"Sooner or later they are going to have to face up to the fact that [their] paper is almost certainly flawed beyond repair."

"Abstracts" (misnomer) from 15th International Conference on Human Retroviruses

Exacerbated signs of an immunosuppressive AIDS-like disease in macaques infected with multiple retroviruses
http://www.retrovirology.com/content/8/S1/A207

Restricted infection of xenotropic murine leukemia virus-related virus in human lymphoid tissue
http://www.retrovirology.com/content/8/S1/A208

Heme oxygenase-1 activation inhibits XMRV pathogenesis and carcinogenesis in prostate cancer cells
http://www.retrovirology.com/content/8/S1/A218

XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?
http://www.retrovirology.com/content/8/S1/A219

A prototype RT-PCR assay for detection of XMRV in multiple human sample types
http://www.retrovirology.com/content/8/S1/A220

Immune correlates of XMRV infection
http://www.retrovirology.com/content/8/S1/A221

Prevalence of XMRV in blood donors, HTLV and HIV cohorts
http://www.retrovirology.com/content/8/S1/A222

The effects of XMRV gene expression on the mouse prostate
http://www.retrovirology.com/content/8/S1/A223

XMRV: usage of receptors and potential co-receptors
http://www.retrovirology.com/content/8/S1/A224

Cell line tropism and replication of XMRV
http://www.retrovirology.com/content/8/S1/A225

Independent evolution of intracellular transposons from exogenous IAP-related retroviruses in a broad range of mammalian species
http://www.retrovirology.com/content/8/S1/A226

Structure of the xenotropic murine leukaemia virus-related virus matrix protein
http://www.retrovirology.com/content/8/S1/A227

Development of XMRV producing B Cell lines from lymphomas from patients with Chronic Fatigue Syndrome
http://www.retrovirology.com/content/8/S1/A230

Multi-laboratory evaluations of XMRV nucleic acid detection assays
http://www.retrovirology.com/content/8/S1/A231

Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related virus
http://www.retrovirology.com/content/8/S1/A232

Detection of MLV-like gag sequences in blood samples from a New York state CFS cohort
http://www.retrovirology.com/content/8/S1/A234

Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns
http://www.retrovirology.com/content/8/S1/A235

In vitro assembly of xenotropic murine leukemia virus-related virus CA-NC protein
http://www.retrovirology.com/content/8/S1/A236

XMRV infection in human diseases
http://www.retrovirology.com/content/8/S1/A238

Human infection or lab artifact: will the real XMRV please stand up?
http://www.retrovirology.com/content/8/S1/A241

Hi, "the protocols they have described, if followed to the letter, can yield the data they have reported," yet the protocols were NOT followed to the letter by others.

One reason, they stated in a written response posted online Monday, is that they have isolated XMRV from one chronic fatigue syndrome patient and decoded its genetic sequence. That sequence, they write, is different from the genetic sequences of two known XMRV samples...âSequence data demonstrates that this virus is clearly distinct,â the researchers wrote in their statement.

But the three sequences â published in a federally maintained genetic database known as GenBank â are nearly identical, several retrovirologists pointed out. The differences among the sequences amount to very few bases among more than 8,000.

Proving yet again that the WPI "researchers" are either morons or simply liars.

The thing is that it couldn't really be lying, as they would be doing it better.

The Stoye comments are interesting. Given WPI's own admissions they cannot replicate their results using just the Science methods. When WPI reported back on phase IIb of the Blood Working Group and it turned out they were worse at identifying their own chosen "known positives" than a monkey would do, Mikovits was even quoted as saying:

"We don't do direct PCR. We were asked to do that for the purpose of [the Blood Working Group] study"

They're now saying that they are needing +42 days of culturing in order to produce reliable results and that is supposedly what they are going to do for the next phase of the BWG and also for the Lipkin study. Nothing is said in the Science paper about the need for culturing to detect XMRV.

So yes, they've already implicitly retracted their Science findings.

CDC confirms XMRV is infectious

[spam removed by ERV]

But Dr Speedy,

- That is a "quick and dirty" study with just some PCR and serology.
- PlosOne has a "paid to publish" format!
- PlosOne's peer review system sucks balls!
- Bill Switzer is not even a PhD but a mere MPH!!11!

On a side note, while I above stated that I don't think WPI was actually lying given the apparent silliness of these "disctinct XMRV findings", let's assume the worst:

Suppose WPI were to "fake" XMRV diversity, could they accomplish this with their culturing methods? For instance, could they have theoretically cultured a VP62 strain for (say) six months in their lab and now report this "distict" strain of XMRV and provide this as proof that XMRV is more diverse than first thought?

Or would such a "finding" be easily recognizable by scientists in the field (for instance, because it wouldn't really evolve that much and/or would be easily traceble to its origin)?

