CharonY

That would an extemely rare event as most mutations are neutral. And it is unlikely to be just genetic anyway. But of course mutations are also under selection, that is how evolution works.

You are aware that that these events are not that long ago and folks had (maybe still have) great parents with memories of that event? And that they still draw a direct line to their current situation (and issues such as illegal Israeli settlements certainly don't help the relationship). Also your example is a bit ironic as conflict within the empire even before the slow (hundreds of years) decline were rife with internal conflict of the conquered regions. And the successor states kept waging war for many years after that. During that time, the self identification of the people (including language and culture) have changed and their relationship to the Romans (either as successor or rivals) eventually diminished (after all, they could beat up Austrians now). I doubt that this is the timeline you are thinking about resolving it, though I hope. Edit: crossposted with StringJunky. Just an uninformed thought- I wonder how targeted this attack ultimately is. While any death of innocents is lamentable- at least in theory it doesn't sound like a mass-casualty attack. But again, I have not read much detail on it.

Look, rocks have been getting away with too much for too long. Why should we cut them slack just because they are mineral-based? We carbon-based life forms have to do all the moving and throwing and then we also have take the blame?

I think it is clear that Hamas and Hezbollah are in fact terrorist organizations, and stating it as such won't incur any modnotes for that reason. However, this is should not mean that any actions conducted by Israel should be deemed ethical. I will note that Israel should not be necessarily singled out in principle in the question of what responses are considered appropriate and how much collateral damage (which ultimately just means innocent deaths) are warranted for what level of perceived security (see the USA as an example). But again, it seems like trying to figure who is worse and therefore more entitled to killing folks, a race to the moral bottom. Now, there are uninformed folks who do glorify (to various degrees) Hamas actions, which is nothing but despicable, but again, that should not be a carte blanche for indiscriminate retaliation and other amoral actions (including actions in the West Bank. The conflict does not have a sole source and a sole perpetrator and one being the bad guy does not make the other one the good guy.

Well I banned them from use in our biosecure rooms for that reason. The contamination risk would be too high. But if I tried in BSL1 areas the fight would not be worth my energy.

It is a bit of an issue when one really wants to have a good vs bad narrative where both sides are engaging in unethical behavior. It too frequently devolves into a race to the bottom rather than stepping back and condemning the paths (plural) taken. Worse, alternatives (improbable and difficult as they might be) get drowned out.

I would think that carriers would also be a limitation in many areas. Not that I would need pagers in my lab. I'd just like to get folks using pipettors instead of playing with their cell phones every few minutes. Gosh, I feel old.

Huh, makes sense. I would ban cellphones from the lab, if I could.

I do wonder about safety of supply chains in general. With increasing complexity a lot of shady things can be hidden, it seems. I think in hospitals pagers are still in use. I was told by a resident (a while back though) that they prefer it over cell phones when on call, as they feared getting spammed and distracted and prefered to have a seperate system that alerts them to emergencies.

It seems that this might be a common theme to several of the discussions. I.e. starting off with non-standard definitions and then extrapolating from there. The issue is that it basically dismantles established frameworks around which discussions can be formed.

Mechanistically that rings true. I think there are multiple elements at play here. My suspicion is that social media exposure to consistent messages from divergent sources creates some sort of trust in the information (and folks might also trust their social network, though studies are a bit unclear about that). During COVID-19 we found consistent misinformation and conspiracy theories floated about and in many cases folks things are true, because the authorities are hiding "something". It certainly did not help that politicians weaponized expert opinion without much transparency or insight. We found that at least in quite a few cases, introducing transparency, showing goodwill and explaining the various factors did help to dismantle some of the conspiracy theories. There were of course hardliners, but to my surprise quite a few were more on the afraid side than true conspiracy believers. But I do agree, conspiracy thinking is easier and I do think that there is something that facilitates these things at an unprecedented pace. I hate to say social media as this smacks of lazy thinking, but I do feel that this is something that has changed our ability to think in ways that were are not really coping well with.

