The Fight is on...Imperial College XMRV Study

bullybeef

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If people in the UK receive positive results back from the US, questions will have to be asked. Maybe the CDC have successfully replicated XMRV and Europe are going to try and pass it off as a continental virus. I really think the WPI have to come out quickly and respond to this.

Dr. Kerr is working on replications in the UK with the help of the WPI. Maybe he has successfully replicated the tests and Weesly wanted to get in first.
 
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George

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From ME Agenda

http://meagenda.wordpress.com/2010/...nds-no-proof-that-a-virus-is-the-cause-of-me/


January 5, 2010 meagenda BBC: Research finds no proof that a virus is the cause of ME
Shortlink: http://wp.me/p5foE-2AN
Ed: At the time of publishing, no paper or abstract is available. Research criteria and methodology is unconfirmed.
Although a number of UK XMRV related studies have already been identified since the publication of the WPI study in Science, in October, this study co-authored by Prof Simon Wessely had not been publicly reported on.
Dr Jonathan Kerr, based at St. Georges University, London, is involved in several XMRV studies with Whittemore Peterson Institute researcher, Dr Judy Mikovits, and with others, including UK Dr Amalok Bansal and New York, Dr Derek Enlander.
According to an unofficial summary published by Dr Charles Shepherd on behalf of the ME Association following the APPG on ME meeting on 2 December:
XMRV was discussed in some detail at the Medical Research Council Expert Group Workshop on November 19/20 where there were four UK researchers present who are actively involved in XMRV research:
Dr Jonathan Stoye National Institute for Medical Research
Dr Kate Bishop NIMR
Dr Jonathan Kerr St Georges Hospital
Dr Suzanne Hagan Glasgow Caledonian University

There are several other UK virologists involved with XMRV research as well including Prof Greg Towers at University College London, whom CS recently met for an afternoon discussion.
So replication studies and other XMRV research is taking place, or is about to take place, here in the UK.
MERUK plus IRISH ME TRUST has just funded an XMRV replication study in Sweden.
The MEA Ramsay Research Fund has money available for UK studies but money does not appear to be an immediate problem in the UK.
It looks as though there may even be some early results from replication studies before the end of the year.
Was Dr Charles Shepherd aware of this Wessely/McClure study? Professor Chris Mathias of Imperial College London was listed as a participant in the MRCs December CFS/ME Research Workshop.
 
K

_Kim_

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:sofa: (my favorite smilie)
Since this is the second time that someone has posted their fondness for the smilie on the sofa, I'm promoting her to the front page of the smilie menu. Yellow Mr. Cool already has a blue look-alike from our former smilie list, so he's going to [More].
 

parvofighter

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NO - This is BRILLIANT NEWS!

I gleefully beg to differ on whether this is good news or bad. I think it's BRILLIANT news!:D:D:D:D

"Dr" Wesseley and his unscientific ilk have drawn their line in the sand and it is going to spell their doom. What could be BETTER than a huge statement in major media - that is based on Reeves et al disease - not Canadian/Fukuda criteria? What could be better than a virtual admission of incompetence - zero XMRV findings, with this boneheaded and entirely flimsy statement:

Professor Myra McClure, one of the Imperial College London investigators, said: "We are confident that our results show there is no link between XMRV and chronic fatigue syndrome, at least in the UK."
C'mon folks. This is a simple matter of listening to Science. I do feel sorry for retrovirologist McClure - possibly completely "Clured-out" of the massive "oops" in patient selection. OR her PCR is as shoddy as Wesseley's "science"., and she's not a good enough scientist to know it.

Take heart guys - this is a WONDERFUL case of hubris that is going to seriously discredit the CBT/GET lobby. Remember the calibre of the WPI work - it's top notch. Remember the 75 retrovirologists zooming to the meeting @ the Cleveland Clinic. Remember that 3 different labs (NCI/Cleveland Clinic/WPI) have already tested the science of WPI.

