jonlucc

> Even Twitter was having problems

Is that a surprise? They're not who I would think of first as a gold standard for high viewership live streams.

I'm not sure how much I can say; I don't work for a CGM company, but my company is very interested in diabetes. There are non-device reasons you can't use a CGM indefinitely. The site becomes less reliable over time, and it varies from peron to person. I'm not sure if the Stelo has addressed any of those, or if the G7 was overly cautious, or something else, but there are biological things happening at the site that affect the time too.

I'm not sure of the current progress, but I was at a conference a couple years ago, and the Dupixent folks were presenting. It was right after the approval for pediatric atopic derm, and they were hopeful that for people with severe allergies, they could essentially use dupixent to wipe out the immune sensitivity to allergens and then retrain. This is pretty extreme, so you'd only want to do it in patients with life-threatening allergies, but it was an interesting plan.

Most companies don't have 2.1M employees.

At my work, there are certain areas that we are not allowed to have any cameras, and that includes all personal cell phones. I have a colleague whose daughter was at school during an active shooter incident, and she was able to use her phone but he was not able to receive her calls or texts. She was not killed, but I am glad she had a cell phone that day, and I wish he had his too.

I've worked on studies of mice that went to ISS. I understand the ethical concern. Ultimately, mice are used regularly as a model of human disease. The study I worked on specifically considered whether a particular treatment could help people in space avoid muscle and bone loss.

That is why doctors are supposed to consent their patients and weigh those risks. For what it’s worth, the risk of incontinence form prostate cancer surgery has been dropping quickly as traditional surgery is replaced by robotic surgery, sparing the nerve that runs close under the prostate.

At least in pre-clinical research, there’s also a mechanism by which regulatory agencies can sometimes force industry to pay for replication studies. It’s a little complicated, because sometimes there aren’t many groups who can reliably do the study, and clinical trials are so expensive and time-consuming to run, it would be difficult to do at that scale. Rodent studies are generally under $1M and monkey studies are generally under $5M (up a lot recently). Clinical trials are in the hundreds of millions of dollars and take years to run.

Completely anecdotally, I find this to be true. I do pre-clinical research (disclaimer: for a pharma company), and if you hand me a paper describing some research result in my field, it’s much more likely to reproduce in my hands if it’s from industry. I know from talking to my academic research friends that there are a ton of shortcuts, rotating inexperienced staff, and misaligned incentives. I’m not saying pharma is perfect, but in my experience, they’re more reproducible.

Fwiw, I do not know of any data in my realm which have been molded, cherry picked, intentionally misrepresented, falsified, or otherwise fake or flawed. I don’t work with clinical trial data, so if that were happening, it wouldn’t be on my desk.

Hank Green just posted a video about this recently, and he addresses this. In the past, helium was extracted alongside natural gas, but there is no reason the two need to be linked. As natural gas prices go down and helium prices go up, it makes sense to drill helium pockets only for the helium, and there are a few operations to do exactly this underway.

Grimes isn't her given name. It's a chosen name, which is common in performers.

I work in preclinical pharma research, so I have spent a good amount of time trying to recapitulate published data in animal models, so not quite clinical trial data. People who do this work learn how to evaluate trustworthiness. It can be as granular as "this lab is the only one publishing this kind of information, so we'll be skeptical" to a bit more broad "this class of drug isn't expected to have that biology" to "I trust this company over that institution". We route around the fact that some information isn't reliable, and that's not always because of dishonesty or fraud.

I'm not a clinician and don't deal with them regularly, but the impression I get is that new studies are published by researchers who have a lot of connections (dubbed thought leaders). They present at conferences. Other clinicians pick up the use case that matches their need (this patient has failed other therapies for this indication, let's try this new thing I'm now aware of). Then as experience grows, clinicians have more nuanced understanding of the use cases for that new information and its reliability. Frustratingly, this can take years, but that's bug that's also a feature.

Every clinical trial paper I've read has a discussion of inclusion and exclusion criteria. I think for the trial to be registered, it has to include this information.

Why would the statisticians be anonymous? I'm aware of at least a couple cases in which an independent set of statisticians were provided the data from a clinical trial specifically for a re-analysis. In one case, they showed some pretty concerning inconsistencies and the other confirmed no effect on the primary analysis, but suggested some sub-populations that might have shown an effect if a future study was properly powered. That follow-up clinical trial was just published showing pretty remarkable effect in the sub-population. I don't think there's reason to believe either independent analysis was anything other than independent.

There is already a mechanism for companies to submit questions to the FDA prior to clinical trial initiation. I'm not in these conversations, but I know the type of questions can be things like: would you accept this endpoint as a proxy for this indication, would you be satisfied with the effect size we expect, and are there other safety concerns you would expect us to evaluate other than those in our current plan. I assume EMA and other regulatory bodies have a similar process, but I'm not positive.

Disclaimer: I work in pharma, but pre-clinically. I am not involved in these clinical or regulatory issues.

I purchased hardware (a wheel), a new game, and started playing it because a streamer whose taste generally aligns with mine was playing that game this weekend. Then, I had him playing on one monitor while I played on the other. I don't think I'm alone in this.

While technically true, and is, in my opinion, one way to avoid jailing political enemies just to take them off the ballot, there's a reason candidates do a lot of rallies while they're campaigning. If a candidate is actually in jail, they'll legally be on the ballot, but they'll face a very steep uphill battle for the practical needs of a campaign.