Thanks for clarifying. This is a distinction without consequence as any drop has to be within the same tolerance as new productions. I suspected that this is the part that of your comment and I tried to explain by amending my statement that: The point you are seemingly unclear about is that a) there are allowable variation in batch production and b) the product also has to remain within this tolerance during its shelf life (as per the guidelines). In other words if you take a random sample from the shelf and compare it to a fresh product the levels all fall within that limit and you would be unable to distinguish which is which. I.e. if you have a sample with 94% of its potency, it could be a degraded from originally 97% (which I think is what you think about) or it could be a new batch that started off with 94%. Assuming that I am not misunderstanding the guidelines somehow (and so far I am not seeing any information from your end that addresses it), it does mean that any medication pulled from a shelf has to work within the same tolerance as a freshly produced batch. In other words, you ignore the issue of tolerances in manufacturing and then make things up from there, gotcha. Again, this is not how the analysis works. I will note that the comment that started it was related to industrial guidelines regarding shelf life and while you were thinking about degradation within individual packages, I was thinking about the actual process (i.e. batch variation and stability testing) which fall under the guidelines. I have admitted that my initial language use was sloppy as I was taking the context under consideration without spelling it out, but again I have tried to provide context, which seemingly is continued to be ignored (and again, feel free to debunk them). OK that seems like a clear claim. Can you show me the guideline showing the differences in allowable limits and how they factor in the degradation in use. I have only done (blind) stability testing myself and was under the impression they were looking for the same tolerances. The only case I am aware of is tightening the tolerance for stability testing over manufacturing when degradation is faster than expected (the example I gave above for the thyroid medication was such a case). I.e. the stability values have to be tighter than the manufacturing tolerances, which seems to be the opposite to what you were stating.

Agreed. And I think it is true for most such theories. There is a mistrust in authorities and experts that drives these beliefs.

Considering it is Trump, likelihood ain't low that he would be golfing.

In that case I suggest your read up on the concept of significance in testing and revisit the references I provided. Specifically the quote I provided outlines what is considered a significant change: Or conversely it means, if those criteria are met, there is no significant difference within the product. I am not clear why this seems to keep tripping you up. Perhaps to clarify, and please answer really specific. If we test the product within its shelf life and do not see a significant change in all those criteria, how do you think does it affect potency? I believe that might be the crux why you don't think that following the guidelines would result in the same potency as fresh products (i.e. within error margins). (Just as a side note, there are some intricacies between potency and stability testing, but given that the very basics seem to be confounding, I doubt that this is what is meant and really is caused that many standards were developed on HPLCs). Please provide a citation for that claim. I will repeat another tidbit of information that you ignored, but which is important in this context (and which hopefully does not trip you up further. From what I recall, industry standards generally allow for variations of around 10% (though I assume there are exceptions, as noted). I do not have any regulatory documents for those (again, have never been involved in process control) but USP documents generally indicate expectations of 90-110% (USP documents are paywalled, but here is a doc referring to that). https://www.usp.org/sites/default/files/usp/document/FAQs/strength-stability-testing-compounded-preparations.pdf However, there are drugs requiring more stringent requirements, when degradation rates are uneven, such as for a thyroid drug: Again, note that there are upper and lower boundaries, which conform to the preparation requirements and are extended to the shelf-life. In other words, you can think of the potency of any product as a bell curve, with boundaries at 90-110. Following all guidelines would ensure that all products, fresh or on the shelf within the expiration date would fall into the same range. Now, obviously if you take a fresh product and test it once and then half a year later, test the same package again, you might measure but you would only know because you are drawing from the same package. If you were provided with a anonymous samples (fresh and shelf product mixed) you wouldn't know as all should fall within that range. Perhaps to shorten this overlong discussion, how about you simply find a regulatory document (or at least a paper that describes the regulation) that supports your claim that a lower potency than the accepted batch-to-batch variation during its shelf life is in fact acceptable (or at least contradicts the references I have provided) and that having it otherwise would be detrimental to health care (your second claim).

Not sure if being good with a computer is a criterion, but it should be noted that the goal of this study is more learning about processes and mechanisms involved related to vaccination hesitancy, rather than identifying population-wide parameters. The cohort is skewed to some degree as they used a commercial system which seeks out participants according to desired parameters and at minimum participants would need to sign on the platform, which can create a bias on its own. I wouldn't necessarily hold it against this study, as a) it is largely impossible to create perfectly representative cohorts (i.e. there is always some kind of bias, one just need to be aware if and how it impacts the outcome) and b) the main goal is behind the curtains, so to speak and not necessarily be representative of the US population (and they refer to studies looking at demographics for this information, instead). Aside from the computer aspects the cohort is not very representative, with 60% female, and, if I read the graph correctly, having a higher educational level than average, but also having a lower income profile. I am just guessing, but I suspect that it might be linked to a motivation to register with the commercial platform . The authors noted some other limitations, including being paid a flat fee, but argue for that some issues are mitigated. The demographic limitation is also reflected in the study due to the lack of an analysis of their outcome related to it. Rather they just compared the predictive power of their findings relative to (previously established) demographic variables. So again, a focus more on mechanism, which is also focussed on in the discussion section. The study falls under the "motivated reasoning" type of research and I do agree that a larger and more representative cohort could be interesting to figure out finer patterns.

