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That is basically true. The development itself did not start from zero but was prioritized so it was faster because more folks worked on it. Phase III are smaller and faster than some other vaccine trials but it benefitted from an actual bad situation: the virus was spreading rapidly and had in many countries a high prevalence. So while other vaccines might have taken years to identify enough infected folks to estimate efficacy, in the pandemic the numbers were reached much faster. Production is not an issue as it is regulated and controlled the same way as others. It is fast because more companies work together to make it happen. If you are talking about development and testing, Area54 basically addressed that. If you are surprised that things happen faster because more folks and more money was dedicated to the project then I am not sure what to tell you. Would you feel better if they waited until you think it took enough time?

This or something similar is pretty much the same tactic everyone I know use. There is no other way to keep up with the workload. Though deleting seems like an interesting idea that I have not thought about- usually stuff just lingers in my inbox (and I have unanswered emails going back years on my conscience that I really should delete). Yes, there are the zero inbox methods or focused inbox and so on, but at some point (mostly around grant deadlines) things break down on my end. I have allocated a bit more time to emails as my teaching load has been reduced but I have set my inbox on refresh only every 3 hours or so. I found that if I finally found some precious time for writing, inbox notifications tend to destroy my focus. I know a colleague who is extremely successful with tons of collaborations all over the globe. When she showed me her inbox after an hour working on them there were still over 400 unread emails to go through (for the same day). Usually in her case showing up physically (even if you need to take a plane) can be faster. But also in her case she really prioritizes her undergrads with a patience that I can only admire. But it also means that some projects end up in email hell...

It is you who is unaware about the contents of the studies. There are no knockouts (which generally refer to genetic deletions) and stopping hyperinflammation would at best be addressing a symptom, but not the disease. You keep saying mRNA editing (well, actually m'rna, which is not a thing), except that there is no editing involved. Apparently you are not understanding how vaccines work (or immune responses). Vaccines prime the body to specific parts of the virus (or other pathogens). The immune response then becomes targeted and is able to clear the pathogen. It is not even vaguely the same approach. Antibodies produced in the process are (and have to be) specific to the pathogen. Even if you change somehow antibody regulation, it won't suddenly target the disease. All you have established so far is that you need to read more about how the immune system and vaccination works before making broader claims.

OP seems to start with a wrong assumption. The genetics of skin colour is not related to the environment per se, or at least not the way OP seems to imply (i.e. focussing on genetic aspects not the adaptive melatonin production in response to sun exposure). Sun intensity can be a selective trait favouring those that have darker skin. But it does not cause genetic changes. In other words the birth of a child with darker skin will occur with the same likelihood regardless where they are born. What OP actually is seemingly asking is how long it would take to have mutations resulting in darker skin. This is not only a random process, but it is not a yes/no answer, either. There are several alleles associated with skin colour and there are obviously many different shades as a result. So if even if your breeding program would only select for folks who identify themselves as white, you might not have strictly a gene pool that concentrates all the alleles which are associated with a lack of pigmentation.

The terms have been around since the 90s, I believe. However, the easiest way to think about it is that in this context man or woman corresponds to the gender which a person identifies with. Trans or Cis refers to the relationship between their identification and their sex. A transgender person therefore was born with a different sex than what they identify with, whereas a for cis-person both are aligned. So a trans-man would be someone who was born female and underwent gender re-assignment, which typically includes testosterone supplementation. As that person identifies as a man, it would make no sense to compete with women (and vice versa). As such, your examples simply did not make sense to me. If that is the basis for the confusion, it would appear that you might have missed the basic premise of OP.

