CharonY

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).

Fundamentally yes, but the results are basically tumors.

You seem to be arguing both sides. Your earlier posts seem to argue that transgender women would be physically superior to cisgender women in a variety of sports. The proposed solution was to to make an open competition for the highest levels of a given sport. You have made the claim that this would be impossible, but have not substantiated that. I provided a couple of examples which so far were soundly ignored so at this point it is absolutely unclear what you are arguing in the first place.

This types of comments just indicate ignorance. Have you read the article I posted earlier? If you are not willing to educate yourself at least slightly on the matter and you basically keep trying to discuss form a position where the strength of the opinion far outweighs knowledge and only serves to derail the discussion. The weak attempt to ridicule the situation really just makes it worse. If someone says they prefer women as sexual partners, do you doubt that? If someone says that they prefer men, do you doubt that? What do you think is the basis of that? If you are not willing to accept the basic biology underlying these issues, I do not see a meaningful way to engage on that matter as you are discussing issues based on your personal reality. Or try to answer answer my question before. What do you think makes you identify yourself as a man. Because someone told you so? Or is there something else. And if so, what could the something else be?

As iNow mentioned, the way you feel is determined to a large degree by your biology. The way your body produces and responds to hormones, the number and variations of receptors and so on all influence why you feel like a man for example. But there is a spectrum, i.e. not all men are equally attracted (or at all) to women, for example. Most of the spectrum finds a range in two broad categories, but quite a few (around 1% of the population cluster more in the middle of the area, where the various biological inputs in aggregate do not fall into one of those neat categories. To put it bluntly, you do not need to check what type your gonads are to feel a certain way. It all happens beyond the consciousness, which is why one cannot simply erase it. One can have separate discussion regarding how that impacts free will (and if Eise is around, it will be very interesting discussion), but I think you do realize that quite a few associated traits are quite hardwired (such as sexual preferences) and cannot be altered at will.

! Moderator Note Nothing of value discussed here. Locked. To OP, do not open another thread with this topic.

These are good points. Especially with regard to sports I find it laughable that folks are so hung up on some objective measure, whereas literally everything in a sport is based on the creative design of a game. Fundamentally, I have not heard any argument that addresses why performance differences cannot be used to create competition categories, whereas almost everything in sports is (e.g. different leagues, or competition levels). Taking F1, for example, from what I understand it is actually open but few women qualified. This is perhaps not terribly surprising as only few women compete in it, so there it is unclear whether gender influences performance. But here essentially again a measure (i.e. time) is used to gate who gets to compete in a Grand Prix. I was curious about jockeys and I found a recent study (https://doi.org/10.1177%2F1527002520975839) indicating that there is no difference in performance between men and women, though women rarely get to participate. I.e. it appears that women just have fewer opportunities to compete in the first place. It is still puzzling to me (and I am repeating myself here, but it does not seem to get addressed) that there is the assumption that any evaluation of transgender would be highly subjective, yet at the same time they maintain that the performance of female transgender athletes puts them categorically above a cisgender women. If they do, it should be easy enough to measure. And if you cannot measure, why would you need make a new category? And of course, with further understanding of the biology of sexes we now also know that the binary gender distinction is a categorization based on convenience, which covers the vast majority of cases. Yet clearly, the distinction ignores detailed biological realities and is therefore not inherently objective. I fail to see how this is relevant to the discussion. Feminine is a group of traits that are traditionally associated with what we consider to be women. I.e. it is a collection of cultural traits that are part of the gender constructs in a given society. Depending on society the certain traits can be either feminine or masculine. In the Mosuo society, for example, making business decisions is considered a feminine activity, whereas in most others it is more associated with men. But again, other than to complicate matters I am not sure how that helps in any way. Edit: However, if you think feminine is an objective indicator of sorts, then I think that could be the root of the issue. Perhaps read the link I provided earlier and see how that relates to your thinking on that issue.

I think you need to read some basic texts to challenge your notions. It goes beyond chromosomal pairing, and especially advances in high-throughput genetic analyses have started to show how biology diverges from our preconceptions. Here is a decent and easy read: https://www.scientificamerican.com/article/sex-redefined-the-idea-of-2-sexes-is-overly-simplistic1/

