And Who Pays for This?

In a recent Nature article they indicate that the most recent recommendation for treating Type 2 Diabetes is surgical.

They state:

Clinical guidelines published this week announce what may be the most radical change in the treatment of type 2 diabetes for almost a century. Appearing in Diabetes Care, a journal of the American Diabetes Association, and endorsed by 45 professional societies around the world, the guidelines propose that surgery involving the manipulation of the stomach or intestine be considered as a standard treatment option for appropriate candidates. This development follows multiple clinical trials showing that gastrointestinal surgery can improve blood-sugar levels more effectively than any lifestyle or pharmaceutical intervention, and even lead to long-term remission of the disease

Let us examine some basic facts:

1. Type 2 Diabetes is a glucose metabolism malfunction. It is essentially an overpowering of the pancreas and its ability to maintain insulin secretion at levels to maintain safe glucose levels.

2. Glucose is  byproduct of carbohydrate intake and its breakdown. More carbs in the more glucose produced and the more stress on the pancreas and its ability to handle the load.

3. Excess carb intake leads to obesity. Obesity is thus a measure of this overload.

4. A BMI of 25 or less is generally a metric for good glucose control and it generally is reflective of HbA1c, the 60 day average glucose load.

5. Excess glucose also creates an excess free radical problem which in turn can result in a plethora of disorders including cancers.

6. To keep the glucose low one need only keep the carbs down and in turn the weight down.

7. A pound of added weight is an excess of 3500 Kcal of food intake. If one consumes 2,000 Kcal per day and has a BMR of 2,000 then the net is zero. If however the BMR is less then one starts gaining weight, usually reflective of a carb overload.

8. The zero costs solution is intake control and proper weight balance. It is really cheap, at zero.

Now the suggestion for significant invasive surgery are say a cost of $75,000 or more is insane. On the other-hand if the fattys get us old folks to pay for it then one guesses it is the ultimate gift of the ACA. And some candidates want free universal health care. Nothing is free folks!

The NY Times and Prostate Cancer

The Times has a propensity of having women write on prostate cancer and result in telling men they should just forget it.

The latest writer, who it appears spent a short time at MIT sans degree, is pushing the "watchful waiting" approach, or why spend money on a lot of old useless men argument.

She states:

Without the word “cancer,” Dr. Epstein said, men may not take seriously the need for regular biopsies and other tests. He and his colleagues at Johns Hopkins proposed a grading system to make it clear that Gleason 6 cells are less frightening than higher-grade tumors, but not necessarily benign. In the Gleason system, which involves a pathologist’s assessment of how ominous the prostate cells look, 6 is actually pretty much the lowest score for cells that are cancer, despite the Gleason scale officially starting at 2. The highest is a 10. But many men, hearing that their cancer is a 6, assume the worst.

The problem with prostate cancer it is real sneaky. Some are indolent, some are real killers. How does one tell the difference. No good answer. There are tests now that use the biopsied material to give better prognostic values but this write up totally ignores this. One wonders why? Ignorance or deliberate. 

One also wonders why almost every other day we have another female reporter, no males yet, telling men not to worry! Perhaps they have run out of Trump stories.

Prostate Cancer and Older Men

If any man had the nerve to say that only a few women die of breast cancer after 65 so why test any more there would be am uproar. Furthermore if a man wrote this in the NY Times he would be hanged in effigy. However it is OK for a woman to write in the NY Times:

Because most prostate cancer develops slowly, it doesn’t typically threaten survival or cause troubling symptoms for eight to 10 years. Even medical associations that disagree with some of the 2012 conclusions, like the American Urological Association, therefore discourage PSA testing for men with limited life expectancy.

 One should at least see that she uses the word "typically". What if it is NOT typical, then it is OK for the man to die?

Perhaps we could try to get this covered as part of the NY Mayor's speech control, we could fine her say a few million for even thinking such a thought! By the way, what is a limited life expectancy, it all too often is in the eye of the beholder. It should not be some columnist in the NY Times.

Language and Gender

The Washington Post has a reasonable take on language and the recent dictum on how to use it in New York City. It concludes:

Feel uncomfortable about being forced to use terms that express social status views (“Milord”) or religious views (“Your Holiness”) that you may not endorse? Well, you should feel uncomfortable about people being forced to use “ze,” which expresses a view about gender that they might not endorse. And, more broadly, I think we should all feel uncomfortable about government regulators forcing people to say things that convey and support the government’s ideology about gender.

But there is a bigger problem. You see the Romance Languages, such as Spanish, have gender specific nouns, verbs, etc. So if this applies to English does that mean we must change all of our Spanish, and the list goes on, to gender non specific. I remember my first Latin word when I was still quite young, agricola. Farmer. It is feminine. It was not until now that I wonder why it is feminine, I assume most farmers were men or at most fifty fifty back in 100 BC.

Perhaps when I look at my Italian, French. Greek, Russian as well I am going to have a problem. It is not discriminatory to change one language, why not all 235 spoken in New York. We are discriminating against English. Think of all those subway signs.

I have been using they, theirs and them just to avoid sex discrimination. Yes I know it is grammatically incorrect but it got me out of a few sensitive discussions. But this perhaps is a step too far. Then again there is that pesky First Amendment, but well who cares about those first Ten Amendments anyhow!

The Executive Assistant

The last time I had a Secretary, aka Executive Assistant, who was really just that was sometime in 1986 or 1987. I managed a 20 country corporation with travel, expenses, scheduling, etc with something call Email and the Internet. It really worked, even back when I used Delphi as an Internet Service Provider with an early release of Eudora thanks to Irwin Jacobs. I also had a mobile phone so that if there were any questions over some 11 time zones I could address them.

Now I see that Theranos CEO is looking for both an Executive and Personal Assistant, two people. Perhaps that is why things are such a mess. You do not need assistants you need focus and leadership and you really must know something. Really. If I had a delay problem on the Internet backbone I had to analyze the delay characteristics on a piece of paper at at worst use Excel for a quick analysis of a solution.

As Entrepreneur reports:

After voiding thousands of faulty diagnostic tests and saying goodbye to its company president, Theranos is looking for some new blood, including an executive assistant as well as a personal assistant to CEO Elizabeth Holmes. With each passing week, the list of controversies and challenges Theranos faces grows longer. Since October, the biotech company has confronted scrutiny for deception regarding its technology, the accuracy of its blood tests and its failure to adhere to scientific standards. The government has threatened sanctions against its lab operations and top executives, and president Sunny Balwani has entered early retirement in an obvious “you can’t fire me, I quit” move. At the same time, Theranos is adding new executives and board members to bolster its credibility, the company is sending out tens of thousands of notices regarding the invalidity of its tests.

Perhaps good leadership is better than more employees, especially as the walls are on fire.

One could see the problem back in 2014. In a New Yorker puff piece:

Holmes was driven from Palo Alto to the San Francisco airport, where she boarded a seven-seat Gulfstream 150 for a flight to Chicago. She would be speaking at a panel; from there she would fly to Cleveland to attend meetings at the .... She was travelling alone. Members of the Theranos board sometimes worry about Holmes. “My wife and I feel that one of our jobs is to bring her out,” .... told me. They invite her to the theatre, and this year threw her a thirtieth-birthday party at their home, which was attended by her parents, her brother, ....., and several members of the board and their spouses. .... and his wife, .... have tried, without success, to fix her up on dates. Her mother told me, “As a parent, I do hope that at some point she will have time for herself.” This concern is lost on Holmes. The plane had reached cruising altitude, far above a bank of clouds, and another green vegetable drink had materialized in her hand. “I have done something, and we have done something, that has changed people’s lives,” she told me. “I would much rather live a life of purpose than one in which I might have other things but not that.” Also, she said, with a smile, “I think I’m very young. Still.”

Now I have from time to time been snookered but this was just too obvious even then. Remember, always look behind the wizards curtain, there may be a great deal of just smoke and mirrors. Or as some of these well known politicians had advocated; "trust but verify". If you cannot verify then you better find someone who can!

The Trivium and Ockham

In the 14th Century at Oxford and in Paris scholars studied first the Trivium; grammar, logic and rhetoric. For Grammar the ultimate question was; what does this word mean? Likewise for Logic; does this syllogism ring true? Finally in rhetoric: can I make an argument based upon facts using logic to convince my audience? Disputation was the forum of discussion. Namely opposing parties and inquisitors were allowed to engage the party presenting the argument in challenging the position. Debate was open.

