The Augmented Human Being – A Conversation with George Church - <AUTHOR> https://www.edge.org/conversation/george_church-the-augmented-human-being <comment><USER2> Nice to see George Church advocating a SENS view of aging research more prominently these days - that the scientific community should be trying to reverse the progression of aging, not just trying to slow down that progression, for all the obvious reasons such as the one quoted below. More of the eminent researchers who support SENS (Church is on the SENS Research Foundation advisory board) need to do this.

"[Reversal of aging] is a much better target, in any case, than prolonging longevity because, A, it takes years to decades to even prove that you have extended longevity. Also, if you've done it on somebody that's quite old, the economic consequences are dire; that's the part of your life where you spend huge amounts on medicine and don't improve the quality of life tremendously. If you can reverse it to an age where you essentially don't use any medicine, this will be much more cost effective."</comment>


Show HN: Flutter - Control Spotify or iTunes Using Gestures thru Webcam - <AUTHOR> http://flutter.io

<comment><USER2> Amazing, works very well.

I assume it is looking for 5 fingers. I noticed if i folded my thumb in, it did not recognize the gesture so maybe an edge case where people missing fingers can't use this.

Also when I scratched my face briefly it did recognize it... funny.

I would strongly recommend trying to build a web demo somewhere down the line. Even if it requires flash to get the webcam working, I'm sure your conversions would go through the roof if you could show how well it worked instantly on your landing page.

Small note -- the blurring of the image is distracting rather than focusing. Down the line maybe think about a better landing page image.

<comment><USER3> Just tried this: 4 fingers with my thumb tucked across my palm worked fine for me.

</comment></comment><comment><AUTHOR> We hated using the keyboard and mouse for controlling music in the background or watching movies on our computers from a few feet away. So we decided to solve this problem by using hand gestures to control music and videos via the built-in webcam in your computer.

Please download and try it. Do let us know what you think in your comments below or by emailing us at feedback [at] flutter.io.

Currently, it works for Mac OSX 10.6 and up.

<comment><USER4> is the download broken?

<comment><AUTHOR> hi wmw, it should work as long as you have Mac. If you are on other OS then it will ask you to leave your email address for future invite.

Are you on Mac? Can you tell us what happened?

<comment><USER4> after typing in my email and name i got this: The link that you have given is not valid. Please verify that you have copied the link completely. This incident will be reported.

</comment></comment></comment></comment><comment><USER5> I hardly ever get excited after downloading something, maybe a, wow that's cool, but when I installed this (which was very easy) and it just worked, I actually clapped and said 'this is fucking awesome.'

<comment><USER6> I had the exact same feeling. You see these gesture controls in movies and demos and they seem great, but it's _truly_ exciting when you get to use it yourself.

Love it!

<comment><USER7> Ajju thanks for the encouragement. We are glad you liked it. If you have more usage ideas or feature requests, do let us know.

<comment><USER8> Thought that this was great - how about a next/previous track gesture, and being able to change the frequency that it checks for the hand? (it looks like it's time based)

</comment></comment></comment></comment><comment><USER9> I believe one of the co-founders is Navneet Dalal, who, along with Bill Triggs, developed the "Histograms of Oriented Gradients" (HOG) features that are widely used across all of computer vision†. Thus, I'm guessing that there's some serious vision in use for this app, which is pretty awesome!

(My apologies to the other co-founders, who are likely just as talented!)

† <http://en.wikipedia.org/wiki/Histogram_of_oriented_gradients>

<comment><AUTHOR> Yes, he is the brains behind this!

</comment></comment><comment><USER10> This is awesome.

However, music control isn't a pain point for me. What I _would_ pay for is a start/pause gesture for Netflix/Hulu/Amazon Video. Worst thing about TV on a computer.

<comment><AUTHOR> Luke - that's a great point. We're working on it and it will be in the next version!

<comment><USER11> Once you guys have that down, take my money and I'll bolt an iMac to my wall.

</comment></comment></comment><comment><USER12> I just ask my very non-technical girlfriend to come see this new app I downloaded. I showed her flutter.io working in action. She shrieked and said, "that's awesome, how do I get it?". That's a very good sign for you guys...nice job.

<comment><AUTHOR> Haha - that's great. Thanks!!

</comment></comment><comment><USER13> Though I know there's a chance you'd not be willing to share the information, I'd love to learn a little bit about how you built this product.

It appears as though you're using ML to recognize the gestures—anything else you could share would be fascinating. I'll be sending in a job application, as well!

<comment><AUTHOR> You're right. We use image processing, computer vision & machine learning to detect Flutters. Our entire tech stack is custom written as we are solving some quite challenging & difficult AI problems.

</comment></comment><comment><USER14> Interesting/cool project, though I do wonder how you plan on keeping it simple when you expand and add additional actions?

The UX of controlling media using the Xbox Kinect leaves a lot to be desired - it's cumbersome.

I've had my mac mini connected to my tv for awhile and am very interested in the Internet TV space in re: what will become the standard way we control such technology? Will it be thru gestures, airplay on iphone/ipad type technology, voice driven or a mix of all?

For many years I've been using a wireless gyration mouse/keyboard (demo of Internet TV setup <http://www.youtube.com/watch?v=l-IryK4wsUM>) and recently I started to use Chrome's voice search to quickly bring things up especially if my wireless keyboard isn't reachable.

After seeing this and my years of enjoying the Internet on my TV I'm thinking a few short gestures like this app uses and mix of voice driven actions might provide the best UX.

Based on the views and comments of video I link to above people want the Internet on their TV and all it provides. We just haven't figured out the best UX for it.

<comment><AUTHOR> Paul - that is a great observation and feedback. We believe that future will be about us using touch, voice, and gesture all three depending on context and circumstances. We do plan to keep it simple, and we have some great ideas for it.

</comment></comment><comment><USER15> This is amazingly useful... just not on the pc.

Implement it for Android and you can charge me 30€ so i can easily control the mp3 player in my car.

<comment><USER5> I think you'd have to take a slightly different approach for use in the car..unless you had a mount for your phone on the windshield.

</comment></comment><comment><USER16> "The music swirled and dived for a moment. Another voice broke in, presumably Halfrunt. He said "Vell, Zapbod's just zis guy, you know?" but got no further because an electric pencil flew across the cabin and through the radio's on/off-sensitive airspace. Zaphod turned and glared at Trillian -- she had thrown the pencil. "

HHGTTG - Douglas Adams

</comment><comment><USER17> Flutter in action: [http://www.youtube.com/watch?v=IxsGgW6sQHI&feature=youtu...](http://www.youtube.com/watch?v=IxsGgW6sQHI&feature=youtu.be&a)

<comment><USER18> Expected reaction, having just a blurred-out image on your landing page: "Sure, whatever, it probably doesn't work that well...".

Expected reaction, having a video demonstration of the product on your landing page: "THIS IS FRICKIN' AWESOME!".

Please, please, but a video on your landing page. You will thank yourself after checking your conversion rate.

<comment><AUTHOR> Hi, thanks so much for letting us know. We will put the video. The one on YouTube is old, but we will do it very soon. thanks!!

</comment></comment></comment><comment><USER19> This is very cool. It worked perfectly even in the dimly lit room I am sitting in.

What I've been wanting and have thought about developing myself is a universal play/pause control that pauses whatever you happen to be listening to at the moment, whether it be a desktop client like iTunes, Spotify, Rdio, etc, or if it is something running in a web browser like Pandora, Soundcloud, Youtube, etc.

This app takes a step towards this in the way it handles iTunes and Spotify at the same time, by controlling whichever app had focus last.

I imagine for web browser control a browser extension would necessary. And ideally a plugin architecture would exist to allow 3rd parties to add support for additional apps.

<comment><USER20> A different but functionally similar idea would be an automatic pausing of all other services when you start playing one (i.e. when I start playing a Youtube video, automatically pause iTunes).

<comment><USER21> There needs to be a way to override those behaviours though, as there are situations where the audio of a YouTube video (for example) isn't very interesting, and you'd rather listen to music. Lack of background-playing in the iOS YouTube-app is still an annoyance to me.

</comment></comment></comment><comment><USER22> Really cool. I was just playing with it and my girlfriend walked over to ask me a question. I held up my hand to my computer as if to say "Hold on, computer."

It was a bit surreal. Very cool. Can't wait for more gestures or a generalized way to program my own gestures. I would love to be able to gesture "Switch to iTerm.app" by doing an OK sign or something. Sign language letters maybe?

Anyway, thanks. Really enjoy it already, can't wait for more. Also, I would pay money for this. If it had all of the play/pause/forward/back functionality I think I'd give you 4.99 if it was accurate. Just sayin'.

<comment><USER23> My thoughts almost exactly on the programmable front... like Better Touch Tool but rather No touch Tool, although the latter name does retain the locker-room hilarity of the former.

Perhaps a gesture to bring up the app switching ribbon and a gesture to reference the item (numbered from left to right maybe.)

I'd also like to have the option to calibrate it, my eyes are painfully photosensitive and I tend to work in very dimly-lit conditions.

</comment></comment><comment><USER24> What's nice about this is you don't need to switch screens to pause the music if you find yourself writing/coding and need some quiet when you're in the zone. Granted you can do this with the mac play/pause physical buttons but that would require your eyes to look down and pause your thought process.

This happened to me just now after I installed Flutter, and it seemed to me that physical gestures didn't interrupt my higher brain functions. Of course when I noticed this it made me interrupt my work and come to HN to leave this comment. The irony.

