ChristianKl

Sequences

Using Credence Calibration for Everything
NLP and other Self-Improvement
The Grueling Subject
Medical Paradigms

Wiki Contributions

Comments

ChristianKl's Shortform

I have a lot of uncertainty here so, let me write a shortform for now. I'm not sure to what extend the following thoughts are true and I'm happy about comments

It seems that the body has two immune defense levels. One is in the mucosal immune system and there's a second that leads to antibodies in the blood.

SARS-CoV-2 infections usually first are in the upper respiratory tract where the mucosal system provides defense and not in where the immune system that provides antibodies that are active in the blood can fight the infection. https://www.frontiersin.org/articles/10.3389/fimmu.2020.611337/full

As a result vaccines that are injected into the blood don't help much with asymptomatic infection as asymptomatic infections are mostly in the upper respiratory tract and thus don't really stop blood-vaccinated individuals from infecting others. 

RaDVaC that's injected into the upper respiratory tract however has a good chance to lead to the mucosal immune system providing building antibodies against the virus. 

RaDVaC also has the advantage of allowing us to target mutations from new strains very fast.

5x increased infection rate over Delta means that everyone is likely be infected with Omicron regardles of being vaccinated with our existing vaccines. 

Cooking up our own RaDVaC might be the only decent move we have in defense of Omicron.

(while we are at it, someone should really give RaDVaC money to fund their research)

Why don't our vaccines get updated to the delta spike protein?

Developing a new version of the vaccine would probably face significant regulatory hurdle, and thus take time.

According to Pfizer, it should take 100 days. If they would have started that when it become clear that Delta will be soon the prevailing variant, we would have had access to the updated vaccine for a few months.

There's an expectation for new variants to become dominant every few months.

The best prediction seems to be those new variants will be varients of what's currently the most common variant and thus a vaccine that's updated against delta will be nearer to new variants.

The vaccine industry is either way going to sell as many vaccines as it can produce for the foreseeable future.

That's an argument why the companies don't want to do it on their own but not one for the lack of political pressure on them. It would be one of the main things a politician like Biden could do to actually fight the pandemic if that would be a political priority.

James_Miller's Shortform

A human made post-singularity AI would surpass the intellectual capabilities of ETs maybe 30 seconds after it did ours.

No, ETs likely have lived millions of years with post-singularity AI and to the extend they aren't themselves AI upgraded their cognitive capacity significantly.

James_Miller's Shortform

Eric Weinstein & Michael Shermer: An honest dialogue about UFOs seems to me to cover the UFO topic well. The videos publically available aren't great evidence for UFO's but all the information we have about how part of the US military claims to see UFO's is very hard to bring together in a coherent scenario that makes sense. 

ChristianKl's Shortform

Yesterday, I talked with a friend who together with her boyfriend got COVID. He was vaccinated, she wasn't. She had to go to the hospital while he didn't. However both have now the same long-COVID symptoms. 

It's an anecdote and I'd really love if someone would actually study the question of how effective our vaccines are for preventing long-COVID...

Latacora might be of interest to some AI Safety organizations

As part of being inside Google DeepMind I would expect that this gives DeepMind already good access to security expertise. If you think that an external service like Latacora can do things that internal Google services can't, can you expand the argument of why you think so?

Latacora might be of interest to some AI Safety organizations

It seems like MIRI already had a very strong security policy that strongly inhibited their ability to do their job. By hiring professionals like Latacora, they might not only make MIRI more secure but might also provide helpful advice about what practices are creating an unnecessary burden.

Use Tools For What They're For

If they are so confident that their vaccines are stellar successes, why did they specify in their contracts with European governments that they could not be held liable for side effects?

Courts of law can make companies liable for "side effects" whether or not there's scientific evidence that the "side effects" are caused by the drugs. 

If you for example look at LYMErix it's not clear that the side effects were really that severe but they were still enough to get the vaccine withdrawn.

Use Tools For What They're For

The two swiss labs Novartis and Roche, who respectively commercialize Lucentis and Avastin in Europe (undistinguishable treatments both created by Genetech, an American lab bought back by Roche - also, Novartis owns 33.33% of Roche), tried a legal action against France. I assume it was to outlaw the use of Avastin in the eyes. 

That seems unlikely to me. Our health system doesn't work in a way that there's a normal process for outlawing drugs for being used for certain purposes. 

Let's start with, Lucentis and Avastin are similar but the are not undistinguishable. They are both monoclononal antibodies against the same target but not the same. That's why you have for example two different English Wikipedia pages for them which you don't have for drugs were the same substance gets marketed under different brand names.

https://go.drugbank.com/drugs/DB01270 and https://go.drugbank.com/drugs/DB00112 give you the sequences of the antibodies and even without comparing every letter you see that the molecular weight of one is a third of the other.

When repacking a drug that intravenously into one that's optimized for intravitreal delievery it's plausible that some optimization can be made. Wikipedia suggests that there's  review that even suggests low certainty evidence that there are clinically relevant differences. While those difference might be just the result of p-hacking it's plausible that they are real.

Even the French Wikipedia doesn't go into detail but a more likely scenario is that someone in the French health service thought that covering Lucentis with public health insurance is a waste of money when Avastin exists that costs 1/40 as much and that they ran a lawsuit to get French public health insurance to cover Lucentis. 

If money wouldn't be any concern, then the act of repackaging drugs to be better for a given clinical application makes a lot of sense. The key issue is how much profit a company deserves for doing that and the amount feels excessive for the service that's provided.

Use Tools For What They're For

Novartis was so miffed that they successfully lobbied for forbidding using Avastin in AMD cases

Can you be more specific to what you are referring to? What specific regulatory are you calling "forbidding using Avastin in AMD cases". What forbids off-label use here?

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