Along comes William of Ockham and his adversary John XXII, the alleged Bishop of Rome whose intent was to remain in luxury at Avignon. Ockham challenged the Grammar and Logic of John, and the result was the beginning of what we now recognize as individualism; namely the fact that each individual is equal before God and the Law and that further it is the responsibility of the individual to act to secure their salvation. Collectivism, socialism, is the counter to Christian thought, it is not the group which seeks salvation, it is the individual.

In a speech today the current Bishop of Rome opines:

The day’s first reading, taken from the Letter of Saint James, is a forceful warning to the rich who accumulate wealth by exploiting the people. “Riches in themselves are good,” the Pope explained, but they are “relative, not absolute” goods. He criticized the so-called “theology of prosperity”— according to which “God shows you that you are just if He give you great riches,” saying those who follow it are mistaken. The problem lies in being attached to wealth, because, as the Pope recalled, “You cannot serve both God and riches.” These become “chains” that “take away the freedom to follow Jesus.” In the reading, St James writes, “Behold, the wages you withheld from the workers who harvested your fields are crying aloud; and the cries of the harvesters have reached the ears of the Lord Almighty.”

When riches are created by exploiting the people, by those rich people who exploit [others], they take advantage of the work of the people, and those poor people become slaves. We think of the here and now, the same thing happens all over the world. “I want to work.” “Good, they’ll make you a contract, from September to June.” Without a pension, without health care… Then they suspend it, and in July and August they have to eat air. And in September, they laugh at you about it. Those who do that are true bloodsuckers, and they live by spilling the blood of the people who they make slaves of labour. The exploitation of labour is a mortal sin.

Now let us begin with grammar. What do we mean by exploiting? Let us take a simple economic example in a capitalist society. Let us assume that the alleged exploiter owns a coffee shop. In order to sell coffee he must: (i) make good quality coffee, (ii) provide good service, and (iii) sell it at a competitive price. Now how does this capitalist accomplish this? Simply. First; revenue less expense equals profit. If the "profit" is negative then he goes out of business, unless of course the Bishop of Rome somehow underwrites his expenses. Now how does the Revenue get set? Well it is the market, namely the prices set by the competition. Lots of suppliers drive prices down. Lots of suppliers creates demand for labor and drives costs up. At some point the market clears. Happens all the time especially in a commodity bushiness. Thus the Expenses are dictated by the market not by the Bishop of Rome. Exploitation does not exist as an act of the owner but as a consequence of the dynamics of a market. Price settles to a level and salaries meet the level for survivable businesses. Simple. Economics 101.

Thus we return to Grammar. What does "exploitation" mean? There is no exploitation in a capitalist market, it is just the meeting of supply and demand on both the revenue and the expense side. The paragraph about the months and the contract appear confused. Must one supply pension, health care and the like, Perhaps, but that must be included in the total cost. It is not a gift, it is not charity, at least in an economically viable environment. If we were in some Marxist environment, then perhaps.

The the statement that exploitation, apparently defined as not providing a pension, is a mortal sin. Looking at the Old Testament, and then to the New, I saw nothing; perhaps this was written on the third stone Moses left on the mountain. Exploitation means no health care and no pension. But if the salary is at market then why not buy your own health care, why is it a moral imperative?

I suspect we need more Grammar, more Logic, more Rhetoric and a little disputation. Words mean something, so do the realities of the market.

Yet perhaps we should examine some recent comments by the NY Times on the Jesuits.  As they noted:

The human cargo was loaded on ships at a bustling wharf in the nation’s capital, destined for the plantations of the Deep South. Some slaves pleaded for rosaries as they were rounded up, praying for deliverance. But on this day, in the fall of 1838, no one was spared: not the 2-month-old baby and her mother, not the field hands, not the shoemaker and not Cornelius Hawkins, who was about 13 years old when he was forced onboard. Their panic and desperation would be mostly forgotten for more than a century. But this was no ordinary slave sale. The enslaved African-Americans had belonged to the nation’s most prominent Jesuit priests. And they were sold, along with scores of others, to help secure the future of the premier Catholic institution of higher learning at the time, known today as Georgetown University.

Yes the Washington based home of Presidents, Diplomats and CIA Heads was also the home of slaves and sold these slaves to preserve itself. This was done well withing the movement in the North to abolish slavery as a morally reprehensible act. Yet to these Jesuits it was a business transaction. Thus if one follows the Logic of the Bishop of Rome these people, the Jesuits, should be guilty to mortal sins, thus anathema, since clearly they were in chains and their freedom was taken away, again and again. Then perhaps we should rip these sinners from their graves on the Washington cemeteries and declare them anathema.

One should always be certain that their house is clean before complaining of others.

Garbage in Garbage Out?

In an article today in the NY Times the author comments on the Facebook debacle with its search algorithms. First of all I had Faceboook shortly after it came out and forced by my students at MIT to joining the future. Then after seeing it as a total distraction left several years ago, as I suspect did the students. Today, I, at almost 75, and my granddaughter just 13, see Facebook used only by "old folks", those 50 year olds who insist on telling everyone about their most intimate thoughts.

The Times author does bemoan the neutrality of the algorithm. She states: 

The first step forward is for Facebook, and anyone who uses algorithms in subjective decision making, to drop the pretense that they are neutral. Even Google, whose powerful ranking algorithm can decide the fate of companies, or politicians, by changing search results, defines its search algorithms as “computer programs that look for clues to give you back exactly what you want.” But this is not just about what we want. What we are shown is shaped by these algorithms, which are shaped by what the companies want from us, and there is nothing neutral about that.

Indeed, algorithms are anything but neutral. I recall doing clustering algorithms back in the day to discriminate Soviet subs from whales. No matter, whenever I changed a weighting constant I could change everything. 

You see the "algorithm" may itself be neutral, or at least as neutral as possible but the constants and weights  or how they are derived are not. That is where opinion comes in. And sadly we now know the West Coast bias, a  true bias to the left, controls the world view.

What Facebook hope to achieve in a meeting like this is uncertain. One suspects that not one of the "conservatives" would have a clue about an algorithm, no less understand how bias is inserted.

Some Thoughts on Kendall Square

Kendall Square was a dilapidated location when I first went to MIT over fifty years ago. A dying location with a small bar with great free pickles. A desolated T Station and dark at night. Behind the old buildings were small strip mall like edifices housing electronics start ups. Back then the entrepreneurs actually made things that pushed society ahead, unlike many of the newer Apps companies.

MIT has finally gotten approval for a new Kendall Square.

But take a look, it will have massive glass sided buildings with acres of concrete. For those of us who understand micro environments this will create a massive heat source and will distort the environment even more than it already is.

The current buildings are a bit better because they have more balanced facades. All glass is a well know contributor at least to local warming, just look at the Gehry building in LA. It almost fries people in its grasp.

The intent of this design is to be open and invite people. The real question is how do people get there? The parking has become either extortionary, $50 per work day or more, or no-existent.  The T has some access but it too is limited. What this is creating is a dense multi usage area where it appears that no usage will be optimized.

Residential use most likely be very upper income, akin to Battery City and its environs. Buildings like this are really not appropriate for raw start ups, despite the claims of the local incubators.

Cambridge housing is already going through the roof and soon this whole section of Cambridge will be gentrified. The final step will be the removal of the asbestos infested Court House, another example of Government sophistication.

This area has consequences, it will now be interesting to see what the unintended ones are.

The Attack of the Hackers?

Just a brief note. I tried to install Adobe Flash and down came Intel TrueKey some unwanted and un-removeable software that appears to hack into my passwords. I think! Just try and get rid of it...no way. Beware, I guess we just block Adobe and Intel (which owns McAfee) You would think they would ask...one wonders who owns TrueKey, NSA? I am truly amazed by the total lack of informing and getting some form of agreement to proceed....just a warning to you folks!

Is This Global Warming?

 

The flower measured above is pictured below taken this AM.

For thirty years we have been recording the date of first bloom on a selected set of species plants and Hemerocallis is excellent. H minor is an early bloomer and we have about 25 years worth of data. The chart shows the days from the first of the year that the plat bloomed. Now blooming is driven by two factors; number of daylight hours and average temperature. Clearly there has been no change in daylight hours but a change in ambient temperature.

