All of Alexey Lapitsky's Comments + Replies

Covid 8/12: The Worst Is Over

The effect could be different in Vietnam because of cultural differences, strictness of regulation or somethings else. Same as vaccine program compliance.

The central point is about adequacy of governmental decisions, not about compliance to them.

There are plenty of regulations about hospital food or child nutrition in the US that follow the dietary guidance. I have not looked into it but it would not surprise me if they regulate macro calorie intake for military (not that it matters for the central point of discussion).

1CraigMichael5moI don't believe this. I could get Taco Bell and cookies and other junk food in my high school cafeteria out of proportion to the pyramid. No one was regulating calories or macros. Maybe. But the point that USDA dietary guidelines causing are obesity is obviously wrong because the guidelines are the same in other parts of the world and they're thin. At best you could say "contributing" in some vague way, but even that's wrong. Try strictly following the USDA diet guidelines, literally to the letter and calorie and macro and I will guarantee you that you will lose weight. I can also guarantee you that you will be in a group of maybe, 4 Americans that actually do this outside of metabolic wards. The strictness of the regulations of pyramid in the US is basically zero, and the Vietnamese government doesn't go around punishing people eating fat or sugar either. I think you're closer to the mark when you talk about cultural differences, but sill not quiet on it. Scott (or Scott channeling Stephan) was on the mark here [https://slatestarcodex.com/2017/04/25/book-review-the-hungry-brain/]: I'm generally for free markets, but they are guaranteed to make populations fatter overtime.
Covid 8/12: The Worst Is Over

I would not underestimate the importance of US dietary guidelines.

For example, dietary guidelines are followed by schools, hospitals and military. They are also taught in medical schools and used by doctors to advise their patients. Additionally, lots of countries semi-blindly follow whatever guidelines US comes up with (see the parallel with covid treatments & measures?)

My gut feeling is that those guidelines directly contributed to a vast number of deaths / lost QALYs. 

1CraigMichael5moOkay. Why would those guidelines be awful for Americans but great for the Vietnamese? Are they? Like to the exact calorie and proportion?
Covid vaccine safety: how correct are these allegations?

even though J&J is not mRNA-based

The core point is that even J&J is not a traditional vaccine. It's also genetic (DNA-based) with a classic non-LNP delivery mechanism using an adenovirus. From what I understand, it penetrates a different subset of cells (using ACE receptors, afaik) that get killed by the immune system in the same way as with mRNA-vaccines.

Covid 7/15: Rates of Change

Strongly upvoted as well, and I agree with Vanilla_cabs - I don't think it helps classifying everybody concerned about covid vaccines as anti-vaxers. Maybe we need a better term.

Here is an analysis taking into account recovered people with natural immunity in the US:

https://youtu.be/vJy8jdunpFw?t=520

 

Personally, I'm wondering if antibody dependent enhancement could explain some weird patterns we are starting seeing now in highly-vaccinated places.

1Kenny6moThe better phrase would be 'people with concerns about COVID vaccines'. (Hopefully these people would also have specific, and reasonable, concerns too.) 'Anti-vax' seems to reasonably cover people skeptical of, or hostile to, vaccination generally.
How do the ivermectin meta-reviews come to so different conclusions?

The negative meta-study is borderline malicious.

"This article has an embarrassing history whereby treatment arms in the study of Niaee were reversed, attracting protest from Dr Niaee himself. This egregious error has been corrected in the revised version, but with no change to the Conclusions in spite of dramatic change…" - from BIRDGroup twitter

Pubpeer is also useful in cases like this:

https://pubpeer.com/publications/955418F3D4D39742CFFA8C1B023AA3

Best of LessWrong: Jan 10 - Jan 17

Similarly to Hacker Newsletter there is a weekly digest of Lesswrong posts on Rational Newsletter.

Anti-Aging: State of the Art

Interesting, thanks! My thinking is that:

  1. Methylation increases with age and predicts biological age
  2. Methylation affects protein synthesis in a semi-random way

Those points mean that epigenetics at least partially causes all hallmarks dependent on protein synthesis (loss of proteostasis, intercellular communication, etc). Meaning that epigenetics is at least partially upstream of at least a few hallmarks.

