nhaliday + meta:medicine   67

Plague of Frogs | West Hunter
For a few years the herpetologists were concerned yet happy. Concerned, because many frog populations were crashing and some were going extinct. Happy, because confused puppies in Washington were giving them money, something that hardly ever happens to frogmen. The theory was that amphibians were ‘canaries in a coal mine’, uniquely sensitive to environmental degradation.

...

It took some time for herpetologists to admit that this chytrid fungus is the main culprit – some are still resisting. First, it was a lot like how doctors resisted Semmelweiss’ discoveries about the cause of puerperal fever – since doctors were the main method of transmission. How did this fungus get to the cloud forests of Costa Rica? On the boots of herpetologists, of course.

The second problem is Occam’s butterknife: even though this chytrid fungus is the main culprit, it’s just got to be more complicated than that. Even if it isn’t. People in the life sciences – biology and medicine – routinely reject simple hypotheses that do a good job of explaining the data for more complex hypotheses that don’t. College taught them to think – unwisely.
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february 2018 by nhaliday
Behaving Discretely: Heuristic Thinking in the Emergency Department
I find compelling evidence of heuristic thinking in this setting: patients arriving in the emergency department just after their 40th birthday are roughly 10% more likely to be tested for and 20% more likely to be diagnosed with ischemic heart disease (IHD) than patients arriving just before this date, despite the fact that the incidence of heart disease increases smoothly with age.

Figure 1: Proportion of ED patients tested for heart attack
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december 2017 by nhaliday
Health Services as Credence Goods: A Field Experiment by Felix Gottschalk, Wanda Mimra, Christian Waibel :: SSRN
A test patient who does not need treatment is sent to 180 dentists to receive treatment recommendations. In the experiment, we vary two factors: First, the information that the patient signals to the dentist. Second, we vary the perceived socioeconomic status (SES) of the test patient. Furthermore, we collected data to construct several measures of short- and long-term demand and competition as well as dentist and practice characteristics. We find that the patient receives an overtreatment recommendation in _more than every fourth visit_. A low short-term demand, indicating excess capacities, leads to significantly more overtreatment recommendations. Physician density and their price level, however, do not have a significant effect on overtreatment. Furthermore, we observe significantly less overtreatment recommendations for the patient with higher SES compared to lower SES under standard information. More signalled information however does not significantly reduce overtreatment.

How much dentists are ethically concerned about overtreatment; a vignette-based survey in Switzerland: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474445/
Are Dentists Overtreating Your Teeth?: https://well.blogs.nytimes.com/2011/11/28/are-dentists-overtreating-your-teeth/
Have you had a rash of fillings after years of healthy teeth? The culprit may be “microcavities,” and not every dentist thinks they need to be treated, reports today’s Science Times.
How Dentists Rip Us Off: https://www.dentistat.com/ReaderDigestArticle.pdf

https://www.npr.org/templates/story/story.php?storyId=130356647
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october 2017 by nhaliday
Evidence-based | West Hunter
The central notion of evidence-based medicine is that our understanding of human biology is imperfect. Some of the idea we come up with for treating and preventing disease are effective, but most are not, worse than useless. So we need careful, rigorous statistical studies before implementing those ideas on a wide scale. A good example of doing this the wrong way was when when doctors started recommending having babies sleep prone, which roughly doubled the incidence of sudden infant death syndrome for the next several decades.

It seems to me that our understanding of psychology, sociology, economics, political science, and education is at least as imperfect as our understanding of biomedicine.

https://westhunt.wordpress.com/2015/01/24/evidence-based/#comment-65904
“Measure twice, cut once” – can’t get much more elitist than that!

Carefully testing innovations on a small scale before widely implementing them is pretty much the opposite of what self-appointed elites have done. Are you deef or something?

https://westhunt.wordpress.com/2015/01/24/evidence-based/#comment-66035
To the extent that they diverge from accepted best practice, physicians, on average, add negative value. I’ve seen this in action, and statistical studies back it up. In other words, Gregory House is a fictional character.
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september 2017 by nhaliday
Of mice and men: why animal trial results don’t always translate to humans
It showed that of the most-cited animal studies in prestigious scientific journals, such as Nature and Cell, only 37% were replicated in subsequent human randomised trials and 18% were contradicted in human trials. It is safe to assume that less-cited animal studies in lesser journals would have an even lower strike rate.
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september 2017 by nhaliday
Of Mice and Men | West Hunter
It’s not always easy figuring out how a pathogen causes disease. There is an example in mice for which the solution was very difficult, so difficult that we would probably have failed to discover the cause of a similarly obscure infectious disease in humans.

Mycoplasma pulmonis causes a chronic obstructive lung disease in mice, but it wasn’t easy to show this. The disease was first described in 1915, and by 1940, people began to suspect Mycoplasma pulmonis might be the cause. But then again, maybe not. It was often found in mice that seemed healthy. Pure cultures of this organism did not consistently produce lung disease – which means that it didn’t satisfy Koch’s postulates, in particular postulate 1 (The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.) and postulate 3 (The cultured microorganism should cause disease when introduced into a healthy organism.).

Well, those postulates are not logic itself, but rather a useful heuristic. Koch knew that, even if lots of other people don’t.

This respiratory disease of mice is long-lasting, but slow to begin. It can take half a lifetime – a mouse lifetime, that is – and that made finding the cause harder. It required patience, which means I certainly couldn’t have done it.

Here’s how they solved it. You can raise germ-free mice. In the early 1970s, researchers injected various candidate pathogens into different groups of germ-free mice and waited to see which, if any, developed this chronic lung disease. It was Mycoplasma pulmonis , all right, but it had taken 60 years to find out.

It turned out that susceptibility differed between different mouse strains – genetic susceptibility was important. Co-infection with other pathogens affected the course of the disease. Microenvironmental details mattered – mainly ammonia in cages where the bedding wasn’t changed often enough. But it didn’t happen without that mycoplasma, which was a key causal link, something every engineer understands but many MDs don’t.

If there was a similarly obscure infectious disease of humans, say one that involved a fairly common bug found in both the just and the unjust, one that took decades for symptoms to manifest – would we have solved it? Probably not.

Cooties are everywhere.

gay germ search: https://westhunt.wordpress.com/2013/07/21/of-mice-and-men/#comment-15905
It’s hard to say, depends on how complicated the path of causation is. Assuming that I’m even right, of course. Some good autopsy studies might be fruitful – you’d look for microanatomical brain differences, as with nartcolepsy. Differences in gene expression, maybe. You could look for a pathogen – using the digital version of RDA (representational difference analysis), say on discordant twins. Do some old-fashioned epidemiology. Look for marker antibodies, signs of some sort of immunological event.

Do all of the above on gay rams – lots easier to get started, much less whining from those being vivisected.

Patrick Moore found the virus causing Kaposi’s sarcoma without any funding at all. I’m sure Peter Thiel could afford a serious try.
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september 2017 by nhaliday
Medicine as a pseudoscience | West Hunter
The idea that venesection was a good thing, or at least not so bad, on the grounds that one in a few hundred people have hemochromatosis (in Northern Europe) reminds me of the people who don’t wear a seatbelt, since it would keep them from being thrown out of their convertible into a waiting haystack, complete with nubile farmer’s daughter. Daughters. It could happen. But it’s not the way to bet.

Back in the good old days, Charles II, age 53, had a fit one Sunday evening, while fondling two of his mistresses.

Monday they bled him (cupping and scarifying) of eight ounces of blood. Followed by an antimony emetic, vitriol in peony water, purgative pills, and a clyster. Followed by another clyster after two hours. Then syrup of blackthorn, more antimony, and rock salt. Next, more laxatives, white hellebore root up the nostrils. Powdered cowslip flowers. More purgatives. Then Spanish Fly. They shaved his head and stuck blistering plasters all over it, plastered the soles of his feet with tar and pigeon-dung, then said good-night.

...

Friday. The king was worse. He tells them not to let poor Nelly starve. They try the Oriental Bezoar Stone, and more bleeding. Dies at noon.

