YouTube Bans Award-Winning Short - <AUTHOR> http://www.cartoonbrew.com/ideas-commentary/youtube-continues-hurt-independent-animators-bans-award-winning-animated-short-153430.html <comment><USER4> The case of this article is unfortunate, but it's actually missing what I think is the more serious problem with YouTube for independent artists right now.. This is just a problem of an unfortunate strike against a video - <USER2> imagine that it will be fixed under appeal. These things happen, as a great great number of videos need to be evaluated by staff against a complicated set of criteria and precedents. It doesn't actually speak very much about any kind of systemic bias against independent artists.

What DOES create a problem for artists is the tuning of the algorithms to be highly preferential to long form frequently posted content E.g video game commentary. This is a big problem for creators who work in short, high effort, highly polished media - E.g animators.

This really really bums me out. I was an employee at YouTube during their period of great growth and I absolutely loved the platform and potential for compensation that they gave to niche and indy animators and musicians, and had great hope for a future where the democratization of video distribution would lead to a flourishing of art and entertainment that caters to a higher common denominator than the over-polished, focus group approved, mass market creativity that passes for main-stream.

Sadly, it looks like the prime goal of increasing return visits and raw view time has lead to algorithmic optimization of that same mass-media race-to-the- bottom in quality and diversity in search of a broadly palatable and compulsively consumable product. It saddens me and I still feel that they could have it both ways if they took a more aware approach to niche content. YouTube offers monetization - the fact that artists even need Patreon means that GoogTube is ignoring a need, and thus a business opportunity. Just because a piece of work may only appeal to 50,000 people world wide doesn't necessarily mean that it has less value or merit than one that appeals to 10 million.

I support quite a few animators on Patreon, and the impression I get is that they are all struggling to keep working on it as a primary job.

<comment><USER5> "When you're young, you look at television and think, 'There's a conspiracy. The networks have conspired to dumb us down.' But when you get a little older, you realize that's not true. The networks are in business to give people exactly what they want. That's a far more depressing thought. Conspiracy is optimistic! You can shoot the bastards! We can have a revolution! But the networks are really in business to give people what they want. It's the truth."

\--Steve Jobs

The algorithms are they way they are because YouTube has figured out what people actually want to watch. Surprise, most people still want to watch "lowest common denominator" content, just like they did before digital media.

<comment><USER6> Put another way by Terry Pratchett,

"And so the children of the revolution were faced with the age-old problem: it wasn't that you had the wrong kind of government, which was obvious, but that you had the wrong kind of people. As soon as you saw people as things to be measured, they didn't measure up."

<comment><USER7> Please! It's Brecht:

      Would it not be easier
      In that case for the government
      To dissolve the people
      And elect another?

Poem in Die Welt (1959)

<comment><USER6> Ha, nice! Thanks, I love finding out about the origins of his aphorisms.

</comment></comment></comment></comment></comment><comment><USER8> It's impossible to believe that Youtube blocks this video, but can't tell that the copies are the same video.

Which means they have provisions to block a _providers_ video. Not the _content_ of a video. They're happy to publish other copies of the same "inappropriate" content, and to monetize it.

But they won't let the original author monetize it.

If this is something other than "being evil", I don't know what it is.

</comment><comment><USER9> Is there a tipping point where the independent content creators tire of this? Patreon seems to have some traction and just seems a good fit for artistic endeavours, the fact that you need $100 in income from YouTube before they pay out must mean there are a lot of people with a lot of viewers whose income they hold in perpetuity. Same with Spotify, is there a point at which creators withhold their content, or is the lure of large viewer numbers irresistible ?

<comment><USER10> For some things, like churned out entertainment for children, tweens and teens, YouTube probably has a lock. Those groups don't care about any of this. For The rest, fragmentation seems inevitable to me.

</comment></comment><comment><USER11> I'm kind of surprised that Patreon hasn't made a spinoff platform to compete with YouTube for all the YouTubers flocking to their donation service.

<comment><USER12> I wouldn't be surprised if they're playing with one; they're regularly sending out "how to grow your audience" suggestions to creators that want everyone to make video content, regardless of how appropriate it is to their craft and/or personality.

That said: making a YouTube is a hell of a lot of work and a huge investment. Yes I'm sure you can kludge up a simple clone of the basics in Your Favorite Language in six hours, but can you build the infrastructure to deal with the inevitable copyright infringement, avoid falling foul to widely varying obscenity laws across the globe, hire people to screen for that sort of thing, there's a whole bunch of stuff above and beyond "managing some AWS virtual storage for video files".

<comment><USER13> >That said: making a YouTube is a hell of a lot of work and a huge investment. Yes I'm sure you can kludge up a simple clone of the basics in Your Favorite Language in six hours, but can you build the infrastructure to deal with the inevitable copyright infringement, avoid falling foul to widely varying obscenity laws across the globe, hire people to screen for that sort of thing, there's a whole bunch of stuff above and beyond "

As I know, current Patreon's stance on what to do with it when they reach that stage, is to focus on English speaking speaking audience, and have no legal presence outside of US.

As the US is the only paying off market for 9 out of 10 of any online media businesses, it makes sense.

