Astral Codex Ten Podcast

https://astralcodexten.substack.com/p/addendum-to-luvox-post   In my post yesterday, I quoted a Vox article describing work by Dr. Ed Mills and others to get the FDA to approve Luvox for COVID. As of that point, the FDA didn’t know how to process an application without a sponsoring drug company: [Professor Ed] Mills, who thinks that fluvoxamine and budesonide are both appropriate to prescribe to patients sick with Covid-19, compares public messaging on fluvoxamine to communications about Merck’s drug molnupiravir. The evidence for molnupiravir is in many ways weaker than the evidence for fluvoxamine, but molnupiravir was produced by a major pharmaceutical company that can shepherd it through the process of becoming a recommended drug. On a call last week, Mills said, the FDA told him “they don’t know how to deal with submissions where there isn’t someone to be responsible for it.” But it looks like just as I published, he and his colleagues found a way around the problem:

https://astralcodexten.substack.com/p/the-fda-has-punted-decisions-about   I. Here’s my pitch for fluvoxamine (Luvox) for COVID. In the midst of all the hype about ivermectin and hydroxychloroquine, scientists put together the giant 4,000-person TOGETHER trial, intended to test all these exciting COVID early treatments. You know what happened next: ivermectin and hydroxychloroquine crashed and burned. But a different drug, the SSRI antidepressant fluvoxamine, actually did really well! It decreased COVID hospitalizations by about 30% - not the perfect cure rate the rumors attributed to ivermectin, but a substantial decrease. Given the size and professionalism of this study, and another smaller one that also got positive results, I and many others take Luvox pretty seriously. At this point I’d give it 60-40 it works. Can you prescribe a medication when you’re only 60% confident in it? There’s some thorny philosophical issues around this, but I think in the end you have to compare risks and benefits. What are the risks? Like every medication, including Tylenol, aspirin, etc, Luvox has some common minor side effects and some rare major ones. But let’s step back a second. Fluvoxamine is a bog-standard SSRI. Its side effects are generic SSRI side effects. We give SSRIs to 30 million people a year, or about 10% of all Americans. As a psychiatrist, I’m not supposed to say flippant things like “we give SSRIs out like candy”. We do careful risk-benefit analysis and when appropriate we screen patients for various risk factors. But after we do all that stuff, we give them to 10% of Americans, compared to 12% of Americans who got candy last Halloween. So you can draw your own conclusion about how severe we think the risks are. For some reason the same experts who don’t mind prescribing SSRIs when people have mild depression freak out about prescribing them when they’re the only evidence-based oral medication for a deadly global pandemic. “What about SSRI withdrawal?”, they ask. After a ten day course? On 100 mg imipramine-equivalent dose? Minimal. “What about long QT syndrome?” The VA system took 35,000 high-risk older patients off of an unusually-likely-to-cause-QT-syndrome SSRI in 2011, and were unable to find any evidence that this prevented even a single case of the syndrome, let alone any negative outcome!

https://astralcodexten.substack.com/p/mantic-monday-let-me-google-that Let Me Google That For You New from Google this month: Creating A Prediction Market On Google Cloud. Google announces that they’ve been running an internal prediction market for the past year, with “over 175,000 predictions from over 10,000 Google employees”. 1 Predictive analytics.jpg Most of it’s classified because they’re predicting stuff about Google’s corporate secrets, but some friendly Googlers were at least willing to walk me through the article and clarify pieces I didn’t understand. The market, called Gleangen, is actually the second prediction market Google’s tried. The first, in 2007, was called Prophit - the team included occasional ACX commenter Patri Friedman, who’s since moved into the charter city space. (source) Prophit wound down because the founders left and nobody really knew what to do with; you can read about some of their findings here. In 2020, with all the uncertainty around coronavirus, some Googlers decided to try again. Gleangen is the result. Unlike most prediction markets, anybody can create a question on Gleangen. This usually goes badly: most people are terrible at writing questions with objective resolutions. Google manages by having a dedicated team of moderators who go over everything and amend it when needed. The market pays out in play money and the right to be on a leaderboard. So far it’s not doing much else. The Googlers I talked to saw no evidence that company executives were paying much attention to it when making decisions. Why not? Hal Varian, Google’s chief economist, said in a Conversation with Tyler Cowen: COWEN: Why doesn’t business use more prediction markets? They would seem to make sense, right? Bet on ideas. Aggregate information. We’ve all read Hayek. VARIAN: Right. And we had a prediction market [referring to Prophit in 2007]. I’ll tell you the problem with it. The problem is, the things that we really wanted to get a probability assessment on were things that were so sensitive that we thought we would violate the SEC rules on insider knowledge because, if a small group of people knows about some acquisition or something like that, there is a secret among this small group.