<comment><AUTHOR> Glad you noticed it. We want you to never think about controlling your music at all. This is one of the things I love too... we listen to music in a background, so controlling it should be in the background too.

</comment></comment><comment><USER25> Flutter seems to keep the camera on 100% of the time which prevents apps like Skype from using the camera for video chats. I'm not sure if there is a good workaround for that?

<comment><AUTHOR> Andrew - great observation. On top of your menubar, there's Flutter icon. Click on it, and it will give you simple flutter on and flutter off capability.

<comment><USER11> Feature Request: Designate a gesture to turn Flutter off.

<comment><AUTHOR> Great idea. Although, you probably will have to turn it on manually.

</comment></comment></comment></comment><comment><USER26> This is fantastic! I can't wait until it's extended with more gestures for next track, etc, but this initial version is so awesome! Nice work.

</comment><comment><USER27> There is another, more fully-featured app called FluidTunes which I used quite a while ago. Not sure if it still works on the latest version of iTunes: <http://majicjungle.com/fluidtunes.html>

</comment><comment><USER28> This is awesome, but one question/suggestion: when a user is going through the "How to Use Flutter" tutorial, do the gestures work then, or only once the tutorial is closed? I kept trying to do it, but there wasn't a response until I closed the tutorial.

<comment><AUTHOR> Only when tutorial is done and you're using iTunes or Spotify. First time you bring up either of the apps, it will notify you through top menu bar that Flutter is controlling it now.

Once that happens, you can control in the background or even if it is minimized.

</comment></comment><comment><USER29> One of the few occasions that I wish I had a mac.

Few questions: Aren't you entering a field which has patents covering gesture controls on media exactly like this?

A comparative advantage of mice and keyboards is that a minor amount of energy, (but large amounts of co-ordination) are leveraged into larger changes. Wont this limit the number of the gesture controls you can incorporate?

(OTOH - if you had enough fidelity, you would just need a dummy keyboard. You would just have to map finger movements with key presses. you could just create a webcam of your own as well.)

</comment><comment><USER30> Very cool although with CPU usage at about 30% on my Air I won't be able to use it much. If you can figure out a way to drop average CPU usage down to reduce heat & power usage that would be a big deal.

<comment><AUTHOR> Hi Hedgehog - thats a great point. We thought of it, and when you're not doing a gesture, CPU usage should drop to around 2-3%. Let us know if it doesn't. In our test, average CPU usage was around 5%.

<comment><USER30> Interesting. It does seem to drop to about 5% if I'm not in front using the computer and not in front of it but otherwise floats between about 7% and 20%. This is on a MacBookAir4,2, based on a few minutes of testing it seems like it's about 65% additional power consumption when the machine is otherwise mostly idle. I'm actually impressed though that you got power consumption as low as it is. Photo Booth consumes about 6.5% so I'd guess that's the lower limit for Flutter, maybe default to disabling Flutter while the computer is on battery?

</comment></comment></comment><comment><USER31> Soooooo. Doesn't this open up a whole new realm of privacy concerns? Who cares if Path has my contacts list, I'm more concerned that you guys are watching me surf for porn!

<comment><AUTHOR> Legit concern. This is why we've built an app w/o a server component, so everything happens on your machine. We do not capture anything from your webcam. It all happens on your machine. On top of it, there's a turn off capability which will allow you to turn it off for time being.

<comment><USER32> I presume the connection opened to AWS on boot is just for tracking purposes, yes? :)

<comment><AUTHOR> Yes, that is correct.

</comment></comment></comment></comment><comment><USER33> Hi guys. Since there seems to be an ML component, I was wondering how this was built. Do you start with a basic hypothesis and see if it holds for some training set and then refine it or right off the bat go with a generic classifier like SVM (with some features in mind) or something like that and then tweak it? Also, how did you choose the dataset for this ?

This project is very cool. Congratulations and good luck!

</comment><comment><USER34> Would be nice if we could get this to work with other media players by emulating the media keys (really want to use this with vlc on my macbook)

<comment><AUTHOR> We would include VLC very shortly. On the list.

</comment></comment><comment><USER35> I was blown away when I saw a demo of Flutter a couple of months ago. Their Spotify and iTunes integration only scratches the surface of all the gestures that they supported in that demo. I can't wait for them to add some additional gestures, such as skipping to the next track, and PC support so that I can get rid of my keyboard with the dedicated music player controls.

</comment><comment><USER36> This must be amazing app to download as it is clear from the feedback received. Please don't forget that we are a large enough community who uses windows. Especially in India. We are already excited even before you have our version. the kind of capabilities it gives, would be amazing to download. Congrats in advance to the team.

</comment><comment><USER37> Fantastic app, does a fantastic job of recognizing my palm - unfortunately, it seems to also really like my face. After the tenth or so time that it had paused my music without me raising a hand, I realized that every time I turn my right cheek to the camera, Flutter pauses my music. Which is a little troublesome :)

<comment><AUTHOR> This is a great feedback. If you don't mind, take a picture and bluetooth and send it to us at Feedback [at] flutter.io

</comment></comment><comment><USER38> This is fantastic - absolutely the most satisfying method of interaction with an app that I've experienced in a long time. Expand the gesture set to include skip forward/back and it's a winning consumer app. Personally, I'd love (and would pay for) a library allowing me to add gesture control to my own apps.

</comment><comment><USER39> Now that's what I call a very awesome MVP!

</comment><comment><USER40> Amazing, the single gesture is _very_ well implemented.

Can't wait to swish my hands around to skip songs! :) And once you have that, you should build a futuristic minority report kind of a demo video ;)

Also, if you're looking to hire, you should definitely put a "Team" page up on your site.

</comment><comment><USER41> I did a similar hand gesture recognition software to control image viewer as part of my computer vision course project. It was really fun to do. I believe, presentations and lectures are the places where this kind of technology really makes a lot of difference. Good luck with your startup!

</comment><comment><USER23> Blown away.

How far are you guys from full Minority Report-ization of my Mac?

I mentioned in another post that I tend to work in very dimly lit spaces due to painfully photosensitive eyes. A non-mandatory calibration dialogue would probably be a handy thing for folks like me.

</comment><comment><USER42> Neat and simple, but as an end user I would use this a lot more on my TV than on my MAC/PC. Samsung built in cam below.

[http://www.youtube.com/watch?v=Szr5hGU3EK0&feature=relat...](http://www.youtube.com/watch?v=Szr5hGU3EK0&feature=related)

</comment><comment><USER43> Wow - I originally didn't download because I've used something similar before that worked only kind of well.

This works fantastically and is usable enough for daily use as a simple way to control iTunes or Spotify. Well done!

I'll look forward to more gestures.

</comment><comment><USER44> I saw Samsung demoing some similar technology during SXSW (using a kinect that was hooked up to a mac mini and being displayed on one of their LED tv's), and it didn't work anywhere near as well. Congrats.

</comment><comment><USER45> Please note that this seems to be available for Mac users only right now.

</comment><comment><USER46> Looks awesome, can't wait for a Linux version, so that I can try it out!

</comment><comment><USER47> Works great once I realized that I couldn't be so close to the camera, but does anybody have any tips on disabling the green iSight LED on my macbook pro (short of covering it)?

<comment><AUTHOR> Would you want that as a feature? Keep camera on but turn off the light? Hmm...

<comment><USER48> Sounds like being able to do that could be a huge security/privacy concern...

</comment></comment></comment><comment><AUTHOR> A user just created a video for us - Thank You So Much!! :) <http://www.youtube.com/watch?v=lhnlUMHUlNc>

</comment><comment><USER49> Quick note. Your site assumes I am using Chrome - FF doesn't save downloads in the bottom left hand corner. Easy for me to figure out, impossible for someone like my mom.

</comment><comment><USER50> Brilliant work! truly awesome . Shall i expect more in future for WEB like this ? <http://depthjs.media.mit.edu/>

</comment><comment><USER51> Hey guys this is some really cool stuff. If you can integrate this with browser gestures to scroll, refresh, and move back and forward on pages. This would be awesome.

</comment><comment><USER52> I _so_ hope this is an art project and in a few days we'll have a website of people making funny gestures to the camera to pause and play Justin Bieber songs ;)

</comment><comment><USER53> In case anyone was wondering, I can confirm "mirror stops" work: try facing your laptop towards a mirror and doing your gestures from behind the computer- wow!

</comment><comment><USER54> On Lion it seems to register itself automatically in startup items. There is no Preferences or Settings window to change this either.

Very awesome overall.

</comment><comment><USER55> This works incredibly well. I wasn't sure how accurate this could be without the kinect-style depth sensor but it's surprisingly accurate. Great work guys!

</comment><comment><USER56> So this is Mac only?

<comment><AUTHOR> Yes, at the moment. We will add support for other OS very soon.

</comment></comment><comment><USER57> I've been sitting here for like five minutes just starting and stopping. About every third time I laugh and say (out loud) "that's so awesome."

</comment><comment><USER58> It would be interesting to know what piece of technology, or framework, they're using for recognizing gestures using the webcam.

<comment><USER32> I'm not sure, but this looks like a good starting point? <http://www.movesinstitute.org/~kolsch/HandVu/HandVu.html>

</comment></comment><comment><USER59> It seems like the Minority Report future of gesture based control is not that far off. Great app!

