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Feb 2, 2023
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I think IVM advocates started gaining popularity- with very loud lack of interest from most scientists- before the media started commenting.

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Feb 1, 2023
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"I'm not 100% sure why Strongyloides emerged as the top contender"

From quick noodling around because it's often prevalent in a lot of places, prevalence is unrecognised, it causes a bunch of symptoms that can be mistaken for other things, and medical professionals don't tend to test for it regularly so are unaware if a patient is suffering from an infestation.

https://www.racgp.org.au/afp/2016/january-february/chronic-strongyloidiasis-don-t-look-and-you-won-t

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.... university administration, ....

That was hilarious. Thank you for that - made my day.

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Short rule of thumb for me. If Alex Jones is on the side of something, it isn't worth even considering. There is too much going on in life

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Have to sort of disagree with EY on this one.

You've got "stupidity" in the sense of a bad world model that produces random conclusions, but then you've also got "stupidity" in the sense that smart people have looked at an idea and think it's dumb. The first one isn't anti-correlated with reality, but the second one definitely is- and there are things that can selectively bias people in favor of that sort of thing. For example, when experts and credible sources disproportionately belong to a political class that you oppose, when you rely for your livelihood on the attention that comes from being contrarian, when you're enamored by the narrative of being a lone voice of truth in a world of illusions, and so on.

Alex Jones ticks enough of those boxes that him taking a stand on a controversial issue is pretty decent evidence that experts take the opposite stand- which is pretty decent evidence that his position is false.

Also, suppose you've already seen some evidence for and against a position, and have a lot of uncertainty about whether it's true. If you unexpectedly discover that there's a prolific and very dumb counter-culture promoting one side of the issue, shouldn't you wonder whether the evidence you've seen was biased by that group's efforts and adjust your credence accordingly? Reversed stupidity may not be intelligence for a blank slate, but if there's any chance you've been influenced by stupid, reversing it by a proportional amount just seems prudent.

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I'm surprised Scott didn't link to this instead:

https://slatestarcodex.com/2019/02/04/respectability-cascades/

Scott has better epistemic hygiene than Matt Ball.

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"They're turning the frogs gay!" isn't a theory that environmental endocrine disruptors are affecting sexual development in amphibian populations. It's a theory that the US government is using chemical warfare as a form of population control by feminizing men and turning them gay to stop procreation. One of the side effects of this plot is that now most frogs are homosexuals. Suffice it to say, Alex Jones is wrong about this.

Alex Jones was using a bit of pop coverage about a known scientific phenomenon, distorting it, and folding it into a ludicrous conspiracy theory. Being suspicious of Alex Jones endorsed conspiracies doesn't require you to dispute every single detail found in them, however strained.

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Feb 2, 2023
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I don't know. How many? I suspect not a lot. I'm not sure the answer is greater than zero. The causality is oddly inverted here as Jones's conspiracy theories trade on popular media coverage of scientific findings.

What we have is a Scott Alexander anecdote where Scott brings up in polite company that what Alex Jones was talking bout was actually real and feels admonished for this. There's not much we can make of that, though it is notable that what Alex Jones was talking about wasn't real if you actually understand what his whole rant about the frogs being turned gay is about, so there's that.

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If you assumed that what Alex Jones says must be wrong, then you'd assume he was wrong about them turning the frogs gay (whether it's a side-effect or regardless of intentionality).

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Do you think the person was asserting that if Alex Jones believe it is a good idea to breath air, then Alex Jones must be wrong? I think we're able to give credit to how people colloquially communicate ideas and presume they probably mean that Alex Jones is apt to be on the wrong side of issues controversial issues that aren't conventionally accepted among people with greater credibility. That's usually what people mean when they express something like this.

If the response is, "But he wasn't wrong about the gay frog thing!," then I think it is worth noting that he was, in fact, wrong about that, both in the particulars of the assertion and what theory he was trying to communicate with that. That he loosely based it on a widely covered phenomenon that isn't all that controversial misses the point.

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Yes, but let's face it: This is some noise-ass, low-veracity Bayesian evidence, to be fair, and probably shouldn't budge your needle much in one direction or the other.

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If you know someone to be a pathological liar, disbelieving everything they say that you can't independently verify is not only a good bet, I would argue it's your ethical duty.

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No, it gives that pathological liar an easy means of convincing you of falsehoods.

