Category Archives: Social issues ( be civil ! )

Kuru continues to inform

Neurologists of my generation were fascinated with Kuru, a disease of the (formerly) obscure Fore tribe of New Guinea. Who would have thought they would tell us a good deal about protein structure and dynamics?

It is a fascinating story including a Nobelist pedophile (Carleton Gajdusek) https://en.wikipedia.org/wiki/Daniel_Carleton_Gajdusek and another (future) Nobelist who I probably ate lunch with when we were both medical students in the same Medical Fraternity but don’t remember –https://en.wikipedia.org/wiki/Stanley_B._Prusiner

Kuru is a horrible neurodegeneration starting with incoordination, followed by dementia and death in a vegetative state in 4 months to 2 years. For the cognoscenti — the pathology is neuronal loss, astrocytosis, microglial proliferation, loss of myelinated fibers and the kuru plaque.

It is estimated that it killed 3,000 members of the 30,000 member tribe. The mode of transmission turned out to be ritual cannibalism (flesh of the dead was eaten by the living before burial). Once that stopped the disease disappeared.

It is a prion disease, e.g. a disease due to a protein (called PrP) we all have but in an abnormal conformation (called PrpSc). Like Vonnegut’s Ice-9 (https://en.wikipedia.org/wiki/Ice-nine) PrPSc causes normal PrP to assume its conformation, causing it to aggregate and form an insoluble mess. We still don’t know the structure of PrPSc (because it’s an insoluble mess). Even now, “the detailed structure of PrPSc remains unresolved” but ‘it seems to be’ very similar to amyloid [ Nature vol. 512 pp. 32 – 34 ’14]. Not only that, but we don’t know what PrP actually does, and mice with no PrP at all are normal [ Nature vol. 365 p. 386 ’93 ]. For much more on prions please see https://luysii.wordpress.com/2014/03/30/a-primer-on-prions/

Prusiner’s idea that prion diseases were due to a protein, with no DNA or RNA involved met with incredible resistance for several reasons. This was the era of DNA makes RNA makes protein, and Prisoner was asking us to believe that a protein could essentially reproduce without any DNA or RNA. This was also the era in which X-ray crystallography was showing us ‘the’ structure of proteins, and it was hard to accept that there could be more than one.

There are several other prion diseases of humans (all horrible) — mad cow disease, Jakob Creutzfeldt disease, Familial fatal insomnia, etc. etc. and others in animals. All involve the same protein PrP.

One can take brain homogenates for an infected animal, inoculate it into a normal animal and watch progressive formation of PrPSc insoluble aggregates and neurodegeneration. A huge research effort has gone into purifying these homogenates so the possibility of any DNA or RNA causing the problem is very low. There still is one hold out — Laura Manuelidis who would have been a classmate had I gone to Yale Med instead of Penn. n

Enter [ Nature vol. 522 pp. 423 – 424, 478 – 481 ’15 ] which continued to study the genetic makeup of the Fore tribe. In an excellent example of natural selection in action, a new variant of PrP appeared in the tribe. At amino acid #127, valine is substituted for glycine (G127V is how this sort of thing is notated). Don’t be confused if you’re somewhat conversant with the literature — we all have a polymorphism at amino acid #129 of the protein, which can be either methionine or valine. It is thought that people with one methionine and one valine on each gene at 129 were somewhat protected against prion disease (presumably it affects the binding between identical prion proteins required for conformational change to PrPSc.

What’s the big deal? Well, this work shows that mice with one copy of V127 are protected against kuru prions. The really impressive point is that the mice are also protected against variant Creutzfedlt disease prions. Mice with two copies of V127 are completely protected against all forms of human prion disease . So something about V/V at #127 prevents the conformation change to PrPSc. We don’t know what it is as the normal structure of the variant hasn’t been determined as yet.

This is quite exciting, and work is certain to go on to find short peptide sequences mimicking the conformation around #127 to see if they’ll also work against prion diseases.

