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So this guy criticises recycling by creating an economic model that fails to take into consideration externalities of product consumption and discard. Not a very useful model and we would do well to not pay it much heed

Taffy's story is awesome. Thanks for pointing me to a great read.

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There is no Roman numeral m only M, so if they are sticking with convention shouldn't it be capitalised?

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Probably because it's not a numeral, but rather an abbreviation for mille.

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This argument is pure propeganda from the pharmaceutical companies.

The modern world of lifesaving pharmaceuticals exists despite the American market's attempts to subvert it, not due to its largesse

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Your comment is not an argument. You are just stating that you disagree with nothing to back it up. It adds nothing to discussion. And accusing me of "propeganda" is just juvenile and uncalled for.

But if you really believe that, hen why are so many of these drugs developed in America? Why aren't other countries inventing way better drugs?

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My comment may not be a persuasive argument, but either is yours. Where are your facts? Your referenced points? You state just as much opinion as I do.

So, let's go through a quick run-down of the 'major' pharmaceutical companies of the world, and where they are headquartered.

Company Revenue (USD) Headquarters

Novartis 53.6 Bn Switzerland

Roche 47.8 Bn Switzerland

Sanofi 36.9 Bn France

GSK 34.9 Bn UK

AstraZeneca 26 Bn UK/Sweden

Bayer 43.4 bn Germany

Baxter 15.3bn US

Pfizer 49 Bn US

Merck 42.23 Bn US

BMS 18.8 bn US

So, 4 of the top 10 pharmaceutical companies by revenue are headquartered in the US. By Revenue, those 4 account for 125.3 Bn out of a pie of 367.9 Bn; or 34%.

It is not easy to get a list of the number of drugs under clinical trial, or the number of drugs that were recently brought to market by various manufacturers; and, as a side matter, a number of the more innovative drugs brought to market recently were all developed by small pharmaceutical companies (Boceprevir, Telaprevir, Imatinib, Ipilumimab) that were later acquired by the big boys. So a small pharma company did the innovating, usually funded by a university or the product of particuarly profound insights by PhD students; turned into successful drugs; run through to the stage 3 trial stage and then, once all the development costs are done and dusted, acquired for a discount price of the predicted future revenue stream

So tell me, where are all the drugs being developed by america? I would say the rest of the world is more than pulling it's weight. In fact, given rough population parity between the European first world and the United states, it could in fact be argued that the United states is not pulling it's weight.

I await your reasoned response

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My comment was actually an argument - that the cost of drugs is necessary to fund their development. Your comment was just stating that you disagree, with no argument.

It's certainly interesting that Europe has more drug companies headquartered there. Though that doesn't necessarily mean all their operations and revenue are in those countries, but whatever.

It's irrelevant because Europe still has a patent system and still sells drugs to the US under our system. It's not like India where any company can manufacture the drug and patents are rarely enforced.

As for university funded research being sold privately, I agree that is sad and should be illegal.

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Medications are not easily ameniable to arbitrage as they are not classified as equivalent goods with regard to customs- special licenses are required (often) to import them.

Plus, there are quality issues with third world drugs (which may or may not be valid) which rear their head when buying sight unseen

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I'm not quite sure how paragraph 2 follows from your first paragraph?

coild you describe your point more clearly?

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The existence of whistleblowers doesn't invalidate every possible conspiracy theory. We can't assume comprehensive awareness by proposing: If that were true then it would have been leaked. Every known government secret is eventually revealed. That's a tautology. Generalizing it to every imaginable secret is a failure to understand the limits of inductive reasoning. The people who know how much Snowden knew regularly indicate that they still have more to hide. I'm suggesting that our awareness is limited to a variety of "lesser" secrets. These secrets are callously and ineptly executed by design. They inspire whistleblowers to act before they become aware of "greater" secrets. Their revelation also, apparently, lulls the public into complacency. Exposure to "greater" secrets is gradual and divergent. We will never be fully aware of what mk-ultra involved. Most of the documentation has been destroyed. It was actually kept secret despite being far more sinister. It's the greatest (known) example of this fallacy. The documents with "tens of thousands, perhaps a hundred thousand people in positions to read them" weren't leaked intentionally. They were discovered because they had been improperly filed and, for that reason alone, survived destruction. Alien visitation is extremely unlikely for numerous reasons. We don't have to go nearly that far to support a potentially actual conspiracy. We need only assume that the perpetrators are motivated by power and/or have advanced technology. They were able to hide a mind control program utilizing torturous methods 40 years ago. My point was that its worth conjecturing about what they may be doing now. They have apparent motives and we can extrapolate realisticly advanced technology. My second paragraph was just an example I threw together in the spirit of that activity.

