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Accumulation of lipids in adrenal glands, spleen and liver are expected with lipids. Inert tissues tend to be things like adipose tissue where metabolic turnover is low. However, perhaps I have confused you a bit, it is not a function of the tissue alone. To add some detail, elimination of compounds often is connected to metabolic modification. By attaching stuff to a given compounds they could e.g. be made more hydrophilic, which increases the rate in which they eliminated. The liver is one of the core organs for this process. For some compounds this process is for whatever reasons, very slow. But even then bioaccumulation typically only occurs if we get exposed to a compound faster than we can eliminate. If, on the other hand you get exposed only once, the elimination rate determines the time frame where a compound resides in your body. Eventually pretty much everything goes away (via hair, urine or feces, typically) eventually. Stuff that sticks around for a long time (and again, there is no indication that this is true for LNPs) tend to be hydrophobic and often reside in adipose tissue. Ovaries are not a storage organ and have a well-controlled lipid metabolism. There is more data out there. Some files available for the vaccines in the EU and US process indicated that the committee has seen 2 weeks of data. The key is not the length, but to provide sufficient data to estimate elimination. I.e. often you do not monitor until the levels are below the detection limit, but rather you measure the rate of elimination and calculate half times based on that. Sometimes folks may ask for final elimination times, I suspect when it is critical to how the drug works, but that is outside my expertise. For your other question I would prefer if you could transcribe the post and highlight your specific question. I would rather try to help you understand the underlying mechanism rather than argue indirectly with a random twitter person. One thing to keep in mind, and I sense something based on your question, too. The report is not original research trying to find and explain new things. Instead it is based on established pharmacokinetic frameworks. In other words, to fully evaluate the findings one need to understand how those measures are used and how to interpret them. I am not an expert in that area myself, though I have decent knowledge of most of the involved analytical methods (and I have friends that I talk to who are experts). These data are then provided to a panel who then evaluates things like safety based on the provided information. Folks that seemingly see these type of data the first time in their life and try to make sense out of them simply lack the qualification to interpret them. It is like me trying to figure out general relativity by watching movies involving black holes.

To model the behavior of the universe in ways that minimize human bias; to move forward with the recognition that all models are only at best provisional, and with a willingness to reject them when evidence demonstrates that they're flawed and unrepresentative in some way. Science is about building maps, and our task is to recall that all maps can always be made better and also that the map is not the territory.

His comment is uninformed. There is nothing in the spike protein mRNA that makes it vastly more stable, and the instability of mRNA is well known. It is fairly common to use surrogates for these type of studies. Even if it was much more stable, we would be looking at a couple more days at best, which, unless you are talking about mayflies rarely falls under the moniker of long-term effects. I just quickly calculated the total detectable lipid concentration, which dropped by that amount. So yes, it is cumulative for all organs. Again, it is based on how we generally metabolize lipids. As we are not getting continuous injections, what happens is that the total amount of lipids gets distributed and eventually eliminated. We also know which organs conduct much of the lipid metabolism so I am not sure why at this point we should all pretend not to understand how lipid metabolism works. Again, I think the basic thing that you and the twitter post seem to misunderstand is how compounds, including lipids get metabolized and eliminated. I am sure that if you look at ADME profiles, you will find something for those LNPs. Moreover, the post seems to be confused about how elimination studies are done. If you want to understand how it is eliminated from the body you would go and measure generally blood and liver values as well as identify those compound in waste (i.e. urine and feces). And guess what, that is what they did and how they estimate elimination rates (some other routine methods involve simple blood plasma analyses. Quickly screening lit has indicate that terminal terminal half life for ALC-0315 and ALC-0159 were ~3 and 8 days, respectively. It is not a hypothesis, it is how the liver works. It is how we metabolize things. What you propose is that for some reasons LNPs changes how our organs work. If the liver would simply accumulate harmful substances we would be all dead. A steady state also does not see-saw. If the compound was delivered at a steady rate the concentration would remain steady and then decline slowly as the compound is being eliminated. However drugs can be released in bursts or re-distributed unevenly (e.g. the compound can be released from other organs back into the bloodstream). The main source in this case is leakage from the injection site into the bloodstream. Again, not a hypothesis, there is huge body of literature out there showing how liposomes, LNPs and similar compounds pass through our body, get eliminated and/or can get modified to control said elimination. We should not assume that science collectively forgot how basic animal physiology works just because a random guy on twitter doesn't. Again, there are plenty of studies looking at mRNA as well as LNP degradation and metabolization, as well as basic liver functions. And I want to recall that one of the biggest challenges mRNA vaccines faced are the fact that those were eliminated too quickly to reliably create an immune response. Similarly, early LNPS were cleared too rapidly which added to the issue. Thus, much of the work surrounded stabilization of mRNA in vivo. So suddenly assuming that it is somehow very stable just goes against all the basic biochemistry we understand regarding those molecules. In addition, the whole molecule is not terribly stable outside of the body, either, which is why they require storage at low temps. I am not sure why you want to discuss tweets from a person who clearly has no expertise on that matter. Although it does not fall strictly into my area of expertise either, it is easy to see that the author of the tweet has not found it necessary to educate themselves on the subject matter before taking it to the social media (and yes, the irony is not entirely lost on me, considering my postings here). Take Gregoriadis and Neerjun (https://doi.org/10.1111/j.1432-1033.1974.tb03681.x) which is one of the early papers looking how one could control uptake and elimination. There are tons of advances to control elimination rate, tissue specificity and overall stability in the lit, with detail that goes far beyond my knowledge. So any argument that argues that something mysterious is happening here, is likely based on ignorance. So what I think you propose is that for some reasons the main organs for lipid metabolization (and subsequent elimination) will only be active for the first two days or so, then all residual LNPS would magically bypass these organs and mechanism, accumulate in ovaries and stay there forever? So instead on measuring well known excretion routes we should instead focus on something that a random twitter guy does not understand? I would advise you look for some reliable sources. I am not sure whether the person has an agenda or is just badly misinformed, but either way I would urge you to find someone better to follow as neither of us is going to learn anything by feeding trolls.