Then kindly specify the point where I was factually incorrect. The issue is that you keep insinuating things but not specifying what you consider wrong and which context was missing. The only thing I can think of (with no help from your side) is that I said "no drop in quality" rather than "no significant drop in quality", which, as admittedly is a bit sloppy, though I assumed by now that most folks would know that in science lingo we do refer to statistical significance when we refer to differences. If that is your point of contention, which, I repeat, you have yet to specify, I see it more it fairly hypocritical that you demand increasing precision from someone while apparently no putting much effort into being precise yourself. Then how about being more precise in what you want to say. Your last post just adds to the confusion as, again, the selective quoting does not really change anything of the discussion and forces me to interpret what you intend to say. So let me put some final effort in to help you understand where I see that you might have misinterpreted things: It doesn't really- the guidelines are pretty firm on them meeting the stability requirements, unless there is a specific point you want to make that makes it relevant. For example they might require storage at high humidity or light for moisture or photosensitive drugs. Yet the same baseline has to be reached in terms of potency of the active ingredients. I have outlined that detains in the guidance document earlier, kindly refer to where you might disagree with them or how the quote you provided might supersede FDA regulations. Or do you mean any other specific parameters (see, you do not specify that, so I have to start guessing again) that are unrelated to drug quality (especially for accelerated testing) ? What other test protocols are you referring to here? Again, in the document the parameters are listed. I should also add there are certain intricacies regarding the methods, especially HPLC (which is still standard in many areas) can have trouble separating active ingredient from degradation products (though LCMS takes care of that). But IIRC for many drugs batch testing is allowable within +/- 10% for most drugs, except when there is indication that therapeutic effects change within that range (but I have not been involved in production testing, so cannot say for sure). That is true, but as pointed out repeatedly, the manufacturer has to make sure that there is no (statistically significant) drop in potency or other relevant quality indicators used for the approval. If you read the first couple of paragraph in your article, you would have seen that. It occured to me that you might be unaware that batches also have (allowable) variations. I.e. the point is that stability should be comparable to batch variations. This is totally irrelevant as we have already discussed that the true shelf life might extend beyond the indicated shelf life. The issue is (in case you have forgotten) whether manufacturer arbitrarily decide on the self life and purposefully put a shorter in to make a profit. I have pointed out that they cannot just decide on a date, rather have to do stability testing to ensure that during the indicated time period no loss of potency is observed. You keep insinuating that this is somehow incorrect, yet fail to point out what that is beyond providing quotes that do not appear to provide any additional context. Telling me to read what you wrote and not misinterpreting it seems really lazy at this point, I am afraid. It looks to me that you fundamentally misunderstand something but perhaps someone else can figure out what it is as I apparently am not able to interpret your writing the you want it to mean.

Freud is not really used in any relevant form as far as I can tell, but there are branches in psychology that admittedly have rather dubious frameworks. That being said, and I think I made the argument already somewhere, a bit difference is the high level approach of social and related sciences. Psychology straddles both words, with but all deal with high level of complexity and therefore tend to be more narrative. In a somewhat similar vein, many biological models are also more qualitative and predictions are only valid in small domains. But much is also semantics. Natural science is definitely a different beast compared to social sciences. But that does not necessarily make them not a science. At minimum, they provide falsifiable hypotheses that can be tested, though method-wise they are also more prone to methodological errors. Conversely, one can contort (not directed at anyone specific) arguments as much as one wants, but for example religious beliefs or spiritual enlightenment will ever be science.

Can you clarify what you attempt to argue here? If you read your posted article: That is what is being regulated and I have provided the regulatory requirements by the FDA. At this point it starts to look more like backpedalling of your original demand. I suspect that you assume that drugs lose potency the moment they hit the shelf and as such, stability testing as I outlined initially cannot be happening. And that assumption might be intuitive, but after presumably reading the regulatory demands and the FDA interpretation of the regulations I would have assumed that this assumption should have been modified. Instead, this looks a bit like doubling down by selective quoting.