TL;DR: Just because I'm paranoid doesn't mean someone isn't out to get me.

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thanks

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I haven't heard much about CRISPR-Cas9 in population studies/experiments like this - my understanding was that you need to insert the RNA. Since RNA is so unstable it is usually a 'one shot' process transfecting cells with plasmids through infusion.

Is the proposed mechanism to release a virus with the appropriate RNA scaffolds in the wild?

This strikes me as extremely dangerous

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No you introduce it into the genome of the mosquito and then release the mosquito. No virus involved. It is best to read the paper and its references.

What makes you think it is dangerous?

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I haven't seen the paper. Was it referenced in this thread?

If you're just genetically engineering the mosquito to be unable to transmit the virus, I can't see the harm in it. But if you are releasing a virus to act as your vector for genetic modification of the mosquitos, then I would think that has the potential to veer wildly off plan

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The paper is linked at the top of this whole thread. The technology could be used to prevent transmission or drive the mosquitos to extinction. Preventing transmission is harder because there are so many diseases to prevent.

How do you think it might veer wildly off plan?

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My bad re article.

Using a virus as a vector? The highly mutable nature of a virus. It's been engineered to perform a specific function, and within some limits of mutation it will still perform that function. There's a wide range of further mutations that will perform no noticeable function, and then there's a small space where it might do something that no-one expected. I mean, let's not get all doomsday about this - viruses are mutating and changing and leaping species all the time. We never know what nature will do for itself and how those effects will percolate through ecosystems.

My strongly held view is that we should be not be engineering with vectors. I do and have for a long time believed that species engineering (such as with this proposed system, although I was unaware of it until just now) is the way forward.

When I was completing my Biochem major I used to dream about ways to engineer our pestilent species out of existence, rabbits, cane toads and carp. Although in 2009 CRISPR wasn't even published and most of my thoughts revolved around chromosome engineering and X inactivation schemes to wipe the males of the species out. Not surprisingly, I wasn't the first to think of it and there was some great research out on those subjects

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Can you explain what the advantage of the gene drive system is here? Looking at the paper, I see "Cassette exchange progeny" was only successful 0.05-0.38% of the time (table 1). So they need ~10,000 flies to get 10 mutants. Then in Supp Figure 3 I see detection of the "modified" DNA in the WT flies, and Figure 1c shows a good proportion of WT flies (denoted as "+/+" in that figure) were infertile as well!

So it seems if we just select those pre-existing infertile mutants we can get the same effect as using all these gene modification and gene drive techniques. I don't see what the advantage is supposed to be.

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Sorry for the long delay. I think the problem is you need to understand what a gene drive is to understand the significance of this work. Have a look at the second paper I linked to and also George Church's I link lower down.

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The best evidence today actually says that you don't need to finish your course [0]. Not that you are wrong in the human consumption aspect. but finishing courses could strengthen resistance and spread of resistant organisms by creating a selective pressure in the organism (the human) to only have bacterial colonization from those that are resistant

[0] https://www.mja.com.au/insight/2015/5/stop-antibiotics-exper...

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While that's interesting I don't think it's "best evidence".

Unfortunately our mechanisms for determining best evidence are woefully slow, complex, and expensive. Systematic reviews, for instance. Either this process needs to be improved (an excellent candidate for AI) or a nearly-as-good surrogate needs to be supported by policy makers.

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what are your thoughts on how an AI would perform this task?

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My thoughts on this are loosely formed :)

However....

