1) If a graphical plot turns data into something visual, an audio "plot" turns data into something audible. Your output is an audio file rather than an image or video file. The typical applications of this are to turn a boolean flag into a chime (e.g. text message received). Your important insight is that this can be extended to longer-form audio outputs.

2) When is audio more advantageous than image or video?

  - When you cannot look at a screen (driving, working out)
  - When there are too many screens (control room)
  - In a very dark environment where visibility is impeded
  - If you are blind or vision-impaired

Perhaps the most interesting application would be in a car, which is where people spend a great deal of time and have their ears and brains (but not their eyes) free. Some ideas:

a) Could you generate different sounds based on the importance of a text message (doing something like Gmail's importance filtering) signaling that you don't really need to respond to this particular message right now while driving?

b) Could you have audio feedback for important things along the road? For example, the problem with the Trapster app (trapster.com) is that I need to look at the phone to see where the speedtraps are. You can imagine an integrated audio feed that could give information like this and also tell you your constantly updated ETA (via Google Maps API call). Or you could listen to the pulse of your company on the road to do something semi-useful, and drill down into notable events via voice.

c) The really interesting thing is if you could pair this with a set of defined voice control commands. As motivation: an audible plot can't be backtracked like a visual plot. With a visual plot your eyes can just scan back to the left. To scan back and re-heard the sound you just heard requires rewinding and replaying. But it could be interesting to set up a small set of voice commands that allow not just rewinding, but rewinding and zooming. So you hear an important "BEEP" and you want to say something like "STOP. ZOOM" and set up the heuristics such that this identifies the right BEEP and then gives an audio drill-down of exactly what that BEEP represented.

d) Done right, you might be able to turn a subset of webservices into a sort of voice-controlled data radio for the road. People spend thousands of hours in their cars so it's a real opportunity.

http://techcrunch.com/2013/04/23/counsyl http://techcrunch.com/2013/04/25/sv-angel-health-informatics

Comments URL: https://news.ycombinator.com/item?id=5599001

Points: 27

# Comments: 2

http://www.reddit.com/r/Bitcoin/comments/1a51xx/now_that_its...

  [Submitted March 12]

  It's DanielTaylor again and I wanted to create a simple yet 
  intuitive post to explain the folks out there what happened  
  a couple of hours ago. This might also be useful for 
  bloggers or journalists who might be going to write about 
  it in the following hours.

  TL;DR

  The programs that read the blockchain, the bitcoin ledger, 
  disagree.

  Due to a bug in 0.7, it says that HIS is the correct 
  version of this ledger and 0.8 says that HIS is the correct 
  version.

  Miners (the people who add pages to the blockchain) are 
  told to switch to the 0.7 program so that this version 
  gains more support and the other one is discarded. 
  (orphaned).

  Regular users are not affected. Their transactions are 
  included in both ledgers and don't need to change any 
  programs.

  During that time, though, there is a slight chance of a 
  double-spend ocurring. That is why people recommended 
  merchants and exchanges to wait until there is one single 
  blockchain again before processing purchases and 
  merchandise.

  ...

  What's a double-spend?

  This is the reason why some merchants and exchanges stopped   
  processing incoming bitcoins for a couple of hours.

  The bitcoin network prevents people from spending the same 
  coins by mantaining this unique ledger, the blockchain. But 
  now that there were two of them, it was theoretically 
  possible to broadcast two different transactions with the 
  same coins and still get some confirmations.

  With some luck, someone could sneakily sneakily* buy a 
  television to a merchant who was reading the 0.8 ledger and 
  have the transaction confirmed. At the same time he could 
  have sent the same coins back to himself and, with some 
  luck, have the transaction confirmed on the 0.7 ledger.

  What happens is that, in the end when 0.7 wins, the thief 
  will have the television and his bitcoins. Remember that 
  there were two different versions of the same coins!

  This is not something easy to do and requires a lot of luck 
  because the blocks mined (the pages added to the ledger)  
  must be mined precisely in the correct order. But still, in 
  this situation it was easier to pull off and so it was 
  recommended for merchants and exchanges to temporarily stop 
  processing incoming transactions.

  Now the situation has resolved and the blockchain keeps 
  growing happily, page by page, block y block.

