All of Kamil Pabis's Comments + Replies

Omicron Post #7

Given the data we have getting an "illicit" fourth booster shot might be the safer play. The mRNA vaccines continue to work, especially against severe disease, the effect is just much diminished.

1tkpwaeub1moThat's what I did. I'll let you know how it works out. See you on the other side.
Universal counterargument against “badness of death” is wrong

Also, is there even any evidence for this assertion? If we stipulate that absolutist monarchies are about as bad as a dictatorship then how did that assertion work out historically? Over the last 10'000 years when lifespans were much shorter dictatorships and related systems flourished. The ascent of democracy has paralleled an increase in lifespans. Correlation does not imply causation, but at least it makes it more likely, whereas the dictator argument is just speculation as far as I can tell.

Book Review: Open Borders
  1. Thank you for making a great point! Large countries do implement limits on internal migration to ensure political stability. The Chinese system is called hukou if anyone wants to read up on it; I am no expert myself. I would, however, disagree that these limitations suggest there is no free movement. In fact, the very existence of these limitations suggests we should open up compared to the baselines, but perhaps not fully.
    The population of Shanghai grew almost 100% from 14M to 27M within the last 20 years - and the city transformed into a wealthy metropol
... (read more)
Book Review: Open Borders

You are right, the same is true in Germany as well. There is even some evidence for lower crime rates for certain immigrant groups (e.g., first generation immigrants from Turkey, or SE-Asian/Chinese immigrants, if I recall correctly). Still, more crimes means more crimes, even if this is due to demographics, and the voters will punish the pro-immigrant parties accordingly.

3Jiro3moThe "lower crime rates for certain immigrant groups" is exactly why these figures are deceptive. If certain groups have lower crime rates, don't lump together high crime and low crime subgroups as "immigrants" and claim that immigrants as a whole are neutral on crime rate.
NVIDIA and Microsoft releases 530B parameter transformer model, Megatron-Turing NLG

How limiting are poor corpus quality and limited size for these models? For example, Megatron-Turing NLG was only trained on PubMed extracts but not on PubMed Central, which is part of the Pile dataset. Was this perhaps intentional or an oversight?

Regarding medical texts, I see many shortcomings of the training data. PubMed Central is much smaller at 5 million entries than the whole PubMed corpus at 30 million entries, which seems to be unavailable due to copyright issues. However, perhaps bigger is not better?

Regarding books, how relevant is the limited s... (read more)

7gwern3moNot very, now. Compute & implementation are more limiting. Corpus quality definitely affects how much bang per FLOP you get, at a moderate (neither extreme nor negligible) sort of constant factor. The Pile is better than what OA used, so an otherwise-identical GPT-3 trained on it would be noticeably better. (But this only goes so far and you will have a hard time doing much better than The Pile in terms of cleaner higher-quality text.) Corpus size is unimportant because existing corpuses are enough: the optimal training method is to do 1 epoch, never reusing any data. But you are usually limited by compute, and the compute you have uniquely specifies the model size and n. Even for Nvidia/MS using their supercomputer with 5k+ A100s, that n is a lot smaller than what The Pile etc already contains. (See the part about over/undersampling and how few tokens they trained on compared to the full dataset. GPT-3 did the same thing: oversampled WP and books, but then didn't use more than a fraction of their CC subset etc.) So in other words, PMC vs PM is irrelevant because even if you bothered to get the full PM corpus, they already had more text than they could afford to train on. They don't want to throw out the other data in order to train on mostly PM, so just PMC is fine. (When you have too much data, what you can do to get some value out of it is you can filter it more aggressively to cut it down to just that amount you can afford - but filtering itself is an open research challenge: lots of nasty software engineering, and you may wind up sabotaging your model if you eliminate too much data diversity by mistaking diverse difficult data for bad data & filtering it out. And if you do it right, you're still limited by the first point that data cleaning only buys you so much in constant factors.)
Covid 10/7: Steady as She Goes

As far as I can tell, if they suspend one of two available mRNA vaccines this is bound to have zero effect on vaccination rates in the young because the other one can fill the gap.

