Medicare for All?

The current mantra amongst the left is "Medicare for All". (See Sanders Plan S 1804). They have no idea what they mean but that has never stopped the left before. I recall Thomas Paine and his analysis of social services and he felt compelled to say what it was and how it would be paid for. Not with the left, just shout out the mantra.

Medicare as it now stands has two components:

1. Recipients have paid into the system, 3.5% of one's gross, not net or limited, income for a lifetime, say from 18 years old to 65. That is 47 years of paying insurance premiums. Then you still pay for Parts B and D, and for that you get 80% coverage from a provider willing to accept Medicare. You also may end up paying for an additional coverage plan. One should recall that if you were in the top 35% income bracket you will never get back what you put in, on average!

2. Coverage is for medical and hospital care and some medications. No dental.

Thus Medicare today means you have paid and continue to pay and that your coverage is limited.

Now what is "Medicare for ALL"? As the NY Times notes:

“Medicare for all” has become a rallying cry for progressive Democrats, though it means different things to different people. Supporters generally agree that it is a way to achieve universal coverage with a system of national health insurance in which a single public program would pay most of the bills, but care would still be delivered by private doctors and hospitals. One-third of Senate Democrats and more than half of House Democrats who will serve in the new Congress have endorsed proposals to open Medicare to all Americans, regardless of age. A Medicare-for-all bill drafted by Senator Bernie Sanders, independent of Vermont, has been endorsed by 15 Democratic senators, including several potential presidential candidates: Cory Booker of New Jersey, Kirsten Gillibrand of New York, Kamala Harris of California and Elizabeth Warren of Massachusetts.

What they mean is that anyone who has never paid a penny will get what those of us who have paid all their lives. Social Justice be damned, any justice be damned. In addition it would be, if Sanders and the left have their way, "free", yes, totally free, unless of course you have any money, which they will take to pay for it.

I keep thinking of the TSA. They are generally brutes with a badge. Now they will be the ones managing this system. So if you like full body pat downs, insulting and man-handling characters, this is just what you want. So ten years ago I fought Obamacare, thirty six years ago Hillary Care, and now thank God I have that Irish passport! At least I can find a nice pub.

Just think of a Government run anything, except the military. Think Post Office, TSA, IRS, NJ Transit, Amtrak, and keep going. None work! What I wonder do these people really have in mind?

The un or under employed millennials think "free" everything. But for me and the 35% like me, we get near nothing but pay the carry. Who pays? As they say, you no longer live with mommy!

Yet then along comes a left wing Presidential candidate. She states after bemoaning the situation with her mother (I went through the same two decades earlier so I have first hand knowldge, it is always difficult):

I believe that health care should be a right, but the reality is that it is still a privilege in this country. We need that to change. When someone gets sick, there is already so much else to deal with: the physical pain for the patient, the emotional pain for the family. There is often a sense of desperation — of helplessness — as we grapple with the fear of the unknown. Medical procedures already have risks. Prescription drugs already have side effects. Financial anxiety should not be one of them.

Logistics, alone, can be overwhelming. I remember that as my mother’s condition worsened, she needed more care than we could provide. I wanted to hire a home health care aide for her. But my mother didn’t want help.

One agrees, financial difficulty should not be a problem. But equity and a form of justice should be considered. Although we do have Matthew 20:1-16 wherein it states about the Laborers in the field:

⁸ “When evening came, the owner of the vineyard said to his foreman, ‘Call the workers and pay them their wages, beginning with the last ones hired and going on to the first.’
⁹ “The workers who were hired about five in the afternoon came and each received a denarius.  So when those came who were hired first, they expected to receive more. But each one of them also received a denarius. When they received it, they began to grumble against the landowner. ‘These who were hired last worked only one hour,’ they said, ‘and you have made them equal to us who have borne the burden of the work and the heat of the day.’
¹³ “But he answered one of them, ‘I am not being unfair to you, friend. Didn’t you agree to work for a denarius?  Take your pay and go. I want to give the one who was hired last the same as I gave you. ¹⁵ Don’t I have the right to do what I want with my own money? Or are you envious because I am generous?’
¹⁶ “So the last will be first, and the first will be last.”

But one can ask; did not these workers enter into a contract? And was not the contract honored, albeit differently for groups but equitably for each as agreed. Yet one then must ask based upon contract law, where the conclusion at the end comes from? Is this the basis for Medicare for All? Why not Marx, namely "according to one's need" Is there a moral requirement to make some contribution. By someone at some point. Or are we establishing the "free rider" principle.

