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Logic 101 and XMRV

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by alex3619, Jun 1, 2011.

  1. alex3619

    alex3619 Senior Member

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    Hi aquariusgirl, I don't have any links, all the discussions were private. Some were on a research forum, some were to Vance Spence.

    High intracellular calcium would trigger prolonged acetylcholine activation in the peripheral vasculature, resulting in blood pressure drops. In my model this was postulated as a result of not elevated calcium itself, but elevated citric acid. Citric acid is a product of the mitochondria, and I will get back to that, but it is a powerful chelator. It can block both calcium and magnesium. The cell senses this, and so releases a massive burst of calcium to compensate when it needs to trigger a calcium signal. High levels of calcium will activate a molecule called calmodulin for up to six hours. Calmodulin will trigger nitric oxide and hence vasodilation. Blood pressure drops.

    The high citrate hypothesis was popular through most of the nineties, then it died. The mitochondria make it, and can release it, it also pointed to nitric oxide and peroxynitrite as these destroy the enzyme that converts it to something else. I discussed this at length with Marty Pall. This enzyme is called aconitase, and it has one other important property. It is not made in the mitochondria, but must be folded and imported. That folding process requires glutathione, and high oxidative stress makes the glutathione unavailable. I had long discussions with Rich on this topic.

    The evidence for citrate was high early morning urinary citrate in CFS patients (none defined as ME, it was not a diagnosis used then). They also found two other putative biomarkers. In around 2000 (I don't recall exactly) a UK group found that the other two biomarkers were breakdown products of two amino acids, serine and glycine. So they claimed the results were an artifact. However, they never explained why the breakdown occured. They only showed they could not find the two breakdown products in their samples. I do not recall what definition was used for the CFS patients - Oxford is likely, and so suspect, but it could have been Fukuda.

    This same team then went on to show the could not find elevated urinary citrate. Almost everyone considered the matter closed. I did not. First, they didn't show where the high citrate came from, why it was a "failed" test. Second, their protocol could not work, a point that most missed because they were unfamiliar with the original research. The original research stipulated very early morning citrate, at no other time of day. The tests fails at other times, a point the original researchers did not emphasize enough. This means the citrate is released during sleep, presuming the finding is correct. The UK counterstudy used fasting CFS patients - fasting causes citrate levels to drop. The presumption they used was that fasting is the same as sleeping. At no point did they state the urine samples were early morning after sleep. It might have been, but it was never stated.

    Now the body releases antioxidants during sleep, including melatonin. I was working on the "citrate flush hypothesis". Citrate is a great metal chelator. Theoretically it can flush the cells of divalent cationic metals, especially iron. I postulated that the mitochondria in CfS were releasing citrate overnight to flush the cells and remove metals, a known cause of oxidative stress. If this is correct, then many patients with oxidative stress, not just ME or CFS patients, could be found with high early morning (early waking is more accurate given our sleep issues) citrate.

    Now the citrate bursts will disturb calcium, and calcium is one of two critical intracellular messengers. It will disturb every path that requires calcium to trigger, but it will also disturb the other messenger. This is a complex pattern, and one I wanted to look into more deeply. Recently I have become interested again, but I do not want to discuss that just yet.

    I have not worked on my model in nearly a decade. It needs updating. Sorry for the long post, but you are only getting the highlights, not the details.

    Bye
    Alex

    ps Just to clarify a minor point, nitric oxide does not destroy aconitase, only temporarily inactivates it. Peroxynitrite does destroy it however.
  2. In Vitro Infidelium

    In Vitro Infidelium Guest

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    Pragmatically optimal is a condition that is perspective driven one needs to ask pragmatically optimal for who ? Much of the angst that surrounds the current discussion of XMRV, in my view results from an unwillingness to acknowledge that there a multiple interests in any human endeavour, all of which may have valid claims to a definition of what is pragmatically optimal. One can not use logic to differentiate between competing values other than by invoking an if, then process to provide an a priori notion of a preferred value. Certainly its possible to envisage a deductive process which yields an answer such as: if the maximal return (for example as expressed as effective treatment for CFS), is required, then action z is the pragmatically optimal option. Without the preset condition effective treatment for CFS there is no logical way to differentiate between option z and any other option, because the operant values of the processes under consideration have not been factored in to the process under examination.

