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ryankemper

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Non-opioid MoA in Fentanyl explains failure of Naloxone in opioid crisis (2019)

ncbi.nlm.nih.gov
4 points·by ryankemper·5 tahun yang lalu·1 comments

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ryankemper
·5 tahun yang lalu·discuss
As an operator you're always making a tradeoff between the "negatives" of a license and the "positives" enabled by the actual software.

So for one example, the recent (bait and) switch of Elasticsearch to SSPL effectively means that for many actual real-world users of Elasticsearch, the benefits of staying on the official Elastic branch has ceased to be worth the costs of the license when your alternative is running FOSS Elasticsearch/Opensearch.

So to answer your actual question - presumably as an operator you want to use the AGPL-licensed code more than you want to avoid those same negatives of AGPL.
ryankemper
·5 tahun yang lalu·discuss
> There’s nothing silly about a novel virus having greater abilities to overcome barriers when compared to other pathogens that humans have had years decades and centuries to develop defenses again.

This isn't really quite accurate though. Before SARS-CoV-2 ever emerged, our immune systems already had defenses against it. This is because of the already-extant circulating hCoVs.

This is why something like 80% of blood samples taken before SARS-CoV-2 emerged showed T-cell cross-reactivity. From the perspective of our immune system, it was never a "novel" virus. It was novel to scientists and politicians but not to the human immune system.
ryankemper
·5 tahun yang lalu·discuss
> You are removing roughly 10% of the population in the U.S., or 2% worldwide.

These numbers seem way too low if you're talking about the prevalence of people that have been exposed to SARS-CoV-2.
ryankemper
·5 tahun yang lalu·discuss
> Seems like the simplest answer is just "actions that have reduced the spread of one disease have also reduced the spread of another, that's historically less widespread already."

This is not the simplest answer, and the evidence that the measures have really slowed spread is extremely low except in places like New Zealand and Australia which are small islands in Oceania.

---

> A bias towards testing for Covid wouldn't explain fewer cases of the flu unless those cases of the flu were coming back as Covid falsely instead of so further diagnosis was stopped.

Exactly this. I'm partial to the viral interference hypothesis, but what you don't seem to realize is that if you get infected for SARS-CoV-2 and recover in 7-14 days, you will still test PCR+ for months after. This goes into the widespread mistuning of the cycle threshold. Case in point: They tested George Floyd's corpse for COVID-19 and he was PCR+, despite having recovered from COVID-19 a couple months before. The test hit on the remnant viral debris from his long-gone infection.
ryankemper
·5 tahun yang lalu·discuss
Actually, what you're saying is untrue. The overwhelming evidence shows that children spread COVID less than adults do.

My favorite is this: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2006100?articleTo...

The study isolated SARS-CoV-2 samples from every positive case, sequenced genome of virus, and tracked the mutation patterns. So, that will avoid a lot of the errors that improper qPCR usage can result in.

First things first, age and viral susceptibility:

> Of the 564 children under the age of 10 years in the targeted testing group, 38 (6.7%) tested positive, in contrast to positive test result in 1183 of 8635 persons who were 10 years of age or older (13.7%). In analyses involving participants up to 20 years of age, we observed a gradual increase with older age in the percentage who tested positive (Fig. S5).

That's more about who got it, but there's some discussion of transmission here where the senior author talks about it: https://www.sciencemuseumgroup.org.uk/blog/hunting-down-covi...

> Children under 10 are less likely to get infected than adults and if they get infected, they are less likely to get seriously ill. What is interesting is that even if children do get infected, they are less likely to transmit the disease to others than adults. We have not found a single instance of a child infecting parents.

> There is an amazing diversity in the way in which we react to the virus.