This won’t be a huge advance for the population at large, as prion diseases, as classically known, are quite rare. Creutzfeldt disease hits 1 person out of a million each year.

There are far bigger fish to fry however. There is some evidence that the neurofibrillary tangles (tau protein) of Alzheimer’s disease and the Lewy bodies (alpha-Synuclein) of Parkinsonism, spread cell to cell by a ‘prionlike’ mechanism [ Nature vol.485 pp. 651 – 655 ’12, Neuron vol. 73 pp. 1204 – 1215 ’12 ]. Could this sort of thing be blocked by a small amino acid change in one of them (or better a small drug like peptide?).

Stay tuned.

Outside information on the Greek financial crisis

Definitely off topic, but I wrote the following to a an international banker friend of 50+ years experience about the Greek financial crisis

“But of more immediate import, what sayeth the banker about shutting the banks in Greece for a week. In this article http://www.theguardian.com/business/live/2015/jun/28/greek-crisis-ecb-emergency-liquidity-referendum-bailout-live#block-55907903e4b024248ae9a5ed people were taking Euros out, but if the banks don’t have any and the Europeans won’t give more, what happens then. Gotterdammerung?”

I got the following back

Possibly. Martial law? It happened here in the 30s – the “bank holiday(s)”. Having lived thru 2 bank runs, I can tell you it is a time when rationality is absent. The presumption is the Greek authorities have been planning for this. Greeks are used to violent demonstrations,. I would expect some bank buildings being burned. For a few days the country can function. More and I can not see anything but Grexit. I see a gigantic game of chicken. The Germans have been blinking up until now but the internal political cost to Merkel may be too great. Germany has MUCH to lose if Greece leaves the EU.

The twists and turns of topoisomerase (pun intended)

It is very sad that my late friend Nick Cozzarelli isn’t around to enjoy the latest exploits of the enzyme class he did so much great work on — the topoisomerases. For a social note about him see the end of the post.

We tend to be quite glib about just what goes on inside a nucleus when DNA is opened up and transcribed into mRNA by RNA polymerase II (Pol II). We think of DNA has a linear sequence of 4 different elements (which it is) and stop there. But DNA is a double helix, and the two strands of the helix wind around each other every 10 elements (nucleotides), meaning that within the confines of our nuclei this happens 320,000,000 times.

I’ve written a series of six posts on what we would see if our nuclei were enlarged  by a factor of 100,000 (which is the amount of compaction our DNA must undergo to fit inside the 10 micron (10 millionths of a meter) in diameter nucleus (since if fully extended our DNA would be 1 meter long. So if you compacted the distance from New York to Seattle (2840 miles or 14,995,200 feet) down by this factor you’d get a sphere 150 feet in diameter or half the length of a football (US) field. Now imagine blowing up the diameter and length of the DNA helix by 100,000 and you’d get something looking like a 2,840 mil long strand of linguini which twists on itself  320,000,000 times. The two strands are 3/8th of an inch thick. They twist around each other every 9/16ths of an inch.

For the gory details start at https://luysii.wordpress.com/2010/03/22/the-cell-nucleus-and-its-dna-on-a-human-scale-i/ and follow the links.

Well, we know that for DNA to be copied into mRNA it must be untwisted, the strands separated so RNA polymerase II (Pol II) can get to it.  Pol II is enormous — a mass of 500 kiloDaltons and 7 times thicker at 140 Angstroms than the DNA helix of 20 Angstrom thickness.

Consider the fos gene (which we’ll be talking about later). It contains 380 amino acids (meaning that the gene contains at least 1140 nucleotides ). The actual gene is longer because of introns (3,461 nucleotides), which means that the gene contains 346 complete turns of the double helix, all of which must be unwound to transcribe it into mRNA.

So it’s time for an experiment. Get about 3 feet of cord roughly 3/8 of an inch thick. Tie the ends together, loop one end around a hook in your closet, put a pencil in the other end and rotate it about 100 times (or until you get tired). Keeping everything the same, have a friend put another pencil between the two strands in the middle, separating them. Now pull on the strands to make the separation wider and move the middle pencil toward one end. In the direction of motion the stands will coil even tighter (supercoiling) and behind they’ll unwind.