</comment><comment><USER60> You have built something people will want to talk about but why limit to spotify or iTunes :)

<comment><AUTHOR> Hi, we are not limiting it to that. We want to add more to the list. It just takes time... we're still a small 3 people team. Know any great engineers/designers who can help us execute faster? :)

</comment></comment><comment><USER61> Please allow me to control a presentation in Keynote. I've wanted this feature for so long.

</comment><comment><USER62> Looks very interesting.

The download link seems be down though (internal server error).

<comment><AUTHOR> Hi. Can you please try again? It just worked for me? If you still get an error then please send email to Feedback [at] flutter.io an we will send you diff link. Thanks so much. M

<comment><USER62> Seems to be an encoding error of sorts. I have a norwegian character in my name (Ø), i used switched it for O and the download worked fine.

The app works great, really cool!

</comment></comment></comment><comment><USER63> This is so freakishly awesome !!!

</comment><comment><USER49> This is so good that I'm putting VLC away to use iTunes to listen to my music library.

</comment><comment><USER64> issue is that even when i am not controlling the playlist and randomly moving my hand it recognizes it as gesture... seems like lot needs to be done to differentiate between noise and actual gesture. anyways nice try.

</comment><comment><USER32> Great app. Looking forward to support for more gestures!

</comment><comment><USER65> That's amazing.

I... wow.

Take my money.

</comment><comment><USER66> Wonderful job guys!!! very very impressive

</comment><comment><USER67> Desperately want a skip gesture.

<comment><AUTHOR> We will try to get in out ASAP!

</comment></comment><comment><USER68> i imagine you guys are already working on the skip/back functions. Awesome initiative!

<comment><AUTHOR> Yes, idea is to allow you to listen to music or watch movies without touching keyboard or mouse.

</comment></comment><comment><USER69> Makes me feel like a jedi !!!

</comment><comment><USER70> This is amazing!!

</comment><comment><USER71> Great job guys!

</comment><comment><USER72> Brilliant work!

</comment><comment><USER73> this is sick, like @zigfu

</comment><comment><USER74> It would be cool if this also let me clap as a gesture. And it would be cool if you sold an arduino kit that let me hook up my light switches.

</comment><comment><USER75> Congrats guys, this is very cool.

</comment><comment><USER76> Surveillance in the name of convenience has gone too far. I can see a future where companies offer services as wrappers around visually analyzing people's behavior in their own homes. They will sell that data just as they do now. That's not a future I encourage.

<comment><AUTHOR> That's a great point. This is why we've built an app w/o a server component, so everything happens on your machine.</comment></comment>


WTL (Wave Threshold Logic) Primer - <AUTHOR> https://docs.google.com/viewer?url=http://nebula.wsimg.com/282bb4ac56b1e17a5b8ff819f03ade5a%3FAccessKeyId%3D63CF6890887317CC859D%26disposition%3D0 <comment><USER3> This is good old asynchronous logic with separate no-data state, renamed (probably, for patent reasons).

<comment><AUTHOR> I did post about them earlier. [1]

I think there may be some novelty to the design of their "threshold gate" at the silicon level to avoid metastability issues and thus enable their design tool flow.

They seem to have since pivoted, though, to something akin to neuromorphic computing popularized by the large asynchronous circuitry in IBM's TrueNorth chip.

The work towards making deep learning power-efficient will be important, and I think that's where they're heading.

There are area tradeoffs, but if you have efficiency gain, then you can take advantage of "dark-silicon".

Asynchronous design's time may really indeed be coming. [2]

[1] [https://news.ycombinator.com/item?id=10625233](https://news.ycombinator.com/item?id=10625233)

[2] [https://news.ycombinator.com/item?id=11425533](https://news.ycombinator.com/item?id=11425533)

<comment><USER3> Having no-data symbol in the alphabet is a sure-fire way to have very stable circuitry. I am rusty in the details (I did development a long time ago and not returned for a while), but for O(width) AND-NOTs, two Miller C elements and glitch-free synthesis you can get async logic without metastability issues, just by design.

There is a Russian chip named NeuroMatrix: [https://en.wikipedia.org/wiki/NeuroMatrix](https://en.wikipedia.org/wiki/NeuroMatrix)

It's main accelerator exploits the idea that deep neural networks need less precision in layers closer to output. So it uses variable-width variable-count multiply-add circuit within single 64x64 multiply-add circuit. At the start there are, say, only two multiplications done, 32x64, but in the last layer you can fire up to 64 multiplications.

Was this circuit built with async logic, it will be even faster, because in clocked logic they have to control depth to get to clock frequency for worst case (1x64x64) and can't gain anything except multiplication count for 64x1x1 case. In async setting, the use in the 64x1x1 would be blazingly fast - <USER2> bit depth!

(I can be wrong here and there - right now I am editing VHDL grammar, adapting it for ANTLR4, sorry; I hope you get the idea, though)

I don't know how DeepNorth operates. But I believe they use the same trick or something close to it - it's cheap and impressive.

</comment></comment></comment><comment><USER4> haha... self timed domino .. published like 10-15 years ago already.

this won't work for many reasons that everyone in the industry already knows. High fan-out back to many gates that are spatially distant means that you need not only complex routing, but also complex sizing of the feedback inverter. So.. this won't even fit in with automatic place and route of complex cells. And good luck doing this custom in an efficient way such as making it a semi standard cell library.

Furthermore, the feedback inverter only works in simple cases such as the cascaded gates you show, when the switching of the one gate depends only on one fan-out. If it depends on more than one fan-out, the feedback inverter essentially requires another logic gate in front of it, which simply just blew up your entire circuit size and any power savings you were attempting.

</comment><comment><USER5> This is just NULL-Convention Logic, renamed so they could trademark it. I mentioned NCL in a comment under the micropipelines [https://news.ycombinator.com/item?id=11425533](https://news.ycombinator.com/item?id=11425533)</comment>


How expensive do prescription drugs need to be to fund research? - <AUTHOR> https://www.theatlantic.com/health/archive/2019/03/drug-prices-high-cost-research-and-development/585253/ <comment><USER2> This is such a complicated issue, I'd highly recommend the following as a primer:

[https://www.forbes.com/sites/matthewherper/2015/10/13/four-r...](https://www.forbes.com/sites/matthewherper/2015/10/13/four- reasons-drugs-are-expensive-of-which-two-are-false)

Also Derek Lowe is invariably awesome in this space, one highlight:

[https://blogs.sciencemag.org/pipeline/archives/2019/02/05/ta...](https://blogs.sciencemag.org/pipeline/archives/2019/02/05/targets- versus-drugs)

Drugs occasionally need to be expensive, particularly on-patent drugs, to make the endeavor worthwhile. That said, it's a two-way street. Making drugs insanely expensive (as has been happening more recently) is breaking the implicit trust that those in the medical field must work hard to maintain. Traditionally pharma was careful not to abuse the inherent "your money or your life" dynamic, it seems these days that is breaking down. It's sad because for very powerful drugs (i.e. gene therapy treatments) the cost is actually quite high to even make the drug (I've heard quotes in the 100's of K even in the 1-2 M), which means the treatment has to be expensive. That said we need to work hard to bring that down, and there's absolutely no place for the kinds of shenanigans going on with insulin among others:

[https://www.nytimes.com/2019/01/18/opinion/cost-insurance- di...](https://www.nytimes.com/2019/01/18/opinion/cost-insurance-diabetes- insulin.html)

With abusive practices like this, how can you ask patients to trust you when you say, "yes but this time I actually need it to be this high"?

<comment><USER3> > "your money or your life"

> (I've heard quotes in the 100's of K even in the 1-2 M)

The thing is that no one+ has that kind of money. So it ends being your money or _his_ life, over and over again. This has long since moved from the space of individual decision making to public policy. But we in the United States refuse to face up to that. We like to pretend that the doctor and patient should be the only ones that have any say in deciding what to do and if anyone outside that room balks at the price tag, no matter how high, they are an evil insurance company or government bureaucrat that doesn't care about human life or something. That's naive and silly. Spending $1 million of public or collective funds on a single individual isn't something that should be done automatically or that we should do out of a sense of guilt.

+Okay a few, but not enough to make a market.

<comment><USER4> That's what insurance is _for_. When you buy insurance you're making an agreement to socialize risk, so you're never faced with a $1M bill to save your life.

<comment><USER3> Health insurance, despite the name, isn't insurance.

Insurance is paying small sums, at EV negative cost, to mitigate the risk from a rare but very expensive cost.

Health insurance isn't underwritten and pays out for routine expenses. It isn't insurance.

<comment><USER5> I think you are trying to say it is _more_ than an insurance, because it _also_ pays out for routine expenses?

<comment><USER3> No, it's not a strict superset because of the underwriting issue.

<comment><USER4> Even without underwriting it's still insurance, which is "a practice or arrangement by which a company or government agency provides a guarantee of compensation for specified loss, damage, illness, or death in return for payment of a premium" according to Google's dictionary.

<comment><USER3> If there was a soup kitchen that charged something, maybe on a sliding scale, but not nearly enough to cover costs, it would meat the dictionary definition of a "restaurant". Calling it that would nonetheless be misleading.

<comment><USER4> Yes but in this case, virtually everyone agrees with the precise dictionary definition of insurance and uses it in daily conversation all the time. Very few would agree with you that health insurance without underwriting should not be called insurance. Political discourse, everyday conversation, and the law itself still call it insurance.

(And while I don't think you meant the comparison this literally, I'll point out that health insurance companies do cover their costs. In fact, they're generally quite profitable.)