(To preempt: yes, Anonymous is not always good. No, I don't believe that Internet justice is always bad, or that it would be bad in this case, especially as all formal avenues appear to have been exhausted and the perpetrator is scot free.)

  People can inject just about anything they want into 
  themselves

http://www.leagle.com/xmlResult.aspx?page=4&xmldoc=19981...

  In Court, Plaintiff argued that he should have the right to 
  take whatever treatment he wishes due to his terminal 
  condition regardless of whether the FDA approves the 
  treatment as effective or safe, and that to prohibit him 
  from taking the treatment he wishes violates his rights 
  under the United States Constitution.4 The United States 
  Supreme Court previously addressed and rejected this  
  argument in Rutherford. In Rutherford, cancer patients 
  requested the right to use Laetrile, arguing, as does 
  Plaintiff, that for terminally ill patients the 
  effectiveness or safety of the proposed treatment is 
  irrelevant since such treatment is a last chance effort. 
  However, as identified by the Supreme Court in Rutherford, 
  to permit terminally ill patients to seek any type of 
  treatment regardless of the effectiveness of such treatment 
  would create a cottage industry existing solely to provide 
  potential panaceas to highly vulnerable patients. The 
  language of the Supreme Court in rejecting the Laetrile 
  argument is equally applicable here.

  "If history is any guide, this new market would not be long 
  overlooked. Since the turn of the century, resourceful 
  entrepreneurs have advertised a wide variety of purportedly 
  simple and painless cures for cancer, including liniments    
  of turpentine, mustard, oil, eggs, and ammonia; peat moss; 
  arrangements of colored floodlamps; pastes made from   
  glycerin and limburger cheese; mineral tablets; and 
  `Fountain of Youth' mixtures of spices, oil, and suet. In 
  citing these examples, we do not, of course, intend to 
  deprecate the sincerity of Laetrile's current proponents, 
  or to imply any opinion on whether that drug may ultimately 
  prove safe and effective for cancer treatment. But this 
  historical experience does suggest why Congress could 
  reasonably have determined to protect the terminally ill, 
  no less than other patients, from the vast range of self-
  styled panaceas that inventive minds can devise."

The absolute worst case scenario is that they lose some money and die a little sooner. The best case scenario is that they live!

To say that someone else can or should have the power to constrain another human in this way, to keep them from a chance at living, in the name of "protecting" them from doctors or companies...well, we are likely at a fundamental philosophical impasse. Which is why I return to my original point. Feel free to stay in the United States with the FDA. Those with a different cast of mind need a jurisdiction where we can take conscious risks, where we aren't "protected" from medical innovation.

First, many (most?) medical advances seem crazy and kooky because they haven't been tried before. So it's not usually as obvious as "this is a proven scam" vs. "this really works". It's much more frequently "this is unproven". And like Barry Marshall's famous self-experiment with H. pylori, someone has to be first for it to ever get proven.

Second, when the government gets it wrong, it gets it catastrophically wrong. The USDA Food Pyramid recommending "6-11 servings of grain" is still being slavishly followed, and in the fullness of time we might well find it partially responsible for the epidemic of obesity and type II diabetes. The FDA is still doing Phase I/II/III clinical trials despite all the evidence in favor of adaptive trials. And tens of millions of people were irradiated by TSA x-ray scanners fast-tracked through the FDA approval process, scanners criticized by UCSF scientists, scanners which have now (finally) been withdrawn. These errors are magnified in impact because no one can opt-out, because a .gov has a bully pulpit, and because strong political incentives exist to silence criticisms.

Third, if people have the right to euthanasia, or the right to walk near bridges, I do believe they have the right to try what treatments they want. Frankly I don't consider someone else's medical affairs my business, anymore than I'd ask why they had an abortion. You can argue that vaccinations present a public health issue, and I might agree with you there. But otherwise this strikes me as a right to privacy and right to bodily integrity issue.

http://www.cato.org/pubs/regulation/regv27n2/v27n2-8.pdf

http://marginalrevolution.com/marginalrevolution/2011/10/and...

http://fdareview.org/harm.shtml

  The delay and large reduction in the total number of new 
  drugs has had terrible consequences. It is difficult to 
  estimate how many lives the post-1962 FDA controls have 
  cost, but the number is likely to be substantial; 
  Gieringer (1985) estimates the loss of life from delay 
  alone to be in the hundreds of thousands (not to mention 
  millions of patients who endured unnecessary morbidity). ... 