This should make it harder for Pol II to do its work (or for enzymes which copy DNA to more DNA). This is where the various topoisomerase come in. They cut DNA allowing supercoils to unwind. They remain attached to the DNA they cut so that the DNA can be put back together. There are basically two classes of topoisomerase — Type I topoisomerase cuts one strand, leaving the other intact, type II cuts both.

Who would have thought that type II topoisomerase would be involved in the day to day function of our brain.

Neurons are extended things, with information flowing from dendrites on one side of the cell body to much longer axons on the other. The flow involves depolarization of the cell body as impulses travel toward the axon. We know that certain genes are turned on by this activity (e.g. the DNA coding for the protein is transcribed into mRNA which is translated into protein by the ribosome). They are called activity dependent genes.

This is where [ Cell vol. 1496 – 1498, 1592 – 1605 ’15 ] comes in. Prior to neuronal activity, when activity dependent genes are expressed at low levels, the genes still show the hallmarks of highly expressed genes (e.g. binding by transcription factors and RNA polymerase II, Histone H3 trimethylation of lysine #4 {H3K4Me3 } at promoters).

This work shows that such genes are highly negatively supercoiled (see above) preventing RNA polymerase II (Pol II) from extending into the gene body. On depolarization of the cell body in some way Topoisomerase IIB is activated, leading to double strand breaks (dsbs) within promoters allowing the DNA to unwind and Pol II to productively elongate through gene bodies.

There is evidence that neuronal stimulation leads to dsbs ( Nature NeuroScience vol. 16 pp. 613 – 621 ’13 ) throughout the transcription of immediate early genes (e.g. genes turned on by neural activity). The evidence is that there is phosphorylation of serine #139 on histone variant H2AX (gammaH2AX) which is a chromatin mark deposited on adjacent histones by the DNA damage response pathway immediately after DSBs are found.

Etoposide (a topoisomerase inhibitor) traps the enzyme in a state where it remains bound to the DNA of the dsb. On etoposide Rx, there is an increase in activity dependent genes (Fos, FosB, Npas4). Inhibition of topiosomerase IIB (the most prevalent topoisomerase in neurons) by RNA interference (RNAi) leads to blunted activity dependent induction of these genes. This implies that DNA cutting by topoisomerase IIB is required for gene activation in response to neuronal activity.  Other evidence is that knocking down topoisomerase  using RNA interference (RNAi) stops activity dependent gene transcription.

Further supporting this idea, the authors induced dsbs at promoters of activity dependent genes (Fos, fosB, Npas4) using the CRISPR system. A significant increase in transcription was found when the Fos promoter was targeted.

I frankly find this incredible. Double strand breaks are considered bad things for good reason and the cell mounts huge redundant machines to repair them, yet apparently neurons, the longest lived cells in our bodies are doing this day in and day out. The work is so fantastic that it needs to be replicated.

Social Note: Nick Cozzarelli is one of the reasons Princeton was such a great institution back in the 50s (and hopefully still is). Nick’s father was an immigrant shoemaker living in Jersey City, N. J. Princeton recognized his talent, took him in, allowing him to work his way through on scholarship, waiting tables in commons, etc. etc. He obtained a PhD in biochemistry from Harvard and later became a prof at Berkeley, where he edited the Proceedings of the National Academy of Sciences USA for 10 years. He passed away far too soon of Burkitt’s lymphoma in his late 60s. We were friends as undergraduates and in grad school.