1cistrane3moIf you completely neglect the effect this will produce on vaccine hesitant population, and consider only these Nordic countries which have plentiful supplies of both mRNA vaccines and over 70% vaccination rate.
Humanity is Winning the Fight Against Infectious Disease

Do you think this is a problem? It appears to me that no development is possible without some tail risk (which we obviously want to minimize wherever possible!). Can we come up with a realistic world in which technologic progress is used for peaceful purposes exclusively and never causes any negative surprises? Or a world that develops with zero tail risk?

2adamzerner4moIMO yes, it is a gigantic problem. I agree that there are tradeoffs where progress implies some amount of tail risk as a consequence. The thing is that I don't think we are navigating those tradeoffs well. The analogy I like to use is that our technological progress is like giving a machine gun to a child. Bad things are bound to happen. To use that analogy, when/if we mature to the level of Competent Adult or something, that would be the time to start playing with machine guns.
1acylhalide4moHow theoretical or practical an answer are you looking for? Might be relevant - we are exposed to tail risks even if we do not develop. And we are likely not even aware of the complete set of tail risks we already face as of today. Even observing these requires new development. And ofcourse we also want development for various reasons pertaining to growth. Question is whether new developments reduce pre-existing tail risks better than they create new ones. Again, observing these risks often takes more development than the development itself.
Should I treat pain differently if it’s “all in my head?”

My personal experience is that it's true hence I would caution against too much rest. Wrist pain is a very vague term, no idea what you have, but I have battled RSI for over half a decade (mostly of the fingers) and at some point it got so bad that I wanted to quit my degree and it felt like even reading a book or newspaper was too painful. By all means, use your voice, contralateral arm or legs and feet to take over some repetetive tasks.

However, you need to use, strengthen and stretch your wrists as well. Targeted massage and strengthening with a physiot... (read more)

We need a new philosophy of progress

Trying to organize my thoughts on progress a bit:

I do not think we lack a "philosophy of progress" as much as the OP.  I would like to argue that progress is real and that there is decent literature on this topic that not enough people read. Moreover, the topic of progress is a good recruitment tool for EA and rationalism. I find it more exciting and powerful than the bleak nihilism offered by atheism, meek criticism of pseudoscience offered by “the skeptics” movements and the vague (but obviously not misguided) appeals to the noble human nature proff... (read more)

A deeper look at doxepin and the FDA

I do not think that is true, at least in Europe where hundreds of millions of people use generic drugs every day. In Germany, in the UK and in Austria a doctor will amost always prescribe a generic when available and people will often buy a generic over the counter. While sometimes too conservative, the very reason why we need the FDA, the EMA, et al. is exactly to make sure that generics* work well -- and they almost always do, one cannot use rare counter examples to disprove that. Do we have any hard data to suggest that generics are somehow unsafe?

* i.e. not some Indian blackmarket knock-off that isn't FDA/EMA approved

4ChristianKl5moAs I said, the Ranbaxy saga. It shows that even when there's a whistleblower from the manufacturer that tells the FDA that a manufacturer is fraudulent it takes the FDA years to do something about it. The approval consists of believing the company that the studies they provide are true. The FDA doesn't have subpoena power over Indian factories producing generics and it doesn't do independent quality checking beyond believing the companies.
Josh Jacobson's Shortform

With such highly subjective soft outcomes a lot depends on the way the question is phrased and interpreted (if self-reporting). Thus comparing different populations and studies is almost impossible without really carefully digging into the original publications and even then it is fraught with problems.

If I have a rash post-vaccine and I go to see my GP or pharamcist, am I seeking medical help and is this worrisome? If I get up and later realize that I need to lie down or else I will faint (vasovagal syncope, around one in ten people have some form of need... (read more)

How good are our mouse models (psychology, biology, medicine, etc.), ignoring translation into humans, just in terms of understanding mice? (Same question for drosophila.)