I am having difficulties understanding what you are trying to say. After re-assignment surgery testosterone suppressors are used in addition to estrogens, both of which reduce testosterone levels. After an about one year- regimen the levels are typically stably reduced to that of cis-women and I believe current regulations require that transgender women need to maintain these low levels in order to compete. I.e. in you example only the cis-woman is expected have higher testosterone levels. If the trans-woman show enhanced testosterone levels, it is not because of hormone therapy, it is despite of it (and again, these tests are done routinely, so I also do not quite understand why you seem to claim that they aren't and I cannot see anyone stating that they shouldn't). Or do you mean transgender men? Because they would get testosterone supplements. In that case you need to be more specific (heh) in your explanation as most of the discussion was about how transgender women might have an unfair advantage. And from what I understand trans-men are allowed to compete without restrictions.

Considering that the discussion is 4 pages deep, this claim is more than a little weird. I still fail to see why your are so hang up on testosterone, as I mentioned a few times, the levels are the same in trans as well as a cis-women. I did not say that the do not need to be screened. I said that screening did not reveal any statistical differences. In fact, simple testosterone testing would likely be very inclusive, but in the lit Prometheus provided the discussion is more fundamental as the concern also highlighted in OP is about whether a) there is lingering competitive advantage regardless of testosterone levels b) whether that inadvertently creates a non-inclusive situation for cis-women in spots. I agree. I think the overall discussion is at the interface between being inclusionary, but for all women (trans and cis) and trying to come up with a scenario were neither are unduly penalized. But I also think that currently the body of knowledge has not advanced to a point where we can make clear claims. The call for prolonging therapy time is evidence of how information has changed during these discussion. I think that the current 12 month rule was in part implemented as it was found that after about this time period testosterone levels are reduced to the same levels as cis-women. The gist of the Lundgren group (and others) is that physiological advantages extend beyond that point.

Thank you Prometheus, I am aware of at least the review from the Lundberg group (the paper I mentioned with regard to muscle loss was from their group). From what I remember the authors discusses elite athlete mainly in the context between men and women (not transgender) and the actual discussion of transgender performance is based on their (and others) work showing that testosterone suppression only resulted in limited performance reduction. However this was on the non-elite level (i.e. they extrapolate from their first part where they highlight differences between female and male elite athletes) and is mostly based on measures such as grip strength, rather than sports performance. I.e. in many ways it is talking about the potential advantages of transgender women in sports. And that is where my thinking goes to mostly. So far the discussion talks about unfair advantages of transgender women and how they could dominate the field making it impossible for non-transgender women to compete. I have found bachelor theses calculating high likelihood for transgender women getting all top spots. I have to admit that I am not particularly interested in sports, but from what I can tell these scenarios are not happening and as mentioned above and as long as there is little evidence of exclusion of non-transgender women I feel that is no strong indicator for a need to be exclude transgender athletes. The assay seems to discuss ethical aspects and perhaps addresses what OP has in mind. I will need to track the full text down and read it in order to follow their argument, though.

As mentioned above, after reassignment, testosterone level are virtually indistinguishable. Also as already mentioned, there is a paucity on data indicating that there is a problem. If you have access to studies that demonstrate an actual issue, please share them. All articles I have found point to a very limited number of studies among non-elite athletes showing either no performance difference or only potential differences (i.e. lack of significant muscle loss, but no indication whether that would had any impact on training on the elite athlete level). I.e. all I have seen so far continues to indicate that the theoretical worry is not well funded on facts. And with that lack of evidence I do not think that exclusionary policies are a good idea. One could make a philosophical argument and let's say some sport is going to be dominated by transgender women, the question that one could then raise is whether that is important. Of course that is a related but also somehow separate discussion but one then would also need to figure out what the pros and cons are. OP has asked at some point whether sports should be stratified according to some performance parameters and while some sports are (e.g. by weight as mentioned), some are not (e.g. there is no height-based classifier in volleyball). So what then is fairness based on what kind of distinction do we perceive to be beneficial for a sport?