Dr. Speedy--
There is nothing to *CONFIIIIIIRM* about XMRV being infectious. We already know it can infect human cell-lines and PBMC. We know that it does not replicate well in their theoretical target cell, PBMC, to the extent they are literally dead-end host cells. But you can take lots of viruses and infect not just human cells, but actual humans, and its not really a big deal (see: every paper looking at zoonotic events in hunters in Africa).

1-- That does not say anything about whether XMRV is a real, pathogenic agent circulating in humans and causing disease
2-- That doesnt 'magically' make the sequences Mikovits uploaded to GenBank not clearly contamination
3-- That doesnt 'magically' make the sequences Alter uploaded to GenBank not clearly ERVs

If the field can still move forward, it is *in spite* of Mikovits and the WPI, not because of them.

With all due respect, culturing as a test is nonsense. PCR is many times more sensitive. The only thing culturing is better at than PCR is getting contaminated.

Oh, right.

We're talking single nucleotide differences in a retrovirus, for crying out loud. You can't easily distinguish that from polymerase errors. WPI has nada except an army of fans and their passionate beliefs. As Trine wrote.

I wonder if I could make a homeopathic tincture of some antivirals and sell it to the fanatics who ascribe to the XMRV/CFS theory regardless of new data. Some might think that a tad unethical but I'd fathom a guess that a bunch of those same wingnuts also believe in homeopathy. (I have to figure out a new plan since this science gig I've been doing for 25 years is circling the drain.) Afterall, at least using a homeopathic antiretroviral won't hurt anyone. Of course, it won't help them either........unless it was all in their head. Ethical dilemma solved.

Evening,

All joking aside, when is the first lawsuit going to be filed against VIPdx, and the Clinical Director of the WPI (Aka 'Dr' Jamie)? I dare say when the dam breaks the fall-out will suck all the money donated right back out of the WPI pot, but VIPdx will simply fold; and 'Dr' Jamie will just lose her right to practice (assuming she still has one of course).

Shame about the, what was it $11-14m joint venture with the University, and the other work that the WPI MUST surely be doing, but have chosen to remain very quiet about.

Was there not a clinic being opened? And other 'stuff' like other research and even 'treatments' being touted, right? You know all that $4 million or so from hard-up desperate people - where has it gone, surely not all into 'XMRV'?

I thought you Americans were into litigation? I mean we Brits are catching up, but you guys are the pro's - so when will the first proceedings take place? And what can be done anyhow?

After all the hype there are still people who had their blood tested believing that CFS = Human Infectious Retrovirus = HIV = AIDS = a quantifiable cause for all their years of suffering and humiliation.

When this broke in 2009 if I had been in the first five years of my diagnosis of CFS/ME, then I have no doubt that I too would have submitted to the blood tests. I was desperate to 'prove' this crappy label was not responsible for the extent of my suffering.

As it was I spent my cash on run of the mill immunologists seeing as parvovirus and others were suspected by them as being the initial trigger. But that initial infection seemed to run it's course, though it also appeared to have knocked my immune system or somesuch and... well... I shan't bore those who think they have heard all the tales before...

Then came the 'quacks' and my desperation was running at levels of madness I hope nobody ever feels the need to repeat. Alternative practitioners of 'cures' do not come with the implied expertise of scientists like those who have continued to promote the XMRV = infectious human retrovirus = anti-retroviral treatment or else - policy.

My empathy towards those who have tested 'positive' remains as true today as ever. I have no empathy for some of the idiots still frequenting some forums assuming to speak with such authority for all of us labelled the same.

Originally, the 'link' 'proving' that 69%* and then 95%* of CFS sufferers' BLOOD(critically assessed by woohoo criteria that also really really took 'mentally ill' peeps out of the equation because you can't be mentally ill AND have 'CFS' - oh no) was infected with this 'human retrovirus' was exciting. It seemed to 'fit' it seemed... well... after a fashion... too good to be bloody true!

Now I am not saying that this little retrovirus thingamajig ain't real, in some form or other, or for that matter, that Singh is not going to announce at some point that her Prostate Cancer study was wrong in concluding an 'XMRV' presence. Though maybe she, like Mikovits, will also conclude 'A XMRV'-like retorvirus is now responsible for that one - who knows?

What I do know is that the longer the resistence of the WPI and others continues in this vain, the longer the damn insistence that ARVs are sooo cool and that anyone 'postive' who doesn't take them should be afraid, very afraid; and that anyone with kids, should be afraid, very afraid; and anyone having sex should be... well you get the idea - basically just be afraid: the harder it is going to be to get anyone to take CFS sufferers as seriously again.

Tarnished once more. Should be bloody used to it I guess. Might even write a book on the subject... 'How to remove stains and not influence people'.

(*or whatever the exact figues am in a pissy mood and can't be arsed to check them again)

Actually Amy Dockser Marcus with the WSJ has done a more professional job than Ms. Tsouderos in terms of following journalistic principles and protocols. Like science, journalism requires adherence to standard protocols. As for cupcakes - no free lunches in journalism either.