Most people didn’t suffer this kind of problem with doctors, since they never saw one. Charles had six. Now Bach and Handel saw the same eye surgeon, John Taylor – who blinded both of them. Not everyone can put that on his resume!

You may wonder how medicine continued to exist, if it had a negative effect, on the whole. There’s always the placebo effect – at least there would be, if it existed. Any real placebo effect is very small: I’d guess exactly zero. But there is regression to the mean. You see the doctor when you’re feeling worse than average – and afterwards, if he doesn’t kill you outright, you’re likely to feel better. Which would have happened whether you’d seen him or not, but they didn’t often do RCTs back in the day – I think James Lind was the first (1747).

Back in the late 19th century, Christian Scientists did better than others when sick, because they didn’t believe in medicine. For reasons I think mistaken, because Mary Baker Eddy rejected the reality of the entire material world, but hey, it worked. Parenthetically, what triggered all that New Age nonsense in 19th century New England? Hash?

This did not change until fairly recently. Sometime in the early 20th medicine, clinical medicine, what doctors do, hit break-even. Now we can’t do without it. I wonder if there are, or will be, other examples of such a pile of crap turning (mostly) into a real science.

good tweet: https://twitter.com/bowmanthebard/status/897146294191390720
The brilliant GP I've had for 35+ years has retired. How can I find another one who meets my requirements?

1 is overweight
2 drinks more than officially recommended amounts
3 has an amused, tolerant atitude to human failings
4 is well aware that we're all going to die anyway, & there are better or worse ways to die
5 has a healthy skeptical attitude to mainstream medical science
6 is wholly dismissive of "a|ternative” medicine
7 believes in evolution
8 thinks most diseases get better without intervention, & knows the dangers of false positives
9 understands the base rate fallacy

EconPapers: Was Civil War Surgery Effective?: http://econpapers.repec.org/paper/htrhcecon/444.htm
contra Greg Cochran:
To shed light on the subject, I analyze a data set created by Dr. Edmund Andrews, a Civil war surgeon with the 1st Illinois Light Artillery. Dr. Andrews’s data can be rendered into an observational data set on surgical intervention and recovery, with controls for wound location and severity. The data also admits instruments for the surgical decision. My analysis suggests that Civil War surgery was effective, and increased the probability of survival of the typical wounded soldier, with average treatment effect of 0.25-0.28.

Medical Prehistory: https://westhunt.wordpress.com/2016/03/14/medical-prehistory/
What ancient medical treatments worked?

https://westhunt.wordpress.com/2016/03/14/medical-prehistory/#comment-76878
In some very, very limited conditions, bleeding?
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Bad for you 99% of the time.

https://westhunt.wordpress.com/2016/03/14/medical-prehistory/#comment-76947
Colchicine – used to treat gout – discovered by the Ancient Greeks.

https://westhunt.wordpress.com/2016/03/14/medical-prehistory/#comment-76973
Dracunculiasis (Guinea worm)
Wrap the emerging end of the worm around a stick and slowly pull it out.
(3,500 years later, this remains the standard treatment.)
https://en.wikipedia.org/wiki/Ebers_Papyrus

https://westhunt.wordpress.com/2016/03/14/medical-prehistory/#comment-76971
Some of the progress is from formal medicine, most is from civil engineering, better nutrition ( ag science and physical chemistry), less crowded housing.

Nurses vs doctors: https://westhunt.wordpress.com/2014/10/01/nurses-vs-doctors/
Medicine, the things that doctors do, was an ineffective pseudoscience until fairly recently. Until 1800 or so, they were wrong about almost everything. Bleeding, cupping, purging, the four humors – useless. In the 1800s, some began to realize that they were wrong, and became medical nihilists that improved outcomes by doing less. Some patients themselves came to this realization, as when Civil War casualties hid from the surgeons and had better outcomes. Sometime in the early 20th century, MDs reached break-even, and became an increasingly positive influence on human health. As Lewis Thomas said, medicine is the youngest science.

Nursing, on the other hand, has always been useful. Just making sure that a patient is warm and nourished when too sick to take care of himself has helped many survive. In fact, some of the truly crushing epidemics have been greatly exacerbated when there were too few healthy people to take care of the sick.

Nursing must be old, but it can’t have existed forever. Whenever it came into existence, it must have changed the selective forces acting on the human immune system. Before nursing, being sufficiently incapacitated would have been uniformly fatal – afterwards, immune responses that involved a period of incapacitation (with eventual recovery) could have been selectively favored.

when MDs broke even: https://westhunt.wordpress.com/2014/10/01/nurses-vs-doctors/#comment-58981
I’d guess the 1930s. Lewis Thomas thought that he was living through big changes. They had a working serum therapy for lobar pneumonia ( antibody-based). They had many new vaccines ( diphtheria in 1923, whopping cough in 1926, BCG and tetanus in 1927, yellow fever in 1935, typhus in 1937.) Vitamins had been mostly worked out. Insulin was discovered in 1929. Blood transfusions. The sulfa drugs, first broad-spectrum antibiotics, showed up in 1935.

DALYs per doctor: https://westhunt.wordpress.com/2018/01/22/dalys-per-doctor/
The disability-adjusted life year (DALY) is a measure of overall disease burden – the number of years lost. I’m wondering just much harm premodern medicine did, per doctor. How many healthy years of life did a typical doctor destroy (net) in past times?

...

It looks as if the average doctor (in Western medicine) killed a bunch of people over his career ( when contrasted with doing nothing). In the Charles Manson class.

Eventually the market saw through this illusion. Only took a couple of thousand years.

https://westhunt.wordpress.com/2018/01/22/dalys-per-doctor/#comment-100741
That a very large part of healthcare spending is done for non-health reasons. He has a chapter on this in his new book, also check out his paper “Showing That You Care: The Evolution of Health Altruism” http://mason.gmu.edu/~rhanson/showcare.pdf
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I ran into too much stupidity to finish the article. Hanson’s a loon. For example when he talks about the paradox of blacks being more sentenced on drug offenses than whites although they use drugs at similar rate. No paradox: guys go to the big house for dealing, not for using. Where does he live – Mars?

I had the same reaction when Hanson parroted some dipshit anthropologist arguing that the stupid things people do while drunk are due to social expectations, not really the alcohol.
Horseshit.

I don’t think that being totally unable to understand everybody around you necessarily leads to deep insights.

https://westhunt.wordpress.com/2018/01/22/dalys-per-doctor/#comment-100744
What I’ve wondered is if there was anything that doctors did that actually was helpful and if perhaps that little bit of success helped them fool people into thinking the rest of it helped.
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Setting bones. extracting arrows: spoon of Diocles. Colchicine for gout. Extracting the Guinea worm. Sometimes they got away with removing the stone. There must be others.
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Quinine is relatively recent: post-1500. Obstetrical forceps also. Caesarean deliveries were almost always fatal to the mother until fairly recently.

Opium has been around for a long while : it works.

https://westhunt.wordpress.com/2018/01/22/dalys-per-doctor/#comment-100839
If pre-modern medicine was indeed worse than useless – how do you explain no one noticing that patients who get expensive treatments are worse off than those who didn’t?
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were worse off. People are kinda dumb – you’ve noticed?
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My impression is that while people may be “kinda dumb”, ancient customs typically aren’t.
Even if we assume that all people who lived prior to the 19th century were too dumb to make the rational observation, wouldn’t you expect this ancient practice to be subject to selective pressure?
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Your impression is wrong. Do you think that there some slick reason for Carthaginians incinerating their first-born?

Theodoric of York, bloodletting: https://www.youtube.com/watch?v=yvff3TViXmY

details on blood-letting and hemochromatosis: https://westhunt.wordpress.com/2018/01/22/dalys-per-doctor/#comment-100746

Starting Over: https://westhunt.wordpress.com/2018/01/23/starting-over/
Looking back on it, human health would have … [more]
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august 2017 by nhaliday
Low-Hanging Fruit: Nyekulturny | West Hunter
The methodology is what’s really interesting.  Kim Lewis and Slava Epstein sorted individual soil bacteria into chambers of a device they call the iChip, which is then buried in the ground – the point being that something like 98% of soil bacteria cannot be cultured in standard media, while in this approach, key compounds (whatever they are) can diffuse in from the soil, allowing something like 50% of soil bacteria species to grow.  They then tested the bacterial colonies (10,000 of them) to see if any slammed S. aureus – and some did.