---

(I recognize I only presented one study here - there's only so much time in the day :P - but the other high-quality studies I've seen confirm this. Mechanistically it makes sense if you look at the enormous T-cell cross-reactivity in those age groups. And BTW, data on school closures for Influenza (which children seem to transmit much more readily) showed that school closures were ineffective anyway because they would just spread it more outside of school)
ryankemper
·5 tahun yang lalu·discuss
For context, in India there's about 27,000 deaths per day in a normal year (napkin math: 7.344 deaths per 1000 from https://www.macrotrends.net/countries/IND/india/death-rate, multiplied by the indian population size of 1.390 billion, divided by 365 days per year). Currently there are around 2700 deaths being attributed to COVID-19 per day.

I am much more concerned about poverty, starvation, death, and decreased non-COVID vaccination rates, than I am about COVID itself, for a country like India. SARS-CoV-2 primarily kills the very old and the very unhealthy, particularly diseases of modernity (this is not a value judgement but rather a statement of fact).

The indian life expectancy is somewhere around 68 years. Compare that to 78.7 in the US (https://www.cdc.gov/nchs/fastats/life-expectancy.htm). We've seen in the US how we likely caused iatrogenic harm in places like New York by practicing early invasive ventilation. We've seen (although we don't have the true long-term data yet) the impacts of unnecessarily suspending elective surgeries (such as was done in my state of California for a month despite a total availability of ICU capacity, and the fact that even if there weren't capacity many outpatient surgeries are more valuable than an extra COVID-bed-day)

Here's just one small example of the ramifications of succumbing to fear: https://www.bbc.com/news/world-asia-56425115

> It estimates that there have been 228,000 additional deaths of children under five in these six countries due to crucial services, ranging from nutrition benefits to immunisation, being halted.

> It says the number of children being treated for severe malnutrition fell by more than 80% in Bangladesh and Nepal, and immunisation among children dropped by 35% and 65% in India and Pakistan respectively.

> The report also says that child mortality rose the highest in India in 2020 - up by 15.4% - followed by Bangladesh at 13%. Sri Lanka saw the sharpest increase in maternal deaths - 21.5% followed by Pakistan's 21.3%.

It should go without saying that a 15.4% increase in child mortality is NOT a result of the SARS-CoV-2 virus, which spares children. It's a result of missed medical appointments, decreased non-COVID vaccinations, economic disruption, and the general environment of largely unnecessary and maladaptive fear and anxiety that the populace has collectively been exposed to.
ryankemper
·5 tahun yang lalu·discuss
> OK, but you can make the same argument for COVID. It seems to me that the slides are at least comparing apples with apples.

If you look at the rates of acute side effects to the vaccines, I forget the exact number but it's at least like 80%. It's insanely high. SARS-2 absolutely does not produce that given the massive proportion of asymptomatic individuals and significant amount of paucisymptomatic individuals
ryankemper
·5 tahun yang lalu·discuss
That doesn't compare vaccination to naturalistic rates at all. It just gives rates of reinfection for those with antibodies versus without.
ryankemper
·5 tahun yang lalu·discuss
A coding camp is the opposite of hustling. It's called "bootcamp" for a reason - it's there to impose some structure for those who need it.

Also bootcamp is very overhyped. There's some great people that come out of them, but I think mainly the hype is the fact that college is overrated (this is a cliche opinion I know) so bootcamps are there to try to exploit some of the delta that the myopic focus on college degrees creates. But many boot camps are super myopic in their own ways.
ryankemper
·5 tahun yang lalu·discuss
What dataset are you referring to?
ryankemper
·5 tahun yang lalu·discuss
Second shot syndrome is apparently worse in the young (20's / 30's) due to the stronger immune response. I wasn't assuming that everyone who gets the syndrome would be asymp. but just that many would.
ryankemper
·5 tahun yang lalu·discuss
> fwiw, new and better better technologies need to get used for the first time, eventually.

No-one disputed that, I'm just pointing out that it is a very valid point for someone to say "I have concerns that we're rushing out an experimental vaccine". You might take issue with the specific wording (I don't) but the general point I hope we can agree on.
ryankemper
·5 tahun yang lalu·discuss
> Difference is that I know person that got COVID in November and now has issues with memory.