Thus is this data suggestive, conclusive, just noise? There appears to be a trend but it is a bit too scattered. I cannot explain the differences even though there may be micro-environmental issues. The latter are such things as trees there blocking sun and then removed. Nature is always changing conditions. We also have the total precipitation as well albeit considered small in the case.

Just some thoughts and more to come.

Time Changes: Bologna 1316 and MIT 2016

Seven hundred years and one expects a change, of some type. As MIT announces:

MIT is honored to welcome actor, filmmaker, co-founder of Water.org, and native Cantabrigian Matt Damon as the guest speaker for the 2016 Commencement Exercises. 

 Yes it is a movie actor whose role as a South Boston vagabond who managed to show that without any education he could out smart any MIT Math post doc.

Then in 1316 at Bologna we have this description (from a Ciba Symposium document in 1945[1]): 

The graduation ceremony at Bologna was presided over by the Archdeacon. Graduation consisted of two parts, the private examination and the public examination called conventus, or conventactio. The private examination was the real test of competence, the so-called public examination being, in practice, a mere ceremony. The candidate who had passed the private examination and was admitted to the public one, was called a licentiate. Generally, the licentiate proceeded to the ceremony which made him a full doctor after a very short interval. On the day of the public examination, the love of pageantry characteristic of the medieval, and especially of the Italian mind was allowed ample gratification. Before the appointed day, the candidate, preceded by the beadles of the Archdeacon, rode around the city inviting public officials or private friends to the ceremony or to the ensuing banquet. On the day of the conventus the candidate was accompanied to the cathedral by the presenting doctors and by fellow students lodging in the same house with him. The idea of the ceremony was essentially the same as that of the “commencement” of American universities. It derived from the principle of Roman law according to which a man was invested with office by a solemn performance of its functions. 

By this act a new doctor was recognized by his colleagues, and received among the doctors, he., into the teaching guild or brotherhood. Arriving at the cathedral, the licentiate delivered a speech and read a thesis which he defended against opponents who were selected from among the students. He was then presented by his sponsor or promoter to the Archdeacon who delivered a complimentary oration and concluded by solemnly conferring the degree of doctor by the authority of the Pope and in the name of the Holy Trinity.” A gold ring was placed upon his finger, either in token of his espousal to science or as a symbol of the doctor s claim to equality with knights, the magisterial cap was placed upon his head, and the sponsor left him with a paternal embrace, the kiss of peace, and a benediction. The ceremony concluded, all present were required to escort him in triumph through the town, surrounded by a mounted cavalcade of personal friends and wealthier students and preceded by three university pipers and four university trumpeters. It appears that in the case of poorer students these expensive ceremonies were dispensed with. 

Proof of the great importance attached to the graduation is the fact that Charles V granted to the college the right of conferring knighthood upon doctors; and that the doctors of the college were themselves knights and counts of the Lateran.   One of the most interesting differences between the University of Bologna and the other universities lies in the relationship between the various faculties. In Paris and in other European universities, the doctors and students of all faculties were united in a single body. In ancient Bologna there was no connection between the faculty of law and that of the arts, i.e., liberal arts and medicine, other than that the students of both received their degrees from the same chancellor, the Archdeacon of Bologna. The organization of law students attained a high development earlier than that of the students of medicine.

At that time the focus was on the new Doctor, and recognized now as a Knight, pari passu with the equivalent in society. The work of the student now a Doctor was the focus on the event.

It appears that we now "Hood" the new Doctors off stage and bring to the fore the characters who portray what the new Doctors were incapable of doing. Things have changed in 700 years, perhaps not really for the better. Are we honoring the right people?

---

[1] THE ORIGIN OF THE UNIVERSITY OF BOLOGNA, ARTURO CASTIGLIONI, M.D., Yale University, School of Medicine, Ciba Symposium, VOLUME 7, NUMBERS 5 AND 6 , AUGUST-SEPTEMBER 1945.

FED Balance Sheet May 2016

The above is the total FED Balance Sheet. It appears to be stable for the past two years.

A little closer and no change.

Finally the key two items. The problem is; how do they unwind the old mortgage stuff? That will be the painful step. Also they have ratcheted up additional currency and that may also need unwinding. The above shows the Easings over time, stability now is there but it is a very unstable stability.

Some Observations on the Workforce

The above is an analysis by element of the workforce as a percent of the total population comparing August 2006 to the current. It is interesting to see what is happening.

1. Professional is increasing. Just what that represents is questionable.

2. Education and Health is the largest increase. We understand that one.

3. Construction takes a big hit. Now you really cannot outsource construction so this is a serious number.

4. Government contracted and this is due mainly to the Recession.

5. Leisure is up but one suspects that is minimum wage jobs and has displaced other higher income jobs.

6. Manufacturing has taken a big hit. This is both demand and outsourcing.

7. Information is down but not clear if this may also be outsourcing.

Overall this is not a pretty picture.

What if Rosalind Franklin Used a Laptop with Powerpoint?

I have been watching a Broad Institute set of talks on CRISPR. For the most part they are superb but there was a thought that arose.

Back in the early 50's and thru probably;y the early 90's at least we used transparencies or 35 mm slides in presentations. They were both time consuming to produce, expensive, and were cumbersome. Half the time people put the 35 mm backwards/up side down or mixed them up.

Now with your laptop and PowerPoint you can make real time changes and you can click through hundreds of content dense slides in a femto second.

Then I thought of Rosalind Franklin and Jim Watson and the famous X Ray diffraction pattern. What if she had this on a PowerPoint slide presentation and just flipped through it at the speed of light while walking about as if in some TED Talk! Would "Jim" have taken poorer notes, would they have forever messed up the double helix, would Pauling had seen his mistake and published?

Sometimes technology may not be beneficial. Talks with infinite data packed on uncountable slides and spoken as if one is in some evangelical group meeting may not get the point across. Oftentimes great ideas occur in a pause, a new idea presented, then a slight respite, and connections occur.

Not that I am against PowerPoint slides, I am a big abuser of them, always have been, but simplicity and clarity are critical. One does not have to tell the audience every fact you gathered, just the important ones. And also, keep the preaching to the Church! Oh yes, and take the mike off before you start commenting.....

Yield Curve May 2016

The yield curve as of yesterday is nearly flat. This is one of the lowest and flattest yields ever and driven by FED policy. It may be good for the Stock Market and may reflect the abysmal growth in the economy but it lacks reality. Money should have value.

The above is the 30:30 spread, the shortest to longest. It has reached a record LOW! That should be a concern, no faith in growth.

The 90:10 spread is shown above an it too is at all time low.

One suspects that things will not be getting any better at this level.

More on Employment

We have not been examining the details here as we had during the Crash of 08'. But perhaps a re-look as we approach election year is worth it.

First one of my favorite charts is what is Core versus Government. Government here is Government plus Education plus Health Care. You see the ACA, Medicare, Medicaid make them one as well. The ration was about 41% in 05' Now it is 45% and rising again. That means that almost one person works in doing something productive for every person being supported doing Government related things. This means two things. More Government and less real value production.

Looking in more detail we see Ed and Health on a steady climb! It is nu-relentless.  Government is now climbing again as well.

 The above shows all other sectors. It appears better than it looks because it does no reflect a significant population growth.

The above was the split in 2010 and below is today.

It is worth examining the differences.

Some Thoughts on Russian Networks

During the period from 1960 thru 1990 Russia developed a variety of networks, many for military use and many for central command and control. Based upon my own personal first hand experience working with them they clear were ate the same level as the west. Thus in rethinking the book by Peters which I reviewed I thought that his title was most likely totally out of place.

Using the title How Not to Network a Nation: The Uneasy History of the Soviet Internet was in my opinion out of place. The Internet was a construct that grew out of the arrogance of AT&T more than any uniqueness on the part of US technology. If AT&T had agreed to work with ARPA then this would have just been an extension of the monopoly network. Instead the arrogance of the monopolist, the entity that saw itself above everything else, created the creative destruction that led to its collapse.

Thus there is a real story of a set of brilliant technologists in Russia that may very well go untold. It was not a question of "How Not to" but the advantage the early ARPA team had in facing an adversary, not Russia but AT&T, and having the resources to overcome it.

Perhaps some day there will be a work on Soviet networks, a works which commends the efforts of many brilliant men and women in Russia who created a parallel universe and who when the borders fell allowed in a seamless manner the full expansion of the global IP network.

