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Apr 9
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Johnson isn't trying to live forever with his current routine. He explains in this interview that he's just trying to stay healthy until the singularity:

https://www.youtube.com/watch?v=OqlPU1CKEpI&t=100s

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"A ‘vaccine-like’ version of Wegovy is on the drawing board at Novo Nordisk (Stat+). If you are convinced you need this permanently it would be a lot cheaper and easier in this form, but this is the kind of thing you want to be able to reverse, especially as technology improves."

It sounds like the "vaccine-like" version is just the same sort of GLP-1 molecule, but it would just last a year instead of a week. So it's not permanent, and there's no real need for it to be reversible.

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Re the sock. Out of desperate necessity, I've developed a talent for getting accurate oxygen readings on babies and children with adult pulse oximeters.

Step 1: if you can't get the kid to be still, you usually don't need to worry as much and can drive to ER.

Step 2: Use the foot or entire hand.

Step 3: If your child is unfortunate enough to be admitted to the hospital and monitored, use the opportunity to get the adult pulse oximeter to match their reading.

(But first order something yummy for yourself to eat)

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"Sulfur dioxide in particular is a huge deal. The estimate here is that a 1 ppb drop in levels, a 10% decline in pollution, would increase life expectancy by a whopping 1.2 years. Huge if even partially true, I have not looked into the science."

My priors on most health effects of low levels of pollution is that this is exactly the sort of area I expect bad science to rule the day. Good studies are somewhere between difficult and impossible to do, and I would expect that all the right people will be lining up to say how awful the effects of pollution are and how good the science is, even when that's not true. And there is really no strong interest group on the other side to point out how the entire field is nonsense. So I'd be interested in someone like you or Scott Alexander doing a deeper dive and investigating how good the evidence is for things like this.

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Also, don't they also say that the recent uptrend in global warming is largely due to reduced sulphur dioxide emissions??

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"Of all the low hanging fruits in health care, ‘lots of capable people want to be doctors and we should train more of them to be doctors’ has to be the lowest hanging of all."

Oh no, there's a lower one. Lots of capable people are *already* doctors and want to be doctors in the US, and we should let them do that.

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the fruit here is so low hanging that it's fallen off the tree and fermented into a sweet liquor. I totally agree that "being a doctor who wants to come to the US should be a free pass in." And not to engage in a fruit limbo one-upping contest here, but there's an even lower hanging one: there are doctors, already credentialed from reliable programs in fine respectable countries abroad, already have navigated the arcane process to come and live in the US, who would like to practice medicine, and we force them to undergo a lot of further (often demeaning - like for someone who practiced for 15 years having to go back as a resident) training before they are allowed to brutally reduce our medical costs and cure our illnesses.

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"So yes, assuming this is a full cure then this does seem worth it for America, on the principle that a life saved is worth about $10 million. In theory we should be willing to pay at least $5 million for this drug, possibly up to $10 million, before it would cost more than it is worth."

I think this is missing out a key component of the cost/benefit analysis. A relatively small portion of the benefit is the lives saved over the next ~15 years, at a cost of $4 million each. But a much bigger portion of the benefit is the lives saved over the next several decades, at whatever the marginal cost of the drug is. And then there's all of the medical advances that will build on drugs like this that can be used to treat other disease.

Overall, I'm skeptical that, at a societal level, saving a toddler's life is worth it at $4 million each, at least under a cold-hearted cost/benefit analysis. But factoring in those other benefits, I think the calculus could change quite a bit.

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As I understand, the entire compact of patent is that the inventor gets to take 100% of the surplus as profit for ~15 years or so, and then the cost drops to marginal cost of production and all of society benefits.

I think that $4 mil probably is close to the max they could charge, but that is actually a fair and just reward for their innovation, *Provided they don't try to game the patent system to prevent generics from existing when the patent expires (which has happened to many drugs)

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On the "people used to eat much more" part I strongly feel like this is misled.

We have a large body of litterature suggesting the reason for weight gain is essentially "calories in - calories out" along very strong mechanistic plausibility.

We also know even modern nutritional epidemiology is extremely flawed and prone to methodological errors.