The answer to me is fairly straightforward, for the established measures there are already parameters in place, so in your mind it is clear. For the second measures are being discussed and since they are not clear (yet) you assume it is different quality. Yet, as OP ascertains that transgender athletes have, objectively, a different quality in performance, it would simply mean that one need to establish thresholds to distinguish those features. If they do not exist, then obviously the distinction was meaningless. If they exist, it becomes a measure of identifying usable thresholds. That is one standard approach you use in science, when you want to categorize based on continuous variables. There is likely some assumption in your mind that makes you hard to see that. For example, in sports where speed is the key parameter, athlete speed/acceleration/time can be measured. Then, if an athlete reaches a certain threshold (or several) and perhaps adding consistency to the mix, you can define when someone gets entry to the open league. In others, one might decide to measure muscle properties/densities and so on. By making these measures gender neutral, in categories where women are likely to underperform compared to men, they are also more likely not to pass the threshold without having an outright, and arbitrary ban. After all, the assertion was that somehow the distinction between women and transgender women is objective. If that is so, I want to see measures to support that and then we can use those measures to define new categories. Again, it does not seem as arbitrary by separating certain weight groups by, say 8 pounds, others by 15 (or keep the highest open ended). And likewise it encourages cutting and other measures to keep weight at weigh-ins and how folks bounce between the different weight classes. I mean, the obvious reason why this is so hard for some folks to get behind might be because they have a strong idea about gender or sex in mind, and consider that an objective measure and anything potentially breaking might be seen as less objective. But again, science (not politics) have moved away from that, using measures, not assumptions.

Simple, someone needed to come up with categories there, too. Do you think they pulled out those from a magic science drawer that provides objective answers to all questions? They had to think how a given category could be useful to make the sport interesting but also safe and those changed over time. Likewise they could simply e.g. look at pre-qualifier performance to decide thresholds. No idea where you see the difficulty. In fact, you seem to forget basic science here. Your premise was that there are categorical (rather than gradual) performance differences related to transgender athletes. If that is true, simple performance tests should reveal them. If not, then those issues were not that categorical after all. So yes, scientific thinking compels me to these arguments. What about you?

No, the scale just indicates weight. The organization sets weight limits.

There is precedence already. The weight categories set in contact sports, for example. Or how disabilities are weighed in paralympics, as SJ, said. None of the rules in sports are perfect and sometimes create weird incentives. I do not see how this is fundamentally different or impossible. As it has been said before, sports are games with made-up rules. And rules have been amended continuously to adapt to changing conditions such as accommodating broadcasting schedules, forcing athletes to show more (or less) cleavage and so on. Making up new ones to be more accommodating does not seem too much of a stretch here, especially with examples already being used.

Many countries had established systems after SARS and those that did maintain them did better. Many countries reduced such monitoring efforts (including the US) after there are no outbreaks after a little while. After the catastrophic start, China did actually control the virus somewhat well, and one does not need espionage to get at least rough ideas. At least not with a disease of this magnitude. If folks opened up without having the disease under control, catastrophic failures of the medical system follows. That has not happened in China, which does not really have a brilliant system to begin with. Moreover, excess death analyses of China during 2020 mostly found excess deaths in Wuhan, but little elsewhere. Considering the amount of travel to and from China (which is part of the issue) it is naïve to assume that the Chinese government could fully control tat type of information.

That is a cliché that US Americans believe and which is unlikely to be true. Idea of free speech and related concepts are ancient and did not start with the USA. Moreover, the US had many, many issues with it. McCarthy, anyone? Not that the US under the last administration did not try that. Instead they muzzled the agency responsible for keeping folks safe. I am not saying that China did the right thing, but at least eventually they openly declared that the outbreak was an issue and did something (whether it was the right thing might be debatable). In the US meanwhile, the officials offered mixed messages and were not able to clearly communicate the severity of the disease. The differences in countries that did that and the US is clearly visible in the death counts (which is even worse when one also includes undercounted cases). In short, freedom of speech is an ideal that many American hold dear in principle. In effect, there are many mechanisms that undermine it, which tend to show up when the system becomes more authoritarian. This is basically also true for Europe, looking at some countries who recently have become more authoritarian (e.g. Hungary or Poland), some of the measures almost always include limitations of freedom of expression of some sort.

We have seen that depending on leadership, the US is not even transparent to its own citizen. So would the magic entity be? The other issue of course being that folks need to have a good system to detect diseases in the first place. And considering how bad the US and Europe were in detecting and tracing cases, it seems that we need an organization led by a coalition of NZ, Taiwan and Vietnam. I do suspect that this is not what you had in mind. What the pandemic has shown is that we are do not have a good system to contain asymptomatic spread. Of course, changing the world in a way that contain any travel would reduce spread of such diseases. But that is generally not acceptable to folks. Of course one potential system is to shut down travel from and to any country in which a new outbreak is detected. Though again, I think that economic considerations would take precedent. And I will also note that some folks think that diseases only originate in far-away countries and as the recent epidemics and pandemics showed, it is clearly not the case (though tropical areas with rich wildlife have more reservoirs for zoonotic diseases).

