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Comment: Re:How about the linked article? (Score 1) 140

by ponos (#47902975) Attached to: If We Can't Kill Cancer, Can We Control It?

Your criticism of the study I mentioned is reasonable, but in the domain of cancer treatment, a hazard ratio for death (a hard endpoint) of 0.67 is good and, in that sense, if you require much stronger evidence and even better trials you may deprive patients of a useful drug in the meantime. The FDA wants to strike a balance between getting an effective drug to patients as soon as possible and not letting pass ineffective treatments. So, as with most things in life, the kind of evidence I cited is often considered "good enough" even though imperfect.

The evidence for the impact of point mutations can be found in several domains, but the simplest observations comes from hereditary syndromes like Li-Fraumeni. A single change in a nucleotide of the TP53 gene and cancer risk increases to almost 100% in affected individuals. This has been repeatedly observed in many different famliies and also in different syndromes (say, retinoblastoma and RB1 gene). Anyway, the evidence for what is called the "somatic mutation theory" is overwhelming and, despite thoughtful criticism, it is probably accepted as the most plausible theory of carcinogenesis (for the moment!). That's why projects like "Cancer Genome Atlas" get massive funding.

So, yes, point mutations are extremely important. Aneuploidy is also important, but in contrast with a well-described mutation, like the BRAF V600E in melanoma, it does not present an immediate, specific target. As I said, people are working on aneuploidy and maybe something new will come from that, but I don't think it's a "low-hanging fruit".

PS Note that somatic mutations do not exclude aneuploidy and vice versa...

Comment: Re:How about the linked article? (Score 2) 140

by ponos (#47902173) Attached to: If We Can't Kill Cancer, Can We Control It?

"Nevertheless, having a targeted treatment is often better than no treatment at all."

Perhaps, but I doubt there is any good evidence for this. Weak effects and noisy data don't mix well, we are probably taught all sorts of incorrect things based on spurious results. I would suggest getting away from these targeted treatments of at most limited benefit and work on figuring out how to turn aneuploidy as a drug target.

FDA approval typically requires randomized controlled trials, so when a treatment is available it has been tested at least against placebo (if that was the best available treatment at the moment of approval). That's why I say "better than no treatment". A drug that is not better than placebo usually does not make it past the approval stage (and if it does, approval can be quickly revoked, for example bevacizumab in breast cancer: http://www.nytimes.com/2011/11...)

What sort of evidence would you expect? For example, the study which established the targeted agent trastuzumab is available online: http://www.nejm.org/doi/full/1.... Bias and noise are unavoidable, but with my knowledge of statistics the result seems reasonably clear.

Anyway, with respect to your other comment, aneuploidy is not an obvious target but people are working on it and on drugs that interact with the mitotic machinery. Let's hope they will be successful.

Comment: Re:How about the linked article? (Score 2) 140

by ponos (#47901697) Attached to: If We Can't Kill Cancer, Can We Control It?

Well, if the cancer cells are aneuploid (like the vast majority apparently are) and thus genetically unstable we shouldn't expect a targeted treatment like this to be effective for long.

Many targeted treatments have been disappointing in actual practice and very few are effective in the long term (imatinib is a good example). Nevertheless, having a targeted treatment is often better than no treatment at all. Furthermore, due to different, non-overlapping toxicites, these treatments are often feasible in patients who have received chemotherapy in the past or together with chemotherapy (trastuzumab, for example).

In the end, cancer is entropy. That's why it's hard.

Comment: Re:Baking Soda May Help! (Score 4, Insightful) 140

by ponos (#47901277) Attached to: If We Can't Kill Cancer, Can We Control It?

2) Consider the annual sales and profits of Big Pharma. Then the same for Big Food. IF there's a simple cure using natural food and basic ingredients that big pharma cannot patent, what's Coca Cola, Pepsico and other similarly large companies waiting for to steal big pharma's lunch?