There will be many science papers coming out, some of which will be shoddy, some of which will not be. We need to step back, take a deep breath, and then relentlessly critique the science. But in the interim, we can have a blast poking fun at hubris. To whit:
UK scientists say they can find no proof that a particular virus is the cause of chronic fatigue syndrome (CFS) or ME, contrary to recent claims.
"If it had been there, we would have found it."
They analysed blood samples from 186 patients with CFS and found none had the virus
This makes our job of highlighting shoddy science all the easier. Hubris. Lousy patient selection. Flaky PCR. And HUGE hype - and political influence. Yes, there may be minor differences in genetic sequence among XMRV strains. That said, from what we know of the slow replication of this virus, a good PCR assay should be able to pick up multiple strains. They didn't. So they're doing our work for us, and this massive BBC announcement is the first vital step in illuminating their incompetence.

What better way to discredit and humiliate this unscientific lobby, and their spurious "scientific methods" than a great big honking clarion call from them? Yes, there will be other bad research. But give it time. The facts will surface, and when they do - the CBT/GET lobby will have even more egg on their faces. Well deserved - we couldn't have scripted this better.

Mark my words, the BBC will not take kindly to being used as a whipping-boy of Wesseley. In the interim, revel in how humiliating it will be for Wesseley et al when they are proven wrong. Listen to science. Listen to science. Listen to science.

And for a commercial interlude, here's a lovely analogy by a German cardiologist, noting the finding of patients dying of Parvovirus B19 myocarditis in Germany. But not France??!!!!:eek: :eek::eek::eek:

The NIMBY Syndrome in Medicine: Do (Heart) Viruses Respect National Borders?
it is surprising that (researchers) found (Cocksackie Virus-B) enteroviruses to be the only cardiotropic viral agents active in France. In contrast, endomyocardial biopsies in Germany consistently and almost exclusively contain parvovirus B19 (PVB19) and human herpes virus type 6 whereas CV-B is a rare finding.

How can this astonishing difference be explained?

Does CV-B show a tropism for wine-drinking humans while PVB19 is mainly attracted to beer drinkers?
Is there a mechanism preventing viruses from crossing the French-German border?
:D:Retro wink:

Or is the difference not a real one, but is due to methodological differences (PCR primers?)
in identifying small amounts of viral genome.


In Summary: As PVB19 may lead to endothelial dysfunction and is found in the majority of patients with a clinical picture of acute myocardial infarction despite a normal coronary anatomy, one might expect to find also PVB19 genomes in French patients dying of acute myocardial infarction.​
Source: http://content.onlinejacc.org/cgi/content/short/52/1/82
Letter to the Editor: A Geographical Mystery:
Do Cardiotropic Viruses Respect National Borders?
J Am Coll Cardiol, 2008

And finally - one of my favorites on hubris:

OZYMANDIAS (aka Wesseley/Reeves et al.)

I met a traveller from an antique land
Who said: Two vast and trunkless legs of stone
Stand in the desert. Near them, on the sand,
Half sunk, a shattered visage lies, whose frown
And wrinkled lip, and sneer of cold command
Tell that its sculptor well those passions read
Which yet survive, stamped on these lifeless things,

The hand that mocked them and the heart that fed.
And on the pedestal these words appear:
"My name is Ozymandias, king of kings:
Look on my works, ye Mighty, and despair!"

Nothing beside remains. Round the decay
Of that colossal wreck, boundless and bare
The lone and level sands stretch far away
Percey Bysshe Shelley​

Yummy. Bring it ON!
 
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Parvo

Hi Parvo,

I love your optimism!! Thanks for providing a positive aspect to this ridiculous news.

I also loved all of your quotes about the German/Italian thing relating to heart viruses. This one was my favorite:

Is there a mechanism preventing viruses from crossing the French-German border?

This case must indeed be similiar to that case that someone mentioned in another thread - that lyme disease doesn't cross the border into Canada. They must have great border guards that give intensive questions to ticks and turn them back at that point! Wow!

Sorry, couldn't resist the silliness,

Maxine
 

flybro

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I love parvo

NO - This is BRILLIANT NEWS!

