Lack of Detection of XMRV in Seminal Plasma from HIV-1 Infected Men in The Netherland

[SOC]

And same crap journals (PlosOne, Retrovirogy) in al this neg studies

<snip>

how could this crap still pass peer reviews?????

I imagine the PlosOne and Retrovirology connection is highly relevant. I believe I was told PlosOne is not peer-reviewed, but I'm not sure if that's true. Anybody know?

I suspect Retrovirology of a very incestuous review system for XMRV papers in which Wessely, Reeves and their cohorts review each others' "research". Just my nasty suspicion, though.

EDIT: I did a very quick investigation and found that PlosOne is actually nominally peer-reviewed. The question is whether the people who review and decide to publish are actually academic peers who would know the background of the topic. There is some question about whether papers on topics that are important (or newsworthy), but have a very small group of knowledgeable researchers are adequately vetted in this publication format.

Here's a blog article that discusses some of the pros and cons of open access scientific publishing. http://journalology.blogspot.com/2007/01/peer-review-lite-at-plos-one.html

I overdid yesterday and don't have the mental energy to do any further research. If someone else is interested, go for it.

EDIT AGAIN: Told you I'm off today. Eric already addressed this a lot more coherently. Sorry.

 

[leelaplay]

Part of the problem with PLOS is that people pay to get their articles published. Hmmmm - why would researchers do that?

Too tired to check now, but I think that they also might select who will "review" their article - but someone will have to do the digging on that to confirm.

"PLoS journals use a business model in which our expenses—including those of peer review, journal production, and online hosting and archiving—are recovered in part by charging a publication fee to the authors or research sponsors for each article they publish. For PLoS ONE the publication fee is US$1350."

 

[ixchelkali]

A local outbreak of CFS in the USA in 1984 was postulated to be associated with XMRV [1], [8].

Wrong

That statement isn't wrong. They cite van Kuppeveld et al, and the van Kuppeveld paper DID postulate that:

As technical aspects do not seem to provide an explanation, the difference might be explained by the two cohorts studied. Our patients met the Oxford criteria for chronic fatigue syndrome, whereas the patients studied by Lombardi et al were reported to fulfil the Centers for Disease Control criteria,7 but this is unlikely to explain the absence of XMRV in our patients samples. Unfortunately, the paper of Lombardi and colleagues lacked a clear description of their patient cohort. Recently, at the Tri-Society Annual Conference 2009 in Lisbon, a presentation reported that the peripheral blood mononuclear cells were derived from patients from the outbreak of chronic fatigue syndrome at Incline village at the northern border of Lake Tahoe, United States (1984-5).19 This outbreak has long been thought to have been caused by a viral infection and has been associated with a number of viruses, most notably Epstein-Barr virus20 and human herpes virus 6,21 but firm evidence for a role of viruses in this particular outbreak has never been provided. It is possible that the study of Lombardi et al has unravelled the viral cause of the chronic fatigue syndrome outbreak, but it seems unlikely that their study demonstrates a viral association for sporadic chronic fatigue syndrome cases, such as those we tested, or represents the majority of patients.

Now, THAT was wrong, but this paper is correct that "it has been postulated." Which is one of the problems of having stuff like that make it into published studies, because the more it is cited, the more the original error is compounded.

But the part in the discussion when they say

"The latter patients were from a local outbreak of CFS in Incline, Lake Tahoe, USA, with an already suspected viral aetiology,"

now THAT's wrong. But of course, they could argue that it was van Kuppeveld's error, not theirs, but they should have checked their facts. Judy Mikovit's response to the comments on the Science paper has been out on the Science website since May ("only 25 samples in (1) came from patients identified during the 1984 to 1988 CFS outbreak in Incline Village, Nevada. The remaining 76 samples included patients with sporadic cases from 12 U.S. states and Canada, including California, New York, North Carolina, Wisconsin, Michigan, Oregon, New Mexico, New Jersey, North Dakota, Texas, and Florida").

