. Further man never knew if God had given such grace.

Chapter 5 discusses the issue of; if grace is God’s, then what is the worth of man trying? (p 63) This is followed by the Timothy statements by Paul on free will and the possible conflicts with grace. Many of these complex ideas led to the ascetic life and the separation from society of the hermits. Whereas the martyr was the sine qua non of the pre-Constantine period, the monk the author alleges is that in the post-Constantine period (p 69). The author then discusses the details of the monastic life as it developed over this period.

Chapter 7 discusses the martyrs. In particular it focuses upon the cult of the martyrs. The Church calendar became a continually celebration of martyr after martyr. There was a culture brought to the faithful centered on one martyr after another. The martyrs were in the past but they became the nexus to the present. On pp 98-99 the author discusses this in detail The calendar went from social to sacred, from the celebration of pagan events to the remembrances of the dead. Ironically as the times went by the calendar became not only sacred by the day but even by the hour, a time for one prayer after another. Chapter 8 then is a discussion of how secular festivals could be incorporated. On p 111 there is the Augustine dictum of “abstain as far as you can from worthless spectacles”. Paganism slowly but then aggressively was persecuted. Chapter 9 is a discussion of the further Christianization of time. On p 131 there is a discussion of time being an element of the Christianization of all life.

Now the author contends that there is some universal acceptance of these principles across Western Europe. There does not seem to be evidence of this acceptance. Admittedly in Church controlled domains like monasteries and in Bishoprics, the religious times were practiced, yet as the population, in what would become France and even in Ireland, the people lived is ex-urban locations, and the monasteries were often segregated. England until Gregory I was even turning pagan. By the late 6th century the Irish monks like Columbanus had spread out across Gaul and down into Italy, such as at Bobbio, and their monasteries were open to all but distant from many. Thus it is questionable as to how universally acceptance and practice were.

In Chapter 10 there is a discussion of place. Christianity states the author abandoned place qua geography, and used place as worship. The discussion on pp 140-141 details some of this. The old Roman world was filled with holy places, albeit pagan. Christianity abandoned this, almost as a way to sever the tie to the old ways. On p 142 the author uses the martyrs as a bridge to the past during this period. It was a bridge that allowed them to connect the world of persecuted Christianity with the “new” world dominated now by Christianity. As he states on p 155 the places became locations of history and not holiness.

Chapters 11 and 12 discuss the isolation of the monasteries and the frontiers they created and then how these could be broken down. Chapter 13 adds the invasion of the ascetic into the daily lives.

Chapter 14 is a conclusion. It is here where I may have my greatest concerns. Here the author discusses Gregory I. Gregory was in a sense the last and in the sense the first of a generation of Bishops of Rome. Elected by the people, he looked westward. He befriended the Merovingians, especially the brutal Brunhilda. One must wonder how that was managed and as one reads his letters they are letters from a Bishop at once a religious leader and at once a true politician. He wanted to keep the Merovingians in the Church, albeit a brutal people. He managed the wife of the Lombard king, who eventually managed peace with the Lombards and Rome. He managed people in his lands, and he used some of the best of Roman management style to survive. At the same time he was the Bishop of Rome who truly severed the tie to Byzantium. On pp 224-225 the author commences on this discourse.

The last sentence of the book (p 228):

“The massive secularity of John Chrysostom’s and Augustine’s world had drained out of Gregory’s. There was little room for the secular in it. The Devil was close, always ready to swallow up the world and the flesh.”

I find this difficult to agree with. In reading Gregory‘s letters, and there are many, one sees a man who balances the secular with the sacred. On the one hand he can write of Job and how to preach and on the other how to govern and how to handle complex situations. In the correspondence with Columbanus one sees a set of discussions on such issues as the true date of Easter but one sees an Irish monk, never dominated by Rome, and the Bishop of Rome respectfully but aggressively making their points. He was a politician and a political leader. He managed to keep invaders at arm’s length, discuss politics with barely civilized kings and queens and also managed to fear the people of Rome. Whether it is Gregory of Tours or Gregory of Rome, the devil often seemed a distant concern.  

It could be argued that the Middle Ages in the West is the period from Gregory I to Ockham (400-1350). It was a period of Church dominance, sacred and secular. Gregory became the first Bishop of Rome to both sever the ties to Byzantium and at the same time establish political parallelisms with the emerging rulers of the developing nations. Ockham represents the first major denial of papal secular authority. Marsilius also parallels that effort but in many ways it is Ockham that introduces the individual, via both nominalism, as well as his papal analyses. In fact the very move from Rome to Avignon was a break from what the Bishop of Rome was to be, in Rome, not Avignon.