</comment></comment></comment></comment></comment></comment></comment></comment></comment><comment><USER6> Interestingly in the case of the the Abiraterone example used in the article, none of the R&D was even done by JNJ. The original work was done at The Institute of Cancer Research, an academic/charity drug discovery institute. JNJ actually only market this drug because of acquisitions rather than R&D efforts. Which is the way that a lot of pharma is going these days, letting smaller biotechs take the high risk of developing a therapeutic and buying them up before FDA/EMA approval.

<comment><USER7> I don't buy that argument. It's like saying I should sell something I bought at the store for free, because I didn't pay the cost to make it directly (someone else did, and I paid them).

The research had to be done, and JNJ bought the company that did it. The price they had to pay was impacted by the cost of the research.

<comment><USER8> But if the product you're selling in your store was made using charity? Or gifted you by the government? then high prices couldn't be justified by R&D costs.

<comment><USER7> True, but remember that you're not just paying for the research cost of Drug_X when you price Drug_X. You're also paying for all the research that failed, that didn't produce a useful drug. If you spend 100 million researching 100 drugs, and one of them produces something you can sell, you don't need to make back 1 million when selling that drug. You need to make back 100 million, plus a profit.

<comment><USER9> This is patently false. Without regulation, all goods are priced by what the market will bear. It might be true that if successful drug doesn't make enough to cover the cost of failed drugs the company will go out of business but that has nothing to do with pricing.

The problem is that without competition drug companies can keep raising the price as long as enough people will buy it at the new price so that they make more money than all of the people buying it at the old price. That is why really old drugs that have been around for a long time have their prices increase. Not because there was some new research but because the lack of alternatives means they can just do it.

</comment></comment></comment></comment></comment><comment><USER10> Patent expirations don't factor into this article very much, but there's this:

 _The simple explanation for excessive drug prices is monopoly pricing. Through patent protection and FDA marketing exclusivity, the U.S. government grants pharmaceutical companies a monopoly on brand-name drugs. But monopolies are a recipe for excessive prices. A company will raise prices until its profits start to drop._

That monopoly is very fleeting.

By the time a drug makes it to market, it's typically been about ten years since the patent was issued. That gives a drug company about 8 or so years of exclusivity before any other drug maker can produce the drug without infringement.

<comment><USER11> Indeed. Companies have a limited time to recoup costs. Once the patent runs out, that $10,000 drug turns into a $500 drug. Forever. That benefit can't be ignored.

<comment><USER12> There are many ways to extend the patent or the effect of the patent: [https://www.upcounsel.com/how-long-does-a-drug-patent- last](https://www.upcounsel.com/how-long-does-a-drug-patent-last)

<comment><USER11> There are and some of them are an abuse of the system. However, most drugs pretty quietly go generic.

A good example is Lipitor. For Pfizer it brought in over $11B per year in revenue. Cost was around $150 per month. You can now get a month's supply for $5.94 according to GoodRx. That's a 96% reduction in the cost.

</comment></comment></comment></comment><comment><USER13> The answer will always be, "more expensive than they are now". It's not like there will ever be a point at which more money, if available, could not in any way be used for some kind of drug research that might be useful. It's like saying "how much money do you need in order to keep from ever dying?" There will always be health problems, and there will always be some at least semi- plausible way in which we could spend money to try to research a way to at least ameliorate the condition.

So, this doesn't mean we shouldn't spend some money, or even a lot. But, it will never be enough, so at some point we will have to say, "we could spend more, and it might give us a little more life, but let's not."

I don't think we're remotely ready for that conversation.

<comment><USER14> [https://www.nytimes.com/2009/07/19/magazine/19healthcare-t.h...](https://www.nytimes.com/2009/07/19/magazine/19healthcare-t.html)

"Why We Must Ration Health Care" by Peter Singer. New York Times Opinion Section.

Unfortunately this is a very difficult conversation to have between people and their physicians, between family members, and with ourselves. It ties into another very difficult discussion of facing death. In a democracy the lowest common denominator argument wins out with catchy slogans, in-group signaling, burying uncomfortable facts, avoiding short term sacrifice, and/or wielding anecdotes instead of rational analysis. Thus the rationing happens when it is least effective - during a crisis when significant human, monetary, and time resources are drained. And not much earlier when some planning and hard work could greatly ease the burden.

<comment><USER11> When people always ask "how come healthcare is so much more affordable in countries outside the US?", the correct answer is rationing.

If you need joint replacement surgery in Canada, you can expect a wait of many months to years. Canada has made the call that they will put a certain dollar amount into joint replacement and if the demand is higher, then people will just have to wait.

Same thing with the latest and greatest drugs. Some countries just say "no".

If you want an affordable healthcare system in the US, then rationing has to be a part of the equation. As others have pointed out, we already ration in the US, but trustfully, if you have good insurance, you'll get very good care in the US. The question is whether all that extra care is actually producing better outcomes.

<comment><USER15> Rationing also makes some outcomes summarily worse.

If you have a relatively minor problem, you're put in a line. For months (or years) of waiting, your problem becomes worse, and when you finally get to be treated, the treatment is much costlier and less effective.

This is to say nothing about your actual suffering from the problem, and from knowing that it's deliberately not being treated.

<comment><USER16> Joint replacement waiting a few months likely won't cause that much harm. I mean it can but it's statistical probably justified. And in fact it's guaranteed that these systems are trying to balance that.

</comment></comment></comment></comment></comment><comment><USER17> If you're going to rip sick people off to pad your bottom line and reward your executives and shareholders, at least have the courage to be upfront about it.

It's weird to say this, but maybe the world needs more Martin Shkreli's. That way there's no room to doubt the motivations of virtually all large drug companies (at least in the US).

</comment><comment><USER18> I saw a show earlier this week, an insulin shot costs 2$ in rest of the world and 100+$ in the US.

Isn't this loot?

<comment><USER19> > I saw a show earlier this week, an insulin shot costs 2$ in rest of the > world and 100+$ in the US.

"Insulin" is not a singular thing. For various reasons, lower-cost insulins are difficult to impossible to find in the US, which is a problem.

Also, _some_ insulins are $2/dose in _some parts of the world_. Most insulins in the developed world are significantly more expensive than that (to whomever is paying for it), though still significantly less than what they cost in the US.

<comment><USER18> Yes, US users pay a lot for insulin. Price has shot up from single digit dollar to 3 digit from 70s to today

</comment></comment></comment><comment><USER20> It's the ultimate prediction problem. And short term, computational bio methods are driving R&D costs up, not down. But arguably, techniques like DeepFold constitute current best hope

[https://moalquraishi.wordpress.com/2018/12/09/alphafold- casp...](https://moalquraishi.wordpress.com/2018/12/09/alphafold-casp13-what- just-happened/)

<comment><USER21> Garbage in / garbage out. You can't get away from reliable and predictable data. At that part is shockingly lacking. We have much better, sensitive and high-though put methods these days, but we are still relying on mice or cell culture data. We should be using ML to find what's dissonance and missing links in the data, not to predict what will work.

</comment></comment><comment><USER22> However expensive it is, it should cost the same in all markets globally, whether it's being purchased by a patient in cash, by an NGO, by a state Healthcare system, or by an insurance company. I'm tired of paying a five hundred percent markup to subsidize markets thousands of miles away.

<comment><USER23> You're not subsidizing the markets far away. Price discrimination isn't subsidizing. The supplier is just able to extract the maximum price from each market.

<comment><USER24> > The supplier is just able to extract the maximum price from each market.

And they are able to do that because laws have been passed in their favor to legally bar other people from simply importing the exact same products from other markets where they are sold at much lower prices.

Price discrimination isn't subsidizing, per se, but the _scope_ for price discrimination is very limited in the absence of government support due to arbitrage. Governments interfering in the market to enable price discrimination is very much a form of subsidy, even if the money isn't passing through the government on its way to the supplier.

<comment><USER23> I think I agree with this entirely.

</comment></comment></comment></comment><comment><USER25> If the government is willing to dole out research loans at appropriate terms all medication can be profitable.

</comment><comment><USER26> Why is it expected that private industry the only funder of research? Isn't that something that governments should have a stake in and also fund basic scientific research in?

That's like saying, how expensive does an iphone need to be to fund material science research?

<comment> barry-cotter No one expects private industry to fund all research and they don't. Governments fund a lot of basic and applied research, in pharmaceuticals and many other domains. What they don't really find is drug development, taking a drug from the "This looks good" stage through animal models, safety testing and efficacy testing.

</comment></comment><comment><USER27> When the question is stated like that it becomes really questionable whether cost of drugs should have anything to do with drug research cost.

Those two things look like they should be completely separate, done by separate entities with separate funding.

<comment><USER28> I think the reason you want them connected is the ability to channel private capital towards achieving medical progress.

If there is a disease which costs the general population tens of billions of dollars a year, either in providing healthcare or in an inability to carry on a normal life, work, look after yourself and so on, then there is an inherent and huge pot of money which can go to solving the problem. If you sever the connection, you rely solely on funding achieved through political processes. Which given the level of expensive failure inherent to the process, tabloid campaigns, lack of public understanding, and short termism from politicians, does not seem like something we should rely on.

For instance, can you imagine what the reaction would have been if the hundreds of millions spent on alpha-beta clearance for Alzheimers had been spent by public bodies? Future funding would depend on a battle waged on twitter, opinion pages and talk radio.