As a digression, the piece from Matthew above has various interpretations. One is that which I noted, namely a Master can decide what to pay workers irrespective of their individual contributions. The more classic interpretation was that one who came to the Lord late in life would receive the same redemption as one who had been faithful all their life. This was to act as an incentive for Gentile conversions. Needless to say there can be multiple interpretations. But the operative phrase is "generous". That means that the person paying may pay whatever they so think. However with Medicare for All it raises the question as to who is paying. Clearly it is the taxpayer, and as structured now the taxpayer pays proportional to their total income, similar to the above. But if the Master were forced to pay for those who have done no work in the field, would that not change the parable?

 Having an equitable yet exceptional health care system is complicated. Medicare is somewhat akin to the above parable, we all agree to participate, wait till we are 65, hopefully, then continue to pay whether we are ever ill or not. That is the essence of insurance and that is Medicare. If we want a plan for all others, hopefully not eliminating choice as is the case with the New York Plan we discussed, then any new plan must at the very least not be a Medicare plan or any adjunct to it, but a stand alone plan with clear financial monitoring. What that is I do not know nor does it appear do any of the sycophants proposing it. This whole movement may make Obamacare look rational! Perhaps they will eliminate the need for Medical School, allow only the use of an aspirin, and focus on infrastructure by building bigger graveyards!

Welcome to the never ending debate on health care. But remember the "back of the envelope" calculation. Health care costs are about $3.5 trillion, there are about 330 million citizens and thus per citizen it is $11,000 pa. Sick or not. Young or old. So where is that money coming from. Current Medicare participants are paying between $1,500 to $4,500 pa for 80% coverage. They are left with 20% of the $11,000. But, and this is critical, Medicare starts at 65 but one contributes from day one of employment, for many that is 18. So do we give a 25 year old the same benefit but at what cost! This issue is; who pays. The second issue is: since cost is critical, will the Government control this "plan" like it does all others? An "iron fist".

FED Balance Sheet - Slow Unroll

As we end 2018 and we now look at an active FED we should be watching both the Yield Curve and the Balance Sheet. We benchmark it here.

As shown above it is now dropping, some $400 billion is unwound already. To dump this garbage they have to discount greatly. As a note, the FED BS if marked to market is now well in insolvency, they are making Sears look fantastic. Just wait till folks understand this one.

The FED still holds a ton of MBS, those old junk notes on bad home loans. Even market to market they are worthless or close to it.

The above combined Treasury obligations where the FED was borrower of last resort. They are dropping but even if marked to market are underwater.

The above is the total. As we have argued for a decade this is as critical as the Yield Curve and so far no one has downloaded from the FED.

Obesity and Cancer

We have argued based upon extensive evidence that obesity is a driver of multiple cancers. A recent paper Kern et al notes:

Obesity promotes the development of numerous cancers, such as liver and colorectal cancers, which is at least partly due to obesity-induced, chronic, low-grade inflammation. In particular, the recruitment and activation of immune cell subsets in the white adipose tissue systemically increase proinflammatory cytokines, such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). These proinflammatory cytokines not only impair insulin action in metabolic tissues, but also favor cancer development. Here, we review the current state of knowledge on how obesity affects inflammatory TNFα and IL-6 signaling in hepatocellular carcinoma and colorectal cancers. 

They continue:

During obesity-driven, low-grade inflammation, hepatic NF-κB serves as an antiapoptotic survival factor, which promotes the proliferation of HCC progenitor cells and HCC development. In contrast, hepatic inactivation of IKK2 increases diethylnitrosamine (DEN)-induced HCC burden. In line with this evidence, hepatic NEMO deficiency causes spontaneous progression of TNFα-mediated chronic hepatitis to HCC. This detrimental effect of hepatic NEMO deficiency is potentiated under obese conditions presumably by enhanced liver inflammation and hepatic lipid accumulation. This supports the notion that NEMO acts as a tumor suppressor in the liver. Surprisingly, hepatic NEMO-deficient mice are protected against diet-induced obesity and exhibit improved insulin sensitivity...

There is thus evidence that controlling obesity, not just blood glucose, is a critical task.

What If?

Ten years ago I wrote about the mess that the proposed trillion dollar handout was to cause and further that the FED was loading up on junk while handing out free money to the already well endowed.