  If the U.S. system resulted in appreciably safer drugs, we 
  would expect to see far fewer postmarket safety 
  withdrawals in the United States than in other countries. 
  Bakke et al. (1995) compared safety withdrawals in the 
  United States with those in Great Britain and Spain, each 
  of which approved more drugs than the United States during 
  the same time period. Yet, approximately 3 percent of all 
  drug approvals were withdrawn for safety reasons in the 
  United States, approximately 3 percent in Spain, and 
  approximately 4 percent in Great Britain. There is no 
  evidence that the U.S. drug lag brings greater safety.

The only way to prove this definitively is a side-by-side experiment with a new jurisdiction in which patients and entrepreneurs alike are free to choose and the FDA has no power.

Both of those are fine as preferences. The trouble arises because every US citizen is forced to have the global minimum of risk-tolerances across the population. It would be as if you could not try a development version till it became user-friendly enough for your grandparents. Specifically, in the US, you can't be an early adopter: the FDA does not allow citizens to opt-out unless they leave the borders of the USA. Indeed, in Cowan vs. US (1998) it successfully sued in federal court to prevent a dying AIDS patient from trying an experimental drug:

http://www.leagle.com/xmlResult.aspx?page=4&xmldoc=19981...

  Plaintiff requests that Dr. Davis be authorized to inject 
  Plaintiff with the with the experimental goat neutralizing 
  antibody drug [1] and that the FDA be enjoined from 
  interfering with Dr. Davis' treatment of Plaintiff. ...

  The Court is sympathetic to Plaintiff's situation. 
  However, the law is very clear, and under the current 
  statutes and regulations, Plaintiff's physician may not 
  administer the goat neutralizing antibody drug absent 
  prior approval of the FDA. In Court, Plaintiff argued that 
  he should have the right to take whatever treatment he 
  wishes due to his terminal condition regardless of whether 
  the FDA approves the treatment as effective or safe, and 
  that to prohibit him from taking the treatment he wishes 
  violates his rights under the US Constitution. ...

  This Court is in no way criticizing the intentions of 
  Plaintiff and his physician or the potential effectiveness 
  of the proposed treatment. Plaintiff's physician should 
  pursue approval of his Investigational New Drug 
  application as quickly as possible. Plaintiff's doctor 
  must obtain appropriate approval through the proper 
  regulatory authorities. As much as this Court may 
  empathize with Plaintiff, the authority to provide some 
  type of exemptions for individuals such as Plaintiff rests 
  with Congress and not with this Court.

http://blogs.wsj.com/health/2008/10/17/lance-armstrong-and-b...

  “We did a safety review, consulted with experts on PML, 
  and worked closely with FDA to come up with a risk 
  management program that allowed us to bring it back on the 
  market in a way that limited its use,” a Biogen 
  spokeswoman told the Law Blog. The plan prohibits giving 
  Tysabri for unapproved uses.

  Biogen Idec is running an early-stage trial of the drug in 
  multiple myeloma, but Baron doesn’t meet the criteria to 
  participate.

  Baron’s a prominent donor to the Democratic party, and 
  many of his powerful friends, including Lance Armstrong 
  and Bill Clinton, made appeals on his behalf. And the 
  family agreed not to sue if anything goes wrong.

  Ultimately, his doctors at the Mayo Clinic worked directly 
  with the FDA to find a “legal basis” for giving Baron 
  Tysabri. The deal was announced on Baron’s son’s blog late 
  yesterday.

But this is not really optimal. If you are an academic, you accept the concept of QC/quality checking, but you aren't stuck with just one journal to submit to. You can revise and resubmit somewhere else. And if you are an end-user, you don't have to take a reviewer's opinion into account when choosing between movies, books, bikes, or virtually any other physical good with star ratings on Amazon.com. Except for drugs. Then you, as the end-user, cannot opt-out and take the FDA's opinions with a grain of salt. In part this is because the FDA will sue you directly. In part it is because companies that even think of trying this route will get slapped by the FDA for trying to game the system, and subsequently find their approvals slowed or (nowadays) outright denied.

