The Courier Mail: Australian scientists prove CFS is real and have discovered a test for it

[Esther12]

Thanks Indigophoton. So it sounds like Ron just doesn't think that they're ready to publish something yet.

There were some bits about criticism in there that seemed a bit odd to me.

'Given the power to criticize'? Who should I request that power from? As someone who thinks it can be quite helpful to make anonymous criticisms on the internet, and that Janet would have done well to listen and respond to some of the criticisms being made, I wasn't too impressed by that part of the discussion.

I had thought that the OMF were planning to release data openly in order to encourage more criticism so that they could improve their work - that would seem a healthier attitude to criticism to me.

 

[Joh]

This is from Ron Davis' latest video (an automatic generated YouTube-transcript)
on publishing the nano-needle findings:

I think we

have to publish and so I think we're

going to stop very soon here and at

least published the first paper to show

what we're doing we've been slow to

publish mostly because we've been

understaffed and we always want to

collect more data and put the

publication off and we have to stop

doing that we're gonna have to put stuff

together and now publish (...)

I had thought that the OMF were planning to release data openly

Apparently the data will soon be made accessible to researchers (according to this article (if it's ok to post an HR article here)).

 

[Forbin]

If you're hitting a paywall when trying to read the article at the top of the thread, this worked for me:

1) Clear your browser cache/history
2) Google "sonya marshall-gradisnik"
3) When you see the results, click on "NEWS" at the top of the screen.
4) The first result should be a link to this story. Click on that.

It worked for me. Trying to access the link from inside s4me.info always took me to the subscription page. Once at the subscription page, you'll always go back there. That's why you need to clear your cache.
[ For me, even if I try to go back to the actual page after having just viewed it, I will be sent to the subscription page. It will be necessary to clear my browser history again. ]


P.S. If you search for "Sonya Marshall-Gradisnik" on Pubmed she has her name on 41 papers, the majority of them on ME/CFS. Four of those were published in 2017.

 

[Subtropical Island]

Some study conclusions from the Australian group have been exactly "overhyped rubbish". One SNP study compared the number of alleles (not prevalence percentages) for some SNPs between patients and controls, and concluded there were differences. But since the number of patients and controls was quite a bit different (approximately 50 patients versus 35-40 controls if I recall correctly), directly comparing the raw numbers was completely meaningless. They didn't really mention that, however, and still used the comparison to claim a significant difference.

Their other SNP studies weren't as shockingly bad, but didn't make statistical corrections to account for the high likelihood of a fluke false positive when comparing a large number of outcomes (different SNPs) between patients and controls. That's common practice in SNP studies, unfortunately, but that doesn't make it any more acceptable - the results are still almost completely useless, except perhaps for narrowing down what to look at properly in a later study.

But my impression is that their non-SNP studies have used better methodology, so are more likely to be relevant. And most researchers are not competent when it comes to statistics or genetics, so the flaws might be due to a single source which is external to the core group of researchers, or due to honest mistakes. However they do have a duty to understand what they're doing to a minimal extent, to avoid such fundamental errors.

Sounds like useful feedback for the research group
- is it worth sending them a short email to tell them?
I remember finding statistical methods to be a frustrating add on at the end of an experiment as a student because I wasn't comfortable with the stats involved (statistics is not taught from first principles to non-specialists). I understood why we needed to apply them. I had learned how to apply it like a recipe but it (how the equation actually worked) wasn't something I truly understood and therefore I always felt clumsy and vulnerable in applying any of them. My understanding of the science was fine, as was my experimental method in general but the statistics was substandard, and I knew it. Having someone who did understand statistics go over the numbers, help make sure I was applying the method well, would have been awkwardly but gratefully received.
I remember wishing that there was someone in the team who specialised in stats to check us on that part. Contrary to some popular opinion, researchers at the student level can be outstandingly good at some aspects of the subject and quite incompetent in others. Perhaps that's something someone with this competency could offer to help?
Maybe I'm being over-idealistic but that's what I thought criticism was for: to _help_ researchers produce better science. I wonder if there are any statisticians floating about willing to offer an hour here or there to review studies pre-publication... there's a lot of this sort of support work that seems to be la king in publications these days. But maybe I'm getting old and rambling in my middle age.