I can only wonder what Nick would say about the latest twists of the topoisomerase story

At the 55th

This is a mostly nonscientific post concerning the 55th reunion of the Princeton Class of 1960 last weekend. First the Science. Nick Cozzarelli was one of the most distinguished members of our class — great work on Topoisomerase, editor of PNAS for 10 years which established a prize named for him for the best paper each year. No one I’ve ever talked to in the class knew of him or his work. Shirley Tilghman, president of Princeton certainly did, and was shocked to hear of his untimely passing from Burkitt’s lymphoma when I told her of it at our 50th, saying he was a great scientist. However, he’s one of the reasons Princeton back then was a great institution (and hopefully still is). The son of an immigrant shoemaker in Newark NJ, he was taken in, given a scholarship, and worked his way through, serving meals in commons etc. etc. I made sure the undergraduates picking up a little cash by pouring drinks and serving meals at reunions heard about him. He was a good friend.  R. I. P. Nick.

Another friend, an emeritus prof of chemical engineering, referees a lot of papers. He estimates that 80% of the papers in his field, quantum chemistry, coming from China are absolute trash. According to him China gives bonuses to people getting published in high impact journals. What he finds particularly appalling is that he writes up a detailed list of corrections and improvements for the paper, and then finds it published totally unchanged in another journal.

He and I reminisced about our great undergraduate advisor Paul Schleyer with the department chair (who of course knew of him since he is one of the most cited and prolific (1,400 papers) chemists of the 20th century). He’s another reason Princeton was such a great institution back then (and hopefully still is). For details please see https://luysii.wordpress.com/2014/12/15/paul-schleyer-1930-2014-a-remembrance/ and https://luysii.wordpress.com/2014/12/14/paul-schleyer-1930-2014-r-i-p/

I finally saw the new Chemistry building (under construction at the 50th) and it is gorgeous. The NMR set up is particularly impressive, with the megaHertz of the machinery a factor of 15 greater than those we first started using in the 60s. Alas Varian is no more. It was bought a few years ago by another company which terminated the business. For where the money came from see https://luysii.wordpress.com/2011/05/16/princeton-chemistry-department-the-new-oberlin/.

In a remarkable coincidence, my wife an I were able to chat with the son of a neurologist in my call group, just finishing up his PhD in Chemistry there. How improbable is that?

Now for the nonScientific part.

For those undergraduates reading this at similar institutions, some advice — get to know as many of your classmates as you can. Premeds at Princeton back then had to take a lot of the same courses — biology, basic chemistry, organic chemistry, calculus, physics etc. etc. So we got to know each other. The rest of the class, not so much unless we were in other organizations (in my case, the marching band, Triangle club, and the eating club). At reunions I always meet classmates that I wish I knew back then and form new friendships.

Sometimes that isn’t always easy, with everyone working out the various important issues present from 18 to 22. A classmate’s wife described the men of the class at their 25th reunion as ‘roosters’, crowing and impressing each other. Not the case 30 years later. Everyone glad just to be there and catch up.

Princeton was all male back then. The current wives (some being #2, #3, #5) are an impressive bunch. They were uniformly intelligent and interesting. Not a bimbo in the lot of them, although most were very attractive physically. So the class may have slept with bimbos, but they were no longer in evidence.

Various seminars were held. I went to one about America’s relation to food. The panelists were 6 trim females with a fair amount of pseudoscience and touchy feely crap emitted, but at least the cautionary tale of the trash in the popular press about diet was mentioned (e.g. the paper about eat chocolate lose weight). What was fascinating was that the incidence of obesity (BMI over 29) in the group of several hundred listeners was at most 5%, proving, once again, that obesity in the USA is largely a class phenomenon. Also noted, is that I only saw one or two undergraduates and graduates smoking, again a class phenomenon, something Americans don’t like to talk about, but there nonetheless.

A memorial service for classmates was held in the chapel (built in 1929 but designed to appear that it was built in 1299). The organ is magnificent as were the acoustics, the sound surrounding you rather than coming at you. Bach and Vidor were performed by the organist. Apparently there was quite a battle about which to do first — refurbish the organ or the chapel acoustics. The stone had roughened distorting the sound so it didn’t echo properly. Clear plastic was applied to smooth the stone and then the organ was fixed. If you can hear a concert there please do so. Great composers write for the space their music will be performed in as well as the instruments it will be performed on, certainly true of Gabrielli, Bach and Vidor.