We need to carve out a jurisdiction where patients and entrepreneurs alike are free to take informed risks, recognizing up front that sick people do die in medicine, and also recognizing that society already allows people to take incredible risks in other contexts (joining the military, bungee jumping, walking tightropes). Whether that new jurisdiction is Singapore, or Estonia, or a seastead, or a medical cruise ship, or something else is to be determined. But that has to be the goal.

[1] In case a "goat antibody" sounds weird to you, it's a common thing in molecular biology. Google it, or see for example Thermo's web page: http://www.pierce-antibodies.com/custom-antibodies/goat-anti...

  I remember reading an academic article that showed how the 
  real cost was almost always 1/20 of that

The best response to Light and Warburton is that if it really took only $43 million to ship a drug, then they should raise the capital and start a drug company. It would be by far the most capital-efficient and successful drug company of the last 50 years. If they have really figured out how to cut all the fat, they would be hailed throughout the industry.

But I hope to persuade you that when someone outside the industry is off by two orders of magnitude ($43M vs. $4B), it is likely that they are the ones who have missed something important. I encourage you to read Derek Lowe's more detailed critique here:

http://pipeline.corante.com/archives/2011/03/07/the_costs_of...

http://pipeline.corante.com/archives/2011/03/08/that_43_mill...

  It's faster to run experiments on animals than people. 

  I think you are vastly overestimating what society has to 
  gain by deregulating medicine. You'll get a one-time gain 
  of 10 years of progress at the cost of an unknown number of 
  lives.

In scenario I, we do it status quo and safe, with no deaths. Very generously, let us grant that a cure appears in 10 years. This is generous because a regulated market may never iterate upon the cure if it is radical/different (e.g. Barry Marshall and H. pylori).

In scenario II, we accelerate the cure in a deregulated market. The R&D phase takes 1 year and costs us 100 deaths from test pilots / early adopters; the scaling phase takes 2 years and costs us another 900 deaths from volunteers. These numbers are vastly in excess of any reasonable safety testing paradigm in a deregulated space (no one died in Banting & Best's experiments) and I cite them as extremely conservative upper bounds.

Ok. Then in scenario I, the status quo, you had

  - 0 die from testing
  - cure appears at end of 10 years
  - 10 million people die over those 10 years
  - 10 million deaths

  - 1000 die from testing over 3 years
  - 3 million die from disease over those yeers
  - cure appears in year 3
  - no further deaths
  - 3 million + 1000 total deaths

And we kind of know what a safe-but-not-necessarily-effective market for drugs will look like: the supplement industry. Supplements are cheap, they vary in effectiveness on a per person basis, and they have undoubtedly produced some really great things (creatine, omega 3). Take a look at this awesome graphic:

http://www.informationisbeautiful.net/play/snake-oil-supplem...

The thing is, with centralized regulation for efficacy two things happen. First, many of the bubbles on that graph never appear in the first place. Second, because they never appear, they never accumulate enough evidence/market size to rise up the list. We are choking the channel if centralized regulators require our minimum viable products to be not just safe, but highly efficacious.

The best way to see this is that centralized regulation kills iteration. Talk to anyone in the drug space: they'd love to be able to change their dosing methodology (altering dosage amount, frequency, formulation) or otherwise take advantage of serendipitous post-market findings. Viagra, famously, was initially intended to medicate blood pressure[1].

But right now they can't even change the labels on their drugs without the FDA's approval, which is why the average layman gets a folded-up chemistry textbook[2] rather than a user-friendly instruction manual, let alone a website which totes up other people's experiences with the drug. To get a sense of how much that could contribute to the patient user experience, see Help Remedies[3], which can get away with better UI/UX because they're dealing in generics.

Anyway, on net, I think something like a pharmacogenomic erowid.org [4,5] is the best way to establish efficacy. That would be distributed and the data would be public and constantly updated, with sample sizes far in excess of the current FDA process. Patients would get accounts and link their genomic information with the site after buying any new drug, and input their own survey data in order to see other people's (aggregated, anonymized) experiences. This would mean that you can launch safe drugs of unproven efficacy, and then collect efficacy data at a far larger scale than we do today. But this kind of innovation will only be possible in a jurisdiction outside the FDA's thumb.