 

[Jonathan Edwards]

I think it has to do with getting donations.
The OMF need to let people know that things are happening, and research is "finding things" but at the same time, Ron doesn't have enough to publish by the sounds of it.

So the videos help keep patients interested enough to continue donating.

I see that but if there is anything to report, any sort of 'finding', why not show appropriate controls as one would in a scientific presentation so that scientific viewers can judge the material? It does not need to take up any significant amount of time. Unless such controls have been done there isn't really any 'finding' anyway. It is not a problem of having enough to publish - all you need is enough to show a result, much as one often does in a preliminary communication at a conference. Why is the OMF any different from other research groups who present data and controls once they have them?

 

[Forbin]

In his latest video, Dr. Davis does mention that they tested the nano-needle on 11 patients and 10 healthy controls and the results have been "absolutely consistent." After salt is added to the samples, all of the patients show an increase in impedance and none of the controls do.

[See video at 6:40]



Since this technology seems like it may still be in a proof of concept stage, I don't know if the patient and control samples would have been blinded in those tests.

 

[Kalliope]

There is a discussion of the article on Reddit as well
Chronic Fatigue Syndrome: Aussie scientists' breakthrough

 

[Londinium]

My personal view is that NCNED do some interesting work even if the SNP studies are underpowered and I’m a fan of a wide range of research groups being involved rather than an eggs in one basket approach. When I’m back home from doing the Christmas trip to the in-laws I’ll try and dig out the patent application that seemed to indicate they’d managed to replicate the result (which would be far more statistically valid if they’d found one particular SNP in a focussed study compared to the first study’s look-at-everything approach).

The OMF stuff is promising but as yet unpublished, and I was pleased to hear on the latest OMF update that they do now plan to publish soon.

 

[Trish]

Why is the OMF any different from other research groups who present data and controls once they have them?

As I understand it, Ron Davis and his team are working on two separate things - the nanoneedle as a diagnostic instrument, which looks promising but is still in very early stages having only been tested on a few patients and controls. I don't get the impression they have done a proper study with it yet.

And the severe illness study where they are collecting samples and data from 30 bedbound patients and doing a massive range of different -omics on these. They are making this data available to other researchers. From what I remember of Ron's talks, so far they have mostly negative results - things they looked for but didn't find like viruses in the blood. Maybe that wasn't considered publishable yet.

It seems to me to be a sort of preliminary exploration, looking for differences that can then lead to hypotheses to be tested on different cohorts of patients. Maybe it's hard to get such speculative, exploratory stuff published.

I do worry that Ron and his team are making promises of imminent progress that they can't really back up yet. He's so keen to give patients (and his own family) hope, that perhaps he sounds more optimistic than his data justifies so far.

I wonder, @Jonathan Edwards whether you have an opinion on the NIH in house study that is taking a similar approach - taking 30 patients and 30 healthy controls and putting them through a huge battery of tests to collect data and hopefully learn useful directions for future hypothesis testing. They also don't intend to publish anything until they have collected and analysed all the data.

 

[deleder2k]

Has anyone tried Nifedipine which the Aussie researchers are interested in? I've tried Verapamil. Both are calcium channel blockers, but I can't seem to figure out what the difference is. I had experienced no effect. The pain specialist at the hospital gave me Verapamil after I had him read a study about a possible calcium issue in PWME. I benefit from drinking alcohol. Also tried nitrates with no luck.

 

[Joel]

Thanks Indigophoton. So it sounds like Ron just doesn't think that they're ready to publish something yet.

There were some bits about criticism in there that seemed a bit odd to me.

'Given the power to criticize'? Who should I request that power from? As someone who thinks it can be quite helpful to make anonymous criticisms on the internet, and that Janet would have done well to listen and respond to some of the criticisms being made, I wasn't too impressed by that part of the discussion.

I had thought that the OMF were planning to release data openly in order to encourage more criticism so that they could improve their work - that would seem a healthier attitude to criticism to me.

I agree with Dr Davis in part and disagree in part. Can anonymous reviewers be nasty (or I would personally think of it more as having a negative motive)? Yes. But sometimes they are just right to criticise. Can anonymous ppl on the net be nasty (Or have a motive)? Yes. But sometimes they are just right to criticise. I think it's a bit dangerous to disregard all anonymous criticism on the basis that it's anonymous because you have to guard against your own natural, often subconscious, tendency to want to dismiss criticism and this mindset might make you prone to rejecting valid criticism rather than accepting it.