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The key here is that there has to be another "side" in the argument that the pathological liar is diametrically opposed to. If propositions imply that one is false and one is true, you can make safe inferences on the other position based on which side the liar is on.

Obviously most issues aren't that clean, but as a heuristic, it could be a lot worse.

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The Nazis were well known for lying. And when they found a bunch of bodies in the Katyn forest and blamed it on the Soviets, the natural assumption would be the Nazis were blaming one of their own numerous massacres on another "side". But they were actually telling the truth in that instance, and your heuristic would repeatedly fail if you assumed the opposite side of a known liar must be a truthteller. It's entirely feasible for two liars to be opposed to each other.

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That's the other obvious failure mode of this heuristic, yes. But the majority of people are not outright liars, especially in the scientific community, so it's still useful in this instance and many others. (Also, it should go without saying that no individual failure of a heuristic makes it invalid; the existence of solar eclipses does not make the "dark outside -> it's night time" heuristic useless.)

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disbelieving != believing the opposite

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This was during the southeast Delta death surge…ivermectin as prescribed in Florida is clearly ineffective:

A recent study examining trends in ivermectin dispensing from outpatient retail pharmacies in the United States during the COVID-19 pandemic showed an increase from an average of 3,600 prescriptions per week at the pre-pandemic baseline (March 16, 2019–March 13, 2020) to a peak of 39,000 prescriptions in the week ending on January 8, 2021.1 Since early July 2021, outpatient ivermectin dispensing has again begun to rapidly increase, reaching more than 88,000 prescriptions in the week ending August 13, 2021. This represents a 24-fold increase from the pre-pandemic baseline. (Figure)

https://emergency.cdc.gov/han/2021/han00449.asp

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Unfortunately patient self advocacy is like playing chutes and ladders. Encounter a medical problem for you or your loved one and find out- there's no hand holding

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That's literally the same as arguing that eating sugar is bad because Hitler ate sugar. So if Alex Jones said that eating healthy is good then all reasonable people should go eat only fries at McDonalds 3 times a day 7 days a week?

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This is a false equivalence, because Alex Jones believes lots of true things he doesn't put on his show. What he chooses to put on his show is filtered for controversy and sensationalism. Nothing he puts on his show will be anything people generally agree is true.

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Well if you want to believe everything that people generally agree is true then you can just do that and cut out the Alex Jones involvement.

Believing everything that people generally agree is true is a pretty good strategy in life. You'll be right more often than you're wrong, and when you're wrong then at least you don't lose too many friends over it.

But if you're happy to just follow the believe-what-everyone-else-believes strategy then you needn't waste your time reading rationalist-adjacent blogs like this, which are about the often-quixotic struggle to do ever so slightly better than the general consensus.

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Well, I don't think that it's quite this simple these days, as compared to say 70 years ago. To an extent, there are now two mainstreams, the "establishment" and "anti-establishment" ones, to vaguely gesture at their essence. Many reasonable people believe that certain prevalent and high-status expert endorsed narratives are thoroughly wrong or "not even wrong". Arguably, Alex Jones serves a useful role in trawling through the "anti-establishment" thought-space and gathering all of its worst trash in one place. I wonder if there's an "establishment" equivalent.

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70 years ago there was also an establishment and an anti-establishment. The anti-establishment included Civil Rights activists, draft-resisters, folk/rock musicians, etc. And, admittedly, lots of wackos.

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I think the point is that Alex Jones generally airs the opposite of what people generally agree on, so it's still valuable information, thus you shouldn't cut out people like him. If you want to go for "believe everything people generally agree on", it's a lot less effort to watch AJones and believe the opposite, than to go around and ask everyone about what they believe on those same issues.

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Some things are only worth a rough heuristic.

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It's not bad as a first approximation. But to then go on and say that a first approximation is all you need and no one should do further analysis, is stupid.

Jones is, in fact, right sometimes, even when he says controversial things. And some things he's wrong about have decent evidence for them.

Whether a drug has massive value against Covid is certainly a question worth more than a rough heuristic.

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You're giving Alex Jones a hell of a lot of power over you there.

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He seems to be a very powerful person, having caused a gigibucks worth of hurt feelings and all.