I gleefully beg to differ on whether this is good news or bad. I think it's BRILLIANT news!:D:D:D:D

"Dr" Wesseley and his unscientific ilk have drawn their line in the sand and it is going to spell their doom. What could be BETTER than a huge statement in major media - that is based on Reeves et al disease - not Canadian/Fukuda criteria? What could be better than a virtual admission of incompetence - zero XMRV findings, with this boneheaded and entirely flimsy statement



 

Cort

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I hope Parvo is right. This is what I see:

  • They had a very sick population
  • Many had infectious onset
  • Few were working
  • Patients with psychiatric disorders were not included
  • They didn't have any healthy controls but they did test their ability to find XMRV - and they could find it - but not in the CFS patients.
  • They didn't look at the sequences in the Science study - instead they looked at other sequences they knew occurred in XMRV

I'm not worried about the cohort; those people were sick enough to find at least some XMRV in there. As someone noted its all about the methodology. I'm not worried about Wessely - all he did was provide the patients and they looked like they were sick enough. He certainly couldn't beforehand remove those that had XMRV.

My take is either they made a mistake, or XMRV is not in the UK (and hence is not the cause of the disease there), or the WPI found something that's close to XMRV but is different. Cooperative Diagnostics is doing much the same thing (looking for different sequences) and appears to be having similar results.

We really need to have a PCR expert to explain how these things can happen. Should have drug one up before this. Anyone know anyone?

Something very different happened in this study!
 

Esther12

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[What better way to discredit and humiliate this unscientific lobby, and their spurious "scientific methods" than a great big honking clarion call from them? Yes, there will be other bad research. But give it time. The facts will surface, and when they do - the CBT/GET lobby will have even more egg on their faces. Well deserved - we couldn't have scripted this better.
I kind of agree. It seems that there are so many people interested in XMRV, that if there is a strong link with CFS, it will be found.

I kind of disagree, in that I'm not so confident that there is, and worry that if there is not it could strengthen the hands of the quacks. We'll have to wait and see.
 

Dr. Yes

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I've read the article twice now, and a few things stick out:

"All patients had undergone medical screening to exclude detectable organic illness, including a minimum of physical examination, urinalysis, full blood count, urea and electrolytes, thyroid function tests, liver function tests, 9 a.m. cortisol and ESR."

Does this mean that anyone with any positive results in any of these labs was excluded from the study? First of all, that would not be consistent with using the Fukuda physical criteria, but would be with the Oxford criteria. This is a key issue about this study, and needs great clarification by Wessely, who apparently was responsible for cohort selection...??

"All subjects met the CDC criteria [10]"

Here they reference the Fukuda criteria but it's odd that they say "the CDC criteria", knowing full well that those criteria have changed.

"Of note was that 45% said their illness definitely related to a viral illness and 45% said it might relate to a viral illness."

Yes that is of note because those are surprisingly low numbers -- esp. the latter one.

"Both studies use the widely accepted 1994 clinical case definition of CFS10. Lombardi et al. reported that their cases “presented with severe disability” and we provide quantifiable evidence confirming high levels of disability in our subjects."

Now they seem to be saying they used the Fukuda criteria, though it still is not clear whether they used if for overall selection or just used the psychiatric exclusionary criteria in Fukuda. Also, obviously, the Canadian criteria were not used. And, the level of disability does not seem comparable.

O.K. I'm going to read through this again but. . .

Normally wouldn't you:


  1. Test a set of samples that you knew were positive to make sure your PCR was set up correctly?


  1. Yes you would... There's a lot about their study design that I find a bit confusing.. And yes, when they mention that they used a "blinded" PCR technician, that's a clear swipe at the WPI et al...

    Having read the paper I remain surprised by the unprofessional discussion... It is very unusual for researchers to make statements like "Based on our molecular data, we do not share the conviction that XMRV may be a contributory factor in the pathogenesis of CFS, at least in the U.K." based on a single study this early in the game. They might say "we did not find evidence" of it, but it is rare to draw conclusions in the actual research paper, esp. this early on.

    The "at least not in the UK" mantra seems to me, as I mentioned earlier, to be an attempt by Wessely et al to keep their 'claim' on at least those CFS patients who test negative for XMRV. And, again, this really smacks of a pre-emptive, highly political study aimed at limiting funding and interest in XMRV studies in the UK.
 
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Good lord I hope they are disproven!
Alas if all this turns out to be nothing, but there is no need to be pessimistic at this stage, merely apprehensive and cautious. But hey, still a little worrying! :worried:
Agreeing with the definitive statements by the researchers, they are awfully sure of themselves for one study?
 