If he thinks he can't trust his results then he's absolutely right to look into that first. That seems a much better reason to delay publication to me.

 

[Snow Leopard]

Tl;dr: RD says that he a) finds peer review a little intimidating, and b) is not sufficiently confident in his results yet.

It means they don't have meaningful results yet. It's all hype at this point.

 

[Inara]

@Joel, you can critisize in a respectful and constructive way, and you can critisize disrespectfully. Why choose the nasty way? As researcher you must address the reviewer's points nonetheless if you want your results published, so there is no need for disrespect.

Anonymity (e.g. in the internet) gives many people the possibility to be assholes. There are people who don't care about it but I don't like being addressed in a nasty and disrespectful manner. This shouldn't happen in a publishing process.

Our group never made the experience of disrespectful critic by the reviewer, though.

 

[Alvin]

That is a disgraceful comment.

And I say that as somebody who agrees that, on the publicly available evidence so far, their studies are under powered, and their claims are premature.

I'm sorry your offended but i don't think repeated grandiose statements and proclamations makes them special.

One reason (probably the main reason) that his team was not funded by the NIH grant was because his team does not publish their work.

I completely agree that they should publish, i wrote a long synopsis of my opinion on this (was it here or on the other place, i forget) but their wanting to change the academic system by not publishing is not gonna fly and being innovative and spry is great but they still have to play the game to get the funds.

Edit: I found the posts i was referring to, do we have a policy about linking to the other place?

Some study conclusions from the Australian group have been exactly "overhyped rubbish"

But over hyped rubbish gets so much support, especially in this thread. It is those of us who don't like it that are the problem.

I don't actually think that is what good science is about. Most good science is done by hard working people that nobody has ever heard of with a commitment to particular problem . 'Bringing in' people with names does not have a track record for being productive. To my mind the real problem with ME/CFS is in trying to identify from the symptoms what the physiological problem really is. I doubt it is metabolic failure. Unless people know what question to ask they will not get the right answer.

I agree that we need a disease mechanism, desperately, it would even help with smashing the PACErs, i mean who will buy we can cure narcolepsy by pretending the patient doesn't have it
20 years ago it was psychosomatic, today...
If i understand your meaning your saying big names won't help, to a point i agree, but if you bring in people with the needed specialties it would certainly help, a disease mechanism will also help get the right specialties

I also do not really understand this stuff about not publishing. Publishing does not slow anything down. And it is easy to put out results in brief form in conference proceedings. I always used to put out data as soon as I thought we were sure it was meaningful. The delay from experiment to public knowledge was rarely more than three months. I do not see any reason why other people cannot do this. What I find unhelpful is the putting out of videos with oblique references to some findings without any controls or proper account of methods.

I very much agree, they can certainly publish their nanoneedle research, as long as they don't get ahead of their data they should publish what they have so far (and perhaps stop publicly insulting the NIH, biting the hand they want to feed them and all).

 

[Trish]

I very much agree, they can certainly publish their nanoneedle research, as long as they don't get ahead of their data they should publish what they have so far (and perhaps stop publicly insulting the NIH, biting the hand they want to feed them and all).

I have probably said this already, but I think Ron Davis is an exhausted elderly man desperately trying to help his desperately sick son. He also is a kind man who wants to help us all, and give us hope.

He is clearly a very clever man in his field, which, as I understand it has mainly been focused on genetics and the technology for elucidating the genome. He has moved sideways to try to get more research going on ME for obvious reasons, at a time when he might have expected to have retired.

I can see why he has acted as he has, focusing on getting data as best he can, and trying everything to try to find a direction for more focused research and hypothesis testing. Because this is a 'non-standard' way of going about scientific research, it probably does not fit well with the requirements of publication, at least in the early development stages for equipment, and data collection stages for the severely ill study.

I can see the bind he has got himself into with this that means he was not considered a prime candidate for NIH funding.

I don't blame him for the public insulting of the NIH, I think that was all down to someone else to whom he naturally expressed his disappointment.

I hope something worthwhile will come from his work, but I do also understand the criticisms of the hype that has surrounded it. When determination to solve a problem spills over into apparent claims that they will be the ones to find a solution, that becomes problematic.