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A sensitive instrument is one that can pick up and amplify small signals that others miss, and no doubt this "sensitivity" has been an integral part of what has made your writing as successful as it has been. Getting overwhelmed more easily than you might otherwise be is the other side of that tradeoff, and it's great that you're not letting the tough side of that get in the way of giving things the response you know they're due.

Thanks for taking the time to respond to him, even though it hasn't been fun. I doubt I'm the only one that notices and appreciates the effort.

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> Dr. Ioannidis is known to be unusually rigorous and this is part of his pro-rigor crusade

I'm not familiar with all his work, but I think he deserves a reputation for self-promotion more than a reputation for rigor. I think his most famous essay is "Why Most Published Research Findings Are False", and I think this paper is notable for its sensational headline much more than for its careful analysis.

https://en.wikipedia.org/wiki/Why_Most_Published_Research_Findings_Are_False#Reception

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That's his most famous paper but it's not his most cited.

https://scholar.google.com/citations?user=JiiMY_wAAAAJ&hl=en

He was also involved in this fairly important early paper on COVID seroprevalence

https://pubmed.ncbi.nlm.nih.gov/33615345/

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An important but wrong paper on seroprevalence. That really tarnished his reputation.

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I took him to ask about that at https://slatestarcodex.com/2013/02/17/90-of-all-claims-about-the-problems-with-medical-studies-are-wrong/ but I do appreciate a lot of his work, and think that at that point he was one of the few people sounding the alarm at all.

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The early seroprevalence study had quite a few serious problems - but even worse he used it to generalize from non-representative sampling to wrongly characterize the virulence of COVID by a wide margin.

Also:

https://replicationindex.com/2019/01/15/ioannidis-2005-was-wrong-most-published-research-findings-are-not-false/

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And:

It's too perfect that this response to Ioannidis was co-authored by someone (Sander Greenland) who had positive things to say about Alexandros' analysis on Andrew Gelman's blog.

https://journals.plos.org/plosmedicine/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0040168

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Fabulous stuff, all of it.

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I didn't really have an opinion on Ioannidis before COVID times. But during the pandemic, I got a quite poor impression of him.

He was one of the early figures to warn that COVID might be an overrated problem, especially that mortality might be lower than common estimates, and gave his own, much lower estimates, of the problem. Even then I had the impression that his data looked rather cherry-picked. He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions, which would have been more alarming. That data was cleaner than what he took. But this was during the first few weeks of the pandemic, in a chaotic situation, and no data was really good, so that was still kind of ok.

But the real problem was that he didn't update when better studies came out. A year later, he would still stick to his old estimates in public interviews, even though there were much better studies by then, and his estimates were far out of the plausible range. Honestly, it was getting ridiculous.

I know that he deserves big praise for uncovering the replication crisis, but I really think that his performance during COVID was a scientific and Bayesian failure. Perhaps he became hyper-skeptical of studies after the replication crisis (or was so before, which made him detect it). But the issue is that he didn't just concluded "We don't know", but that he concluded "We don't know, so don't take the estimates from the literature, but take my own even more fishy estimates instead." And sticked with that.

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I agree the pandemic was not his best moment.

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Ah, interesting. I've never read SBM before but there's a pretty extensive criticism here

https://sciencebasedmedicine.org/what-the-heck-happened-to-john-ioannidis/

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Wow, thanks for sharing! I didn't know that it was so bad.

It's sad that such a brilliant mind can be trapped in some believe and totally disconnect from evidence about it. There are quite a few tragic cases like this, like physicist Roger Penrose or mathematician Michael Atiyah. Ioannidis is not there yet, but he might be heading that way.

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I'm not necessarily saying I agree with all of the criticism, just surprised to find it all in a neat little package here.

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I didn't really follow what Ioannides did, he isn't a public figure here in Europe. For example, I didn't know about his attacks on the PhD student.

But I noticed some bits, especially in March 2020, and later sporadically when he gave interviews to the news here, and my impression is pretty consistent with the article. It's just that the article contains a lot more of the same stuff.

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When you refer to the tragic case of Robert Penrose, what do you have in mind? His theory of Conformal Cyclic Cosmology, or something else?

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I was rather thinking of his concept of consciousness. He started with the idea that consciousness can impossibly be restricted by Gödel's incompleteness theorem, and thus computers can never become conscious. In more elaborate versions he insists that consciousness is impossible without resorting to quantum gravity effects in the brain. All this is completely detached from any evidence (in fact, there is lots of evidence against it) except for his gut feeling of what properties consciousness should have.