The systematic review and meta-analyses processes involve reading screeds of text and data; organising it; analysing it; weighing it against measures of quality; and conducting (often counter-intuitive) statistical procedures.

This is the sort of thing that takes humans a loooooong time and is prone to error. A domain-specific AI would surely excel at tasks like this.

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There is so much ... hype around this technology. But some of their use cases aren't all that useful, and their technology (while supposing to be cheaper) is often done on handheld units at the moment in isolated regions.

Let me explain:

Use cases outlined in this article that have minimal real medical benefit, but sound great:

- Home blood testing (why? there are only 2 types of people who may find this useful: patients on Warfarin, and patients on dialysis. Dialysis patients (if not on home dialysis) get tested 3 times a week when they go to dialysis. INR is usually stable once established, ceteris paribus)

- Field blood testing (Mostly pointless. Clinical signs are much more useful in a casualty situation. Arterial blood gasses are useful in resus rooms in emergency departments but in the field you want to keep them breathing, not go reversing exotic blood gas abnormalities)

For the majority of tests (EUC, CMP, LFT, FBC, Coagulation studies) in rural/isolated places, the i-stat machine is used in australia. This is priced ok... around $40 per cartridge for around 6-10 results.

The i-stat works with not much more than a couple of drops of blood as well, although it needs to be drawn from a vein, not a finger-prick.

Other tests, like lipids, or antibody markers, etc, are rarer and much more expensive. It would be great to have them cheap (but again, we don't really know how cheap theranos is saying tests are going to be) which may make them more common, but again there just isn't much benefit in taking them regularly.

Theranos may well be a white elephant. which is unfortunate. The promised technology (fingerprint testing) would be great. But I can't comprehend how they could go for 12 years without a product. And as a doctor, I would be very suprised if the technology works as advertised. There is unfortunately too much hype surrounding this product for me to believe that we will get what has been promoted, but you never know and I would love to be pleasantly surprised.

I wonder how popular this viewpoint will be here on HN - the home of lifehacking and microanalysis of bodyfunction (often without the corresponding knowledge to go with it, but prefaced with a view that 'more data will always be better').

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My biggest concern with Theranos, which I haven't really seen acknowledged in any of these articles, is that multiparametric panels on asymptomatic individuals will lead to a proliferation of false positives. Running hundreds of tests whenever a patient decides to do so doesn't make sense unless that ultimately enables better clinical outcomes for patients. And this is true regardless of whether the underlying measurement technology that Theranos has developed actually works or not.

It's discussed in a journal article from earlier this year by a pathologist:

> panel profiling, which was introduced in the 1970s as a way of identifying early biochemical changes of disease in asymptomatic individuals, had been abandoned in the 1980s, not so much for the cost. It has long been realized that with multiparametric testing, approximately 5% of results will be false positives, i.e., test results outside the reference intervals, in otherwise normal subjects. This is due to the definition of reference intervals, as being values between the 2.5 and 97.5 percentile of a reference (normal) population. The high cost of investigating seemingly abnormal results in normal people, and the added anxiety of patients, has led to the complete replacement of such biochemical profiling with what is now known as “discrete testing”. In the latter, tests are performed by the testing laboratory, only if requested specifically by the physician.

http://www.degruyter.com/view/j/cclm.2015.53.issue-7/cclm-20...

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This is a really valid criticism. I often send patients home from the emergency department with values outside of the normal, usually without discussing that finding with them (ie, it is not useful for a patient with some level of kidney failure to know that their sodium is 130, and has been on every presentation they have had for years). Trying to have a conversation with every second patient about why this value is slightly outside of reference and how the reference ranges are actually calculated is not productive and will likely only lead to confusion and obsfucation of the actual reason they presented

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The medical community should reconsider the standard policy of not having that conversation. While it may be medically sound practice, the insurance industry takes these reference values as Gospel Truth. Your life insurance premiums and coverage are predicated on how much deviation you exhibit from the reference ranges.

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Only in countries that are allowed to differentiate on the basis of lab tests. Which is not the case where I practice.