It was interesting that Ms. Tsouderos truncated Dr. Racaniello's quote about antibodies. What he actually said was the antibodies aren't specific to XMRV and could be to a different retrovirus.

So if it isn't XMRV which one is it? Or does this open the door to the possibility to as yet unknown retrovirus? Science is as much about possibilities as it is negatives.

The thing is that it couldn't really be lying, as they would be doing it better.

On the other hand, if someone is not lying, wouldn't they do it even better? They don't need to lie well to scientists to lie to patients.

Re: lawsuit

Not soon enough to get them disqualified from winning hundreds of thousands of dollars from Chase Community Giving next week.

Re: Racaniello quote

I don't see too many ways of reading "not specific to". I'm not sure that a different retrovirus is the only possibility. Why do patients think that not XMRV equals not anything?

With all due respect, culturing as a test is nonsense. PCR is many times more sensitive. The only thing culturing is better at than PCR is getting contaminated. Oh, right.

PCR is extremely easy to contaminate as well. Just ask Dr. Montagnier and his contamination...I mean...magical teleporting DNA.

It was interesting that Ms. Tsouderos truncated Dr. Racaniello's quote about antibodies. What he actually said was the antibodies aren't specific to XMRV and could be to a different retrovirus.

KAL-- Trine was referencing her correspondence with Coffin, Racaniello, and Stoye.

You cracked her email account and know she 'truncated' the quote?

Or did you confuse a statement from 'Virology Blog' with her personal email?

Accusing a journalist of misrepresenting their sources is just as bad as someone accusing a scientist of misrepresenting their data. Bad form, KAL.

Uh Erv,

Trine basically spit out a press release story that added very little to the May 6 article - nothing intrepid about that and from a journalistic point of view not very impressive. Would you like to crack my email to read the release and compare?

As well, I never said that Trine misrepresented her source - where on earth did you get that from? (I have the highest respect for Dr. Racaniello.)

As for email please point out where in this sentence the word email appears:

"But virologist Vincent Racaniello of Columbia University said that canât be true. âThere is no way they can say that the antibodies are specific for XMRV,â Racaniello said."

Herp durp, KAL. Yeah, it didnt add NUTHIN! Only extremely damning quotes from the two scientists who wrote the support article for Lombardi et al. DURP.

And "I never said that Trine misrepresented her source" DURP! "I only said she truncated the quote from her source, thus misrepresenting his views on this topic", aka, a 'quotemine'. Thats, liek, TOTALLY different! DURP.

And maybe a 'clue' about the email would be the fact she talked about her communication with the three scientists, and didnt reference 'Virology Blog' or a forum or any other internet medium, like she has in the past. Of course, it helps not to be blinded with rage when you read an article so you can actually read what is written, and not what you want it to say.

Yeah, no, keep spreading the 'SHE MISREPRESENTED RACANIELLO!!! THIS IS THE REAL QUOTE!!!' meme, asshole.

Shame about the, what was it $11-14m joint venture with the University, and the other work that the WPI MUST surely be doing, but have chosen to remain very quiet about.

Was there not a clinic being opened? And other 'stuff' like other research and even 'treatments' being touted, right? You know all that $4 million or so from hard-up desperate people - where has it gone, surely not all into 'XMRV'?

They did one fairly small study with the Virochip before XMRV, but there's no sign they're doing anything else now. The P in WPI bailed pretty early on after getting annoyed that they're doing nothing else, and it sounds now like he probably thinks it's contamination. They're probably too far out in lala-land to be taken seriously if they did publish anything else now.

It is a real shame they decided to go like that, the WPI should've been the best thing ever to happen for CFS research. Harvey Whittemore might be a bit of a dick, but having a billionaire with a few politicians in his pocket on our side should be pretty useful. It's gonna be pretty hard for them to come back from where Mikovits is taking it now though, and we haven't even seen any signs that they want to try.

Kiwi,

I noticed yesterday that Anne Whittemore and Mikovits are to meet with British Members of Parliament later this month ahead of the Invest in ME Conference: http://www.meassociation.org.uk/?p=6129

I just want someone to ask for details of what else the WPI are up to, you know? Where has all the money gone specifically? What are their plans for the clinic (they seem to have cash-flow problems again)? And if they get all this extra cash through Chase - what will it be used for? Some accountability, you know?

They don't seem to be doing themselves any favours to migigate the effects of the 'link' if indeed the 95% of blood 'infection' proves unsustainable.

Thousands of sufferers are happily donating their cash with no idea as to what those pennies will be actually used for...

N.B.

It appears Ms. Tsouderos and Prof Racaniello are to hold a Live health chat - 'Virus Advice' next Tuesday:

http://www.sun-sentinel.com/health/ct-health-chat-viruses,0,3358676.htm…

Be interesting to hear Trine and the Professor speak about 'XMRV' and I guess they will be fielding questions from the 'kooks' (is that the correct phrase ERV? :)).

