CharonY

The world record is not a great indicator as it highlights a highly trained and able individual. So beside biological factors which may or may not be sex-based, there are also extremely high levels of training and selection. If you look at various ultramarathon races you do see women ending up in the top 5-10, which is quite interesting, if you also consider that only between 14-23% of ultramarathon runners are women. I.e. there is a smaller pool to identify and train talent than for men. Looking at larger numbers it then shows that the sex-based differences diminish. Which is why I posted the suggestion for an open competition and suggested performance-based leagues in the first place. But mind you, I am not yet convinced that there is an universal issue. I started off with that thought, mostly based on articles in the news I read, which shines through in my couple of first posts, but then I read a few academic papers and my thoughts are a bit more nuanced.

It is only a nitpick, but I would qualify this by stating that anatomy becomes an issue on the mid-high level of competition and that the difference depends quite a bit on the type of running. Obviously some training often beats out no training at all in most types of races. But also look at this : Sure, it still means that in the vast majority of types of races men outrun women, but obviously the anatomic advantage does not translate universally. If it was that easy one could e.g. make hip-distance based leagues for example. Then the question could be expanded to other issues regarding fairness. Competition on the highest levels often requires a lot of money for highly technical training. Or perhaps the ability to enhance athletes without being found out for doping. So wealth (of the organization) can skew results. As others have mentioned, height differences are not considered an issue and so on. So I am wondering what specifically makes this case so much more egregious that it needs to be looked on specifically over other issues. Let's say for example there are cis-gendered women with high testosterone levels and which have some increases in muscle mass among their peers and a transgender woman who, due to early transition has similar levels and performance. Who gets to perform in which group?

So that argument has some merit from a scientific perspective as they argue that the data provided is too thin to fully assess the pharmacokinetics of the formulation. Fundamentally this criticism has some merit and the context makes more sense than the posts you have provided earlier. But before I get into that, I want to emphasize that in the context of OP long-term effects are not expected. For starters, even with incomplete data we see evidence of some elimination. As noted, the test concentrations was much higher relative to the animal weights as for the human formulation, so especially with hydrophilic compounds, it is likely that clearance will happen slower in rats compared to humans (i.e. more will circulate for a longer time). But more importantly, I want to point out the earlier argument with regard to monitoring health endpoint and its relationship to concentrations. The rats were injected with 300-1000x the dose of their human counterparts (adjusted for weight) and a basic assumption of the effects of drugs is that they follow a dose-relationship (which is also the rationale behind PK and related analyses). So fundamentally you will expect the stronger effects when the concentration is high. Now with respect to the animal studies this has several implications. One is that the levels are massively higher than a person relative to their weight is going to encounter. I.e. any adverse effects should be pronounced in the animal. Second, clearance will be overall slower, as the small body needs to process a lot of material. For humans the relative dose is much lower. So going back to the health effects, there were separate studies submitted to the various drug agencies based on injecting rats concentrations between 10-100ug of the drug three times a week apart (followed by a 3 week resting period) and compared to a control group. A snippet of the results is here: In other words, even if injected with over a 1000x of the concentration of the drug several times, there was no indication of serious health effects other than inflammation (which is expected). The increases in the spleen were expected to be related to the inflammatory response, which can lead to the formation of blood cells, which is supported by bone marrow data. This was not the only study, another experiment was presented with more rats at single dose and also looked at organ abnormalities and found none. I.e. the toxicity studies directly look at damages caused by the vaccine components and the conclusion is that even at extremely high concentrations there are no unexpected damages in animal models. Thus, even if LNPs were lingering around, they would be as such low concentration that harmful effects are extremely unlikely. These findings are so far supported by clinical data in humans. So together the point here is that one should not think that the one report is the full data provided to the drug agencies nor should one expect that any given data point can be easily extrapolated to health issues. Rather, different experiments provide different insights and the panel's job is to look at the full package and make a decision from there. It would take a bit to explain how area under the curve analyses are conducted and how they are used, but I will for now note that full PK studies are often not required for vaccines. In part because you do not get regular doses of it, so that overdoses and similar events are not an issue. That being said, similar to the tox data, there is also more PK data out there covering about 2 weeks from which they estimated elimination rates: The public details can be found either on docs provided by the European Medicines Agency, but equivalents should also be found from basically all approving countries. If you are interested in more detail how elimination rates are calculated I could do that if I have a few minutes, but should probably be a different thread.

I believe ovarian teratomas are an example. Tumors certainly do not equate death. But they do not form into full organisms.

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.

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?