Now we have a Government shutdown. It has been going on for a while but I thought what would happen if it lasted a couple of months and nobody really noticed. NY State stepped up to keep the Statue of Liberty open etc so this may be a test to show how useless the Feds are.

Just a thought.

Merry Christmas

Factum Est Autem In Diebus Illis Exiit Edictum A Caesare Augusto Ut Describeretur Universus Orbis

Haec Descriptio Prima Facta Est Praeside Syriae Cyrino

Et Ibant Omnes Ut Profiterentur Singuli In Suam Civitatem

Ascendit Autem Et Ioseph A Galilaea De Civitate Nazareth In Iudaeam Civitatem David Quae Vocatur Bethleem Eo Quod Esset De Domo Et Familia David

Ut Profiteretur Cum Maria Desponsata Sibi Uxore Praegnate

Factum Est Autem Cum Essent Ibi Impleti Sunt Dies Ut Pareret

Et Peperit Filium Suum Primogenitum Et Pannis Eum Involvit Et Reclinavit Eum In Praesepio Quia Non Erat Eis Locus In Diversorio

Et Pastores Erant In Regione Eadem Vigilantes Et Custodientes Vigilias Noctis Supra Gregem Suum

Et Ecce Angelus Domini Stetit Iuxta Illos Et Claritas Dei Circumfulsit Illos Et Timuerunt Timore Magno

Et Dixit Illis Angelus Nolite Timere Ecce Enim Evangelizo Vobis Gaudium Magnum Quod Erit Omni Populo

Quia Natus Est Vobis Hodie Salvator Qui Est Christus Dominus In Civitate David

Et Hoc Vobis Signum Invenietis Infantem Pannis Involutum Et Positum In Praesepio

Et Subito Facta Est Cum Angelo Multitudo Militiae Caelestis Laudantium Deum Et Dicentium

Gloria In Altissimis Deo Et In Terra Pax In Hominibus Bonae Voluntatis

Et Factum Est Ut Discesserunt Ab Eis Angeli In Caelum Pastores Loquebantur Ad Invicem Transeamus Usque Bethleem Et Videamus Hoc Verbum Quod Factum Est Quod Fecit Dominus Et Ostendit Nobis

Et Venerunt Festinantes Et Invenerunt Mariam Et Ioseph Et Infantem Positum In Praesepio

Videntes Autem Cognoverunt De Verbo Quod Dictum Erat Illis De Puero Hoc

Et Omnes Qui Audierunt Mirati Sunt Et De His Quae Dicta Erant A Pastoribus Ad Ipsos

Maria Autem Conservabat Omnia Verba Haec Conferens In Corde Suo

Et Reversi Sunt Pastores Glorificantes Et Laudantes Deum In Omnibus Quae Audierant Et Viderant Sicut Dictum Est Ad Illos

The Creed, or Whatever

The book by Rubenstein, When Jesus Became God, is exceptionally well written and approachable by the lay reader. It addresses the topic of Christology, namely just what was Jesus Christ, man, God, both, and are there three Gods, one, a blend. This has been a major issue in Christianity. It is a monotheistic religion, namely one God, but in the Gospel writing we see Jesus as Son of God, but equal to the Father, and then the Holy Spirit, somehow a third entity acting upon the Apostles. Add to this mix the background of many in Greek philosophy and Greek philosophical terms. Finally add the ascension of Constantine, the "first" Christian emperor in Constantinople who see a cacophony of voices with opinions on this "Trinity" of Gods, yet being just one God. Rubenstein notes that battles would ensure at bakers, merchants, sailors, bar keeps as to what Jesus and the three really were. To Constantine he needed unity not dissension.

The battle was between, at this time, Arians and non-Arians. Arians saw Jesus as Son of God with all that such a relationship brings. The non-Arians are those who saw unity in the Trinity, unity and equality.

Enter Greek, its words, its meanings, its philosophical underpinnings. Enter also the collection of egos acting as Bishops fighting viciously against opposing sides, seeking the approval of Constantine with execution being the adversarial tactic.

The book takes you from before Nicaea to during the Council to many of the events proximate to its ending. It covers the theological issues, the political intrigues, and the religious infighting. There were Councils after this which settled a few issues but not all.

A key set of observations that the author opines on are:

1. The dominant role of Constantine, who at this point is frankly not even a Christian not having been baptized until just before his death.