<comment><USER29> Furthermore, you could pretty much forget about funding for socially/politically unpopular diseases - I can certainly imagine some voters rabidly requesting their representatives that HIV drugs shouldn't be funded at all because God's punishment should be allowed to take its course.

</comment></comment></comment><comment><USER30> This article fails to mention the Quality Adjusted Life Year (QALY) concept. In theory we ought to set maximum prices that third-party payers (governments and private insurance) would pay for drugs based on how many years the drug would add to the patient's life and how much it would improve the patient's quality of life. Setting that maximum insured price would allow the free market to work through price signals and encourage drug companies to focus their research on areas most likely to deliver real benefits to public health. The US federal government currently values a human life at something in the range of $100K per year for regulatory purposes so that would give a starting point.

Of course the notion of setting limits on drug prices is politically fraught due to misguided concerns over "socialism", "big government", "death panels", etc.

[https://en.wikipedia.org/wiki/Quality- adjusted_life_year](https://en.wikipedia.org/wiki/Quality-adjusted_life_year)

</comment><comment><USER31> They can be free (edit: or rather the patent burden can be eliminated), and we can fund research in different ways.

Dean Baker has been banging on about this for years.

</comment><comment><USER32> How expensive do tolls have to be to fund roads?

</comment><comment><USER33> How marketable do prescription drugs need to be to have their R&D funded?

<comment><USER34> I never understood the change in US law allowing direct-to-consumer advertising of prescription-only medication. Doctors are told not to write scripts to family, friends and themselves, so how the hell can I make an informed decision about my cancer treatment using a 30 second infomercial?

<comment><USER35> Doesn't this boil down to Citizens United - if corporations are allowed to use money as they see fit because money is roughly equivalent to free speech then all three branches of government are responding to the entities with the most of it - in this case big pharma.

<comment><USER34> I am not making any reference to Citizens United. This started in the US in 1981 and there was FDA guidance issued in '85\. "The FDA said in 1985 that drug makers could air ads, but they also had to follow rigid rules for disclosing side effects and other information." [1]

1: [https://www.statnews.com/2015/12/11/untold-story-tvs- first-p...](https://www.statnews.com/2015/12/11/untold-story-tvs-first- prescription-drug-ad/)

</comment></comment></comment></comment><comment><USER32> How much do governments care about health outcomes?

<comment> barry-cotter Not that much. we could cut healthcare spending in half with very few noticeable effects on outcomes.

[https://en.wikipedia.org/wiki/RAND_Health_Insurance_Experime...](https://en.wikipedia.org/wiki/RAND_Health_Insurance_Experime..). An early paper with interim results from the RAND HIE concluded that health insurance without coinsurance "leads to more people using services and to more services per user," referring to both outpatient and inpatient services.[5] Subsequent RAND HIE publications "rule[d] out all but a minimal influence, favorable or adverse, of free care for the average participant"[6] but determined that a "low income initially sick group assigned to the HMO... [had a] greater risk of dying" than those assigned to fee-for-service (FFS) care.[7] The experiment also demonstrated that cost sharing reduced "appropriate or needed" medical care as well as "inappropriate or unnecessary" medical care. [https://en.wikipedia.org/wiki/Oregon_Medicaid_health_experim...](https://en.wikipedia.org/wiki/Oregon_Medicaid_health_experim..). Approximately two years after the lottery, researchers found that Medicaid had no statistically significant impact on physical health measures, but "it did increase use of health care services, raise rates of diabetes detection and management, lower rates of depression, and reduce financial strain."[4][5]

<comment><USER21> That Oregon study was too limited in scope, variables, population, and time. It just wasn't well done. Now if your goal is to decrease state spending shorterm, then this is definitely a dumb move, and we didn't even need that "experiment".

It's about how you value your population and the type of society you are trying to develop.

</comment></comment></comment><comment><USER36> This article raises important issues but it also cherry picks some findings and makes some unsupported claims. I am not able to link / dig up sources for all of the below, but I should probably do so at some point bc there is a lot of incomplete and biased info out there (on all sides)

\- article claims that spending on meds is biggest source of overspending compared to other developed countries. The article they link to only evaluates a few specific cost areas and does not present sufficient evidence to support the claim in the article. Under 10% of US healthcare spend is on rx drugs, that's middle-of-the-pack compared to OECD. Biggest driver of us HC spend is hospital and physician care (50% of spend). Also hospital spend has grown faster than drug spend last few years. [https://www.cdc.gov/nchs/fastats/health- expenditures.htm](https://www.cdc.gov/nchs/fastats/health-expenditures.htm)

\- the study that analyzes cost of developing cancer drugs ignores cost of failure. The article i think mentions that one study includes cost of failure for cancer drugs but puts failure rate at 25%; I don't know what sample they are looking at or how they define failure, but historically cancer drugs have a less than 10% chance of getting approved from phase 1

\- the article says that most cost is "early" and cheap i.e. in phase 2 failure. It is true that 60%+ of phase 2 fail, but phase 2 failure is not early or cheap. The article mentions the cost of running a phase 2 study but ignores all the costs required to get to phase 2. It can cost $100-200M+ Just to get to phase 2 and only 35-40% of drugs make it past that. Only mentioning the cost of a phase 2, and not all the stuff that is before phase 2, is misleading and makes me wonder whether the authors are biased. Phase 2 failure is the biggest driver of cost of drug development. Paul et al 2010 nature rev drug discovery

\- it criticizes the tufts studies bc the numbers are proprietary. That's fair but just bc the dataset isn't public doesn't mean the results are wrong. The studies the article mentions to "refute" the tufts data are even more flawed than the tufts one (see above point about the cancer drug cost study that ignores cost of failure).

\- mentions the tufts study includes "capitalized" costs. Even excluding those costs, the cost of developing a drug is over $1B

\- mentions that companies only develop cancer drugs because they are most profitable. But doesn't mention that developing drugs for almost any other indication is not profitable. If developing drugs was really so cheap and profitable, pharma would be developing a lot more drugs than it is

\- does not discuss the declining returns to pharma r&d, erooms law, and pharmas use of the balance sheet to fund r&d in recent years because pharma r&d is failing and they have to buy drugs from startups

\- ignores all r&d spend by non big pharma. Most drugs are developed by small companies not pharma, but pharma buys the small companies before the drugs are commercialized. So all the industry's profits accrue to big pharma but r&d costs are spread out

To me, the fact that this article makes claims that either neglect nuance or are unsupported by the articles they link to, that they criticize certain articles that support high cost of r&d but do not criticize articles that show low cost of r&d, and the use of either misleading, wrong or unexplained data points makes me strongly think this is a biased article

</comment><comment><USER37> Not at all if research is publicly funded for the public good

<comment> barry-cotter The research part of R&D is publicly funded, the development part isn't, and it's very, very expensive. On average about a billion dollars.

<comment><USER38> The idea that development is not publicly funded is a myth. Regulators define every step, put in a good deal of the money, and do a lot of the organizing. A lot of the rest is done in coordination with researchers at hospitals and universities that are often publicly funded. As with most large industry involved research efforts, the government and academia are heavily involved in the effort. Only the profit is privatized. It has always been thus.

<comment> barry-cotter If your model of the pharmaceutical industry were true they would have very, very high profit margins. They don't. Privatised profit and socialised losses is a great way of making an individual profit but the pharmaceutical industry is not politically connected enough to do that.

[https://www.forbes.com/sites/johnlamattina/2018/01/23/about-...](https://www.forbes.com/sites/johnlamattina/2018/01/23/about- those-soaring-pharma-profits/)

> The average return on equity for key industries from 2014 – 2016 shows that > biopharma's profits stand at 16.2%, significantly lower than Computer > Sciences (31.6%), Beverages (27.4%), Aerospace/Defense (23.0%), and Trucking > (19.1%) while modestly higher than Software System/Applications (15.2%) and > Healthcare Support Services (14.4%).

> Another measure, Internal Rate of Return (IRR) is even more telling. IRR > calculates the sales/cash flows resulting from R&D investments, ties R&D and > the returns it generates together, and is a more appropriate metric for > biopharma productivity. Deloitte reports that the IRR for biopharma R&D has > been steadily falling from 10.1% in 2010 to 3.2% in 2017. Even Wall Street > hasn't bought into the "pharma soaring profits" view. Since February 1, > 2014, while the Dow has risen 63%, the stock prices of a number of major > pharma companies have been muted with Pfizer and Bristol-Myers each growing > by about 15%, and Merck and AstraZeneca by roughly 6.5%. Even Lilly's growth > of 43% still lags the Dow.

<comment><USER38> This is an industry that has had 15-20% returns for decades. I'm not sure what "computer sciences" is as an industry separate from the rest of software, but saying there are some sectors more profitable than pharma says not much. Pharma is huge as a fraction of GDP and consistently profitable because its profit is based on rents. If it is flagging in recent years it is because public sector spending on research is flagging and hasn't yielded as many cash cows as usual.

</comment></comment></comment></comment></comment><comment><USER39> Infinitely expensive?

How many hypotheses do we want to test? As many as possible.</comment>


Changing The World - for computer scientists - <AUTHOR> http://weblogs.mozillazine.org/roc/archives/2010/04/changing_the_wo.html <comment><AUTHOR> Before anyone complains about roc's multi-column layout, let me preemptively link to <http://lab.arc90.com/experiments/readability/></comment>


Protein sequencing gone awry: 1 sample, 27 labs, 20 results - <AUTHOR> http://arstechnica.com/science/news/2009/05/protein-sequencing-gone-awry-1-sample-27-labs-20-results.ars

<comment><USER2> _The proteins are chopped into smaller fragments using an enzyme called trypsin..._

That's known as bottom up analysis. It is currently the most popular way to do it, and IMHO it's crap.