Not sure what being correct about information theory of aging would exactly mean or what other evidence to expect. Intuitively it feels that our efforts should focus upstream and that there are more low hanging fruits in epigenetics than in most of the other hallmarks.

1JackH1yThat seems plausible! The only thing I'll say is that from what I've heard, epigenetic reprogramming in vivo may be particularly challenging in many tissues in the body. Therefore, I suspect mTOR inhibitors and senolytics may be lower hanging fruit for anti-aging therapies approved first.
Anti-Aging: State of the Art

Very curious to hear a bit more about why you are skeptical about epigenetics and information theory of aging as the primary cause. But I completely agree that it's not the only cause!

"Being sufficient to slow aging" is a pretty low bar, I have virtually no doubt that reprogramming will slow aging (it already has been done experimentally with mice).

4JackH1yI don't see a lot of evidence for the information aging theory in the literature, and most geroscientists don't seem to think that epigenetics is the master regulator of the other hallmarks. This isn't to say it's not true, just that there's insufficient evidence at this point. Sinclair discusses all of the hallmarks, but focuses on epigenetics as the most important - which is incidentally the one he studies. Bear in mind as an academic this is something are incetivised to do - to tell a narrative that fits their research agenda, to attract funding. Looking at the field as a whole, there is consensus about the hallmarks but not so much consensus about the information aging theory, and in fact I don't know of any other major geroscience researchers who have endorsed the information theory of aging. It's too early to say that he's incorrect, but the theory seems unlikely from my reading.
Anti-Aging: State of the Art

Thanks for an amazing post, Jack!

I think it's worth mentioning that damage accumulation as the root cause is not the consensus view anymore.

To quote Josh Mitteldorf, there are three views:

  1. (from the “programmed” school) Aging is programmed via epigenetics. The body downregulates repair mechanisms as we get older, while upregulating apoptosis and inflammation to such an extent that they are causes of significant damage.
  2. (from the “damage” school) The body accumulates damage as we get older. The body tries to rescue itself from the damage by upregulating repai
... (read more)
3JackH1yHi Alexey, So, having talked to a number of people in longevity biotech, I'm skeptical as to whether view (1) i.e. Sinclair's 'information theory of aging' which posits epigenetic aging is the master regulator for the other hallmarks is accurate, and that cellular reprogramming alone is sufficient to slow aging. I think the information theory of aging [https://hplus.club/blog/a-summary-of-david-sinclairs-information-theory-of-aging/#:~:text=Regulating%20gene%20expression%20is%20the,female%20in%20the%20example%20here).] is good PR for the field, [https://www.youtube.com/watch?v=_G2gy1zBilA] but I don't think it's entirely correct. Still, the next 5 years of research will provide more clarity as to the relationship between epigenetic alterations and the other hallmarks of aging. I hope (1) is true although from the data I've seen and people I've spoken to behind the scenes, I don't think it's likely that cellular reprogramming alone will be enough. I think the hallmarks develop to some extent independently, even though there is some level of cross-talk between them, and will have to be individually addressed.
How do you assess the quality / reliability of a scientific study?

I am using https://scite.ai/ with a plugin for browsers, but I would love a similar service with user-generated flags.

[Link] Faster than Light in Our Model of Physics: Some Preliminary Thoughts—Stephen Wolfram Writings

I'm not pretending to even remotely understand the math in question, but, subjectively, his team is doing novel research. The initial results look promising and it looks like they are constantly making progress even though they started pretty recently. The papers are being peer reviewed and they are actively engaging with community.

I know that they are constantly trying to find areas which could generate novel predictions, but maybe it's a bit too early to demand so much rigor at this point?

Not directly related to your comment, but I don't understand why there is so much negativity coming from our community and I don't see why objections could not be respectful.