 

[Eric Johnson from I&I]

> but this paper is correct that "it has been postulated."

Ah, but you've used the past perfect simple. That makes it work. Their use of the simple past makes it sound like it was postulated in 1984. Forgive my intolerable pedantry, I've recently been studying this stuff.

 

[ixchelkali]

I think that they missed out a possible reason for not detecting XMRV... That they were using an inadequate methodology..

I was thinking that, too. The discussion of the study's limitations was better than most of them have been, but no one wants to say "One possible limitation of our study is that perhaps our assays are crap"

Again total no cooperation: if they state that XMRV prelevance is lower in europe, let them test some US samples too...or ask at least WPI for some samples to be sure that their methodology is okay..

Yes, I think the idea of checking to see if XMRV is present in semen is a good one. It would be nice to know if XMRV is apt to be sexually transmitted. But it seems to me that if you want to find the answer to that, it would make more sense to test the semen of men whose blood has tested positive for XMRV. Or at least, as you say, test your assays on some known positive controls.

These things seems so basic to me. If I, as a lay person, can see them, why don't they? Isn't that simply basic scientific methodology? Okay, assuming for the moment that they aren't part of some conspiracy to discredit the XMRV discovery, is it that they just jumped on the XMRV gravy train? Saw some research funding dollars available and said, "Hey, we're virologists, we can get some of that."?

Let's hope Vincent Racaniello is right that science is self-correcting.

 

[urbantravels]

PLoS One has been discussed around here before, hasn't it?

It's sorta-kinda peer reviewed, but not rigorously - not in the way major scientific journals do it. Things are just looked at quickly for anything egregiously unscientific. After that, it's up to the audience to evaluate the science. The scientific community knows that things appear there on a quick-and-dirty basis and should be viewed accordingly.

Ila Singh's group used it PLoS One to push out their early findings on Raltegravir. It certainly seems to have its uses. Based on that kind of quick publication, we could see clinical trials start up a lot more quickly than they could before these fast outlets were available. Heck, even these negative XMRV papers have their uses - helping delineate what doesn't work and ways the virus doesn't seem findable.

It's just important to know how much weight to place on a PLoS One publication versus something that appears in the top-level journals - PNAS, Science or Nature. And for that good stuff, you have to wait...and wait...and sometimes wait some more...

We're all so impatient to see the science move forward quickly -- outlets like PLoS One seem to help it do that. But everyone should realize how big a grain of salt you need to bring along when you read this stuff!

 

[V99]

That statement isn't wrong. They cite van Kuppeveld et al, and the van Kuppeveld paper DID postulate that:

Now, THAT was wrong, but this paper is correct that "it has been postulated." Which is one of the problems of having stuff like that make it into published studies, because the more it is cited, the more the original error is compounded.

But the part in the discussion when they say now THAT's wrong. But of course, they could argue that it was van Kuppeveld's error, not theirs, but they should have checked their facts. Judy Mikovit's response to the comments on the Science paper has been out on the Science website since May ("only 25 samples in (1) came from patients identified during the 1984 to 1988 CFS outbreak in Incline Village, Nevada. The remaining 76 samples included patients with sporadic cases from 12 U.S. states and Canada, including California, New York, North Carolina, Wisconsin, Michigan, Oregon, New Mexico, New Jersey, North Dakota, Texas, and Florida").

Where do I say I'm referring to the statement? It is the local outbreak which is wrong, but you knew that.

The magic trick is to read the papers, unlike those who only reference them.

 

[Bob]

Okay, assuming for the moment that they aren't part of some conspiracy to discredit the XMRV discovery, is it that they just jumped on the XMRV gravy train? Saw some research funding dollars available and said, "Hey, we're virologists, we can get some of that."?

That's the way I see this study as well... But it's a shame that the authors can't admit the limitations of their methodology... They could at least have explicitly said that the XMRV viral load might have been too low to detect, which they seemed to imply when they stated that the HIV viral load was too low to detect in many of their samples... An admission that viral load has a lower limit for detection of the virus does not seem like something to be embarrassed about from the perspective of the authors... Although, not knowing what that lower limit is, does display a certain amount of ignorance.