You can do intact whole protein analysis and that's much better. More higher end instruments will do both, starting with the intact protein, measuring its mass, and then breaking it down and measuring the mass of the peptides.

The breaking down part is not deterministic but with the mass of the whole protein and the genetic sequence and a few runs you can figure out exactly what's what.

None of that will tell you what the 3D shape of the protein is. That's a whole other ball of wax.

\--EDIT--

 _the initially deposited data had several problems, including incomplete files, proprietary software formats, and screenshots of data displays in software rather than actual data files_

Yep, there's companies that can help you with that: <http://www.bioanalyte.com/>

</comment><comment><USER3> I like how Ars is able to make a complex topic more accessible. MS-based proteomics is still young, and it will take a few years for things to stabilize. RNA expression arrays were in much the same state several years ago. The key is to make sure that the variation comes from the biological samples, and perhaps the instrumentation, with the methods not being a source for those differences. Two things that the field needs to do is (a) make raw data available so that experiments can be reproduced and (b) uses consistent data formats. Standards can/will follow.

One experiment I would like to see is the same lab doing the same experiment multiple times on the same sample on different instruments (of the same make and model). Results should be interesting.

<comment><USER4> The advantage that RNA expression arrays has over mass-spec is that the techniques used are just a highly scaled up version of the northern and/or southern (depending on the method) hybridization blots that have been in use forever. The corresponding protein technique (western blots) requires individual anti-bodies, and as such is just not scalable to the same degree.

So, instead we are left with mass-spec solutions that miss a ton of data. Not all peptides can be read on a mass-spec, and if you do get a peptide, it's up to the software to figure out what it was.

Also, the data analysis in proteomics has been a known issue for many years. There are little to no standards since it takes so long to run samples. At the same point in the microarray field, the statistical and data analysis techniques were largely worked out. But again, this is due to the 'simplicity' of the measurements. It is just plain easier to measure known RNA or DNA sequences.

That's not to say mass-spec isn't useful, because it is. But I highly doubt it will be able to ever give us a complete picture of the proteome.

It's kinda funny, because we are seeing a shift in the transcriptome world that is now moving toward rapid sequencing approaches that mirror mass-spec a great deal.

</comment></comment><comment><USER5> Could anyone please tell me the names of some companies/non-profits researching proteomic sequencing? Preferably ones trying to work out the kinks that the article references? I live in the Boston area and used to analyze genomic data for accuracy and consistency and would love to help with this problem.

<comment><USER2> Seattle Proteome Center (SPC) <http://www.proteomecenter.org/>

<comment><USER5> Thank you! Their site gives a better idea about what's actually going on in the world about proteomics, and is a great start about finding affiliate companies.</comment></comment></comment>


You've Gotta Fight for Your Right to... OLPC - <AUTHOR> http://wilshipley.com/blog/2006/11/youve-gotta-fight-for-your-right-to.html

<comment><USER2> I understood the point of the article... but damn, it made me respect the OLPC _less_ , and confirmed my suspicions about NN. You see a village without power and your first thought is to make a laptop --- yikes, maybe you can include some cake with that.

<comment><USER3> If I see a village without power, it may very well have been a village _with_ power, but had its power source stolen, or broken without ability to repair, or just destroyed out of spite. However, when I see a village without education, I know that this is a village that has not yet been touched by education. Education is viral; when you give real, useful information to people, it stays with them forever, and no one can take it away from them. Drilling a well, say, only helps those already-powerful who lay claim to the well. No one can lay claim to a mind.

</comment></comment><comment><USER4> Would have been awkward if I were in his position and asked "Uh, hmm, would I, uh, know your name?", and he would respond "Yes."

Being the brutally frank person I am, I would have then said "What do you do?" after reading his card.

</comment><comment><USER5> Would have been better without all the juvenile comments. Could have made it seem like a Feynmann story, but no.

</comment><comment><USER6> Note, this is from 2006.

<comment><AUTHOR> _"... Note, this is from 2006. ..."_

Hey this is classic _"Wil Shipley"_. It's worth the read just for the writing style and humour. But it's insightful gems like this:

 _"... There's an interesting side-effect to this last kind of fight, the fight for good. When you're not doing it for your own ego, you can win just by convincing others to join your side. If you get enough people to fight for you, you can even win without anyone actually knowing it was you. ..."_

that make reading the article worthwhile.</comment></comment>


CloudFront Update – HTTPS and TLS v1.1/v1.2 to the Origin, Add/Modify Headers - <AUTHOR> https://aws.amazon.com/blogs/aws/cloudfront-update-https-tls-v1-1v1-2-to-the-origin-addmodify-headers/ <comment><USER2> Well, all great, but my issue is 15-30 minutes per purge or distribution update and also the inability to have to distributions with the same CNAMEs and switch easily between the active. Anyway, this minor update is welcome!</comment>


Daughters of WWII refugees are more likely to have mental illness: study - <AUTHOR> https://www.axios.com/daughters-of-wwii-refugees-are-more-likely-to-have-mental-illness-2513872556.html <comment><USER3> Missing from the headline: this is only daughters _of female refugees_. Sons of refugees had unchanged mental illness rates, but so did daughters of male refugees.

That's pretty surprising, and while it doesn't rule out a gender-roles explanation (maybe male refugees didn't describe their experiences as often?), it does gesture pointedly at epigenetic causes.

Also notable: the study had a clever control (non-refugee first cousins of refugee children) which seems to account for both population genetics and gender distinctions in hospitalization.

</comment><comment><USER4> I closely knew a man who was a 'second generation World War II victim'. Outwardly a normal person but utterly unable to normally function in society. The government recognized his plight and put him on a lifelong pension which he used to try to do as much good as he could in the neighborhood where he lived (and where he was hugely popular).

</comment><comment><USER5> Links between early life adversity and later pace of aging and risk of age- related disease may be mediated by cytomegalovirus exposure.

[https://doi.org/10.3389/fimmu.2017.01263](https://doi.org/10.3389/fimmu.2017.01263)

"The paper here finds that persistent cytomegalovirus infection is likely the mediating mechanism linking early life stress and later increased risk of age- related disease, acting through accelerated immune system dysfunction. This implies that the early stress may or may not be all that important, as - <USER2> whatever reason - the groups selected as examples of stress in early life are also more likely to be infected. That might be the short-term detrimental effects of stress on immune function, or it could be a matter of being in close contact with more distinct groups of people during childhood, as is the case for the adopted individuals in the study here. Cytomegalovirus is a persistent herpesvirus that the immune system cannot effectively clear from the body. Near everyone becomes infected at some point in life, and extensive evidence links this infection with immune system dysfunction. Increasing numbers of immune cells become dedicated to uselessly fighting cytomegalovirus, and ever fewer are left for everything else the immune system must accomplish. Other than this long-term corrosion, cytomegalovirus doesn't cause obvious symptoms in the vast majority of people - few notice the initial infection."

This is also compatible as a mechanism to explain greater disease risk in descendants, since growing up in an infected household presumably raises the risk of early infection with cytomegalovirus.

<comment><USER6> How does this relate to OP, which found a difference between _genders_ living in the same places, and which is about mental illness, not age-related illness?

Edit: Oh, you work at an age-related disease website, so you comment exclusively through that lens.

</comment></comment><comment><USER7> Interesting. But the study only looks at hospitalization. Is it possible that women are more likely to go to the hospital than men?

<comment><USER8> I reckon men with mental issues tend to end up in jail in many cases.

<comment><USER4> Drugs too, homeless as well.

</comment></comment></comment><comment><USER9> As a person with MDD, I'm glad studies like these are coming out. This is the best resource material I've seen about MDD and it's helped me a lot [https://www.youtube.com/watch?v=NOAgplgTxfc](https://www.youtube.com/watch?v=NOAgplgTxfc)

<comment><USER10> I'll second this video recommendation. Robert Sapolsky is an incredible researcher and lecturer.

</comment></comment><comment><USER11> This is a crazy coincidence. Me and my sister are trying to get help for my mom right now for the very same thing, and our grandma was a WWII refugee from Finland.

</comment><comment><USER12> Can we use this knowledge to do something about the children and especially the daughters of the refugees coming out of Syria now?

<comment><USER13> Are there that many women and children coming out of Syria? It seems like most of the migrants into the E.U are working aged men.

</comment></comment><comment><USER14> Read _The Last 100 Days_ or listen to Dan Carlin's _Ghosts of the Ostfront_ podcasts to get a sense of how apocalyptic that conflict was. No wonder the psychic scars persist for generations.

</comment><comment><USER15> Women tend to also have a lot more social baggage hung on them. It makes me wonder if the evacuation and trauma made it particularly difficult to figure out how to fit in socially in a new place.

(I mean as just one element that may have contributed.)

<comment><USER16> >Women tend to have a lot more social baggage

There are studies that show that women internalise emotional traumata much deeper than men, thus have a higher risk of PTSD (Can't remember if this is linked to the on-average better memory of women).

As far as I know this is unrelated to the fact that women are more likely to seek help for mental issues (which would naturally skew the numbers towards women).