I know this isn't going to be the most popular solution, but I find that Twitch Turbo isn't much discussed. I think it's $8 and eliminates ads from all channels. It may make more sense financially for some viewers, but it doesn't support any streamers.

All they have to do is allow sorting by total cost. It shows it on the search results, but will not allow you to sort by it.

AirBnBs can have yards, kitchens, multiple bedrooms, and locations hotels don't exist. I think those are the main things that benefitted them as they grew, and that market is still largely only served by AirBnB and VRBO. I haven't had the problems that everyone else in the thread seems to have, but that could be because of the places I choose. They have filters for no-contact check-in, so I have never once had to meet the "host".

Well based on their materials and methods, the antibiotics were all ordered from Sigma, which is not a pharma company, and I doubt they stand to gain much from the study.

What kind of manufacture do you think benefits from this outcome?

Honestly, for PCR, this is a larger N than I would guess is needed. In general, rats kept in constant conditions don't have a ton of variation, even in fairly high-sensitivity assays. I would expect a lot more samples if you were sampling wild rats from the subway system.

I recently looked at a disease course over time for several hundred genes. I only used 6 animals per time point, and both the disease mice and non-disease mice have very little inter-mouse variation at each time point for the vast majority of the genes.

I don't work with antibiotics or directly with the microbiome, but I have some questions about how these rats were housed. As background, I work in autoimmune pharma discovery, and my role is primarily with rodent models of disease. I also sit on my institution's IACUC, so I see a lot of other departments' protocols.

One thing that has become common in some facilities is housing males and females in separate rooms. Female mice and rats get pretty stressed when you house them next to males, or when you handle males first and then females after. This is a damned-if-you-do-damned-if-you-don't situation, because either these rats were housed in different rooms, which could cause microbiome differences, or they were housed together, which could cause stress, which could cause microbiome differences.

I think overall, this study is reasonable, and the fact that it confirms previous studies bolsters the hypothesis, but I'm not sure how you actually tease these out without a mechanistic proposition.

Lastly, based on my experience, there's something a little odd about their weight data. We use weight as a loose proxy for wellness, so it's regularly measured. The body weight for both the males and females are about 30g higher than I'd expect for this age (8 woa). Most rats and mice are very consistent weight for a given age, and this is just a minor red flag, but it makes me wonder more about their husbandry.

Just my 2 cents.

Isn't that just a longer way to say that it's a shortage of pay rate, benefits, and willingness to train? If the market is booming, and pay rates haven't caught up, aren't they short?

Just to add to this, the last thing that will be taken over by computers is tox testing. This is the last step that says "this drug is safe enough in primates to test in humans". It's the most complicated type of animal testing, because it is necessarily the interaction of every system in the body that could cause a tox issue.

So sure, we use modeling, and it's getting better, but it's not going to replace toxicology studies any time soon, unless every other human system is replicated in silico first.

Short answer: we are.

Clinical trials are expensive. NHP (Non-human primate) studies are also expensive, but orders of magnitude less expensive than human studies. We pharma researchers don't want to put stuff into humans if there's risk of failure, especially if that failure is a tox finding and not just low efficacy.

So we de-risk as much as possible. We go so far as to prove everything on human cells, then buy mice with humanized portions of their genome to test the target in mice that are more like humans in the way we need them to be. Then we test in NHPs, because it's very unsafe to assume that a drug that works and is safe in cells is safe in primates.

In a current project, I'm dealing with the fallout of this exact problem. We did a ton of testing, modeling, in vitro work, rodent work, then we dosed in monkeys and it caused a massive tox signal. We have to go back to the drawing board and explain what happened to the monkeys, how we're going to address it, maybe kill the whole program, and find a new path forward. It passed all of the rigorous pre-monkey testing. And I'm at a major pharma company, where we have pretty specialized teams doing most of this work.

edited to correct an error

Yes, alopecia areata is generally a progressive disease. It might be worth discussing with your doctor early. I'm not too familiar with the European regulatory landscape, but I would guess any JAK inhibitor would need to prove efficacy in a European-listed trial of AA to seek approval there, and maybe you'd be a candidate.

Practically, then, how do researchers access Elsevier articles? I work in big pharma, and if there's an article I don't have access to, I just request it through our information services office, and it is emailed to me almost instantly. Presumably, that is charged to my department. Is there a similar system in place at MIT? Does it come out of research budgets now?

> 3 or 4 12 hour shifts a week is normal for salaried nurses. $5200/wk isn't. It's over double.

It's a normal shift schedule, and they pay travel nurses much more than staff nurses to work the same shift schedule. These are typically 3 month contracts, but not always.

> I'm not sure what you're trying to say. Yes, it may be a full week of 12 hour shifts, but it's still a much higher pay. And if you get the next week off, it's a fantastic deal.

I don't disagree, but a lot of people do not want to work (or feel like they can't provide good care for) 12 hours every day for a week.

Hospitals have been paying 4x staff rates for travel nurses for multiple years now, though.

I replied to the parent, but the highest quotes are probably emergency contracts for 5 or 7 shifts of 12 hours but only for a week. Longer contracts are often 3 months at 3 or 4 shifts per week.