Actually, if a cure was "known" Big Pharma "A" would want to produce it first and charge $$$$$, before Big Pharma "B" does it. It's not like Big Pharma works as a single organism. Multiple companies, competition and all that. Furthermore, don't forget "little pharma". The drug mentioned in the article comes from a little drug company, Agios, not some multi-billion behemoth.Several new drugs have been created by start-ups and were later sold. In fact, Big Pharma mostly does the last part of the pipeline (human trials, FDA accreditations and marketing) but the first part of the drug-discovery process often comes from little inventors who are not afraid to take risks.

I happen to know two people who are in the drug "startup" business and would be quite happy to make $$$$$ selling a cure for cancer to Big Pharma. These are the people that actually do in vitro/in vivo experiments and, trust me, if compound ZZZ were very effective they would be very happy to test it immediately, even if it meant loss of billions for other companies.

Comment: How about the linked article? (Score 5, Informative) 140

by ponos (#47901253) Attached to: If We Can't Kill Cancer, Can We Control It?

Let me give you a brief summary of TFA:
- Some cancers have IDH1, IDH2 mutations that change cellular metabolism
- This drug is the first targeting the IDH2 enzyme that has been tested in humans
- 6 out of 7 patients whose disease (leucemia) had the specific IDH2 mutations had "objective response" to the drug, ie the disease burden was reduced. Note, this does not mean cure.

Now, this is obviously good news, in the same spirit as previous targeted agents like vemurafenib, erlotinib, trastuzumab, crizotinib, especially since it concerns a new aspect of cellular functioning (metabolism). It's too early to say whether the drug will have long lasting impact, but we'll know more after phase II/III trials. It does seem promising.

For patients with AML or MDS and documented IDH2 mutation, the study (NCT01915498) is still recruiting in several centers around the US and in Paris/France (Institut Gustave-Russy). More information can be found in clinicaltrials.gov (http://www.clinicaltrials.gov/ct2/results?term=NCT01915498&Search=Search).

Comment: Learning is hard (Score 1) 182

by ponos (#47898457) Attached to: The MOOC Revolution That Wasn't

In other news, learning is hard. What did you expect, that people would magically learn the hardest of subjects simply because it is on t3h internetz? I have done MOOCs and I think it's great. I got the chance to hear some famous professors, read some good textbooks. I never expected it to be simple and I had to abandon some courses, but the final result is a net positive: I finished 2-3 courses I would never have had otherwise. So what if I didn't do the other 3 or 4?

Too much hype leads to disillusionment, as usual, but MOOCs have their place.

Comment: Custom software (Score 1) 207

by ponos (#47896009) Attached to: Early iPhone 6 Benchmark Results Show Only Modest Gains For A8

Apple has absolute control of the software ecosystem and can probably gain significant performance from appropriate optimizations. The android landscape is much more heterogeneous and probably less optimized for each individual device. Think consoles vs PC.

Raw benchmarks like this one may not properly reflect user's perception of performance when different ecosystems are compared. In the end, I expect the iPhone 6 to feel at least as fast as the fastest Android devices in real use cases.

Comment: Re:Not quite (Score 2) 228

by ponos (#47859785) Attached to: DNA sequencing of coffee's best use:

Not really, mainly because the two things we are talking about are consumed for their effect. Maybe I am not understanding your question?

Some of the effects are undesirable. Muscle tremor, anxiety are usually not reasons to drink coffee. Similarly, nausea and disequilibrium are not reasons to drink alcohol. With almost any pharmacologically active substance a spectrum of undesirable effects can become apparent before significant risk of lethality.

So, with reference to my initial post, I still believe that 1000mg of caffeine can induce toxic (not necessarily lethal, of course) effects that are, I suppose, undesirable for most people. I guess I can't make it clearer than that.

Comment: Re:Not quite (Score 1) 228

by ponos (#47856609) Attached to: DNA sequencing of coffee's best use:

This is the first hit I get on Google for "dsm iv caffeine intoxication". Immediately under the title text it says "These criteria are obsolete"

Indeed, you are right. The DSM-IV is still in use but, technically speaking, it has been replaced by the newer DSM V, which also includes a diagnosis of caffeine intoxication. I don't have a DSM V handbook within reach, but I'm sure you can find out the details.