2. The lack of almost any role by the Bishop of Rome, now the Pope in the Catholic Church. It would not be until the beginning of the next millennium that the concept of a powerful Pope would evolve.

3. The sustaining of a multiplicity of views in the context of deadly conflict.

In the end Rubenstein alludes to the fact that Mohammed and his interpretation had but one God, the Father if you will, and that Jesus was a prophet, as was Moses and in turn as was Mohammed. This simplicity Rubenstein argues was what the Muslim faith spread so rapidly, it simplified so much of the extreme complexity of the Christology. Yet I would argue that this was but one of the many reasons for its spread. One must remember that Muslim faith spread from about 625 onwards whereas the events in this tale are surrounding the period of Nicaea, 325, three hundred years earlier. I would argue that it also was the oppression of the Emperors in Constantinople, the wars with the Persians, the influx of Germanic tribes and a conflux of many other factors.

There is also the maintaining of the Arian faith amongst the newcomers such as the Lombards which lasts well into the 7th Century. There is the detailed theological work using Aristotle by Aquinas in the 13th century and finally the abandonment of this by Ockham in the 14th century, reverting to faith rather than reason.

The greatest challenge in a book of this type is setting the stage for Greek words and meanings circa the 4th century. Such terms as person, essence, substance, and so forth, have meanings in Greek at the time which were modified from Aristotle and his followers, and then as we get to the Scholastics, modified again, and frankly read today may have no nexus to the reality of the time and place of these arguments. I would like to have seen some discussion of this issue, one which I have struggled with in trying to understand early 7th century works. Add to this the complexity of meanings as one crosses the Mediterranean, from Constantinople to Alexandria, then to Syria and beyond.

Overall Rubenstein does a great job for a book of this type. The writing is clear, focused, organized. The explanation and very reasonable and the interplay with the Greek is included. For anyone interested in the battle with Christology this is a superb beginning.

Creeds and their enforcement are sensitive issues. The Eastern Orthodox Church still has core differences, and even amongst Western churches there are material discrepancies. Thus public shows of reciting one Creed or another can and do often result in conflicts, often based upon gross ignorance of the underlying issues. Rubenstein adds to our understanding greatly.

Merry Christmas ... Bah Humbug!

 The above is the flat, yes flat, Yield curve! No where to go but up!

 The spreads are disappearing. They go to zero and then negative. Have not seen that since Carter!

 Now look at the above. The Yield Curve is FLAT. That means that the short term cost of money equals the long term opportunity. Namely why borrow to build if you go no where! Thanks to the FED. Now this gets worse. Yes worse. The cost of our debt has exploded, and that will drop the long term growth inverting the Yield Curve totally. Again, thanks FED.

Now the DOW etc. It is on its way to 15,000! Yes folks, 15,000. Why? Simply that we have the worst communicating group ever in Government. Pull the Twitter switch folks! Think, write, then read it to the American folks. Let us know what you are doing.

I have seen this before. It is the owners of a family company making decisions by shooting from the hip and having all the employees erratically chasing him about. But this is a Government not a family owned business. We all own the business, it is our country. Stop it please with the Twitter stuff.

This is not a Recession looming, it is a potential collapse. Enough with the Twitter. Send in the adults. And oh by the way, in my many years of business I always found that the most pressing issues occurred during the so-called Christmas recess!

Some Thoughts on Government Shutdown

As with many of these political arguments, I do not have a horse in the race only have some exposure to the massive Government structures. So let's look at a few Departments.

Department of Energy: Fundamentally it makes and houses nuclear weapons, the old AEC. Then all sorts of stuff was added. Forty years ago they added the electric car. Then along came Tesla and did in a year what DoE spent 40+ failing to do. So just dump all but the AEC stuff, move it to DoD. Close it down.

Department of Education: Well we have thousands of school boards, trillions of school taxes and a collection of politicos in DC disconnected from reality. Close it up.

HHS: Keep this one. It has FDA, NCI, etc.

Department of Agriculture: Now 150 years ago it made sense. Now not so much. Massive companies grow stuff now, so we would be better off managing it through FTC.

Department of Treasury: I guess we keep it.

Department of State: Now this is a real boondoggle, It made sense when communications was by sailing ship and before the President could pick up a phone or video conference. It should be cut in half at least!

Department of Interior: Well, parks and stuff. Outsource it.

