9 ms·

Paper at https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf https://www.pnas.org/content/pnas/early/2019/04/24/190127411... Pleasantly surp

Paper at https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf https://www.pnas.org/content/pnas/early/2019/04/24/190127411... Pleasantly surprised to discover that it was legally available! The test appears to be ridiculously good. Perfect separation of 40 subjects into those who have been diagnosed with CFS and those who are known to be healthy, from blood samples. I want to see this replicated, by people who are not the original authors; but if this test is anything like as good as it looks, it's revolutionary.

danieltillett 8y ago
I have to agree with you here - the separation is too good. You just never get anything in the real world that works this well with complex diseases.
- rfugger 8y ago
  This is true, but everything is complex only up to the point when you begin to understand it. Scurvy was a complex disease until the discovery that it was cured and prevented by citrus fruit(1). Now we have the technology to skip right to the discovery of vitamin C, a miraculous 100% accurate test for scurvy. I know I'm oversimplifying, but I think the point is valid. This is why discovery of a biomarker is so crucial -- it begins to "decomplexify" the disease so we can properly define it and start to find treatments for it. (1) Ok, it's never really that simple: http://mentalfloss.com/article/24149/how-scurvy-was-cured-then-cure-was-lost http://mentalfloss.com/article/24149/how-scurvy-was-cured-th...
  - rjsw 8y ago
    Maybe link to the original blog article [1], your link is just a summary. [1] http://idlewords.com/2010/03/scott_and_scurvy.htm http://idlewords.com/2010/03/scott_and_scurvy.htm
    - rfugger 8y ago
      Thanks -- I just copied the first link I found in a search engine.
- gwern 8y ago
  It is suspicious but look at the scatterplots: https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf#page=4 https://www.pnas.org/content/pnas/early/2019/04/24/190127411... It really is pretty much perfect separation on their metric. When the effect size is that large...
  - ufo 8y ago
    One thing that would be interesting to investigate in the future would be to see how the test behaves for CFS patients who are not as severely ill, or for non-CFS patients that are currently ill from a different disease.
  - mirekrusin 8y ago
    Exacly, just sorting it would show it better, it feels like it should just output percentage with (arbitrary/based on population %age/whatever) threshold that is outside of the test.
- deleted 8y ago
  [deleted]
- kurthr 8y ago
  AIDS was once considered a very complex disease, but it has a very accurate (HIV) test today. My big concern would be if, like cancer, there are really many diseases and Chronic Fatigue symptoms are common, not differentiating.
  - erentz 8y ago
    That could still be very interesting. Eg. There are some other illnesses like MS where patients can get fatigued in a similar way to CFS, but not always. If we find a similar response between the fatigued and non fatigued MS patients for example, that could still point to something that is going on causing the fatigue in both cases. Ron Davis’s line on this was to point out having one disease doesn’t mean you can’t have any others. There are a lot of other interesting overlaps showing up. One of the more interesting to me (because I have it) is that about 40% of CFS patients are testing positive for small fiber polyneuropathy on punch biopsies that appear to be autoimmune in origin. Is that itself an underlying cause of some 40% of CFS cases or is it just a common comorbid condition that whatever triggers CFS also triggers?
  - GordonS 8y ago
    I've done a lot of reading on CFS and fibromyalgia, and this has been my opinion too. For starters, these are both diagnosis of exclusion; these labels are also used by lazy doctors who lack a deeper understanding of their field (anecdotally, both personal and otherwise), or who are reluctant to run expensive tests for rarer conditions; and many people with these conditions have been found to have small fiber neuropathy.
  - Someone 8y ago
    AIDS, like CFS, was never considered a disease in the medical sense. They both are called “syndrome”, which is medical short-hand for “interesting enough to study further, but frankly, we don’t know shit about what’s causing this”. https://en.wikipedia.org/wiki/Syndrome https://en.wikipedia.org/wiki/Syndrome: ”A syndrome is a set of medical signs and symptoms that are correlated with each other and, often, with a particular disease or disorder.” That’s why AIDS became “HIV infection” when medical science discovered what caused AIDS. If this research gets confirmed, and a mechanism is found, that will happen here, too. However, as you say, if that happens, there’s a good chance there are people currently diagnosed with CFS who don’t show this biomarker. If so, those people run the risk of getting stigmatized even more than current CFS sufferers do. The real solution to that problem, I think, would be for the world to accept that, if you have a mental problem, a) that doesn’t imply you put it there, and b) it doesn’t imply you should be able to get it out without outside help. Only a few centuries ago, people were being blamed of being “unfaithful to god” when they got sick, be it due to a bacterial infection or due to mental illness. I see blaming people for their mental problems as a remnant of that.