> I don't know a single person that has that after flue and cold - and those are with us much longer.

Look into ME/CFS, whose existence is still contested (or rather I should say, whether it's a physical or psychogenic illness is disputed). I know you're just speaking anecdotally but just wanted to mention that post-viral issues (fatigue, memory, etc) absolutely does happen.

> As for viruses mutations etc. do we for sure know that this one is not man made?

At most SARS-2 is the result of extensive gain of function research on https://en.wikipedia.org/wiki/RaTG13. I don't know any credible individual that thinks it's fully artificial / manmade (and to be clear, my definition of "credible" is not the "anyone who agrees with the WHO/CDC and nobody else" definition that the establishment relies on).

Personally I think it's more likely that SARS-2 was GoF'd into existence rather than was a purely natural zoonotic leap, whereas I think the probability that it was fully artificial is almost zero.
ryankemper
·5 tahun yang lalu·discuss
The fact that the vaccines create just a single spike protein and the real virus creates much more is actually one of the issues.

First: does the rate at which the cells are made to artificially produce spike protein follow a different curve than the rate at which SARS-2 would? i.e. could mRNA vaccination cause a much more aggressive "inflammatory cliff", thus the huge percentage of "mild" adverse reactions (mild meaning, you feel like death for a day but end up fine with no detectable long-term issues)? It's possible.

And switching to efficacy, while personally I think resistance to the spike protein alone will be sufficient, because SARS-2 does not have the same ability to mutate/evolve the way Influenza does (for example, I can't imagine SARS-2 evolving away from the spike protein), it's very possible that the diverse epitopes produced by real SARS-2 infection give a much more robust and enduring immunity.
ryankemper
·5 tahun yang lalu·discuss
(Not the one you responded to) I know what an mRNA vaccine is and the only clearcut answer is that "yes, obviously the long-tail risks of mRNA vaccines could outpace the long-tail risk of COVID-19". The statement is also true when you say "...COVID-19 could outpace...mRNA vaccines" as well, if that's not clear.

BTW the "long tail" of COVID-19 in children is totally unproven and the whole "long haulers" phenomenom is likely (a) a small part normal post-viral fatigue which we see with basically any virus, and (b) mostly psychosomatic/psychogenic illness.
ryankemper
·5 tahun yang lalu·discuss
> Also don't think the long-tail risk of an mRNA vaccine can be worse then COVID's long-tail risk.

It absolutely could, and that should be self-evident.

> Also pretty sure risk of death outweighs literally any possible long-tail risk, so still seems sensible for the young to get the vax.

This is just not true. The risk of death in children from COVID-19 is so low you literally should not ever worry about it. If you want to compare numbers in an academic sense go ahead, but the fact that actual adults are wasting valuable cognitive and emotional energy worrying about their kids is a great tragedy.

The recorded COVID-19 deaths in children are, by the way, using the absurd definition of a COVID-19 case/death that most of the western world is using; a definition where having PCR-confirmed SARS-2 infection means that ANY death is classified as a COVID death. This is not how this is supposed to work; there is supposed to be a distinction between the virus and the disease, but we define the disease as merely having the virus! It's completely absurd. Indeed I'm writing an article about this concept (pathological vs physiological) right now
ryankemper
·5 tahun yang lalu·discuss
We've never taken such an attitude for any other endemic respiratory pathogen in existence, and for good reason. It's completely absurd and ignores not only the important health benefits of regular social contact, including direct physical contact, as well as the literal benefits of exchanging pathogens with others.

You and the other commenters arguing your "side" also seem to completely ignore the phenomenom of natural immunity, which I think very obviously has been fallaciously denied by "experts" precisely because they want to convince everyone in the world to get this vaccine. They're already talking about yearly booster shots because most people's mental models are from Flu which has a much greater space of possible genetic configurations, whereas SARS-2 is relatively constrained in how it can evolve and thus should not need a yearly booster if this weren't just about making absurd amounts of money (which it is).