    Im not suggesting there arent very real problems involved in the values and choices surrounding and underlying medical research but if we want to be able influence research direction, then we have to be able to engage with the human processes (what you call political) and that requires an acknowledgement of the (at least potential) validity of those multiple the values and choices that surround and underlay medical research. Identifying that which is not logically of our optimal interest as being evil will not place us in a position of being effective negotiators.

    Im not actually convinced by that the deductive position you have arrived regarding XMRV research is actually logically strong. If we start by describing the problem as a search task (find the cause of illness) then there are well understood optimal evolutionary driven patterns that have been described by biologists in the food searching behaviour animals . At the simplest level there are just two elements, localised intense searching, followed by movement to a fresh area, where intense search re-commences. The differential aspect between species is how much time has to elapse between achieving a reward of food and moving to a new location; in some species search is prolonged and movement to a new area is much delayed, in other species, the failure to achieve rapid success prompts movement to a new area. Continued survival of a given species maintaining a particular search behaviour is clearly related to how well suited the behaviour is to a given environment and the food type exploited by that species, but there is no logical differentiation between behaviours that differ by the delay/move relationship. My suggestion is that the current consensus approach of science as a social process, does actually yield a group signalling about the value of moving to fresh pastures that is likely close to optimal. Of course things will be left uninvestigated, but as a socially mediated process, the time to move on element is wholly logical.

    IVI
  3. In Vitro Infidelium

    In Vitro Infidelium Guest

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    To which the only reasoned response can be: Et tu quoque, though I do like the irony of being implicated (verging on sin ?) of being guilty of ad hominemism.

    IVI
  4. alex3619

    alex3619 Senior Member

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    I agree with nearly all of your post - I spent of lot of time studying artificial life, a computer simulation method for understanding group-think in simplistic animal models.

    The claims you make about value judgments are correct in my view, and you are essentially restating my own argument from a slightly different perspective. This approach is consistent with systems theoretic views of science and societies.

    I have tried to promote the view that those with differing opinions are not "evil", or "wrong" but have different perspective. This argument applies to anyone who is genuinely engaged, I would not extend it to trolls. For example, I sometimes disagree with your views, but I always try to understand them - one can't pursue any agenda without understanding other people's views. Simply asserting that someone is wrong because you disagree leads to a form of "group-think" in my view. Those who think like this flock together. It is not compatible with a search for understanding and solutions.

    Naturally I disagree that my own arguments are not logically strong, but then I cannot claim to be unbiased on that. My arguments are influenced by an 18 year involvement in ME/CFS research - this is not an argument that I am an authority, it is an argument that I have a defined position based on long history and current science, which leads to different value judgments and a different interpretation of current science than for some others. I expect there will be contrary views to mine, and it would disappoint me if there were not. Science cannot function properly if everyone agrees with everything.

    Bye
    Alex
  5. alex3619

    alex3619 Senior Member

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    Hi Angela,

    I have not had time/energy to follow up on philosophical history and modern philosophy. My position is based on basic philosophy, basic Popper, some systems training, and way too much time to think. I have been driven both by a need for perfectionism, and a need for pragmatism. My philosophical stance I have always considered a hybrid of Popperian and Skepticism.

    Danged if it does not have a name: Pancritical Rationalism. Bartley effectively espouses the philosophy I have been developing for myself, according to a superficial reading. Now I want to read more. :D

    Thank you for pointing me in this direction. I do wonder how my adoption of a systems position will modify his philosophy. It should be an interesting read at least, but it may be a while before I get hold if it - I think I will have to order if from Amazon, at $37 for the paperback, but there is at least one source I can go to locally that I will have to track down.

    I tried sending this as a pm but your inbox is full.

    Bye
    Alex
  6. Sing

    Sing Senior Member

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    Alex,

    Two questions and a comment:

    1. What are the episodic and semantic forms of memory?

    2. I take some Aricept before bed, which keeps acetylcholine from breaking down as fast, and it seems to help with memory. I remember dreams on it, which I otherwise don't, and the next day my memory works a little better. However, my blood pressure has given me increasing problems with morning lows, in particular. According to what you understand about acetylcholine in ME/CFS, would you consider a drug like Aricept that keeps acetylcholine in the system longer a poor idea?