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I think the Penrose and Atiyah cases are somewhat different.

Penrose started going publicly off the rails about Consciousness And All That with "The Emperor's New Mind", published in 1989 when he was 58 and still (so far as I can tell) a genuinely brilliant mind.

Atiyah started going off the rails in his late 80s, when he was fairly clearly losing his mind. This wasn't a matter of a brilliant mathematician/physicist getting taken in by a bad idea, it was a matter of a _formerly_ brilliant mathematician/physicist no longer being able to tell good ideas from bad ones. A very different kind of tragedy.

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Fair point.

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"He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions"

This has probably been argued elsewhere, but cruise ship passengers tend to be older and fatter than the general population. Italy also has a lot of old people.

The sources may be clean from the point of view that the populations are isolated, but they aren't representative in other ways.

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True, and these things need to be accounted for. But this is possible and should be done, and the data should not be completely thrown out of the window. In the Bergamo region with about 1,000,000 people, the number of deaths in March 2020 was six times as high as in a normal month. So this March had half as many deaths as otherwise a whole year! Of course, this can become a bit less worse at other places if you adjust for age.

But Ioannidis arrived at the prediction:

"If we had not known about a new virus out there, and had not checked individuals with PCR tests, the number of total deaths due to “influenza-like illness” would not seem unusual this year. At most, we might have casually noted that flu this season seems to be a bit worse than average. The media coverage would have been less than for an NBA game between the two most indifferent teams."

Granted, this was mid-March 2020, but at this time preliminary death numbers from (smaller) parts of Bergamo were already available. There was just no way to arrive at his conclusion by "adjusting for age". Still, if he had corrected his estimates one or two months later, that would have been fine. But he sticked to them (and actively propagated them) long after the point where they were simply ridiculous.

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The general population isn't the primary comparison due to age. The cruise ship data WERE controlled by age - but they didn't control for factors like SES - which I think would likely make cruise passengers HEALTHIER (more active, better baseline health, more access to care, etc.) than their age-matched peers

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I had been quite a fan of Ioannidis.

As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):

https://youtu.be/NTXgbN6uB1I

And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:

https://statmodeling.stat.columbia.edu/2020/04/30/updated-santa-clara-study-of-coronavirus-infection/

Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.

OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.

And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.

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I'm repeating this comment because it appeared to get truncated above? (I'm not familiar with this comment interface)

I had been quite a fan of Ioannidis.

As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):

https://youtu.be/NTXgbN6uB1I

And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:

https://statmodeling.stat.columbia.edu/2020/04/30/updated-santa-clara-study-of-coronavirus-infection/

Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.

OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.

And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.

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typo: contraian

this (thankfully) isn't a typical post, but the extremely detailed, technical analysis of a minor current thing from 2 years ago is peak ACX energy

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This is still a major topic and will continue to be a major topic as long Covid generates millions of disabled ppl

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pedantic typo patrol: "...equal number of studies on both size."

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Thanks, fixed.

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We have done an intensive study of viral load dynamics in our phase 2 platform trial. Ivermectin got dropped pretty quickly (pre-specified futility rule was met). In contrast, known effective antivirals such as casirivimab/imdevimab and remdesivir showed an effect on viral load dynamics pretty quickly.

https://www.medrxiv.org/content/10.1101/2022.07.15.22277570v1

https://www.medrxiv.org/content/10.1101/2022.10.17.22281161v1

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Alexandros blocked me on Twitter long ago just for repeatedly asking whether there was one good RCT supporting ivermectin. He apparently runs a startup, yet has the time to write a series of posts that literally total over 86,000 words (a sizeable non-fiction book!) just to respond to ONE blog post from Scott. And he did this over the space of a few months.

In other words, he has been engaged in a 24/7 side hustle--writing a full non-fiction book in a few months -- and moreover, it was all on a very narrow question about whether one particular blogger was mean about a particular drug that supposedly is a miracle cure for Covid (even though no rigorous study has ever shown that). Odd choice of priorities.

And despite aiming towards rationality, he is keen to write thousands of words nitpicking at the tiniest flaws in any negative ivermectin study, even while defending much worse studies or websites that defend ivermectin. Blatant double standard.