In this context I don't think a handful of decades old studies constitute sufficient evidence to infer that "it seems improbable that too many calories in and too few calories out are the cause of modern obesity" as the author does.

Even at a quick glance one can easily find flaws in many of the studies he cites, highlighting how he things they're "more evidentiary than the usual [...]".

Children being served given amounts of food? But they don't measure how much they actually eat.

Soldiers supposedly eating upwards of 5500 kcal not gaining weight on a mere "3 hours of moderate activity a day" ? Give me a break ....

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It also doesn't make sense from an evolution perspective. Starvation used to kill lots of people! It was probably the main population limiter for thousands of years! But humans used to just consume an extra 50% of food energy that...just didn't get used? That doesn't pass the smell test to me.

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>But humans used to just consume an extra 50% of food energy that...just didn't get used? <

The claim is not that this energy didn't get used, it's the other way around. The energy that is stored as fat is the type that isn't used (unless it gets used later). The energy that isn't stored as fat is the kind that gets used to do things: movement, heat production, brain work, secretion of hormones, etc. So if these people used to eat more without getting fat, it would necessarily mean that they used more energy for doing more things.

The % of incoming energy a person uses for doing stuff versus the % she stores for later use is highly variable and mutable in time. When my homeostasis mechanism (whatever it is) gets the idea that food is scarce (I'm either dieting or suffering famine) then my energy use is brought to minimum, I'm tired, cold, inactive both physiologically and physically, and storing as much energy for later use as possible. Moreover, there are several known chemicals that affect the state of this mechanism quite a lot, e.g. stimulants make you use more energy and store less of it, Lithium the other way around, etc. If people were eating more back then while staying leaner, the natural explanation would be that there's something in the environment that pushes our homeostasis mechanisms towards more storing. It's totally feasible as a hypothesis, there is nothing that would make such a case theoretically not possible. We just don't have enough data to know.

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The claim is that even people "who did limited physical activity" were not gaining weight, despite eating a lot more. It's not a physical impossibility that this excess energy was just burned off to maintain a higher body temperature, but I find that explanation implausible.

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> maintain a higher body temperature

Did people tend to be mildly sick more often in the past? I could imagine a situation where people are running mild fevers more days than not to counteract various illnesses picked up in the course of life.

And/or we're miscalculating just how much more work and effort people did day to day compared to modern times.

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"And/or we're miscalculating just how much more work and effort people did day to day compared to modern times."

It seems more likely that we would miscalculate how much people are eating rather than how much people are working, but it could be either/both.

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I think the post didn't sufficiently account for all the movement people used to do outside the categories of work and exercise. We don't think of walking as being "a workout," but many more people in the past walked for hours a day. Riding a horse or driving a carriage is also more activity than sitting in a car. Doing your own housework, fixing your own appliances, simple carpentry, lawn care with a manual mower. Much more laborious cleaning and cooking.

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> Someone should buy 23AndMe purely to safeguard its data

Has anyone managed to demonstrate a credible attack vector that results in significant damage to a persons life due to their DNA being leaked? I can only think of super rare edge cases, such as an a sperm donor who wants their DNA sequenced but doesn't want their 15 bio kids to find them.

> You have something that is 95%-99% to be essentially fine (depending on your threshold for fine) but will sometimes kill you

It was ~99.9% fine if you were under 30 with a BMI under 30 and no respiratory problems. And yet ~nobody in the government was saying this publicly or saying that night clubs should remain open as long as they don't admit people older than 40. Instead, high school students and retirees were treated as if they're in the same risk group.

> America utterly failed to make tests available in reasonable fashion

Yes, but in 2021 they've also failed to tell people to stop getting tested if they're only hanging out with people under 40 or with vaccinated people. I've seen plenty of people waste time getting tests in summer 2021 when everyone in their social circle had the vaccine.

> ‘I’m 28. And I’m scheduled to die in May.’

I do wonder if this person has considered/tried any illicit substances before choosing to commit suicide. If you're going to die anyway, why not first spend a month or two doing acid, smoking weed and doing lines of ketamine? Heck, if death is the only other option, I'd try opiates as a measure of last resort.