The authors do make an obscure admission that there is "an argument" that one reason "for not detecting XMRV" could be the same reason that they don't detect HIV in so many of the samples from the heterosexual men who are taking anti-retrovirals, resulting in "viral RNA levels in blood plasma below the detection limit". It's a shame that they didn't explicitly state this in their conclusion...

None of the homosexual men studied here were treated with anti-retroviral drugs, but from the heterosexual men, an argument for not detecting XMRV could be that 90% of them are taking antiretroviral therapy, resulting in HIV-1 viral RNA levels in blood plasma below the detection limit.

 

[Bob]

PLoS One has been discussed around here before, hasn't it?

It's sorta-kinda peer reviewed, but not rigorously - not in the way major scientific journals do it. Things are just looked at quickly for anything egregiously unscientific. After that, it's up to the audience to evaluate the science. The scientific community knows that things appear there on a quick-and-dirty basis and should be viewed accordingly.

Ila Singh's group used it PLoS One to push out their early findings on Raltegravir. It certainly seems to have its uses. Based on that kind of quick publication, we could see clinical trials start up a lot more quickly than they could before these fast outlets were available. Heck, even these negative XMRV papers have their uses - helping delineate what doesn't work and ways the virus doesn't seem findable.

It's just important to know how much weight to place on a PLoS One publication versus something that appears in the top-level journals - PNAS, Science or Nature. And for that good stuff, you have to wait...and wait...and sometimes wait some more...

We're all so impatient to see the science move forward quickly -- outlets like PLoS One seem to help it do that. But everyone should realize how big a grain of salt you need to bring along when you read this stuff!

Yes, I suppose journals like PlosOne are a similar phenomena to the internet... The internet enables freedom of expression, and it empowers ordinary people by allowing the easy dissemination of information by the masses, taking power away from the elites. And it means that it is impossible for powerful governments and institutions to suppress information. But at the same time, there is a lot of low quality, and inaccurate, information out there, and so it is up to society, and individuals, how they use and interpret that information. At the end of the day, it must be a good thing for information to be freely available, and it is up to us to filter and interpret that information, just like we do on this forum.

 

[Megan]

I think it is important to look at gay men and HIV positive people so this type of study is important. Maybe it's possible it's not in semen and that's why we havent heard about an epidemic of CFS in gay men? I understand some of the points people here have been making, but doesn't this address one of the biggest questions surrounding XMRV/CFS - if it is sexually transmissible via semen then why didn't CFS show up first or still mostly in gay male populations?

I do note from the methodology section of the paper it sounds like they did use the Lombardi test as they have referenced it and stated they used Lombardi primers (at least for the first part of the PCR). It sounds to me like it was a nested PCR on the GAG part of XMRV, though its not clear if the second round of the PCR was the same as what Lombardi used?

I better add here that I don't have the scientific knowledge to really make this comparison. I just noting that on the face of it this is how it looks. If anyone with proper technical knowledge is able to give feedback on this it would be helpful.

I wonder too if the WPI have looked at these groups or looked at semen. Hard to believe they haven't! Would be interesting to hear from them on this.

 

[V99]

It may be that HIV patients who get XMRV die quicker? The ARV's may also make XMRV harder to find. Lot's of studies needed on these questions.

 

[Cort]

it is a LIE

wpi told 100000000000000 times by now that the 101 samples came not from lake tahoe solely

and after that: Ruscetti/Mikovits, after telling this 1000000000000000 times, even answered questions from Kuppeveld and co in Science where the samples came from, that they came from entire usa/canada

after all this, nobody can be serious to put this outdated crap again in a paper........