2Kenny1yI agree – it seems perfectly fine research, and, as you mention, novel. I also think it's not only too early but besides the point to demand rigor at all. Or, it's fine to demand rigor, but no one's obligated to supply it – not even Wolfram or his team or the wider 'community'. It's fine to ignore them too! But yes, it's unreasonable to expect a lot of rigor given how young this 'field' is. I also thank that – *reasonably – our priors regarding the computational, i.e. practical, difficulty of simulating our universe (or something similar) at the level of 'space quanta' is immense. String theory seems to have run into similar problems – and it's been one of the premier fields in physics for decades. AFAIK, our simulations of the Standard Model, or other quantum mechanical models, are extremely limited too. Why would we expect any more fundamental theory to be even that much more difficult to compute/simulate/analyze? I think that, given the extremely young age of this topic of research, the kind of qualitative 'eyeball or ad-hoc program' analysis Wolfram provides in his published work is eminently sensible and reasonable. It should be very much exploratory at such an early stage. The math is a bit advanced at times but the 'raw' research is much simpler – basically very simple computer programs, but lots of them. This is Wolfram's big/unique trick (IMO): just enumerate literally all of the possibilities for some class or set of simple programs and, often first, look at some visualizations of the programs, e.g. their evolution, and look for patterns, first with your eyes/brain and then, incrementally, with more and more 'search' programs. If possible, one might find good 'mathematical' compressions of the data/info/behavior of the programs, and, more rarely, a good 'mechanistic' understanding as well. He wrote and published a book – available free online here [https://www.wolframscience.com/nks/] – that's a massive infodump of basically all of his thoughts an
The Conceited Folly of Certainty

Thanks for the article!

How could such a brilliant individual let personal dogma and rigid belief (overconfidence, in fact), supersede rational discussion

I would not go as far as to say that his beliefs were not rational or dogmatic. One can also argue that Einstein's intuition was correct and that he was right to challenge the Copenhagen interpretation.

Longevity interventions when young

Have you looked at the claims that whey protein contains NR? I briefly looked at the commonly referred papers but I could not see anything relevant, let alone specific numbers.

1George1yNo... and searching for it I can only find things like: https://selfhacked.com/blog/nicotinamide-riboside/ [https://selfhacked.com/blog/nicotinamide-riboside/] Which are referring to other forms of B3 being found in whey protein. The things with NR is that it's considered a form of B3 (which is the **** way "vitamins" work in that for some of them the "vitamin" is actually any substance that after some point turns by some % into a specific metabolite) and some other forms of B3 are found in whey protein. I haven't seen claims of NR specifically being found in whey protein, so I have no idea and a quick google doesn't reveal much for me other than stuff like the above.
Longevity interventions when young
I'm not 100% sure this article is in tune with LW

It absolutely is! Thank you for writing this post and I'm looking forward to your follow up articles.

Cheers!

Announcing Rational Newsletter

Thank you, the newsletter is alive and well :) I've managed to keep the updates weekly and I'm planning on continuing doing that.


There are a couple of hundred people subscribed so far.

System 2 as working-memory augmented System 1 reasoning

Thank you for such a well-structured and concise summary of the research! I really like this sequence.

Pretty interesting to see where all of that could lead from the evolutionary (working memory / type 2 processes in animals) and from the mental disorder perspective.

2Kaj_Sotala2yThanks! Glad you like it.
Raw Post: Talking With My Brother

Thanks for sharing!

You put quite a lot of effort into being reasonable and not antagonising your brother and it looks like you did a great job! In heated discussions like that, especially with family members, I'd recommend trying out NVC (Nonviolent communication).

Can't help but give you one example: "I finally told him ... [that] ... I felt like he was treating me with contempt". That might get perceived as an accusation or a judgement. I'd rephrase it (oversimplifying) as "I don't feel understood, could you give my poin... (read more)

I've reworded this reply about 5 times now, and I'm not sure why the words are proving slippery.

Basically, my experience with NVC and other such frameworks is that they most often get offered to people who are already working hard to communicate well. Quite naturally, since they're probably receptive to help in that effort and interested in analyzing their conversational dynamics in detail. Unfortunately, it's the people who lack good communication skills who probably need NVC. When the people who are already careful communicators are a... (read more)

Announcing Rational Newsletter

Thank you! RSS feed is definitely coming in the future.

1DoubleFelix2yDid the RSS feed ever come about? I don't see it anywhere obvious there.