Comments

1. #1 Roger Kulp

   October 1, 2010

   Here’s an article that explains it better.

2. #2 titmouse

   October 1, 2010

   Yesterday I listened to a coupla PhDs talking about Airborne. They said you can stop a cold before it starts if you take it early enough.

   I said, I heard it was a scam and they might want to look into it a little deeper. But they were all, “it works for me.”

   *sigh*

   Yes, a vitamin pill probably won’t hurt them. But that can’t be our only concern any longer.

   The signal-to-noise ratio in medicine has gone all noisy the past ten years or so. Time to reign it the f_ck in.

   All the young people filling up ever-expanding naturopathic, chiropractic, and traditional Chinese medicine programs in the US. How can they ever wake up from their collective delusion without losing everything?

   explosion of medical bullsh_t over the past 10 years

3. #3 jen

   October 1, 2010

   ERV: you made this comment:
   “What a crazy random happenstance Judy chose to support antivaccination efforts at AutismOne.”

   Judy did nothing of the sort. I was at this conference and heard her speak. She did not EVER implicate or discourage vaccination.

   Please get your facts straight because you appear to be guilty of the exact thing you accuse other people of. You don’t back up what you say with facts.

4. #4 ERV

   October 1, 2010

   Uh huh.

   Judy just chose to present at an antivax conference. Lending her credibility to every other speaker there, as well as the movement as a whole. She also repeats the claims of anti-vaxers (VACCINES GAYVE MAH BABBY AUTIZOOM!!!!), despite no evidence to support that claim, anywhere.

   Meanwhile, the WPI apparently supported her appearance there. They also perpetuate the vaccine–>MAH POOR BABBY!!! hypothesis, as The Princess Who Cannot Be Named was ‘cured’ of CFS (with homeopathy and yoga) until that evil, evil MMR.

   You might be stupid, jen, but dont assume other are, especially my readers.

5. #5 qetzal

   October 1, 2010

   jen, I’m really curious. ERV very clearly noted two different things Judy did to support antivax efforts:

   - She offered totally unfounded, and frankly idiotic speculation about how “vaccines would lead to autism.”

   - She spoke at a conference sponsored by antivax wackaloons (aka AutismOne & Generation Rescue).

   And yet you say ERV offered no facts to back up what she said. So do you not consider the above items facts? Or do you not think they support antivax efforts?

   One might wonder about your comprehension and rationality. But then, you apparently attended the Autism Redefined conference voluntarily, so perhaps there’s no need to wonder at all.

6. #6 German Santanilla

   October 1, 2010

   “these viruses live and divide and grow . . .” Viruses live and divide? Maybe in the new Zombie ruled post apocalyptic world she live in . .

7. #7 divalent

   October 1, 2010

   Jen said: “She [Judy Mikovits] did not EVER implicate or discourage vaccination…”

   “On that note, if I might speculate a little bit,” she [Judy Mikovits] said, “This might even explain why vaccines would lead to autism in some children,…”

   I dunno: seems to be a pretty clear admission that she thinks vaccines are “implicated” in autism, don’t ya think?

8. #8 gf1

   October 2, 2010

   To me it doesn’t sound like Science has yet had a change of heart. Or at least, the blog on the Science website has always aired concerns about contamination, and the new piece doesn’t sound any more negative on XMRV/CFS to me.

   Alter seems pretty confident that contamination isn’t an issue, and was working on his paper in the midst of this controversy and after Huber announced that she believed her reagents were contaminated. Huber’s positive results were evenly spread between CFS and controls – with the positive studies this is not the case, but we are lacking info on exactly how/when they were blinded.

   I don’t find either side of this argument very convincing at the moment.

   Re Autism: If XMRV was related to autism and affected by things like vaccines, then couldn’t this explain why parents report a temporal association, but there’s no difference in autism rates between vaccinated and un-vaccinated children? ie: If your child has XMRV (and whatever other preconditions are required) then they will develop autism but this process could be sped-up/ kick-started by a vaccine – although if the vaccines are avoided something else will do the job instead.

   I don’t think any of that is likely to be true or was a sensible thing to have said, but wouldn’t it fit with Mikovits’ speculations and what we know about autism/vaccines (not an issue I’ve been following closely)?

   Also, is Autism One really an anti-Vax conference? Or is this like saying the Tea-Parties are motivated by racism? Largely true but maybe not entirely fair?

9. #9 daedalus2u

   October 2, 2010

   One of the most replicated physical features of autism is a larger brain with more neurons and a larger number of minicolumns.

   The number of minicolumns is fixed during the first trimester in utero. Nothing months or years later can change that number.

   I think she was trolling for funding. Telling the delusional anti-vax people what they want to hear so they will give her money.

   Unfortunately that is the way that getting funding works. The honest and good scientist who knows his/her limits and doesn’t lie has difficulty competing with the frauds who say “I will cure cancer/CFS/autism/stupidity/ugliness with this funding”.

10. #10 RRM

    October 2, 2010

    Perhaps not peer reviewed published material, but in one of her presentations during the XMRV workshop, Mikovits presented some results of her autism-xmrv connection: a whopping 82% (14 out of 17) of children with autism were infected with xmrv.

    See abstract P_19 (at pages 36) at http://regist2.virology-education.com/abstractbook/2010_8.pdf

11. #11 gf1

    October 2, 2010

    That autism abstract does look a bit poo. Silly to judge from so little info, but the results sound a bit scatter gun, and what you might expect with contamination.

12. #12 qetzal

    October 2, 2010

    @ gf1,

    Actually, the best scientific results indicate autism is NOT correlated with vaccines at all. So no, it wouldn’t fit with Mikovits’s speculation.

    As for the conference, I don’t know how one decides if it was an “anti-vax conference” per se. Vaccines are certainly mentioned in an awful lot of the abstracts. That by itself is suspect, since the science indicates no link between vaccines and autism.

    But that’s really beside the point. Both sponsors of the conference, AutismOne and Generation Rescue, are rabidly anti-vaccine, and are convinced beyond reason that vaccines are a, if not the, major cause of autism. (Again, in spite of the science.)

    @ RRM,

    Given the fact that NO ONE* has been able to confirm Mikovits’s results with XMRV to date, I’m no more persuaded by her claims for autism than I am by her claims for CFS.