"If you tell a lie big enough and keep repeating it, people will eventually come to believe it."- Goebbels

maybe this fellow has inspired the Amsterdam researchers...


only goal of this study:

-xmrv wasnt there in me/cfs
-it isn't there in other people in the netherlands
-it is not transmittable by sexual contact/blood (HIV patients dont get it, and they got HIV, and if it was transmissive they would also have XMRV) (this crap is not my way of logical reasoning but that of these "scientists")

so (kuppeveld and this study together) we don't need a blood ban in netherlands/europe,

because: blood ban means XMRV is serious, big news and panic. and XMRV in CFS means the end of the weasly/van der meer school

I think it does make sense to look at AIDS patients; they do, after all, have compromised immune systems; that would seem to make them good candidates to pick up pathogens.

These are AIDS researchers; they have no bone to pick with CFS and they are not trying to make a statement about CFS. They are simply researchers determining if XMRV is present in their patients. There's no need or reason to interpret whatever they report as 'lies'. Comments comparing them to Goebbels - one of the masterminds of the Holocaust - are way over the top in my opinion.

The researchers may be correct or incorrect. Its not like the HIV research world gives a hoot about CFS or knows anything about it. Why would they even care to lie? I suggest that we give them a break about what they say about CFS - it isn't that pertinent anyway.

They took their shot at finding XMRV in their group and didn't find any. I would concentrate on comparing their methods to the WPI's methods and leave it at that.

 

[Cort]

I think it is important to look at gay men and HIV positive people so this type of study is important. Maybe it's possible it's not in semen and that's why we havent heard about an epidemic of CFS in gay men? I understand some of the points people here have been making, but doesn't this address one of the biggest questions surrounding XMRV/CFS - if it is sexually transmissible via semen then why didn't CFS show up first or still mostly in gay male populations?

I do note from the methodology section of the paper it sounds like they did use the Lombardi test as they have referenced it and stated they used Lombardi primers (at least for the first part of the PCR). It sounds to me like it was a nested PCR on the GAG part of XMRV, though its not clear if the second round of the PCR was the same as what Lombardi used?

I better add here that I don't have the scientific knowledge to really make this comparison. I just noting that on the face of it this is how it looks. If anyone with proper technical knowledge is able to give feedback on this it would be helpful.

I wonder too if the WPI have looked at these groups or looked at semen. Hard to believe they haven't! Would be interesting to hear from them on this.

Honestly, XMRV is a real puzzle. CFS, after all, does not look like an infectious disorder and nobody has suggested it is for a long time. While some families do have it most do not - yet the families clearly have been exposed to whatever infectious agents are present. The fact that they are not sick takes the genetic susceptibility factor out of it. I think the WPI is thinking it might cause different problems in different members of the family. I wonder if anyone has done a study of co-morbid disorders in the families of CFS patients. What shows up in families? FM, IBS, MS???????

XMRV is clearly not going to be an easy virus to figure out in any way. Its quite tricky. You would at least expect family members to become ill in the same way because not only are they genetically similar but they also live in the same environment - they have the same infections...their 'terrain' is very similar....so why wouldn't they tend to come down with CFS if they were all exposed to XMRV? If anybody would they would.

HIV was so much 'cleaner'; huge viral loads - obvious infectious transmission... - a classic presentation.

 

[V99]

The problem with these researchers is that they claim to have read the papers they sourced.

Rivotril, isn't comparing them to Goebbels, the word used was inspired.

Honestly, XMRV is a real puzzle. CFS, after all, does not look like an infectious disorder and nobody has suggested it is for a long time.

ME does look like an infectious disorder, always has. And many doctors are still claiming it to be.

 

[lansbergen]

ME does look like an infectious disorder, always have.

Yes it does, indeed.

 

[Cort]

The problem with these researchers is that they claim to have read the papers they sourced.

Rivotril, isn't comparing them to Goebbels, the word used was inspired.



ME does look like an infectious disorder, always has. And many doctors are still claiming it to be.

Using a statement by a Nazi, whatever the context, and saying that he inspired medical researchers is enough for me.

I 'm not going to get into a discussion on the difference between ME and CFS. THere is a big difference between getting an infection and coming down with something and being an infectious disorder. If ME was an infectious disorder it would predominantly show up in the family members, sexual contacts of people ME patients were in contact with - depending on the route of transmission.