In any case, you should know that there are people like me - very much in the minority - who refuse to submit to such absurdities and will keep fighting. We will continue to be literally as well as metaphorically discriminated against until your "side" stops brainwashing people into a completely disproportionate response to an endemic respiratory virus.

You can stay inside with a mask on while vaccinated all you want. Be my guest. But please stop advocating for and/or supporting mandates and restrictions on the rest of us who have not caught your specific strain of agoraphobia, germaphobia, OCD and misanthropy.
ryankemper
·5 tahun yang lalu·discuss
It is true; the PDF linked in the GC has to make a number of assumptions and is very obviously made from a point of bias (which does not invalidate its claims but warrants extra scrutiny).

Also it's comparing raw ICU admissions, but there are a number of really nasty adverse reactions that don't throw you in the ICU. The general "second shot syndrome" that something like half of people getting Pfizer/Moderna experience is a great example of that. Yeah it's not bad enough to send them to the ICU, but for many people COVID-19 would be literally asymptomatic or would be minimally symptomatic, whereas the second shot syndrome can be quite brutal.
ryankemper
·5 tahun yang lalu·discuss
> The chance the disease kills you is 1 in 100

It's 6 in 1000 if you listen to the CDC; personally I think the real number is closer to 3 in 1000. That's not too far off from what you said but I prefer being more explicit rather than using such a fuzzy resolution.

And just to be explicit, that's the general IFR, the IFR for, say, people in their 20's, or even people in their 40's, is a fraction of that.

---

Anyway, your point about risk management is somewhat true, but it is much more true if you apply that logic to the general public's fear of SARS-2 in the first place. I can't find it in my notes but surveys that have asked people what their chance of dying is if they catch the virus, are off by MULTIPLE orders of magnitude. And young people rank their individual risk of death higher than old people do (both estimate too high, even the old people), presumably due to them being more "plugged in" to "the system" so to speak.

Personally speaking, since I'm in my 20's, almost everyone I know who has gotten the vaccine has done so because they believe outright falsehoods about the virus that have been propagated not just by the media but by our so-called health experts themselves.

For example, I have multiple friends who had PCR-confirmed COVID-19, recovered months ago, and still got the vaccine. In the times I've probed at them to see why, they muttered some vague things about "the variants" and essentially said that the variants bypass naturalistic immunity which is just completely false.

I know for a fact that my likelihood of an acute adverse reaction (the all-too-common "feeling like death for a day" reaction) is far higher than the likelihood of comparable symptoms from SARS-2 infection. So I'm not getting the vaccine, and I'm not embarrassed to say so. For many people, the risks of the virus are less than risks of the vaccine; however, much less people than you would think. We don't have good enough data yet but I'd bet it crosses over somewhere in the 40's or 50's age range.

There's a huge difference between being an "anti-vaxxer" in the true sense of the word - i.e. you think all vaccines are inherently bad, period - and being someone who takes the same attitude towards vaccines that we do towards drugs: no drug is inherently safe; rather drugs that are proven to be safe are safe. By extension, no vaccine is inherently safe; vaccines that are proven to be safe are safe.

The latter statement is my personal view of it, and unfortunately such a statement can get you banned from social media platforms if you get unlucky.

This binary way of dividing the world into "anti-vaxxer" vs not, "AIDS denialist" vs not, etc is not just oversimplified but is intentionally done to suppress dissent. I refuse to participate in such a culture and I humbly implore you to do so as well.
ryankemper
·5 tahun yang lalu·discuss
Thanks. To avoid repeating myself: https://news.ycombinator.com/item?id=26799734

TL;DR you can probably s/mRNA/adenovirus vector/g although I will grant that adenovirus vector seems less "experimental" than mRNA does