    *That includes Alter. He reported finding retroviral seqs, but they weren’t XMRV!

13. #13 DrDuke

    October 2, 2010

    Everything in science (and in most other areas of life) is a package deal. Multiple lines of evidence should all point to the same answer. Not just other labs being able to replicate the results of this experiment using identical samples and identical methods but also completely independent methods and samples agreeing with the same results.

    The big problem with XMRV-CFS is not lack of PCR confirmation, but lack of epidemiological and other evidence. Yes, a very few cases of CFS seem to be epidemiologically linked in a way that could suggest a virus or bacteria cause, but NOT a retrovirus. And not a mouse retrovirus. People who work with mice are not at high risk of CFS. People who work with MuLVs, including X-MuLVs have never been noted to get CFS.

    With the HIV-AIDS link, it was abundantly clear, long before a virus was identified, that the cases were linked via sex, transfusions, and other intimate or blood-blood contact. Casual contact like sharing eating utensils, or kissing, does not spread HIV.

    With Influenza, casual contact does spread the virus, and again the epidemiology, serology, DNA sequences, and many other lines of evidence all add up to the same conclusions.

    With XMRV, nothing other than the WPI data and a few other PCR-based studies, support any link to CFS or prostate cancer.

14. #14 theshortearedowl

    October 3, 2010

    The damage has been done.

    From Age of Autism:

    I got that far and was *headdesk* before I even clicked “read on”.

15. #15 Mary

    October 3, 2010

    Oh yes the government and some of their scientists and doctors always do the right thing and should always be believed. Just see below. No conspiracy theory here. Just the bold faced truth coming out years later. What other experiments were carried out on various populations that included children. I can think of a few.

    Secretary Clinton & Secretary Sibelius Release Joint Statement on the Horrific Medical Experiments Carried Out in Guatemala

    Joint Statement by Secretaries Clinton and Sebelius on a 1946-1948 Study

    Following is a joint statement by Secretary of State Hillary Rodham Clinton and Secretary of Health and Human Services Kathleen Sebelius on the U.S. Public Health Service Sexually Transmitted Disease Inoculation Study of 1946-1948:

    The sexually transmitted disease inoculation study conducted from 1946-1948 in Guatemala was clearly unethical. Although these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health. We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices. The conduct exhibited during the study does not represent the values of the United States, or our commitment to human dignity and great respect for the people of Guatemala. The study is a sad reminder that adequate human subject safeguards did not exist a half-century ago.

    Today, the regulations that govern U.S.-funded human medical research prohibit these kinds of appalling violations. The United States is unwavering in our commitment to ensure that all human medical studies conducted today meet exacting U.S. and international legal and ethical standards. In the spirit of this commitment to ethical research, we are launching a thorough investigation into the specifics of this case from 1946. In addition, through the Presidential Commission for the Study of Bioethical Issues we are also convening a body of international experts to review and report on the most effective methods to ensure that all human medical research conducted around the globe today meets rigorous ethical standards.

    The people of Guatemala are our close friends and neighbors in the Americas. Our countries partner together on a range of issues, and our people are bound together by shared values, commerce, and by the many Guatemalan Americans who enrich our country. As we move forward to better understand this appalling event, we reaffirm the importance of our relationship with Guatemala, and our respect for the Guatemalan people, as well as our commitment to the highest standards of ethics in medical research.

16. #16 Dr Aust

    October 3, 2010

    You would think all of this would be making the University of Nevada very, very nervous. If the XMRV saga all turns out to be a wild goose chase, then their role in lending the WPI and Mikovits legitimacy (in return, as usual, for lots of funding/PR/endowment $$$) is likely to earn them a great deal of bad press – to put it mildly – in the scientific and medical community.

    One might recall that the academic Department where Andrew Wakefield did his work no longer exists, the bosses all retired with startling haste, and all those still in medicine or research who had been involved with Wakefield’s work in any way have spent the years since desperately trying to live it down. The Royal Free Medical School itself was merging with a bigger place (University College) anyway, but most of its ranking people were gone in a very few years and the smell of Wakefield’s dishonesty, and the RFH’s failure to spot him as a wrong’un, hangs over the memory of the place to this day.

    Of course, none of that addresses the kind of problem ERV skewers, namely that once the myth that “Research says it was a vaccine/virus” (“and so we were right all along…”) is out into the wild, there is no getting it back. But it remains true that a mainstream research institution with its fingers in the pie has a lot to lose if it all turns bad, mainly because others will say: “How could you not have seen this coming?”

17. #17 daedalus2u

    October 3, 2010

    There are some inconsistencies in the numbers. The abstract says 16 families had more than one child participating, but only 29 children participated.

    That abstract has a lot of dog whistles in it for fringe, quack and anti-vax groups.

    Autism is not recognized as a “neuroimmune disorder” and no one in the autism mainstream considers it to be characterized by “chronic active microbial infections”, only quacks selling stuff to counter the “microbial infections” that no (actual) health care professional can diagnose or treat.

    No one in the CFS mainstream considers CFS to be a “neuroimmune disorder” either (not really sure what a neuroimmune disorder is exactly). The same with fibromyalgia. They are known conditions but the causes remain unknown. They do affect the nervous system and the immune system but they are not known to be “neuroimmune disorders”.

    Lyme disease is an infection by a certain microorganism. Proper treatment with the proper antibiotics is curative, that is the infection is resolved. I presume that what they were actually meaning is “chronic Lyme disease” which is a made-up condition that has no accepted clinical reality. It is used to explain the state of health that some people have which has no known medical explanation.

    “Chronic Lyme disease” is a made up term like Morgellon’s, a term made up by non-medical individuals. There is a cult-like following of people with vague and often quite severe symptoms that have no diagnosable medical cause. The usual diagnosis that comes with the constellation of symptoms some call Morgellon’s is delusion of parasitosis. I think a better term would be hallucination of parasitosis. I discuss that on my blog, and what I think it really is.

    http://daedalus2u.blogspot.com/2008/02/morgellons-disease-hallucinatory.html

    Steve Novella, at Science Based Medicine has written about it, so has Peter Lipson at White Coat Underground. Mark Crislip has written about chronic Lyme disease in the context of the State of Connecticut prosecuting a professional organization on infectious disease because they would not recognize “chronic Lyme disease” as an actual disease that could be treated with chronic administration of antibiotics. Quacks treating “chronic Lyme disease” with chronic antibiotics wanted health insurance reimbursement for their quack treatments, so they exerted political pressure because they didn’t have any science.