DHS: Now here if the homeland police. They control not just borders but have empowered hundreds of thousands of agents to control our interstate travel. In many ways this may be the most destructive and abusive entity in the Federal Government. TSA is in my opinion incompetently and abusively run. But it seems we keep giving it more police powers, we need less!

DoD: Well this is a good one. In the old days the Army protected the country and the Navy protected us on the seas and in foreign ports. The Air Force was to do both. But 9/11 showed us that not a single aircraft or anti-aircraft could protect us from four straying aircraft. One wonders what Gatwick in the US would look like.

Treasury: Somebody had to raise the money for all this stuff.

EPA; Reason should prevail and people should be protected.

and the list goes on. It would be interesting to see what could really be done from the ground up again.

Happy Ten Years Old

As I sit here in the Detroit Airport, having been fully body searched by a large TCA creature with a sadistic smile as he made certain that this grey haired 75 year old male in a suit was fully inspected from genital to genital, and you want these morons managing your health care, I think that today marks the 10th anniversary of this blog.

I have had some who asked why I write this thing. Good question, think of Detroit! In ten years we have seen in my opinion four major trends. First Government wants to take over more and more each day. Second, fantastic advances have taken place in medicine, unfortunately many to be undone by the burly man at Detroit with a badge. Third, the US knows less about other nations than at any other time. And vice versa. Fourth the control of privacy and information has gleefully been handed over to entities who have what appears in opinion to have no ethics, and are clueless about the topic.

Of course we have global warming, social justice,income inequality, deep state, immigration, etc as topics du jour. But the two most serious concerns for the next ten years is more Government takeovers and loss of privacy.

It will be interesting to see what happens over the next ten years. This blog has accumulates several million words and 300,000 readers. I refuse  Facebook, Twitter etc, they just want my identity. Google seems to allow me to speak, but there too one must wonder.

So looking forward, I am excited to see what it brings. Hopefully my flight arrives before than, and yes that that homunculus does not come back for a "feel". And just think, I am not crossing a border.

Too Much Time on His Hands

I know nothing about Clemson. I think it is some southern college but in reading a NY Times article proposing that human extinction may be a good thing, I would not recommend the place to any of my grand kids. Really.

The author states:

One might ask here whether, given this view, it would also be a good thing for those of us who are currently here to end our lives in order to prevent further animal suffering. Although I do not have a final answer to this question, we should recognize that the case of future humans is very different from the case of currently existing humans. To demand of currently existing humans that they should end their lives would introduce significant suffering among those who have much to lose by dying. In contrast, preventing future humans from existing does not introduce such suffering, since those human beings will not exist and therefore not have lives to sacrifice. The two situations, then, are not analogous. It may well be, then, that the extinction of humanity would make the world better off and yet would be a tragedy. I don’t want to say this for sure, since the issue is quite complex. But it certainly seems a live possibility, and that by itself disturbs me.

Frankly, who asked him anyhow. My minor was philosophy as an undergraduate but at a Catholic School it was trying to understand Aquinas. Which is why I now am a follower of Ockham...not Aquinas.

Now as I struggle with the inner workings of various cancers, hopefully trying to make a small contribution, I from time to time return to Ockham, and his philosophy. He introduced the concept of individualism, that individuals count, that individuals have duties in a religious context and that individuals are citizens and not subjects. Not bad for the 14th century.

But along comes this Southern erstwhile philosopher who posits what he does above makes one ask have we entered the world of the absurd. 

Humans have intelligence, and that intelligence can, has, and most likely will always be used to sustain existence. Yes, along comes from time to time abject evil, not much we can do about it but recognize it and eliminate it. But doing away with the entire human race.

Humans are part of the ecosystem. A complex ecosystem, and one which has from time to time gone through shifts. But for the last 3,000 years out of 6 billion we have managed somewhat well. Other species have wiped out other species. Just look at insects, or how about influenza. We are in a continual war with our partners on this planet. But understanding that and then understanding how to accommodate is also essential.

Thus if carbon dioxide is a problem, we should not tax our way out of it, or have some Southern philosopher kill off all humanity, but find a solution. We have done so with many other issues over the centuries, why not this time as well! Let's not let Southern philosophers kill off humanity, please!