- ipunchghosts 8y ago
  Who care is the separation is "too good." It's a lead. This is what science is. You find leads and followup on them. Lots of dead ends in the process.
  - sagebird 8y ago
    You should care if it “too good” because it could be a sign of overfitting or tampering with data during analysis to reach a desired conclusion. Replication should shed some light here.
- Gatsky 8y ago
  Of course skepticism is warranted however an important distinction to make is that they are measuring a whole cell phenotype, rather than some surrogate such as gene expression or a circulating molecule. I work on cancer biomarkers, and phenotypic readouts work much better than you might expect.
erentz 8y ago
I’m also very interested in seeing how strong the effect is when tested on mild and moderately ill patients. I hope they follow up with that. (The study group OMF have been using has been 20 severely sick patients, which is a good plate to start.)
- rtp 8y ago
  From the paper: Of the 20 ME/CFS patients studied, 5 were severely ill and 15 were moderately affected by their condition
  - erentz 8y ago
    Oh! That’s good news. (I’ve been following the OMFs work for a while now and somewhere along the way I got it into my head they were all severely ill.)
GordonS 8y ago
Keep in mind that CFS is a currently a diagnosis of exclusion - many people labelled with CFS may in fact have another, undiagnosed illness. For example, it's been found that a lot of CFS (and fibromyalgia) patients turn out to have small fiber neuropathy (damage to he nerve fibers that signal pain), and neurotoxins have been shown to cause general fatigue (I'm in mobile, so no references for now I'm afraid). The skin biopsy test for small fiber neuropathy isn't routinely done because there aren't that many labs capable of testing the sample, and it's relatively expensive. Of course, for all we know neuropathy could be a symptom of CFS... but the point is there is a lot of cross-over, and there is no diagnostic test specifically for CFS.
- wavepruner 8y ago
  I found out last year the root cause of my CFS is life-long mercury toxicity (a well understood neurotoxin). I am responding very positively to treatment. I rarely talk about it because people get very upset when I tell them about the evidence of where the mercury came from.
  - febeling 8y ago
    Nice curiosity gap there. Where did the mercury come from?
    - thom 8y ago
      Going to assume given the way this is phrased that the poster means a vaccination.
    - everly 8y ago
      IMO he is clearly implying it came from a vaccine(s) but he is trying to do it without being seen as an anti-vaxxer.
      - p1necone 8y ago
        Surely you'd have to have a lot of vaccines for it to compare to the amount you get from other sources (mostly seafood afaik?)
kens 8y ago
Thanks for the paper link. I read the paper and it's really a semiconductor sensor engineering paper, not a biology paper. The paper seems very preliminary; it shows that CFS and non-CFS sample have widely different impedances under osmotic stress, but the mechanism behind this is entirely hand-waving. If I'm reading the paper correctly, the samples were peripheral blood mononuclear cells (i.e. lots of different cell types) in their own plasma. It would be nice to have samples that weren't so heterogeneous, since it's unclear what type of cell is causing the effect, or if it is something in the plasma. It would be nice if the paper gave the actual measured resistances, rather than % deviation from normalized impedance which is an unusual unit. The paper's use of machine learning seems entirely pointless, basically drawing the obvious line between the two sets of points. The discussion section didn't seem to have anything concrete. It reminded me of a patent application where you try to list everything that might possibly turn out to be vaguely related. I apologize for the negativity; the paper's result is very exciting so I hope it pans out, but I found the paper itself disappointing.
- sagebird 8y ago
  The use of machine learning needs to be explained. I’m half expecting it to boil down to “we evolved the neural nets until it perfectly separated the two groups” — overfitting “learning”.
  - ufo 8y ago
    I also had that impression at first but it seems that they are just using Support Vector Machines to draw the separating boundary between the two group of points.
  - Smaug123 8y ago
    If you look at the graphs by eye, there is an extremely obvious divide. SVM just let them find it automatically, but if you gave a human those graphs, they could instantly point out where the line is.
  - thereisnospork 8y ago
    Why does it need to be explained if the test can be proven to be extensible? Asprin worked for nearly 100 years before anyone had any clue how (ditto with many, many more modern drugs).