An interesting study looks at factors related to COVID-19 refusal. There has been an ongoing debate whether hesitancy was fueled by lack of good information or whether there are other drivers. This study focuses on how folks process information and found an important impact in the form of deliberate ignorance: https://doi.org/10.1038/s41541-024-00951-8

I think event hat needs to be qualified, as to the former, men are likely to be successful in suicide. But women are more likely to attempt it. A recent study puts it at 1.78 odds ratio (https://doi.org/10.1016/j.jad.2022.05.096). This is roughly in line with studies dating back to the 80s (going as high as about 2.5 fold). One of the key differences is the type of suicide attempt. Women tend to try poisoning, which is very ineffective. Men tend to use more violent methods, especially guns. There is a link to violent behaviour, either against themselves or others, which is indeed a gender difference. Women are less likely to engage in such, for example. The tricky bit is to figure out the psychological impact and how it manifests in men vs women (I am sure there are studies out there, but I am unfamiliar with the topic). As mentioned, men more frequently engage in violent behaviour and are more likely to be both, perpetrator and victim. In women, there is an imbalance, especially when it comes to severe injuries. That being said, there is a very specific burden for men that are victim of abuse, which is related to toxic masculine ideals. I.e. the stereotype that strong men should just suck it up. But there is increasing recognition on this issue, luckily (though still not enough). But that points to yet another issue in gender differences in psychological impact. For example when it comes to dealing with trauma, it is likely that societal expectations color how individuals cope or fail to cope with it. Some studies looking at differences between trauma associated with accidents and victimization, it seems that women are roughly similarly affected by either form of trauma (which in itself is interesting), but men are more likely to have more negative self perception and other symptoms when confronted with victimization vs accidental trauma ( https://doi.org/10.1080/20008198.2021.1975952). Depending on study, women do seem to have an overall higher rate of symptoms, such as PTSD, but also tend to cope better than men. The narrative there has been that women are better at emotion-focussed coping (doi:10.1093/brief-treatment/mhn004). Of course, as these studies might be colored by societal expectations themselves (which can be an issue of psychological studies).

Not really. The indicated changes are considered not statistically significant and generally also applied to batch production. I.e. the product is still virtually indistinguishable from fresh products. In case you are not familiar with the concept, in most of biology and medicine significance is established at the 5% level. There might be exceptions for certain types of drugs, where threshold can be lower, but I believe that these are outside of the general guidelines. The main quality concession there is related to accelerated (i.e. high temperature) experiments, as long as potency is not affected. Or are you referring to something else, in which case please clarify as I am curious to see why you'd think that I am not reading (or understanding) what I post.

Yupp, often for initial approval manufacturers can provide shelf life data from production batches, provided they are reresentative and following the same guidelines. That data can sometimes only cover 12 month, but they can amend it after they make longer tests. There is a bit of a push to provide manufacturers with incentives to make longer tests or work within SLEP or similar mechanisms to prolong dates. But for longer periods at home storing conditions could complicate things.

Of course I can, at least for the US (I believe Health Canada is mostly following FDA guidelines, but am not sure). The requirements are outlined in the code of federal regulations specifically 21 CFR 211.166 outlines the general requirements for stability testing https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=211.166. Additional requirements are outlined in 211.165: There are also other passages of relevance (such the the regulation requiring expiration dates 21 CFR 211.137 and other regulations that I am not familiar with might also apply. The FDA is using these regulations and has built a set of requirements for the industry. A guidance document outlining the specifics (as per the FDA) can be found here: https://www.fda.gov/media/71707/download A significant change from the original formulation is considered if any of the following is observed during the stability study: In addition there are additional criteria, depending on the packaging. Note that they minimum test time is 12 months (or 6 under accelerated schemes). However, the industry standard is usually 2-3 years. The reason is, that (contrary to some assumptions in this thread) having a very short shelf life might make it difficult to sell. The reason why testing is rarely done beyond that is that as indicated in the guidelines, the testing has to be representative of the production. So if the manufacturer change packaging (in a substantial way) or formulation, they have to redo the whole process (meaning in many cases adding years to the process). So keeping it at the 2 years keeps things a bit more flexible. Also keeping the same schedule will result in ideally almost identical degradation profiles, without the need of additional statistical evaluation and one can basically just point at the previous approval. However, this is the reason why you might be able to find the same drug from the same manufacturer with different expiration dates. They may have tested one version for longer than another. I should add that there are relaxed requirements if the mechanism of degradation and its kinetics for certain drugs is very well known. Though in many cases folks tend to prefer to do empirical testing for their formulations to avoid arguing, if possible. It may depend on the specific types of pharmaceuticals. The areas where I am more familiar with tend to have more complex formulation requirements.

Well, except that the online cohort has resulted in a massive drop in abilities. IOW it just doesn't work as well as traditional teaching. First cohorts from the pandemic have arrived at universities and the results are dismal. We have been doing hybrid teaching for a little while and similar as during the emergency phase of the pandemic, remote students are consistently doing worse and it has been pretty much accepted learning loss is a worldwide phenomenon due to COVID-19. I will note that there are not a whole lot of studies out there, and few used standardized testing for cross-comparison. In fact, some simply used student scores during the pandemic, which is problematic, as remote teaching has resulted in a massive flood of cheating. In some cases you could see your questions posted online on certain websites in real-time.