...

I could be wrong, but I wonder if part of the explanation is that microbiology – the subject – is in relative decline, suffering because of funding and status competition with molecular biology and genomics (sexier and less useful than microbiology) . That and the fact that big pharma is not enthusiastic about biological products.
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july 2017 by nhaliday
Vioxx | West Hunter
The Vigor study was submitted in February 2001. The New England Journal of Medicine, a few months later, found that the authors had failed to mention some strokes and heart attacks near the end of the trial. The authors used a cutoff for cardiovascular effects (bad news) that was earlier than the cutoff for gastrointestinal effects (good news). why? Because they were weasels, of course. There was a lot of money riding on this drug’s success.

Other people began to notice the increased heart risks – looking at data from HMOs and such. Merck fought back. There was an MD at Stanford that was concerned about Vioxx: Merck called up the dean of Stanford Medical School at home and warned him about possible loss of financial support: he told them to go fuck themselves.

...

Now it is true that there were studies that showed greater efficacy: 21 such were reported by Scott S. Reuben, former chief of acute pain at Baystate medical Center in Springfield Mass. But as it turns out, he made them all up. There’s is no evidence that Merck knew about this, but it does perhaps say something about the general climate in big pharma.

Merck knew the gist of this for four years before they pulled the plug on the drug. They had their their drug reps lie about cardio risks, threatened researchers and sued journals that talked about the emerging cardio risks. Few physicians were aware of these risks, even though a close reading of the journals would have suggested it – because hardly any physicians read the journals.

Epidemiologists think that Vioxx caused something like 40,000 deaths.

...

In the 70s corporations were the bad guys, whether they were or not. Today, billionaires are your friend.
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july 2017 by nhaliday
Alzheimers | West Hunter
Some disease syndromes almost have to be caused by pathogens – for example, any with a fitness impact (prevalence x fitness reduction) > 2% or so, too big to be caused by mutational pressure. I don’t think that this is the case for AD: it hits so late in life that the fitness impact is minimal. However, that hardly means that it can’t be caused by a pathogen or pathogens – a big fraction of all disease syndromes are, including many that strike in old age. That possibility is always worth checking out, not least because infectious diseases are generally easier to prevent and/or treat.

There is new work that strongly suggests that pathogens are the root cause. It appears that the amyloid is an antimicrobial peptide. amyloid-beta binds to invading microbes and then surrounds and entraps them. ‘When researchers injected Salmonella into mice’s hippocampi, a brain area damaged in Alzheimer’s, A-beta quickly sprang into action. It swarmed the bugs and formed aggregates called fibrils and plaques. “Overnight you see the plaques throughout the hippocampus where the bugs were, and then in each single plaque is a single bacterium,” Tanzi says. ‘

obesity and pathogens: https://westhunt.wordpress.com/2016/05/29/alzheimers/#comment-79757
not sure about this guy, but interesting: https://westhunt.wordpress.com/2016/05/29/alzheimers/#comment-79748
http://perfecthealthdiet.com/2010/06/is-alzheimer%E2%80%99s-caused-by-a-bacterial-infection-of-the-brain/

https://westhunt.wordpress.com/2016/12/13/the-twelfth-battle-of-the-isonzo/
All too often we see large, long-lasting research efforts that never produce, never achieve their goal.

For example, the amyloid hypothesis [accumulation of amyloid-beta oligomers is the cause of Alzheimers] has been dominant for more than 20 years, and has driven development of something like 15 drugs. None of them have worked. At the same time the well-known increased risk from APOe4 has been almost entirely ignored, even though it ought to be a clue to the cause.

In general, when a research effort has been spinning its wheels for a generation or more, shouldn’t we try something different? We could at least try putting a fraction of those research dollars into alternative approaches that have not yet failed repeatedly.

Mostly this applies to research efforts that at least wish they were science. ‘educational research’ is in a special class, and I hardly know what to recommend. Most of the remedial actions that occur to me violate one or more of the Geneva conventions.

APOe4 related to lymphatic system: https://en.wikipedia.org/wiki/Apolipoprotein_E

https://westhunt.wordpress.com/2012/03/06/spontaneous-generation/#comment-2236
Look,if I could find out the sort of places that I usually misplace my keys – if I did, which I don’t – I could find the keys more easily the next time I lose them. If you find out that practitioners of a given field are not very competent, it marks that field as a likely place to look for relatively easy discovery. Thus medicine is a promising field, because on the whole doctors are not terribly good investigators. For example, none of the drugs developed for Alzheimers have worked at all, which suggests that our ideas on the causation of Alzheimers are likely wrong. Which suggests that it may (repeat may) be possible to make good progress on Alzheimers, either by an entirely empirical approach, which is way underrated nowadays, or by dumping the current explanation, finding a better one, and applying it.

You could start by looking at basic notions of field X and asking yourself: How do we really know that? Is there serious statistical evidence? Does that notion even accord with basic theory? This sort of checking is entirely possible. In most of the social sciences, we don’t, there isn’t, and it doesn’t.

Hygiene and the world distribution of Alzheimer’s disease: Epidemiological evidence for a relationship between microbial environment and age-adjusted disease burden: https://academic.oup.com/emph/article/2013/1/173/1861845/Hygiene-and-the-world-distribution-of-Alzheimer-s

Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease: http://stm.sciencemag.org/content/8/340/340ra72

Fungus, the bogeyman: http://www.economist.com/news/science-and-technology/21676754-curious-result-hints-possibility-dementia-caused-fungal
Fungus and dementia
paper: http://www.nature.com/articles/srep15015

Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors: https://advances.sciencemag.org/content/5/1/eaau3333
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july 2017 by nhaliday
Genomic analysis of family data reveals additional genetic effects on intelligence and personality | bioRxiv
methodology:
Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003520
Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005804

Missing Heritability – found?: https://westhunt.wordpress.com/2017/02/09/missing-heritability-found/
There is an interesting new paper out on genetics and IQ. The claim is that they have found the missing heritability – in rare variants, generally different in each family.

Some of the variants, the ones we find with GWAS, are fairly common and fitness-neutral: the variant that slightly increases IQ confers the same fitness (or very close to the same) as the one that slightly decreases IQ – presumably because of other effects it has. If this weren’t the case, it would be impossible for both of the variants to remain common.

The rare variants that affect IQ will generally decrease IQ – and since pleiotropy is the norm, usually they’ll be deleterious in other ways as well. Genetic load.

Happy families are all alike; every unhappy family is unhappy in its own way.: https://westhunt.wordpress.com/2017/06/06/happy-families-are-all-alike-every-unhappy-family-is-unhappy-in-its-own-way/
It now looks as if the majority of the genetic variance in IQ is the product of mutational load, and the same may be true for many psychological traits. To the extent this is the case, a lot of human psychological variation must be non-adaptive. Maybe some personality variation fulfills an evolutionary function, but a lot does not. Being a dumb asshole may be a bug, rather than a feature. More generally, this kind of analysis could show us whether particular low-fitness syndromes, like autism, were ever strategies – I suspect not.

It’s bad new news for medicine and psychiatry, though. It would suggest that what we call a given type of mental illness, like schizophrenia, is really a grab-bag of many different syndromes. The ultimate causes are extremely varied: at best, there may be shared intermediate causal factors. Not good news for drug development: individualized medicine is a threat, not a promise.

see also comment at: https://pinboard.in/u:nhaliday/b:a6ab4034b0d0

https://www.reddit.com/r/slatestarcodex/comments/5sldfa/genomic_analysis_of_family_data_reveals/
So the big implication here is that it's better than I had dared hope - like Yang/Visscher/Hsu have argued, the old GCTA estimate of ~0.3 is indeed a rather loose lower bound on additive genetic variants, and the rest of the missing heritability is just the relatively uncommon additive variants (ie <1% frequency), and so, like Yang demonstrated with height, using much more comprehensive imputation of SNP scores or using whole-genomes will be able to explain almost all of the genetic contribution. In other words, with better imputation panels, we can go back and squeeze out better polygenic scores from old GWASes, new GWASes will be able to reach and break the 0.3 upper bound, and eventually we can feasibly predict 0.5-0.8. Between the expanding sample sizes from biobanks, the still-falling price of whole genomes, the gradual development of better regression methods (informative priors, biological annotation information, networks, genetic correlations), and better imputation, the future of GWAS polygenic scores is bright. Which obviously will be extremely helpful for embryo selection/genome synthesis.

