Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome • Hacker News Board

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#161

Post by CuriouslyC » Tue, Aug 01, 2017, 4:02 PM UTC

dotancohen wrote: post #130

CuriouslyC wrote: post #115

Earlier quoted context omitted.

It isn't really that much of a problem. If you collect data on a large enough cohort of symptomatic individuals, you can recover separate subtypes through cluster analysis.

Cluster analysis will require thousands of not tens of thousands of cases to study. And since we don't know even how many diseases there are, this will have to be an unsupervised CA, so for each case you'll be looking tens if not hundreds of parameters. Machine Learning techniques are well suited to crunching this type of data, but don't underestimate the difficulty in collecting so much data.

You don't need thousands of cases, but you probably do need on the order of around a thousand samples. A hundred individuals with ten samples each over time isn't that challenging. I've done it successfully with mouse work at that scale.

I've found that in biological systems, individual variation can be as large as population variation, particularly for something "reactive" like the immune system, which is tied into stress response.

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#162

Post by tomhoward » Tue, Aug 01, 2017, 4:20 PM UTC

nradov wrote: post #152

tomhoward wrote: post #59

Earlier quoted context omitted.

> "Do you know what they call 'alternative medicine' that's been proved to work? Medicine." - Tim Minchin, Storm, 2008 I've been a big fan of Tim Minchin's, and thanks to living in one of the cities where he built much of his early fame, I've seen and enjoyed much of his work. But I feel like a form of Godwin's Law should apply to this quote. It's been done to death, it contributes nothing of value to the discussions…

This is not true. The medical field does a lot of research which is totally unrelated to drug development. Pick up a random collection of medical journals and look for yourself.

Indeed, I neglected to mention the other main motivator for undertaking research: to be published in journals. Thanks for pointing it out.

Seriously though, can you not see how the medical research system (and most importantly, the kinds of things that will be included in studies) is influenced by the fact that any study must seek to deliver on a commercial incentive, a political one, or at the very least, be likely to published in a reputable journal [1]?

[1] Incidentally, this is also, indirectly, a commercial incentive, given that journal publications are used as a key metric for ranking research universities internationally, which has a major bearing on funding.

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#163

Post by komali2 » Tue, Aug 01, 2017, 4:46 PM UTC

koube wrote: post #34

komali2 wrote: post #29

Earlier quoted context omitted.

Curious about this. I often find engineers motivated purely by the desire to solve the problem. Was just at defcon - witnessed many people vaguely wandering around the tables of teams trying to hack devices, then getting sucked in as they offered solutions and inevitably got involved with trying to solve the problem. Did it myself a couple times, even though I had planned on attending more talks.

They hate solving problems when someone comes up to them with a strange and incomplete description and says "can you fix my problem"? The made a whole show about this called the IT Crowd where they play a tape that says "Have you tried turning it on and off again" instead of legitimately answering phones. https://en.wikipedia.org/wiki/The_IT_Crowd Here's a subreddit where people complain about the problems that peopl…

Huh, I had never thought of that - the daily issues that patients bring a doctor I can see as a parallel to an engineer being presented with "can you fix my email?" - complete with user stupidity - "My heart don't feel good" "Did you quit smoking and start exercising like I told you to?" "No."

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#164

Post by nradov » Tue, Aug 01, 2017, 5:17 PM UTC

tomhoward wrote: post #162

nradov wrote: post #152

Earlier quoted context omitted.

This is not true. The medical field does a lot of research which is totally unrelated to drug development. Pick up a random collection of medical journals and look for yourself.

Indeed, I neglected to mention the other main motivator for undertaking research: to be published in journals. Thanks for pointing it out. Seriously though, can you not see how the medical research system (and most importantly, the kinds of things that will be included in studies) is influenced by the fact that any study must seek to deliver on a commercial incentive, a political one, or at the very least, be likely…

If the research isn't worth publishing in a reputable journal then it probably isn't worth doing. I'm not sure what point you're trying to make.

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#165

Post by mrow84 » Tue, Aug 01, 2017, 6:10 PM UTC

CuriouslyC wrote: post #161

dotancohen wrote: post #130

Earlier quoted context omitted.

Cluster analysis will require thousands of not tens of thousands of cases to study. And since we don't know even how many diseases there are, this will have to be an unsupervised CA, so for each case you'll be looking tens if not hundreds of parameters. Machine Learning techniques are well suited to crunching this type of data, but don't underestimate the difficulty in collecting so much data.

You don't need thousands of cases, but you probably do need on the order of around a thousand samples. A hundred individuals with ten samples each over time isn't that challenging. I've done it successfully with mouse work at that scale. I've found that in biological systems, individual variation can be as large as population variation, particularly for something "reactive" like the immune system, which is tied into…

Don't you have to be concerned about differences between the structure of individual variability as opposed to population variability?

Perhaps for the distinctions you are trying to draw it is not an issue?

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#166

Post by CuriouslyC » Tue, Aug 01, 2017, 8:08 PM UTC

mrow84 wrote: post #165

CuriouslyC wrote: post #161

Earlier quoted context omitted.

You don't need thousands of cases, but you probably do need on the order of around a thousand samples. A hundred individuals with ten samples each over time isn't that challenging. I've done it successfully with mouse work at that scale. I've found that in biological systems, individual variation can be as large as population variation, particularly for something "reactive" like the immune system, which is tied into…

Don't you have to be concerned about differences between the structure of individual variability as opposed to population variability? Perhaps for the distinctions you are trying to draw it is not an issue?