Jack

The only part I don't understand is why we are not suggesting that the few positives in the latest CDC study on XMRV are also likely to be due to contamination.

@Jack:19

I've enumerated some of the early WPI finances at:
http://cfsmirror.blogspot.com/2011/02/creating-research-base-isnt-like-…

The Whittemore's offered up a lot more cash than they appear to have actually parted with and in terms of funding the CFS/XMRV research, the US Government has provided (up to 2008) more to the WPI than had come from either the Whittemores personally or from revenue from WPI fundraising. Of course more funds may have come in from individuals in 2009 and 2010 but there appears to have been little in the way of reasearch progress since the Science paper was published on the basis of work funded up to 2008. The WPI have put out figures suggesting 3,000 people have been tested via the VIPdx laboratory (owned by Harvey Whittemore), this would likely equate to around a $1million in fees paid by people for a test that appears meaningless and has only served to raise anxiety about an organism that has no connection to disease causation and is at best only very weakly infective. Even if the WPI motivation was benign, is this really the kind of behaviour that would be expected of charitable institution ?

IVI

is this really the kind of behaviour that would be expected of charitable institution ?

I remember seeing one of their most ardent supporters post on their Cause Wall about literally donating out of her food money.

IVI - I do believe that the WPI have been led by the nose, and no their behaviour (and lack of published information), is not what I would expect from a 'non-profit' and 'heart is in the right place' organisation, that has become the 'only hope' for some very desperate and blinkered people.

This was flagged up yesterday. It is a 'new' study from Lombardi and Mikovits about 'gene expression analysis establishing an immunological pattern in XMRV-positive patients'.

ERV - over to you dear heart:

http://www.prohealth.com/library/showarticle.cfm?libid=16156

If you can still feel willing to dance, that is :)

When ProHealth posts articles about anything, it's not good. That site is a woo-factory, a woo-pandering woo-a-licious woofest.

So from the abstract of the "new study"

"Background: The recent identification of xenotropic murine leukemia virus-related virus (XMRV) in the blood of patients with chronic fatigue syndrome (CFS) establishes that a retrovirus may play a role in the pathology in this disease.

Knowledge of the immune response might lead to a better understanding of the role XMRV plays in this syndrome. Our objective was to investigate the cytokine and chemokine response in XMRV-associated CFS."

First of all, finding XMRV in the blood of patients diagnosed with CFS, does not mean that XMRV is a pathogen that causes CFS. Secondly, how does one know that the "immune response" is down to XMRV, might be something else.

Shouldn't they be producing a few more replication studies -- if the first premise is wrong, then following research will be bullshit.

XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?

http://www.retrovirology.com/content/8/S1/A219

Now I am very interested to what this paper is going to say.

Why am I interested?

Well, quite a while ago, I contacted one of the researchers in that study by email and told them they needed to study the mucosa and figure out what the heck the crimson crescents are in CFS patients.

I received emails back from all the researchers I contacted thanking me for the suggestion and/or stating that they may consider looking look into that. And none of them heard of crimson crescents, probably because there are no medical journals that I know of that have tried to explain this phenomenon.

So I'm very interested if they are looking at the crimson crescents as I suggested. Studying them and figuring out what those are may be of a lot of importance in my opinion (even if they have nothing to to with XMRV). I'd be more interested if somebody as little as me has influenced science.

I am not one to sit back and watch. All researchers I contacted with the exception of Dr. Coffin have been interested in communication, which I think is phenomenal.

And here is the full text:

Xenotropic Murine Leukemia Virus-related Virus-associated Chronic Fatigue Syndrome Reveals a Distinct Inflammatory Signature

http://www.serendipitycat.no/wp-content/uploads/2011/05/XMRV%5ECFS_Infl…

I think this study is very important, but I have a feeling that people are going to dismiss it because it mentions XMRV. Inflammatory signatures may aid in diagnosis, identifying subgroups, and it can be used to demonstrate how well treatments work even in the COMPLETE ABSENCE of XMRV.

I think this may be the most important paper yet, and I hope it is not ignored because the the XMRV acronym.

My point is that identifying a distinct inflammatory signature (along with all the different subgroups) in ME/CFS is all we really need to begin exploring potential treatments. Replication shouldn't be too trivial as long as they use a relatively strict selection criteria to exclude those with things depression or other illnesses.

And I am not talking about ARVs. I am simply talking about immunomodulators.

For now, until there is more evidence to prove or disprove an association, let's not let names of retroviruses and acronyms halt the progress science. Let's continue to push science forward.

"And the band played on."