Same thing with CDN, if they go that way, they only have to deal with much smaller loads, and have no need for multi-dc replication.

If they only have to deal with the most creative and valuable share of makers that they will skim from yt, the will not have to deal with exabytes of cat videos and other garbage content.

Same on the legal from, for as long as most content is original, the only issue will most likely be music, but there is already a thriving industry of RIAA-free music licensing specifically for makers thanks to YT yielding to requests for automated takedowns/DeMo/and revenue divertions.

Maker relationships? Very straight, steal top 10% makers from YT, depriving it of majority of genuine creative content. Here YT can't counter that with pretty much anything: Google sells ads, Patreon sells makers themselves. Google stays with cat videos, while Patreoners take the tasty stuff.

Predicament looks rather dim for YT unless they will have the willpower to make a U-turn in their relationship with the creative community

</comment></comment></comment><comment><USER14> Deciding whether nudity (or anything, really) is "artistic" is hard, and probably doesn't scale. There may not be a good solution for this problem in the general case.

<comment><USER15> Maybe this isn't a problem we should be trying to solve with computers right now, then. We've managed to survive as a species and as a western society for years making these kinds of determinations using people, maybe we should continue to do that.

<comment><USER16> The problem is then that the only possible way to implement that is crowdsourced voting/flagging, and enough people out there don't get some kinds of art that they would flag it that way. I think _most_ controversial modern art would not survive on a platform like Youtube where everyday people make a determination on the palatability of it.

<comment><USER17> That's just plainly false. It's entirely possible to implement it using employees that are human reviewers.

If that's not profitable then they should rework their business model until it is profitable.

<comment><USER18> It is entirely possible that the numbers don't work. From a business point of view if the only downside is that some art videos get incorrectly categorized then correctly categorized after a manual review then reworking their business model doesn't make much sense.

This is bad PR for sure but I don't think the system is failing that badly. The rate at which video is uploaded is truly stagerring, and that's assuming that the successes of the automation deters many bad actors.

</comment></comment></comment></comment></comment><comment><USER19> I say it again and again: it's time to finally regulate the big social media/tech giants (Amazon, FB, Youtube, Twitter, but also big email providers like Gmail, AOL).

Account closures and content removals _must_ have a way to appeal operator decisions in a court of law. My telco provider is legally barred from shutting down my account unless I'm 3 months behind in payments - so why isn't the same valid for the tech giants? In fact, the services of Facebook and Whatsapp are something I more depend on than having a landline, but I'm straight outta luck if either service decides to ban me.

And no, "choose another provider" is not a valid option, as there is _no_ alternative because no service allows me to transfer my identity (e.g. email address) so old contacts can reach me, unlike with phone numbers.

<comment><USER20> > And no, "choose another provider" is not a valid option, as there is no > alternative because no service allows me to transfer my identity (e.g. email > address) so old contacts can reach me, unlike with phone numbers.

With a bit of foresight there certainly is, your own domain pointing at gmail?

gmail removes your account, your email still works you just have to point it at a different backend.

But therein lies the rub right? It costs money and people won't pay it, they'll take the free option every time.

Personally I find it hard to see how these companies can be regulated in the way that you want for services that they give away for free.

<comment><USER19> > With a bit of foresight there certainly is, your own domain pointing at > gmail?

That costs money for the Google Apps Enterprise suite, and you're still dealing with a company that isn't known for customer service - you may point your MX records somewhere else but still can't access old emails when they terminate you for whatever stupid reason.

(Yes, backups are a solution but many people blindly trust the cloud)

<comment><USER20> Fundamentally companies are not obligated to give you their services for free, which seems to be what you're demanding?

Now if you were to argue that companies must give you the opportunity to download your data before they close your account, that I would agree with. I'd even say a grace period of a few days so you can practically change your email might be worth considering, but I don't see how you can possibly argue that companies must give their services away for free just because they're good at what they do.

<comment><USER19> > Fundamentally companies are not obligated to give you their services for > free, which seems to be what you're demanding?

No, what I demand is that there must be a right to due process in an independent court of law for services deemed essential for modern social life. Right now, an underpaid person, who does nothing but watch the most vile content imaginable, can close my account because he has no time to properly assess art, political commentary or historically significant imagery (Napalm Girl), and I have _no way at all_ to actually talk to a human to appeal - <USER3> if I'm a _real_ customer who has paid for both Twitter and FB ads. All I have (at least for FB) is a "reply" box but no matter what you type in there you get canned responses back but definitely no human.

<comment><USER20> Then have government provide an "official" email/youtube platform or hell roll your own, which with email at least is perfectly possible.

Using these services is literally a choice, it is in many ways the _best_ choice, but it's not the only choice available.

<comment><USER19> > Then have government provide an "official" email/youtube platform

Lol I won't ever hand that level of personal data to a government institution. Having a private company as a custodian of the data at least protects me/my data from government snooping (okay, does not apply to the US with their NSLs).

> or hell roll your own, which with email at least is perfectly possible.