[1] http://www.mc.vanderbilt.edu/lens/article/?id=116

[2] http://dailymed.nlm.nih.gov/

[3] http://www.helpineedhelp.com

[4] http://www.pharmgkb.org/

[5] http://www.erowid.org/

1) First, FDA fast-tracks many bad things. Hundreds of millions of people were irradiated by scanners that FDA waved on through because a fellow .gov agency (TSA) sponsored them. So: even the risk-averse can't trust a single centralized regulator to be "risk-averse" rather than "pro-government". We need multiple regulators (see my posts elsewhere in the thread), where you can use things approved by the slower/expensive/safest one while I can use items approved by the faster/cheaper/riskier ones.

http://arstechnica.com/science/2010/11/fda-sidesteps-safety-...

  Dr. Holdren passed the letter on to the Food and Drug 
  Administration for review. But, in the FDA's response, the 
  agency gave the issues little more than a data-driven brush 
  off. They cite five studies in response to the professors' 
  request for independent verification of the safety of these 
  X-rays; however, three are more than a decade old, and none 
  of them deal specifically with the low-energy X-rays the 
  professors are concerned about. The letter also doesn't 
  mention the FDA's own classification of X-rays as 
  carcinogens in 2005.

http://www.myraqa.com/blog/how_long_is_90_days

  By law, FDA must respond to your 510(k) within 90 days, and 
  typically they do. The thing you have to understand is that 
  FDA measures 90 days about the same way the NFL measures 
  the 60 minutes in a football game. It's not unusual for the 
  clock to spend more time stopped than running.

Thalidomide in particular is to the FDA what 9/11 is to the TSA, it's the justification for everything they do. If you get into the history books you'll see that Frances Kelsey never actually suspected teratogenic effects; she suspected neurological issues. Moreover, thalidomide was actually a very efficacious drug for morning sickness, it was just unsafe. Yet the 1962 revision to the FD&C act added efficacy testing on top of safety testing.

That's weird. The thing is, toxicological/safety testing, even aggressive safety testing is "only" in the tens of millions, not billions. It's efficacy testing (and then comparative effectiveness) that really piles on the dollars. If the lesson of thalidomide was that we should do aggressive safety testing, then no one got the message, because Kefauver & Harris' 1962 amendments to FD&C meant we ended up spending several hundred billion dollars on efficacy instead.

Perhaps then the lesson from thalidomide might be that pregnant mothers should be much more risk-averse in what drugs they take. It's not really a lesson that says "we need to delay all drugs more", because due to pharmacogenomics some side effects are only going to be apparent when you introduce them into humans on a large scale anyway.

Moreover, risk can't be eliminated, and different people will have different risk profiles. What if a 70 year old man with terminal cancer wants to take an experimental, non-FDA approved drug? Do you sue like the FDA did in Cowan vs. US to prevent him from doing so?

For that matter, what if a 25 year old pregnant woman wants to take a new drug? Do we prevent her from doing so? Maybe we should, but we currently don't stop pregnant women from drinking alcohol or smoking cigarettes.

One has to think very carefully about whether every tragedy means one must ban or mandate something with a federal law.

Regarding patents, they are a form of artificial scarcity on the sales end. Regulation is a form of artificial scarcity on the R&D end. That's why regulatory affairs and IP are the two most important departments in any pharma company.

It's useful to think about what the pharma industry would look like with no FDA and no IP protection. It'd look a lot like food, energy drinks, or supplement manufacturers, making commodity products with marketing as the primary source of margin. Generic drug manufacturers are a good first step towards this; we'll see more of this in the near future with the pharma cliff and end of many major drug patents.

Incidentally, the intersection between regulation and IP produces some extremely bizarre behavior:

http://www.fda.gov/downloads/Drugs/.../Guidances/ucm079342.p...

  This guidance is intended to provide industry with 
  information on how the Food and Drug Administration (FDA) 
  is applying the 180-day generic drug exclusivity provisions 
  of the Federal Food, Drug, and Cosmetic Act (the Act) in 
  light of recent court decisions. The guidance
  addresses the issue of the elimination of the "successful 
  defense" requirement, which required an abbreviated new 
  application (ANDA) applicant to be sued for patent 
  infringement and to prevail in the litigation to receive 
  the 180-day period of marketing exclusivity.