The argument that this supports mutation-selection balance is weaker but plausible. I hope that it's true, because if that's why there is so much genetic variation in intelligence, then that strongly encourages genetic engineering - there is no good reason or Chesterton fence for intelligence variants being non-fixed, it's just that evolution is too slow to purge the constantly-accumulating bad variants. And we can do better.
https://rubenarslan.github.io/generation_scotland_pedigree_gcta/

The surprising implications of familial association in disease risk: https://arxiv.org/abs/1707.00014
https://spottedtoad.wordpress.com/2017/06/09/personalized-medicine-wont-work-but-race-based-medicine-probably-will/
As Greg Cochran has pointed out, this probably isn’t going to work. There are a few genes like BRCA1 (which makes you more likely to get breast and ovarian cancer) that we can detect and might affect treatment, but an awful lot of disease turns out to be just the result of random chance and deleterious mutation. This means that you can’t easily tailor disease treatment to people’s genes, because everybody is fucked up in their own special way. If Johnny is schizophrenic because of 100 random errors in the genes that code for his neurons, and Jack is schizophrenic because of 100 other random errors, there’s very little way to test a drug to work for either of them- they’re the only one in the world, most likely, with that specific pattern of errors. This is, presumably why the incidence of schizophrenia and autism rises in populations when dads get older- more random errors in sperm formation mean more random errors in the baby’s genes, and more things that go wrong down the line.

The looming crisis in human genetics: http://www.economist.com/node/14742737
Some awkward news ahead
- Geoffrey Miller

Human geneticists have reached a private crisis of conscience, and it will become public knowledge in 2010. The crisis has depressing health implications and alarming political ones. In a nutshell: the new genetics will reveal much less than hoped about how to cure disease, and much more than feared about human evolution and inequality, including genetic differences between classes, ethnicities and races.

2009!
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june 2017 by nhaliday
Is Pharma Research Worse Than Chance? | Slate Star Codex
Here’s one hypothesis: at the highest level, the brain doesn’t have that many variables to affect, or all the variables are connected. If you smack the brain really really hard in some direction or other, you will probably treat some psychiatric disease. Drugs of abuse are ones that smack the brain really hard in some direction or other. They do something. So find the psychiatric illness that’s treated by smacking the brain in that direction, and you’re good.

Actual carefully-researched psychiatric drugs are exquisitely selected for having few side effects. The goal is something like an SSRI – mild stomach discomfort, some problems having sex, but overall you can be on them forever and barely notice their existence. In the grand scheme of things their side effects are tiny – in most placebo-controlled studies, people have a really hard time telling whether they’re in the experimental or the placebo group.

...

But given that we’re all very excited to learn about ketamine and MDMA, and given that if their original promise survives further testing we will consider them great discoveries, it suggests we chose the wrong part of the tradeoff curve. Or at least it suggests a different way of framing that tradeoff curve. A drug that makes you feel extreme side effects for a few hours – but also has very strong and lasting treatment effects – is better than a drug with few side effects and weaker treatment effects. That suggests a new direction pharmaceutical companies might take: look for the chemicals that have the strongest and wackiest effects on the human mind. Then see if any of them also treat some disease.

I think this is impossible with current incentives. There’s too little risk-tolerance at every stage in the system. But if everyone rallied around the idea, it might be that trying the top hundred craziest things Alexander Shulgin dreamed up on whatever your rat model is would be orders of magnitude more productive than whatever people are doing now.
ratty  yvain  ssc  reflection  psychiatry  medicine  pharma  drugs  error  efficiency  random  meta:medicine  flexibility  outcome-risk  incentives  stagnation  innovation  low-hanging  tradeoffs  realness  perturbation  degrees-of-freedom  volo-avolo  null-result 
june 2017 by nhaliday
I hate every ape I see | West Hunter
Chimpanzees, although expensive, are really useful for medical research, since they’re much closer to humans than any other experimental animal. Yet the Feds are phasing out chimp research, and are sending them off to Club Chimp. Francis Collins, director of NIH, says that “new scientific methods and technologies have rendered their use in research largely unnecessary.” Collins is full of crap, as usual.
west-hunter  scitariat  rant  ideas  science  medicine  model-organism  meta:medicine  realness  westminster  kumbaya-kult  is-ought  people  track-record  commentary  current-events  ethics 
may 2017 by nhaliday
Germ theory of disease - Wikipedia
The germ theory was proposed by Girolamo Fracastoro in 1546, and expanded upon by Marcus von Plenciz in 1762. Such views were held in disdain, however, and Galen's miasma theory remained dominant among scientists and doctors. The nature of this doctrine prevented them from understanding how diseases actually progressed, with predictable consequences. By the early nineteenth century, smallpox vaccination was commonplace in Europe, though doctors were unaware of how it worked or how to extend the principle to other diseases. Similar treatments had been prevalent in India from just before 1000 A.D.[2] [N 1] A transitional period began in the late 1850s as the work of Louis Pasteur and Robert Koch provided convincing evidence; by 1880, miasma theory was struggling to compete with the germ theory of disease. Eventually, a "golden era" of bacteriology ensued, in which the theory quickly led to the identification of the actual organisms that cause many diseases.[3][4] Viruses were discovered in the 1890s.
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may 2017 by nhaliday
Interview: Mostly Sealing Wax | West Hunter
https://soundcloud.com/user-519115521/greg-cochran-part-2
https://medium.com/@houstoneuler/annotating-part-2-of-the-greg-cochran-interview-with-james-miller-678ba33f74fc

- conformity and Google, defense and spying (China knows prob almost all our "secrets")
- in the past you could just find new things faster than people could reverse-engineer. part of the problem is that innovation is slowing down today (part of the reason for convergence by China/developing world).
- introgression from archaics of various kinds
- mutational load and IQ, wrath of khan neanderthal
- trade and antiquity (not that useful besides ideas tbh), Roman empire, disease, smallpox
- spices needed to be grown elsewhere, but besides that...
- analogy: caste system in India (why no Brahmin car repairmen?), slavery in Greco-Roman times, more water mills in medieval times (rivers better in north, but still could have done it), new elite not liking getting hands dirty, low status of engineers, rise of finance
- crookery in finance, hedge fund edge might be substantially insider trading
- long-term wisdom of moving all manufacturing to China...?
- economic myopia: British financialization before WW1 vis-a-vis Germany. North vs. South and cotton/industry, camels in Middle East vs. wagons in Europe
- Western medicine easier to convert to science than Eastern, pseudoscience and wrong theories better than bag of recipes
- Greeks definitely knew some things that were lost (eg, line in Pliny makes reference to combinatorics calculation rediscovered by German dude much later. think he's referring to Catalan numbers?), Lucio Russo book
- Indo-Europeans, Western Europe, Amerindians, India, British Isles, gender, disease, and conquest
- no farming (Dark Age), then why were people still farming on Shetland Islands north of Scotland?
- "symbolic" walls, bodies with arrows
- family stuff, children learning, talking dog, memory and aging
- Chinese/Japanese writing difficulty and children learning to read
- Hatfield-McCoy feud: the McCoy family was actually a case study in a neurological journal. they had anger management issues because of cancers of their adrenal gland (!!).

the Chinese know...: https://macropolo.org/casting-off-real-beijings-cryptic-warnings-finance-taking-economy/
Over the last couple of years, a cryptic idiom has crept into the way China’s top leaders talk about risks in the country’s financial system: tuo shi xiang xu (脱实向虚), which loosely translates as “casting off the real for the empty.” Premier Li Keqiang warned against it at his press conference at the end of the 2016 National People’s Congress (NPC). At this year’s NPC, Li inserted this very expression into his annual work report. And in April, while on an inspection tour of Guangxi, President Xi Jinping used the term, saying that China must “unceasingly promote industrial modernization, raise the level of manufacturing, and not allow the real to be cast off for the empty.”