The only evidence for infectious transmission is in the outbreaks- which we don't for whatever reason hear about anymore.

I would point out that Mike Hillerby recently stated 80% of the 1,000 CFS patients they'd sampled had XMRV. Maybe those are all acute onset but since acute onset makes up about 75% of the patients - that's still a huge group - in which there is little evidence, as of yet, of consistent transmission to family members or sexual partners.

That didn't even show up to my recollection in the Incline Village ME outbreak although I could be wrong. I just don't remember it being mentioned in the papers.

 

[V99]

"If you tell a lie big enough and keep repeating it, people will eventually come to believe it."

No, it is the quote that inspires.

I also never brought up the discussion on ME CFS ME/CFS CFS/ME.

An infectious agent doesn't always have to be sexually transmitted. It has always been thought to be infectious, nothing has changed.

 

[lansbergen]

THere is a big difference between getting an infection and coming down with something and being an infectious disorder. If ME was an infectious disorder it would predominantly show up in the family members, sexual contacts of people ME patients were in contact with - depending on the route of transmission..

Have a look at http://en.wikipedia.org/wiki/Infectious_disease
and http://en.wikipedia.org/wiki/Infection

 

[urbantravels]

Honestly, XMRV is a real puzzle. CFS, after all, does not look like an infectious disorder and nobody has suggested it is for a long time. While some families do have it most do not - yet the families clearly have been exposed to whatever infectious agents are present. The fact that they are not sick takes the genetic susceptibility factor out of it.

Cort, you're going to get a lot of people disagreeing with you there, including me.

First, let me quote from p. 194 of Osler's Web, in referral to the outbreak among the North Carolina orchestra members: "As [Seymour] Grufferman and his associates knew, the only logical explanation for the immune dysfunction among both the sick and the well musicians was that everyone has been exposed to some infectious, immune-altering pathogen, a minority had become ill. This pattern - widespread exposure resulting in overt symptoms of disease among only a portion of those infected - was the standard outcome of nearly all known transmissible agents." (emphasis mine).

This is true even of HIV/AIDS. Not everyone who gets exposed gets sick.

Both epidemic outbreaks and sporadic cases are *perfectly* consistent with the presence of an infectious agent. This seems to be what we have in ME/CFS.

ME/CFS has looked like a duck, walked like a duck, quacked like a duck, all along - so much so that it became a non-disease in the minds of many only BECAUSE they couldn't find the infectious pathogen. Dr. Bell (also quoted in Osler's Web): "You need to have the organism to talk business."

It is also not correct to say that since all family members don't get it, genetics are taken out of the equation. That would only be true if all family members share 100% of their genes. There is only one kind of relative where that is true - identical twins. Have there been identical twin studies in ME/CFS? Assuredly not yet - we barely have the funding to continue to look for a pathogen! But such a study might tell us something.

Of course there *are* anecdotal reports, and plenty of them, of multiple family members getting CFS. But we have no idea if anecdotal reports represent a meaningful pattern without, once again, better research.

I think we all know there are a lot of reasons why the continued search for a pathogen got pushed off track after the outbreaks of the 80s, but ME/CFS never stopped looking (or feeling) like an infectious disease. I think, besides the politics and lack of funds and groupthink, etc., of which we are all so well aware, the other reason no pathogen turned up is that we have here a rather hard-to-find pathogen. It has been the misfortune of ME/CFS to come along at a time when science was, no doubt, a little *too* excited about its ability to identify viruses and retroviruses, and when they couldn't find the pathogen, it became easier to assume there wasn't any.

 

[Rivotril]

No, it is the quote that inspires.

I also never brought up the discussion on ME CFS ME/CFS CFS/ME.
.

V99 thanks, you said exactly what i wanted to reply to these comments.
I knew the quote, without remembering who said it, needed google to discover whose words it were.
if it would be for instance goethe's or einstein's, i would have used the same quote.
it is just the quote, you said it right.