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kraussvonespyon The legacy of lies in Alzheimer's science

If it helps, here’s info from Dr. Derek Lowe, a 30+ year pharma chemist and author of In The Pipeline. For further research on the topic, he has many other posts on the topic, some of which are linked in the links below.

https://www.science.org/content/blog-post/aduhelm-again

https://www.science.org/content/blog-post/goodbye-aduhelm

https://www.science.org/content/blog-post/alzheimer-s-and-in...

kraussvonespyon The legacy of lies in Alzheimer's science

“But once you're already experiencing symptoms, there are other problem which clearing out the amyloid alone won't stop.”

Ok, maybe we’re just arguing different points here. I’ll grant that amyloids have something to do with all of this. I’m having a more difficult time understanding why one would suggest these drugs to a diagnosed Alzheimer’s patient at a point where it can no longer help.

Or is the long term thought that drugs like these will eventually be used a lot earlier as a prophylactic to those at high risk?

kraussvonespyon The legacy of lies in Alzheimer's science

Those quoting the 30% figure may want to research where that figure comes from and what it actually means:

“Derek Lowe has worked on drug discovery for over three decades, including on candidate treatments for Alzheimer’s. He writes Science’s In The Pipeline blog covering the pharmaceutical industry.

“Amyloid is going to be — has to be — a part of the Alzheimer’s story, but it is not, cannot be a simple ‘Amyloid causes Alzheimer’s, stop the amyloid and stop the disease,'” he told Big Think.

“Although the effect of the drug will be described as being about a third, it consists, on average, of a difference of about 3 points on a 144-point combined scale of thinking and daily activities,” Professor Paresh Malhotra, Head of the Division of Neurology at Imperial College London, said of donanemab.

What’s more, lecanemab only improved scores by 0.45 points on an 18-point scale assessing patients’ abilities to think, remember, and perform daily tasks.

“That’s a minimal difference, and people are unlikely to perceive any real alteration in cognitive functioning,” Alberto Espay, a professor of neurology at the University of Cincinnati College of Medicine, told KFF Health News.

At the same time, these potentially invisible benefits come with the risk of visible side effects. Both drugs caused users’ brains to shrink slightly. Moreover, as many as a quarter of participants suffered inflammation and brain bleeds, some severe. Three people in the donanemab trial actually died due to treatment-related side effects.”

https://bigthink.com/health/alzheimers-treatments-lecanemab-...

And here’s a Lowe follow-up on hard data released later:

https://www.science.org/content/blog-post/lilly-s-alzheimer-...

kraussvonespyon Majority of US teens have lost trust in Big Tech

Yes but only if you stay a private company. Once you issue stock, those like-minded individuals are going to be pressured to enshitify to maximize shareholder value. Or pressure the like minded to get acquired by a big pile of enshitification like Broadcom.

kraussvonespyon How America's universities became debt factories

Which is bad too because if you turn your hobby into your career, you end up not having a hobby anymore. In order to have a happy life, you have to have a vocation and an avocation that are separate from each other.

kraussvonespyon How America's universities became debt factories

And in the US, bankruptcy doesn't help with the student debt, so if the majority of your debt is student loans, there's really nothing that can be done other than die to get rid of them. And I'm 100% certain that if the student loan - industrial complex could saddle relatives and kids with that debt after death, they'd sure go after that too.

kraussvonespyon The Worst Website in the Entire World

What that arngren.net is missing is the cheesy Johnson Smith ads for X-ray specs! and Sea Monkeys! Johnson Smith was like the cheap claw machine of magazine ads. You knew that all you were going to get was crap, but it was fun crap. Maybe it helped that it took like 2 months to come and you were imagining how great it would be the whole time.

kraussvonespyon We gotta stop ignoring AI's hallucination problem

I'm by no means an expert but I've seen some of what's being used to train AI, and I have to wonder if the hallucinations aren't coming from collisions of errors that got introduced while training. For example, if you don't have accurate text descriptions of the photos you want to ingest, you use BLIP or something similar to describe the photos, knowing that BLIP was also automatically trained with a certain percentage of inaccurate descriptions. So you're using a flawed AI image description model to give flawed descriptions of the photos you're ingesting, which then introduces even more errors into the photo models. The flawed photo models generate flawed pictures with flawed descriptions, which are then ingested into the next round of models.