No it's not, good luck setting up your own mail server - even with DKIM, SPF and whatnot configured the major mail providers will classify you as potential spammer. Thanks to greedy Viagra sellers and casinos, email is all but ruined for small-ish or even single-person operations.

<comment><USER21> >Lol I won't ever hand that level of personal data to a government institution.

But you would to a private one? Why?

</comment></comment></comment></comment></comment></comment></comment></comment><comment><USER22> Without wanting to stand up for YouTube—I don't—this complaint:

> While Villa Antropoff contains a few short scenes of cartoon nudity, Youtube > makes clear exceptions in its policies for works that are presented in > "artistic contexts." The fact that a Youtube employee could have reviewed > this film and not recognized the film's artistic context illustrates a > serious breakdown in the company's ability to police content based on its > own policies.

seems a bridge slightly too far. To be sure, it would have been nice if the YouTube reviewer had recognised the artistic context to the piece, but the failure of one reviewer to do so seems to be evidence of a mistake, or at worst of misapplication of policies, not of a company run amok (although there is plenty of evidence of that elsewhere). Since there is a process for appeal, that seems like the step that should be taken before, or at least in parallel with, public complaint (although the author mentions that Lunohod has decided not to appeal).

<comment><USER23> The idea that everyone who is a reviewer will have exactly the same appraisal of what's obscene, extremist, hateful, or even pornography, is ludicrous. No one even agrees on what art is.

</comment></comment><comment><USER24> Why doesn't Youtube have a few formally trained filmmakers or film theorists on staff that they can kick these sorts of edge cases up to? Someone with a filmmaking or film theory education would instantly classify this short as art that should be available on Youtube. I could see this video being given an age restriction, but never banned.

<comment><USER25> According to google, 300 hours of video are uploaded to YouTube... _every minute_.

There's just no way to have humans moderate that. And if we assume they'd only decide on films where the ban was appealed, I'd bet it's still too much to do.

Weirdly, the creator of the film in question said they wouldn't appeal the ruling.

<comment><USER26> I disagree there's "too much to do" when it comes to having humans moderate reported or detected cases of terms violations.

We have a near crisis with people having a harder and harder time finding jobs that don't require college degrees. A lot of older job fields machines can do just as well, so a lot of old jobs are going away. The people are there.

Google is sitting on many billions of dollars it just doesn't want to spend (like $100B or so, I believe?). The money to pay for people is there.

However, Google would not be nearly as profitable if it wasn't automating away jobs that as we've continually seen, automation is pretty bad at doing. This is a business decision, plain and simple. New jobs for humans aren't opening up because tech companies are insisting on using automation to do things automation isn't good at.

<comment><USER27> At 300 hours/minute they'd need 18,000 pairs of eyes judging videos constantly (not all videos need to be judged immediately, but that's fine). Assuming a normal employee works 50 weeks of 40 hours a year, that means that each employee is only working about 23% of the time. In the end they'd need about 80,000 employees to judge everything that gets uploaded. Wikipedia says they had 57,100 employees in 2015. With inefficiency (HR, payroll, managers, manager-managers, devs to write video audit software, etc), they'd need to triple their workforce solely to keep up with youtube.

<comment><USER26> As both I and the parent suggested, you'd only need humans reviewing content that is reported or automatically flagged. And you'd have a second level set of people for appeals handling.

<comment><USER28> Right but if, like is happening in this case, the owner of the video intentionally does not appeal... then what?

</comment></comment></comment></comment></comment></comment><comment><USER29> If you run a fitness-channel on YouTube (I do) and your thumbnail contains a topless body, the video will not be monetized. No more sixpack tutorials I guess...

<comment><USER30> Why not just create a static title card for your thumbnail?

<comment><USER31> Because that doesn't attract viewers like nudity does. How many times have you seen a half naked chick as the thumbnail, yet never appears in the video?

<comment><USER32> Remember when YT immediately counted every view regardless of how long someone watched, and there was this plague of clickbait? For example headless women showing their cleavage in the thumbnail, because there were enough horny idiots dumb enough to click the thumbnail.

That's why they switched to 30 seconds initially, and now to something more percentage based i think

(Funny enough it is practically impossible to Google the articles that described these changes when they first happened; I read them bs k then and I've been looking for them for ten minutes to no avail)</comment></comment></comment></comment>


Please evaluate our site - <AUTHOR>

Boston Launch: www.genotrope.com could you please check out the site and critique and comment? As a cold start peer produced database, the data is only robust for the Boston Market currently. If you are from Austin..etc.. the experience will be less than fulfilling for now, so to get the idea, use a Boston company like Lotus or ITA software in your profile. Then you will be able to see what companies are matched to you. Feel free to add your companies and founder/investor connections. thanks <comment><USER2> First thing I noticed was the graph of companies. I figured the site was a database of corporate relationships (company A funded company B, which acquired company C, etc..). Then I saw the 'job hacks' tab, and the 'Opportunities at Emerging and Start-up Technology Companies' tab on the top. Ah, this is a job site.

The message needs to be clearer: This is a job site (which happens to have a nice company analyzer) or this is a Company database (which happens to have job listings). There is probably too much info on the front page.

I would probably lean toward the Company database that has jobs version over the other.