On a sadder note. I know of 4 suicides of class members (we started with around 725). Probably there are more. Also a good friend and classmate’s wife and daughter appeared to accept an award in his name. Although still alive he is incontinent, unable to walk and demented from Alzheimer’s. Despite degrees from Princeton, Harvard and Penn, Board examiner in Neurology blah blah blah, I was totally unable to help him. All I could do was offer emotional chicken soup to his wife, something my immigrant grandmother did with her 4th grade education in the dry goods store she ran. That’s why it’s good to be retired from neurology and not see this day after day.

Finally the P-rade. It is a great emotional lift for the psyche to march a mile or so to the reviewing stand being cheered by probably 1,000 – 2,000 younger graduates the whole time. The younger they got the louder the cheers and the drunker they were. It’s pretty hard not to feel good after that. I have heard that the only weekend event where more beer is consumed than Princeton reunions is the Indianapolis 500.  Along those lines, I only saw one truly drunk individuals among the 250 or so classmates and significant others although just about everyone had alcohol.  The alcoholics are no longer around for the 55th.

A Touching Mother’s Day Story

Yes, a touching mother’s day story for you all. It was 48 years ago, and I was an intern at a big city hospital on rotation in the emergency room. The ER entrance was half a block from an intersection with a bar on each corner. On a Saturday night, we knew better than to try to get some sleep before 2AM or until we’d put in 2 chest tubes (to drain blood from the lungs, which had been shot or stabbed). The bartenders were an intelligent lot — they had to be quick thinking to defuse situations, and we came to know them by name. So it was 3AM 48 years ago and Tyrone was trudging past on his way home, and I was just outside the ER getting some cool night air, things having quieted down.

“Happy Mother’s day, Tyrone” sayeth I

“Thanks Doc, but every day is Mother’s day with me”

“Why, Tyrone?”

“Because every day I get called a mother— “

Disentangling Heredity and Environmental effects on IQ

No sensible person thinks intelligence is completely determined by heredity or by environment. Recent Swedish work [ Proc. Natl. Acad. Sci. vol. 112 pp.4612 – 4617 ’15 ] tries to control for heredity while measuring environmental effects on IQ, assuming that IQ measures intelligence, a position some find contentious. Every Swedish 18 year old man is conscripted into the military apparently. IQ tests are given to all. Amazingly the authors found 436 sibships where the brothers had been raised apart.

The intelligence of the biological and adoptive parents wasn’t measured. Rather the surrogate of educational level was used instead. It was divided into 5 classes.

What did they find? Adopted sibs had an IQ 4.41 points higher than the nonAdopted sib (recall that average IQ is stated to be 100 points although it’s been rising, and that IQ levels of the population fall on the Bell (Gaussian) curve, with a standard deviation of 15 points). These results are not surprising, as few willingly give children up for adoption, so the adopted environment was quite likely better. The educational level of the adoptive parents was an average of 2.6 points higher.

Next, the authors measured the effect of the surrogate marker for intelligence (educational level) on IQ. For each point in the 5 point scale that the adoptive parent was at a higher educational level than the biologic ones there was an increase in IQ of the adopted sib relative to the unadopted one. This is as unequivocal evidence as we have for the effect of environment and educational level on IQ.

We’ll never have perfect data, and many caveats about this work are possible, but it is an impressive effort. 436 sibs is a huge number compared to the twins who’ve been reared apart and studied this way.

Just how large an effect do you think it was? I’ve already told you everything you need to know.

Each additional unit of rearing parental education was associated with 2 IQ units. Are you surprised? I was, because I thought the effect would be much larger. So environment is important in determining intelligence, just not so much.

Hillary’s stroke

Hillary Clinton had a stroke toward the end of 2012. It was not due to the faint she had presumably because of the flu in mid December. The information given out at the time was extremely sketchy and confusing (see the copy of the post of 31 Dec ’12 at the end).