At what point do all of the accumulated errors in training make it so that all models are doing is hallucinating based on all of the flawed training data? Do we need to hire a bunch of humans to accurately classify the first couple of levels of what the models are ingesting or something similar, and would anyone actually pay for that to happen?

kraussvonespyon Tell HN: Microsoft.com added 192.168.1.1 to their DNS record

How dare you besmirch the reputation of The Awesome Store!

https://theamazingworldofgumball.fandom.com/wiki/Awesome_Sto...

kraussvonespyon CDC on depression and mortality: wealth, smoking, exercise reduce risk of death

100% agreed. The current system of "Sorry you feel suicidal / horribly depressed. Here are some meds that are statistically unlikely to help you but you won't know whether they help or not until ~60 days after you start taking them. What if these don't work? We'll shovel you a slightly different permutation of the same meds in hopes that what didn't work the last time will work this time. By the way, it will be another 60 days before you know whether the new meds are working or not" is terribly broken.

Is it any wonder that depressed and schizophrenic people smoke?

kraussvonespyon CDC on depression and mortality: wealth, smoking, exercise reduce risk of death

You're right. It looks like there are studies that indicate that dopamine is also increased by nicotine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946180/

Edit: er, sorry, you were probably talking about Buspar, not nicotine in regards to dopamine. Buspar does increase seratonin and dopamine, both of which are tickled to varying degrees by nicotine.

kraussvonespyon CDC on depression and mortality: wealth, smoking, exercise reduce risk of death

Nicotine has antidepressive effects through increasing bioavailability of serotonin. It also shines as an antipsychotic. I’m failing to find the study right off but something like 80-90% of schizophrenics are smokers.

Buspar works in smoking cessation therapy as it helps balance the drop in serotonin when quitting smoking.

kraussvonespyon I rode with an ice road trucker to the Arctic Circle

McPhee is truly a national treasure. If you're interested, that article was one of several published in his book Uncommon Carriers which includes a train and river barge voyage. Looking for a Ship is also great as it follows a merchant marine through various stages of that job.

The Curve of Binding Energy is a fascinating study of Theodore Taylor, the engineer behind the smallest nuke warhead in the world, and his concerns that terrorists may be able to build warheads themselves.

Pretty much any McPhee book or article is fascinating. His book Oranges is all about farming oranges, processing orange juice so it can sit in refrigerated vats for months (and how it is reconstituted through "flavor packs" that give it back the OJ flavors after long storage) and all kind of other orange stories. No matter what rabbit hole McPhee jumps down, his research and writing are nothing short of engrossing.

kraussvonespyon Compilation of claims/reports of LK-99 replication efforts

I'm not a chemist so this may be a dumb question, but is it possible that polymorphs are coming into play here, and the less official labs are better at contaminating the sample with the correct polymorph?

kraussvonespyon US universities need to stop elitist discrimination that Europe abandoned

I feel like you might have missed my last paragraph.

TL;DR: Traditional college maybe made sense before college debt became an albatross around college grad's necks. Time to find more reasonable alternatives for those that don't want that albatross.

kraussvonespyon US universities need to stop elitist discrimination that Europe abandoned

I've argued before that the "useless majors and departments" are useful for general studies, and general studies are good for everyone. Filler prereqs are a part of all of the college concept of creating a well rounded individual. In addition, the dorm life of college is a great half way step towards living by yourself. You generally hang out with people who in many cases will become your life's best friends.

I used to feel that way strongly. All of this made sense when most people could go to a state school and earn their way through with little or no loans. Today being a well rounded student with some great friends and a bit of independent living at a state school is likely to still saddle you with a 6 figure loan.

So even though I really thing the above is the right way for people to pursue an education / career after high school, it simply makes little sense for a lot of students. To the end I'd really like to see more institutions like WGU that allow you to get through school a lot more cheaply by doing everything remotely and measuring outcomes rather than measuring grades and the number of classes you took. And somehow we need to convince employers that colleges like WGU are the best alternative for a lot of really talented potential employees.

kraussvonespyon LK-99: The live online race for a room-temperature superconductor

Could the material need to be "seeded" by the proper polymorph?

https://en.wikipedia.org/wiki/Disappearing_polymorphs

kraussvonespyon How the Cheesecake Factory defied the restaurant industry’s rules of success

After reading this article, it kind of feels like CF is a modern version of Howard Johnson's. Big menu, lots of dessert, more of the food is cooked in house, safe place for picky eaters. It may suffer the same fate as Hojo too in that preparing for that many different entrees and making that much food in house ensures a high cost of waste, which is in part what I suspect did HoJo in over time.

kraussvonespyon How the Cheesecake Factory defied the restaurant industry’s rules of success

I recommended the Why Doctors Hate Their Computers to my GP doc. The next time I saw her and asked her about it, she was PISSED. She said she spends about as much time working on EMR info as she does seeing patients, and it really irritated her to know how many docs just don't pay any attention to what's in the EMR.

She's a great doc.

kraussvonespyon A novel about video games became a surprise best seller

Political books are a different animal than other books. You'll find political donors buying a huge number of copies to propel the book to the top of the charts to make a political statement. (my ideas can't be crazy if 50K people bought my book on the first day!)