    Now a general comment: I think we are in great need of big picture views and insights. They don't come just out of amassing details, but sometimes require a level shift.

    Einstein and some of the other great innovative scientists got their clues/insights from dreams, interestingly. The message came in a symbolic form which they were able to interpret and apply. If my memory serves me, not only the theory of relativity but also the double helix, the light bulb, and the sewing machine also came this way. Maybe the locomotive did too. I could look this up. Each of these innovators was fully involved and working hard on the subject and then a dream came with the metaphoric insight which showed the way forward.

    I am not saying that dreaming is the only way either, but that there are other levels of mind which can help. Maybe you will be someone who sees through the fog--in spite of brain fog, because this kind of intuition is not a regular, pedestrian, mental process. Any of us who really applies himself and cares might come to such a big picture insight. I don't think the true big picture insights come to people who don't care, but to those who are passionate about their subject.
  7. alex3619

    alex3619 Senior Member

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    Hi Sing, I did look at dreams and other issues in creativity many years ago. As part of an advanced philosophy class we studied a book by Boden, I forget the name, which looked at this. Didn't like the book, did like the class, which was about logical analysis of the claims - we did not care what the book was actually about.

    The guy who came up with the answers to Lorenzo's Oil also had it in a dream. People who can't let a problem alone, who study it all the time, who are emotionally involved, tend to dream about it. Some are better at this than others.

    Me I can't stop analyzing, and I think about ME/CFS issues for hours every day - have done for a very long time now. I am still waiting for that Eureka dream though (no, not the one where I am running naked down the street screaming, which is also a Eureka dream). :D

    Semantic memories are about ideas, concepts. Episodic memories are about events. If you can remember what a dog it, what dogs do, what dogs look like, then that is semantic memory. If you can remember the day you got your pet dog as a puppy, or any other event, that is episodic memory. I have almost no memory of my past, it is like I can remember a book that talks about my past - a big grey blur that I can remember the high points. So I can fake memory - most people would have no idea if I did not tell them. I do suspect I have the memories still, it is recall of memory that is impaired.

    I am not sure about treating acetylcholine. Enhanced acetylcholine might increase blood flow to the brain, which could be a good thing, and might explain your improved memory and reduced brain fog. Timing might be important though - drugs like that may be better tolerated at one time than another. If you change the time of day you take it, you might respond differently. Elevated acetylcholine may lower blood pressure though - but only iirc if it affects muscarinic receptors, the type in the blood vessels. So your morning lower blood pressure fits as a side effect.

    The systems theoretic approaches are an attempt to create methodologies for systematic construction of big pictures. They are not easy nor completely reliable, just another tool.

    Bye,
    Alex
  8. WillowJ

    WillowJ Senior Member

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    I was very fortunate in my training. It was only undergrad school, but the science faculty was very careful to teach reasoning. I had a course required for biology majors which covered logic, experimental design, and ethics. We also had ethics and reasoning in a course which covered current events and was required for biology, pre-med, chemistry, science education, and similar majors. I can't say how happy I was when I first switched to biology and the first thing I heard out of my professor's mouth was how he disliked "what page in the book is the answer to this question on" sort of questions and would be using application questions to teach reasoning. He now leads a program which teaches other professors in other departments to teach reasoning.

    Edit: this is not meant to brag about myself. Just really happy with my university experience. (Well, all except the part where I way overdid it physically, crashed badly and long, and am still paying the price! When I got back home, my doctor did not want to test for or treat anything there was any indication of or reason to suspect, but he did want to test me for AIDS, because I looked that sick).
  9. WillowJ

    WillowJ Senior Member

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    I agree with that!
  10. alex3619

    alex3619 Senior Member

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    Hi WillowJ, it is good to know that some educational institutions still get it, the course at the University of Queensland was optional, and the research design course was postgrad. This is not a universal problem, but it is a common problem.

    I too am still paying for overdoing things at university, a decade later.

