CharonY

Indeed. He spent a ton of time to create those. His initial lectures were, by all accounts, horrible. Typical for someone with a deep understanding of the subject but without really understanding the knowledge gap between himself and his audience. That being said it is true for most scientists that they tend to be better known if they do more outreach, book writing etc., as there are obviously more interactions with the public. Much research which is critical for a given field simply does not percolate through society. And perhaps conversely, folks who are stuck in the lab or entirely focused on research, rarely become famous except if there are some breakthroughs that somehow chimes with the public. It does help to have a Nobel prize, though.

While I agree to some extent, I think the objective is a tricky word. There is always some context in history and historiography is an important element to interpret how folks interpreted events. History is rarely only about the sequence of events and the moment someone tried to connect dots it is almost impossible to not be coloured somewhat by the experience, knowledge and perspective of the historian. Even in science history the story of Henrietta Lacks or the role of Rosalind Franklin can be accurately presented in very different ways.

Nope, if you closely read what I was writing I said that "Transition is a medical process controlled by the physician following best practices. ". I.e. the physician works with the patient and figures out a process that works for them. However, as we are discussing transgender athletes and specifically testosterone has been mentioned a couple of times it is rather clear that we are talking about folks who have undergone some form of hormone therapy. For example, folks only taking psychological counseling would obviously not lower their testosterone levels by that. And again, there are well-established regimens and targets for folks undergoing transgender hormone therapy which is done in close supervision with their physicians. Only if the therapy holds, do testosterone levels remain suppressed in the range corresponding to their transition targets. So it is generally not something folks can just toy around with, and especially unlikely in feminizing treatment as overdosing does not provide a performance boost as in doping (the opposite, actually) and on top can have side effects if not carefully managed. But again, that is something a transgender person agrees to do to address issues such as clearly diagnosed gender dysphoria. So again, do you think that there are folks that are mainly just transitioning for the purpose in dropping into an easier competition bracket?

Yes, basically. At very low doses most mercury can be excreted with a half life of a few days to two weeks. However, especially at higher dosages the excretion pattern becomes more biphasic with a the fast phase (i.e. <2 weeks half life) only eliminating part of the ingested mercury. The rest follows a much slower (1-2 months half life) elimination pattern. If your intake outpaces the elimination time, you start accumulating which can result in issues.

I think the question was more how close Japan was to surrender even without the twin atomic bombs (or after the first). That being said, when it comes to the morality of the issue, the firebombings (or general attacks involving civilian targets) has been part of the discussion. That being said, I am not sure what the general consensus is (or if one exists). Certainly it generated quite a bit of literature and discussion.

For starters, because how the drugs work. As part of the transition you take estrogen and androgen blockers. If dosed correctly, testosterone values settle around levels of cisgender women. These drugs also eventually reduce performance. So how would cheating look like? Do you mean they fake transition and only take just enough to dip that they barely fall into the women's bracket without losing too many advantages? I have a hard time following the actually proposed scenario here. I also have no idea what the one size fits all refers too. Transition is a medical process controlled by the physician following best practices. Do you mean to say that instead of taking what their MD describes folks instead aim for arbitrary competition levels? You know that we are still talking about a medical procedure to address a specific condition (e.g. gender dysphoria). How about you spell out exactly what you think a transgender person is actually doing instead of making insinuations and make me guess. I try to be clear and tend to provide references but I do not feel I am getting anything back here.

Yet we still face massive inequity in vaccine distributions, we did not have a global strategy to combat the global threat and worse, we got folks driving the virus up by pretending it is harmless or does not exist. Countries which so far were able to at least somewhat control it are at danger of facing the variants. Rich countries meanwhile pretend that with vaccination the threat is over and might spread more virus around without getting sick.

Do you have evidence that folks would increase their regimen beyond their recommended dosages? Also note that typical targets during transitions are typically below competition thresholds from what I have seen. So if their transition is well adjusted, their levels should be below those thresholds. If levels are that high usually treatment continues until they fall in the typical female range. If I understand you correctly, you just assume that folks would overdose? If that has not been reported, we would arguing a strawman here. Also, do you understand the concept of *increased* risk? If someone is taking medication for transition, which element increases their risk beyond base level? Finally, it seems that the rest of the thread was arguing about the increases performance and testosterone levels and now the issue is that they are taking too much drugs to reduce their levels? Is there anything they are allowed to do?

*Points at global co-operation during current pandemic*

Quickly followed by new border walls. Now everywhere.

Same here, and the pandemic has vastly deepened it.

So, this part implies that they take drugs specifically to make a testosterone target for competition purposes. Your follow-up post does not really help me to further contextualize it and as such remains open to a number of interpretations. So for example it could be read as if you are assuming that transgender folks are taking drugs to make competition targets. That of course is not the case, as transgender hormone treatment is part of their regular regimen with the aim to decrease testosterone levels. So considering that there are doing it anyway, there is no increased risk. Another interpretation is that you are generally objecting to hormonal therapy in principle. As such, I do not understand what your argument is aiming at. I also have got issues with your other response to my earlier post, but maybe we can start here.

Honest question, did you read any of that and if so how do you get to this interpretation. Are you aware what transition entails? I have the feeling that you work under a number of assumptions which are likely to be misunderstandings, but your comments are too cryptic to me to figure out where they are.

I think that the example is counterproductive as it actually does not necessarily indicate the effects of transition. While they are likely to retain an advantage, I would like to see actual data by how much that declines over a given treatment regimen. Studies haves shown for example that military transwomen retained some performance benefits over their peers, but not all of them. See e.g. http://dx.doi.org/10.1136/bjsports-2020-102329: In other words, one needs data rather than opinion or anecdotes to dissect this issue.

The link I provided shows an analysis of averages, which is shrinking with distance, which considering the sample size gives a decent estimate of expected differences. If one is really interested one might get more data from the authors. A discussion of possible female advantages can be found here. https://link.springer.com/article/10.1007/s40279-020-01417-2 So going back to you, have you similar data to question those conclusions? Note that for ultradistance open water competitions women beat out men by over 10% and hold records, too (papers from Knechtle et al.). So there is good reason to assume endurance advantage (discussed in the paper).

To the first part, I do not think that any of us without deep reading into the biology of long-distance running can really make but the most superficial assumption on what traits are really critical for ultramarathons and how that relates to gender differences. To the second part, having a lot of data is exactly the point. If your hypothesis is that men have categoric advantages over women in the performance of anything, we want to get large data sets and look how the distribution is. For example if the top 0.01% is all men but we see large overlap in the rest of the 99.99% of the distribution then we can not clearly conclude that men are biologically advantaged. Rather, it points to a fact that there is a small group of men (over all women and most other men) that might be . And then it would make much less sense to exclude transgender women in that given category. Conversely, if we got a large or at least clear separation in performance then one might conclude the opposite.

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?