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3 Dec 2017 | Interview with Nancy Kilmas on 'Unrest'

Discussion in 'General ME/CFS News' started by Sasha, Dec 8, 2017.

  1. Sasha

    Sasha Senior Member (Voting Rights)

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    It's only short but I like this bit:

    Whole thing here (please give them the traffic!): http://wlrn.org/post/beyond-tired-n...al&utm_source=twitter.com&utm_campaign=buffer
     
  2. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I give Dr Klimas all credit for taking this seriously. What worries me is that this was ten or maybe twenty years ago and since then nothing has been confirmed that could be called 'an awful lot wrong with the immune system'. I worry that people seeing the film will take it that these findings are established and that treatments have been developed. That is rather reinforced by Jen saying she is lucky to have access to treatments. I think there is a serious risk that people are going to feel let down when they realise this is not the reality.
     
  3. Esther12

    Esther12 Senior Member (Voting Rights)

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    Yes, I share that concern. It did feel like a film made by someone who had not been ill that long, so was lacking some justified cynicism. I suspect that's part of the reason why the film was able to make some sort of emotional connection with a wider audience though?

    I worry that this element of the film could lead to more people feeling pressured to try speculative treatments that are unlikely to help, when we'd be much better off using that money to conduct rigorous research. Also, if people are embracing one set of unfounded theories/treatments, that makes advocacy efforts around PACE and other forms of quackery more difficult.
     
  4. ahimsa

    ahimsa Senior Member (Voting Rights)

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  5. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I can't say that I really recognise any of those as being established findings. I worry when lists like this are put up as if they were agreed findings. For cytokines the findings have been all over the place. I do not really believe in the Th1/Th2 business and TNF is put in the Th1 group so I am not sure what to make of the list as it stands.
     
  6. ahimsa

    ahimsa Senior Member (Voting Rights)

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    Thanks. I'm certainly not planning on getting any of these tests!

    I thought they were meant as markers still being researched, not yet established clinical tests a patient should do, but perhaps I've misunderstood.

    Have you watched the video? I may have taken that chart out of context.
     
  7. Seven

    Seven Established Member (Voting Rights)

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    To clarify, this immune findings are not bizarre or unique to CFS (except for the low NK activity which is in research) for example: In my case I have low NK cells, this is accepted internationally as NK cell dysfunction (please google), I do not remember the ICD code. And her treatment was standard for that (in my case antivirals to lower the herpes infection). I know another patient who had low IGG subclass. Also a known immune deficiency and treated accordingly. Some have low cd4s......

    We are all a bit different, and need to be treated depending on what is going on (this is unfortunately symptom treatment) she is not saying the immune system is the cause per say (it could be a consequence)

    Also anybody with CFS has to look at sleep study, hormones, OI, .... For now all we have is to relieve symptoms until we know the cause.
    But I am testimony if you get the systems under control, it is not cure, but you will feel SOOOOO much less miserable: When I was checked first time I felt HORRRIBLE and I had: a hh6v, coazaxie b2, Parvo virus b19 and EBV infection!!!!!! After those went away (all by standard recognized Test) and my CBC got better, I feel much more decent (still my cytokine profile and lymphocyte subset)is a mess. I also still struggle with low NK number. But have gone up and down in the years.
     
  8. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    It was not that they were not established as clinical tests but that they were not established as reproducible research findings that we can take as established fact. I have not sen the video and will try to do that now.
     
    Last edited: Jan 11, 2018
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  9. Seven

    Seven Established Member (Voting Rights)

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    The problem is the immune issues you see are different per person, that does not mean as an individual you do not care, I know a few people and they all had different issues: One had sojern, another some IGG subclass deficiency.... That we are not the same does not mean the standard finds do not apply, the only bizarre one I heard of was IGM or IGG subclass I think it was (so not standard treatment because was a not so common one) The point being, the findings are mostly standard known issues, they are not reproducible because the spectrum is wide.
    I have also known another patient where all was ok on the immune system and nothing was given (still has CFS) so we are all different. We have to address our individual issues (until we can find the initial issue / CFS cause).\
    Edit: Sorry forgot to add I also have colitis and POTs both tested and treated at standard treatment.
     
    Last edited: Jan 10, 2018
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  10. Amw66

    Amw66 Senior Member (Voting Rights)

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    Oh to be able to access such testing. ......
     
  11. Forbin

    Forbin Senior Member (Voting Rights)

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    This is a fascinating video. If I understand it correctly, they have tried to simulate the complex interactions of the immune system using a large computer system specifically built for that purpose. They believe that, in both ME/CFS and Gulf War Syndrome, the immune system has been perturbed out of its normal stable state and has landed in another abnormal but also stable state. The immune system is stuck in this alternate mode not because of a continuing infection or other outside pressure, but because the alternate mode is self-reinforcing and thus stable. In Gulf War Syndrome, they've run thousands of "in silico [silicon]" simulations to test various ways of "knocking" the immune system back into its normal state. The most promising method seems to be a non-intuitive two-step process. They will soon be running trials of this in GWS patients.