Politicians use the books for fundraising and can end up with a lot of surplus books. I suspect that the donors that purchased Clinton's book needed to free up some garage / warehouse space and dumped them when they were no long a useful political tool.

kraussvonespyon Ketamine no better than placebo at alleviating depression, unusual trial finds

n=1 and all but ketamine is the only med out of 30+ that I've tried for my TRD over the last 40+ years that actually helped me long term. Every other med either had side effects that were worse than being depressed or they just didn't work beyond the first few weeks which I attribute to the initial placebo effect.

What I try to stress to people who ask is that ketamine is a powerful agent of neuroplasticity. So, so many people expect to take a pill and just feel better. With ketamine, you have to stay as positive as you can before, during and for days afterwards to reprogram your brain to be more positive. The people that I know that have had success with ketamine are those that either had therapists working with them during or right after the experience, or those who followed the "must work hard at being positive for 2-3 days after taking ketamine" advice.

This is a med that I suspect you could actually damage yourself permanently if you just take the med and then go right back to doomscrolling social media or something similarly negative. The initial experience can make you feel better for a day or two, which is huge because no other antidepressant has that kind of quick impact. But if you work at it during that 2-3 days after, you can become a more positive person permanently.

I'm hoping that it gets more accepted over time and can be prescribed by psychiatrists because compared to most other "here's some pills, hopefully you'll feel better in 6 weeks and if not, we'll give you more pills that will hopefully work in 6 weeks" depression meds, it works really fast. For someone on the verge of suicide, it can be a truly miracle med.

kraussvonespyon Thales seizes control of ESA demonstration satellite in cybersecurity exercise

James Pavur has some interesting papers on various types of satellite hacking, from using ML to determine that some "space debris" might actually be hidden spacecraft [0] to VSAT security [1] to Cyber Antisatellite weapons [2], and other interesting stuff [3].

[0]:https://ora.ox.ac.uk/objects/uuid:9af9771d-74cd-49f3-88e3-f3...

[1]:http://www.cs.ox.ac.uk/files/11922/Pavur%20et%20al%20A%20tal...

[2]:https://ora.ox.ac.uk/objects/uuid:6e4194fa-474b-41cb-81fa-db...

[3]:https://www.cs.ox.ac.uk/people/publications/date/James.Pavur...

Note: I'm not associated with Dr. Pavur in any way other than being fascinated by some of his papers and Defcon presentations.

kraussvonespyon What happened with ASUS routers this morning?

https://xkcd.com/2259/

I found that one just after spending all day chasing an odd WAN issue for a customer. A few years ago in the era of half/full duplex in ethernet, duplex mismatches sometimes manifested in some truly weird ways. It was at that point that I did start to believe in ghosts. At least ghosts in the network.

kraussvonespyon Ask HN: What would you recommend a 16 year old to pursue career wise?

This would interest me as an employer of tech people. Interest in topics like ML/AI or quantum computing or crypto algorithms or reverse engineering all show that you're capable of figuring out complex technical issues without help from others.

kraussvonespyon A Gambler Who Beat Roulette

That's something I should ask myself too when re-reading it. It has elements of: scientific heroism, science and technology ethics, the hacker mentality, and "science the shit out of it". The characters are quirky and interesting. It's Zen and the Art of Motorcycle maintenance in that it makes you think about some of the more interesting corners of technology ethics. The writing is gentle and affable with interesting tangents and rabbit holes. It's maybe more comfort than enlightenment after reading it so many times, but it's still thought provoking.

kraussvonespyon A Gambler Who Beat Roulette

The article mentioned the book The Eudaemonic Pie by Thomas Bass. This was recommended to me back in the late 80s by my favorite professor in undergrad. It is quite good, a rare book that I go back and read every year or two.

kraussvonespyon Pizza rolls and the meaning of midcentury food

I'm finding the same with other products too. There are a bunch of Aldi generic foods (like Mac & Cheese, tortillas, salsa, corn chips) that I like the taste of better than the more expensive name brand. Does this mean that the brand name has been reducing quality over time where the generics have been sticking more to their original recipe?

kraussvonespyon Pizza rolls and the meaning of midcentury food

Maybe just another derivative of the turnover or pocket pie? Empanadas, pasties, calzones, bierocks/Runzas, samosas all fall into the turnover category. Alton Brown's Good Eats had at least one show on turnovers and some of the different ethnic variations.

kraussvonespyon Nvidia Unveils CuLitho: A “Breakthrough in Computational Lithography”

Agreed. culitho wasn't an English word until nVidia marketing extruded it into the world.

In my defense, I was trying to vaguely reference the Problem with Popplers episode of Futurama but failed.

kraussvonespyon Nvidia Unveils CuLitho: A “Breakthrough in Computational Lithography”

culitho may have been the only remaining trademark-able word left in the English language.