    It sure looks to me like those pushing the XMRV are going down the “chronic Lyme disease” path, but instead of treating “chronic Lyme disease” with chronic antibiotics they will treat XMRV with chronic antiretrovirals.

    I predict there will be a poorly done trial which will show that chronic antiretrovirals produce improvement in CFS, autism, etc. and then there will then be political lobbying to get health insurance reimbursement for using antiretrovirals for CFS, autism and everything else that can be blamed on XMRV. I hope I am wrong, but hype and politics has trumped good science in the past, especially when it involves disorders with a neuropsychiatric component. The people who developed the lobotomy actually won the Nobel Prize for it.

18. #18 daedalus2u

    October 3, 2010

    Oh wait, I spoke too soon, there has already been a poorly done clinical trial.

    That link to the press release on the phase III clinical trial of Ampligen on CFS is interesting. It turns out there has only been a single phase III clinical trial of Ampligen on CFS (AMP 516) that was completed in 2004. The wikipedia article on Ampligen has the scoop. The press release must have referred to retrospective analysis of archived samples.

    There is currently an open clinical trial of Ampligen on CFS, but it is open label and the patients need to pay for all costs related to the therapy.

    “An Open-Label Study of Poly I: Poly C12U (Ampligen®) in Patients with Severely Debilitating Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME). The FDA approved the study for cost recovery. Patients enrolled in the study are responsible for costs related to the therapy, e.g., drug cost, infusion cost, cost of supplies, diagnostic and other laboratory testing.”

    Ampligen doesn’t have quite the side effect profile of an antiretroviral. It might even work better if it is open label and the patients have to pay full cost. The more expensive a placebo is, the better it works.

    There was another study done AMP502. The PI of that one was affiliated with Hahnemann University. If you are thinking, Hahnemann, that name sounds familiar, you are right, it is named after Samuel Hahnemann, the developer of homeopathy.

    http://hahnemannhospital.staywellsolutionsonline.com/Library/Encyclopedia/85,P00182

19. #19 jakob

    October 3, 2010

    daedalus “Low NO” has been discussed in cfs, via the theories of martin pall who states that he beleives a NO/ONO cylcle problem in cfs is possibly involved in the mix

20. #20 divalent

    October 3, 2010

    Open label study … Patients enrolled in the study are responsible for costs related to the therapy, e.g., drug cost, infusion cost, cost of supplies, diagnostic and other laboratory testing…”

    Yeah, I can see how that works: It’s open label, and patient pays the cost of the treatment. “Congratulations, patient X, you have made it into the study. You have been assigned to the placebo arm. Please show up to the clinic for ‘treatment’ next monday; report first to the pharmacy and purchase your placebo drug, infusion lines, alcohol wipes, and needles. Then head to clinic room with your supplies and placebo and meet Nurse Bubba. Hand him the treatment fee of $500, and get treated. Report back the following Monday (and every Monday for the next 6 months) to repeat the above.”

    “Unfortunately, most health insurance plans do not cover unproven or ineffective treatment, so cash or credit cards only please. (Be thankful you are in the placebo arm: the test drug is significantly more expensive.)”

21. #21 Peter W

    October 3, 2010

    …and if a cult develops; who will be responsible? ==> Medical science (“you guys and gals”), 98% resonsible because you *could* have prevented it. erv, I don’t agree with your comment that”coming down harder, earlier” would make any difference. I agree with your intent. But it wouldn’t have worked. Patients are evaluating credibility of players on broader factors.

    I’ll give you only one example:- In this thread there is much eloquent discussion of quackery. At this moment the UK equivalent of the NHS has just granted $millions for study of the “Lightning Process” in chidren with CFS. What is this? A quack program developed by a “kinesiologist” Phil Parker (http://www.skepdic.com/lightningprocess.html). More about the quack – http://www.healinghawk.com/prospectushealing.htm Quote:- “…Phil Parker is already known to many as an inspirational teacher, therapist, healer and author. His personal healing journey began when, whilst working with his patients as an osteopath. He discovered that their bodies would suddenly tell him important bits of information about them and their past, which to his surprise turned out to be factually correct! He further developed this ability to step into other people’s bodies over the years to assist them in their healing with amazing results”

    What do you guys think of this? Really. A leading Western intellectual power (UK) supporting this shit? It is being dished out to CFS groups on a platter – here guys, suck this up. It will fix you. The UK CFS groups are fighting against this quackery tooth and nail. Where are the voices of scientific rationalism to help them? Where are YOU supporting them against this absolute shit?

    And here is the credibility issue:- this quack program is actively supported by **same** UK individuals that are very vocal against the WPI and against any association between CFS and XMRV connection. In fact, the research is being run by one such individual (Esther Crawley) that has actively targeted the WPI as being only a money raising exercise.

    Now, really, these are separate issues. She may be 100% right and this is not invalidate by her support of quackery.

    But can you blame a CFS patient for being skeptical about her skepticism – even though she may be right. Or that when you in the US (erv) raise concerns about he WPI you inherit a skeptical viewpoint from patients? Can you understand why a (future) 100% correct refutation of XMRV – CFS connection might be questioned by a CFS sufferer leading to the said “cult”?

    Patients are not scientists but they are not stupid. Most know that many of these UK individuals have a documented conflict of interest – involvement with medical insurers (http://www.meactionuk.org.uk/magical-medicine.pdf). Those that accuse the WPI of money grabbing. Yet on the other other hand support “what the body tells me” quackery instead of real medical research.

    I’d be interested in the opinions of this group – do you think the UK government should be dishing out money to research based on premises like this? In the UK gene researchers, biomedical scientists are starved for funds while crap like this is getting money. I would think that no matter how tenuous a biomedical hypthesis it should get money over this crap.

    And, while this is actually a separate issue for a busy scientist, to what extent do you think it is the responsibility of medical science to support the cause and speak out against this type of quackery? You guys and gals are part of it.

    I respectfully suggest to you that if you, as rational voices, spoke out on items like this UK support for quackery you would be quite revered and *trusted* by the CFS community. (You might even be treated like rock stars). There would be very little chance of an “XMRV cult” developing if/when the connection was refuted. Because they would *believe* and trust you. But if you do not speak out on obvious crap (above is only one example) why would they trust you on the esoteric crap if/when xmrv-cfs is formally refuted?