Further to my last the Lombardi and Mikovits paper was published in the Journal 'in vivo 25: 307-314 (2011)'.
This is my understanding, but I canne find it captain. Although the full paper can be downloaded here:
http://www.megaupload.com/?d=V980UCHY
As an aside this was also apparently referred to by Mikovits last year at a retrovirology conference in Prague:
http://www.crm2010.org/images/stories/pdf/CRM2010-Programme-and-Abstrac…
That would be on page 58, in case you boffin-types care to take a peek.
Any light that can be shed on this Lomardi paper would be mucho appreciated.
Ta Ta For Now :)

I was on that conference in Prague and went to look on that poster, but J.M. decided to present some data about XMRV in prostate cancer patients. This looked to me like a complete set of data ready to be published, but I'm still waiting for that one. No need to say that most of the retrovirologist were more sceptical than enthusiastic about the incredible number of XMRV-positive cancer patients with virus loads in their plasma...

Jack-- I def have something to say about that paper, but Im waiting to get one more piece of info before I say anything. Ill probably have a post up tomorrow or Tues :)

Hey thanks Camaro and ERV.

I guess ERV your dancing shoes are still ready to rock and roll :)

Interestingly enough, an XMRV symposium is scheduled the day after the 15th International Conference on Human Retroviruses.

XMRV Symposium -
Brussel 9 juni 2011

XMRV, a novel retrovirus is here to stay

June 9th - Faculteit geneeskunde en farmacie

Vrije Universiteit Brussel
Laarbeeklaan 103 - 1090 Brussel

4 pm - 7 pm

Info: MarleenVL@ehmb.be

Presenters:

Mikovits (USA)
Hansen (USA)
Cabrera (Spain)
de Meirleir (Belgium)
possibly 5th speaker (USA)

Admission: free

Programme to be announced next week

Regarding the new Lombardi paper you just have to know that they simply ignore the fact that XMRV in CFS is far from being proven. They don't even mention all other papers in their introduction and discussion, which happens sometimes also in other publications in other journals, but is nevertheless no good scientific practice.

I think this study is very important, but I have a feeling that people are going to dismiss it because it mentions XMRV. Inflammatory signatures may aid in diagnosis, identifying subgroups, and it can be used to demonstrate how well treatments work even in the COMPLETE ABSENCE of XMRV.

I think this may be the most important paper yet, and I hope it is not ignored because the the XMRV acronym.

I don't know the first thing about cytokines, but I'd guess if this doesn't get ignored because of the XMRV claims it'd be useful without being huge. We've had people talking about cytokine levels being abnormal for years now, it'd be nice to have a study that could nail down what those abnormalities actually are. Looking at figure 1 their 93% specificity and 96% sensitivity seems a bit hard to believe though, it looks like there's just too much noise in there to be much use for a clinical test.

Even if you grant them their claim that the patients were all XMRV+ this does nothing to prove it has anything to do with it. Without comparing it to XMRV- patients (but I guess that's hard to do, their super-great testing's probably up to about 300% testing positive by now the way it was going) it doesn't tell us much about that.

That symposium lineup's looking pretty anaemic too

Kiwi - the answer is simple - just use all those 'diagnosed' with CFS that don't 'fit' their preferred criteria for inclusion - you know those peeps who happen to have depression - gods forbid - or who meet one 'criteria' and not another.
Simple. Or I am :)

From what I can tell there are numerous quite severe flaws in the recent WPI-cytokine/chemokine paper.

1. According to another of Dr. Mikovits' presentations*, all of the patients in this study came from the original Incline Village outbreak cohort and were diagnosed by Dr. Dan Peterson. All samples were collected prior to the WPI's 'discovery' of XMRV in CFS patients' blood and were from a very homogenous cohort, therefore the patients' putative XMRV status was not the stratifying factor for their participation in the study. As such, the cytokine/chemokine profile reported in the study could simply be due to it being such a relatively homogenous cohort and have absolutely nothing to do with the patients' putative XMRV status. If the WPI really wanted to see if this cytokine/chemokine profile was due to XMRV infection then they could have used samples which either came from the patients in the Science study, which the WPI stated were randomly chosen from their Biobank, or if these samples were not still available then another group of samples which were randomly selected from their Biobank, tested for XMRV status and then analyzed. Since they did not randomly select patients and determine XMRV status in order to select their cohort this study is quite limited in it's findings and show absolutely nothing in regards to legitimising XMRV's potential involvement in CFS.

2. Also something I just thought about last night and is really kind of mind-blowing to think about, shouldn't the WPI have selected as controls other individuals with gamma clonal T-cell rearrangements in order to determine if the cytokine/chemokine profile was due to this rather than XMRV/CFS status as the study implies? Since they did not, is this study anything more than pulp?

*http://www.wpinstitute.org/news/docs/Invest_in_ME_20090529_Mikovits.pdf

Hi John,
1. I believe (but do not know for certain) that WPI used the selection of XMRV+ patients, because they were pretty certain these people would be as defined for having 'CFS' as they could possibly hope them to be. Not because of their alleged positivity - yeah I know it could be a pants explanation but 'tis a popular one doing the rounds.
2. Haven't got a clue :)

@John

That WPI only used samples from one single outbreak is a good find and pretty bizarre (given the fact that this isn't mentioned in the paper) if you ask me.

