Me and my cofounder Chris have been quietly working on Encycla for a while now. Previously, I started LocalWiki[1] and DavisWiki[2]. What I couldn't stop thinking about was: is Wikipedia really "it" in terms of web-wide knowledge sharing?
There's been lots of note-taking apps and personal knowledge sharing tools developed in the past few years. But there's a big difference between working with people you already know and collaborating with anyone on the internet.
Right now, if you're interested in, say DIY air purifiers[3], you could throw up a document or webpage. But there's no good way for people you don't already know to work on it, to make it their own. If you're writing software, the answer is obvious: publish a Git repository on GitHub/GitLab.
With Encycla, we're building a sort of "GitHub for knowledge": a place where you can create simple, topical webpages that others can fork and asynchronously push & pull changes from (without knowing about Git or anything technical).
On the backend, every page on Encycla is a git repository containing Markdown that you can clone, edit independently of the Encycla website, push to other services (such as GitHub, GitLab), etc.
Yes, this is one reason why an approach using a form of soluble ACE2 is so promising; mutations that would normally cause e.g. monoclonal antibodies to stop working (as detailed with the mink mutation) would in theory not stop the 'decoy receptor' approach.
Despite the fact soluble ACE2 is not looking like it'll be developed in time to impact the pandemic, there is a silver lining:
Interestingly, in this n=1 case report, it looks like the soluble ACE2 is unlikely to have worked as an antiviral; the patient already had a high level of antibodies, as you can see in the Lancet paper above. So /if/ the patient's improvements can be ascribed to the soluble ACE2 treatment, it's likely the improvement was because of the effect the soluble ACE2 had on the person's renin-angiotensin system.
And if this holds, then it's likely many of these same improvements would be possible using a common class of widely-available blood pressure medications called ARBs.
This approach would not neutralize the virus, but instead stop the body from damaging itself. That's the theory, at least.
There are ~20 trials of ARBs for COVID-19 in progress now, though almost all are underdosed.
It was not blinded. It was open-label and the outcomes were subjective (ICU admission). The doctors involved with the trial knew who got what and may have biased their actions based on that. Given the subjective outcome and small number of participants, this is particularly important. The trial would be slightly underpowered even if it were blinded.
Other studies on Vitamin D are retrospective cohort / observational studies which are heavily biased with possible confounders with respect to Vitamin D.
My personal opinion is that Vitamin D may help in COVID-19 but this trial does not 'confirm' that. Someone should run a similar trial with more participants and/or a fully blinded trial / a trial with more outcomes (biomarkers, etc).
I think the table in that paper is just confusing. The parenthesized numbers are for portion of the total number of people, rather than the portion of that category.
For instance, there are 137 current smokers. 108 are listed as non-severe. 29 are listed as severe. This means 108/137 = 79% non-severe, 29/137 21% severe.
Never smoked: 927 total, 793/927 non-severe (86%), 134/927 severe (14%).
Hope that makes sense. That table confused me too. Don't start smoking!
Please see my twitter account for lots on this. I'm in contact with a bunch of top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas axis; ARB usage for viral diseases) and will be posting a summary update soon:
It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2.
This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts.
The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post.
It is related, but it's pretty complicated. For some information on this and the potential relationship, see my twitter account: https://twitter.com/__philipn__
If anyone is reading this with connections to the Gates Foundation: Please contact Dr. Robert Kruse at John Hopkins. https://twitter.com/RobertLKruse. I have been trying to get in touch with people at Gates. This announcement unfortunately features no contact email address :(
Dr. Kruse is developing an extremely promising therapeutic, ACE2-fc, which will both neutralize the virus and treat the symptoms of the disease. It has been shown to work in vitro; variants have been tested in animals models; and its been through Phase II human trials for a different indication. A variant of the therapy, soluble ACE2, is being trialed in humans now in China.
Details on the approach can be found in his paper here:
One reason is constitutionality. The "One man, one vote" principal likely has to be upheld for a voting system used in the US to be ruled as constitutional.
Ranked Choice Voting is sometimes called Instant Runoff Voting when used in a single-winner election. But it can be used in multi-winner elections.
If it's used for a multi-winner election, it gives results that are proportional in representation. For instance, this is how it's used in the city council elections in Cambridge, MA. Sometimes it's referred to as "Single Transferable Vote" when used for multi-winner elections.
"Ranked Choice Voting" is an umbrella term that refers to the ranked ballots, round-by-round elimination of candidates, etc.
There's been lots of note-taking apps and personal knowledge sharing tools developed in the past few years. But there's a big difference between working with people you already know and collaborating with anyone on the internet.
Right now, if you're interested in, say DIY air purifiers[3], you could throw up a document or webpage. But there's no good way for people you don't already know to work on it, to make it their own. If you're writing software, the answer is obvious: publish a Git repository on GitHub/GitLab.
With Encycla, we're building a sort of "GitHub for knowledge": a place where you can create simple, topical webpages that others can fork and asynchronously push & pull changes from (without knowing about Git or anything technical).
On the backend, every page on Encycla is a git repository containing Markdown that you can clone, edit independently of the Encycla website, push to other services (such as GitHub, GitLab), etc.
1. https://localwiki.org
2. https://localwiki.org/davis
3. https://encycla.com/Corsi-Rosenthal_Cube