Dx Revision Watch

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This is the perfect chance for the UK organizations to expose the unscience behind the science. They have ammo now. But do they have guns and do they know how to load them? (As opposed to the response of our advocacy group to XMRV and Reeves' comments in the Times, which was to lock the ammo in a box and hide it in the back of the closet lest someone get hurt....)
Hah!

With fence-sitting-blow-with-the-wind Dr Charles Shepherd (ME Association), and PACE Trial supporters Action for M.E.?
I don't think so - not even a pea shooter.

Although a number of UK XMRV related studies have already been identified since the publication of the WPI study in Science, in October, this study co-authored by Simon Wessely has not been publicly reported on.

A lid has been kept very tightly on this.

We knew that Jonathan Kerr, St. George's University, London, is involved in several XMRV studies with Dr Judy Mikovits, and with others, including UK Dr Amalok Bansal and New York, Dr Derek Enlander. I can confirm from an FOI that the Prof Greg Towers PhD project (University College London) is MRC funded but criteria and some additional information as yet unconfirmed, as UCL say they don't hold this information.

According to an unofficial summary published by Dr Charles Shepherd on behalf of the ME Association following the APPG on ME meeting on 2 December:

"XMRV was discussed in some detail at the Medical Research Council Expert Group Workshop on November 19/20 where there were four UK researchers present who are actively involved in XMRV research:

• Dr Jonathan Stoye - National Institute for Medical Research
• Dr Kate Bishop - NIMR
• Dr Jonathan Kerr - St George's Hospital
• Dr Suzanne Hagan - Glasgow Caledonian University

There are several other UK virologists involved with XMRV research as well - including Prof Greg Towers at University College London, whom CS recently met for an afternoon discussion.

(Ed: No mention of Prof McClure/Wessely.)

So replication studies and other XMRV research is taking place, or is about to take place, here in the UK.

MERUK plus IRISH ME TRUST has just funded an XMRV replication study in Sweden.

The MEA Ramsay Research Fund has money available for UK studies - but money does not appear to be an immediate problem in the UK.

It looks as though there may even be some early results from replication studies before the end of the year."​

It had been thought that these "early results" may have been a reference to the National Institute for Medical Research, based on a remark by Dr Des Turner, Chair APPG on ME.

Has Dr Shepherd been aware of this Wessely/McClure study? Professor Chris Mathias, of Imperial College London (where the study was carried out), was listed as a participant in the MRC's December CFS/ME Research Workshop.


Psychiatrist, Professor Simon Wessely, King's College London, has been claiming since 2001 to have quit the field of CFS research.

On 20 September 2001, the Guardian had published an article by Health Editor, Sarah Boseley:

In this exceedingly emotive piece of journalism, Ms Boseley had reported:

“Prof Wessely has quit the field – and is not the only professional to have ceased involvement with CFS.”
Storm brews over ‘all in mind’ theory of ME, Guardian, 20 September 2001
Just a week later in the Guardian, Ms Boseley wrote:

“Simon Wessely, of the Department of Psychological Medicine at Guy’s, King’s and St Thomas’s School of Medicine in London, is a former key figure in the study of ME/CFS who has felt the heat and largely backed out of the kitchen.”
A very modern epidemic, Guardian, 27 September 2001
More recently, in November 2006, the Group on Scientific Research into ME (GSRME) reported:

“[...] Wessely gave up the [CFS] research side of his work…”
Report of the GSRME: Page 19, Section 3.2 Other Evidence We Received: Prof Simon Wessely

In November 2009, Professor Wessely wrote to an enquirer:

"...I also do very little these days around CFS – I still see patients every week, and I keep reasonably abreast of the literature, but it hasn’t been my main interest now for many years."
Wessely also wrote to a second enquirer, in November, (that response has since been pulled from Co-Cure and from my site, at Wessely's request) but failed to mention to either enquirer that he was, himself, collaborating in an XMRV study.

Since 2002, Wessely has published around 30 papers and articles on CFS and is also an adviser on the design and execution of the MRC funded PACE Trial.

Not a bad output from someone who has allegedly "quit the fiield" , "[given] up the [CFS] side of his work" and who does "very little these days"...