Being able to use reason to discuss various scientific phenomena requires an arena where that reason is respected. True personal attacks show me that the attacker has reached the limits of their reasoning power, and have resorted to lashing out emotionally. I've been exposed to some fantastic discussions in the time I've been here, and the common vein running through all of them was critical thinking and knowledge winning out over fallacies and ignorance, and members who are eager to practice civility and learn as opposed to just being right.

The line that set this off is "This types of comments just indicate ignorance." and in the context of the exchange, the topic was already known, so it was not (or should not have been) ambiguous to those in the conversation. What was being discussed was based in science, so it's much less of an opinion and much more about what you can support. ———— But Phi is absolutely correct: being called ignorant is not a personal attack in the context of our rules if it refers to some issue being discussed. Disagreement is not, either. If you assert an opinion as if it were a fact (especially an uninformed opinion), or something contrary to facts, then one should expect pushback. "You cannot dictate to others" would be an example of pushback. It's not like only one person is not allowed to dictate to others. OTOH, "you lack integrity, honesty, decency and are too cowardly to enforce a rather simple rule. Now go f**k yourself" is a string of personal attacks. As I've written before, "This is a place to discuss science, not a self-esteem support group. Civility is required, but this does not extend to walking on eggshells to accommodate fragile egos."

For future consideration ... 'You are 'gnorant' is ambiguous. 'You are ignorant of such-and-such a fact' is not. But certainly people should stop being so sensitive, and easily offended; this is a place to exchange opinions ( among other things ). As Prof. J Peterson says, when you have an opinion, you're bound to offend some people. ( the alternative is not to have an opinion, or be denied an opinion, which is much worse )

You have that poster somewhere in your house, I just know it. Don't count Tom out though. Have you ever seen what an atomic physicist can do with a Breville BTA830XL Die-Cast 4-slice long-slot toaster? "Come with me, if you want to eat toast!"

Thanks for the reply. There are plenty of sources* for proof of NFA and DFA Equivalence. And again: I was curious about nondeterminism in the context of this thread; Carl Hewitt's papers and the mathematics used in the Actor model of computation. It is hard to apply your arguments about nondeterminism if you define nondeterminism in another way than the authors that this tread is about. I addressed this earlier: In the theory of computation there are more than one mathematical model for instance Turing machine and lambda calculus. The actor model, the topic of this thread, is a concurrent model. That needs to be taken into account when discussing determinism and nondeterminism. Yes you are allowed to say that. "Allowed" does not mean it is necessary or appropriate to say it. Example: https://courses.grainger.illinois.edu/cs373/fa2013/Lectures/lec05.pdf

“beta decay reactions” are ones that swap a proton and neutron. In a decay, both the particle and its associated neutrino (one of them is an antiparticle) is released. In the detection reaction, the particle is absorbed and the neutrino emitted see http://hyperphysics.phy-astr.gsu.edu/hbase/Particles/neutrino2.html If a reaction needs e.g. 10 MeV to occur and your source is giving you 5 MeV particles, you won’t cause the reaction. One would need to check the specifics of the solar neutrino spectrum and the specific reaction to see how much of an issue this is. The muon mass is > 100 MeV and tau mass is ~1776 MeV, so they definitely require added energy. A bare neutron is only a few MeV more massive than a proton, and the energy difference in a nuclear shell is of similar magnitude. edit: from this document from SLAC it looks like the solar neutrinos are all under 20 MeV (p.208, graph on 209) So if they changed to muon neutrinos along the way, they don't have enough energy to create muons in a n—>p reaction