I think the answer is pretty much similar, there is no convincing evidence that the prosthetics provided an unfair advantage. And this suffers from the issue that others already pointed out for the other example, it is fictional. I.e. if much of the concerns and evidence are based on fictional accounts and speculations it is probably fair to say that at this point there is simply no good reason to be non-inclusive. While this may change at some point (say, if prosthetics are clearly providing performance enhancement) it may be time to re-open the discussion.

I think there is a delicate balance here that needs to be found. My first reading was similar to yours. However, there is an extensive context of exclusion which I initially did not consider. The big issue is that historically many exclusionary policies have been enacted base on such potential and potentially unfounded concerns. Many of these have deep impacts to this day. Examples include anti-drug or health policies. For example, it was believed that black folks feel less pain, have thicker skin and are more susceptible to addiction. These has resulted in systematic maltreatment based on these myths which apparently are still persistent among health care providers. So I think that before any measures are considered, one should actually find strong evidence for the need of action in the first place. After all, sports carry inherent risks as others have pointed out and as far as I can see there are no substantial studies indicating that inclusion of transgender folks significantly increases risk beyond the usual baseline. And I do agree that the invented scenarios are probably not a good basis to start of this discussion. However, I think the resulting discussion made it clear that OP provided the opinion in good faith. While the points about how problematic the starting might be are valid, further discussion of motivation might derail the topic needlessly.

If folks had taken it seriously and had been committed to social distancing the pandemic would have been over in Summer last year. The vaccine is needed because folks are still downplaying the risks of the disease, like you do.

So no you still not acknowledging that these technologies are unrelated and therefore carry different risks. So there appears no balls for a meaningful discussion here. Basically it is the same as trying to bin the risks of nuclear power to combustion engines. Also your desire to downplay the impact of b the disease is nothing short of ridiculous. Some of the worst flu seasons in the US killed about 60k folks, which was a huge deal for the medical community. COVID-19 killed 500k. It is more than obvious that the mortality rate means little if everyone is susceptible.

I think that is the crux of the matter. If everyone would make perfect decisions, it would not matter on which level things are done. But whether a centralized or decentralized approach works better depends on the likelihood of bad decisions along the way (and their respective impact) as well as structural limitations, such as e.g. level of coordination required. For disease outbreaks decentralized responses tend to be result in worse outcomes as a lot of coordination is required, ranging from building supply chains for e.g. testing and PPEs, travel restrictions (including between provinces) contact tracing and so on. Now, the big question here is whether that also applies to minimum wage.

It is going to be off-topic a bit, but I think COVID-19 is not a good case. While you could state that a decentralized approach has been good for Nova Scotia, the precise opposite can be said about, say Quebec. An actual comparison would need to be done between countries with decentralized vs centralized approaches and recent reviews from Canadian researchers (e.g. Hansen and Amelie, 2020 JMIR Pub Health Surveill). Showed that the decentralized Canadian approach resulted in worse outcomes compared to countries with a stronger, centralized strategy, even if they had worse infrastructure and other issues to deal with.

For starters, an mRNA vaccine has no relation with CRISPR/CAS gene editing strategies. The former is a simple encapsulated mRNA which neither replicates nor can it be integrated into the genome. In fact, one of the main challenges of developing a vaccine was to keep the mRNA stable enough. So, considering that the vaccine has no relationship with the rest of your argument, is there something else you might want to discuss?

I think the concerns are mostly in the area of contact sports and related injury risk, but again much of it is based on a certain amount of extrapolation (a Swedish study showing that testosterone reduction does only lead to minor muscle mass loss, for example) rather than actual performance data. I think it is one of the (many) areas that would benefit from more precise data. But in general I think the whole way sports are set up are to a large degree arbitrary, anyway. For example in basketball taller players have large benefits, so one could at least in theory argue that to ensure fairness, there should be a height cap. And obviously there are no principles that would prohibit any arbitrary number or set of rules. Edit: Also, the scope of the issue might actually be fairly small so there is also the question whether the concern is actually balanced well with the real-life situation.

That is a good point.