<comment><USER15> _There are studies that show that women internalise emotional traumata much deeper than men, thus have a higher risk of PTSD (Can 't remember if this is linked to the on-average better memory of women)._

This in no way rebuts my thought. What if they are related? What if women internalize trauma more and suffer PTSD more in part because the entire social fabric of their life experience is fundamentally different from men?

This has been my experience as a woman. I do something a man would do, it gets a completely different reaction, and not in a good way. Trying to make my own life work gets me seemingly perceived as some kind of evil feminist. Men who try to figure out how to make money are not viewed as some kind of political activist or troublemaker, threatening the status quo.

I have gotten insane amounts of pushback for what I feel are completely innocuous behaviors. I have terrible eyesight, so I tend to sit up front in meetings or classes. This gets interpreted by other people as Type A personality extremely aggressive, ambitious behavior and prominent people will publicly comment on what an aberration it is. Their comments clearly come from a place of judging it to be disruptive, egomaniacal behavior. No one ever thinks "Well, maybe she can't see the presentation well enough from the back of the room." It is always framed in terms of me being an uppity woman who does not know my place in the world.

My "place" clearly being back row seats. Which reminds me of the historical expectation that blacks in the US had to sit at the back of the bus and stand up and give their seat to a white person if there weren't enough seats for everyone.

<comment><USER16> I did not intend to rebut! I saw you downvoted for no given reason (as so often these days on HN) and wanted to support your comment. People interested in this topic will have no problem finding the relevant studies, which is why I didn't even bother to include links.

I just wish people didn't abuse the downvote button so often. Instead of pushing irrelevant or toxic comments down, it's used to punish differing opinions. (Sorry for the offtopic rant)

<comment><USER15> Thank you for the clarification.

</comment></comment></comment></comment></comment><comment><USER17> [https://en.wikipedia.org/wiki/Epigenetics](https://en.wikipedia.org/wiki/Epigenetics)

if you know that this is heavily triggered by emotional / feels, then you can see why women might be more suceptible to these things. (as they are generally raised in a way to be more on the feels side of things, there is actually no natural difference, only imprinted later in life.)

<comment><USER18> Certainly there was a difference back then in how male and female children were allowed to deal with emotion. I was viciously beaten as a child in the early sixties for crying - as were my brothers - to teach me not to. My sister wasn't until older, if at all. These beatings could go on for very long periods of time, until breathing became convulsive, and continued after that point, too. When my younger brother died in his teens, my "training" held and I wasn't able to cry (but I've got that back in spades, since.) This was only somewhat extreme for the time. So back then, was there a "feels" (repression) difference for men and women? Oh, yeah, by no accident.

However, I believe the evidence shows this actually leaves males more vulnerable to trauma and PTSD, not less. I don't have links for that, just memory of the science, but what you deal with during the day is perhaps less likely to keep you up at night.</comment></comment>


Telecom Lobbyists Successfully Remove Canada from Wireless Pricing Report - <AUTHOR> https://www.iphoneincanada.ca/carriers/telecom-lobbyists-remove-canada-wireless-report/ <comment><USER2> Canada is a cesspool of oligopolies, from TV to Cell Phone to Banks, etc.The excuse is always "if we don't then some foreign/US company could come in and destroy our culture." Which of course is bullshit. A handful of companies are making billions and billions off the backs of Canadian with worse service and it won't get any better unless the oligopolies are broken.

<comment><USER3> This sounds a bit like the general situation in Australia.

It annoyed me to no end when I lived there but the locals didn't seem to worry.

<comment><USER4> > This sounds a bit like the general situation in Australia.

As a Canadian living in Australia since 2011, I have to disagree. Politically Canada is much more of a protectionist nanny state than Australia.

For mobile service in particular (i.e., the topic of this dicussion), Australia is much more competitive than Canada despite also being a very large, sparsely populated country. I pay $25/month for unlimited calls and 18 GB of 4G data ([https://www.aldimobile.com.au/plans/value- packs/](https://www.aldimobile.com.au/plans/value-packs/)). Unlike Canada, Australia allows strong, foreign competitors to provide mobile service (e.g., Vodafone and Optus).

Other ways in which Australia is less protectionist than Canada: \- parallel private healthcare system \- parallel private education system (although not at university level) \- buy alcohol anywhere, not just at government owned stores \- no dairy and poultry "supply management" \- foreign owned supermarkets (e.g., Aldi)

Australia is far from perfect (e.g., the natural gas cartel is far too powerful) but on the whole there's far less government interference that protects cozy domestic oligopolies compared Canada.

<comment><USER3> Sorry, I guess I was unclear. I wasn't talking about the Telstra situation. It's not great but it also not Canada level bad. I also wasn't talking about healthcare/alcohol etc.

I think where Australia suffers is in things like imported goods (often there's an extra 20-40% markup beyond the maybe 5% higher shipping cost. Or sometimes it's shipped directly from China, but still way more expensive. I think many brand owners have just decided Australia will be able to tolerate a higher cost than the rest of the world.

<comment><USER5> > I think where Australia suffers is in things like imported goods (often > there's an extra 20-40% markup beyond the maybe 5% higher shipping cost.

Oh yeah, crazy that somewhere in the middle of nowhere is more expensive than one that is not.

<comment><USER6> So sure it's hardly the whole logistics story (volume, volume, volume)... but Australia is actually _closer_ to S.E Asia (where a large volume of e.g. electronics goods are made or assembled) than the U.S.

</comment></comment></comment></comment></comment></comment><comment><USER7> Around 2013, the Canadian government considered allowing Verizon to enter the Canadian market by buying WIND Mobile, a small budget carrier which was looking for foreign investors. They were faced with a huge fearmongering campaign orchestrated by the big three carriers, with TV ads like this:

[https://www.youtube.com/watch?v=ndQv6wwaNyM](https://www.youtube.com/watch?v=ndQv6wwaNyM)

Needless to say that Verizon backed out of the deal immediately.

<comment><USER8> Fun, if a bit rough, parody of that too. [https://youtu.be/kC0uMKXsVM4](https://youtu.be/kC0uMKXsVM4)

When I was travelling in the U.S. a few weeks ago, I was able to buy a month's unlimited data and North American calling and SMS on some random MVNO from some random phone shop in middle of nowhere NY, including a new SIM and activation, for less than one pays for a month with a cap here in Ontario.

Even the corrupt, cronyistic telecom arrangements in the U.S.† are dramatically better than those in Canada.

† Not that the U.S. is particularly bad for this, by world standards.

</comment></comment><comment><USER9> Sadly, telecommunications (Rogers, Telus, Bell) and air transportation (WestJet, Air Canada) are affected by oligopoly.

The situation in Quebec is slightly better thanks to a 4th telecom company, Videotron, which brings mobile plans and internet prices lower than in the rest of Canada.

It's funny how sometimes you'll see the exactly same "promotion" offerings from the Robelus trio...

<comment><USER7> It's not just telecommunications and air transport. Everywhere you look, you'll find sectors where foreign competition is prohibited or strictly managed in a way that keeps prices artificially high.

An example? Cheese. Under CETA (the Canada-EU free trade agreement), only Canadian dairy producers can import cheese from the EU into Canada. These producers will set its price artificially high as to match the price of Canadian cheese plus a premium. This way, they ensure consumers will buy Canadian cheese instead, as it appears to be cheaper.

It's just crazy how much lobbying can do.

<comment><USER10> Interesting. What would stop someone else setting up a new dairy producer and import it without applying the crazy markup you mention?

<comment><USER7> You need to be part of the supply management scheme, that is, you need to be producing and supplying milk in Canada. So an import-only business wouldn't be able to do it. I am not too sure on the details, but you can read more about it here: [https://www.theglobeandmail.com/report-on-business/rob- comme...](https://www.theglobeandmail.com/report-on-business/rob- commentary/as-ceta-looms-canada-braces-for-the-european-cheese- invasion/article34647025/)

</comment></comment></comment></comment><comment><USER11> Pricing in Canada for mobile plans are downright awful! I can buy a plan from Australia and use it there in Canada for cheaper with international roaming.

I remember only 10 years ago that Canadian telcos still considered moving between state lines as 'roaming'. I don't know if it's still the case.

<comment><USER7> Some Canadian carriers are indeed still selling plans with local calls only. In 2019. It's depressing.

<comment><USER12> Yeah! Freedom. Paying CAD45 for 4GB, when in UK I had unlimited data for GBP10.

Edit: did the low UK price offend someone?

<comment><USER13> where did you get unlimited data for GBP10?

<comment><USER12> GiffGaff, subsidiary of O2

</comment></comment></comment></comment></comment><comment><USER14> I recently had a discussion with a colleague about this:

Wouldn't it be much more efficient to start a telco with just 1 plan: unlimited everything for a fixed price.

Literally just charge $30/month or so (I haven't done the math on what is economically viable) for a flat fee plan. No strings attached, except maybe rate limit after a substantial amount of data to prevent abuse (like 50gb/day).

Also: no contracts, let people cancel when they want. And don't sell devices, just the SIM card.

This way you'll have:

\- no need for usage metering systems

\- very simple billing systems

\- minimal need for marketing

\- much less support calls (at least no angry customers due to unexpected costs)

\- a very simple self-service portal

Now, I know I'm being naive here, it'll be next to impossible to start a service like this because the physical infrastructure (the base stations) are owned by the ancient behemoth telcos that have roamed the earth for past century.

But just imagine how great a telco can be if you were just to trim the fat, legacy and greed away.