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PS, when I spent 5 minutes pasting Alexandros' blog posts into Microsoft Word, the result is 291 pages long (single spaced). Even if someone was unemployed, who has the energy for that kind of monomania?

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I do if it's called "Playing Civilization VI"

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Why not play a better one? Blegh.

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If he doesn't have two toddlers I can say from experience where that time might come from

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I think it's probably bad to make fun of people for spending too much time obsessively trying to get things right, even if you think they failed.

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I'd agree. But given the double standard (which you repeatedly and correctly note), he is not "trying to get things right." He's trying to defend ivermectin at all costs -- he comes up with the smallest nitpicks at any study showing that ivermectin doesn't work, while defending much lower-quality pro-ivermectin studies on the grounds that "but there's a STAT article" or "but this guy won a science competition" or some similarly one-sided argument.

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Okay, so what we're generally implying when we accuse somebody of having 'double standards' is that they're deliberately misinterpreting data. But when you're dealing with this much data, and a discourse that spans months, asymmetries in your application of epistemic rigor are bound to emerge.

In my submission, this doesn't really confirm a deliberate misinterpretation of the data. Scott does a reasonably good job being generous about that here.

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Yeah, especially since many here, including me, are prone to doing exactly that. And besides, I'm not sure it's a bad trait. It makes life harder for the person who has it, but it probably also makes them likelier to obsessively try to get something right, and succeed at doing so.

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To be clear, it's not bad to obsess over getting something right. But I think it's to obsess over defending a predetermined position at all costs (have you read my friend Julia Galef's book on the scout mindset?)

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Scott, I admire you for following through on writing this. My guess is that holding yourself to your pledged sucked, but you did it because you'd said you would, and also because you felt bad about some errors of yours Alexandros had pointed out. Jeez, write something you enjoy the hell out of next.

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I absolutely hate this kind of thing. Alexandros can invest his time however he likes. And blocking people for repeatedly tweeting the same thing at you is generally reasonable behavior.

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Yes, he can indeed invest his time in eminently ridiculous ways. Up to him. But it is still subject to ridicule by other people who are interested in what's actually true. If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence.

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I expect Scott put way more time into writing this response than he wanted to. In fact my guess is that working on it SUCKED, and that he held himself to doing so anyway because he said he would, and also because he felt bad about so genuine mistakes that Alexandros pointed out. Want to make fun of Scott's obsessiveness too?

"If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence."

Also, the thing none of us know about Alexandros is why he's persisting. Is he so invested in being Ivermectin Man that he can't allow himself to see how bad the case for it is? (That's my theory.) Does he know so little about research he can't tell good from bad? Does he know the evidence for Ivermectin's terrible, but he's cynically pretending it is not because he's profiting from being an advocate for the drug? But you're not addressing that question -- just throwing rotten eggs at him.

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Could be any or all of the above, but the thing is that even by you, there is no reasonable explanation. All of them are bad for Alexandros. So why are you so eager to keep weighing in on behalf of someone for whom there is no possible rational defense?

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Because I think that laughing at someone who's been bested is meanspirited. If the mockery is mixed with new information or a new take on what happens, then I experience it differently -- then it's an angry, substantive comment.

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Because I think that laughing at someone for making a lot of effort trying to get to what they think is the truth is incredibly toxic for everyone.

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But we don't have to pretend that everyone is trying to get at the truth. Alexandros is applying an absurd double standard whereby any negative ivermectin study has to be scrutinized for every tiny flaw whereas pro-ivermectin studies will be excused for far greater flaws.

There is plenty of room for good faith people to engage in discussions without always being derailed by the impulse to give the benefit of the doubt to people who don't deserve it.

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PS, I didn't repeatedly tweet the same thing at all. Here's how it ended. If someone had good evidence on their side, why wouldn't they cite it rather than blocking me? https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Ff08ee13f-d59f-4ffa-82af-1bb6e6b9685a_550x787.png

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Look, I'm no fan of Alexandros but I don't think you really score any points against him here. Why would he block you on Twitter for repeatedly asking whether there is one good RCT supporting Ivermectin? He thinks there are multiple good RCT's, doesn't he? Seems more likely that he pointed to studies that he considered good RCT's, you said, "no they're not because . . ." and he got tired of arguing with you.