Does the fact that people suffer from side effects before dying surprise you? Using the reference you provided above, people die (LD50) at about 490g of pure alcohol (ie >1lt of hard liquor), yet most would agree that toxicity is apparent way before that amount. Caffeine is similar.

Comment: Re:Not quite (Score 1) 228

by ponos (#47855185) Attached to: DNA sequencing of coffee's best use:

[quote]
Toxic levels of caffeine: 12,000 mg (for an 176 pound person) [just-think-it.com].
[/quote]
You are right with respect to the LD50, obviously referring to lethality. However, 1000mg of caffeine is certainly sufficient for caffeine intoxication as per the DSM-IV disorder (code 305.90). It all depends on how you interpret "toxic" in this context.

Comment: Consensus is about the process (Score 4, Insightful) 770

by ponos (#47853279) Attached to: How Scientific Consensus Has Gotten a Bad Reputation

I think there is a subtle difference between being right (in the usual sense of providing a model that happens to accurately represent measurable stuff) and the process of scientific discussion. Consensus is just an outcome of a process, ie collaboration. That process is extremely important but does not guarantee being right.

In the end, without resorting to unnecessary complicated terms, if a bunch of people who are supposed to know what they are saying all agree on something that is not immediately testable (say, long-term human impact on the climate), odds are they are more likely to be right than some random wacko or idiot reporter because they spent some time discussing together and have highlighted potential errors.

In the absence of definitive hard data, which will only be available in retrospect, we have to pick sides. Consensus seems a safer bet than the probability that some random guy is the new Galileo or Einstein.

Comment: Decaf makes some sense (Score 2) 228

by ponos (#47851853) Attached to: DNA sequencing of coffee's best use:

I imagine taste depends a lot on environmental factors, like soil nutrients, sun and stuff like that. Creating a genetically engineered plant is probably harder than simply improving culture conditions to get a good product. Although you could probably improve some aspects of the product by bio-engineering, in real life I don't think anyone will care to improve taste. Most probably they would sell you cheaper beans that resist infection or transportation or bad climate. I never heard Monsanto advertise their products as "great taste", but then again I wouldn't know.

Adding caffeine is also so simple that you shouldn't have to modify plants to get it. In fact, caffeine is dirt cheap (http://www.alibaba.com/showroom/caffeine.html). Even pharma-grade caffeine for the lab is like $0.50 for an almost toxic dose of 1000mg, if you want to "enrich" your coffee.

Decaf, if you enjoy it, would be an interesting bio-engineering project. I don't know if the plant really needs the caffeine for something else (it is somewhat related to DNA, being itself a purine), but simply deleting or attenuating the gene that catalyzes the conversion should be really simple. In fact, you don't need the whole genome sequence to do that, only the locus of the gene.

Anyway, bio-engineering something that tastes good and is healthy is probably at least as hard as all other aspects of the production, even if you have the DNA sequence. Being a fan of the KISS principle, I'd rather have my coffee prepared by people with some decent traditional know-how.

Comment: Re:It's a shame Creative will be suing this. (Score 2) 89

by ponos (#47794365) Attached to: RAYA: Real-time Audio Engine Simulation In Quake

There was a company back in 1997 that had a fantastic (series of) cards that did all this 3d transformation, reflection, deflection and occlusion of audio in hardware.

AMD TrueAudio on Kaveri processors and newer GPUs supposedly does just that. I haven't seen any game supporting it, though. Would be a nice feature I think.

Comment: Re:Enterprise grade AC (Score 1) 427

by ponos (#47636247) Attached to: Ask Slashdot: Life Beyond the WRT54G Series?

This is an expensive solution, but I am tempted. Is it better than the equivalent top-end consumer grade products like the Netgear R7000 or the Asus RT68? Specifically, I was thinking of the combination Ubiquiti EdgeRouter PoE + Ubiquiti UniFi AP AC which is almost $700 of gear. Is it worth it for a gigabit home network with a 300MBps fiber connection?

Wasn't there something about a PASCAL programmer knowing the value of everything and the Wirth of nothing?

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