<comment><USER15> I think this will happen with the new wave of telecom companies that rely on satellites instead of ground towers (probably in the next decade or so)

<comment><USER16> > I think this will happen with the new wave of telecom companies that rely on > satellites instead of ground towers

Maybe. If you look at the total available bandwidth of the satellite systems vs their potential subscriber base, I think metering will probably happen at a lower level than many people expect.

Perhaps they'll upgrade to much better radios in the future and the whole issue will be resolved.

</comment></comment></comment><comment><USER17> For us living in Canada, we know we pay more than anyone else. And we're constantly reminded of how the Bell, Telus and Rogers mafia keeps it that way.

<comment><USER18> I live in Canada and everyone says this, I don't think it's really that true.

I was in California for this summer - I paid about the same for a cell service there as I do here...

All numbers in USD.

For a quick comparison of "premium" cell providers, an unlimited (15gb before throttling) verizon wireless line is $70 per month [0]. A comparable Canadian plan for Bell is $56 per month for 10gb before throttling, or $71 per month for 20 gb before throttling.

Most people don't pay that much in reality, because of group discounts and so on, but that applies in both cases.

The story is similar if we look at budget cell phone providers. Google Fi (US) provides unlimited talk and text for $20gb/month with data for $10gb/month. Freedom mobile (Canada) doesn't provide as much flexibility, and you have to select your amount of data up front, but for any amount of data it's cheaper. E.g. for 2gb it's $30/month instead of $40. [2]

[0] [https://www.verizonwireless.com/plans/](https://www.verizonwireless.com/plans/) \- change the number of lines to 1, this is 15gb data before throttling per their faq [https://www.verizonwireless.com/support/verizon-plan- unlimit...](https://www.verizonwireless.com/support/verizon-plan-unlimited- faqs/)

[1] Remember to convert CAD to USD [https://www.bell.ca/Mobility/Cell_phone_plans/Unlimited- plan...](https://www.bell.ca/Mobility/Cell_phone_plans/Unlimited-plans)

[2] Click on "Freedom Plans" here, remember to convert CAD to USD [https://www.freedommobile.ca/en-CA/plans](https://www.freedommobile.ca/en- CA/plans)

<comment><USER19> My bell plan is 95 CAD and gives 4GB/mo so I'm not sure where your numbers came from. I must have missed that deal

<comment><USER20> That's a terrible plan, you should definitely shop around. I'm paying $50 CAD for "Unlimited" (8GB before throttling) with Freedom.

The problem with Freedom is that their network is tiny, but even Telus and Rogers are both offering 10GB for $75 right now.

<comment><USER21> The problem with Freedom is there network isn't good enough so people try them and go back to one of the others that has coverage where they travel.

<comment><USER20> In my experience Freedom is just fine if you live in a city with good coverage and don't plan on spending much any time travelling through areas they don't serve. But if you travel much locally it's a non-starter.

<comment><USER22> In my experience, friends don't get signal in lecture halls in downtown Toronto on Freedom

<comment><USER20> Huh, I haven't had any signal problems like that, but I'm not in Toronto, so I don't know what the network's like there.

</comment></comment></comment></comment></comment></comment></comment></comment><comment><USER23> This is _insane_... how can the Canadian populace (and by extension, the government) _not_ pass laws that forbid this nonsense? Its incredible that the Canadian people are not up in arms over this shit.

</comment><comment><USER24> I lived in Canada for 2 years. The week I moved there is when T-Mobile started offering free unlimited roaming in Canada. In my time in Canada I kept my T-Mobile plan and didn't even have to get an unlimited plan since I already had unlimited roaming. Since my bill was sent to a Washington address, I guess I got in on some loophole. The best part was that my coverage was phenominal... I had access to Telus, Wind and Bell in my area.

My prior trip to BC scouting for a home (a month earlier) cost me hundreds of dollars in international calls and data usage. The phone plans in Canada are shockingly bad. Being able to circumvent them was a godsend.

</comment><comment><USER3> I remember the spectacular pricing of around $10-15/MB in Canadian mobile networks back around 2004-2005, just when 3G was getting started. (So it was really 2G pricing.)

As a reference, typical European pricing was around $2/MB at the time, IIRC. The US of course had their typical "plans" that made price comparisons hard.

It's fascinating that the network owners in Canada have managed to keep prices so high, for so long.

We were launching a mobile J2ME-based service back then; I remember thinking we'd get back to Canada when they'd got their data pricing in order but that never happened...

<comment><USER25> Canadians' situation is definitely an after-thought for app developers.

The NPR app keeps pre-buffering several hundred mb of audio when I start it and chews through my data. Ugh.

And then there's the time my bank forced me to update their app and I wasn't on wifi...

<comment><USER25> $10/mb vs $2/mb...

Things have diverted more. French plans now have 25x the data for lower prices than Canadian plans...

</comment></comment></comment><comment><USER26> Time to post this again: [https://palladiummag.com/2019/09/19/how-not-to- build-a-count...](https://palladiummag.com/2019/09/19/how-not-to-build-a- country-canadas-late-soviet-pessimism/)

<comment><USER27> [https://news.ycombinator.com/item?id=21101065](https://news.ycombinator.com/item?id=21101065)</comment></comment>


How A Self-Promoting Blogger Makes $1.3mil A Year & Still Gets No Respect[video] - <AUTHOR> http://mixergy.com/timothy-sykes-investimonials/

<comment><USER2> Tim Sykes is very nearly a con-artist who profits off the gullibility of others. Any success his trades and his readers have is based on just as much luck as it is any penny-stock technical trading strategies.

This is coming from a non-paying reader of his blog. He purposely overemphasizes his accurate calls (which _might_ have happened due to his reasoning, or just as likely not) and brushes the flaws under the proverbial rug.

<comment><USER3> Tim is a good trader, but like most successful business people he understands how to market. His persona, whether constructed or representative of his real self (it doesn't matter), is a great marketing tool that he has been able to leverage into a successful career. All great marketers emphasize their successes and try to forget their failures--does Steve Jobs still talk about the Lisa?

I think what people forget is that what people like Tim sell is information. He's a trader, yes, and a successful one at that. But for some reason people think that simply copying what Tim does will make them a successful trader as well. This is no more true than how many of the tech giants have tried to copy the iPod or iPhone--none of them have been as successful as the original because copying features (read: copying trades) is not the same thing as capturing the soul of the strategy.

Every marketer sells to gullibility. You can judge for yourself the morality of an individual marketer's tactics given the customer they are going after, but why on earth is it wrong to sell information to willing buyers? Wild deception in marketing practices will almost always lead to complete failure, and Tim has been around long enough to, I think, be able to pass that hurdle.

</comment></comment><comment><USER4> and probably never will.</comment>


TensorFlow Implementation of Deep Convolutional Generative Adversarial Networks - <AUTHOR> https://github.com/carpedm20/DCGAN-tensorflow <comment><USER2> I have an idea for anyone who is interest in getting their hands dirty with TensorFlow.

There is a very large conservation group in Fort Lauderdale that works with Sea Turtles.[1] Thousands of turtles are born on Fort Lauderdale beach every year, however, there is a problem because once hatched they move towards a light source. So they are crossing the road towards hotels with bright lights and street lamps at night instead of crawling into the ocean. What the volunteers are doing is collecting massive quantities of data to show how devastating artificial lights are to the baby turtles.

They have a massive quantity of data and they have a very good idea of when the eggs will hatch. They go out on the beach when the eggs hatch and pretty much make sure all the turtles make it to the ocean. Great program. They use data like air temperature and amount of daylight to try and figure out when the eggs will hatch so they are ready to usher them into the ocean.

They have years of data. They know the data is linked to hatching times. But, they don't have sophisticated models.

If someone wanted an interesting project to start using TensorFlow with I would suggest getting in touch with S.T.O.P. and request their data sets so see if a prediction model can be developed for when the eggs hatch. Being able to know when the eggs hatch would help the scores of volunteers who are out on the beach protecting sea turtles.

[1] [http://seaturtleop.com/](http://seaturtleop.com/)

<comment><USER3> I understand that it's difficult for people not experienced with machine learning to tell what problems are actually suited for what models, but using deep learning / Tensorflow for this is like using Hadoop to sort a 10 megabyte file of numbers. Or writing a new Ruby on Rails app and deploying to AWS in order to create a survey for a class project.

Plain ol' statistics, plotting, and some hand rolled features (this is bascially "data science") is probably the best fit for this problem, especially since it doesn't seem to me like this would be a massive dataset.

<comment><USER4> This is the big problem when an technique breaks through to name recognition in mass media. The last big one was SVM/kernel methods but it wasn't this bad. Now we have lots of people running around wanting to hit things with the "Deep Learning" hammer, with no real idea where it is appropriate (or worse, offering to do it for your company without much better understanding)

</comment></comment></comment><comment><USER5> I can't recommend this video because I haven't watched it yet but looking at the slides it looks like a good survey talk about generative models and an intro to DCGAN [https://www.youtube.com/watch?v=KeJINHjyzOU](https://www.youtube.com/watch?v=KeJINHjyzOU)

</comment><comment><USER6> They all look the same to me.

<kidding>

Love to see with with more training data.

</comment><comment><USER7> > "Deep Convolutional Generative Adversarial Networks"

Only 4 qualifiers? We can do better.. 5, 6 even 7 are now on the horizon!

</comment><comment><USER8> _ "</comment>