Such an odd turn of phrase is easy to overlook, but it belies concerns about a significant shift in the way that China’s economy works. What Xi and Li were warning against is typically called financialization in developed economies. It’s when “real” companies—industrial firms, manufacturers, utility companies, property developers, and anyone else that produces a tangible product or service—take their money and, rather than put it back into their businesses, invest it in “empty”, or speculative, assets. It occurs when the returns on financial investments outstrip those in the real economy, leading to a disproportionate amount of money being routed into the financial system.

https://twitter.com/gcochran99/status/1160589827651203073
https://archive.is/Yzjyv
Bad day for Lehman Bros.
--
Good day for everyone else, then.
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may 2017 by nhaliday
Low-Hanging Poop | West Hunter
Obviously, sheer disgust made it hard for doctors to embrace this treatment.  There’s a lesson here: in the search for low-hanging fruit,  reconsider approaches that are embarrassing, or offensive, or downright disgusting.
west-hunter  scitariat  stories  discussion  medicine  meta:medicine  being-right  info-dynamics  epistemic  emotion  sanctity-degradation  education  low-hanging  error  bounded-cognition  embodied  policy  ideas  the-trenches  alt-inst  innovation  discovery  prioritizing  arbitrage  judgement 
may 2017 by nhaliday
Vavilovian mimicry - Wikipedia
Rye started out as a weed
https://westhunt.wordpress.com/2014/07/23/secondary-crops/
It seems to me that there may be some social parallels: bandits turning into governments, alchemists into chemists, Galenic doctors into almost-scientific medicine.
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april 2017 by nhaliday
Educational Romanticism & Economic Development | pseudoerasmus
https://twitter.com/GarettJones/status/852339296358940672
deleeted

https://twitter.com/GarettJones/status/943238170312929280
https://archive.is/p5hRA

Did Nations that Boosted Education Grow Faster?: http://econlog.econlib.org/archives/2012/10/did_nations_tha.html
On average, no relationship. The trendline points down slightly, but for the time being let's just call it a draw. It's a well-known fact that countries that started the 1960's with high education levels grew faster (example), but this graph is about something different. This graph shows that countries that increased their education levels did not grow faster.

Where has all the education gone?: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1016.2704&rep=rep1&type=pdf

https://twitter.com/GarettJones/status/948052794681966593
https://archive.is/kjxqp

https://twitter.com/GarettJones/status/950952412503822337
https://archive.is/3YPic

https://twitter.com/pseudoerasmus/status/862961420065001472
http://hanushek.stanford.edu/publications/schooling-educational-achievement-and-latin-american-growth-puzzle

The Case Against Education: What's Taking So Long, Bryan Caplan: http://econlog.econlib.org/archives/2015/03/the_case_agains_9.html

The World Might Be Better Off Without College for Everyone: https://www.theatlantic.com/magazine/archive/2018/01/whats-college-good-for/546590/
Students don't seem to be getting much out of higher education.
- Bryan Caplan

College: Capital or Signal?: http://www.economicmanblog.com/2017/02/25/college-capital-or-signal/
After his review of the literature, Caplan concludes that roughly 80% of the earnings effect from college comes from signalling, with only 20% the result of skill building. Put this together with his earlier observations about the private returns to college education, along with its exploding cost, and Caplan thinks that the social returns are negative. The policy implications of this will come as very bitter medicine for friends of Bernie Sanders.

Doubting the Null Hypothesis: http://www.arnoldkling.com/blog/doubting-the-null-hypothesis/

Is higher education/college in the US more about skill-building or about signaling?: https://www.quora.com/Is-higher-education-college-in-the-US-more-about-skill-building-or-about-signaling
ballpark: 50% signaling, 30% selection, 20% addition to human capital
more signaling in art history, more human capital in engineering, more selection in philosophy

Econ Duel! Is Education Signaling or Skill Building?: http://marginalrevolution.com/marginalrevolution/2016/03/econ-duel-is-education-signaling-or-skill-building.html
Marginal Revolution University has a brand new feature, Econ Duel! Our first Econ Duel features Tyler and me debating the question, Is education more about signaling or skill building?

Against Tulip Subsidies: https://slatestarcodex.com/2015/06/06/against-tulip-subsidies/

https://www.overcomingbias.com/2018/01/read-the-case-against-education.html

https://nintil.com/2018/02/05/notes-on-the-case-against-education/

https://www.nationalreview.com/magazine/2018-02-19-0000/bryan-caplan-case-against-education-review

https://spottedtoad.wordpress.com/2018/02/12/the-case-against-education/
Most American public school kids are low-income; about half are non-white; most are fairly low skilled academically. For most American kids, the majority of the waking hours they spend not engaged with electronic media are at school; the majority of their in-person relationships are at school; the most important relationships they have with an adult who is not their parent is with their teacher. For their parents, the most important in-person source of community is also their kids’ school. Young people need adult mirrors, models, mentors, and in an earlier era these might have been provided by extended families, but in our own era this all falls upon schools.

Caplan gestures towards work and earlier labor force participation as alternatives to school for many if not all kids. And I empathize: the years that I would point to as making me who I am were ones where I was working, not studying. But they were years spent working in schools, as a teacher or assistant. If schools did not exist, is there an alternative that we genuinely believe would arise to draw young people into the life of their community?

...

It is not an accident that the state that spends the least on education is Utah, where the LDS church can take up some of the slack for schools, while next door Wyoming spends almost the most of any state at $16,000 per student. Education is now the one surviving binding principle of the society as a whole, the one black box everyone will agree to, and so while you can press for less subsidization of education by government, and for privatization of costs, as Caplan does, there’s really nothing people can substitute for it. This is partially about signaling, sure, but it’s also because outside of schools and a few religious enclaves our society is but a darkling plain beset by winds.

This doesn’t mean that we should leave Caplan’s critique on the shelf. Much of education is focused on an insane, zero-sum race for finite rewards. Much of schooling does push kids, parents, schools, and school systems towards a solution ad absurdum, where anything less than 100 percent of kids headed to a doctorate and the big coding job in the sky is a sign of failure of everyone concerned.

But let’s approach this with an eye towards the limits of the possible and the reality of diminishing returns.

https://westhunt.wordpress.com/2018/01/27/poison-ivy-halls/
https://westhunt.wordpress.com/2018/01/27/poison-ivy-halls/#comment-101293
The real reason the left would support Moander: the usual reason. because he’s an enemy.

https://westhunt.wordpress.com/2018/02/01/bright-college-days-part-i/
I have a problem in thinking about education, since my preferences and personal educational experience are atypical, so I can’t just gut it out. On the other hand, knowing that puts me ahead of a lot of people that seem convinced that all real people, including all Arab cabdrivers, think and feel just as they do.

One important fact, relevant to this review. I don’t like Caplan. I think he doesn’t understand – can’t understand – human nature, and although that sometimes confers a different and interesting perspective, it’s not a royal road to truth. Nor would I want to share a foxhole with him: I don’t trust him. So if I say that I agree with some parts of this book, you should believe me.

...

Caplan doesn’t talk about possible ways of improving knowledge acquisition and retention. Maybe he thinks that’s impossible, and he may be right, at least within a conventional universe of possibilities. That’s a bit outside of his thesis, anyhow. Me it interests.

He dismisses objections from educational psychologists who claim that studying a subject improves you in subtle ways even after you forget all of it. I too find that hard to believe. On the other hand, it looks to me as if poorly-digested fragments of information picked up in college have some effect on public policy later in life: it is no coincidence that most prominent people in public life (at a given moment) share a lot of the same ideas. People are vaguely remembering the same crap from the same sources, or related sources. It’s correlated crap, which has a much stronger effect than random crap.