    There are a few individuals that have generated this sort of respect for themselves in the eyes of patients. Unfortunately only a few.

    Anthony Komaroff, John Coffin,…….. a few others.

    And let’s do a second point. In his article Robin Weiss repeats the misconception that CFS is defined only by a “fairly broad spectrum of signs and symptoms”. Most CFS patients do not know the intracies of PCR bands, binding proteins, viral envelopes etc. But they are not stupid. Most *do* know that the “fairly broad, ill-defined” bullshit is not a view shared by clinical experts. Delineation between CFS and various other conditions based on clinical symptoms has been done to death in published studies and comnmentaries. The symptom of post exertional malaise (PEM) is both objectively verifiable (by Vo2 max, CSF lactate buildup and other oxidative stress markers) and is unique to
    CFS. They know this is well documented in peer reviewed articles. Pubished studies (Lenard Jason et al and others) also clarify how the research definitions used by some groups obfuscate the entire issue by selecting depressed patients while excluding the very group that CFS was named after. Why is this obvious elephant in the room dismissed so casually? Easy. It is only dismissed casually by those that have no clue whatsoever about the state of CFS science.

    So, why does Robin Weiss undermine his credibility in retro-virology with such an inane comment that exemplifies his lack off knowledge?

    God knows. Again this in no way invalidates his virology viewpoint. But can you understand that, through the eyes of a patient this unnecessary comment undermines his credibility. And why they might inadvertently downplay his entire viewpoint. If he wanted to be taken seriously by the patients he should have left it out. Shame that only a sentence or two in an otherwise credible article was his undoing.

    From a patient’s perspective that is. They are such an inconvenience these patients. Unfortunately they are the “customer” in this matter.

    …Peter W, Melbourne Aus.

22. #22 gf1

    October 3, 2010

    I agree with what Paul W says about the way that those CFS experts who are vocal WPI sceptics seem to be promoting their own forms of quackery. The Lightning Process sounds like a lot of fun, but maybe not a priority for miniscule CFS budgets – they claim it works for MS too, surely there’s more money to go around there?

    Equally, some of the people the WPI have been claiming are legitimate CFS experts seem pretty quacky to me too. It seems like it’s not possible to spend more than a couple of years researching CFS before going barmy.

    The WPI does seem nutty in a few different ways – but Ruscetti seems so heavily involved and so un-nutty. Maybe he’s just signing off on stuff and presuming it’s been done properly?

    Some of the things people are saying here do make me think that the WPI could be a genuinely corrupt, quacky organisation… but it would be crazy if they’d managed to sucker someone like Ruscetti, sucker Science, have Alter backing them up…

    all so the Whittemore’s can con patients suffering from the same condition as their daughter? I don’t know. They seem much more like true believers than cynical rip-off merchants. I’m still hopeful that if the evidence becomes clear and the WPI have got it wrong, then they’ll do what they can to convince patients of this too.

    I suppose that would be the danger time. If Mikovits has so committed herself to XMRV and it then turned out to be wrong she’d have to choose between lucrative quackery or respectable penury – a corrupting situation if ever there was one.

    re Morgellons:

    Why has this controversy been going on for so long? Surely you can just place some patients under intense supervision and then see how their sores appear. It seems like patients are eager for that sort of thorough investigation, and this should be a relatively easy one to sort out.

    I worry that when doctors or sceptics start claiming that those diagnosed with Morgellons are really suffering from delusional parasitosis they’re just going to be pushing all sorts of people further away from mainstream medicine. It’s not that unusual for someone to suffer from a skin condition of unknown cause – they’re normally just given some steroid cream and left to it. (I just flicked through Eczema on wikipedia – it reminded me of CFS in a few ways).

23. #23 daedalus2u

    October 3, 2010

    jakob, no, Martin Pall has the idea that high nitric oxide is what leads to peroxynitrite damage and CFS symptoms. He is 180 degrees wrong. It is low NO that leads to the peroxynitrite damage. It isn’t really peroxynitrite “damage”, it is normal signaling via peroxynitrite that doesn’t go to completion because the NO level isn’t high enough.

    I explain the actual physiology of NO in the context of CFS here.

    http://www.chronicfatiguetreatments.com/wordpress/treatments/chronic-fatigue-syndrome-nitric-oxide/

    I have a technique to raise NO levels that is non-invasive, natural and (I think) will have no adverse side effects because it ties into physiology and is the body’s own way for raising NO/NOx levels. That is why one of the symptoms of CFS is sweating, particularly at night. When the body needs more NO/NOx it releases NH3/urea to the biofilm of AOB it is supposed to have on the external skin. Without that biofilm the NH3/urea does nothing and the NO/NOx level doesn’t go up.

    Well said Peter W. Experts in CFS know that they don’t know what is causing it. Non-experts rush in and tell the experts they do know. Usually the non-experts are completely FoS. I have read enough about CFS to understand that it is a constellation of symptoms that do have a common cause. It is extremely difficult for non-experts to appreciate subtle things. The whole issue of PTSD is related, for a very long time is was considered to be malingering. It is the same mindset that considered PTSD to be malingering that considers CFS to be psychosomatic or psychological. I see both as purely physiological responses to certain environmental stimuli.

24. #24 daedalus2u

    October 3, 2010

    gf1, it is like essentially all disorders that have a neuropsychiatric component, the first inclination is to “other” the person with the disorder and then blame them for not behaving the way they should behave. There is such stigma attached to any thing that can be characterized as a neuropsychiatric disorder that patients and even clinicians are in denial over them. By “othering” the person with the disorder, the person doing the “othering” gets to feel that they are not like them, and so what ever disorder it is won’t happen to them. It is magical thinking, but that is how most of human unconscious thought works, via magical thinking.

    All of these disorders, CFS, PTSD, fibromyalgia, Morgellon’s, RA, have a component of “brain fog”, which I think is “the same” as chemo-brain. There isn’t any “damage”, it is just that the “gain” in the brain is turned down so low it doesn’t function properly. You need a certain dynamic range, where some parts are turned up while other parts are turned down. If you don’t have that, things kind of work, but not so well.