Determination of ADME (absorption, distribution, metabolism, excretion) is standard in pharma. Whenever you produce a drug, you document what happens to it in the body, as it it is critical to assess things like dosages. Moreover, assessing the elimination time also allows monitoring things like acute effects. I.e. if you know stuff ends up in various organs, but is eliminated say in 10 days or so, you know that the time window for monitoring for acute effects might be around 20 days or so. Anything after that are either unlikely to be associated with the drug and/or have to be secondary effects. In other words, it is standard info you provide if you want approval for your drug. It is therefore not surprising nor and indicator of any issues. That is not generally how things work. The only mechanism would be if it reaches mostly inert tissue or is has properties that take a very long time to eliminate (PCBs and other organohalogens come to mind). If you did those elimination tests there, you won't see clearance at all. Again, most of the stuff circulates and gets redistributed and given how fast things get out (compared to the persisting compounds) there is little reason to believe that a lot can maintain in a given niche. LNPs and constituents of their lipid shells are quite well investigated and are not known to have these persistent properties. I.e. you (and possibly the twitter user) are proposing an entirely novel mechanism without a shred of evidence at this point. Sorry if I appear hostile, I am more annoyed at the twitter user than you as it seems to me that the question are not honest questions. I can accept that you are not familiar with the standard pharmacological data (and I am only familiar in passing), so it may be something extraordinary to you. But do you accept that if I tell you that this is a standard approach? Can you also accept that lipids have a natural way of getting eliminated from the body and that the values are established? Also have you thought about the comment I made earlier that the rats were injected with a much, much higher dose than humans are per weight? If so, no worries and we can continue to work on your question and figure what you might not understand. But if you are already set in your beliefs, better tell me now, else you would be wasting my time (and then I might get annoyed).

We would more likely to be taken over by cockroaches, since they are most adapted to extreme environments, including thermonuclear radiation. They are already taking over to be one of the largest total masses of biological entities on the planet.

Again depends. Statisticians would compare incidence in the active and control groups, accounting for type 1 error inflation. Doctors would follow up and assess the severity and likelihood of causal link (which is often subjective - it helps if there is some known or plausible causal pathway). But are the myocarditis cases detected during post marketing surveillance rather than clinical trials? So the adverse event wasn't detected in the clinical trials but only when it was released and used by millions. This happens with particularly rare adverse events.

I think the point made about basketball (it tends to discriminate towards very tall people) is a fair one, as it underscores that all sports at the higher levels are going to be somewhat exclusionary and attract people with a certain anatomical blueprint. No one has proposed "professional short people's basketball," or "football (American usage) for the small-boned." In this sense, all sports (except those based purely on grace and finesse, like diving) tend to filter out those whose body type does not adapt well to its contact situations or need for inertial mass. The problem seems to be mainly with limited cases where someone can be overqualified with respect to a woman's league due to having been a biological male in the past and thus attained a bone structure and mass that might lead to rather brutal outcomes for other league players. If gender leagues were eliminated, then the tendency would be to recruit, in contact sports, those with more formidable musculoskeletal systems and we would have a sports world composed almost entirely of cis-males and trans-females, and very few cis-females who were not extreme outliers. Which would bring us back to the question of having some other criteria for leagues that somehow permitted the smaller and more gracile a venue for play. It's possible we would need to redefine sport, and what societies want from it. Do we want sports to be a professional business in which we can marvel at superb physical specimens far beyond the average human? This is somewhat akin to advertizing wherein we see stunningly gorgeous and idealized representations of ourselves using or wearing a product. We are invited to project ourselves into some realm of perfection well removed from our own. Now I'm rambling a bit. A sure sign I have no good answer to this whole conundrum.

I asked Zapatos to stop the personal attacks, I did that in this post: You then posted this: I replied to that rather ignorant post with this: But then we have yet more ignorance, ignorance of the facts: So you are either blind, incompetent, ignorant or just rather dim, how you conned your way into being designated a moderator is a mystery. There are people hurling personal insults around, you are either dim or in fact secretly want them to say these things to me. Yes I KNOW THAT IS NOT THE POST I REPORTED but it is the post that you referred to when you defended Zapatos after he made three accusations against me. You are on record as actively defending posts that do not attack someone's argument but do attack their character and intelligence, so its fair game, you are ignorant and you want to see others insult me because you disagree with something I said somewhere. This is so obvious, you lack integrity, honesty, decency and are too cowardly to enforce a rather simple rule. Now go f**k yourself.