danieltillett 8y ago

I have to agree with you here - the separation is too good. You just never get anything in the real world that works this well with complex diseases.

rfugger 8y ago
This is true, but everything is complex only up to the point when you begin to understand it. Scurvy was a complex disease until the discovery that it was cured and prevented by citrus fruit(1). Now we have the technology to skip right to the discovery of vitamin C, a miraculous 100% accurate test for scurvy. I know I'm oversimplifying, but I think the point is valid. This is why discovery of a biomarker is so crucial -- it begins to "decomplexify" the disease so we can properly define it and start to find treatments for it. (1) Ok, it's never really that simple: http://mentalfloss.com/article/24149/how-scurvy-was-cured-then-cure-was-lost http://mentalfloss.com/article/24149/how-scurvy-was-cured-th...
- rjsw 8y ago
  Maybe link to the original blog article [1], your link is just a summary. [1] http://idlewords.com/2010/03/scott_and_scurvy.htm http://idlewords.com/2010/03/scott_and_scurvy.htm
  - rfugger 8y ago
    Thanks -- I just copied the first link I found in a search engine.
gwern 8y ago
It is suspicious but look at the scatterplots: https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf#page=4 https://www.pnas.org/content/pnas/early/2019/04/24/190127411... It really is pretty much perfect separation on their metric. When the effect size is that large...
- ufo 8y ago
  One thing that would be interesting to investigate in the future would be to see how the test behaves for CFS patients who are not as severely ill, or for non-CFS patients that are currently ill from a different disease.
- mirekrusin 8y ago
  Exacly, just sorting it would show it better, it feels like it should just output percentage with (arbitrary/based on population %age/whatever) threshold that is outside of the test.
deleted 8y ago
[deleted]
kurthr 8y ago
AIDS was once considered a very complex disease, but it has a very accurate (HIV) test today. My big concern would be if, like cancer, there are really many diseases and Chronic Fatigue symptoms are common, not differentiating.
- erentz 8y ago
  That could still be very interesting. Eg. There are some other illnesses like MS where patients can get fatigued in a similar way to CFS, but not always. If we find a similar response between the fatigued and non fatigued MS patients for example, that could still point to something that is going on causing the fatigue in both cases. Ron Davis’s line on this was to point out having one disease doesn’t mean you can’t have any others. There are a lot of other interesting overlaps showing up. One of the more interesting to me (because I have it) is that about 40% of CFS patients are testing positive for small fiber polyneuropathy on punch biopsies that appear to be autoimmune in origin. Is that itself an underlying cause of some 40% of CFS cases or is it just a common comorbid condition that whatever triggers CFS also triggers?
- GordonS 8y ago
  I've done a lot of reading on CFS and fibromyalgia, and this has been my opinion too. For starters, these are both diagnosis of exclusion; these labels are also used by lazy doctors who lack a deeper understanding of their field (anecdotally, both personal and otherwise), or who are reluctant to run expensive tests for rarer conditions; and many people with these conditions have been found to have small fiber neuropathy.
- Someone 8y ago
  AIDS, like CFS, was never considered a disease in the medical sense. They both are called “syndrome”, which is medical short-hand for “interesting enough to study further, but frankly, we don’t know shit about what’s causing this”. https://en.wikipedia.org/wiki/Syndrome https://en.wikipedia.org/wiki/Syndrome: ”A syndrome is a set of medical signs and symptoms that are correlated with each other and, often, with a particular disease or disorder.” That’s why AIDS became “HIV infection” when medical science discovered what caused AIDS. If this research gets confirmed, and a mechanism is found, that will happen here, too. However, as you say, if that happens, there’s a good chance there are people currently diagnosed with CFS who don’t show this biomarker. If so, those people run the risk of getting stigmatized even more than current CFS sufferers do. The real solution to that problem, I think, would be for the world to accept that, if you have a mental problem, a) that doesn’t imply you put it there, and b) it doesn’t imply you should be able to get it out without outside help. Only a few centuries ago, people were being blamed of being “unfaithful to god” when they got sick, be it due to a bacterial infection or due to mental illness. I see blaming people for their mental problems as a remnant of that.
ipunchghosts 8y ago
Who care is the separation is "too good." It's a lead. This is what science is. You find leads and followup on them. Lots of dead ends in the process.
- sagebird 8y ago
  You should care if it “too good” because it could be a sign of overfitting or tampering with data during analysis to reach a desired conclusion. Replication should shed some light here.
Gatsky 8y ago
Of course skepticism is warranted however an important distinction to make is that they are measuring a whole cell phenotype, rather than some surrogate such as gene expression or a circulating molecule. I work on cancer biomarkers, and phenotypic readouts work much better than you might expect.