    One of the first things that doesn’t work so well is socialization. People start to not behave the “right” way, and so xenophobia starts to kick in and what ever they are saying gets dismissed because it comes from one “of them”, from someone who is an “other”.

25. #25 jakob

    October 3, 2010

    daedalus my knowledge of the NO cycle is limited but I remember once I wrote to martin pall to debate a matter with him and I found him very open to being contacted and I am almost certain he would reply and debate the issue with you, I am sure it could be quite interesting for you both, if you have spotted a floor in his theory I am sure he would be interested to hear your viewpoint, which I personally think is a mark of a good scientist, someone willing to listen to the critisism and explain why they came to the conclusion or to take on the critisism and adapt, so I personally would suggest you drop him a line, I am sure his email is easily findable or contact address etc,
    regards

26. #26 daedalus2u

    October 3, 2010

    I read this comment of his

    http://www.ncbi.nlm.nih.gov/pubmed/15936892

    and this reply

    http://www.ncbi.nlm.nih.gov/pubmed/16216438

    and it really turned me off from contacting him or trying to work with him.

    My perception of his approach is analogous to Abbie’s perception of the approach of those pushing the XMRV idea. Are the XMRV people receptive to being told they are wrong? No, they are not.

    Low NO does explain all the symptoms of CFS, but NO physiology is complex and not well understood. Unfortunately he is using the common but wrong understanding. I don’t have any of my own data to show him that he is wrong but he is. His conceptualization is simply incompatible with the data that is in the literature. It isn’t my data, it is the data of the whole NO research community.

27. #27 theshortearedowl

    October 3, 2010

    re Morgellons:

    Why has this controversy been going on for so long? Surely you can just place some patients under intense supervision and then see how their sores appear. It seems like patients are eager for that sort of thorough investigation, and this should be a relatively easy one to sort out.

    There is no controversy. These patients think they have red and blue fibres that no one else can see coming out of their skin. It’s psychological or neuropsychological. The founder of the Morgellon’s Research Foundation has been suspected of Munchausen’s by proxy (the case was in her son).

28. #28 Jon H

    October 3, 2010

    daedelus wrote: “The PI of that one was affiliated with Hahnemann University. If you are thinking, Hahnemann, that name sounds familiar, you are right, it is named after Samuel Hahnemann, the developer of homeopathy.”

    I’m not sure how much homeopathy they still do. Note that the link you provide is to information hosted by, apparently, some generic health info source, and in fact to get there from the Hahnemann site you have to click ‘agree’ on a disclaimer!

    The Hahnemann site itself doesn’t seem to contain any information about homeopathy or other alternative treatments, and their ‘find a doctor’ function doesn’t let you search for woo providers.

    I’m a bit sensitive to this because Hahnemann’s medical school functions were taken over by Drexel University, where I got my bachelor’s. I admit, at the time of the deal, my response was “oh, great”. But Drexel’s medical school programs don’t appear to include any woo: http://www.drexelmed.edu/Home/AcademicPrograms.aspx

    As far as I can tell, the Hahnemann name is kept for historical reasons. Ownership has changed hands many times since the 1800s.

29. #29 Prometheus

    October 4, 2010

    John H.@#27

    “I’m a bit sensitive to this because Hahnemann’s medical school functions were taken over by Drexel University…..”

    Hahnemann and Andrew Taylor Sill have their names plastered all over the place and it really has no relation to what is going on inside anymore. By the 1930s Hahnemann Philadelphia was a regional cardiac hospital.

    I got to explain A.T.Sill’s ophidiphobia to an O.D. this weekend….he was not pleased.

    Strange how the woo trappings linger long after the public has moved on to the next pair of cargo pants or pet rock.

    In 40 or 50 years there will probably be a sports figure inviting us to “Join the league and fight fatigue with Mikovits Mango juice!”

    Just as our cereal boxes are yet haunted by the ghosts of battle creek and the ‘cure’ for masturbation is used to make s’mores.

30. #30 gf1

    October 4, 2010

    @ theshortearedowl:

    re “These patients think they have red and blue fibres that no one else can see coming out of their skin” – that’s not my understanding of Morgellons, which is admittedly very limited.

    re “suspected of Munchausen’s by proxy” – hmmm… That’s a diagnosis which is no longer recognised in any UK court following some rather flawed ‘expert’ testimony and a series of over-turned convictions. An even less respectable disease than Morgellons!

31. #31 daedalus2u

    October 4, 2010

    gf1, Courts are not called upon to determine a diagnosis, they are called upon to determine guilt or innocence.

    No differential medical diagnosis carries with it any criminal culpability. Criminal culpability is determined in a court of law, a differential medical diagnosis is arrived at to determine differential medical treatment.

    The standards of evidence for a differential medical diagnosis are quite different than the standards of evidence for a determination of guilt.

32. #32 gf1

    October 4, 2010

    Right, but there had been a few cases where mothers were imprisoned for harming their children based upon the evidence of M by proxy experts. It later came out that their testimony was unsound (including some really poor statistical errors) and this has led to a somewhat greater sympathy for those who are suspected of Munchausen’s by proxy and scepticism of those who claim that they are fit to accurately diagnose it.

    Given the moral implication of a diagnosis of M by P I think that it should require a high evidential standard.

33. #33 ZenMonkey

    October 4, 2010

    Regarding Ampligen, that’s been going on since way before the XMRV thing. I don’t know the specifics but I’ve been told that it’s available on a limited basis to ME/CFS patients in Canada. (Not as part of a study.) Hemispherx has been involved with a lot of questionable behavior; we were expecting FDA approval at least a year ago, probably more, but it required more study.

    As for the XMRV-autism thing, all I’ll say is RAAAAGE.

34. #34 theshortearedowl

    October 4, 2010

    Apologies for potential thread derailment.

    @gf1

    No, Munchausen by proxy is very real, although in some cases hard to diagnose. The UK courts, quite rightly, decided that individual cases of harm of children should not be influenced by a controversial psychiatric diagnosis. Courts in the US have paid out over vaccines causing autism; it isn’t evidence that medical science recognised the claim to true.

    Morgellons is just delusional parasitosis, although with the added quirk of fibres coming out of the skin.

35. #35 gf1

    October 4, 2010

    If M by P is defined roughly as ‘someone deliberately causing harm to another in order to gain some personal benefit through the hardship of the other’ – then this undoubtedly does occur.