    Bye
    Alex
  11. markmc20001

    markmc20001 Guest

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    Hi Alex,

    Glad you had an epiphany so to speak.

    I've been sick so long (since about 10) I never had the energy or cognitive function to make it through much college. However, I've done ok with my handi-cap until I became housebound few years ago. I don't need to impress anybody, I know what I can do. My point is, I agree with your statement.

    During my career as a mechanical design engineer, I was often tasked with fixing problems that others had failed on. Most memorable experience was with some guy who had a PHD from Russia.(I respect education, and would have gone ALOT farther with more) He and one other guy before him, had tried four seperate times(two times each), to fix a design for semiconductor furnace. Their were 100+ of these furnaces failing at the customers "wafer fab" sight in the field. Downtime for these machines is upwards of $10000 dollars an hour. For each machine. Talk about some uptight directors, and Vice Presidents! The problem was given to me to fix, the guy with CFS who could barely read, see straight, and talk. I delivered a solution like I always did, ahead of schedule. I that solved the problem and made everybody happy. Never even really got a thanks from anybody on that. Probably saved the companies relationship with that customer though.

    My background also involves designing automated high speed automation too. Its somewhat similar to virology in one way at least. If you need to move something to the same spot over and over again down too .0005". You better keep everything the same and be consistent. When nobody replicated WPI tests exactly, that is a red flag. That would be the FIRST thing I would do if trouble shooting a problem. Try and reproduce the original findings for a starting point..

    Anyways. I consider myself good problem solver. I can think out of the box and create stuff from a blank sheet of paper that works and is real. I never took what anybody else told me at face value, because it was likely I could make a mistake by just taking somebody's word for how to set something up. Didn't matter who it was. I had to come up with my own conclusion/solution, or prove to myself that somebody's else's idea was the best approach.

    I say stupid stuff on here at times, but I consider everything. Motives, politics, science, etc...

    I'm also from the US. We have a news station called FOX news. It's basically propaganda masquerading as news media. They edit videos, pay guests to come on with views that meet their agenda, have reporters that also repeat the same talking points. Its mostly about politics though. They can convince a chicken to vote for colonel sanders(Kentucky Fried Chicken dude) with all the SPIN and garbage. Why couldn't that technique apply to XMRV research news? It's possible Oslers web suggests it, conflicting stories and information suggests it. Just because a virus is created in a lab, doesn't mean it can't infect people. Right?

    Look up newscorp in wikipedia, and you will see FOX news is part of news corp. A media organization with many MANY TV stations, newspapers, magazines, publishing companies, etc... around the world. They can make any view point they want a reality.

    Here is my point. The WPI is not involved in this punishing battle because it's fun. They have a daughter they are desperately trying to help.

    On the other hand, the CDC, similar folk in the UK, and other organizations have a PROVEN track record of at least negliegence, and I would even say mis-conduct around around CFS/ME handling. the proof is there, people tear that stuff apart every day here.

    Then you have Coffin who finds XMRV and claims it is contamination from an unpublished study. Then wants to leave XMRV all behind? It's not an isolated inccident. How is that scientific? In my book of troubling shooting precision machinery, if I see something like that going on it's a big flahshing siren. How about the WPI taking years to complete its study. then the UK coming out with 4 papers claiming contamination is possible, in days? the cooperative news media tried to SPIN it like it was the end of the debate. Bob has posted tons of info in other threads with hard facts and links proving that XMRV has not been given a fair scientific shake. But like you said, it's not about science any more. It's politics.

    Politics against science does not work. WPI and Alter, etc are trying to use science, but the other side is using politics, news SPIN, volume of negative marginal papers, a seemingly unlimited budget, and other tactics to drown out the truth. We see it here everyday.
  12. Sing

    Sing Senior Member

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    There is so much here to respond to!

    Alex, thank you very much for responding to my questions. Like you, I guess I am left with semantic memory more than episodic. Little facts I need to remember, I repeat over and over silently. Isn't it amazing how other people don't realize the huge blanks we might have? I am amazed at how it is possible to fake functionality. Usually I am grateful, but sometimes with doctors, I think they don't believe me.

