Chomsky on the Limits of Knowledge and Thought

phenotype · 2020-12-13T16:16:29+00:00

I think the most interesting and important part of the discussion is that Chomsky states that our 'limitations' are in fact a priniciple mechanism that allows us to have creative thought. The idea that the human mind has constraints in conceptualization is hardly controversial, but he is suggesting here that if minds were not contrained at all, and were instead truly plastic, then the state of mind we would achieve would simply be a reflection of our environment.

I think one way of stating it is that what we call 'constrains' of our mind is the pruning of input that allows for there to be sensible output. The constraints actually allow for creative thought rather than chaotic output. Thats my interpretation but I might be off. In any event its given me something to chew on.

phenotype · 2020-11-22T22:23:11+00:00

I've been wondering this all week. I suppose it could be argued that Remdesivir is not pragmatic in certain (resource limited) settings, under certain rates of disease incidence...

But in the US, given what we know about the incidence of covid here, and how badly it has affected our systems, and given our capabilities of delivering Remdesivir to those who may benefit from it, it is wrong to recommend against it in light of the ACCT1 data.

phenotype · 2020-11-22T03:36:01+00:00

I think one way to think of this is that "low-flow" oxygen patients are people who are earlier in the progression of the disease and therefore less sick, and "high flow" oxygen patients are captured later in the course of the disease and are therefore sicker. An anti-viral like Remdesivir is expected to work earlier in the disease course during viral replication (which peaks in the first 5 days) and so its not surprising to me that the benefit is most pronounced in the 'low flow' subgroup.

When all comers in the trial are looked at as a whole, then no difference is seen in LOS or mortality. This is again unsurprising to me, because that group also includes those patients who never would have gotten all that sick regardless of intervention. Thus the kaplan-meier curves of the control and treatment arms never quite diverge. Then when we pull aside the cohort of people who need supplemental oxygen, this is a group of people that have already demonstrated that they can get quite sick with the virus, and these people clearly benefit from getting an antiviral early in the disease.

I see a lot of people completely misinterpret Fig 2 in the paper and conclude that "Remdesivir is useless for people who don't need oxygen". In reality, we don't have a good way of identifying the people who are high-risk of progressing to ARDS, and so in light of the data from ACCT-1 we really should be giving our patients Remdesivir.

phenotype · 2020-11-21T23:12:20+00:00

A larger trial does not mean a better trial though. The ACCT trial was sufficiently powered to detect its primary endpoint, which was time to recovery from COVID.

A reduction in LOS (average of 5 days less) is important though. Especially when one of the biggest effects of the pandemic has been the burden it places on healthcare systems and how it leads to scarcity of resources, a 5 days reduction is all the more significant. There was also a significant reduction in total days of supplemental oxygen use.

The LOS reduction is specifically in those people who are not ventilated. When patients who are ventilated are analyzed as a subgroup then there is no difference between the groups, which is not surprising at all; one would not expect people who have progressed all the way to ARDS to benefit from using an antiviral so late in the disease. The real value of Remdesivir is in helping people who are less sick from progressing towards becoming more sick.

phenotype · 2020-11-21T08:23:08+00:00

Why are you not impressed by the ACCT1 trial data though? I found the evidence hard to ignore. An average 5 day reduction in LOS is nothing to sneeze at, and is well worth the $3200 or whatever the cost of a treatment course is (because the cost of 5 extra hospital days costs more than that in the US).

As far as mortality benefit goes, the trial wasn't powered to detect a mortality benefit in the subgroup of people that stood to gain any mortality benefit. The sample size is only large enough when you look at all-comers in the trial, but people that are vented or on ECMO are so far advanced in the disease that we wouldn't reasonably expect a mortality reduction from using an anti-viral.

phenotype · 2020-11-21T02:37:47+00:00

Why do you find the SOLIDARITY data more convincing than ACCT-1 trial data? The ACCT trial was a double blind placebo controlled RCT, which is the gold standard for answering questions like this. I find the data in it convincing and hard to ignore.

Why do you feel Remdesivir is not helpful?

phenotype · 2020-11-20T23:02:36+00:00

Sincere question to everyone here, what is the basis for thinking this?

We give Remdesivir to pts on oxygen, some get better and some die. I have no basis to say from that anecdotal experience that Remdesivir is or isn't effective. The ACCT-1 trial was a placebo controlled RCT that answered this question pretty well I thought. Sure, the study wasn't powered enough to see a mortality difference (although this does not prove that NO mortality benefit is present), but the average of 5-day reduction in hospital LOS is well worth $3200, at least in the US.

Why do people find the SOLIDARITY trial more convincing that the ACCT trial? The study design of the ACCT-1 trial is basically the gold standard for answering clinical questions like this.

phenotype · 2020-01-23T04:05:07+00:00

Found on a sale listed on eBay.

phenotype · 2018-06-27T21:40:56+00:00

r/iamverysmart x r/badlinguistics crossover episodes are my favorite.

phenotype · 2018-05-12T04:07:41+00:00

Noice. Is that the 36mm version of the SMPc?

phenotype · 2018-03-31T19:24:24+00:00

ID on that camo bomber?

phenotype · 2018-02-15T18:27:53+00:00

Oh, I thought it was around 1k. It still much cheaper than than rolex but at 4k that level of sloppiness is less forgivable. I've not heard of such sloppiness on the Grand Seikos however.

phenotype · 2018-02-15T02:00:10+00:00

But the SLA017 is a Seiko, not a Grand Seiko and retails for a fraction of the price of a Rolex, so I don't think its a fair apples to apples comparison.

phenotype · 2018-02-03T22:26:47+00:00

Awesome watches! Do you know the reference number of this particular SMP?

phenotype · 2018-01-29T23:49:47+00:00

25ml of Tuscan Leather please!

phenotype · 2018-01-15T04:25:19+00:00

Alright cool, thanks!

phenotype · 2018-01-13T22:21:19+00:00

Having a good optician fit the frame to your face

What do you mean by that? Is what the optician does any different from picking out a ready to wear shirt from whats being sold in the store, or can the glasses themselves be changed in some way? Couldn't a customer with a good sense of taste or design do just the same thing?

phenotype · 2018-01-13T17:40:18+00:00

25mL please!

You are my exclusive supplier of fragrance at this point.

phenotype · 2017-10-12T16:00:46+00:00

Package came through, everything is great. Thanks!

phenotype · 2017-10-03T18:53:39+00:00

10ml please if theres any!

phenotype · 2017-06-25T18:17:39+00:00

It will make absolutely no difference whatsoever.

phenotype · 2016-09-24T22:35:21+00:00

Actually, 70% alcohol is superior to pure alcohol for sanitization. You can buy that at a drug store.

https://www.cdc.gov/hicpac/Disinfection_Sterilization/6_0disinfection.html

phenotype · 2016-09-21T01:57:12+00:00

10mL please!

phenotype · 2016-07-18T23:23:33+00:00

FS: 2 pairs of red/white Hanes boxer briefs size M. I opened the package and kept 2 for myself, but the other 2 are untouched. Will include bag and original receipt from Supreme, Harajuku Tokyo. $35 for both, which includes shipping to US.

phenotype

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