She fainted while giving a speech in Buffalo according to one account and at her home in Washington according to another and was not hospitalized. She is said to have suffered a concussion when she fell. Then on the 30th of December she was hospitalized because a blood clot was found (more later) and placed on blood thinners. She suffered double vision and had to wear corrective glasses (Fresnel lenses) for congressional testimony 23 January 2013.

So she had a blood clot in her head and a neurologic deficit persisting for a few weeks. That’s what a stroke is.

Could it have been due to the head trauma? This is extremely doubtful based on an intense 42 month experience managing acute head injuries.

To get my kids through college, I took a job working for two busy neurosurgeons. When I got there, I was informed that I’d be on call every other night and weekend, taking first call with one of the neurosurgeons backing me up. Neurologists rarely deal with acute head trauma although when the smoke clears we see plenty of its long term side effects (post-traumatic epilepsy, cognitive and coordination problems etc. etc.). I saw plenty of it in soldiers when I was in the service ’68 – ’70, but this was after they’d been stabilized and shipped stateside. Fortunately, my neurosurgical backup was excellent, and I learned and now know far more about acute head trauma than any neurologist should.

We admitted some of the head trauma cases to our service, but most cases had trauma to other parts of the body, so a general surgeon would run the show with our group as consultants. The initial consultant in half the cases was me. If I saw them initially, I followed the patients until discharge. On weekends I covered all our patients and all our consults, usually well over 20 people.

We are told that Hillary had a clot in one of the large draining veins in the back of her head (venous sinuses actually). In all the head trauma I saw (well over 300 I’d guess), I never saw a clot develop there. I’ve spoken to two neuroradiologists still in practice, and they can’t recall seeing such a clot without a skull fracture near the vein. Nothing like this was mentioned at any time about Hillary.

Hillary’s neurologic deficit involved a nerve going to the muscles of her left eye. These start in the brainstem, a part of the brain quite near the site where she is said to have the clot in her vein. The brainstem is crucial in maintaining consciousness, and it is far more likely that the faint in early December was a warning sign of the stroke she had subsequently.

I can’t believe that she would not have been hospitalized had she complained of double vision when she fainted in early December, so it must have come on later.

So the issue is why did she have the stroke, and how likely is it to recur. I seriously doubt that it had anything to do with the head injury she sustained when she fainted. We’ve have two presidents neurologically impaired by stroke in the past century (Woodrow Wilson after World War I and Franklin Delano Roosevelt at Yalta). The results were not happy for the USA or the World.

Certainly all this would be cleared up if her medical records were released. Only Hillary can do this, but at least she cannot destroy them, as although she ‘owns’ them, they are not in her sole possession.

The following is a post written 31 December ’12 when the news of Hillary’s illness first broke showing how fragmentary the information about it was back then (it isn’t a good deal better now).

Medical tribulations of politicians — degrees of transparency

Remarkably on the last day of the year, 3 political figures and their medical problems are in the news. Here they are in order of medical transparency (highest first).

l. George Bush Sr. — the most transparent. We are told what he has (pneumonia), when he was admitted to hospital when he was in the ICU, when he came out. Docs call pneumonia ‘the old man’s friend’ not out of cynicism, but because its a mode of death with (relatively) little suffering. The patient lapses into unconsciousness and usually dies quickly and quietly. It took my cellist’s father only a day or two to pass away this month. Clearly it isn’t invariably fatal, and Bush Sr. was now out of the ICU at last count (he’s 88).

2. Hillary Clinton — admitted to the hospital yesterday with a ‘blood clot’ somewhere, said to be a complication of the concussion she suffered a few weeks ago. Also said to be under treatment with anticoagulants. Most clots due to head trauma are inside the head and treating them with anticoagulants is a disaster. The most likely type of clot given the time from the concussion is a subdural hematoma. It is possible that she’s been so inactive since the concussion that she developed thrombophlebitis in her legs, in which case anticoagulation would be indicated.