    I enjoyed your description of your desired Eureka dreams! You may actually be getting clues from your dreams which aren't being presented this dramatically, but more subtly, because the synthesis and new understanding we want so much in waking life, isn't always such a big deal to the "unconscious", which can just see the point--like a good A student. That is a tip from a former dreamworker--me.

    And in general I wanted to add how impressed I am with the posts on this thread and how well people are trying to think and analyze stuff. Thanks, Everyone, for making the effort to present your ideas!

    Sing
  13. WillowJ

    WillowJ Senior Member

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    It is a very common problem. I think overall, our education systems are failing in some respects.

    A decade later. At least I'm in good company :cool:, but I wish you better and a whiz-bang treatment and even a cure for all of us.
  14. WillowJ

    WillowJ Senior Member

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    sometimes it's not what degree you have, it's how you think. the process of getting a degree is supposed to teach one to think, but sometimes it does the opposite. sometimes the people without degrees think the smartest.

    I don't watch FOX news, but I'm really tired of hearing this claim. FOX is no more propaganda than MSNBC, maybe less. Newsflash, all the big stations are big corporate conglomerations. MSNBC is owned by General Electric. CNN is owned by Time Warner.
    Maybe you should read the Wall Street Journal and Heritage Foundation sometimes. It might make you realize that the other TV stations, Huff Po, and the rest of the other "normal" media (aka MSM) actually have a lot of selection bias, etc.
  15. markmc20001

    markmc20001 Guest

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    sorry Willow. Politics.

    I know. CNN Anderson Cooper(Mr keeping them Honest) steam rolled Dr Andrew Wakefield. They all are suspect far as I'm concerned.

    News Corp owns the Wall Street Journal, and FOX by the way.(source wiki) The left and right beat up on each other, but are both controlled by the same folks so it is one big party. I trust the left to try and screw me less the the right though, but they both are miserable.

    LIke Fareed Zakaria, my favorite is always intereviewing Guys like Henry Kissinger, Mr Zbigniew Brzezinski, George Soros. All very interesting characters with somewhat questionable motives.
  16. WillowJ

    WillowJ Senior Member

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    All suspect I can live with. :D FOX probably seems the most blatant to you because of a worldview clash, so you notice it the most.

    I did see that. :)

    Heritage Foundation is independent, though, and does a really good job of explaining things. You should check it out, if only to understand what the opposing viewpoint actually is.
  17. floydguy

    floydguy Senior Member

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    The Heritage Foundation is independent of what? They are hardly the most objective organization out there. You might as well ring up the Chairman of the Republican Party for his views on a particular topic. I'd suggest the Cato Institute as being a bit more objective. They often bash both sides and I prefer their position of being non-interventionist :)
  18. WillowJ

    WillowJ Senior Member

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    independent of ownership by large corporate conglomerates (see posts #35, 34, and 31 for context). and no, Heritage does criticize the Republicans (for instance, they say President GW Bush was wrong, wrong, wrong to start the bailouts), though not so often as it criticises Democrats (who tend to have a vastly different worldview from Heritage). (and, incidentally, the RNC Chairman will usually not tell you the viewpoint of Heritage and the Republicans on the ground. RNC Party leadership has failed miserably, which is why a lot of one-time Republicans now describe ourselves as Independents.) I do like to read Cato and they have some good stuff, too, but I'm a "classical liberal" (as I prefer to say) or a "conservative" (more recognizable label), not a libertarian, so I prefer Heritage to Cato.

    having similar viewpoints doesn't necessarily make organizations tied together. however, please note that I suggested Heritage as a source of info about other-than-HuffPo views, not as a balanced source (there is no such thing as a neutral source of political information). Cato has a third worldview, and is another valuable source of information about different perspectives.
  19. floydguy

    floydguy Senior Member

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    I was being tongue and cheek. You can't possibly think that these groups are independent of large corporate conglomerates. Take a look at the supporters of these groups such as the Koch Brothers. Yeah, the money might not come directly from corporate coffers but they usually are filtered through "Charitable Foundations".
  20. WillowJ

    WillowJ Senior Member

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    I stand by my statement that there is no such thing as a neutral source of political news.

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