DavidSJ

5 ms·

1.
by DavidSJ 2mo ago
> Worse than 0.01% of humans means that there are 8,000,000 people better than it. I know that's being pedantic I understand what you're saying. Since we're being pedantic, it means that there are (approximately) 800,000 p
2.
by DavidSJ 3mo ago
I've been a regular reader of Alzforum, and cite multiple of their articles in the blog post that was linked up above. https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
3.
by DavidSJ 3mo ago
Perhaps I am just not well-informed but 30% slowdown in progression translates to sufferers have some mild improvement in cognitive tests and live a few months longer. A few years longer. It's obviously frustratingly far from where w
4.
by DavidSJ 3mo ago
Note that not all AD-causing mutations in APP also cause amyloid accumulation, for example APP-Osaka (loss of APP residue E693) results in familial AD without any accumulation of amyloid [0]. This is interestingly similar to the Arctic Mu
5.
by DavidSJ 3mo ago
Yes, there is a clear sequence of how AD pathology develops, starting with amyloidopathy and progressing to tauopathy, but 1) there is as yet no established molecular connection between the two, and 2) one should not conflate pathology wit
6.
by DavidSJ 3mo ago
Thanks, great challenges. One may then ask, what is being remedied in the many, many, studies that claim to successfully target amyloid toxicity in mice? And is this relevant to the processes that occur in AD? I don't think studies r
7.
by DavidSJ 3mo ago
This is a reasonable challenge. I won't and shouldn't be able to convince you that my process was satisfactory, but I'll describe it anyways. I agree that I don't have the qualifications to check whether, for example, a
8.
by DavidSJ 3mo ago
I did. I started out very skeptical, then got convinced by the quality of the evidence.
9.
by DavidSJ 3mo ago
That's fair. I responded to hostility with hostility. Perhaps I should have ignored the comment or just responded kindly despite the hostility.
10.
by DavidSJ 3mo ago
The drug was discontinued later. You're thinking of aducanumab. Lecanemab and donanemab have been in widespread use for several years now, and open-label extensions vs. external controls showing increasing benefits over longer treatm
11.
by DavidSJ 3mo ago
Those are amyloid-only mice. It's an amyloid+tau disease, with tau the proximate cause of neurodegeneration. Normal mice don't get tau pathology, whereas even healthy human beings do, however it stays localized until the presence
12.
by DavidSJ 3mo ago
Thanks for these comments! The multiple pathways into a common entrypoint is definitely a challenge to communicate.
13.
by DavidSJ 3mo ago
You read the article in which I discuss the matter you say I was unfamiliar with?
14.
by DavidSJ 3mo ago
Not reverse; the neurons have died. Cease, yes, if the cause is removed early enough. But if you intervene too late (once symptoms are detectable), then the downstream tau pathology, which is what directly kills neurons, likely spreads on i
15.
by DavidSJ 3mo ago
The hypothesis that amyloid is simply a downstream effect, not a cause, is of course worth considering, and where my mind was at when I first approached the literature skeptically. The widespread presence of amyloid-beta plaques in Alzheime
16.
by DavidSJ 3mo ago
Now if we consider amyloid beta therapies: we have treatments that target amyloid beta with varying degrees of success but at least some show definite reductions in amyloid beta plaques. To the best of my knowledge that has not shown to im
17.
by DavidSJ 3mo ago
As noted elsewhere in this thread, which you seem not to have read, I discuss that matter in the article, which you also seem not to have read.
18.
by DavidSJ 3mo ago
What started as an argument to ignore arguments and evidence and instead rely on authority, seems now to have morphed into an argument that we should ignore the authority of the establishment, because of your own personal assessment of the
19.
by DavidSJ 3mo ago
You said the camp promoting the amyloid hypothesis has struggled greatly to come up with evidence to support its position. What did you mean by that if not a read of the quality of the evidence? Why do you continue to frame this as a choice
20.
by DavidSJ 3mo ago
Is your view that amyloid is actually a minority view among researchers? That seems completely wrong based on basically every conference proceeding I've viewed and the volume of papers and citations I've examined. If your view is
21.
by DavidSJ 3mo ago
1. I don't say Derek Lowe is wrong because he's in the minority. Minorities are sometimes right. But since the parent comment was arguing on authority and my lack thereof, I point out only that one shouldn't cherry-pick one&#
22.
by DavidSJ 3mo ago
This frequently comes up as a critique of my article, but I don't claim to be disrupting the field as a smart outsider. Rather, I looked at the field and concluded that the experts seem to know what they're doing. Derek Lowe is ve
23.
by DavidSJ 3mo ago
My oh shit moment was probably deep Q learning in 2013 (I guess that's not gen AI), but GPT-3 was pretty remarkable too.
24.
by DavidSJ 4mo ago
Yes, I can't find a 30%-slowdown number either. I'll add to this: the referenced trial occurred over 8 weeks, so even if we stipulate that the improvements in cognition (which are dubious, as tgv points out in this comment: https
25.
by DavidSJ 4mo ago
Little changed in 18 years: https://web.archive.org/web/20080511133831/https://www.vatic...
26.
by DavidSJ 5mo ago
Given that many of the depicted countries list as having "sufficient production", I guess it's for the usual reason.
27.
by DavidSJ 5mo ago
Ha! You must be using a different username than I knew you by then. Hit me up on one of the many platforms we’re probably both on if you like, would be good to reconnect.
28.
by DavidSJ 5mo ago
Many in this thread, who have evidently spent very little time studying the topic, have confidently concluded the experts are wrong. I, also a non-expert, spent six months studying what the experts are doing, concluded that they actually se
29.
by DavidSJ 5mo ago
There are about 30 million seconds in a year. If they made $100 over the last hundred milliseconds, then that’s $30B annualized. (That said, their numbers are much realer than that.)
30.
by DavidSJ 5mo ago
The original Mac system software was written in Pascal and most Mac toolbox calls took Pascal-style (prefixed by length) rather than C-style (terminated with null character) strings. But you could write application code in either language k

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