If one further looks at the time one also sees the IBM SNA network, akin to many of the centralized schemes we may see in Russia and Europe. But as a backdoor way to get around AT&T we had TCP/IP.

Thus understanding the reality of what occurred, it is not, "How not to" but ask ourselves the question; what really happened. Also one hopes there is a tale of Russia's advances to tell the complete story. From that we can learn that our then adversaries were as bright as we think we were.

The USPSTF is at it Again

The USPSTF had previously made a recommendation that PSA testing did not have any positive effect in mortality. So frankly they said "stop it". Then various studies indicated they were wrong. The two NEJM studies in 2009 that the USPSTF relied upon were fatally flawed for a variety of reasons, many of which we discussed here at the time (See recent NEJM comments ).

The folks at the USPSTF are now back at it again. This time to try and put a stake through the hear of PSAs. It seems they just want to get rid of old men. That's one way to cut Medicare.

The USPSTF has proposed a study whose goals are:

1. Is there direct evidence that prostate cancer-specific antigen (PSA)-based screening for prostate cancer reduces short- or long-term prostate cancer morbidity and mortality and all-cause mortality?
   1. Does the effectiveness of PSA-based screening vary by subpopulation/risk factor (e.g., age, race/ethnicity, family history, and clinical risk assessment)?
2. What are the harms of PSA-based screening for prostate cancer and diagnostic followup?
   1. Do the harms of PSA-based screening for prostate cancer and diagnostic followup vary by subpopulation/risk factor (e.g., age, race/ethnicity, family history, and clinical risk assessment)?
    

Frankly they already seem biased. But that is not just my view. As Medscape notes:

"Finding high-quality data to answer this will be challenging," Dr Hoffman told Medscape Medical News. None of the major screening trials enrolled men younger than 50 years, most subjects were white, and investigators did not routinely assess clinical risk. "While some studies are now recruiting patients to address screening in higher-risk populations, it will likely take at least a decade to determine the effects of screening on morbidity and mortality," he summarized. In the meantime, Dr Hoffman is concerned that "abandoning PSA screening" is proving harmful. The rate of distant-stage prostate cancers in the United States is increasing, according to a population-based study for which he was lead author. However, "it's too early to tell whether this will lead to an increase in prostate cancer mortality," he said. The USPSTF research plan separates the review of evidence about the potential harms of PSA testing, biopsy, and treatment.

Indeed to validate these questions takes time, and a decade is not bad. The issues of "harms" is so individual and personal it appears that only the Government can make the decision for all of us. Why not, but perhaps they did not notice the recent elections!

I have noted the complexity of the PSA test. It is far from perfect. The Bayesian analysis is also far from perfect. Namely increasing PSA, or PSA velocity is not a clear indicator, family history is not a clear indicator, a prior biopsy with HGPIN is not a clear indicator, and a contrast MRI using diffusion weighting is not a clear indicator! So what is? Ultimately it is a biopsy, but even that samples some 1-2% of the tissue.

So what is the solution. For those who recall the Hippocratic Oath, "Do no Harm!"

I Don't Think So

The NY Times discusses the weight gain/loss issue and blames the brain rather than will power. They state:

The root of the problem is not willpower but neuroscience. Metabolic suppression is one of several powerful tools that the brain uses to keep the body within a certain weight range, called the set point. The range, which varies from person to person, is determined by genes and life experience. When dieters’ weight drops below it, they not only burn fewer calories but also produce more hunger-inducing hormones and find eating more rewarding.

No the root problem is that 3500 Kcal equals one pound. And if you only burn 1200 Kcal per day you have a problem if you consume 2400 Kcal per day, you gain 1 pound every 3 days! Now the problem is burn rate. Genetic control has allowed certain peoples to live on fewer calories. Native Americans in certain areas were living off of very few calories and when introduced to a European diet one saw massive levels of obesity and Type 2 Diabetes. When they had fewer calories they did well and survived, it was the diet change that did it.

The problem in my opinion is what we allow ourselves to consume as food. Often also it is the spouse or family that is non-supportive and almost antagonistic to the dieter. The environment during the weight loss period is focused but then after it returns to an excess caloric one where all too often family members reinforce the eating misalignment.

Thus it may very well be will power, but the will power of the family and friends to change.

The Cable Box

As TechDirt notes:

Congress is simply fed up with the FCC's pesky new habit of standing up to giant cable and broadband companies. Congress was outraged when the FCC announced it wanted to stop states from letting large ISPs write horrible, protectionist state laws. Congress was outraged when the FCC announced it wanted to pass actual, functioning net neutrality rules. Congress was even outraged when the FCC decided to raise the standard definition of broadband to 25 Mbps, since it only served to highlight a lack of competition for next-generation broadband service. 

They continue:

A new letter from sixty Congressmen and women (pdf) reads as if it was written by a cable industry lobbyist (because it probably was), deriding the FCC for daring to interrupt the cable industry's glorious history of innovation with a pesky quest for better, cheaper, consumer-facing hardware:

"The Federal Communications Commission's recently proposed rules on the Competitive Availability of Navigation Devices, if adopted, will jeopardize the incredible evolution of video distribution services enabled by generally reasonable regulation. Imposing new, onerous regulations on pay-TV providers would produce very few benefits for consumers, while potentially harming the viability of these providers. The particular obligations being considered by the FCC are all the more troubling because they would mandate compliance with technical standards that do not yet exist, injecting even greater uncertainty into the marketplace.

How horrible! Except it's not true. The FCC's proposal as it currently stands (pdf) says that cable providers can use any technology they see fit, and any copy protection they'd like, to ensure their content can be delivered to third-party hardware under the FCC's rules. 

The Cable Box and Cable modems are antiquated boat anchors that the consumer pays extortionist rates for in my opinion! Most homes have vacuum cleaners that are newer than cable boxes. One wonders if Congress is truly on payrolls. Perhaps the Trump backlash is reflective of the electorate becoming aware of these folks and their persistent attempts to pay service to those lobbyists and companies that fund their campaigns while these people extract money from the poor taxpayer. Often the arrogance of the "elected" officials is amazing. The cable box issue is one of the most powerful symptoms of this in practise. I could buy a cable model from Amazon for just a bit more than $50 retail.  But I am paying $10 per month for the past fifteen years! That is a total of $1,800 for a $50 box! Do these Congress folks have the slightest clue.

Then go to the cable box itself. It uses 1980s technology to operate. I know because I was in Cable then. It is truly a boat anchor. My Amazon unit has voice control etc and costs peanuts and does infinitely more.

One should read the letter from Congress. In fact one should be seriously concerned if your Congress person signed it, you should ask just what they are doing. The system should be open, namely open to vendors, like even wireless! Yikes, Verizon is more open that the Cable folks!

Employment

Overall employment is still weak. The participation is still very low and this impacts Government revenue dramatically.

The above shows this fact that as the population continues to increase employment also does but barely at the rate necessary to provide jobs to those in need.

There may be some hope given the slight increase in participation but one always questions the numbers.

If All Else Fails Listen to the Customer

I used that phrase many times to explain why things did not turn out the way they should have. The analog in Medicine is a paraphrase of Osler which is "If all else fails listen to the patient!" I have seen that one many times.

The NY Times states regarding the Trump win:

But in the end, you have to point the finger at national political journalism, which has too often lost sight of its primary directives in this election season: to help readers and viewers make sense of the presidential chaos; to reduce the confusion, not add to it; to resist the urge to put ratings, clicks and ad sales above the imperative of getting it right.

 Now I try to avoid Presidential politics but this paragraph just stands out. The Times appears to despise Trump and day after day they have been slamming him mercilessly. Ok that's their prerogative. But then to say that their job is to help us poor voters to make sense, it is their very slamming that educates the voters!

Perhaps one should regain composure and ask why this has occurred, a business man who never spent a femtosecond in Government now becoming the putative candidate. Whether you are trying to sell a product or heal a patient you cannot insist that they adhere to your way of dealing with things. The new media has created a distortion field. Yes as the Times notes telephone polls are useless. The young do not answer and the older folks have call blocking. That leaves the middle ground who will most likely say anything! Garbage in etc.

This will be an interesting campaign. It appears that even the establishment does not seem to get it. The alleged "principles" are actually dictated by the public, and apparently they are on the prowl.