Come to think of it - it seems that all those Incline Village patients, all 118 of them, are infected by XMRV (and, of course, at detectable levels ;-) ). That is also pretty bizarre considering the fact that (given the presentation John posted) they weren't selected for XMRV status.

Kiwi - the answer is simple - just use all those 'diagnosed' with CFS that don't 'fit' their preferred criteria for inclusion - you know those peeps who happen to have depression - gods forbid - or who meet one 'criteria' and not another.
Simple. Or I am :)

Despite what you are read, there are plenty of biomarkers to support the diagnosis of CFS. In the first major documented outbreak in NV, doctors noticed that patients had an abnormally low sed rate (many patients have sed rates of 0). There are only 5 diseases that I know of that have sed rates this low, and ME/CFS is one of them. It's even worse that medical students are still taught a sed rate of 0 is normal. There are many more biomarkers I could use as examples, but this was one that was found in the early days.

In the past, they somehow twsited the information that said "There is no single biomarker to confirm the diagnosis of CFS" into "There are no biomakers for CFS." All the weird name changes and bold statements such as "there are no biomarkers" were political move to in attempt to delegitimize the syndrome, hoping that it would just disappear. Well, that obviously didn't work, and advocacy groups are just getting more and more vocal, forcing the government to take action in attempt to save face.

The CCC criteria is very good (while the CDC criteria is complete rubbish). I don't think most true ME/CFS patients even fit the CDC criteria, so I'm not sure who they designed it for. In the end, by using any of these criteria, you are probably a lot more likely to pick up people with other diseases. ME/CFS can cause organic and/or situational anxiety/depression in many or most cases, so it's easy to see why a less knowledgeable human selecting patients for a study could mistake one syndrome for the other. And unfortunately, probably because of the name, many physicians will use CFS as an umbrella diagnosis for patients with chronic complaints (and fatigue) lasting more than 6 months. I don't blame them. They are just using (and believing) the information the CDC provides them.

I think the best way to identify patients is having physicians that have been involved with disease for the past 25 years. They use biomarkers and other testing to support their diagnosis instead of making a complete clinical diagnosis with whoever's criteria.

The funny thing is that the reallycrazyforums have now created this "International M.E. Association" as some online entity and are now collectively constructing "press releases" to "debunk" the "bad science".

The dyslectic makes up the science as he sees fit and then others will translate his musings in English. Here's their magnum opus thus far, a critique of the Singh study:

http://www.imeassoc.com/Response_to_Shin_et_al.html

It seems these people have too much energy instead of too little.

I simply can't be arsed to look RRM. No more pllleeeeaaasseeee :)

At any rate the PACE trial response from the Lancet is out and that should keep em busy for a while:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%296…
You's can get yerself access to the Author's reply too :)

It seems these people have too much energy instead of too little.
At any rate the PACE trial response from the Lancet is out and that should keep em busy for a while:

You know, if they try real hard, no scientist on Planet Earth will want to have anything to do with CFS research.

Which Im starting to suspect is exactly what that group of individuals wants.

Yeah, like ARVs rock and all else is pants baby ;)

Erv, I think you are right, but I see it just a little bit differently. Some people with CFS are angry, want to âblameâ someone and want to âfightâ to get over it. Unfortunately that is the opposite of what they need to do to get better. That mindset keeps triggering the âfight or flightâ state, which is what put them in the CFS state in the first place, triggering it again and again only perpetuates CFS in the long term, even if it makes people feel better in the short term. That is what the âfight or flightâ state does in the short term, it makes you feel as if you have more energy (even when you don't) because you need to feel like you have more energy if you are going to keep running from a bear.

I think that being a part of a group that is âfightingâ something does have a positive effect in reducing the psychological need to individually trigger as severe an individual âfight or flightâ state. When the âfight or flightâ state can't be sustained, humans trigger the âStockholm Syndromeâ state and bond to individuals with the most power in the social power hierarchy, even if those individuals are the ones that put them in the âfight or flightâ state in the first place. This is seen a lot in politics of the fear-mongering-type.

Unfortunately being in the âfight or flightâ state triggers the feeling that you need to âfightâ. If you are running from a bear, it is good to have the feeling that you need to âfightâ, and even to âfight to the deathâ because that is the same as letting the bear catch you. But those feelings are not helpful when what is needed is something that can't be accomplished by fighting, like cooperation.

When you are in the âfight or flightâ state, you have the âhammerâ of âfightingâ and try to apply that to every problem that you have, even when those problems can't be solved by fighting. This is the physiology behind the âdivide and conquerâ strategy. If you push people into the âfight or flightâ state, they will tend to fight amongst themselves, make themselves weaker and then be easier to manipulate and exploit when the âfight or flightâ state fails.