More disturbingly, is that her passing out a few weeks ago is a sign of something more serious going on. Hopefully not.

The powers that be should have told us where the clot actually is.

Update 5:50 PM EST — Well the powers that be did open up and it is a most unusual complication of head injury (and one I’d never seen in nearly 4 decades of practice) — a venous thrombosis in the head. I’m not even sure it’s due to her head injury. It might have even caused her syncope, but presumably she had some sort of radiologic study of her head when she fainted, which should have picked it up. The venous sinuses draining the brain in the back of the head are notoriously asymmetric, so a narrowing attributable to a clot could just be a variant anatomy. One very bad complication of cerebral venous thrombosis back there (which I saw as a complication of chronic mastoid bone infection — not head trauma) is pseudotumor cerebri. I really wonder if these guys have the right diagnosis.

3. Hugo Chavez — Yesterday it was announced that he’s had a third complication since his surgery for cancer 3 weeks ago. Naturally, we’re not told just what this complication actually is. This is consistent with the information that has been released about his case. We know almost nothing about his actual tumor (except that he has one). He most assuredly is not free of cancer as he stated last fall. He is said to have have a bleeding problem and a lung infection as the first two complications.

My guess for this third complication is that it is a dehiscence of his abdominal incision, which must have been fairly large for a 6 hour operation. Dehiscence just means that the wound has spontaneously opened up exposing abdominal contents (which means that peritonitis is not far behind). Why should this happen? Two reasons — he’s had radiation to the area which inhibits wound healing, and he’s been on high dose steroids in the past (and perhaps presently) which also inhibits wound healing.

I don’t think he’s going to be able to take office 10 days hence, and doubt that he’ll come back to Venezuela alive. Transparency has been zilch. Hopefully the people of Venezuela are beginning to realize just how misleading the information they’ve been fed about his health has been.

This is the sort of thing physicians taking care of really sick people deal with daily, which may explain why your doc friends aren’t as jolly as you are at the New Year’s Eve parties you’re about to attend.

Nonetheless, Happy New Year to all ! ! ! !

The dietary guidelines have been changed — what are the faithful to believe now ?

While we were in China dietary guidelines shifted. Cholesterol is no longer bad. Shades of Woody Allen and “Sleeper”. It’s life imitating art.

Sleeper is one of the great Woody Allen movies from the 70s. Woody plays Miles Monroe, the owner of (what else?) a health food store who through some medical mishap is frozen in nitrogen and is awakened 200 years later. He finds that scientific research has shown that cigarettes and fats are good for you. A McDonald’s restaurant is shown with a sign “Over 795 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 Served”

Seriously then, should you believe any dietary guidelines? In my opinion you shouldn’t. In particular I’d forget the guidelines for salt intake (unless you actually have high blood pressure in which case you should definitely limit your salt). People have been fighting over salt guidelines for decades, studies have been done and the results have been claimed to support both sides.

So what’s a body to do? Well here are 4 things which are pretty solid (which few docs would disagree with, myself included)

l. Don’t smoke
2. Don’t drink too much (over 2 drinks a day), or too little (no drinks). Study after study has shown that mortality is lowest with 1 – 2 drinks/day
3. Don’t get fat — by this I mean fat (Body Mass Index over 30) not overweight (Body Mass Index over 25). The mortality curve for BMI in this range is pretty flat. So eat whatever you want, it’s the quantities you must control.
4. Get some exercise — walking a few miles a week is incredibly much better than no exercise at all — it’s probably half as good as intense workouts — compared to doing nothing.

Not very sexy, but you’re very unlikely to find anyone telling you the opposite 50years from now.

It’s off topic, but I’d use the same degree of skepticism about the dire predictions of the Global Warming (AKA Climate change) people, particularly since there has been no change in global mean temperature this century.