These widespread new ideas are usually wrong. They come from somewhere – in part, from higher education. Along this line, Caplan thinks that college has only a weak ideological effect on students. I don’t believe he is correct. In part, this is because most people use a shifting standard: what’s liberal or conservative gets redefined over time. At any given time a population is roughly half left and half right – but the content of those labels changes a lot. There’s a shift.

https://westhunt.wordpress.com/2018/02/01/bright-college-days-part-i/#comment-101492
I put it this way, a while ago: “When you think about it, falsehoods, stupid crap, make the best group identifiers, because anyone might agree with you when you’re obviously right. Signing up to clear nonsense is a better test of group loyalty. A true friend is with you when you’re wrong. Ideally, not just wrong, but barking mad, rolling around in your own vomit wrong.”
--
You just explained the Credo quia absurdum doctrine. I always wondered if it was nonsense. It is not.
--
Someone on twitter caught it first – got all the way to “sliding down the razor blade of life”. Which I explained is now called “transitioning”

What Catholics believe: https://theweek.com/articles/781925/what-catholics-believe
We believe all of these things, fantastical as they may sound, and we believe them for what we consider good reasons, well attested by history, consistent with the most exacting standards of logic. We will profess them in this place of wrath and tears until the extraordinary event referenced above, for which men and women have hoped and prayed for nearly 2,000 years, comes to pass.

https://westhunt.wordpress.com/2018/02/05/bright-college-days-part-ii/
According to Caplan, employers are looking for conformity, conscientiousness, and intelligence. They use completion of high school, or completion of college as a sign of conformity and conscientiousness. College certainly looks as if it’s mostly signaling, and it’s hugely expensive signaling, in terms of college costs and foregone earnings.

But inserting conformity into the merit function is tricky: things become important signals… because they’re important signals. Otherwise useful actions are contraindicated because they’re “not done”. For example, test scores convey useful information. They could help show that an applicant is smart even though he attended a mediocre school – the same role they play in college admissions. But employers seldom request test scores, and although applicants may provide them, few do. Caplan says ” The word on the street… [more]
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april 2017 by nhaliday
Disaster in the South Pacific | West Hunter
Washington didn’t micro-manage American Samoa, not being all that interested. A policy of benign neglect was interpreted by Poyer as an opportunity to act on his best judgment, in the finest traditions of the US Navy. He imposed quarantine. That was harder that it sounds, because of the frequent family visits between West Samoa and American Samoa – but Poyer also had the support of the local chiefs, who understood how serious imported epidemics could be. The people of American Samoa self-blockaded, on top of official quarantine: they sent out canoes to stop any and all visitors. They never had a single case.

Of course there was a disaster. Some people will think that it occurred in West Samoa. Others will think that the real disaster was in American Samoa.
west-hunter  scitariat  history  mostly-modern  usa  anglo  world  developing-world  asia  stories  being-right  disease  parasites-microbiome  epidemiology  government  leadership  medicine  authoritarianism  info-dynamics  public-health  meta:medicine  prudence  statesmen  antidemos  alt-inst  spreading  organizing  decentralized  anglosphere  management 
april 2017 by nhaliday
Placebo interventions for all clinical conditions. - PubMed - NCBI
We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.

How much of the placebo 'effect' is really statistical regression?: https://www.ncbi.nlm.nih.gov/pubmed/6369471
Statistical regression to the mean predicts that patients selected for abnormalcy will, on the average, tend to improve. We argue that most improvements attributed to the placebo effect are actually instances of statistical regression. First, whereas older clinical trials susceptible to regression resulted in a marked improvement in placebo-treated patients, in a modern series of clinical trials whose design tended to protect against regression, we found no significant improvement (median change 0.3 per cent, p greater than 0.05) in placebo-treated patients.

Placebo effects are weak: regression to the mean is the main reason ineffective treatments appear to work: http://www.dcscience.net/2015/12/11/placebo-effects-are-weak-regression-to-the-mean-is-the-main-reason-ineffective-treatments-appear-to-work/

A radical new hypothesis in medicine: give patients drugs they know don’t work: https://www.vox.com/science-and-health/2017/6/1/15711814/open-label-placebo-kaptchuk
People on no treatment got about 30 percent better. And people who were given an open-label placebo got 60 percent improvement in the adequate relief of their irritable bowel syndrome.

Surgery Is One Hell Of A Placebo: https://fivethirtyeight.com/features/surgery-is-one-hell-of-a-placebo/
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march 2017 by nhaliday
I Want a New Drug | West Hunter
Big pharma has taken a new course over the past few years. In the past, most useful drugs originated in some kind of living organism – penicillin, quinine, insulin, etc etc. Nowadays, big pharmaceutical companies use combinatorial chemistry and computer modeling. Merck has sold off its biological-products research arm. This new approach, combined with doubled spending on drug R&D, has been a resounding failure. The rate of development of fundamentally new drugs – ‘new molecular entities’ – is running about 40% of that seen in the 1970s. Since big pharma makes its money from drugs that are still on patent, this slowed innovation is a real threat to their bottom line.

...

I think that this is an instance of a more general trend: often a modern, advanced approach shows up, and it persists long after it’s been shown to be a miserable failure. You can see some of the reasons why: the people trained in the new technique would lose out if it were abandoned. Hard to imagine combinatorial chemists rooting around in a garbage can looking for moldy fruit.
west-hunter  discussion  pharma  medicine  FDA  randy-ayndy  regularizer  critique  minimalism  bio  nature  low-hanging  drugs  error  scitariat  info-dynamics  innovation  ideas  discovery  meta:medicine  stagnation  parasites-microbiome  the-trenches  alt-inst  dirty-hands  regulation  civil-liberty  proposal  corporation  fashun  prioritizing 
february 2017 by nhaliday
INFECTIOUS CAUSATION OF DISEASE: AN EVOLUTIONARY PERSPECTIVE
A New Germ Theory: https://www.theatlantic.com/magazine/archive/1999/02/a-new-germ-theory/377430/
The dictates of evolution virtually demand that the causes of some of humanity's chronic and most baffling "noninfectious" illnesses will turn out to be pathogens -- that is the radical view of a prominent evolutionary biologist

A LATE-SEPTEMBER heat wave enveloped Amherst College, and young people milled about in shorts or sleeveless summer frocks, or read books on the grass. Inside the red-brick buildings framing the leafy quadrangle students listened to lectures on Ellison and Emerson, on Paul Verlaine and the Holy Roman Empire. Few suspected that strains of the organism that causes cholera were growing nearby, in the Life Sciences Building. If they had known, they would probably not have grasped the implications. But these particular strains of cholera make Paul Ewald smile; they are strong evidence that he is on the right track. Knowing the rules of evolutionary biology, he believes, can change the course of infectious disease.

https://www.theatlantic.com/past/docs/issues/99feb/germ2.htm
I HAVE a motto," Gregory Cochran told me recently. "'Big old diseases are infectious.' If it's common, higher than one in a thousand, I get suspicious. And if it's old, if it has been around for a while, I get suspicious."

https://www.theatlantic.com/past/docs/issues/99feb/germ3.htm
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february 2017 by nhaliday
Gundeshapur | West Hunter
Some of the more useful drugs are a product of “traditional medicine”. Colchicine for gout, digitalis, aspirin. The best current drug for falciparum malaria is the result of project 523, where the PLA (at the request of Ho Chi Minh) had people dig through old Chinese herbal manuals. Communism and Taoist magic – the royal road to drug development. Tu Youyou received the Nobel prize for this work in 2015; truly, there are other ways of knowing
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january 2017 by nhaliday
The Experts | West Hunter
It seems to me that not all people called experts actually are. In fact, there are whole fields in which none of the experts are experts. But let’s try to define terms.

...

Along these lines, I’ve read Tetlock’s book, Expert Political Judgment. A funny, funny, book. I will have more to say on that later.

USSR: https://westhunt.wordpress.com/2014/10/20/the-experts/#comment-60760
iraq war:
https://westhunt.wordpress.com/2014/10/20/the-experts/#comment-60653
Of course it is how Bush sold the war. Selling the war involving statements to the press, leaks, etc, not a Congressional resolution, which is the product of that selling job. Leaks to that lying slut at the New York Times, Judith Miller, for example.

