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10Announcing Rational Newsletter
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Covid 8/12: The Worst Is Over
Alexey Lapitsky4y*20

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).

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Covid 8/12: The Worst Is Over
Alexey Lapitsky4y10

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. 

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Covid vaccine safety: how correct are these allegations?
Alexey Lapitsky4y10

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.

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Covid 7/15: Rates of Change
Alexey Lapitsky4y60

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.

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How do the ivermectin meta-reviews come to so different conclusions?
Answer by Alexey LapitskyJun 30, 202160

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

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Best of LessWrong: Jan 10 - Jan 17
Alexey Lapitsky5y10

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

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Anti-Aging: State of the Art
Alexey Lapitsky5y10

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.

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Anti-Aging: State of the Art
Alexey Lapitsky5y10

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).

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Anti-Aging: State of the Art
Alexey Lapitsky5y40

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 repair and renewal pathways in response to the damage.
  3. (also from the “damage” school) Part of the damage the body suffers is dysregulation of methylation. Methylation changes with age are stochastic. Methylation becomes more random with age.

My belief is that (1), (2), and (3) are all occurring, but that (1) predominates over (2). The “damage” school of aging would contend that (1) is excluded, and there are only (2) and (3).

There has been a lot of progress with (1) in the last years which makes me more optimistic in short longevity timelines.

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How do you assess the quality / reliability of a scientific study?
Alexey Lapitsky5y20

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

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