Suzy
 

Esther12

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"All patients had undergone medical screening to exclude detectable organic illness, including a minimum of physical examination, urinalysis, full blood count, urea and electrolytes, thyroid function tests, liver function tests, 9 a.m. cortisol and ESR."

Does this mean that anyone with any positive results in any of these labs was excluded from the study? First of all, that would not be consistent with using the Fukuda physical criteria, but would be with the Oxford criteria. This is a key issue about this study, and needs great clarification by Wessely, who apparently was responsible for cohort selection...??
I was unsure what they meant here too. Are they saying that anyone with unususal cortisol levels does not have CFS? Surely not. That's a big change in the definition of CFS usually used. It would be so incredibly stupid of Wesseley to use a radical redefinition of CFS for this study, that I'm assuming this is not the case for now.

"Of note was that 45% said their illness definitely related to a viral illness and 45% said it might relate to a viral illness."

Yes that is of note because those are surprisingly low numbers -- esp. the latter one.
-
I assumed this meant that 90% of patients thought their illness did or might realte to a virus.
 

Cort

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First they have to find evidence that the study was done incorrectly. We can't assume that it was done incorrectly. My question concerns the different gene sequences used; if both Cooperative Diagnostics and Imperial College have looked conserved sequences of XMRV and failed to find them then I suppose, laymen that I am, that the WPI could have found something else.

The Cleveland Clinic did look at a different XMRV sequence in a few patients - and found it; this convinced them this was XMRV.

The WPI was able to find a whole host of things; they were able to put 'XMRV' infected cells in with other cells and show that XMRV infected those as well. They were able to show that CFS patients with XMRV were responding immunologically to murine retroviruses. I don't know if this finding, if it holds true, effects those others as well.

"All patients had undergone medical screening to exclude detectable organic illness, including a minimum of physical examination, urinalysis, full blood count, urea and electrolytes, thyroid function tests, liver function tests, 9 a.m. cortisol and ESR.
I have the feeling those are pretty standard tests - the tests we've all taken - with no positive results time and time again. Cortisol is a possibility but even the cortisol in ME/CFS is only mildly low - not low enough to draw much of reaction from many physicians.

The XMRV Problem - Of course there's something of a problem with XMRV itself! German studies cannot replicate US studies of prostate cancer patients. Are they looking at different things? Is XMRV heterogeneity greater outside of the US? (Is it a recent escape to the US?). The problem might not be WPI or Imperial - the problem could lie in XMRV itself; its a recently discovered retrovirus - it may have some tricks up its sleeve we don't know about.

I think they actually did try to replicate the patient cohort to some extent; high rates of disability and many with infectious onset. No, the Canadian Consensus wasn't used but if only 19% are working then you gotta think that a good number would have fit that as well. I don't think the problem is in the cohort. I can't imagine that the problem is contamination in WPI- they had NCI and Cleveland Clinic researchers looking over their shoulder. I think some of the work was done in NCI labs. I think they would have caught that. Its got to be something else.

Nancy Klimas warned us about this - there will be reports all over the place; don't give any one too much emphasis.
 
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Robin

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First they have to find evidence that the study was done incorrectly. We can't assume that it was done incorrectly. My question concerns the different gene sequences used; if both Cooperative Diagnostics and Imperial College have looked conserved sequences of XMRV and failed to find them then I suppose, laymen that I am, that the WPI could have found something else.

The Cleveland Clinic did look at a different XMRV sequence in a few patients - and found it; this convinced them this was XMRV.
So this may be an issue of technology rather than science. We do know the CDC is working with the WPI with their tests; if they find nothing that will be a whole different story.

EDIT: and if WPI did find something else, WTF did they find?
 

determined

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we have to wait and see

But I do remember a remark Dr. Klimas made in her presentation that we would hear studies showing xmrv is found in 100% of those with CFS and that it is found in 0% of CFS. The next month or so will be very interesting, to say the least.
 