Actively seeking a nuclear weapons capacity would have meant making fissionables, or building facilities to make fissionables. That hadn’t happened, and it was impossible for Iraq to have done so, given that any such effort had to be undetectable (because we hadn’t detected it with our ‘national technical means’, spy satellites and such) and given their limited resources in men, money, and materiel. Iraq had done nothing along these lines. Absolutely nothing.

https://westhunt.wordpress.com/2014/10/20/the-experts/#comment-60674
You don’t even know what yellow cake is. It is true that Saddam had had a nuclear program before the Gulf War, although it had not come too close to a weapon – but that program had been destroyed, and could not be rebuilt A. in a way invisible to our spy satellites and B with no money, because of sanctions.

The 550 tons of uranium oxide- unenriched uranium oxide – was a leftover from the earlier program. Under UN seal, and those seals had not been broken. Without enrichment, and without a means of enrichment, it was useless.

What’s the point of pushing this nonsense? somebody paying you?

The President was a moron, the Government of the United States proved itself a pack of fools,as did the New York Times, the Washington Post, Congress, virtually all of the pundits, etc. etc. And undoubtedly you were a fool as well: you might as well deal with it, because the truth is not going to go away.

interesting discussion of battle fatigue and desertion: https://westhunt.wordpress.com/2014/10/20/the-experts/#comment-60709
Actually, I don’t know how Freudian those Army psychologists were in 1944: they may have been useless in some other way. The gist is that in the European theater, for example in the Normandy campaign, the US had a much higher rate of psychological casualties than the Germans. “Both British and American psychiatrists were struck by the ‘apparently few cases of psychoneurosis’ among German prisoners of war. ” They were lower in the Red Army, as well.

In the Pacific theater, combat fatigue was even worse for US soldiers, but rare among the Japanese.

...

The infantry took most of the casualties – it was a very dangerous, unpleasant job. People didn’t like being in the infantry. In the American Army, and to a lesser extent, the British Army, getting into medical evacuation channels was a way to avoid getting killed. Not so much in the German Army: suspected malingerers were shot. In the American Army, they weren’t. That’s the most importance difference between the Germans and Americans affecting the ‘combat fatigue’ rate – the Germans didn’t put up with it. They did have some procedures, but they all ended up putting the guy back in combat fairly rapidly.

Even for desertion, only ONE American soldier was executed. In the Germany Army, 20,000. It makes a difference. We ran a soft war: since we ended up with whole divisions out of the fight, we probably would have done better (won faster, lost fewer guys) if we had been harsher on malingerers and deserters.

more on emdees: https://westhunt.wordpress.com/2014/10/20/the-experts/#comment-60697
As for your idea that doctors improve with age, I doubt it. So do some other people: for example, in this article in Annals of Internal Medicine (Systematic review: the relationship between clinical experience and quality of health care), they say “Overall, 32 of the 62 (52%) evaluations reported decreasing performance with increasing years in practice for all outcomes assessed; 13 (21%) reported decreasing performance with increasing experience for some outcomes but no association for others; 2 (3%) reported that performance initially increased with increasing experience, peaked, and then decreased (concave relationship); 13 (21%) reported no association; 1 (2%) reported increasing performance with increasing years in practice for some outcomes but no association for others; and 1 (2%) reported increasing performance with increasing years in practice for all outcomes. Results did not change substantially when the analysis was restricted to studies that used the most objective outcome measures.

I don’t how well that 25-year old doctor with an IQ of 160 would do, never having met anyone like that. I do know a mathematician who has an IQ around 160 and was married to a doctor, but she* dumped him after he put her through med school and came down with lymphoma.

And that libertarian friend I mentioned, who said that although quarantine would have worked against AIDS, better that we didn’t, despite the extra hundreds of thousands of deaths that resulted – why, he’s a doctor.

*all the other fifth-years in her program also dumped their spouses. Catching?

climate change: https://westhunt.wordpress.com/2014/10/20/the-experts/#comment-60787
I think that predicting climate is difficult, considering the complex feedback loops, but I know that almost every right-wing thing said about it that I have checked out turned out to be false.
west-hunter  rant  discussion  social-science  error  history  psychology  military  war  multi  mostly-modern  bounded-cognition  martial  crooked  meta:war  realness  being-right  emotion  scitariat  info-dynamics  poast  world-war  truth  tetlock  alt-inst  expert-experience  epidemiology  public-health  spreading  disease  sex  sexuality  iraq-syria  gender  gender-diff  parenting  usa  europe  germanic  psychiatry  courage  medicine  meta:medicine  age-generation  aging  climate-change  track-record  russia  communism  economics  correlation  nuclear  arms  randy-ayndy  study  evidence-based  data  time  reason  ability-competence  complex-systems  politics  ideology  roots  government  elite  impetus 
january 2017 by nhaliday
Dodging a bullet | West Hunter
Back in the 1950s, Sabin and Salk developed polio vaccines. Salk’s vaccine was inactivated. Sabin’s vaccine was live, but used a weakened strain, strong enough to cause an immune reaction, but weak enough not to cause polio. The live version was also infectious, which amplified its protective effect in the community.

The virus was weakened by passage through a number of cell cultures (live monkey, monkey testicular cultures, monkey kidney cells, etc).

Being a virus, it was grown in cell culture, derived from rhesus monkeys. The problem with all those live cell cultures was the possibility of picking up some other monkey virus. And that happened: 10-30 million Americans received vaccine contaminated with SV40 (Simian vacuolating virus 40) between 1955 and 1963.
west-hunter  stories  medicine  error  bio  nature  disease  cancer  immune  parasites-microbiome  meta:medicine  epidemiology  scitariat  public-health  prudence 
january 2017 by nhaliday
Science Policy | West Hunter
If my 23andme profile revealed that I was the last of the Plantagenets (as some suspect), and therefore rightfully King of the United States and Defender of Mexico, and I asked you for a general view of the right approach to science and technology – where the most promise is, what should be done, etc – what would you say?

genetically personalized medicine: https://westhunt.wordpress.com/2016/12/08/science-policy/#comment-85698
I have no idea how personalized medicine is supposed to work. Suppose that we sequence your entire genome, and then we intend to tailor a therapeutic approach to your genome.

How do we test it? By trying it on a bunch of genetically similar people? The more genetic details we take into account, the smaller that class is. It could easily become so small that it would be difficult to recruit enough people for a reasonable statistical trial. Second, the more details we take into account, the smaller the class that benefits from the whole testing process – which as far as I can see, is just as expensive as conventional Phasei/II etc trials.

What am I missing?

Now if you are a forethoughtful trillionaire, sure: you manufacture lots of clones just to test therapies you might someday need, and cost is no object.

I think I can see ways you could make it work tho [edit: what did I mean by this?...damnit]
west-hunter  discussion  politics  government  policy  science  technology  the-world-is-just-atoms  🔬  scitariat  meta:science  proposal  genetics  genomics  medicine  meta:medicine  multi  ideas  counter-revolution  poast  homo-hetero  generalization  scale  antidemos  alt-inst  applications  dimensionality  high-dimension  bioinformatics  no-go  volo-avolo  magnitude  trump  2016-election  questions 
december 2016 by nhaliday
Books, 2016 | West Hunter
1. The Peloponnesian War
2 The Empire of the Steppes
3. The Columbian Exchange
4. Breaking the Maya Code
5. War Before Civilization
6. The Discourses (Machiavelli)
7. Introduction to Algorithms
8. Rare Earth
9. The Wizard War
10. Night comes to the Cretaceous
11. Microbe Hunters
12. The Youngest Science
13. Plagues and Peoples
14. Project Orion
15. Extraordinary Popular Delusions and the Madness of Crowds
16. Godstalk, P. C. Hodgell
17. Footfall, Larry Niven and Jerry Pournelle
18. On Stranger Tides, Tim Powers
19. His Share of Glory, Cyril Kornbluth
20. Herodotus
21. The Secret History, Procopius

https://westhunt.wordpress.com/2016/12/04/books-2016/#comment-85575
Mukherjee is a moron. Next question?