<comment><USER3> I agree with this one. Btw, I liked the site.

</comment></comment><comment><USER4> The entire site is a confusing mess. That chart is fuzzy and scares me. I don't even want to look at it. Text is horribly contrasted throughout the site. Constantly opening links in a new window when I don't want that. Clicking on the "Limited Access" link to let me do a search loads a page that nearly crashes my browser. Java is slow to load and other portions had to wait.

Don't see why you had to use JAVA to show a graph that has no real value. Cool, we can move the arrows around the central point! But it has no value .. just make it a nice static, clear image

</comment><comment><USER5> Obviously not the most important point to address, but one of the first things I noticed was that there's a grammatical mistake (it's for its) in your introduction. It's a minor error, but it also undermines the professional image you're trying to project

</comment><comment><USER6> From a developer's point of view: HTML 4.0 and table layout stinks! Use CSS. Write in UTF8 and add a DTD. Use mod_rewrite to rewrite your URL (port number in a URL doesn't look profesional).

From a visitor's point of view: The colors suck. And why do I have to log into the app to read the FAQ? The "welcome page" doesn't have navigation, other pages have it. BTW your home page is different from the welcome page, fix that too.

<comment><USER7> No user cares about HTML 4.0 and table layouts. I hate this complaint. Also, don't use mod_rewrite because it adds unnecessary overhead to your webserver.

<comment><USER8> You're right about HTML4/tables... but the suggestion to use something (mod_rewrite or whatever) to get off a non-standard port (8081) is a good one. Non-standard ports look sketchy to many people -- and sometimes company networks even block access to them.

<comment><USER7> Yes but you can do that without mod_rewrite.

</comment></comment></comment></comment><comment><USER9> I guess I don't see the point. People are complaining about fuzzy images or whatever. I thought the interface was okay, but the question of where and how value is being added is not at all clear.

Also, go through your codebase, and anytime you see something like this:

"Please login to access 'Find Companies / Jobs"

...do a total re-write. I'm not logging it to an unfamiliar website, and neither are 95 percent of people.

<comment><AUTHOR> point well taken, since users can enter and edit the database of companies, how would you approach trying to keep some semblance of security for the database without knowing who is modifying it?

<comment><USER10> Anyone can see it, log in to write to it.

<comment><AUTHOR> thats how it works. Then to see matched companies, an email is all that is required for registration to be able to create a profile (past and current employers) and then have Genotrope create a graph of related companies which show up on the find page.

<comment><USER11> Try to get past needing to create a profile. Let the user enter as much data as necessary and save it in the session. If they like what they see they can decide to create a profile.

</comment></comment></comment></comment></comment><comment><USER12> The frontpage doesn't explain what the benefit is for the user, or what he should do to try it out. There's also at least 2x too much on the frontpage, though better graphic design would make it look less distracting.

</comment><comment><USER13> What is the etiquette regarding asking the YCombinator community to review a site? I just recently joined and I absolutely love the interaction with other community members with submissions like this....

...also I have something I'm working on (surprise surprise) and I would like to submit something of this nature for all to see, once things are up. I wanted to know if asking the community to review my site is something that would get me the feedback I'm looking for (I REALLY want to know why my project sucks or won't work) or if it's something that is not encouraged.

<comment><AUTHOR> no etiquette, just post it and they will come. I dont think you will have to worry about what people REALLY think.

<comment><USER13> The fact that the rounded rectangle boxes are not evenly spaced shows lack of attention to detail. (yes I'm being a jerk here, but I've found that negative feedback from others has helped me make my project better)

The graphics are grainy. They should be stark and clean. There is too much use of two colors. It feels too monochromatic.

You need a better descriptions to communicate what benefit you have for people to join. Why should I join? There needs to be a more obvious "in your face" explanation highlighting something. The message should be along the lines of "If I join, then _______ is a possibility for me" - what I mean here is that this is the feeling that needs to be evoked within your visitors perception when they read one of the rounded boxes.

The graph could be a 3D graph, it will look unique and at the same time convey a hidden message to explore the site. It's a subtle message that if somebody sees an object of depth then they have an inclination to explore the site

On the about page, you need to have a margin on the sides. Feel free to make the font size bigger.

I click on the "about" section and have no clear way to get back to the main page - BIG MISTAKE! I see that there is an orange "return" button, but this is not intuitive. Clicking on the logo to take us back to the main page would be more intuitive for users and it will let people believe that this is easily navigable.

</comment></comment></comment><comment><USER14> The images are fuzzy, and the large image is distracting.

</comment><comment><USER15> Wow. An actual Java applet. It's like 1998 all over again. Too much for a simple graph. You should consider replace it with flash... or even pure Dom/Javascript, like these guys: <http://www.genoom.com>

<comment><AUTHOR> thanks yeah, there is a flash version about ready to drop. it is overkill for the simple graph, but when we map all web 2 startups in boson. or compare two VC to see if they have invested together in the past, being able to zoom and pan will be more useful.

<comment><USER16> Did you roll-your-own graph display UI library or use someone elses?