Big Brother is watching you and you’re telling him everything he needs to know (if you’re on Facebook)

Big Brother is watching you and you’re telling him everything he needs to know (if you’re on Facebook). Here’s why. A computer analysis of your ‘likes’ predicts the results of your completing a 100 item personality questionnaire, better than those whom you’ve friended on Facebook. [ Proc.Natl. Acad. Sci. vol. 112 pp. 1036 – 1040 ’15 ] Has the gory details.

We do know that people lie when completing such things and the MMPI (Minnesota Multiphase Personality Inventory) has a scale for lying. Apparently everyone steals from mommy’s purse at some point, and your lie score on the MMPI goes up if you say you never did.

The study used a mere 86,220 volunteers who completed the 100-item International Personality Item Pool (IPIP) Five-Factor Model of personality questionnaire, measuring traits of openness, conscientiousness, extroversion, agreeableness, and neuroticism. The sample used in this study was obtained from the myPersonality project. myPersonality was a popular Facebook application that offered to its users psychometric tests and feedback on their scores. The data was anonymized and is in the public domain. How normal such an individual can be I leave up to you.

Human personality judgments were obtained from the participants’ Facebook friends, who were asked to describe a given participant using 10 of the 100 items of the IPIP personality measure. E.g. the friends were filling out the 10 items as they thought the subject would (or as they saw the subject).

So it’s the same questionnaire. The paper pitted a computer algorithm based on your Likes to predict your IPIP responses against those of your so-called Facebook friends who presumably know much more about you than just your Facebook Likes. The algorithm won. It didn’t win by much. Computer-based judgments (r = 0.56) correlate more strongly with participants’ self-ratings than average human judgements did (r = 0.49). Surprisingly, neither did terribly well, but then we all know that our judgement of ourselves is usually rather different than others. It’s why city people often tell you what they’re ‘really like’, while Montanans don’t. They know that there are so few people around that they’ll see you again. Your long term behavior will tell them everything they need to know.

Update 31 Jan ’15 — I told the people I play piano trios with about the paper. The cellist (a retired Actuary) had an excellent explanation of why the algorithm was more accurate than the friends individually. See if you can think of the reason.

She notes that the 3 of us interact with each other individually, e.g. we act differently for each of our friends, exposing just the parts of our personalities we choose. They aren’t the same for everyone. Obvious, now that she’s thought of it (did you?)

As usual the Poets have said it better

And would some Power the small gift give us
To see ourselves as others see us!
It would from many a blunder free us,
And foolish notion:

Robert Burns (1786)

What a difference a change of administration makes

This is not a scientific post. Having a son who majored in journalism educated me to the various and sundry ways news is slanted. Here in Massachusetts, the administration changed from 8 years of Democratic governance to Republican. Liberals shouldn’t fret as the legislature remains 90% Democratic.

For the past 8 years the local press has been carrying water for increased spending and taxes. We have been regaled with headlines decrying “Draconian cuts” and budget gaps. Such was the case with the outgoing administration, where stories began appearing last December about budget gaps on the order of 700 million. I wrote the reporter asking what this represented in terms of the total budget and never got anything back, ditto for the response from one of the few Republican senators still standing. Throughout the decade I could never get a straight answer as to the actual amount of the budget and the year to year changes in same.

Now we have the following http://www.masslive.com/politics/index.ssf/2015/01/gov_charlie_baker_massachusetts_765_million_budget_gap.html#incart_m-rpt-1, and from the same reporter who never responded last month. Here’s what the reporter was forced to report.

“tax revenues are coming in on target, with an approximately 4.5 percent increase over last year. However, state spending is on target to increase by 7.3 percent“. It will be amusing to see if ‘Draconian cut” stories appear as they have in the past. Mr. Micawber always had a budget gap and so do we.

Along the same lines here’s a heartwarming headline, to disguise an appeal for higher taxes. http://finance.yahoo.com/news/obama-channels-inner-robin-hood-as-rich-get-richer-154533477.html.

Derek Lowe always regrets posting anything remotely political on his blog “In the Pipeline”. Hopefully I won’t. If you must respond, please be civil.

Follow

Get every new post delivered to your Inbox.

Join 75 other followers