    [ I'm just guessing here, but it could be that, superficially, the values of the various immune signaling components are within normal limits in the abnormal mode, but it might be that it's the combined interactions of multiple shifts within the normal range that add up to an abnormal state. ]
     
    Last edited: Jan 11, 2018
  12. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I think the systems dynamics analysis set up by Broderick in this group is important. There is a very bright young scientist called Travis Craddock working on this who I know well from another branch of science in fact. What they are proposing is very similar to what we proposed for rheumatoid arthritis in 1998 - that the disease is a stable 'dip' in a dynamic landscape that once you get into you do not roll out of. Whether you need a computer to model this or not I am not very sure. We did it all without computers. But if you are constructing abstract general models without much data to start with it makes sense.

    The problem is, though, that you have to have some sort of data to test the model. In RA we had data dripping from the walls. We had ESRs of 100, autoantibodies sky high, tissue pathology slides dating back to 1890, immunohistology findings, known genetic predispositions and evidence from cytokine blockade. In ME/CFS there is pretty much nothing to test the model on. I am afraid that combined interactions within the normal range is not going to work. If they are within the normal range you have no reason to think they are doing anything abnormal. You have the Bonferoni problem that you can create thousands and thousands of models and one or other is bound to seem to fit the results by chance.

    I think this modelling effort is really strong, but I do worry that people are trying to run before they can walk when it comes to actual data.
     
  13. Forbin

    Forbin Senior Member (Voting Rights)

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    In the video, Dr. Klimas mentions this:


    [I believe the animal model was a mouse. Just to emphasize, this was a Gulf War Illness model, not ME/CFS.]
     
    Last edited: Jan 11, 2018
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  14. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    the problem with animal models is that they work the way you have engineered them to work. That does not tell you anything about whether they work like the human illness you are 'modelling'. Animal models in rheumatoid arthritis have been almost completely useless and misleading.
     
  15. Forbin

    Forbin Senior Member (Voting Rights)

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    From looking at the video, I think that Dr. Klimas is talking about the post-exercise network analysis being very different in CFS, GWI and normal controls. I think this change in network activity after exercise is why she refers to looking at the system "dynamically."

    In GWI the network is distinctly overactive compared to normal controls after exercise.

    In ME/CFS the network is distinctly underactive compared to normal controls after exercise.

    Klimas 2 small.jpg

    I would assume that getting the post-exercise network analysis in ME/CFS and GWI to look like that of normal controls would be an objective marker of the effectiveness of the treatment. Other indicators she mentioned in the animals were normalization of autonomic and immune function, and normalization of neuroendocrine balance. If the patients also report subjective improvements in symptoms, that would no doubt justify further trials.

    The fact that they were able to do this in a GWI animal model does not mean that they can do it in a human, but we may know more about that relatively soon. In the video, Dr. Klimas says she anticipates that "we will be running this trial [in humans] before Christmas [presumably of 2017]."
     
    Last edited: Jan 13, 2018
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  16. Barry

    Barry Senior Member (Voting Rights)

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    I think there many parallels for this. Self tuning algorithms for process controllers can get into this pickle, dropping into a bad state of tuning but unable to find a way out, sometimes adopting a completely stable but bad state, or sometimes hunting around close to such a state, unable to escape; no doubt many other kinds of self tuning algorithms also.

    If they are right (that 'if' word again) it would be fascinating to know what the biological mechanism were. (The BSP brigade have been convinced all this time the stable state is one of being deconditioned, and the way out of it is mental and physical effort; we know this is not true of course).
     
  17. Forbin

    Forbin Senior Member (Voting Rights)

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  18. alex3619

    alex3619 Senior Member (Voting Rights)

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    One of the issues I think we face is that while many things are wrong they are not sufficiently reliable and present in the patient pool to qualify as diagnostic. On an individual basis things are wrong, on a group basis its not consistent enough, or hasn't been given the technology of the time and the tests run. Things are wrong, but they do not add up to a provable discrete disease entity. Yet for that individual patient there might be an advantage to knowing what is wrong. Its just not generalisable.
     
  19. alex3619

    alex3619 Senior Member (Voting Rights)

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    In chaos theory such states are due to a strange attractor, the balance of forces that keep things moving around that projected attractor. There are maybe a few threads on this on PR, probably old threads.
     
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  20. Flying Dutchman

    Flying Dutchman Established Member

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    Sadly, that's an understatement - it was not 10 or even 20 years ago; Nancy Klimas did that work approx 29 years back.
     
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