If a lab result is outside the normal range and a patient has a reason for it to be outside the normal range, that's fine. If a patient has a deviation that is related to their presenting complaint, that's fine too. If a patient has an unexplained deviation which is not related to the presenting complaint, well, there's a 1 in 20 chance that the variation is statistical only. So you use your clinical judgement. is this a patient who requires outpatient follow-up and repeat, or is this an abberation?

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Actually, there is a one in twenty chance that a normal person would generate the results in question. Not the same thing.

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I have several people in my family who demonstrate various levels of hypochondriasis. Imagine the nonsense over gluten-free and every other fad diet of the last 30 years, non-specific symptoms, alternative "medicine" and that's two or three people in my immediate family. Now let them start ordering their own blood tests and it'll make the anti-vaxing movement look like a cultural blip.

Most people simply aren't smart or informed enough to understand things like "false positives".

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> I wonder how popular this viewpoint will be here on HN - the home of lifehacking and microanalysis of bodyfunction (often without the corresponding knowledge to go with it, but prefaced with a view that 'more data will always be better').

This would be what I see as the fundamental flaw behind Theranos, even if their technology worked (works?) as promised: the idea that more data will always be better is sophomoric (and I select that word judiciously, considering the founder). Evidence-based medicine clearly shows that more data does not, in itself, lead to a better outcome.

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My startup facilitates at home testing of PT/INR levels (for coumadin/warfarin patients). In general, yes, INR levels stabilize, medicare won't pay for at home testing until the patient has been on warfarin for 90 days. However, it is surprising how many critically high or low results we get in an average week.

Studies [1] show that weekly INR testing results in a 55% reduction in strokes, 35% reduction in major bleeds and 39% reduction in deaths.

[1] Henagen C. et al. Lancet 2006; 367:404-11

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I was hoping the product would pivot to passive blood pressure monitoring. I want my blood pressure to be recorded every few seconds, logged and cross-referenced against what I did, ate, and drank. For correlation purposes, knowing those things can be as simple as snapping a photo.

Smart people apparently claim that blood pressure is one of the most reliable indicators of how long you'll live. If so, then it's always seemed strange it's (almost) never measured.

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Now that would be a cool product. Lots of datapoints. I'm skeptical about the claim - yes, it's important, but there are so many variables that feed into it, and I need to be convinced that constant, 24 hr monitoring of BP would enable better management than spot tests, home BP management and the occasional 24 hr ambulatory monitoring.

It's a very consumer-targeted technology, although it would certainly find a place in emergency departments and ICUs. I am at a loss to think of ways as to how we would actually capture the data, although better minds than mine I hope come up with ways.

The problem is that to get a good read on arterial pressure you either need to do it the old fashioned way (occlude the artery and record that pressure, then slowly drop it until it's constantly flowing again - see [0]) - or you need to stick a cannula into an artery, as we do in ICUs, and measure pressure using a transducer.

Even technologies that stress their 'passivity' (see [1]) and try to capture this market use the old fashioned way. I don't see that changing anytime soon - you could try and somehow monitor the stretch of a small artery maybe using some variation of current o2 saturation sensors, coupled with advanced computer models of flow rate and variation in small arterioles, but that is a world away and would seem to me to be highly subject to variation/sensitivity.

My prediction is that this won't be possible until we are commonly implanting biometrics in people, but I guess we will wait and see!

[0] https://en.wikipedia.org/wiki/Korotkoff_sounds [1] http://www.visimobile.com/

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It seemed promising to do some experiments with sewing a BP sleeve into a shirt, then setting up an Arduino to trigger it to inflate/deflate. It should be possible to record the result digitally. It'd be slightly uncomfortable, but even if it's only once per hour, it's still better than zero per hour. The noise would be annoying, but I have some ideas for how to make it quiet. But would anyone actually want such a thing?

Thanks for batting around the idea with me, and for the valuable references. I didn't know there was any other way to measure BP than the old-fashioned way.