The author indicated he was starting with a biography of Gregory. That would be a worthy task by a highly worthy writer.

Overall this book is exceptionally well written and the author makes his arguments forcefully. I would strongly recommend this to anyone trying to understand this critical period not only in the history of the Church but the history of the West.

Saturday, May 16, 2015

1,000 Authors

The explosion in the number of authors on papers has gone into the stratosphere. Nature reports on a recent paper on fruit flies:

Author lists have grown lengthy in many fields of science, but when a Drosophila genomics paper was published with more than 1,000 authors, it sparked discussion online about the meaning of authorship. The paper, published in the journal G3: Genes Genomes Genetics, names 1,014 authors — with more than 900 undergraduate students among them.

This really questions who does what. Why not include the cleaning crew, the folks who built the building, the manufacturing team on the sequencer.

The problem is that it is now impossible to determine who did what. Watson and Crick was enough. Nobel prizes are given to at most three people. This is akin to a new bumper sticker, "My Teenager is an author of a major research paper!" We seem to be going unstable.

Tuesday, May 12, 2015

My Father's Partners

In the late 50s and early 60s my father was in the NYPD Youth Division. During that time he had three partners, policewomen. They were:

Ruth Simon
Gertrude Schimmel
Felicia Shpritzer

Schimmel has just passed at 96! As the NY Times states:

Like all the female members of the department, Ms. Schimmel was assigned to the Bureau of Policewomen when she graduated from the Police Academy. In her early years with the department, her son said, she took part in undercover work breaking up gambling operations. She later joined the Youth Aid Division, which found temporary shelter for children whose parents were ill or otherwise unable to care for them. It was the type of assignment given to women to keep them from confrontations with criminals.

Frankly the Youth Division was  in some ways more difficult than others. The pair would show up at apartments with butchered parents, picking up the terrified children and spending long hours finding homes. Tracking down wandering children, many who had fallen in with the bad set if you will, seeing lives not even started destroyed before a spark of adulthood. The damage done to children before their time could take a toll.

My father had been proud that his partners all managed to succeed in a profession that was male dominated. As the Times noted:

Police Commissioner Michael J. Murphy maintained that women lacked the physical strength and endurance to become sergeants, but the city lost the court battle.

As I recall my father saw these as equal colleagues, never as inferior weaklings. In fact the moral fiber was more critical than the physical, meaning that they had to help the children try to take first steps of regaining their lives, something that the rough and tumble men could not.

I remember all three, I recall the tales of their adventures, never a sharp word, always a team. The classic tale was when Ruthie finally admitted to my father many years latter that she never had bullets, she did not like guns!

Wednesday, May 6, 2015

Battery Waste?

Batteries have been useful but not the most efficient storage medium for energy. However with the introduction of lithium batteries this has improved. However lithium is hazardous waste. A rechargeable battery can go through a recharge cycle a few thousand times at best. If you do it every day, as in a home system, then you may get three to four years of use. Then you have a non-rechargeable toxic boat anchor. Where do you put it? Not as bad as nuclear waste but definitely not "green".

Along comes Tesla who announces a home battery (see the CSM):

All of the new batteries run on the same type of lithium-ion, software-equipped technology found in Tesla's cars, and can be mounted inside or outside of a building.

As Computer World notes:

Europeans have a dimmer view of landfilling lithium ion batteries. "There is always potential contamination to water because they contain metals," says Daniel Cheret, general manager at Belgium-based Umicore Recycling Solutions. The bigger issue is a moral one: the products have a recycling value, so throwing away 2 billion batteries a year is just plain wasteful - especially when so many American landfills are running out of space. "It’s a pity to landfill this material that you could recover," Charet says. He estimates that between 8,000 and 9,000 tons of cobalt is used in the manufacture of lithium ion batteries each year. Each battery contains 10 to 13% cobalt by weight. Umicore recyles all four metals used in lithium ion batteries. 

 As Waste Management World has noted, there is a recyclable option, albeit costly:

With lithium recycling in its infancy, there is currently no main recycling infrastructure in the world that treats only automotive Li-ion batteries. A few pilot plants, such as Umicore's Hoboken plant in Belgium that are at a demonstration stage exist. Lack of standardisation in battery chemistries and changing landscape with respect to different elements under research for battery production other than lithium have made evaluation of the recycled value of the components uncertain for the recyclers.

Overall one should look at the full life cycle here. The "green" puffery is just that unless the plan to recycle safely is in place. Otherwise we will have mountains of un-usable trash!