Russia, Networks, Innovation

Peters' book on Networking the Soviet Union is less a tale of the technology developed in the then Soviet Union than a tale about the structure of the centralized bureaucracy that managed to nearly bankrupt the entity. As regards to the actual technology I would go back to the mid-1970s when I was in Washington. At the time I was at Comsat and was "befriended" by the Technical Attaché at the Czechoslovakian Embassy. Also the home of the Cuban delegation as less than an idle point of interest. As part of my tasks at the time I followed my new friend around as he tried from one occasion to another to collect data on US telecommunications and network systems. At the same time, I had the task of connecting what was then the early stage of the ARPA Net to the Intelsat system connecting Etam West Virginia to Goonhilly in the UK and Trondheim in Norway. In the U*S we basically placed all of this in the public domain so I would guess my "friends" job was fairly easy.

I saw him I believe in the Fall of 1977 at a Conference at Cornell at which time the Diffie Hellman encryption algorithm was discussed. I guess that half the attendees were not necessarily who they may have said they were.

Then some twenty plus years later I now had partners in Russia running my Russian network and the former head of the Czech PTT was now my Czech partner. My former "friend" used to work for him. Small world. Since I had worked on the Comprehensive Test Ban Treaty Negotiations in the late 1970s, doing the networking for the seismometers, my Russian friends clearly knew me. During one of my conversations I was told by my Czech partner, a senior figure both in Czech as well as Soviet circles that they used the Bell System Technical Journals to design their telecom systems and the IEEE journals for data systems.

In fact, one of my Russian partners was one of the first to introduce the Internet to Russia and we completed the task in the late 90s. As such I have a different view than the author, one based on technical facts of the network and its operations.

This book is NOT about the Internet or its Soviet clone from a technical or operational perspective. Rather it is about the Soviet bureaucratic system and the need to make some sense out of its overwhelming administrative overhead using networks on both the economic administrative side and the military side.

Chapter 1 is a discussion of Wiener and Cybernetics. The author presents one of the best discussions regarding the acceptance of Cybernetics in the Soviet Union I have seen. Wiener was a brilliant mathematician and in addition could think in large scale systems. His book on Cybernetics was warmly received in the US but its theme was understanding large scale systems and the US was no longer, at that time, interested in that. It was moving from a War footing and into a capitalist industrial footing in the 50s. The Soviet Union on the other hand was further consolidating a centralized command and control economy and Wiener's ideas rang bells. Thus they adopted his view of the world. Chapter 2 presents a good overview of how the Soviet Union then took these ideas and tried to integrate them into this centralized world.

Chapter 3 is allegedly an attempt to present the networks used. It really is a discussion of the people and the politics and not the technical issues. Although interesting I really wanted to see some discussion of what the Russian had implemented and how their designs differed from ours. There were a mass of varying data protocols and data speeds and network transport mechanisms that were developed in the US and I wondered what did the Soviets do in parallel. The author depicts the Soviet's response as a response to SAGE and then I wondered what the response was to the packet ideas of Baran. In fact, the work of Roberts and in turn Kahn at ARPA were almost all in the open literature and the goal was a survivable network, apparently perceived by the Soviets as a threat. If so I wondered just what they did. I am certain that there must now be a great deal of unclassified CIA and DIA reports that would clarify that but the discussion is missing.

Chapters 4 and 5 go through the 60s and then 70-80s respectively and the author presents the principals who tried to accomplish something in this realm. The politics seemed to be always creating roadblocks and the innovation that ARPA allowed seemed to foster what we have today.

The author has an interesting discussion on the Mansfield Amendment, that in 1969 put an end to DoD funding anything but specific program supported work. Until that time DoD funded what has become the foundation of our information based economy, and with Mansfield we saw a total collapse of that development. I often wondered if the Soviets saw that for what it did.

Overall the book is an excellent presentation of the people and politics of what would become some of the infrastructure in the Soviet Union. I wondered what the role of a RosTelecom would be in that mix, an element not discussed. In addition, the Soviets had satellites the Molyniya System which were not equatorial but polar, and thus their communications ground stations were expensive and subject to failing. Their cable connections were also mixed with spotty interconnections across the wide expanses. The author provides some maps but it would have been more useful to have some detail.

This is a well-organized and presentation of the system, as politics, not the system as technology. Given how closely the Soviets monitored US technology and how open we were then and now, I have often wondered what the Russian created from whole cloth and what was reproduced. The Russians were and are technologically on a par with the West in terms of human capital but it was often the weight of the system that slowed them down. That burden was lifted after the fall but I wonder how much may have returned.

Socialized Medicine

What is Socialized Medicine? Simply it is Medicine which is controlled by the Government. It is the NHS in the UK. Physicians are employees and they get a salary from the Government. They work  40 hours a week, they get a vacation, health benefits, pension etc. They are like the postal service, the subway conductors, the Ferry Boat operators. Yes they are like IRS agents and frankly like all other Government employees. You are sick, well if it is 5 PM and they are off duty hope the replacement is on time and has some clue what they are dong. If you die then like the VA they get a bonus and your family gets the ashes, at best. That way no one can check to see if they lost your body.

Now along comes a group of docs who want to do that in the US. They are Progressives but in reality they are Socialists. I know because my grandmother was head of a Socialist Party in New York. I grew up in a Socialist group and we went to Public Health clinics with white porcelain metal chairs.

Now Eureka reports:

In a dramatic show of physician support for deeper health reform - and for making a decisive break with the private insurance model of financing medical care - 2,231 physicians called today  for the creation of a publicly financed, single-payer national health program that would cover all Americans for all medically necessary care. Single-payer health reform, often called "Medicare for All," has been a hotly debated topic in the presidential primaries, thanks in part to it being a prominent plank in the platform of Sen. Bernie Sanders. The new physicians' proposal is strictly nonpartisan, however. The proposal, which was drafted by a blue-ribbon panel of 39 leading physicians, is announced today in an editorial titled "Moving Forward from the Affordable Care Act to a Single-Payer System" published in the American Journal of Public Health. The editorial links to the full proposal titled "Beyond the Affordable Care Act: A Physicians' Proposal for Single-Payer Health Care Reform" and the names of all the signers, and it appeals for additional physicians to add their names as endorsers. The proposal currently has signers from 48 states and the District of Columbia. "Our nation is at a crossroads," said Dr. Adam Gaffney, a Boston-based pulmonary disease and critical care specialist, lead author of the editorial and co-chair of the Working Group that produced the proposal. "Despite the passage of the Affordable Care Act six years ago, 30 million Americans remain uninsured, an even greater number are underinsured, financial barriers to care like co-pays and deductibles are rising, bureaucracy is growing, provider networks are narrowing, and medical costs are continuing to climb. "Caring relationships are increasingly taking a back seat to the financial prerogatives of insurance firms, corporate providers, and Big Pharma," Gaffney said. "Our patients are suffering and our profession is being degraded and disfigured by these mercenary interests."

Now how much will this cost? We know that under the ACA we are running at about $12,000 per person per year. Then simply 30 million yields $360 billion! No problem, just up Medicare monthly amounts as the Baby Boomers enter. 

I am always amazed by Socialists. Somehow there will always be someone to foot the bill, not them. Perhaps they just want a 9 to 5 job. They should have gone to the Post Office.

A Telephone Company?

Verizon has an asset, a very valuable asset. It is the spectrum. It is not the copper plant, given union costs the copper has become a liability. So sell the copper, they have done a great deal already. A second asset is the property. They have billions in off balance sheet real estate, in New York City and elsewhere. They have monetized some of this via selling off part of 140 West Street, my first place of real employment.

Back to the wireless. With 5G systems the can provide Gbps service to anyone. They are mobile but they are wireless, no copper and no union, and most importantly little competition, it's that asset again.

So what is management doing; they bought AOL and now are looking at Yahoo. AOL was dead in 1996! Time Warner bought a corpse. It has not risen from the dead. And Yahoo, the blood has stopped flowing there ages ago. Somehow corporate management gets infatuated with glitz. I saw this at Verizon before when they tried to get into content, hundreds of millions down the drain!

So what should Verizon do? Well we tried answering that several times a decade ago. Expand wireless. It is an oligopoly with oligopoly rents. Content is a hits business. I saw this at Warner, it only works when you are (1) really smart, and (2) you have a large portfolio. Steve Ross and his group were really smart. They could really pick winners. They also had a large portfolio. Telephone folks are not really smart. They run a utility, albeit a semi regulated one.