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You're describing creating an ambulatory blood pressure cuff. I've had one attached to me and you get used to it fairly quickly, although it failed to measure blood pressure when I was active (I was cycling for a few of the readings, which you think would keep your arm fairly still and not cause a problem) Cool to make it yourself though! Have a look at these further links. The australian prescriber article you may find particuarly useful

http://www.racgp.org.au/download/documents/AFP/2011/November...

http://www.australianprescriber.com/magazine/20/1/18/20

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

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My mom is terminally ill and recently started experiencing orthostatic hypotension, so I just picked up an Omrom armband blood pressure monitor that is trivially easy to use and stores the last 100 measurements for two people.

http://amzn.com/B00KPQB2SS

It's still not what you want, but it looks like things are moving in the direction you suggest. That said, I'm wondering if it is even possible to do what you suggest without being inconvenient to the user. Having an armband inflate and tighten around my arm every few seconds with become infuriatingly annoying. Are there alternatively ways to measure blood pressure that are imperceptible?

What I'm looking forward to seeing is conductive textiles making their way into compression clothing so we can measure heart rate all the time. i.e. a wearable EKG shirt. The use case would be older people at risk for a heart attack and heart fail so we can detect problematic heart abnormalities that are predictive of failure.

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I'm guessing I got downvoted for linking to the product on Amazon. What's the appropriate way to link to something like that so that it doesn't get downvoted?

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You know, when I saw your original comment, it was so helpful that I wanted to respond to you and say thank you, but I suppressed my instincts because I thanked someone else, and it felt like the community would react badly to me saying "Thank you so much!" to every single person.

But now I see that the community actually downvoted your comment rather than rewarded it. Darn.

For what it's worth, and even though this reply is very late: Thank you so much for your time and for the thoughtful and helpful reply. The links, specifically, were the reason it was helpful to me.

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I think your comment was informative, your manner of linking was fine, and that you should ignore the downvote(s) in this case. I guess it might be slightly clearer to use the full "amazon.com" in the URL, and I suppose someone might argue that it's safer to indent it two spaces so it's plain text rather than an active link, but seems good to me as it is. Maybe someone clicked the wrong button, didn't like something else about your wording, or was just in a bad mood.

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Here's what England's NICE say about diagnosing hypertension. COmpare the difference between ambulatory measurement, and home measurement.

We know that most people can't even take their medication properly (many organ transplants fail because people don't comply with the medication regime, for example) so easier blood pressure monitoring would probably be useful. Especially if you combine it with something that can lower blood pressure.

http://www.nice.org.uk/guidance/cg127/chapter/Key-priorities...

> Diagnosing hypertension

> If the clinic blood pressure is 140/90 mmHg or higher, offer ambulatory blood pressure monitoring (ABPM) to confirm the diagnosis of hypertension. [new 2011]

> When using ABPM to confirm a diagnosis of hypertension, ensure that at least two measurements per hour are taken during the person's usual waking hours (for example, between 08:00 and 22:00).

> Use the average value of at least 14 measurements taken during the person's usual waking hours to confirm a diagnosis of hypertension. [new 2011]

> When using home blood pressure monitoring (HBPM) to confirm a diagnosis of hypertension, ensure that:

> for each blood pressure recording, two consecutive measurements are taken, at least 1 minute apart and with the person seated and

> blood pressure is recorded twice daily, ideally in the morning and evening and

> blood pressure recording continues for at least 4 days, ideally for 7 days.

> Discard the measurements taken on the first day and use the average value of all the remaining measurements to confirm a diagnosis of hypertension. [new 2011]

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Kenhub looks great. I recently completed the surgical primary exams in Australia, and before that knocked over a whole body dissection course.

I have some very different ideas about how anatomy could be ideally taught in some scenarios (which I am in the process of developing!) but certainly wish I had of had access to what looks to be an excellent resource you have developed.

It must have taken an age and a small fortune to get your own illustrations! would you ever consider a licensing deal?

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It was/still is our largest investment so far, and probably our biggest asset. Not just illustrations, but we also produce our own videos, write articles and more... We do license our illustrations to institutions, individual instructors etc. And we're always looking for ways to collaborate with others in this space. Medical education is an interesting niche. Shoot me an email and let's chat and see? (email on my profile)

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