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Not to pick on you specifically — everyone does this; I’ve already been irritated by the same thing on another substack tonight — but I do have to wonder how the heck a BMI of 30 became a poor prognostic risk factor regularly casually spoken of in the same breath as an age of 70+ years. In early analyses (wild-type virus, pre-vaccine population), Class I obesity was indeed an added risk factor … one comparable in magnitude to maleness. We of course never hear a peep about how, say, excluding men from crowded public spaces would have been an appropriately nuanced approach in 2020. (My own BMI is well under 30; this overfocus on obesity as a covid risk factor irks me no less.)

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I think that's understating it. Obesity, which is highly associated with significant metabolic degradation, is already a massive risk factor for nearly every disease that exists, it seems very odd that it would not also be for covid.

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asthma and smoking were also counterintuitive; sometimes reality does surprise!

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> demonstrate a credible attack vector that results in significant damage to a persons life due to their DNA being leaked?

print someone else's DNA and leave it at the scene of your crime.

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just kind of joking. 23andMe doesn't actually sequence genomes, they just do SNP panels

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> nobody in the government was saying this publicly or saying that night clubs should remain open as long as they don't admit people older than 40

It's not as if those under-40s would have stayed isolated to their healthy bubbles. The pre-vaccine R0 was extremely high, and those night clubs would have been prime locations for super-spreader events. Then those people would see their parents, interact with coworkers, etc. They would be overwhelmingly fine, but those around them would not.

Delaying those infections to post-vaccination times was an important public health step.

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Yes, yes, that was the official party line, I remember. Challenging that idea could get you banned on all social media.

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> My actual impression is that the elite therapists largely do not market themselves at all. They instead work on referrals and reputation. So you have to know someone who knows.

This is an underrated reason to give therapy a try. Having the direct contact info of a few therapists who know and trust you personally can be incredibly helpful. Even if you end up not needing the help of a therapist for long, think of it like any other professional relationship; maybe they'll be a better fit in the future and they can always open their network to you if you need it.

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The actual problem with the sock was that it had way too high a false positive rate of emergency. Kid kicks sock off a bit, it fire off an alarm, you wake up in a panic and get your sleep disrupted.

However, it did absolutely let us know when our baby with RSV needed to go into the hospital vs convalescing at home. And for 1st time parents it was a nice little bit of piece of mind.

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That's exactly the right problem to have! I love that for most parents. And very much a cost they can decide whether to pay.

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Agreed - was a nice option to have. To be clear, I don't think the actual problem is why the FDA had an issue with it (I agree that your explanation of it is correct).

But the actual practical issue was definitely false positives (and in general it gave a blood ox a few percentage points lower than what was the actual likely at any given time). Though it wouldn't throw an alert until it got below 90% I believe, so it mostly corrected for that.

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Agreed. We bought a similar sock but it would scream an alarm any time it came off the baby's foot and she kicked a lot. We ended up only using it the one time she had a fever, and separately used it a couple of times as an oximeter to put on, take a reading, and take off.

Fwiw the "sock disconnected" alarm was clearly different to the "something is wrong" alarm, but still really loud and impossible to disable - crucially, I couldn't set it so it wouldn't wake up my partner even if I was awake to monitor the baby.

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Typo: "charing" → ?

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Zvi writes: "Also, they are going to put each person on each diet for only two weeks? What is even the point? This does not seem like $189 million well spent." Perhaps the researchers simply could have each rented and watched Morgan Spurlock's "Super Size Me" to get 80% of the learnings.

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"90% of junior doctors in South Korea strike to protest against doctors."

Not to jump up and down on this soapbox, as you kindly quoted me once, but the US is way, way worse on this. Docs in the US don't have to protest, because the AMA, CMS, and the federal healthcare government in general spent most of the 90s/2000s throttling residency spots (which CMS literally pays for only a limited # of) in order to forestall an upcoming terrible disaster of oversupply of doctors. The shortages we have right now - and the push for more and more independent practice from non-MD's - are a direct consequence of that.

I am 100% for less restrictive legal barriers to people practicing medicine, but there's at least a small story to be told about how we have been relaxing the practical, educational (i.e. the hours of study, and times of practice) barriers to practice specific subsets of medicine in order to route around the lack of docs. And that obviously US nurses/etc... have a much stronger lobby than foreign medical people.