The sad fact is that we do not even understand mice very well. There is this old joke that can be paraphrased like this: if I were a mouse I could be cancer free and live forever, because it is so easy to cure these guys of diseases. As it turns out, however, this is not true. Within my field it was long gospel that caloric restriction (discovered some 100 years ago) can robustly extend mouse lifespan until studies in the last 20 years called this into question.

What the joke gets right is that we understand humans even less than mice. In fact, despite the ... (read more)

2Ruby1yThanks! From what you're saying, empirically we know some more things about mice, but that doesn't mean understand better the details of processes going in them much more than humans.
Why is loss of muscle cells not considered one of the hallmarks of aging?

I guess this goes back to the issue of defining things and what you mean by hallmarks. If you define your hallmarks broadly enough they may include almost anything while being so vague that they are only useful for posters and ads. In the case of vague hallmarks you'd be right, if you fix them you're all good. But even in this extreme case I do expect the number of vague hallmarks to grow a little bit over time as we learn more. In fact, to me they feel incomplete and ill-defined already.

Looking at the classic "The Hallmarks of Aging" paper (first publishe... (read more)

2ChristianKl1yAubrey's case for trying to focus on the hallmark is that there are a lot less of them then illnesses and it's thus easier to focus on hallmarks then on illnesses. It seems that this thesis is basically wrong if they are two vague to be individually targeted.
(How) should we pursue human longevity?

My reply comes a bit late since I managed to write a long comment without clicking send and only noticed this now. I will address the errors I see in the TL;DR summary from the POV of a semi-professional biogerontologist:

The disease-based approach to aging this seems to favour is useful, but limited. In fact, if you genuinely want to extend both lifespan and healthspan this excessive focus on the disease-based approach would be inefficient because is inconsistent with everything we know about aging. I would go as far as to say that the disease-based approa... (read more)

Why is loss of muscle cells not considered one of the hallmarks of aging?

Actually, they all do include it, but is is subsumed under stem cell aging, loss of cells and reduced regenerative capacity. Also to clarify what I would consider a misunderstanding. Not everything has to fit. There are probably infintely many causes of aging or at least quite a lot. Most of these fall into the rough categories or "hallmarks" we have come up with like reduced stem cell functioning or damage to biomolecules. Many of these causes are not relevant to immediate life extension which is why they can be ignored for now. Other categories or "hallm... (read more)

2ChristianKl1yI thought the idea of the hallmark was that there was one thing that you could fix and if you fix it then you solved the issue. If you solve stem cell aging you don't automatically get more muscle cells.
5johnswentworth1yGood answer, but I disagree with this specifically. I spent a few days reading up on age-related NMJ dysfunction at one point, and my main takeaway is that it's widely studied mainly because it produces cool images. I have not been able to find any evidence at all that NMJ problems cause age-related loss of muscle strength, despite the large amount of research poured into the subject. (If anyone knows of such evidence, I'd love a link to it.) My current best model is that age related NMJ remodelling is just a side effect of other damage/repair, and doesn't have much functional impact other than making the junctions look a bit different when people image them.
Covid 12/31: Meet the New Year

Does not make that much intuitive sense to me because there are a lot of random mutations happening. If the first dose first (or first dose only) strategy reduces the size of the whole SARS-CoV-2 viriome, there will be fewer viruses and less genetic variation in total. More infections in total means more genetic diversity. More infections means that a vaccinated person will be exposed to more sources of infection, more virions, more different genomes over time, thus also increasing the likelihood of mutants able to escape the immunologic response.

2PPaul1yDoes that assume that the amount of mutations (and therefore the risk of an immune escape) is only dependent on the size of the viriome? But isn't it possible that the risk of an immune escape mutation in the 1-dose vaccinated population is much higher than in the rest of the population? I think if that was much higher, it could swamp the benefit of reduced overall chance for dangerous mutations occurring due to the reduced infections from vaccinating more people (as compared to 2 doses). Not sure of any of this, just trying to think through your intuition.