https://astralcodexten.substack.com/p/the-phrase-no-evidence-is-a-red-flag   https://astralcodexten.substack.com/p/the-phrase-no-evidence-is-a-red-flag Related to: Doctor, There Are Two Types Of No Evidence; A Failure, But Not Of Prediction. I. Click to enlarge Every single one of these statements that had “no evidence” is currently considered true or at least pretty plausible. In an extremely nitpicky sense, these headlines are accurate. Officials were simply describing the then-current state of knowledge. In medicine, anecdotes or hunches aren’t considered “real” evidence. So if there hasn’t been a study showing something, then there’s “no evidence”. In early 2020, there hadn’t yet been a study proving that COVID could be airborne, so there was “no evidence” for it. On the other hand, here is a recent headline: No Evidence That 45,000 People Died Of Vaccine-Related Complications. Here’s another: No Evidence Vaccines Cause Miscarriage. I don’t think the scientists and journalists involved in these stories meant to shrug and say that no study has ever been done so we can’t be sure either way. I think they meant to express strong confidence these things are false.

https://astralcodexten.substack.com/p/ancient-plagues   During our recent discussion of climate change, someone linked me to this New York Magazine piece making the case for doomism. I disagree with it pretty intensely, but most of my complaints are already listed in the sidebar (some scientists also complained, so they had to add a lot of sidebar caveats in) and I don't want to belabor them. The section I find interesting is the one called Climate Plagues: There are now, trapped in Arctic ice, diseases that have not circulated in the air for millions of years — in some cases, since before humans were around to encounter them. Which means our immune systems would have no idea how to fight back when those prehistoric plagues emerge from the ice. The Arctic also stores terrifying bugs from more recent times. In Alaska, already, researchers have discovered remnants of the 1918 flu. They actually extracted it from the cadaver of a frozen woman. that infected as many as 500 million and killed as many as 100 million — about 5 percent of the world’s population and almost six times as many as had died in the world war for which the pandemic served as a kind of gruesome capstone. As the BBC reported in May, scientists suspect smallpox and the bubonic plague are trapped in Siberian ice, too — an abridged history of devastating human sickness, left out like egg salad in the Arctic sun. Experts caution that many of these organisms won’t actually survive the thaw and point to the fastidious lab conditions under which they have already reanimated several of them - the 32,000 year old "extremophile" bacteria revived in 2005, an 8 million-year-old bug brought back to life in 2007, the 3.5 million-year-old one that a Russian scientist self-injected just out of curiosity - to suggest that those are necessary conditions for the return of such ancient plagues. But already last year, a boy was killed and 20 others infected by anthrax released when retreating permafrost exposed the frozen carcass of a reindeer killed by the bacteria at least 75 years earlier; 2,000 present-day reindeer were infected too, carrying and spreading the disease beyond the tundra.  

https://astralcodexten.substack.com/p/does-georgism-work-part-3-can-unimproved   [Lars Doucet won this year’s Book Review Contest with his review of Henry George’s Progress and Poverty. Since then, he’s been researching Georgism in more depth, and wants to follow up with what he’s learned. I’ll be posting three of his Georgism essays here this week, and you can read his other work at Fortress Of Doors] Hi, my name's Lars Doucet (not Scott Alexander), and this is a guest post in an ongoing series that assesses the empirical basis for the economic philosophy of Georgism.