<comment><AUTHOR> see prefuse credit at bottom of graph window

</comment></comment></comment></comment><comment><USER15> "Add your company and the connections to investors and past companies of the founders and executives."

???? So this is for company owners? Why they should reveal their connections?

"Adding companies and links add credit points."

Credits points?

<comment><AUTHOR> it is public knowledge what companies the founders and executives came from. Are you thinking connections like people they know ie friends . look at the graph for y combinator or ITA software and you will see what the connections refer to. Yes companies are the clients.

would you prefer karma rather than credits?

</comment></comment><comment><USER17> A startup built on the idea of tracking startups...what will they think of next.

Looked good though.

</comment><comment><USER18> Add some graceful javascript degradation. I use NoScript and your site is essentially useless.

[http://www.stevetucker.co.uk/javascript-complete- degradation...](http://www.stevetucker.co.uk/javascript-complete- degradation.htm)

</comment><comment><USER19> The 404 not found page is tomcat's default page. A custom page would be better. The favicon is again tomcat's default. As someone mentioned earlier, the image quality needs improvement.

</comment><comment><USER20> Very confusing graphics and layout. Also, strange name. If you have to explain what your name means, you've got a problem.

<comment><USER17> Google and Yahoo are not strange?

<comment><AUTHOR> loopt, xobni, scribd, wufoo, weebly, zenter I dont know, names are hard. Is it memorable? hangoutandlearnaboutyourlocalstartupmarket.com was taken :)

<comment><USER20> exactly why I don't remember some of them. At least scribd is sort of mnemonic.

</comment></comment></comment></comment><comment><USER21> Is this supposed to be like LinkedIn for startups?

Or is it just a research site, like a Hoover's for startups?

<comment><AUTHOR> you could say that, founders move from company to company and create similar work environments and hire similar quality people

<comment><USER21> If it's supposed to be a startup jobs site, you should make that more clear, right at the beginning (maybe split the page into "For Startup Job Seekers" and "For Startup Founders Who Are Hiring", for example).

</comment></comment></comment><comment><USER22> \- Need a clear sentence on what you do or what the site is about.

\- Images have been stretched

</comment><comment><USER23> My advice: hire a graphic designer. the ui is way too cluttered and just plain unpleasant.

</comment><comment><USER24> The image quality is awful and gives the site a cheap feel. I'd use PNG.

</comment><comment><AUTHOR> uncle, uncle,,thanks, may I have another. I was expecting brutal good feedback so keep it coming. Ok, we are down now. will get it back up and try again. thanks for the pressure

</comment><comment><USER25> can't get to the site

</comment><comment><USER26> strangest name I've encountered in a while and thats saying something on today's internet.

</comment><comment><USER27> Too slow to load. I gave up. But from the looks of the other comments here, it's just as well.

Looks like you're getting good (and ruthless) feedback. I'd expect nothing less from this group.

Good luck to you. Let us know when 1.1 is ready.

</comment><comment><AUTHOR> back up, well see how long it lasts

<comment><USER28> Seems to be down again...

<comment><AUTHOR> just checked , is working now, sorry for the problems. finding problems along with getting the feedback

</comment></comment></comment><comment><USER29> YC dotted?

<comment><AUTHOR> i dont know what that means? y (space) combinator in the database

<comment><USER30> sammyo is asking if the site has been brought down due to heavy traffic. Although if YC is nailing your site, you have serious problems.

See "slashdotted" here: <http://en.wikipedia.org/wiki/Slashdotted>

I thought everyone knew that term by now...

<comment><AUTHOR> yea I know the term, didn't connect the dots , brain is YC dotted as well</comment></comment></comment></comment>


How many employees does Google have? - <AUTHOR> http://blogoscoped.com/employees/ <comment><USER2> 16805 Page loads extremely slowly due to (presumably) 16,805 images...

</comment><comment><USER3> That crashed Firefox...</comment>


Is the Alzheimer's "Amyloid Hypothesis" Wrong? (2017) - <AUTHOR> https://www.theatlantic.com/health/archive/2017/02/alzheimers-amyloid-hypothesis/517185/ <comment><USER3> Frightening thought: if (at least some cases of) Alzheimer's really is something akin to "Type III Diabetes", the planet and especially the USA can expect absolutely skyrocketing numbers as today's obese adults age.

[1] [https://newsnetwork.mayoclinic.org/discussion/mayo-clinic- mi...](https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-minute-is- alzheimers-type-3-diabetes/)

[2] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/)

<comment><USER4> If T2D can be reversed with fasting (to purge the pancreas of fat), does that mean we could test things like Acetyle-L-Carnitine in larger dosages in the brain to affect T3D? Or perhaps a variant of 2-hydroxypropyl-beta- cyclodextrin? Has anyone tried experimenting in this area?

Or is this a viral condition as others in the thread have mentioned? Perhaps these are not mutually exclusive?

<comment><USER5> The amyloid, T3D, and viral hypotheses still don't explain why cholesterol, obesity, air pollution, lack of sleep, and sedentary liftestyle positively correlate with Alzheimer's and high caffeine intake and regular exercise negatively correlate with it.