This seems a bit silly, considering how few transgender people are there (of which only a tiny fraction will be athletes). That seems a bit like a loaded question. The issue is that historically the assumptions of the majority of minorities can create rules and laws that disadvantage the latter (and often thereby reinforces notion of the majority). This includes the historic treatment (and criminalization) of LGBTQ folks. Much of today's society has at least made a nominal commitment to start off inclusive (rather than the more exclusive approach based on a strong opinions and nominal, if vague values).

https://theconversation.com/striking-a-balance-between-fairness-in-competition-and-the-rights-of-transgender-athletes-159685 I think this is could be a reasonable take (as opposed to bans):

Absolutely, one of the things I assumed was going to happen when the internet came up is that we would see a massive jump in knowledge generation. I thought that folks would actually go away from fact-learning and more toward knowledge building and application, as facts or details would be so easy to get. As it turns out, at least one of the challenges that the information is actively getting diluted by bad info, and much time needs to be spent to vet information.

I think a big part of it is how schooling might have changed. It in class I noticed that kids are more focused on getting the right answer rather than understanding the why. And despite the fact that MigL has a point, I think there is genuine qualitative change that is associated with how media are consumed. I think there are several connected things that play into it and one of them is the way how media are presented and consumed. Reading papers in class was something I have done for a long time, but in the last 5 years or so, as part of student evaluations it has been consistently criticized as being far too much work. Students are now very uncomfortable when it comes to applying knowledge, they are obsessed with right and wrong answers. Much of it is due to schooling. I am not sure how common it is, but I was told recently that in school students would regularly get question catalogues and all exams would need to be on the list. Consequently, students are really unhappy when the task in an exam is now to apply things and so on. It is not everybody, of course. However, the proportion of folks struggling with this kind of tasks have been increased and curving has become more and more extreme. That being said, there is of course the argument to be made that because folks are consuming media differently, we should teach differently, too (and the question catalogue is presumably one such measure). But honestly, I am a bit at a loss, if reading and synthesizing scientific literature is becoming harder and harder to teach. And at least in my field of expertise I cannot compress information into one interesting tweet.

I agree. Growing up working-class immigrant poor we initially could not afford books, imagine my joy when I found the public library! The town was small and so was the library but at that point it was like an infinite amount of free candy. There is a lot I could lament about the internet experience, but I do feel that having too much info (and much of it of low quality and merely bite-sized) takes away from the desire (and enjoyment) to really dig into something. In the last 10-15 years or so, there is a noticeable shift in how kids experience learn and is heavily impacting their performance when it comes to more complex matters. It also has soundly refuted my assumptions regarding the role of technology in information gathering and learning that I had when I was young. Oh god, we are old, aren't we?

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.

! Moderator Note Does not seem to discuss mainstream biology, moved to speculations. Please take some time to familiarize yourself with the rules regarding speculation threads. https://www.scienceforums.net/forum/29-speculations/#elForumRules

Vaccinated folks are less likely to get infected from the virus in the first place, and even if infected they overall viral load tends to be lower. I.e. they produce fewer particles and the overall (population-wide) reservoir of viruses that could mutate is lower.

I have addressed the issues for the most part above already but I can give a more detailed breakdown for clarity. Overall I do not think that the tweet is well informed (but then so are most, I guess). 1) the mRNA in the vaccine is fragile and we know that it degrades over time. In the Pfizer report we see that the test mRNA they used vanished from the liver within 48 hours. In other words, if we expect effects due to the mRNA, they would need to happen before that time frame, and likely need to involve a higher accumulation than in the liver (as liver inflammation does not seem to be a major issue). 2) it can be expected that the LNP and their load seep out from the injection site, and typically eventually reach the liver. Over time, they would be metabolized and eliminated from the body. The Tweet seem to claim that the liver values are stable but that is not necessarily what we expected. Rather we have steady state situation where elimination is balanced with additional accumulation (i.e. likely the liver is doing its work). In fact, between say hour 2 and 48 h we see a loss of ~30% of the total signal. I.e. even if distributions shift, the total levels will obviously go down, rather than up. As such, very long term effects are unlikely to happen due to accumulation of stuff. If anything happens it is more likely due to something stupid our immune system is doing that could affect the body long-term. 3) We see that much of the short-term accumulation happens in the liver (which again, does most of the lipid metabolism) but also spleen (same reason), each of which have about double the concentration than ovaries. The other site to look for for short-term effects (again the mRNA is gone pat 48 hours) could be e.g. also adrenal glands, where quite a bit accumulates in the 24 hours but I have not seen reports that indicate issues here (again, the issue with endpoints, I outlined above). 4) The kinetics are likely going to be different. The rats got a 50 ug dose whereas the Pfizer/BioNTech vaccine is about 30 ug (IIRC). Given that the average human weighs about 240 times more, the elimination is likely going to be faster. There are a couple of other points I could point out, but I hope that this explains most of it (and let me know if something is unclear (as often I am in a rush and did not proofread it properly).

! Moderator Note Post regarding effects of vaccines have been split from another thread.