That is what is playing out in the XMRV scenario. The âdataâ behind the association of XMRV with CFS was never that great, and there is still no plausible causal mechanism for the physiology of how infection with any virus would cause CFS. But desperate people will do desperate things and desperate people are easier to exploit. Pretend to be their friend, and they will let you exploit them. Sic them on your opponents and you can acquire more power and social authority even as you do nothing to actually solve their problems. None of this needs to be conscious for it to play out this way.

there is still no plausible causal mechanism for the physiology of how infection with any virus would cause CFS

Perhaps I am misinterpreting what you are saying, but what?

I know you have a great understanding of NO, but I think having a great understanding in something very specialized that's where researchers get stuck in their own ideas.

The neurologist thinks it's all the brain. The cardiologist thinks it's all the heart. The virologist thinks it's all viruses. The infectious disease specialist thinks it's all pathogens. The psychologist thinks it's "all in the head". Experts in methylation think it's all about the glutathione-depletion methylation cycle block. And then there are some who think it's all in the gut.

During the first major documented outbreak, 11 out of 12 people got sick that used the same teachers lounge. Just about everyone on the girls' basketball team got sick.

Is it infectious? It's hard to say for sure, but if it's not infectious, there must have been some really potent environmental component during the outbreaks. I personally think there may be an infection/environment link. Perhaps genetics comes to play some, but considering a whole girls' basketball team got ill, I'm not sure how much of an impact genetics has on this illness.

And FYI: I got ill in the same location as the people I speak of but not at the time of the outbreak.

Conclusion: We really haven't got a clue.

Also, a sibling of mine is ill as well. My onset was instantaneous and much more severe. While our symptoms are quite different in a lot of ways, we also share common symptoms.

If you look at our throats, we don't have normal tissue, nor do we have a sore throat. However, doctors have missed this clue since the beginning since the location of the crimson crescents isn't where a doctor looks when examining the throat. I have checked family, friends, and relatives, and no healthy person I have looked at have these characteristic crimson crescents, but from what I have read some healthy people have them (latent virus?).

It's too bad nobody has really studied them thoroughly, but I've been in contact with researchers about this matter and have been told they are looking into it.

If these characteristic red crescents aren't infectious, what the hell are they? They aren't some random occurrence, they are extremely common in CFS. They NEVER go away, and there is no soreness or pain.

Analyst,

'Conclusion: We really haven't got a clue' is - in my humble opinion and based on my own experience in times past - what creates the anger.
That professionals don't 'have a clue', seemingly after 'all this time', and yet more people are being 'diagnosed' purportedly with the same, albeit wholly inadequate and ill-defined, illness; creates frustration, then anger, and then subjective and vidictive attacks on specific researchers and research papers which don't seem 'right' or belittle ones concept of what is 'wrong'.
It is I suggest, a largely emotive response. Acceptance is so very hard, particularly with a longterm fluctuating condition, about which no-one 'seems to be any the wiser'.
You pick yourself up to a lesser but more manageable life given your incapacity - just as other disabled people do - and then WAMMO the chair is kicked from under you again.
It ain't nice and it ain't pretty - but we aren't the only ones having to deal with an illness as uncertain and without known cause or specific treatment.
Hard to accept but true.

And when I say my onset was instantaneous, I mean that.

I went to bed perfectly happy one night, and woke up the next morning literally bed bound only having enough energy to drive to the doctor's office. I had no stress in my life. I actually went to bed really excited that my cousins were coming to visit, but then I couldn't do anything with them when they arrived the next day.

And at the time, I had a severe infection from a tick bite. My doctor took a look at it said my symptoms had nothing to do with the infection, and that I was basically just nuts after coming every week or so. I wasn't prescribed an antibiotic despite having an extremely large lymph node that resolved itself in several weeks. I have never had noticed such a large, hard lymph node in my entire life. My WBC count and bilirubin were a bit elevated, but I was told everything was normal.

And yes, I quite sure I have ME/CFS. I feel there may be a strong link between ME/CFS onset and tick-borne infections (perhaps because many tick-borne infections are quite scary and cause huge surges in stress).

It no longer bothers me that many people don't believe in chronic tick-borne diseases, because I feel that one day they will look back, remember what I told them, and say, "Wow, he was right."

Analyst, what I mean is that the physiology of what causes âfatigueâ is not well understood or appreciated. Fatigue is a âfeelingâ, not an objective physiological state. If you take someone who âfeelsâ fatigued, and give them a gigantic dose of stimulants, they won't âfeelâ fatigued any more, they will feel like they can do anything, they will feel like they can run a marathon. They can't, but they will feel like they can.