CRISPR Accuracy and Precision

A recent paper by Chakrabarti et al notes that:

• The outcome of CRISPR-mediated editing can be predicted
• Not all target sites are edited in a predictable manner
• The precision of DNA editing is mainly determined by the fourth nucleotide upstream of the PAM site
• Chromatin states affect editing of imprecise, but not precise, target sites

In the corresponding Eureka article they note:

Guided by the RNA molecule, the Cas-9 enzyme scans along the genome until it finds the region of interest. When the RNA guide matches the correct DNA sequence, it sticks like Velcro and Cas9 cuts through the DNA. The DNA is broken three letters from the end of the target sequence, and bits of genetic code are then inserted or deleted, seemingly haphazardly, when the cell attempts to repair the break. In this study, the researchers found that the outcome of a particular gene edit depends on the fourth letter from the end of the RNA guide, adjacent to the cutting site. The team discovered that if this letter is an A or a T, there will be a very precise genetic insertion; a C will lead to a relatively precise deletion and a G will lead to many imprecise deletions. Thus, simply avoiding sites containing a G makes genome editing much more predictable.

This means that precision and accuracy may be attained. It has been known that CRISPRs seek certain defined sites on the DNA but there may be multiple sites or sites blocked by closed chromatin. This appears to remedy the issue.

There is a Benefit

The ongoing flap over monitoring for prostate cancers seems to be slowly disappearing except for those who one would guess want to see old men die. The most recent one is in the current NEJM where the study results note:

We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017... Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. 

But they further conclude:

The limitations of our trial are that the analyses according to age were not prespecified in the protocol, were exploratory, and were, among other caveats, sensitive to chance findings and not adjusted for multiple testing. Furthermore, the diagnostic procedures used today differ drastically from those used during the period of enrollment in our trial. As a result of widespread PSA testing today, most men have nonpalpable, PSA-detected tumors, whereas in our trial the majority of the men had clinically detected, palpable tumors. Today, men undergo multiple biopsies or multiparametric magnetic resonance imaging with targeted biopsies, whereas the participants in our trial had only cytologic or sextant biopsies, with few cores investigated as compared with current standards. Today, the clinical domain of localized prostate cancer is different, and the sensitivity for the detection of high-grade cancers during our trial was considerably lower than it is today. In clinically detected prostate cancer, the benefit of radical prostatectomy in otherwise healthy men can be substantial, with a mean gain of almost 3 years of life after 23 years of follow-up.

Namely, the data is old but it demonstrates life saving and with the use of PSA it seem dramatically better.

The data against "watchful waiting" just keeps piling up. As they say; believe them or your lying eyes!

Accuracy vs Precision, Ouch!

There is an MIT News bleeb on the development of a new climate model. They note:

The new model will be built by a consortium of researchers led by Caltech, in partnership with MIT; the Naval Postgraduate School (NPS); and the Jet Propulsion Laboratory (JPL), which Caltech manages for NASA. The consortium, dubbed the Climate Modeling Alliance (CliMA), plans to fuse Earth observations and high-resolution simulations into a model that represents important small-scale features, such as clouds and turbulence, more reliably than existing climate models. The goal is a climate model that projects future changes in critical variables such as cloud cover, rainfall, and sea ice extent more accurately — with uncertainties at least half the size of those in existing models. "Projections with current climate models — for example, of how features such as rainfall extremes will change — still have large uncertainties, and the uncertainties are poorly quantified," says Tapio Schneider, Caltech's Theodore Y. Wu Professor of Environmental Science and Engineering, senior research scientist at JPL, and principal investigator of CliMA. "For cities planning their stormwater management infrastructure to withstand the next 100 years' worth of floods, this is a serious issue; concrete answers about the likely range of climate outcomes are key for planning." .... Current climate modeling relies on dividing up the globe into a grid and then computing what is going on in each sector of the grid, as well as how the sectors interact with each other. The accuracy of any given model depends in part on the resolution at which the model can view the Earth — that is, the size of the grid's sectors. Limitations in available computer processing power mean that those sectors generally cannot be any smaller than tens of kilometers per side. But for climate modeling, the devil is in the details — details that get missed in a too-large grid. For example, low-lying clouds have a significant impact on climate by reflecting sunlight, but the turbulent plumes that sustain them are so small that they fall through the cracks of existing models. Similarly, changes in Arctic sea ice have been linked to wide-ranging effects on everything from polar climate to drought in California, but it is difficult to predict how that ice will change in the future because it is sensitive to the density of cloud cover above the ice and the temperature of ocean currents below, both of which cannot be resolved by current models

I recall decades ago examining random fields, my doctoral thesis, and how complex a problem they are. Now they are totally redoing models. Hopefully accuracy rather than precision is the end result. Then again should we question what we are being told, it is precise but is it accurate? Just a thought.