Why does writing a full non-fiction book while running a start-up suggest that he or the contents of his book are not to be trusted? Maybe he's got lots of energy -- or maybe he's bad at time management -- or maybe he's just overinvested in winning the argument with Scott, even though the practical consequences of his winning or losing are small. All these possible personal failing of his seems kind of irrelevant in the context of a discussion of whether he's right about ivermectin, or whether he's arguing in good faith.

As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. I think he probably believes that.

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If you had multiple exchanges with him, there's no way I'm going to dig through the manure pile of Twitter for them. I did read the exchange you linked, and it's not clear what his view is about good RCT's existing. He once says "no good RCT's" but I don't know what he means -- is it agreement? a sarcastic gibe? If he really thought there were none, I'd expect him to say something like, "yes, OK, all the studies are imperfect, still if you look at the mass of evidence blah blah. . ." Then later he says something like "nothing would convince you." That could mean he's pointed to what he thinks are good RCT's and you dismiss them as not, or I suppose it could mean something else. So this exchange with Alexandros is far from solid evidence that he doesn't believe there are good RCTs. Actually, it's sort of like the case for Ivermectin's efficacy -- you can point to it as evidence for your view, but in fact it's full of holes.

Look, I hope it's clear that I do not think Ivermectin is useful against covid. I just don't like the way you're making fun of Alexandros. I get that he annoys the hell out of you, but if you want to go after him make good points, don't just snigger,

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No, he never pointed to even one good RCT. Earlier in the discussion, he pointed to ivmmeta.com (not a trustworthy website) and the Bryant meta-analysis (also not reliable because it included fraudulent studies). That's all he had.

But say, why are you trying to reconstruct Twitter history from 2021 to critique me on the grounds that Alexandros MIGHT have said something defensible back then? Why do you care so much, such that you're inventing alternative histories in which he had good RCTs to cite (which he didn't)? Why bend over backwards to give every possible benefit of the doubt to him rather than to me?

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Because you're the one trying desperately to defend a pointless smear, I'd wager.

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"As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. "

If he thinks that, he doesn't know what he's talking about, because it is objectively wrong. For example, the TOGETHER trial is not objectively worse than the Borody study -- quite the contrary.

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Hey, I agree that the case for Ivermectin is bad and the case against it is good. It's just not clear what point you're making about Alexandros by saying he's very critical of good studies and goes easy on bad ones. We're all aware of the thing you keep pointing to -- yep, ridiculously hypercritical of studies that weight against Ivermectin. And?

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|or maybe he's just overinvested in winning the argument with Scott

I'll note that Alexandros was clearly expending massive amounts of time and effort on ivermectin advocacy before Scott wrote anything on the subject.

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To give the other side of this thing, his company has produced this: <https://www.balena.io/etcher>, which is a really nice way to flash USBs and which has saved me a bunch of time in the past.

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Wait, really? Hilarious. I have to use that to create Homebridge images for my smart home setup.

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Well, no. He's writing on a controversial topic that inspires fervent support amongst true believers. His comments show he's clearly attracted an audience, and he's baited Scott, who has a huge audience, into writing a long post in response. So whatever else he has done, his efforts have won him a big audience that he can than parlay into either a platform for his ideas or into some kind of monetary profit. You are being rather uncharitable to assume he did all over an obsessive need to prove Scott wrong.

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If you disagree with what he writes, please attack the writing directly, rather than "it is wrong to have a hobby while running a startup".

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If Alexandros had been right, that time would've been extremely well-spent. It's not like he spent any of your money on it.

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Scott's original post had so much stuff in it that if it was on any other subject we would have called it a Gish Gallop. It's unsurprising that responding to everything in it would take such a huge number of words.

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I don't think that's fair. The characteristic of a Gish gallop is that one throws out a large number of basically-independent claims without providing justification for any of them, taking advantage of the facts that (1) one can _state_ something much more quickly than _refuting_ it and (2) if you merely state something and someone else merely denies it, then to most people it looks as if you're in the right and they're in the wrong.

Scott's ivermectin post wasn't like that. It's mostly long because it's looking at a large number of studies, which ivmmeta can simply list in a big table but Scott had to look at in at least a paragraph's worth of detail.

Scott's post was the _exact opposite_ of a Gish gallop: it was very long because it was responding to something else that was long but didn't go into details.

(Maybe you could argue that he should have looked in _more_ detail at some of the studies. That would almost certainly have made his post longer, not shorter.)