The rule there should be; leverage assets. Content does not leverage assets. It tries to compete with other content providers and some are really smart.

So what does the current strike do. It presents an opportunity to Verizon. Sell off the rest of copper, sell it to anyone, but first sell off the buildings with a sale lease back clause, for some period, not forever! Monetize the old stuff and focus on the new.

Biofilms and Drinking Water

Clean drinking water is an essential in any modern society. As has been well known, even the well managed drinking water may be contaminated as a result of the presence of biofilms[1]. External contaminants are carefully restricted but the growth of biofilms is almost inevitable. The growth is often fostered by the pipes themselves with iron based pipes providing a fertile ground for the biofilm[2]. Biofilms are the development of an integrated bio mass resulting from the growth of bacteria and other microorganisms. The biofilm aggregates and builds into a large mass which can degrade pipes, inhibit flow, and initiate bio hazards if the fluid such as water is to be used in a potable manner. Biofilms are a significant cost in the operations and maintenance of various water flow mechanisms in residential and commercial facilities. 

We have prepared an analysis of biofilms and their inhibition in remodified drinking water systems.

There are many nano bacteriostatic mechanisms for surface treatment have been demonstrated to inhibit bacteria and the resultant biofilm growth. The application of additive nano-Se appliqués or other extractive nano-surfacing have been shown to inhibit biofilm growth via the bacteriostatic actions. The nano technology can be applied to the repair and maintenance of existing distribution systems.

This analysis focuses specifically on the use of the nano technology to public water supply systems. Specifically, it addresses the issue of system remediation and the need for a low cost and fast method to purge the biofilm contaminants as well as shielding other contaminants such as lead from public water supply systems. The proposal focuses on the use of PVC treated with the nano surfacing technology as well and the development of the insertion and installation methodologies to achieve a very low cost remediation system.

 

The problem being proposed for study here is the mitigation and inhibition of biofilms in the transport and distribution of water in public water distribution systems. We demonstrate the typical system below.

As the above demonstrates water is generally collected from aquifers, or other storage areas, and at times directly from flowing bodies. It is then treated and purified and perhaps stored in local facilities. Then as demand occurs it is distributed across a local network. It is that local network which is extensive and in many cases aged that biofilms occur. It in this network that seeks to examine the efficacy and cost efficiency of deploying PVC nano-treated insertions. The proposed installation is demonstrated below:

The process is simple: 1. Purge old pipe and clean with a standard "pigging" device and then repurge for all removed biofilm. 2. Insert nano treated PVC sleeve for a new pipe.

Preliminary analysis indicates that this nano treatment will inhibit regrowth of biofilms for extended periods and further the PVC sleeve will inhibit outflow of such elements as lead from the old pipe. The primary purpose of this study therefore is to validate this approach using the existing nano technology based upon data and sample obtained from actual systems in situ.

Biofilms are created by the adhesion of bacterial aggregates on the surfaces of various fluid processing, transport and containment mechanisms. The basic physics surrounding this phenomenon was presented by van Loosdrecht et al and it is based upon the construct of surface energy. The small biological particles can adhere to surfaces and one attaching can create via extracellular membrane extension the foundation for a developing biofilm. The problems with this biofilm are significant in a variety of areas such as oil pipelines as discussed by AlAbbas et al and in desalination as discussed by Elimechem et al in desalination plants. Srey et al provide an excellent survey of the impact of biofilms in the food industry. A typical biofilm encrustation is shown below:

Note the significant growth of biofilm. In the reference by Pervical et al they have extensive discussions regarding the development process in potable water. The effect of chlorine in the water does diminish the growth slightly but it is a common factor not only in loss of flow but in contamination. Fundamentally the process is some three steps as shown below:

The details on the above are also in Kanematsu and Barry. The first step is the development of a protein film on the surface. Then the bacteria reversibly attach and finally the bacteria irreversibly attach and additional biofilm mass grows to cover the bacteria. Another more detailed view will incorporate a combine reversible and then irreversible process initiated by the coating of the surface by a protein like substance shown below.

Note in the above we must have the layer irreversibly adsorbed to allow an initial reversible bacterium to attach. We will explain this later when examining the issues regarding forces. From Fleming and Ridgeway, we have:

The term “biofouling” is referred to as the undesired development of microbial layers on surfaces. This operationally defined term has been adapted from heat exchanger technology where “fouling” is defined generally as the undesired deposition of material on surfaces, including:

 – Scaling, mineral fouling: deposition of inorganic material precipitating on a surface

– Organic fouling: deposition of organic substances (e.g. oil, proteins, humic substances)

– Particle fouling: deposition of, e.g., silica, clay, humic substances and other particles

– Biofouling: adhesion of microorganisms to surfaces and biofilm development

The conditioning film shown above is essential. It is a laying down of proteins and water which adhere to the surface via an adsorption process. We generally suspect that such an adsorption is due to the van der Walls forces from the surface to the structure of the specific proteins. We will expand this discussion latter. Upon completion of the surfacing then the proteins extending from the bacillus manage to penetrate this barrier and also become attached via van der Waals forces. Darouiche discusses the impact of biofilms on medical implants as well. He notes:

The essential factor in the evolution and persistence of infection is the formation of biofilm around implanted devices. Soon after insertion, a conditioning layer composed of host-derived adhesins (including fibrinogen, fibronectin, and collagen) forms on the surface of the implant and invites the adherence of free-floating (planktonic) organisms. Bacterial cell division, recruitment of additional planktonic organisms, and secretion of bacterial products (such as the glycocalyx) follow.

As Batte et al note:

Most of the pipes used in drinking water distribution systems are made of plastic (PVC, PE, etc.) or metal (copper, cast iron) which can become highly corroded (Figure 11). A recent survey of public distribution system pipes in France showed that a large proportion of them are PVC (40%), while the rest are grey iron (22%) or ductile iron (20%) (Cador 2002).

They continue:

The effects of the organic nutrients released by plastic pipes on bacterial growth in drinking water have long been questioned. Organic additives which leach out of plastic have a measurable impact on biofilm accumulation, and are known to promote the multiplication of opportunistic, pathogenic bacteria in laboratory tests. However, no field studies have looked at these events…The lack of information on biofilm dynamics is a limiting factor in managing the quality of water in distribution system and conducting drinking water surveys. In spite of the difficulty of gaining access to the inner surfaces of distribution pipes, biofilm measurement on pipe walls is indispensable if more information on the water contamination risks is to be obtained. New methods need to be developed, adapted, evaluated and optimized. Such methods will create important advantages: continuous, non-destructive, simple, in situ, online information on biofilm location and development.

From Preedy et al we have:

Biofilms are defined as a layer or layers of cells adhered to a substratum which are generally embedded in an organic biological matrix, i.e., extracellular polymeric substances (EPS). It is due to biofilm formation that many bacteria survive in highly diverse and adverse environments as a result of the polymicrobial ecosystem....Not surprisingly, biofilms have formed on a variety of surfaces and are not only restricted to attachment at a solid—liquid interface but have been observed at solid—air and liquid—liquid interfaces, with some having beneficial results as well as detrimental; for example, in industry biofilms are used successfully to separate coal particles from mineral matter. On the other hand, biofilms have been known to cause biofouling reducing mass and heat transfer and effectively increasing corrosion; also from a medical point of view, biofilm colonized implanted medical devices often lead to implant failure.

Current technological areas focus on several areas. The areas are:

Nano Surface Enhancements: These are nanotechnology enhanced titanium surfaces which demonstrate reduction in bacterial infection potential and also demonstrate enhanced tissue and bone growth ensuring improved human acceptance.

Surface Bactericidals for Intracorporeal Applications: These are nanotechnologies for surface coatings of various catheters and the like that result in dramatically reduced risks of infection by inhibiting bacterial growth.   

Selenium Enhanced Bactericidals: This is a selenium based product which enables the control of bacterial growth. It appears to function as a bacteriostatic agent. Combined with a bactericidal agent the combination may affect dramatic control for long periods of bacteria on surfaces. This area of product development appears to have several areas of application: (1) Those applications which can be seen to be applied directly to the skin (cosmetics, wound dressing, etc.), and (2) Those applications which can be used in clinical and consumer applications to treat surfaces for anti-bacterial purposes, (3) The control of growth on various surfaces of harmful flora or fauna.