erentz 8y ago

I’m also very interested in seeing how strong the effect is when tested on mild and moderately ill patients. I hope they follow up with that. (The study group OMF have been using has been 20 severely sick patients, which is a good plate to start.)

rtp 8y ago
From the paper: Of the 20 ME/CFS patients studied, 5 were severely ill and 15 were moderately affected by their condition
- erentz 8y ago
  Oh! That’s good news. (I’ve been following the OMFs work for a while now and somewhere along the way I got it into my head they were all severely ill.)

GordonS 8y ago

Keep in mind that CFS is a currently a diagnosis of exclusion - many people labelled with CFS may in fact have another, undiagnosed illness. For example, it's been found that a lot of CFS (and fibromyalgia) patients turn out to have small fiber neuropathy (damage to he nerve fibers that signal pain), and neurotoxins have been shown to cause general fatigue (I'm in mobile, so no references for now I'm afraid). The skin biopsy test for small fiber neuropathy isn't routinely done because there aren't that many labs capable of testing the sample, and it's relatively expensive. Of course, for all we know neuropathy could be a symptom of CFS... but the point is there is a lot of cross-over, and there is no diagnostic test specifically for CFS.

wavepruner 8y ago
I found out last year the root cause of my CFS is life-long mercury toxicity (a well understood neurotoxin). I am responding very positively to treatment. I rarely talk about it because people get very upset when I tell them about the evidence of where the mercury came from.
- febeling 8y ago
  Nice curiosity gap there. Where did the mercury come from?
  - thom 8y ago
    Going to assume given the way this is phrased that the poster means a vaccination.
  - everly 8y ago
    IMO he is clearly implying it came from a vaccine(s) but he is trying to do it without being seen as an anti-vaxxer.
    - p1necone 8y ago
      Surely you'd have to have a lot of vaccines for it to compare to the amount you get from other sources (mostly seafood afaik?)

kens 8y ago

Thanks for the paper link. I read the paper and it's really a semiconductor sensor engineering paper, not a biology paper. The paper seems very preliminary; it shows that CFS and non-CFS sample have widely different impedances under osmotic stress, but the mechanism behind this is entirely hand-waving. If I'm reading the paper correctly, the samples were peripheral blood mononuclear cells (i.e. lots of different cell types) in their own plasma. It would be nice to have samples that weren't so heterogeneous, since it's unclear what type of cell is causing the effect, or if it is something in the plasma. It would be nice if the paper gave the actual measured resistances, rather than % deviation from normalized impedance which is an unusual unit. The paper's use of machine learning seems entirely pointless, basically drawing the obvious line between the two sets of points. The discussion section didn't seem to have anything concrete. It reminded me of a patent application where you try to list everything that might possibly turn out to be vaguely related. I apologize for the negativity; the paper's result is very exciting so I hope it pans out, but I found the paper itself disappointing.

sagebird 8y ago
The use of machine learning needs to be explained. I’m half expecting it to boil down to “we evolved the neural nets until it perfectly separated the two groups” — overfitting “learning”.
- ufo 8y ago
  I also had that impression at first but it seems that they are just using Support Vector Machines to draw the separating boundary between the two group of points.
- Smaug123 8y ago
  If you look at the graphs by eye, there is an extremely obvious divide. SVM just let them find it automatically, but if you gave a human those graphs, they could instantly point out where the line is.
- thereisnospork 8y ago
  Why does it need to be explained if the test can be proven to be extensible? Asprin worked for nearly 100 years before anyone had any clue how (ditto with many, many more modern drugs).