    But I worry that the term ‘Munchausen by proxy’ extends an unwarranted scientific credibility to accusations of this sort especially seeing as specialist themselves struggle to provide accurate diagnoses, and to understand their own limitations in this respect. If evidence of abuse is found, then action must be taken regardless of the motivations behind it. I’m not at all confident that we can diagnose the motivations of others even when we do have clear evidence of their behaviour: I’m barely aware of why I do things.

    The founder of the Morgellon’s Research Foundation may be abusing her child – but that is a very serious accusation to make without having some clear evidence in support. If she really was abusing her child, would it not have been better for the child to have been placed under continual observation so that real evidence could have been gathered (as M by P researchers have done before)?

    I also think that given the way in which Morgellon’s is diagnosed (seemingly little more is required than a skin condition and google) it seems rather bold to claim that it is ‘really’ delusional parasitosis. It seems that plenty of ‘sceptics’ believe that Morgellons patients do just have a skin condition which means that they pick up fibers in their sores (I remember some disgusting multi-coloured scabs from when I was a child – and I’m pretty sure that they weren’t delusions). I think that there’s a danger that so causally assuming that anyone who thinks they have Morgellons really has delusional parasitosis is going to needlessly push a group of patients away from mainstream medicine.

    If patients really “think they have red and blue fibres that no one else can see coming out of their skin” then this should be carefully documented – it would be easy to do so. I’d be interested to know how their delusions affected their perceptions of photos of their imagined fibers? With such evidence it should be far easier to engage them and their support network in seeking appropriate help.

    (Sorry for the rambling post – end of the day).

36. #36 Prometheus

    October 4, 2010

    You guys are aware that you are talking about two different sovereign legal systems each of which has three very separate courts with distinct and independent evidential/forensic standards of proof….right?

    Motive is a criminal element.

    The end, to wit: the effect on a subject is a matter of equity and or custodianship/custody/intervention by the state.

    The U.K. forensic standards correspond to expert witnesses as aids to the crown in the U.S. they are harshly vetted and subject to impeachment as part of an aggressive adversarial litigious/prosecutorial process.

    Let me know if you really care. I have watched the dance in both systems with Mbp which is now just called FII in the U.K..

37. #37 gf1

    October 5, 2010

    Thanks Prometheus. I thought I’d bee clear when I was talking specifically about the UK system, but three probably were some underpinning cultural assumptions in there too.

    Just to go even more OT, but related to cultural differences: I’ve seen people here write as if it’s normal for US citizens to get a flu shot every year, even the young and healthy – is that right?

38. #38 qetzal

    October 5, 2010

    @gf1 -

    I don’t know what fraction get a flu shot each year in the US. I’m pretty sure it’s a minority of the population, but it’s still fairly common, even in younger adults. Many employers will arrange to have nurses come to the company on a given day & give shots to whomever wants them, usually at no charge to the vaccinee.

    You could probably find the stats at CDC.gov.

39. #39 gf1

    October 6, 2010

    Thanks Qetzal. I think it’s really rare here, but I’ve been considering it after seeing some people here speaking about it as normal and coming across some research on the long-term damage viruses can do eg: those who get flu shots end up with fewer heart problems. Trawling to the doctor for a vaccination is a bit of a chore though – heart problems don’t sound that bad.

40. #40 Richard Jefferys

    October 11, 2010

    New in JID:

    http://www.journals.uchicago.edu/doi/abs/10.1086/657168

    The Journal of Infectious Diseases 2010;202:000–000
    DOI: 10.1086/657168

    BRIEF REPORT

    Xenotropic Murine Leukemia Virus–Related Virus Prevalence in Patients with Chronic Fatigue Syndrome or Chronic Immunomodulatory Conditions

    Timothy J. Henrich,1,3,4,a Jonathan Z. Li,1,3,4,a Donna Felsenstein,3,4 Camille N. Kotton,3,4 Robert M. Plenge,2,4 Florencia Pereyra,1,4,5 Francisco M. Marty,1,4,6 Nina H. Lin,3,4 Paul Grazioso,3 Danielle M. Crochiere,3 Daniel Eggers,3 Daniel R. Kuritzkes,1,3,4 and Athe M. N. Tsibris1,3,4

    Divisions of 1Infectious Diseases and 2Allergy, Immunology, and Rheumatology, Brigham and Women’s Hospital, 3Division of Infectious Diseases, Massachusetts General Hospital, 4Harvard Medical School, 5Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, and 6Dana‐Farber Cancer Institute, Boston, Massachusetts

    We investigated the prevalence of xenotropic murine leukemia virus‐related virus (XMRV) among 293 participants seen at academic hospitals in Boston, Massachusetts. Participants were recruited from the following 5 groups of patients: chronic fatigue syndrome (n=32), human immunodeficiency virus infection (n=43), rheumatoid arthritis (n=97), hematopoietic stem‐cell or solid organ transplant (n=26), or a general cohort of patients presenting for medical care (n=95). XMRV DNA was not detected in any participant samples. We found no association between XMRV and patients with chronic fatigue syndrome or chronic immunomodulatory conditions.

    http://www.journals.uchicago.edu/doi/abs/10.1086/657167

    The Journal of Infectious Diseases 2010;202:000–000
    DOI: 10.1086/657167

    BRIEF REPORT

    Failure to Detect Xenotropic Murine Leukemia Virus–Related Virus in Blood of Individuals at High Risk of Blood‐Borne Viral Infections

    Eleanor Barnes,1 Peter Flanagan,1 Anthony Brown,1 Nicola Robinson,1 Helen Brown,1 Myra McClure,4 Annette Oxenius,5 Jane Collier,3 Jonathan Weber,4 Huldrych F. Günthard,6 Bernard Hirschel,7 Sarah Fidler,4 Rodney Phillips,1,2 and John Frater,1,2

    1Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, Oxford University, and Oxford NIHR Biomedical Research Centre, 2The James Martin 21st Century School, at The Peter Medawar Building for Pathogen Research, South Parks Road, 3Department of Gastroenterology, John Radcliffe Hospital NHS Trust, Oxford, 4Division of Medicine, Wright Fleming Institute, Imperial College London, St. Mary’s Hospital, London, United Kingdom; 5Institute of Microbiology, ETH Zurich, 6Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich, Zurich, and 7Division of Infectious Diseases, University Hospital, CH‐1211 Geneva, Switzerland