Treatments have developed an approach to mitigate the growth of biofilm. This is via the treatment of the surface by nano processing. The treatments may be either by addition of materials such as nano Se or by the selective deletion of surfaces to create a similar nano surfacing effect by the use of lipase and other similar surface treatments. For example, nano Se has been demonstrated to slow down S. aureus proliferation at a dose-dependent rate. Increased lag time (in 40 and 20 μg/mL doses) would allow for the body’s immune system to attack bacteria before exponential growth. We demonstrate some of these results below:

In the above we note that the regrowth of bacteria is dramatically reduced by the application of a Se surface at concentrations of 20-40 micrograms/milliliter. It has also been observed that surface coatings of a density of 100 ng/sq cm of 20-70 nm diameter nano Se on the surface are also adequate. The question we pose herein is; what is the physical process that causes this to occur? Bacterial efficacy has been demonstrated as shown below:

·       Gram positive Staphylococcus epidermidis was decreased by several logs on SeNP-coated paper towels

·       SeNP coatings have also reduced gram negative Pseudomonas aeruginosa, E. coli, MRSA, and ampicillin resistant E. coli

We now examine the physical processes which may account for this twofold process. Namely:

1. Nano Se coatings and lipase nano processing of surfaces tend to create a bacteriostatic environment.

2. Nano Se coatings and nano surface processing tend to create an environment that enhances tissue adhesion.

These appear to be contradictory results. It would appear that both processes are controlled by the same physical mechanism. Yet the outcomes are dramatically different. We attempt to explain some of these effects. However, it should be noted that in our analysis the explanation is yet far from clear.

The following is a brief discussion of some of the basic principles and specific technologies. Details are contained in the papers by Webster and his team at Northeastern and Brown University. We have also examined the literature in general and provides a summary regarding that as well.

Surface Energy

The principal basis for the technology is understanding surface energy as relates to bacterial adhesion and subsequent biofilm growth. We demonstrate the basic principle below for a eukaryotic cell using the approach by Webster. On a smooth surface we have with cells a fibronectin, a glycoprotein, which binds integrins. This allows the pathogen cell to attach to the surface and commence biofilm growth.

The issue then is to create a surface which is not conducive to the binding. This can be accomplished by manipulating the surface energy by mechanical means. We can show that the protein absorption is proportional to the surface energy. We can briefly examine van der Waals forces as discussed by Butt and Kappl. Let us first consider simple Coulomb forces. We can consider three types of surface to external adhesion for vdW. They are shown below:

 Later we shall see that many argue for the simple connection of inverse square where one surface is positive and the other is negative. This is a simple vdW approach. However, the other two can be equally valid depending on the nature of the molecules connecting. Namely in the case of proteins the protein structure can be quite complex depending on the specific amino acid construction. Note that for proteins the bonds generally are inverse fourth power strength due to the dipole-monopole configuration. There may even be cases in certain protein structures where the bonds are inverse sixth power[3].

The adhesion of bacteria to surfaces is a complicated and yet to be satisfactorily answered phenomenon. There are several theories and we will examine one herein. We use the DLVO approach which is a force or energy approach. Alternative approaches using thermodynamically defined terms and Gibbs Free Energy, G, have also been proposed but they do not seem to provide adequate answers. Let us first review some general principles.

The DLVO (Derjaguin, Landau, Vervey, Overbeek) approach uses the two forces; van der Waals and Ionic. The paper by Trefaly and Borkovec is an excellent summary of this and we shall follow its approach.

Now the surface may be seen as below with these two forces:

Note that in close we have an attraction due to van der Waals and then at a distance we have the double layer effect. The scales are not precise but just descriptive. The vdW force is much stronger but there is a positive "barrier" between it and the outer layer. Brownian motion can get a bacterium close to the surface and catch it reversibly in the ionic or DL area. However, to have an irreversible bond something must get to the vdW section, a much stronger section.

Now the bacterium sends out a filament to try to bond to the surface via the vdW forces. It must penetrate the barrier and then bond. In the Boland et al paper we have an example of such bonding showing the extending filaments:

 They discuss what they term cellulose binding domains, CBD, areas of the protein which do the binding in this case to cellulose. They state:

These CBDs have been classified into 10 families (I-X) on the basis of amino acid sequence homology. The amino acid sequences of CBDs in C. cellulovorans and C. josui show high homology with those from other cellulolytic genera such as Bacillus. CBDs in this family contain several highly conserved amino acid sequences:

1. Tryptophane-asparate-phenylalanine-asparagine-asparate-glycine-threonine

2. Isoleucine-alanine-alanine-isoleucine-proline-glutamine

3. Isoleucine-leucine-phenylalanine-valine-glycine

We can then ask; what if we roughen the surface, what will that do? The specific answer is not known and even less understood conceptually. A logical conclusion is that by roughing the surface we increase the positive side by moving the inner vdW in and out and thus make it more difficult to adhere. The Thermodynamic argument is a hand waving discussion of surface energy. But we tried that argument above without success on adhesion of human tissue cells.

As Bok noted in his Thesis:

The forces that govern microbial deposition, adhesion and detachment are still not fully understood, and difficult to relate with each other. In a previous study we successfully investigated the characteristic shear force to prevent adhesion of microbial strains. In the current research we used a more systematic approach by including not only the shear forces to prevent adhesion, but also those that stimulate detachment of adhering bacteria, as well as theoretical adhesion forces calculated using the extended DLVO theory. …

1) A strong hydrodynamic shear force to prevent adhesion relates to a strong hydrodynamic shear force to detach an adhering organism. …

2) A weak hydrodynamic shear force to detach adhering bacteria implies that more bacteria will be stimulated to detach by a passing air-liquid interface through the flow chamber….

3) DLVO interactions determine the characteristic hydrodynamic shear forces to prevent adhesion and to detach adhering micro-organisms as well as the detachment induced by a passing air-liquid interface. …

Thus from the above experimental analyses the DLVO has some merit but it clearly does not describe the entire process. There are significant issues still outstanding to be explained theoretically. Bacterial adhesion and the formation of biofilms is still in the process of being fully understood. Kanematsu and Barry provide an exceptionally strong discussion here but we must resort to experimental data for phenomenological insight. Boland et al also provide a substantial discussion on this but fail to provide a strong analytical basis. Their analysis is useful to better understand some of the phenomenology.

The Thermodynamic Paradigm

The thermodynamic paradigm is based upon certain principles that aggregate large collections of common particles like gas, steam, or a fluid. Thermodynamic principles work in the large like those used in reactors or distillation columns or heat exchangers. We shall review some of these principles and then demonstrate their lack of efficacy in this model.

For example, when considering the process of wetting, one can generally use thermodynamic and surface tension methods. There is a homogeneity on the surface and on the wetting materials. Tran and Webster (2013) have provided an interesting analysis for nano scale wetting. They explain it via the Wenzel and also the Cassie-Baxter models. They all involve surface tension as is done in the core Young's analysis[4].

van Loosdrecht et al were one of the first to explain the adhesion via thermodynamic principles. Then they state:

The Concept of Short-Range Interactions

If adhesion is performed at constant pressure and temperature, and if the molecular composition of the surface does not change, all G's can be replaced by the corresponding interfacial tensions. This concept is restricted to those cases where bacteria and the solid surface are in direct contact and the original phase boundaries are replaced by a new one, namely, the bacterium solid interface. When this new interface is formed, interfacial tensions may be used for a direct estimation of the adhesion Gibbs energy. …

The Concept of Long-Range Interactions

The DLVO theory for colloidal stability can be used to calculate the interaction Gibbs energy between a particle and a surface as a function of the separation distance (H). The balance of interracial Gibbs energies … is the basic premise of this theory. The net interaction Gibbs energy is interpreted in terms of Van der Waals interactions (which are usually attractive) and an electric interaction due to the overlap of the electrical double layers at the charged surfaces. The most important parameters determining the van der Waals interaction are the Hamaker constant, which is a material property, the distance (H) between bacterium and substratum, and the geometry of the system. …

alAbas et al demonstrate oil pipeline biofilm as below:

 

Now in contrast alAbas et al note:

Thermodynamic approach

The thermodynamic approach assumes the system is in equilibrium and the bacterial attachment is a reversible process. The interfacial free energies between the interacting surfaces are compared and calculated, …. This comparison is expressed in the so-called free energy of adhesion. …The microbial adhesion will be favorable when the change in G, is negative (< 0) and will not be energetically favorable if … positive.