I haven't found that to be a big issue.

I choose clustering and dimensionality reduction hyperparameters to penalize clusterings with few repeated individuals (high entropy), while trying to maximize the entropy of the distribution of cluster labels.

To prevent cluster count explosion, you can put a regularization term/prior on the total number of clusters. An exponential or gamma with the expectation set to the square root of the number of distinct individuals is a good starting point.

Of course a big part of any analysis is responding to the data, no single approach will work every time.

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#167

Post by mrow84 » Tue, Aug 01, 2017, 8:47 PM UTC

CuriouslyC wrote: post #166

mrow84 wrote: post #165

Earlier quoted context omitted.

Don't you have to be concerned about differences between the structure of individual variability as opposed to population variability? Perhaps for the distinctions you are trying to draw it is not an issue?

I haven't found that to be a big issue. I choose clustering and dimensionality reduction hyperparameters to penalize clusterings with few repeated individuals (high entropy), while trying to maximize the entropy of the distribution of cluster labels. To prevent cluster count explosion, you can put a regularization term/prior on the total number of clusters. An exponential or gamma with the expectation set to the squa…

All sounds very reasonable - thanks for the insight!

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#168

Post by Shikadi » Tue, Aug 01, 2017, 9:32 PM UTC

Gibbon1 wrote: post #96

kens wrote: post #28

I looked at the paper and the data is kind of strange. Looking at figure 2, there are a bunch of cytokines that have a nice linear progression with increasing levels corresponding to increasing severity of disease. This seems like solid evidence that more cytokine = bad. But if you compare with the controls, mild cases of ME/CFS have less than the control, moderate cases have the same as controls, and severe cases ha…

The thing that currently spazs me out is the Simpson Paradox (Yule–Simpson effect) https://en.wikipedia.org/wiki/Simpson%27s_paradox In short, if your population has two (or more) diseases with similar enough symptoms that they are grouped together, statistical analysis can and does totally fail. And your experiment will produce garbage. So what if Chronic Fatigue Syndrome is really caused by a couple of different th…

Do you know if this has been accounted for with ADHD anxiety and or depression? It has always seemed to me like they represent symptoms rather than the actual cause, especially now that we know serotonin deficiency doesn't cause depression

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#169

Post by vacri » Tue, Aug 01, 2017, 10:11 PM UTC

Sleeep wrote: post #148

vacri wrote: post #82

Earlier quoted context omitted.

> if someone is in pain/unhealthy there is a reason. Rarely it is psychological Work in medicine, and you'll find a lot of malingerers. Some of them don't even realise that they're faking it. Yes, it sucks from your point of view that no-one believes you, but from the other side, a lot of people fake it, and you have to sort out what's actually going on. https://en.wikipedia.org/wiki/Munchausen_syndrome https://en.wi…

How do people fake seizures? Do they just flop around on the ground?

They just shake their limbs back and forth or their body. It's pretty easy for anyone familiar with seizures to tell a fake, since most fakers shake their limbs back and forth evenly - a sort of even sawtooth pattern of movement. However, jerky movement in seizures is contraction-relax-contraction-relax, contracting in one direction only, not back-and-forth jerking. People also aren't conscious during full-body seizures (though they are if it's partial-body), so if they're looking around focusing on things, looking at your response, or talking, that's a giveaway.

One point to note, though, is that you can't just assume that everyone faking a seizure doesn't have epilepsy. Quite a lot of fakers do, and they fake for different reasons. A lot like the attention they get after a seizure. Others come in to have an EEG and think that they need to have a seizure to help the diagnosis, so they 'help out' with good intentions (not common, but common enough). Very very rarely you might encounter a real seizure that looks like a fake, though these are generally other kinds of seizures (various kinds of 'partial' seizures), not the full-body-shaking ones.

Re: Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

#170

Post by weyland » Tue, Aug 01, 2017, 11:42 PM UTC

DanBC wrote: post #149

bogidon wrote: post #47

Earlier quoted context omitted.

> Rarely it is psychological "Medically unexplained physical symptoms (MUPS) are physical symptoms for which no relevant organic pathology can be found. MUPS are very common, comprising up to half of all consultations in primary care and up to one third of those in hospital outpatient clinics.1 Some studies indicate higher prevalence; a landmark study of medical outpatients in North America with new complaints of com…

also, psychological illness can be just as devastating and debilitating as physical illness. OCD for example leads to years of life lost to disability. I don't think the CFS crowd realise how fucking annoying they are when they dismiss psychological illness as "all in your head".

That is a pretty sweeping generalization to make. I've been sick with ME/CFS for several years now and I've never come across another patient dismissing psychological illness as not debilitating. Instead, many that I know have premorbid or comorbid psychological illness and know firsthand how debilitating psychological illness is.

If a person with OCD was told that their illness was due to poor lifestyle choices and that they could be cured of their OCD if they just stop believing they have OCD and that they just need to get to sleep on time and get a bit of exercise, they would probably not appreciate that. This is how people with ME/CFS are treated by many health professionals and medical researchers. There is a large and influential group of psychiatrists that posit that the disease is caused by nothing more than the belief that you have a disease. This is why there is seemingly an intense backlash against psychiatry and a frantic hunt for biomedical proof in ME/CFS.