<comment><USER6> They do, if you consider the recent findings that many viruses have evolved to exploit our colesterol synthesis and transport machinery to spread, it becomes clear that many diseases of aging may have a viral cause : [https://medium.com/@InfinoMe/senescence-links-between- heart-...](https://medium.com/@InfinoMe/senescence-links-between-heart- disease-genomics-and-aging-fa78bde773da)

Rhinovirus, the cause of the common cold, binds to vLDL receptors. vLDL incidentally being the primary risk factor for cardiovascular disease [https://www.ncbi.nlm.nih.gov/pubmed/12857919](https://www.ncbi.nlm.nih.gov/pubmed/12857919)

Influenza requires the cholesterol transport system to bud and spread [http://news.mit.edu/2017/cholesterol-helps-flu-virus- escape-...](http://news.mit.edu/2017/cholesterol-helps-flu-virus-escape- through-host-cell-membrane-1120)

Hepatitis C virus relies on APO-E, our favorite alzheimers gene, to flourish, and APO-E genotype predicts if you will get liver cancer from Hep-B [https://goo.gl/images/Hev5ev](https://goo.gl/images/Hev5ev)

T2D, CVD, and obesity, being characterized by hypercholesterolemia and mitochondrial dysfunction, are illnesses that are supportive of viral infections. They also promote AGE formation, which activates the innate immune system through a variety of RAGE receptors, Galectin-3 being potentially a central axis as it is also part of the senescent phenotype.

<comment><USER7> You tied together a lot of threads that I've been loosely aware of here. Nice post. I hope we a have the chance to elucidate what of these links is relevant and actionable.

<comment><USER6> I'm very confident in the future. What a time it is to be alive.

</comment></comment></comment></comment></comment></comment><comment><USER8> Derek Lowe, of Things I Won't Work With fame, has an interesting post on the subject too: [http://blogs.sciencemag.org/pipeline/archives/2018/06/22/alz...](http://blogs.sciencemag.org/pipeline/archives/2018/06/22/alzheimers- and-infectious-disease-for-real)

</comment><comment><USER9> Somebody on HN recommended "Why do we sleep" by Matthew Walker a few weeks ago. There are references in this book strongly linking lack of sleep to Alzheimer's (diabetes too btw). Maybe somebody else can dig them up I don't have the book at hand, but I echo that previous commenter sentiment: if you are only going to read one book this year - make it this one.

<comment><USER10> Excellent book! I'm only halfway through and it's already influenced the way I treat sleep. Among the most important takeaways is that diet, exercise, and sleep are commingled (as is their effect on disease and disease progression. Diet and exercise affect sleep quality; sleep quality affects dietary cravings and the ability to exercise; and so on. When one of these three pillars (diet, exercise, sleep) is strengthened/compromised, the others may be strengthened/compromised. By simply choosing to do things during the day that will improve your sleep quality at night, you're checking many of the boxes of a healthy lifestyle.

<comment><USER11> Would you also think that this book is interesting for people with a normal sleep pattern?

<comment><USER12> There's a lot of stuff in there, and it is very compelling, but there is really only one take-away from it:

Get lots of sleep.

The book is mostly helpful for people who try to "optimize" things or rationalize why they don't need to follow the rules. He debunks all of the excuses.

If you already get enough sleep, then you don't need the book.

</comment></comment></comment></comment><comment><USER13> This comment from two months ago (when Carl Kasell died) was very interesting:

 _it is not for want of trying. Eli Lily bet the farm and lost, and they aren't alone._ _At this point, we're beginning to think previously unthinkable thoughts like "what if the hypothesis the last 20 years of research was based on (beta amyloid plaques)is just totally wrong"._

 _we've made drugs that reduce plaques. they don't ameliorate the disease._

[https://news.ycombinator.com/item?id=16863945](https://news.ycombinator.com/item?id=16863945)

<comment><USER14> >"we're beginning to think previously unthinkable thoughts"

What made it so previously unthinkable? AFAIK, there was a rough correlation between presence of these plaques and certain symptoms (by "rough" I mean some people with the AD symptoms have no detectable amyloid beta plaques, others without AD symptoms have a lot). Then a bunch of studies where they figured out how to get amyloid beta to kill cells in a dish or make animals sick (or at least p-hacked such).

Was there ever a definitive prediction derived from this hypothesis that was then tested on new data? What is it that makes people have such strong belief?

<comment><USER15> Well, the hypothesis was tested on data... that data being drugs to reduce amyloid plaques, which have only recently been found to not work to ameliorate Alzheimer's.

The amyloid hypothesis looks to be an open-and-shut case of "correlation does not imply causation." The problem is, we don't know what actually causes Alzheimer's, and for the longest time, the amyloid plaque correlation was the only thing that looked like it could be a cause. On top of that, actually testing these hypotheses takes a long time, especially if you take the not- unreasonable attitude that tackling them after on its onset (i.e., before it's readily detectable) may be too late.

<comment><USER16> This is far from the whole story. The pathology of alzheimers as predicted by the Amyloid Hypothesis is (year 0) imbalance in the production, (year 10-30) deposition of abeta causes Tau and other downstream complications that are symptomatic. Existing clinical studies started way too late, after the appearance of significant sympthoms - at least mild cognitive impairment.