He’s suggested that gene interactions are real important in IQ [epistatic rather than additive effects] but he is incorrect. If new to the field, it could take as much as an afternoon to find that out.
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december 2016 by nhaliday
Low-hanging fruit | West Hunter
Think about it: peptic and duodenal ulcer were fairly common, and so were effective antibiotics, starting in the mid-40s. . Every internist in the world – every surgeon – every GP was accidentally curing ulcers – not just one or twice, but again and again. For decades. Almost none of them noticed it, even though it was happening over and over, right in front of their eyes. Those who did notice were ignored until the mid-80s, when Robin Warren and Barry Marshall finally made the discovery stick. Even then, it took something like 10 years for antibiotic treatment of ulcers to become common, even though it was cheap and effective. Or perhaps because it was cheap and effective.

This illustrates an important point: doctors are lousy scientists, lousy researchers. They’re memorizers, not puzzle solvers. Considering that Western medicine was an ineffective pseudoscience – actually, closer to a malignant pseudoscience – for its first two thousand years, we shouldn’t be surprised. Since we’re looking for low-hanging fruit, this is good news. It means that the great discoveries in medicine are probably not mined out. From our point of view, past incompetence predicts future progress. The worse, the better!
stagnation  science  history  medicine  innovation  technology  west-hunter  low-hanging  meta:medicine  the-world-is-just-atoms  🔬  scitariat  info-dynamics  bounded-cognition  error  chart  econotariat  marginal-rev  being-right  ideas  discovery  the-trenches  s:*  alt-inst  ability-competence  cost-benefit  track-record  problem-solving  puzzles 
november 2016 by nhaliday
Personnel decision | West Hunter
Who should be head of the FDA?

https://westhunt.wordpress.com/2016/09/20/personnel-decision/#comment-83814
I think we are about due for a career civil servant within the agency or relatively recently retired from it (ideally to academia), with a PhD or M.D. and probably a pay grade of either GS-15 or Senior Executive Service (SES), who has a reputation for integrity, for intelligence, and for getting things done bureaucratically, with some low profile political connections (at least to the ruling party but ideally to both political parties) in private life as well (e.g. through friendships made at a top college, a politician or top political aide parent, or friendships made while attending a top D.C. private school like Sidwell Friends or St. Albion’s or National Cathedral School).

Few federal agencies call for more subject-matter competence to understand its functions well enough to run it well.
--
The problem is that the typical member of the set you describe is nuts. Members have a lot of incorrect ideas in their heads: in fact, you have to express support of those ideas or you are expelled. So, that means that every educational improvement plan pushed by the Feds fails: you can’t do anything realistic, or you would be a bad person. Every intervention in the Middle East fails: same reason. AIDs shows up, so we abandon quarantine: Fidel Castro deals with the situation 50 times better than we did.

The Aztecs thought that the world would end if they didn’t keep cutting people’s hearts out on an industrial scale. They were crazy. But were they crazier than we are?
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september 2016 by nhaliday
A Simple Explanation for the Replication Crisis in Science · Simply Statistics
The key point here is that in both astronomy and epidemiology expectations are low with respect to individual studies. It’s difficult to have a replication crisis when nobody believes the findings in the first place. Investigators have a culture of distrusting individual one-off findings until they have been replicated numerous times. In my own area of research, the idea that ambient air pollution causes health problems was difficult to believe for decades, until we started seeing the same associations appear in numerous studies conducted all around the world. It’s hard to imagine any single study “proving” that connection, no matter how well it was conducted.
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september 2016 by nhaliday
Eroom's Law - Wikipedia, the free encyclopedia
drug discovery is becoming slower and more expensive over time

While some suspect a lack of "low hanging fruit" as a significant contribution to Eroom's law, this may be less important than the four main causes, as there are still many decades worth of new potential drug targets relative to the number of drugged targets, even if the industry exploits 4-5 new targets per year.[2] There is also space to explore selectively non-selective drugs (or "dirty drugs") that interact with several molecular targets, and which may be particularly effective as central nervous system (CNS) therapeutics, even though few of them have been introduced in the last few decades.[4]
healthcare  medicine  concept  street-fighting  wiki  trends  drugs  pharma  hmm  meta:medicine  stylized-facts  low-hanging  stagnation  discovery  info-dynamics 
september 2016 by nhaliday
The Elephant in the Brain: Hidden Motives in Everday Life
https://www.youtube.com/watch?v=V84_F1QWdeU

A Book Response Prediction: https://www.overcomingbias.com/2017/03/a-book-response-prediction.html
I predict that one of the most common responses will be something like “extraordinary claims require extraordinary evidence.” While the evidence we offer is suggestive, for claims as counterintuitive as ours on topics as important as these, evidence should be held to a higher standard than the one our book meets. We should shut up until we can prove our claims.

I predict that another of the most common responses will be something like “this is all well known.” Wise observers have known and mentioned such things for centuries. Perhaps foolish technocrats who only read in their narrow literatures are ignorant of such things, but our book doesn’t add much to what true scholars and thinkers have long known.

https://nintil.com/2018/01/16/this-review-is-not-about-reviewing-the-elephant-in-the-brain/
http://www.overcomingbias.com/2018/01/a-long-review-of-elephant-in-the-brain.html
https://nintil.com/2018/01/28/ad-hoc-explanations-a-rejoinder-to-hanson/

Elephant in the Brain on Religious Hypocrisy:
http://econlog.econlib.org/archives/2018/01/elephant_in_the.html
http://www.overcomingbias.com/2018/01/caplan-critiques-our-religion-chapter.html
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august 2016 by nhaliday
Reverse Voxsplaining: Drugs vs. Chairs | Slate Star Codex
Let me ask Vox a question: when was the last time that America’s chair industry hiked the price of chairs 400% and suddenly nobody in the country could afford to sit down? When was the last time that the mug industry decided to charge $300 per cup, and everyone had to drink coffee straight from the pot or face bankruptcy? When was the last time greedy shoe executives forced most Americans to go barefoot? And why do you think that is?
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august 2016 by nhaliday
The Bell Curve - The New Yorker
What happens when patients find out how good their doctors really are?
Atul Gawande writing on Cystic Fibrosis and track records for doctors
medicine  longform  gwern  hanson  essay  healthcare  len:long  stories  evidence-based  news  org:mag  meta:medicine  bounded-cognition  nitty-gritty  info-dynamics  track-record 
august 2016 by nhaliday
Information Processing: Bounded cognition
Many people lack standard cognitive tools useful for understanding the world around them. Perhaps the most egregious case: probability and statistics, which are central to understanding health, economics, risk, crime, society, evolution, global warming, etc. Very few people have any facility for calculating risk, visualizing a distribution, understanding the difference between the average, the median, variance, etc.

Risk, Uncertainty, and Heuristics: http://infoproc.blogspot.com/2018/03/risk-uncertainty-and-heuristics.html
Risk = space of outcomes and probabilities are known. Uncertainty = probabilities not known, and even space of possibilities may not be known. Heuristic rules are contrasted with algorithms like maximization of expected utility.

How do smart people make smart decisions? | Gerd Gigerenzer

Helping Doctors and Patients Make Sense of Health Statistics: http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2014/12/WC500178514.pdf
street-fighting  thinking  stats  rationality  hsu  metabuch  models  biases  distribution  pre-2013  scitariat  intelligence  neurons  conceptual-vocab  map-territory  clarity  meta:prediction  nibble  mental-math  bounded-cognition  nitty-gritty  s:*  info-dynamics  quantitative-qualitative  chart  tricki  pdf  white-paper  multi  outcome-risk  uncertainty  heuristic  study  medicine  meta:medicine  decision-making  decision-theory  judgement  grokkability-clarity 
july 2016 by nhaliday
The Checklist - The New Yorker
If something so simple can transform intensive care, what else can it do?
By Atul Gawande
rhetoric  health  medicine  rationality  thinking  workflow  checklists  healthcare  evidence-based  error  org:mag  meta:medicine  bounded-cognition  track-record  info-dynamics 
june 2016 by nhaliday
Solidarity | Slate Star Codex
problems with the UK healthcare system
interesting discussion of nurses vs. doctors in the comments
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may 2016 by nhaliday

bundles : abstractembodiedmetametasci

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