Taxes, It is Alice in Wonderland Time

I am one of those who continuously do and redo their taxes before hand and making certain that they are not only paid but over paid. It is abject terror of the IRS. I feared the old KGB even less.

But we were told we got a great new tax law. Well perhaps but if you live in New Jersey, New York, Massachusetts, or California, good old Democratic strongholds, the new Republican Tax Law raises your taxes, unless you are in Real Estate! Yep, just did the new version, a whopping 10%+ increase.

Thanks Washington. I am really confused, but can't say we did not see it coming. Once Ryan said he was leaving, one could feel the draft from the tax room waif into the living room.

Merry Christmas and Happy New Year.

APOBEC and PCa

In a recent paper on the development of Prostate Cancer (PCa) the authors allege the role to APOBEC is critical. They note[1]:

The researchers collected patient data from close to 300 men who have had their entire cancer genome sequenced to characterise all mutations present in the tumour. Based on the data set, the researchers have developed the computer model which can be used to predict how prostate cancer will develop for a given patient.

'If we have a patient with a particular set of mutations, we can use the model to predict the most likely next mutation that the patient will experience at some point - and how it will affect the patient's clinical situation. As an illustration, we can predict with some probability that if you have mutation A, you are likely to get mutation B before you get C. We can also predict if the next mutation is likely to change the clinical outcome of the disease'…

Mechanism Contributing to the First Mutations in Prostate Cancer Have Been Found. The approximately 300 patients from the study all had their entire genome sequenced. With genome sequencing, it becomes possible to tailor the treatment of the individual - also referred to as personalized medicine. The patients whose data the researchers have used have primarily been so-called early onset patients. This group is defined as men who are diagnosed with prostate cancer before reaching the age of 55 years.

'Prostate cancer develops over many years. We have therefore been particularly interested in the group of patients where the cancer is detected at young age as this allows us to analyses the tumour at an early stage. This is an important element because in this way we get a cleaner picture of the first mutations and alterations that occur in the tumour, to find out what is the initiating factor', …

So far, it has not been known precisely what initiates prostate cancer. However due to the focus on the earliest detected tumours, the researchers uncovered a mutational mechanism involving an enzyme called APOBEC. This enzyme may help trigger the disease - i.e. trigger some of the very first mutations in prostate cancer.

'We hypothesize that this enzyme mutates the prostate cells at a low but constant rate. Each time the cell divides, APOBEC is likely to cause mutations. If you have early-onset prostate cancer, you may have a couple of mutations caused by APOBEC. Twenty years later, you may have 10-20 mutations',  

Now we know a great deal about PCa. There are a multiplicity of genetic aberrations. A Nature Reviews paper has also recently noted[2]:

 

Genome-wide association studies (GWAS) have been successful in deciphering the genetic component of predisposition to many human complex diseases including prostate cancer. Germline variants identified by GWAS progressively unraveled the substantial knowledge gap concerning prostate cancer heritability. With the beginning of the post-GWAS era, more and more studies reveal that, in addition to their value as risk markers, germline variants can exert active roles in prostate oncogenesis. Consequently, current research efforts focus on exploring the biological mechanisms underlying specific susceptibility loci known as causal variants by applying novel and precise analytical methods to available GWAS data. 

Results obtained from these post-GWAS analyses have highlighted the potential of exploiting prostate cancer risk-associated germline variants to identify new gene networks and signalling pathways involved in prostate tumorigenesis. In this Review, we describe the molecular basis of several important prostate cancer-causal variants with an emphasis on using post-GWAS analysis to gain insight into cancer etiology. In addition to discussing the current status of post-GWAS studies, we also summarize the main molecular mechanisms of potential causal variants at prostate cancer risk loci and explore the major challenges in moving from association to functional studies and their implication in clinical translation.

Namely the first paper alleges the discovery of a putative unique and predictable path and the second a plethora of GWAS results.

It is worth examining both paths. However PCa can be strange and multifaceted. Most variants are slow growing as noted. However there are a small percentage which have explosive growth. Just what the differentiator is seems still unknown.

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[1] https://www.eurekalert.org/pub_releases/2018-12/uoct-ruc121118.php

[2] https://www.nature.com/articles/s41568-018-0087-3