I can get into the duct-tape upon duct-tape that led to this bizarre state of affairs, but think about how perverse it is that the FDA was telling companies to break patent law (or at least risk a civil lawsuit) as a matter of policy. That's the kind of thing you uncover when you actually look at how regulations are implemented.

Finally, regarding funding, yes, NIH spends about $31B per year, which is a lot. However, drug companies spend $4B per drug approved[1], which is an incredible amount of money when multiplied across all drugs. I'm not sure exactly how one could stop drug companies from profiting from public domain research as you propose. Are you saying that NIH should get into the business of drug development and/or not allow its funded academics to publish papers or start drug companies?

If you are saying the former, I actually happen to agree that NIH would be reasonably good at drug development, as Francis Collins has proposed, because as a fellow .gov it would be able to play hardball with the FDA in a way that no normal company could. Among other things, it wouldn't fear going out of business, and would be able to appeal to the HHS secretary if FDA retaliated against it. On the other hand, this new NIH-to-FDA pipeline would lose a lot of checks and balances; it'd sort of be like HHS as the large drug co with NIH as the scientists and FDA as the regulatory affairs, without any real check by the market other than the nationalized drug companies of other countries.

Think about how the FDA fast tracked [2] things like TSA body scanners and you'll get a sense for what its actual commitment to safety is when it's a fellow .gov that is sponsoring a drug/device.

As a final point, if you meant instead that NIH should be abolished and academics should stop publishing papers, I think we will actually see the implosion of the US higher ed research establishment over the next 5-10 years due to MOOCs and budget cuts, so that may come to pass as well.

[1] http://www.forbes.com/sites/matthewherper/2012/02/10/the-tru...

[2] http://arstechnica.com/science/2010/11/fda-sidesteps-safety-...

  approved treatments in humans often lag 10 years or so 
  behind what's known to work in animal models

http://www.nobelprize.org/educational/medicine/insulin/disco...

  Early in 1921, Banting took his idea to Professor John    
  Macleod at the University of Toronto, who was a leading 
  figure in the study of diabetes in Canada. 

  Banting and Best began their experiments by removing the 
  pancreas from a dog. ... By giving the diabetic dog a few 
  injections a day, Banting and Best could keep it healthy 
  and free of symptoms.

  The team was eager to start testing on humans. But on whom 
  should they test? Banting and Best began by injecting 
  themselves with the extract. They felt weak and dizzy, but 
  they were not harmed.

  In January 1922 in Toronto, Canada, a 14-year-old boy, 
  Leonard Thompson, was chosen as the first person with 
  diabetes to receive insulin. The test was a success. 
  Leonard, who before the insulin shots was near death, 
  rapidly regained his strength and appetite. The team now 
  expanded their testing to other volunteer diabetics, who 
  reacted just as positively as Leonard to the insulin 
  extract.

  The news of the successful treatment of diabetes with 
  insulin rapidly spread outside of Toronto, and in 1923 the 
  Nobel Committee decided to award Banting and Macleod the 
  Nobel Prize in Physiology or Medicine.

What if we tried that today?

You mean, just rely on the judgment of the experts involved and the verbal consent of the patients?

You mean, just allow the doctors to come up with whatever dose they felt warranted and patients to take whatever dose they feel comfortable with?

You mean, resist having some kind of ostensibly judicious central authority approve all such decisions, and rely on the distributed judgments of all consenting participants involved?

Yes. The typical response is that this is a recipe for anarchy. But history shows that it is a recipe for Nobel Prizes, and it is not like 1920s America was much like Somalia.

Would there be risk? Sure. Some people will not be helped and others might even harmed by new and unproven treatments. That's the price if we're serious about rapid progress, or really any progress. There must always be a first human trial; why not as soon as possible if people really are dying?

Needless to say, this kind of boldness won't fly in the modern US. Outside of the internet, the country has become just too risk averse, too wealthy to pay the price of progress. Our task as hackers then is to create at least one spot on this earth where patients can take whatever treatments they want, where entrepreneurs/technologists can invent whatever drugs/devices they want, and where no regulator has the power to intercede between these two consenting parties. And where we can go from idea to human trials as fast as the patient pleases.