 

[Alvin]

I have probably said this already, but I think Ron Davis is an exhausted elderly man desperately trying to help his desperately sick son. He also is a kind man who wants to help us all, and give us hope.

He is clearly a very clever man in his field, which, as I understand it has mainly been focused on genetics and the technology for elucidating the genome. He has moved sideways to try to get more research going on ME for obvious reasons, at a time when he might have expected to have retired.

No worries, i also repeat myself a lot
I agree that he probably would be retired otherwise, but some people never retire, i know more then a few people who like to stay sharp and are dedicated to what they do.

I can see why he has acted as he has, focusing on getting data as best he can, and trying everything to try to find a direction for more focused research and hypothesis testing. Because this is a 'non-standard' way of going about scientific research, it probably does not fit well with the requirements of publication, at least in the early development stages for equipment, and data collection stages for the severely ill study.

I disagree, the point of publication is to take your data and submit it to a journal to print for others to read and hopefully use and even expand upon. Until we discover all there is to know it will always be a good thing to disseminate acquired knowledge, though the format may evolve its hard to see this need to disseminate changing.
He is fully able to publish a paper introducing his nano needle, explaining what it does, how it works, the testing they have done so far and its potential. In fact he may be able to get a patent on it as well. If he starts claiming his results are sacrosanct then he will tarnish his own credibility, though with current events it seems credibility doesn't actually matter these days so he should get ahead of himself and he will be rewarded for doing so

I can see the bind he has got himself into with this that means he was not considered a prime candidate for NIH funding.

I don't blame him for the public insulting of the NIH, I think that was all down to someone else to whom he naturally expressed his disappointment.

I don't blame him either, i have also had complaints about them and the FDA, but the point is i am not trying to get money or a drug approved, so my opinions are not held against me. Insults get him further away from the money he wants to get which is the problem.

I hope something worthwhile will come from his work, but I do also understand the criticisms of the hype that has surrounded it. When determination to solve a problem spills over into apparent claims that they will be the ones to find a solution, that becomes problematic.

Hubris can strike at any time, though if he believed he can't find a solution so he won't try he certainly will never find it. The balance of it can be done but don't get cocky can is an issue. As i have also repeatedly said we do need many researchers working on this in different areas, but i don't like throwing away money when its so scarce on researchers who are blowing hot air, but as i stated i'm in the minority. Sometimes when you can't beat them you should join them i suppose

 

[Kalliope]

A short article also in Stirling Times.
Researchers may have come up with a test for chronic fatigue syndrome

 

[Joel]

@Joel, you can critisize in a respectful and constructive way, and you can critisize disrespectfully. Why choose the nasty way? As researcher you must address the reviewer's points nonetheless if you want your results published, so there is no need for disrespect.

Anonymity (e.g. in the internet) gives many people the possibility to be assholes. There are people who don't care about it but I don't like being addressed in a nasty and disrespectful manner. This shouldn't happen in a publishing process.

Our group never made the experience of disrespectful critic by the reviewer, though.

Not sure I explained myself well. It is not an uncommon experience for those submitting papers to occasionally receive some nasty criticisms, and more commonly some polite but disingenuous criticisms. Some people are just dicks, and some have personal or professional dislike for you or your research aims. Handling this stuff can be unpleasant, frustrating, unfair. It shouldn't happen, but it does. However, there are also valid criticisms in the process. In my opinion it is not the fact that people are anonymous that causes the problem as plenty of anonymous reviewers (as well as anonymous people on the internet) behave well. And people usually have a reason for being nasty, an ulterior motive which means they'd still do it if it was an open process. Yes, being anonymous makes it easier to be an asshole in a way that you might not if things were more open, but that doesn't mean everyone acts the asshole because they are anonymous. If you start disregarding all anonymous input as invalid criticism then that's a dangerous approach in my view.

 

[Inara]

@Joel, I understand what you mean. Thanks for clarifying.

 

[Snow Leopard]

I have probably said this already, but I think Ron Davis is an exhausted elderly man desperately trying to help his desperately sick son. He also is a kind man who wants to help us all, and give us hope.

This is a good point and brings up the idea of legacy of an old man - it is not merely about any breakthroughs by Davis, but about all the people he can encourage to enter into the field, whether on his team or not.