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The important trait here is not how much detail it has, but that it has many arguments that would take a lot of time and space to respond to--so much that most people would give up because of the volume, regardless of whether the arguments have merit.

Complaining about Alexandros using a huge number of words to respond to Scott isn't fair; Scott said so much that in order to respond fully, he *had* to use a huge number of words.

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I agree that complaining about the length of AM's response to SA is likely unreasonable. (It depends on what that length actually consists of; I haven't looked myself.)

What I'm objecting to is something more specific: "if it was on any other subject we would have called it a Gish gallop". I hope we wouldn't, because "Gish gallop" doesn't just mean "very long thing", it means a particular _kind_ of very long thing, and Scott's post was unambiguously not that kind of very long thing.

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This analysis is great but I'd like to pay more attention to what our prior should be that some existing medication has a substantial benefit in treating a new disease when there isn't a strong theoretical basis supporting that use. My sense is that our prior should be very low. I mean, just ask yourself how much you'd be willing to bet about a large rigorous study showing a 10% drop in deaths from a random drug.

All the argument as to what direction the studies on ivermectin point is great and all, but even in the best case the evidence isn't very strong. I mean, it's not unusual in the slightest in medicine to see some initially suggestive studies only for the effect to turn out to be a mirage.

So while I think pinning down just how much evidence we have for ivermectin is important insofar as it should inform us whether to bother investing in yet more studies the idea that this should be enough to convince you to take the bet against the strongly theoretically supported side-effects (plus a reasonable prior that many drugs have them) seems like a big stretch.

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I agree. On the other hand, one thing Ivermectin has going for it is that it's cheap, easily accessible (and probably quick to make) and well-tolerated. And there weren't many other drugs that were: fluvoxamine and metformin were the only ones I heard about (and actually I don't know whether metformin is cheap or well-tolerated) .It would have been a great thing for the world if some drug like Ivermectin that did give some survival benefit, even a small one, had been discovered. The drug we finally came up with, Paxlovid, is highly effective for unvaccinated people, but it took a long time to develop, is not cheap, not easily accessible, and so unpleasant to take that many people bail before finishing the full course of medication. So I can see giving things like Ivermectin the benefit of the doubt in early research -- though I agree that the pro-Ivermectin people kept going long after it was time to give up.

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"and actually I don't know whether metformin is cheap or well-tolerated"

Reasonably so, there are generics of it available. Well-tolerated - the worst side effects are gastrointestinal and usually calm down in a couple of days (though some people get it worse and can't stay on it).

I've been taking metformin for several years now for Type II diabetes and it didn't stop me contracting Covid. Anecdotes are not data, but that is my lived experience 😁

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If it does anything it's not prevention of illness, it's improving outcomes. A number of studies found it reduces chance of ER visits and hospitalization, but some did not. Pros and cons are easy to find via google. Current official US guidelines are to not prescribe it for people with covid. A couple of the docs on medical Twitter whom I respect think that's a bad recommendation because metformin's way better than nothing. It's certainly not as helpful as Paxlovid, but Paxlovid's expensive and soon a lot of poor folks in the US will not have insurance that will allow them to get Paxlovid. Metformin was also available when Covid began. Paxlovid was ready to use about a year later, but the supply was limited for a while so it was 18 mos. until it was available for all. And of course Metformin could be used in parts of the world where nobody gets Paxlovid. Here are a couple of studies with positive findings:

https://www.nature.com/articles/s41598-022-09639-2

https://www.news-medical.net/news/20230111/Review-shows-metformin-usage-to-be-associated-with-better-COVID-19-outcomes.aspx

Who knows, maybe it reduced your illness severity.

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"Who knows, maybe it reduced your illness severity."

Hard to say, I had a murderous cough (so bad that once I nearly fainted from coughing so hard and not being able to catch my breath). Another family member had no cough but constant vomiting to the point of becoming severely dehydrated (couldn't even keep water down, anything they consumed came right back up). Two other family members just breezed through it like a bad cold.

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Especialy when it come to viral disease. There are very, very few effective antiviral drugs, and those that do exist and work are usually the results of a very long trail of arduous and expensive research.