https://astralcodexten.substack.com/p/does-georgism-work-part-2-can-landlords   [Lars Doucet won this year’s Book Review Contest with his review of Henry George’s Progress and Poverty. Since then, he’s been researching Georgism in more depth, and wants to follow up with what he’s learned. I’ll be posting three of his Georgism essays here this week, and you can read his other work at Fortress Of Doors] Hi, my name's Lars Doucet (not Scott Alexander), and this is a guest post in an ongoing series that assesses the empirical basis for the economic philosophy of Georgism. Part 0 - Book Review: Progress & Poverty Part I  - Is Land Really a Big Deal? Part II - Can Land Value Tax be passed on to Tenants? 👈 (You are here) Part III - Can Unimproved Land Value be Accurately Assessed Separately from Buildings? There were a lot of great comments to Part I. Most zeroed in on the practical aspects of implementing Georgism, such as how to deal with what Gordon Tullock calls The Transitional Gains Trap. Others brought up various perceived political obstacles and a few other topics (yes, I know about zoning, which is also a big deal). With a few exceptions, I didn't see much pushback on the core thesis of Part I, that land is a really big deal. In fact, many of the strongest opponents of LVT seem opposed precisely because they agree that land is a big deal.

https://astralcodexten.substack.com/p/does-georgism-work-is-land-really   [Lars Doucet won this year’s Book Review Contest with his review of Henry George’s Progress and Poverty. Since then, he’s been researching Georgism in more depth, and wants to follow up with what he’s learned. I’ll be posting three of his Georgism essays here this week, and you can read his other work at Fortress Of Doors] Hi, my name's Lars Doucet (not Scott Alexander) and this is a guest post in an ongoing series that assesses the empirical basis for the economic philosophy of Georgism. Part 0 - Book Review: Progress & Poverty Part I  - Is Land Really a Big Deal? 👈 (You are here) Part II - Can Land Value Tax be Passed on to Tenants? Part III - Can Unimproved Land Value be Accurately Assessed Separately from Buildings? Extremely special thanks to Count Bla and Alexandra Elbakyan

https://astralcodexten.substack.com/p/diseasonality [epistemic status: conjecture and speculation in something that isn’t really my field] I. It’s still not totally clear why some diseases are seasonal. Seasonal diseases usually peak in late winter - so around January/February in the Northern Hemisphere and July/August in the Southern. Around the equator, which lacks seasons, they’re less predictable and happen throughout the year. The best known seasonal diseases are flu and colds. But viral diarrhea and chickenpox also qualify, as do older mostly-eradicated diseases like measles and diphtheria.  The seasonal flu (source) The novel coronavirus is probably seasonal-ish, although it’s hard to tell since so much stuff keeps happening to make it better (vaccines) or worse (new variants).   The most common theories for disease seasonality are: Pathogens like the cold Pathogens like low humidity People are cramped indoors during the winter People have low vitamin D during the winter, and vitamin D helps fight pathogens None of these are really satisfactory on their own. Cold and humidity are definitely important - scientists can make flu spread faster or slower in guinea pigs just by altering the temperature and humidity of their cages. But it can’t just be cold and humidity. But if it was just cold, you would expect flu to track temperature instead of seasonality. Alaska is colder in the summer than Florida in the winter, so you might expect more summer flu in Alaska than winter flu in Florida. But Alaska and Florida both have lots of flu in the winter and little flu in the summer. (if it was just humidity, same argument, but change the place names to Arizona and Florida.)

https://astralcodexten.substack.com/p/model-city-monday-12621 Tegucigalpa, Honduras The socialist opposition has won Honduras’ election and pledges to fight against charter cities there. "Immediately upon assuming the presidency, we are going to send the National Congress an initiative for the repeal of the ZEDE law," incoming president Xiomara Castro said. This was what everyone was afraid of. But the last party tried pretty hard to protect ZEDEs from trigger-happy successors, and the constitution currently says that the only way to get rid of them is to win two consecutive 2/3 votes to do so, then give the existing projects ten years to wind down. Can the socialists get a 2/3 majority? Wikipedia predicts the incoming Honduran Congress will look like this: