> There is a tension between empiricism and fundamentalism with much of medical science focusing on fundamentalism.
This is a deeply unfair statement, and also a false dichotomy. Medical science is of course empiric. What you call "fundamentalism" is that compounds need to undergo a rigorous regiment of empiric testing before they are given to potentially millions of people. And no, it's not just because of Thalidomide. Many, many compounds fail clinical trials because of severe side effects, like liver toxicity, severe immune reactions or heart problems. Then there's of course increased risk of cancer, which can take many years to manifest itself empirically. You argue that you prefer living with these uncertainties rather than ME/CFS, and that's of course entirely understandable, but disparaging the field of medical science as focused on "fundamentalism" because we do not give large patient cohorts untested compounds is polemic. I understand where you are coming from, and I'm sorry that you suffer from this terrible condition, but likewise, you should try to understand the other side.
Doctors have been maligning ME/CFS as psychosamatic for decades and generally still do despite a large amount of modern evidence to the contrary. If you have it it’s clearly not, you can get good and bad days that are clearly not dependent on psychological state. In addition I have it due to hEDS which is a condition that is almost never diagnosed due to aforementioned blind spots. Most doctors still think the prevalence rate is 1/50K despite continued research raising that number to 1/15K and 1/500. It takes a long time for this information to percolate through the system.
Doctors, like many professions, have institutional blind spots, I studied these in my search because I was looking for something that had not been found. Most doctors have to consider all people and all conditions, I only have to be concerned with one.
Notably they only recently adopted Bayesian statistics for medical trials despite that math being around for hundreds of years.
I completely understand your frustration with the lack of knowledge and research in ME/CFS. It's a scandal, given the prevalence and seriousness of the condition. Unfortunately, after Covid, ME/CFS was even more politicized as part of the long-Covid discussions and got caught up in the culture wars. I have several friends with ME/CFS and they basically say the same things you do - ignorant doctors, high cost due to medication usually being off-label and not covered by insurance, and even friends don't take the condition seriously.
ME/CFS research is severely underfunded. The reasons for this are not simple, it's partly due to the complexity of the disease which, as cynical as it is, does not make it an attractive research topic for ambitious scientists. Same goes for "Big Pharma". Clinical trials for ME/CFS are extremely complicated, and hence expensive, due to the myriad of symptoms in how the condition can appear. It makes research in this area very difficult and expensive. There's very little funding for ME/CFS research, and that needs to change. Unfortunately, especially in the US, this is not going to happen for Kennedy reasons.
The Bayesian statistics thing is a bit of red herring, though. While your are correct that the math is old, the needed compute resources for doing Bayesian modeling on large trials was simply not there until recently. But it is also correct that it also took a long time until there were official rules regarding this from FDA and EMA. These regulatory things move very, very slowly.
>compounds need to undergo a rigorous regiment of empiric testing before they are given to potentially millions of people
Particularly when the mechanism behind most of these peptides comes down to "promotes more rapid cell growth". The intent may be to repair the skin, muscles, or ligaments, but biology is rarely that specific.
I think the grandparent meant "fundamentalism" as "mechanistic", and lots of things we can know (as you say using the scientific method) to be useful long before we have a good mechanistic explanation of how they work.
Some examples: aspirin (willow bark used for thousands of years, drug synthesized in 1897 and mechanism explained almost 100y later), or general anesthesia used again since mid 1800s and the mechanism is quite still debated.
This is not to downplay all the long term, or developmental, risks that using something novel can result in. But we can empirically know something about the effects without having good mechanistic models.
But it is usually not necessary for approval of a compound to be able to describe how it works on a molecular or cellular level. What you need to show are three things: efficacy, safety and quality, so basically: the compound has the intended clinical benefit, has an acceptable safety profile and can be produced with a consistent manufacturing quality. Most compounds fail because of lack of efficacy (roughly half), and roughly a third because of lack of acceptable safety.
The vast majority of drug candidates don’t make it to the trial stage. Much of the research has to be defensible prior to the trial and what makes them defensible is having a mechanism for action. Of course once a drug is being used off label the starts to be some empirical data which can be used for trials, and it seems that we’ll get lucky with GLP1-As.
You are entirely correct. New compounds for trials do not come out of thin air, you usually derive them from compounds you already know how and why they work. For instance, we know very well how Semaglutide works, same goes for many other peptides that are currently being studied. However, you are correct that we do not understand why they would help for ME/CFS, simply because we do not understand ME/CFS in the first place. As I've written above, it's a severely neglected disease.
Anyway, I don't think we really disagree, I rather misunderstood your original post. It's good to hear that these new peptides are helping with your condition, and I wish you all the best!
I think I would need to see testing on a control group of housebound patients with other conditions to believe this. It's easy for ME testing to pick up markers for being housebound and limited exercise for an extended period of time.
You sound exactly like the tens of doctors that misdiagnosed my aunt (who passed away through euthanasia after her symptoms got too bad to live with late last year).
I understand that the symptoms of ME/CFS might be similar to being obese/depressed or housebound, but the problem is that doctors often jump to that conclusion too quickly and don’t take efforts to diagnose ME/CFS leading to situations like my aunt’s. She was also obese and depressed and has been struggling with those symptoms for about 30 years and has constantly been misdiagnosed the entire time because doctors didn’t figure out that those were symptoms of ME/CFS and not two unrelated conditions coming from two different diagnoses.
Thanks to long-covid putting the symptoms of ME/CFS on the forefront lately, there’s finally been some much needed research into the disease and people like my aunt finally get the diagnosis they should have been getting many years ago.
Well, reading the study, I'm not sure more patients could rescue it from methodological bias. They assumed the premise basically -- we should find a biomarker, which is kind of what this thread is discussing. Then they went trawling for biomarker in a sea of millions of biomarkers. They did this by training an model that produced the desired result, using a grid search for hyper parameters that even further expanded the available degrees of freedom here beyond what they had from the biology. No pre-registration; There are millions of places where the researchers could have made a different decision -- would they still have gotten a publishable result? Oh plus the authors mostly work for the company whose data they use, which is hoping to sell a diagnostic test.
I'm giving you a thorough response because I'm detecting a cavalier anti scientism which I think is sadly becoming more common. This stuff is hard; are you sure you understand it enough to have an informed opinion?
> outside of lacking attribution / retaining copyright, I don't see a problem?
That's a bit like a shoplifter saying "well, outside of not paying for it, I don't see a problem?".
Apache 2.0 clearly says you must include the license, include copyright, state any changes you've made and include the NOTICE file. None of that was done, so this is a pretty clear violation of the license. The copyright holders can demand that this is fixed immediately, seek at least an injunction if that does not happen, and maybe even claim profits made from selling the software while violating the license.
Also, Microsoft regularly sends me legitimate emails regarding "Microsoft Rewards" that are absolutely indistinguishable from phishing, like "Total Prize Drop is here! Your chance to win 1,000,000 USD cash grand prize or one of three customizable Mercedes-Benz cars!", complete with links to login pages and everything. So like this one, just as mail: https://xcancel.com/bing/status/2034720189003231410
The first time I got those I couldn't believe these were legitimate. Thank you Microsoft for teaching your customers how to fall for scams!
I’m a lucky duck, because Microsoft ONLY sends me emails in Spanish. Password reset? Spanish. Ad? Spanish. ToS update? Spanish. When I log in, it’s English, and I’ve never been able to find any setting anywhere in my account saying to use English. It’s so funny, I can’t even understand their ads.
I've had my Kobo Clara HD for almost 8 years and I still use it daily with KOReader.
It's so easy to install KOReader and it's really repairable. I replaced the SD card at one point, and another time I thought it was broken or needed a new battery but came back to life after reseating cables.
Before that I had a kindle and you had to jump through a lot of hoops to install KOreader, and I remember you had to be careful not to upgrade the firmware so it could be jailbroken.
Like I said I've had the Kobo for 8 years, so I hope this is still the case.
KOReader works just as easily, and just as well, on my much newer Kobo Clara BW. I'm not unhappy with the built-in reader software, but keep KOReader installed just in case I want or need it.
Calibre web support, opds catalogue, wallabag, ssh. And it supports so many file formats.
I'd imagine the built in reader has improved a lot over the years, but at the time reading technical pdfs on it was not feasible. KOReader allowed me to rotate to landscape and reflow the pdf text.
I almost got the Clara BW for Christmas, I thought my Clara HD was dead, wasn't sure if it was the battery or screen but it was failing to properly clear and update the screen. Someone actually bought the BW for me but I ended up returning it after I managed to recover the Clara HD.
I was kind of looking forward to the waterproofing, but seems my old one is not yet ready to give up.
Had a few kobos, very good readers, then bought a Box color go 7 ii, mainly because it runs android, so you can used it for so many things. Shame the company is based in china.
I (author) live in Brazil. Kindle is the only E-Ink device on sale here by its official manufacturer. We can import a Kobo or Boox or Bigme, but importing taxes are very steep.
Not all Kindles can be jailbroken. It's a constant cat and mouse game, and if you get a Kindle with up-to-date firmware, there's a good chance you cannot jailbreak it for now. Once jailbroken, you need to make sure it doesn't auto-update the firmware. And personally, I think one should rather support open devices. Even if Amazon loses money on a jailbroken Kindle (which I doubt), in the end, it still hurts open alternatives.
Because you still paid Bezos and then have a bunch of extra work to do to not make it a strictly interior to a Kobo. Tailscale+Koreader+Kavita on my Kobo Libra Color gives me access to my entire library at all times from anywhere. I read a lot more now after getting one.
If you want to know how serious to take this, just look at this gem:
> Enhancing Search: [...] Clearer and more trustworthy results, with results from content on your device easy to understand and clearly distinct from web results
So yeah, you still get web results in your search bar, a feature absolutely zero people want and which is just there to fake Bing success, just with a little divider now next to the applications the search failed to find.
Not just me then? Those integrated search features have been around for so long, and always irritating. I use macOS. Same problem. Searching your computer or searching the web are fundamentally different tasks. I'm curious if anyone actually approaches them the same.
I don't like that default on mac either but in their defense it's super easy to customize. I turned off all but applications and my documents folder for spotlight search.
I think most computer users dislike this but I see a ton of normal folks do this, they don't have the same conceptual boundaries folks on this site do (myself included).
Yeah, but is that a good thing? I think the lack of those conceptual boundaries are exactly why computers are so difficult to learn for some people. Access to web services, and the services themselves, still aren’t reliable enough to support this idea of a completely transparent computer experience where you don’t need to know what machine a file is on.
How? I feel like every time I do my ~1 yearly Windows reinstall I need to google it and then alter half a dozen registry keys and a bunch of group policy settings, and some of them are the "old" settings now replaced with something even more vaguely named (probably on purpose).
Mine was from websites 7 days I think. Randomly stopped booting a month ago (bsod after updates).
Switched to cachyos - I've spoken with at least 5 people who have had the same bsod after updates situation in the last 6 months. If windows at least embraced proper update techniques like with immutable Linux - and enough polish to make the random bsod loop after updates impossible to accur without hardware damage id likely go back for my gaming rig at least - but right now, it feels like garbage ngl
I've used Windows as my primary desktop for ~35 years and I do my absolute best to housekeep, but I still need to reinstall about once a year or so. I'm militant about installing almost nothing on my primary PC and putting all the janky apps on another PC via RDP too.
The computer I'm writing this on, the earliest things showing in Control Panel were installed in February 2012. It's not a rarely used clean machine, it's a daily use home computer/plaything with a lot of stuff installed/removed over the years from application suites to dev environments and esolangs, to editors, viewers, inspectors, emulators, hypervisors, browsers, chat and streaming clients, game stores, networking tools.
That's not a reason for why I didn't need to wipe and fresh install Windows in 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023, 2024, which was what qingcharles was claiming he had to do.
If you need to reinstall Windows so frequently, have you considered giving Linux a shot? I switched 16 years ago and haven't looked back. Until recently, I used Ubuntu and I think I had to reinstall twice in 15 years, one of which was when I got a new laptop.
Last year I switched to NixOS and while my impression is that it's going to be much more stable even than Ubuntu, installation also only takes me 5 minutes. That is, 5 min until my system is in exactly the state I want, including installed software, window manager config, keyboard shortcuts, desktop wallpaper, GUI theme, etc.
I'm not sure what you think happens if random programs are lying around - they affect nothing except waste a miniscule amount of space. I cleaned up the context menu once, probably the autostart once upon a time, search indexer is off and use Everything instead, antivirus is off ...
Of course I'm still on Windows 10 and will be for the foreseeable future.
My desktop running windows 11 started life as windows 7. Has been used on different hardware both amd and intel. Has been cloned multiple times. And the only problem was a recent windows update that beefed security so i couldn't access shared files on an older clone running on another hardware because of using same sid
Not the person your were talking to but at work the Windows machines have a bunch of MDM garbage on them that screws up the OS and requires reimaging every few months. For that reason I have a Powershell script to automatically set up a machine.
Honestly I should. Registry and stuff gets cluttered. Programs don't uninstall cleanly, or they change settings I can't find. On one machine I somehow set it up as a wifi print server or something and for the life of me couldn't find a way to turn it off. But it's such a hassle to setup a computer.
Unclean uninstalled programs also don't impact performance. Unless it really isn't uninstalled and still runs in the background, but that can easily be fixed by a person competent enough to reinstall Windows once a year.
Settings you don't find, will still be not found after reinstalling Windows.
In my case it's not about performance, it's about usability and disk space. And again, that time I somehow started a WiFi access point and couldn't find anything online to turn it off. That laptop also at some point had the new folder option get removed from the right click menu. I had to copy/paste one. There are a lot of weird things that can happen over the years.
What are the practical issues with "cluttered" registry? But also, you can use special apps to track installations and do advanced uninstallations for ~clean uninstalls. Likewise, you could even spend time tracking settings.
So yes, still a hassle, but nothing comparable to setting/reinstalling everything from scratch, that's just pure waste
Maybe I shouldn't have said cluttered. More like programs mess with things and don't always put them back. There are a lot of Microsoft support forum posts that had to reinstall Windows to fix weird issues that only started after the install
It's been a while but from what I remember the easiest way to block this was by disallowing outbound network requests from search/the start menu in the firewall settings. It worked across all versions of Windows I tried it on.
Click Start, type something to bring up search results, click the kabob in the top right (...), click "Search Settings", disable "Show search highlights".
Ha! This is the first time I've even tried the Win10 Search bar in months after constant disappointment from it, and it doesn't even load for me nowadays:
Transferring to a new Android phone without depending on Google cloud is a total nightmare. It doesn't help that there's a ton of outdated information in the net on how to do that. You can see it in this very thread: lots of people saying "do a local Whatsapp backup, transfer the backup manually": this USED to work but does NOT anymore. There is a decryption key in /data/data/com.whatsapp, which of course you can only access on rooted phones (maybe there's a way to approve the transfer when the old phone is still working, not sure).
To the best of my knowledge, it is basically impossible to fully transfer applications locally to new phones without root access.
- do a FULL backup of the apps you want to transfer, that means it must also include "device protected data"
- restore apps on your new phone
If you'd like regular backups of apps: create scheduled backup with NeoBackup to a local folder and sync them with whatever tool you want to external storage. Good luck with that, you'll need it.
> You don't have to use the cloud transfer with WhatsApp. You can simply transfer the backup files manually before you do the first logon. They're in the media folder.
This does not work anymore. The chats are encrypted and the key to decrypt them is not in the backup files.
I tried the exact same thing a few weeks ago with a de-googled phone and it did not work. I had to transfer the /data/data/com.whatsapp folder as well via root access, then it restored the chats (the display of the old phone was dead and hence I couldn't initiate any kind of account transfer to a new phone).
Weird, for me it worked fine. I didn't need to transfer the root parts. Nor did I do anything else on the old phone. I just signed in on the new one with the backups in place.
I don't use Google services or an account either, though I do have Google play installed.
While this will backup all the media files, the chats themselves are encrypted and the key to decrypt them is not included with that backup. The key is in the data partition which you will not be able to access without rooting your phone.
Out of interest, how is that relevant? Are we not able to criticize a FOSS maintainers response unless we run a project of scale ourselves? The maintainer is clearly engaging and knows what the problem is but stalls on the "last mile" which is issue creation. Do you agree?
wolfSSL also sells commercial licenses so it's not like they're going uncompensated for their work. Regardless, we shouldn't put people on pedestals because their title is "FOSS maintainer"
You know a social movement went full circle when a criticism that is so scathing, you couldn't have possibly come up with it and make it trend before, even if you gave it your all, is now a motto and a point of pride for those who follow it.
This is happening at the same time where hundreds of millions of regular variety consumers are being fed propaganda daily about how it's "finally time to switch to Linux", because it's so much better for them, the individual. If only they knew it's apparently not actually about them, never has been, and never will be.
When exactly is 'before'? Before Github existed to put front and center your code and its issues? Before it became an expectation to have a a rich Github profile when you're considered for a job position?
Of course I wouldn't have been able to come up with this statement because the perverted view of OSS devs owing free work to the users of their software was not so pervaisive.
On your edit: a bit rich saying the calls for switching to Linux propaganda, especially with the downturn of UX of windows and macos... Also why just hundreds of millions.. Go for hundreds of billions if you're just going to pull out numbers. Apart from that - even if Linux is not about the users, it is in many cases better for them as-is. Funny how that works with no conflict.
> Also why just hundreds of millions.. Go for hundreds of billions if you're just going to pull out numbers
You see, that would be because I did not just pull out an arbitrary number. "How many Windows users there are" is a reported fact you can just search for, and even the total is not "billions" (plural). I know, I was surprised too. From the horse's mouth: https://blogs.windows.com/windowsexperience/2025/06/24/stay-...
My first comment on this site pointing out that a FOSS user sounds entitled is from 2021. I've been saying it outside the site for 10+ years, spanning back to the time when it wasnt cringe to have a Github sticker on your laptop.
I maintain several FOSS projects, although none as popular as wolfssl and if I want to make a new issue to make it more clean, I usually do it myself, because then I can write it the way I want, and include the information, and only the information, that I think is important. If I ask someone else to do it, there's a pretty good chance they won't write it the way I would like, if they write it up at all.
That's actually impossible to answer. I maintain or contribute to or have contributed to several FOSS projects whose number varies depending on how you want to count them, and neither myself nor anyone else who contributes to any FOSS project has the faintest idea how many people use them, especially if they're included in widely-used distros where the number is anything from zero to $number_of_distro_users.
This is a deeply unfair statement, and also a false dichotomy. Medical science is of course empiric. What you call "fundamentalism" is that compounds need to undergo a rigorous regiment of empiric testing before they are given to potentially millions of people. And no, it's not just because of Thalidomide. Many, many compounds fail clinical trials because of severe side effects, like liver toxicity, severe immune reactions or heart problems. Then there's of course increased risk of cancer, which can take many years to manifest itself empirically. You argue that you prefer living with these uncertainties rather than ME/CFS, and that's of course entirely understandable, but disparaging the field of medical science as focused on "fundamentalism" because we do not give large patient cohorts untested compounds is polemic. I understand where you are coming from, and I'm sorry that you suffer from this terrible condition, but likewise, you should try to understand the other side.
reply