    A xenotropic murine leukemia virus–related virus (XMRV) has recently been reported in association with prostate cancer and chronic fatigue syndrome, with a prevalence of up to 3.7% in the healthy population. We looked for XMRV in 230 patients with human immunodeficiency virus type 1 or hepatitis C infection. XMRV was undetectable in plasma or peripheral blood mononuclear cells by polymerase chain reaction targeting XMRV gag or env. T cell responses to XMRV Gag were undetectable in peripheral blood mononuclear cells by ex vivo gamma interferon enzyme‐linked immunospot assay. In our cohorts, XMRV was not enriched in patients with blood‐borne or sexually transmitted infections from the United Kingdom and Western Europe.

    http://www.journals.uchicago.edu/doi/abs/10.1086/657169

    The Journal of Infectious Diseases 2010;202:000–000
    DOI: 10.1086/657169

    EDITORIAL COMMENTARY

    Current Status of Xenotropic Murine Leukemia Virus–Related Retrovirus in Chronic Fatigue Syndrome and Prostate Cancer: Reach for a Scorecard, Not a Prescription Pad

    Mary Kearney and Frank Maldarelli

    HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

41. #41 Richard Jefferys

    October 11, 2010

    Missed one:

    http://www.journals.uchicago.edu/doi/abs/10.1086/656146

    The Journal of Infectious Diseases 2010;202:000–000
    DOI: 10.1086/656146

    MAJOR ARTICLE

    Detection of Xenotropic Murine Leukemia Virus–Related Virus in Normal and Tumor Tissue of Patients from the Southern United States with Prostate Cancer Is Dependent on Specific Polymerase Chain Reaction Conditions

    Bryan P. Danielson,1 Gustavo E. Ayala,2,3 and Jason T. Kimata1

    Departments of 1Molecular Virology and Microbiology and 2Pathology, and 3Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas

    Background.There are questions regarding the prevalence of xenotropic murine leukemia virus–related virus (XMRV) in patients with prostate cancer and its association with the RNASEL R462Q polymorphism. We therefore investigated whether XMRV infection could be found in patients with prostate cancer from the southern United States, and we sought to verify the association with the R462Q.

    Methods.Prostate tissue specimens of 144 patients with prostate cancer from the southern United States were genotyped for R462Q by real time polymerase chain reaction allelic discrimination and were screened for XMRV proviral DNA by nested polymerase chain reaction specific for the env gene.

    Results.The R462Q polymorphism was found at an allelic frequency of 0.33. XMRV was detected in 32 (22%) of the 144 patients. Patients were significantly more likely to test positive for XMRV in both tumor and normal tissue rather than either alone ( ). A positive result for XMRV was not significantly correlated with the R462Q polymorphism ( ) or clinical pathological parameters of prostate cancer, including Gleason score ( ).

    Conclusions.XMRV is detectable in normal and tumor prostate tissue from patients with prostate cancer, independent of R462Q. The presence of XMRV in normal tissue suggests that infection may precede cancer onset.

42. #42 RRM

    October 14, 2010

    And another negative one regarding xmrv-autism (this one was done by scientists employed by Cooperative Diagnostics (at least some of them), that certainly wanted to find it):

    http://www.molecularautism.com/content/1/1/14

    Abstract (provisional)

    Xenotropic murine leukemia virus-related virus (XMRV) is a retrovirus implicated in prostate cancer and chronic fatigue syndrome (CFS). Press releases have suggested that it could contribute to autism spectrum disorder (ASD). In this study we used two PCR assays and one antibody assay to screen 25 blood samples from autistic children born to mothers with CFS and from 20 mixed controls including family members of the children assayed, people with fibromyalgia and people with chronic Lyme disease. Using a real-time PCR assay, we screened an additional 48 South Carolina autism disorder samples, 96 Italian ASD)samples, 61 South Carolina ASD samples and 184 healthy controls. Despite having the ability to detect low copy number XMRV DNA in a large background of cellular DNA, none of the PCR assays found any evidence of XMRV infection in blood cells from patients or controls. Further, no anti-XMRV antibodies were detected, ruling out possible low level or abortive infections in blood or in other reservoirs. These results imply that XMRV is not associated with autism.

43. #43 asleep

    October 21, 2010

    Well, if this isn’t the absolute backwater of self-confirmed scientific objectivity. If you’ll all take brief pause from your rigorous circlejerk, I would like to point out a few things:

    1. The positive papers (Science, PNAS): It’s as though these don’t exist in this little world. Yes there have been negative studies and yes there have been hypotheses proposed to explain the discrepancies (e.g. contamination, subtleties of processing/methodology, etc). However, none of these hypotheses have yet been proven scientifically and reproducibly to account for the differences. To fully discount one “side” at this point is nothing short of sheer bias.

    2. Paradigm shift: To paraphrase someone else, it’s quite clear that the low-hanging fruit of infectious disease has been mostly picked over. It’s very possible, if not likely, that many remaining etiologically unexplained diseases will require reexamination of basic assumptions/methods. For example, it is very possible that the negative XMRV studies have resulted from currently overlooked subtlties such as sample collection, storage, and/or preparation. There is much reason to believe that this is possible and certainly no scientific proof to date that it is not possible. To discount this a priori again shows nothing but sheer bias.

    3. Science and politics: It’s cute that you all view science as some divine, incorruptible process devoid of political influence (with phrases like “the science shows” or “the epidemiology shows”, etc). Yet, with your example of Wakefield and your accusations against Mikovits, you all fully acknowledge and embrace the idea that politics and other motives are always boiling just under the pristine surface of science. So again, if you want to actually appear objective, please apply social and political context equally to all aspects of the debate, not just the ones you dislike.

44. #44 Kent Heckenlively

    October 21, 2010

    I think this article leaves out a good deal of relevant information.

    First, the Mikovits findings were confirmed by Alter and Lo in a joint study with the NIH, NCI and Harvard University. Alter is the co-discoverer of the hepatitis-C virus as well as winner of the Lasker Prize, equivalent to the Nobel Prize for medical research.

    Second, the data is of such concern that the recent XMRV Conference held at the NIH was opened and attended by Dr. Francis Collins, leader of the Human Genome Project as well as the current head of the NIH. I doubt he would be lending his credibility to this issue if there was a serious concern about contamination.