Personally, i take curcumin supplements, as it is known to bind to abeta even in the cerebrospinal fluid, then it gets cleared out over the blood brain barrier. If the abeta hypothesis is true, high dose curcumin should help delay its onset.

Another thing to do is get your genome sequenced, even with 23andme. If you have apoe4, you should, IMO, take curcumin.

<comment><USER14> Fyi, I have no idea if your regimen (or any) of curcumin is good for you or not but amyloid beta may be protective in some way:

>"Mice with excess beta-amyloid survived longer than the controls and had less bacteria in their brains. Mice lacking beta-amyloid (from the genetic removal of APP) died more often from infection."

[https://www.nih.gov/news-events/nih-research- matters/alzheim...](https://www.nih.gov/news-events/nih-research- matters/alzheimers-protein-may-have-natural-antibiotic-role)

<comment><USER16> Curcumin won't clear out all abeta. Just bind to some and clear it. It also dampens anti-inflammatory pathways (e.g., mild inhibitor of TNF-alpha production). I see the cost-benefit being overall positive for medium-dose curcumin (like 500mg-1g/day).

<comment><USER17> There is quite a lot of somewhat fuzzy evidence for curcumin helping eg. this [https://www.telegraph.co.uk/science/2016/05/20/eating- curry-...](https://www.telegraph.co.uk/science/2016/05/20/eating-curry-may- help-fight-off-dementia-new-study-suggests/)

> 96 participants aged between 40 and 90 over 12 months.

>In tests of verbal and memory skills, those taking the dummy pill suffered a decline in mental function after just six months that was not observed in those who took curcumin

At least it has no negative side effect and tastes good in its chicken korma form.

</comment></comment></comment></comment></comment></comment></comment><comment><USER18> The continued failure of efforts to remove amyloid by immunotherapy is provoking a lot of diversity in theory in the Alzheimer's community. This is economics 101: theorizing is cheap, running trials is expensive. Expect to see more of the cheap thing than the expensive thing.

The challenge in Alzheimer's disease is most likely that it has several mechanisms that are all of similar importance to degeneration. Get rid of one of them and benefits are obscured by the others.

The most likely list is amyloid aggregation, tau aggregation, neuroinflammation (covering microglial dysfunction, persistent infection), energy metabolism issues (covering mitochondrial aging, loss of capillary density, etc), and vascular dementia.

So therapies are needed that can address many of these issues at once. An example is the approach of restoring drainage of cerebrospinal fluid, e.g. at Leucadia Therapeutics. That should reduce all metabolic waste in the brain by restoring a normal sink for amyloid, tau, and anything else that might be an issue along the way.

The amyloid hypothesis seems unlikely to be wrong; there is extensive evidence for amyloid aggregation to cause tau aggegation to cause neurodegeneration. It just isn't the only problem: certainly vascular dementia (present to a clinical level in 30%+ of Alzheimer's patients) is severe enough to question whether it is a major problem in those trials that reduced amyloid and failed to greatly improve dementia. The other big plausible issue is that amyloid is the early stage of Alzheimer's, while tau is the later stage - so messing with amyloid levels is not the way to go for late stage, severely impacted patients. Still has to be done, but it if picking only one, then tau clearance is a better bet.

<comment><USER16> Good summary, but i don't agree with your analysis. The end-game will be early diagnosis of abeta over-production, IMO. You will then treat that and you won't get alzheimers. Few will transition to Tau degeneration, and it's so much harder to fix. I don't think pharma will go big on Tau like they have with abeta. The blood tests for over-production of abeta are almost here - <USER2> expect them to be routine every few years for people over 50.

</comment></comment><comment><USER15> I like Derek's take on it: [http://blogs.sciencemag.org/pipeline/archives/2018/06/12/an-...](http://blogs.sciencemag.org/pipeline/archives/2018/06/12/an- alzheimers-statement)

> If there is any way left to send our ourselves full-tilt into another failed > amyloid trial, our pledge to you is that Lilly will find it. ... we have our > beloved wall, which we shall never forsake. Higher velocity! More power! > Once more into the concrete, my friends! Who's with me?

</comment><comment><USER19> Sadly, no mention of microglia as a possible cause. I can't explain it myself, but someone who was close to me was researching this extensively and was often frustrated by the over-focus on amyloid.

<comment><USER20> I agree. Microglia should be where a lot of the focus should be moving. From my limited recent research on microglia and AD, it seems that plaque build up is actually a symptom that is perhaps caused by dysfunctional microglia, which normally phagocytoze plaques when functioning properly. Microglia secrete all kinds of neurotoxins and cytokines that mediate the inflammatory response. It is highly plausible that progressive damage to microglial function induces a pathological state where the microglia become destructive to the neuronal enivronment.

</comment></comment><comment><USER21> Not everybody has focused on amyloids other approaches are being explored as well. Here's one example that's focused on a bacteria:

[https://www.bizjournals.com/sanfrancisco/news/2018/05/31/alz...](https://www.bizjournals.com/sanfrancisco/news/2018/05/31/alzheimers- disease-cortexyme-verily-infection-ad.html)

</comment><comment><USER22> What if Alzheimers / dementia is cause by air pollution?