They then continue:

DLVO Approach: The drawback of the thermodynamics approach is that it ignores the electrical double-layer interaction with the bacteria… This assumption is invalid as the bacterial cells have a surface-negative or-positive charge. In contrast, the DLVO approach displays a balance between attractive Lifshitz- van der Waals… and repulsive or attractive electrostatic forces … These two forces are function of the distance (d) between the bacteria and surface. In order to calculate the adhesion free energy … the electrostatic interactions between surfaces should be included. The inclusion of electrostatic interactions requires that the zeta potentials of the interacting surfaces be measured, in addition to measuring contact angles...Extended DLVO approach: The extended DLVO theory relates the origin of hydrophobic interactions in microbial adhesion and includes four fundamental interaction energies: Lifshitz-van der Waals, electrostatic, Lewis acid-base, and Brownian motion forces …

 The above approach makes semi-macro thermodynamic assumptions. Specifically, a large mass of surface, liquid and biofilm concentrate. In fact, the dynamics of the process are totally overlooked. This is the general failing of thermodynamic approach; they assume some form of steady state along with homogeneity. In reality we have a dynamic process in a highly heterogeneous environment. We briefly discuss the technology to be employed. The details are contained in the references by Webster discussed herein.

Nano Technology

Nano surface treatments can be accomplished by treating the surface itself or adding nano materials to the surface. The result is a stable nano surface that inhibits bacterial growth and ensuing biofilm development. The Gecko has nano fibrils on its feet that allow it to climb any surface by means of van der Waals attraction as we see in nano material surfaces. The production of nano Se is performed via a proprietary process but fundamentally is the following:

Glutathione +NaOH + Se --à Nano Se

As Mendonca et al note, using reference to Webster's work, the details of surface energy effects and adhesion or lack thereof:

The changes in initial protein–surface interaction are believed to control osteoblast adhesion. This is a critical aspect of the osseointegration process. When implants come into contact with a biological environment, protein adsorption (e.g. plasma fibronectin) that occurs immediately will mediate subsequent cell attachment and proliferation. Cell binding to protein domains of adhesive extracellular matrix proteins involves receptors termed integrin receptors that transmit signals through a collection of proteins on the cytoplasmic face of the contact, termed focal contacts. … Webster and colleagues observed an increased vitronectin adsorption on nanostructured surfaces when compared to conventional surfaces. They also found an increased osteoblast adhesion when compared to other cell types, such as fibroblasts, on the nanosurfaces. … Surface roughness at the nanoscale is an important determinant of protein interactions that ultimately direct cell activity in control of tissue formation at implant surfaces.

Material Processing

To obtain a proper nano surface there are two methods. The additive method uses nano Se which can be made at specific nano size and in a very well controlled and defined distribution so as to assure the proper surface energy. The second approach is the deletive approach whereby a nano surfacing has a process that removes materials in such a controlled manner so as to achieve the same desired surface energy.

Additive

Nano Selenium has been demonstrated as highly effective. In addition, as we demonstrate below it is also safe and sustains the effect on the surface for an extended period of time.

Why Se? The reasons are as follows:

•  Essential micronutrient metalloid, and component of several key antioxidants, detoxifying and metabolic enzymes, in form of selenocysteine, selenomethionine
• Two allotropes: red (bioactive) and grey (crystalline) and  Strong associations with reduction of Reactive Oxygen Species1,2,3 (ROS) as well as  Cofactor of glutathione peroxidase
• Antibacterial activity to a broad range of pathogenic strains
•   Nano Se can be produced at specific nano diameters with minimal dispersion,  Spherical in shape
• Monodisperse—size distribution fits within one bell curve and negatively charged (uncoated)

Deletive

The deletive approach used extraction mechanisms which produce similar effects to the additive mechanism of nano Se. The advantage of such an approach is that it does not add anything to the material. The disadvantage in certain active biological surfaces such as human skin is that it causes immunological effects. However, its used in stable media such as PEEK, Titanium, steel, and other materials used for water flow and containment is that it can be readily effected and at low cost. There are numerous processes to implement nanoscale surface features on metallic or polymeric surfaces. We then utilize one of our processes to create such nanoscale features: Anodization or Chemical etching. The deletive approach provides comparable results to that for Se coatings.

Biofilm Inhibition Results

There have been a variety of biofilm inhibition methods. As Garrett et al note:

Bacterial adhesion has become a significant problem in industry and in the domicile, and much research has been done for deeper understanding of the processes involved. A generic biological model of bacterial adhesion and population growth called the bacterial biofilm growth cycle, has been described and modified many times.

The biofilm growth cycle encompasses bacterial adhesion at all levels, starting with the initial physical attraction of bacteria to a substrate, and ending with the eventual liberation of cell clusters from the biofilm matrix. When describing bacterial adhesion one is simply describing one or more stages of biofilm development, neglecting the fact that the population may not reach maturity. This article provides an overview of bacterial adhesion, cites examples of how bacterial adhesion affects industry and summarizes methods and instrumentation used to improve our understanding of the adhesive properties of bacteria.

The NRC report states[5]:

The pipe surface itself can influence the composition and activity of biofilm populations. Studies have shown that biofilms developed more quickly on iron pipe surfaces than on plastic PVC pipes, despite the fact that adequate corrosion control was applied, the water was biologically treated to reduce AOC levels, and chlorine residuals were consistently maintained…In addition to influencing the development of biofilms, the pipe surface has also been shown to affect the

composition of the microbial communities presents in the biofilm. Iron pipes supported a more diverse microbial population than did PVC pipes. The purpose of these studies is not to indicate that certain pipe materials are preferred over another but to demonstrate the importance of considering the type of materials that come into contact with potable water. 

We examined several issues. Specifically:

1. What is a Biofilm? This we have answered by reference to various studies.

2. How do biofilms form? The answer to this may often depend but it is clearly a dynamic process.

3. What is the physical phenomenon that allows biofilms to adhere and have strong adsorption? This is a work in progress. We believe the thermodynamic approach is problematic at best. It is necessary to consider more detailed dynamic physical phenomenon. We make some suggestions here.

4. What is the effect of nano-surfacing on biofilms? This appears to be uncertain at best. There are contrasting phenomenological results.

5. Why does nano-surfacing enhance adsorption of certain eukaryotic cells such as bone and ligaments while inhibiting the adsorption of prokaryotic cells such as bacteria? This appears not to have been examined.

6. How can nano-surfacing be optimized to minimize biofilms? Argument from surface energy have been proposed but are problematic.

These questions can and have been answered in part but there remains a set of uncertainties that challenge the effective utilization of nano technologies.

We can possibly argue the following explanation from what we have developed herein.

1. The first coating of a surface is by the protein layer. Generally, this is done by some local van der Waals forces since the proteins are close to the surface and are well known to exhibit such forces. Also the protein layer seems to be a prerequisite for adhesion. However, the type of protein layer may very well depend on the surface structure. They structure of proteins vary widely and perhaps if we adjust the nanostructure we selectively change the type of protein adhering to the surface.

2. We know that bacteria seem phenomenologically to require proteins to adhere for them in turn to reversibly adhere to the proteins. This the proteins must be electrostatically and vdW wise strongly attracted to the surface and the cell.

3. After a reversible adhesion then we seem to have the appearance of protein filaments extruding from the bacteria and down through the protein layer, most likely using the protein to overcome the barrier wall normally between van der Waals and electronic forces. Once the filament hits the surface then it adheres irreversibly and the biofilm commences growth.

4. The supposition is that by changing the roughness of the surface we change the types of proteins or the nature of their adhesions on the surface. There does not appear to be any research determining this one way or the other at this time.

The challenge of this analysis is shown below. On the one hand certain biologicals adhere on roughness and others are repelled. One of the continuing questions is why, and what is the fundamental physical reason.

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[1] See EPA Report 1992.

 [2] See NRC 1998 report in detail.

[3] See Petsko and Ringe, Protein Structure and Function, Sinauer (Sunderland, MA) 2004. Pp 8-11.

 [4] See Butt et al, pp161-180.

[5] See p 230-234.