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Even though longvid having a disease burden like cancer or cardiac disease is Obvious Nonsense, the narrower claim that covid has meaningfully raised disease burden in general seems clearly true. Like I don't personally know a single person who's been long-term debilitated by covid - even finding cases of real bad cases is hard - but attendance data from my workplace shows a clear pattern. In the Before Times, the average number of absences to trigger a "you're maybe not getting a raise" each half-year was 7 or so. After covid...that's roughly the number of sick days an employee averages in a month or two. Sure, some of those are probably "mental health days" or other not-strictly-covid things. People also aren't gonna get a test every time, so that increases the odds of generic cold and flulike symptoms leading to calling out Just To Be Safe. But from a business POV, the actual cause doesn't really matter - a sick day is a sick day, the absenteeism exists either way. So it's still a useful approximation to blame the curve shift on "Covid". I'd imagine it's the same situation in schools as well. Hopefully they've likewise updated their policies on absenteeism to grade a bit more on a curve.

(Still want that damn pan-coronavirus intranasal vaccine. It's really annoying not being able to work, even if the actual illness is mild. Written while home sick.)

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If it helps your anecdata, I personally know at least 2 people who got seriously debilitated by long Covid - a next door neighbour and a cousin, so not selected in a way that correlates with ill-health or anything. Both in their 40s; the neighbour is basically disabled, years later. My cousin did (mostly?) recover but was out of the workforce for *months* and feeling subpar for additional months after (I'm not actually sure he ever got back to 100% , but I'm not sure he didn't' either, we're not close)

The rate of people fucked over by it in 2020 seems shockingly high, the rate of long covid from later strains seems much much lower

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Skeptical @ that blag arguing against CICO. Especially if they're citing SMTM's obesity series approvingly - I thought the "It's Probably Not Lithium" LW post pretty thoroughly dismantled that argument. Doesn't really grapple with measurement error, either - it's not just a methodological issue with surveys, it's that accurately measuring both CI and CO is harder than it first appears. All models are wrong, some models are useful...

It's also weird to have a section on the metabolism hypothesis, but neglect the obvious standout from the data, which is that basal metabolism is the bulk of CO even at "heavy" activity level. An appropriately intense workout/sports/whatever might be able to get a higher percentage, if it's sustained long enough...conversely, the amount of calories burned from modern intentional exercise is less than one would think, while also stimulating appetite, quite possibly ending in a net caloric gain. (I'm a fan of thermogenesis, personally - shivering and other subconscious involuntary movements are an easy way to passively burn calories. Much happier dryly chilling than wetly sweating in spandex. Have heard there's ice vests and such for people who don't happen to work in walk-in freezers.)

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Nothing here sounds like a strong argument against the environmental pollution hypothesis. But I'll give you a better argument that you'll like: the basal metabolism rates from the 1953 workers' study don't look like higher than those measured today(?). We would expect these to have dropped, if some environmental pollutant nudged our homeostasis mechanisms to save energy and store it as fat more than previously, as the hypothesis goes.

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Hmm, I meant more the strong version that It's Lithium or It's PFAS or It's [some other candidate pollutant]. As far as I understand, while such pollutants aren't *good* things and we'd probably do well to reduce them on the margin, it's sort of like Gary Taubes On Sugar where people focus too hard on easily-identifiable culprits, but then those specific cases get taken too far with excessive confidence. More generally I buy the case that a lot of modern food is, well, unfood with a bevy of weird stuff that we aren't especially well equipped to metabolize long-term. Polygenic model, if you will. Perhaps the pathway isn't directly towards affecting basal metabolic rate*, either; there's more than one road to the obesity phenotype, which is what people actually care about (I think?). But it probably won't end up being due to This One Weird Trick.

Did see that assertion that average body temperatures have dropped, and thus basal metabolism today must be lower - I haven't heard that claim before, which makes me a bit skeptical since I often peruse posts on nutrition science. Handwaving away the inflammation literature was also weird, unless I missed some recent failed replications. Big If True, I guess?

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