I think there is no biological answers to that. We create gender separated leagues for a variety reasons and the decision would likely be based on what aspect one would like to emphasize.

From what I remember testosterone levels of transgender women are the same as as other female ranges after sex reassignment procedures. One could extend the question also to individuals who are intersex, for example. I am not sure whether there are clear answers to the issue, though. It also does not help that data is sparse, as there are only few elite transgender athletes. Depending on the sport some studies found little difference in performance (non-elite long-distancing running, IIRC). But it is unclear (beside anecdotal evidence) how big the effect would be in the elite athletic scene.

They generally are partially targeted as they are formulated to be preferentially taken up by phagocytotic cells. I am not really sure about tropism data of the current vaccines. I assume you are thinking of the risk of presentation of other cell types via MHC-I among non-professional antigen presenting cells? One of the original fears of mRNA vaccines is that they may have broader tropism resulting in widespread MHC-I presentation leading to severe inflammation. So far, no widespread tissue damage has not been reported, which indicate that the effects are likely more localized and targeted Presentation of antigens is a bit tricky, but fundamentally bits and pieces of proteins can be presented by many cell types via the MHC system. In non-professional antigen presenting cell the main mechanism would be via MHC-I, which allows presentation of peptides (i.e. bits and pieces of proteins) originating from the cytosol. So if such a cell would produce the protein and it gets presented, it could interact with CD8+ T cells likely resulting in target destruction. Attenuated vaccines often result in presentation of both MHC-I and II pathways, for example. With regard to protein turn-over, it is a bit difficult to tell. Synthesized the proteins are broken down and typically only fragments end up being presented (turnover rate of intact proteins in general covers a huge range depending on protein and cell type from hours to months in extreme cases). Those parts can remain around for a while but not necessarily in the same cell, as they may be released or broken down and taken up by other cells (the phagocytic pathway being the main mechanism of MHC-II presentation). It cannot be regenerated as once the mRNA is broken down, no new protein is going to be produced. However I think I have seen data suggesting that it may be around for a while, but cannot recall the paper (most I can think of focus on the duration of the T cell induction, which is related).

Primary targets are dendritic cells, which present antigens to T and B cells. While they can be killed on occasion, they typically have set lifespan which in part is coordinated via apoptosis. It should also be noted that mRNA are short-lived, even if they are presented to non-target cells their effects are limited. Only specific cells present antigens on their surface, in most other cases if you introduce RNA they might produce a protein, but it is often also degraded rather quickly by the proteasome.

There is a lot of lit out there, and I am not sure what the latest info is. However, I *think* that most recent life cycle assessment (i.e. from production until end of life) seem still to favour electric vehicles, especially if the electricity is produced using with low carbon emission. However there are are also studies with different conclusion, and the difference is down to which assumptions are being made. For example, if batteries are made in countries where electricity is mostly generated from coal, then the lifetime emission of electrical cars is at least close to hybrids. Conversely, if manufactured in areas with a high proportion of low carbon electricity, it would be much lower. Also, the longer electrical cars operate, the lower their lifetime footprint becomes over their fossil fuel counterparts. While a new electric car has a higher carbon footprint for production, estimates indicate that a low-capacity EV would reduce carbon emission compared to combustion engines after about 2 years of operations (again depending on how electricity is being produced). So if there is an overall strategy to decarbonize electrical production, it appears that the overall carbon footprint, even including the initially higher carbon cost eventually pays off. Conversely, if electricity is produced mostly via coal and electrical cars are rapidly replaced by new models (within 4 years) then lifecycle emission of EVs may be similar or worse than combustion cars. In other words, the overall decarbonization strategy is a key element in deciding what system is ultimately better.

The French famously make fun of Québécois for their outdated French. I am not sure how the relationship in reverse works.

Yes, my apologies, I tend to post without re-reading especially when I am supposed to do something else. I have added a sentence to also make it slightly clearer what I mean.