    Third, the countries of Canada, Australia, New Zealand, and Great Britain have all banned blood donations from people who have EVER had CFS/ME because of concerns about retroviral transmission.

    I am sorry you feel the need to denigrate such a promising area of research.

    All the best,
    Kent Heckenlively, Esq.
    Contributing Editor, Age of Autism

45. #45 Andrew

    October 22, 2010

    “It does not matter, at this point, whether finding MLV is a random hiccup of science.”

    It will be a hiccup if treatments are found for the underlying biological abnormalities. (near) Cured patients don’t care to argue about viruses that don’t have proven links to disease.

    A number of profound abnormalities have been found in CFS subsets, but researchers have not had the funding to follow through. Despite the massive economic costs of CFS (Over $20 billion per year in the USA – Jason et al Dyn. Med. 2008) there remains a complete lack of funding. This must change, CFS can only be solved with good science and good science costs money.

46. #46 ERV

    October 22, 2010

    Andrew– No one with CFS experimenting with antiretrovirals is ‘cured’. We have talked about that on this blog, repeatedly. And you can bet those poor saps will sure as fuck complain when their fucking kidneys shutdown from years of unnecessary drug use.

    Note to Kent Heckenlively: Everyone is welcome on ERV. Billy Dembski. Casey Luskin. Even Lenny Horowitz. I filter most comments from a certain ‘CFS’ forum, because the members are clearly mentally unstable, and I dont think its ethical to provide them with a fixation.

    But you sir, are not welcome here, you sick fuck.

47. #47 scramton

    October 22, 2010

    reading about what the crazy guy did to his poor kid makes me chronically fatigued

48. #48 lisa

    October 26, 2010

    What a stupid website. Why are you wasting your life this way. Go do something useful. Start a dry-cleaners or something. At least then you would be contributing to society.

49. #49 Richard Jefferys

    October 26, 2010

    More negative prostate cancer data.

    http://cancerres.aacrjournals.org/content/early/2010/10/20/0008-5472.CAN-10-2837.abstract

    Cancer Res. 2010 Oct 21. [Epub ahead of print]

    XMRV: A New Virus in Prostate Cancer?

    Aloia AL, Sfanos KS, Isaacs WB, Zheng Q, Maldarelli F, De Marzo AM, Rein A.

    HIV Drug Resistance Program, National Cancer Institute.

    Abstract

    Several recent papers have reported the presence of a gammaretrovirus, termed “XMRV” (xenotropic murine leukemia virus-related virus) in prostate cancers (PCa). If confirmed, this could have enormous implications for the detection, prevention, and treatment of PCa. However, other papers report failure to detect XMRV in PCa. We tested nearly 800 PCa samples, using a combination of real-time PCR and immunohistochemistry (IHC). The PCR reactions were simultaneously monitored for amplification of a single-copy human gene, in order to confirm the quality of the sample DNA and its suitability for PCR. Controls demonstrated that the PCR assay could detect the XMRV in a single infected cell, even in the presence of a 10,000-fold excess of uninfected human cells. The IHC used two rabbit polyclonal antisera, each prepared against a purified MLV protein. Both antisera always stained XMRV-infected or -transfected cells, but never stained control cells. No evidence for XMRV in PCa was obtained in these experiments. We discuss possible explanations for the discrepancies in the results from different laboratories. It is possible that XMRV is not actually circulating in the human population; even if it is, the data do not seem to support a causal role for this virus in PCa.

50. #50 Wow, just...wow

    October 26, 2010

    The level of maturity and intelligence posted here is a true credit to scienceblogs.

    Really, I am truly astounded by ERV’s profound stupidity and inability to discuss things in a logical, rational manner. Hurling childish insults is soooo scientific.

51. #51 qetzal

    October 26, 2010

    OMG, Wow! The logical, rational discussion and lack of childish insults in your comments has totally convinced me that you’re right and ERV is wrong! Oh, wait….

52. #52 The Chimp's Raging Id

    October 27, 2010

    lisa,

    You’re so right! ERV isn’t making any useful contribution to society whatsoever by being an HIV researcher. HIV is such a trivial thing! What an utter waste of a life it is to try an understand a disease that isn’t affecting a single person! I really can’t understand why she wastes her time on this stuff.

    In case you couldn’t figure it out, moron, yes, that was sarcasm.

53. #53 Jon H

    October 27, 2010

    “Just to go even more OT, but related to cultural differences: I’ve seen people here write as if it’s normal for US citizens to get a flu shot every year, even the young and healthy – is that right?”

    At Harvard Medical School/Harvard Dental School/Harvard School of Public Health, they’re running about six free flu shot clinics. Each runs about two hours, or until the vaccine supply runs out. There’s often several hundred people of all ages at each one.

    True, you’d expect that of a med school / dental school / school of public health. But it also makes sense for anyplace where a lot of people mingle.

54. #54 Jolo5309

    October 28, 2010

    “Just to go even more OT, but related to cultural differences: I’ve seen people here write as if it’s normal for US citizens to get a flu shot every year, even the young and healthy – is that right?”

    I had my flu shot on Friday and had a serious car accident the very next day. I think the two are related*…

    *I don’t

55. #55 Tony Mach

    February 10, 2012

    @ERV,43

    Sorry to be late to the show, but I think you misunderstood Andrew(42). I think what Andrew wanted to express was: “Once the pathology/etiology of CFS has been established, and once a cure will be available that addresses that yet to found cause, no one will care about XMRV”*. I don’t have the impression Andrew thought that XMRV was the cause of CFS.

    I think the sentence “(near) Cured patients don’t care to argue about viruses that don’t have proven links to disease.” does express (in my view) that Andrews position is that XMRV does not have proven links to diseases. And the hicup would then be Mikovits’ work.

    (I know how the XMRV crazies can get to one, so my full sympathies here, but I don’t think Andrew is one.)

    * Alas, I am more pessimistic – HIV-positive HIV-deniers come to my mind. The XMRV disciples already rally against the Rituximab studies (hand in hand with psychosomatic mob)…

56. #56 pacquiao bradley stream

    May 31, 2012

    Just like all other HBO productions, 24/7 is only available to watch if one has an HBO subscription, assuming you do, you can visit HBO.com to get the full Pacquiao Bradley 24/7 schedule. If for some reason you