Fatigue is a symptom that accompanies many different disorders. What is the physiology of fatigue? Why does physiology make us feel tired? Presumably âfatigueâ is a signal that physiology is using to tell us the status of our bodies so that we can evaluate the risk/reward balance in continuing to do stuff. Is there any evidence that the âfatigueâ of CFS is fundamentally different than other types of fatigue? I don't think there is. The only distinguishing feature of the fatigue of CFS is that the fatigue doesn't go away.

I think the problem isn't with the physiology that causes fatigue, the problem is with the physiology that compensates for fatigue. A great many of those fatigue compensatory pathways are triggered by NO. Low NO turns them off, and diverts those resources to ârunning from a bearâ, high NO turns those compensatory pathways back on and diverts resources back to healing, mitochondria biogenesis, and so on.

When you are running from a bear, any level of damage is acceptable if it allows escape. Your body turns off the feelings of fatigue and pain and replaces them with euphoria. You will feel like you can run forever, but you can only run until you drop dead from exhaustion, or until the bear catches you, both of which are the same as âforeverâ a far as your body is concerned. When you are not running from a bear, you still have feelings of fatigue so you don't damage your body needlessly.

When you have an infection, and need to divert resources to your immune system, your body induces feelings of fatigue so that those resources are available. If you ignore the fatigue and use those resources to do other things, they are not available to fight the infection. Sometimes that is a good idea, such as if you are being chased by a bear. Other times it is not a good idea. Masking the feelings of pain and fatigue with analgesics and stimulants doesn't magically give you more resources, it simply masks the feelings of pain and fatigue.

Metabolic insufficiency in any tissue compartment, heart, liver, muscle, lung, can produce feelings of fatigue. What is the common pathway that integrates all those signals together and presents them to the CNS in a form that the CNS interprets as âfatigueâ? The CNS has the ability to override those signals of fatigue and will do so if a bear is chasing you. That signaling has to be related to energy status of the different tissue compartments which has to be integrated so the CNS can figure out what it needs to do to survive.

NO does signal energy status. High NO means high ATP, low NO means low ATP. Physiology then used the ATP level as a signal to turn pathways on and off. Muscle can continue to consume ATP voluntarily until the muscle necroses. What that means is that voluntary muscle activity has the lowest ATP threshold and if you continue to tell your muscles to consume ATP, they will until there isn't any left and they necrose.

How does a viral infection cause fatigue? It somehow has to trigger the physiology of fatigue that triggers the signals of fatigue to the CNS so the CNS can respond appropriately. Responding appropriately depends on the circumstances. It always involves shutting down non-essential systems. What is a ânon-essentialâ system depends on the circumstances. If you are running from a bear, your immune system is a ânon-essentialâ system.

I have an extensive write up of the physiology of fatigue and its connections to NO status. Send me and email and I will send it to you.

Some more XMRV news: the new WPI sequences are now in Genbank.

Also, I find this statement by Singh regarding her study to be pretty interesting (I hadn't read about this 'problem' before):

"The nested PCR was done as described in Lo et al, with one small modification. We used the dUTP-UNG system to prevent contamination of our lab with PCR products.

Since nested PCRs involve opening of tubes containing a PCR product, the danger of this product contaminating other equipment, reagents and samples in the lab is very real. Once contamination has occurred, it is very difficult to get rid of it. Any reputable lab that uses PCR as a test on clinical samples, uses dUTP-UNG. It has been shown to not affect the PCR itself, and to provide a very real safeguard against contamination.

I do not know why Lo et al or Lombardi et al used a process prone to contamination like the nested PCR, and then did not use the dUTP-UNG system (youâll have to ask them). But I could not risk contaminating my lab with PCR amplicons â then every subsequent test we did would be suspect."

Source: http://phoenixrising.me/?p=5568

She sounds rather angry.

I don't know that much about PCR (which I freely admit), so maybe someone could answer these questions for me, which I think would be obvious to someone with even minimal expertise in PCR.

When you get a "positive" detection of XMRV via PCR, isn't it possible to sequence the resulting sample and verify its sequence?

When one does a PCR test and it is "positive", doesn't one "save" it to do other things with? Such as sequence it?

Shouldn't the WPI group still have all those "positive" samples?

If they sequenced them all, wouldn't that go a long way to establishing that they are not "contamination"?

Why haven't they?

They have reported hundreds of positive PCR results (as I understand). Sequencing even 10% of them would go a long way to establishing that they are not contamination.

Yup.

*blink*

So why don't the people funding the WPI group ask the WPI group why they haven't sequenced their positive XMRV PCR results?

It seems to me that not having and publishing sequence results on their "positive" XMRV PCR results this long afterward calls those results into serious question.

I mean, anyone else could just cite the paper, but if the authors cite prior PCR results that they have not even bothered to sequence, when the issue of contamination has been raised, why should anyone allow them to publish a new paper? Or fund any more research?

Daedalus2u - those funding the WPI are in whole or in part those most desperate to believe the belief - maybe ;)