G

George

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Cort I must respectfully disagree

I hope Parvo is right. This is what I see:


  • They had a very sick population
  • Many had infectious onset
  • Few were working
  • 1-Patients with psychiatric disorders were not included
  • 2-They didn't have any healthy controls but they did test their ability to find XMRV - and they could find it - but not in the CFS patients.
  • 3-They didn't look at the sequences in the Science study - instead they looked at other sequences they knew occurred in XMRV


I'm not worried about the cohort; those people were sick enough to find at least some XMRV in there. As someone noted its all about the methodology. I'm not worried about Wessely - all he did was provide the patients and they looked like they were sick enough. He certainly couldn't beforehand remove those that had XMRV.

My take is either they made a mistake, or XMRV is not in the UK (and hence is not the cause of the disease there), or the WPI found something that's close to XMRV but is different. Cooperative Diagnostics is doing much the same thing (looking for different sequences) and appears to be having similar results.

We really need to have a PCR to explain how these things can happen. Should have drug one up before this. Anyone know anyone?

Something very different happened in this study!

The study recruited 186 patients (62% female, age range 1970, mean 39.611.3years) from consecutive referrals to the CFS clinic at King's College Hospital, London. All patients had undergone medical screening to exclude detectable organic illness, including a minimum of physical examination, urinalysis, full blood count, urea and electrolytes, thyroid function tests, liver function tests, 9 a.m. cortisol and ESR. Patients were interviewed using a semi-structured interview for CFS [9] to determine whether they met international consensus criteria for CFS.

met the CDC criteria [10]; patients with the Fukuda-specified exclusionary psychiatric disorders, or somatisation disorder (as per DSM-IV), were not included.
1.If you are excluding detectable organic illness then how are you working with CFS patients? Most of us have some detectable organic illness, POTs, cardiac damage, brain lesions, thyroid problems, low cortisol, etc. While it's true that they ruled out the Fukuda specified exclusionary psychiatric disorders, no one was schizophrenic, or paranoid delusional you notice that they do not specify that they used the Fukuda criteria to choose patients.

They only state that they choose "well defined" very ill patients. The wording is a little to fuzzy for me.

2. They had one positive XMRV "sample". Where did the sample come from? Is this sample from the WPI or Cleveland Clinic or NCI? They don't say. Only that with each run they ran their positive sample and all other samples came up negative.

With 186 persons there wasn't even one false positive??

3. They looked for different Nucleotide sequences than either the Prostate or the Science study? Why would you do this in a "replication study". If you are trying to refute a work you follow it as closely as possible so that you can outline the flaws of the other study.

Rather than try to replicate the study, they did the study differently by their own admission saying in escecence that the Science study was poorly done.??? Gotta say that takes some big brass ones.


Nearly two decades ago, sequences from another retrovirus, the human T-lymphotropic virus type ll, were amplified from the PBMCs of 10/12 (83%) adult and 13/18 paediatric CFS patients, but not from healthy control subjects [21]. However, subsequent studies carried out on small numbers (2030) of CFS patients, failed to confirm evidence for HTLV (type 1 or 11) [22][25] or other retroviruses, including the closely-related simian T lymphotropic virus type l, the prototype foamy virus, simian retrovirus, bovine and feline leukaemia viruses [26] and HIV-1 [23].
Why bring this up in a replication study??

and this statement in a discussion section??

Our own study also differs from that of Lombardi in other respects. Firstly, the PCR operator was blinded to the provenance of the DNA samples. In fact, with the exception of the PCR controls, all 186 DNA test samples originated from CFS patients. Care was taken to grow the XMRV plasmid in a laboratory in which no MLV had been cultured and no MLV vectors used and the PCR was carried out in a CPA-accredited Molecular Diagnostics Unit which processes only human tissue. Multiple (six) water (negative) controls were included in every run to detect low level contamination and a PCR to amplify a sequence that is conserved in most murine leukaemia viruses was included in order to expose any circulating MLV contamination and to detect any variant of XMRV that might be circulating in the UK CFS population.
That's a flat slap in the face to Science and WPI
 

MEKoan

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Since 2002, Wessely has published around 30 papers and articles on CFS and is also an adviser on the design and execution of the MRC funded PACE Trial.

Not a bad output from someone who has allegedly "quit the fiield" , "[given] up the [CFS] side of his work" and who does "very little these days"...
Truly.

And, how interesting is it that someone with such a deeply entrenched vested interests would rush to publish a study which matches his predictions? :worried: Why might that be?