[http://www.sciencemag.org/news/2017/01/brain-pollution- evide...](http://www.sciencemag.org/news/2017/01/brain-pollution-evidence- builds-dirty-air-causes-alzheimer-s-dementia)

A new study also investigates air pollution's role in diabetes

[https://medicine.wustl.edu/news/air-pollution-contributes- si...](https://medicine.wustl.edu/news/air-pollution-contributes- significantly-to-diabetes-globally/)

<comment><USER23> Also found this which looks at urban vs rural rates: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056321/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056321/)

</comment></comment><comment><USER24> considering that another two trials washed out since this article was written, "yes" seems an ever-more plausible and tragic answer.

<comment><USER25> What does "washed out" mean? What were their conclusions?

<comment><USER24> Washing out means that a clinical trial is halted for lack of efficacy. It means the drug candidate in question is safe to ingest, but also doesn't work to treat the condition it was designed to treat. "work" is defined as having met or exceeded predefined clinical endpoints; e.g., "cognitive assessment improves by x% on average in a cohort of Y thousand patients", or "blood cholesterol levels reduced by Z%" or whatever.

It's important and sad to note, too, that the clinical targets of most modern alzheimers drug candidates are comparatively low bars. We're not shooting for a cure, we're shooting for things like "reliably slows down cognitive decline by 6 months", and we can't even do that.

</comment></comment></comment><comment><USER26> When will the medical community take nutrition science seriously? Why don't medical students take courses in diet and nutrition?

There is so much evidence that Alzheimer's is closely linked to lifestyle (specifically diet) and the same lifestyle changes that can stop/reverse Type II diabetes like a ketogenic diet + intermittent fasting is likely highly effective in reducing onset of Alzheimers in old age.

<comment><USER27> Medical students and nurses do take diet and nutrition courses. I'm in a prereq nutrition class right now...

<comment><USER26> And yet the first answer to type II diabetes is insulin therapy and other drugs and not "immediately stop eating sugar and refined carbs"

<comment><USER28> No it isn't. The Practice Guidelines from the American Association of Clinical Endocrinologists are summarized in this PowerPoint presentation from their website.[1] It is not intended for lay consumption, but you can clearly see that there is a large emphasis on diet changes and weight loss. However, as I mentioned in another comment, the reality in practice is that many people are either unwilling or unable to change their lifestyle sufficiently to reverse the condition.

Even before being diagnosed with a disease there are huge returns to regularly exercising and staying fit. You feel better, look better, have more energy, sleep better, the list continues. A doctor saying, "you need to lose weight and exercise, it could help with your diabetes," is a relatively small motivator compared with all of the other benefits.

1\. [https://www.aace.com/files/aace_algorithm_slides.pptx](https://www.aace.com/files/aace_algorithm_slides.pptx)

</comment></comment></comment></comment><comment><USER29> Shockingly nothing anywhere in these comments about the potential ties between herpes (HSV1 specifically) and Alzheimer's: [https://scholar.google.com/scholar?q=alzheimer's+hsv](https://scholar.google.com/scholar?q=alzheimer's+hsv)

Is this a fringe theory?

<comment><USER30> I believe you would expect a correlation between percentage of population with HSV1 and percentage with Alzheimer's in each country. No such correlation exists.

<comment><USER29> Some of the theories seem to hinge on HSV1 and ApoE4 ([https://scholar.google.com/scholar?q=hsv1+apoe4](https://scholar.google.com/scholar?q=hsv1+apoe4)) both being necessary to substantially drive up the risk. One example: [https://www.sciencedirect.com/science/article/pii/S019745800...](https://www.sciencedirect.com/science/article/pii/S0197458006000807)

I don't currently have access, but it'd be nice if someone who did could crack into the statistics of some of these.

</comment></comment></comment><comment><USER31> A related article that I enjoyed: [https://news.harvard.edu/gazette/story/2017/05/devastating-c...](https://news.harvard.edu/gazette/story/2017/05/devastating- chain-of-events-found-in-alzheimers-path/)

</comment><comment><USER32> Is the Amyloid Hypothesis related at all to Prions?

Is there any research or drug research going into Prions and Alzheimer's?

<comment><USER33> seeing as the worst forms are purely hereditary, that would seem unlikely. but what do I know.

</comment></comment><comment><USER34> I only skim reading researches in Alzheimer's, a thing that I suspect is that plagues are a late stage sign for the disease. And to ameliorate it is a bit like thinking that to cure age spots can reverse aging. They are the result of the disease, not the initial factor.

</comment><comment><USER35> There's always the Tau hypothesis (ie it could be a tauopathy.) That would not require exotic explanations like a virus or Diabetes.

</comment><comment><USER36> Well, the fight is not over yet.

Biogen has Aducanumab in phIII trials. Pretty big bet for them.

<comment><USER36> well, and their results they just published are indeed encouraging. Nice bump on their stock.

</comment></comment><comment><USER37> What happened to aducanumab? Wasn't that promising?</comment>