The reason is completely obvious: bacteria have their own biochemistry, thousands of chemical reactions unique to them, which human cells do not use, and which are potential targets for chemical warfare. That's why there are tons of antiobiotics, and lots of compounds, both natural and artificial, show anti-bacterial properties. Viruses don't have any biochemistry at all, because they're not alive. They have *no* chemical reactions unique to them. An effective antiviral needs to interfere delicately but effectively in the chemistry of the invaded human cell, so that it blocks viral entry or reproduction -- which is carried out by human cell reactions -- but doesn't do bad things to the cell.

It's a miracle this is even possible at all, so delicate is the balance to be struck. So the baseline assumption about suggestions that any drug or herbal supplement or whatever is effective that *isn't* the result of some brain-straining enormous expensive effort should be skepticism bordering on incredulity.

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But drugs can help in other ways besides being antivirals My understanding is that metformin's mode of action (assuming it really does help covid patients) doesn't involve blocking viral entry or reproduction, but instead mitigating some of the effects downstream from that, eg cytokine storms. This article talks about that: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154087/

Of course such drugs are much harder to find -- seems almost a matter of luck. If you're looking for a covid antiviral you can just throw a drug in with some pseudovirus and see how well the drug blocks the virus. There's no simple way to find out which of the many drugs in use that do not qualify as antivirals slow down the processes by which covid does a lot of damage in those who are infected. In fact I have no idea how metformin was identified as possibly helpful. Nobody seems to be touting it as an antiviral.

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Sure. Supportive care is still all we've got in many cases, but it rarely changes outcomes in the kind of miraculous reversal way that you get with antibiotics and bubonic plague, say. It can't, because it's not getting at the root of the problem. I mean...if some people are going to go into full tinfoil-hat frenzy because Big Medicine is pooh-poohing folk remedy X that reduces the severity of symptoms or duration of disease by 15% it's just more of the shouting at the clouds that makes me think watching birds in the feeder in my backyard is a more productive use of my time than the Internet.

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But who's going into full tinfoil hat frenzy over this? Since I'm the only person in this discussion speaking up in favor of metformin & similar, it does feel a bit like you're talking about my view. I hope it's clear that I'm not even sure metformin works -- some think if does not. My point, made before you entered the discussion, was that having some cheap, widely available, well-tolerated drug would have made a lot of difference early on in the pandemic (which was when some, including Scott, were talking about fluvoxamine and metformin as a possible drug of that type). Something that at present does nothing more for a covid sufferer than shorten the illness a bit would have made a lot more difference than that early in the pandemic, when few people had immunity, there was no vax and there were no antivirals. And of course in some parts of the world there is still is little or no vax and no antivirals.

And the study I linked to did find considerably more benefit than a 15% redux in symptoms or duration. There was a substantial difference in death rate between metformin users and nonusers.

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I must admit that I scrolled straight to the conclusions, and even that felt like a strain at this stage of the ivermectin conversation. The graph of likely false positive results at the end of the post was quite interesting, and I admire Scott's dedication to this topic. Otherwise, I'm hoping we can all move on to other topics!

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I guess that Scott wrote this in large part because there's a bigger and always relevant meta-topic of what to belive in the absence of "settled science", and how easy it is to make the mistake of thinking that you've gleaned a valuable insight from the messy landscape.

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You seem to be missing the positive results in the MedinCell trial and the new paper on hemagglutination showing that IVM both prevents and reverses RBC clotting associated with poor outcomes.

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This was primarily about the studies we discussed in 2021, with me only mentioning a few especially large and well-done studies since then. Still, those seem interesting - can you give me links to those studies?

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Yeah, Bret Weinstein did a video on those results recently. I thought Scott's original article was a net win for Team Ivermectin in any case- even being right for the wrong reasons makes a case for having a public debate.

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That MedinCell trial also seems very fishy on its face. It randomized 399 people to ivermectin or placebo, and measured how many got infected with Covid in 28 days. https://www.medincell.com/wp-content/uploads/2023/01/PR-results-TTG-VF-EN.pdf In the placebo group, they claim that 105 out of 199 people got a Covid infection in 28 days. Really? Unless this was a challenge trial, it is hard to imagine that over half of people came down with Covid in a 4-week period.

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I'd totally believe those numbers if they'd come from, say, China last December.

MedinCell says they did the study in Bulgaria "between March and November 2022"; I don't know about infection rates there, so off the top of my head I'd say it's questionable but not totally unbelievable.

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