XMRV CFS UK study #II

[flex]

flex,
your apple experiment didn't really follow those steps. The main one is that background research would have shown you that there are certain defining characteristics of an apple. Probably genetics are the best tool to use today. But the smell, taste etc. aren't how you identify an apple. Also, what examinations did your team of scientists do?

As far as the UK studies... watertight, I definitely didn't say that. And usefulness, I agree, not particularly useful. But still science by definition. Science can be done well, and it can be done poorly. WPI did it exceedingly well, and the UK teams did it somewhat poorly. Well below the standard set by the WPI.

I think the big problem is bias. I think Gerwyn's post about the hypothetico deductive model was largely trying to address that. That model is a description of the classic scientific method which tries to address some of the problems inherent in the classic model...bias being one of them.

If, for example, the suspicions of some of us (definitely including myself) that the IC study was biased are true, then it would not be science. Even by the classic model. The act of setting a goal (ie; to not find XMRV) and designing a 'study' to achieve that goal is not science. A hypothesis is not a goal, it is an educated guess. But for now we have no 'proof' that is what occurred, so we have to (unfortunately) treat it as science.

As far as the conclusions, I was wrong. I said the conclusions of the two studies were that those methods can't find it. But really the only conclusions are that they didn't find it. I made an assumption it was there based on the fact that we know that it is in the UK from the commercial testing.

BTW Gerwyn, I looked for the statement about replication in the IC study and didn't see it.

Julius my post was not aimed critically at any of your posts or Gerwyns. In fact I'm not even sure I read yours.
I was simply pointing out the difference between something that is considered useful in terms of a scientific experiment and something that carries no useful conclusion. That's why I used the apple analogy. For the very reason that it was a purposeless and flawed experiment in comparison to the WPI example. However well you could carry out the "apple" experiment, it is still of no value when trying to replicate findings from the WPI study.

I have read a number of professionals stating they could find no flaw in any study so far. The point is they need to look at what is being measured and for what purpose otherwise non confirmatory conclusions are pointless.

Oh, and just to confirm, I didn't really do a scientific experiment on an apple today and I didn't commission a team of scientists to carry out a study on the non existent apple. That would have been a waste of money and reported nothing useful.

Now that rings a bell!!

 

[starryeyes]

Quote Originally Posted by _Kim_ View Post
Is this the same email that was posted on this thread earlier and then removed because it was believed to be fraudulent?

No. That one was just a bit of a rant.

Thanks julius. I never got to see that one. I just wanted to understand what ladybug had posted so I reformatted it.

 

[julius]

hey flex,

I take no offense from your post, I though you were referring from mine because you used the same outline of the SM that I did. Maybe you cut and pasted it from the same source.

With regards to the usefulness of the latest study. It could have been very useful. If they had found XMRV, that would have put the XMRV in the UK debate to rest...and it would have shown that you can find it cheap and easy. Given that they might not have known it would have been hard to find at the time they designed the study, maybe they really wanted to find it (or hypothesized they would).

It's possible they were not wanting the results they got, but published anyways because, well, it's the right thing to do.

 

[cfs since 1998]

I thought it wasn't unreasonable to ask that people not go overboard in criticising every study which doesn't agree with WPI. Particularly when the current study in question involves some good quality scientists who have done good work in the past.

So what do you want us to do, sit back and assume their study was flawless and the conclusions absolute truth? You are going overboard by criticizing people who have made valid criticisms. Nobody is immune to criticism, especially not "good quality scientists". You are right that attacking the quality of the scientists is pointless, but praising them as you are is equally pointless. The whole purpose of this thread is to discuss the study--what's good and what's bad, and that is criticism by the meaning of the word.

 

[_Kim_]

Hi Kim. I've been away from the computer all day so missed a lot of these posts. I certainly seem to have got something wrong with the "tone" of my post. However, I didn't think anything in it was unreasonable, given some of the earlier ones in this thread. Therefore I'm a bit bemused that I should be getting "told off".
Garcia's post was much better than any of mine. I'm happy to leave it to others in future. Sorry for any hassle.

No worries KFG. I was just trying to explain how your post came across. We're a testy bunch right now. On another day or another topic, your comments would have slid right by. Thanks for staying in this with all of us.

 

[Revday]

My heart dropped when I read some of this new study. . I pray that someone else will find and publish positive XMRV findings, sooner then later. Sorry to be negative but 24 years of having CFS is a lot of disappointment. Disclaimer: I have not read all the posts.(way to sick for that) I do want to say that it is awfully easy to turn on others due to years of frustration, unremitting and unspoken sadness, and the stresses of trying to have some quality of Life while having this disease. Not to mention the pain, bla bla bla..... I trust that you know what I mean.
Especially when we have all experienced so much demoralization because of "authorities" lack of understanding, bias, lack of curiosity, .... I believe that it is important to try to leave out the personality issues of others. No matter how personal the whole CFS fight is. I find it difficult to not respond on a personal level in the heat of whatever is being argued. I also think my brain becomes single minded and shut down when I am extra stressed. I find that the UK study's not finding XMRV makes me increasingly anxious. And most people react with, the instinctive, flight or fight when there is a situation that feels like or is about Life or death. I am grateful that I can share some of my feelings here. And that there seems to be a wonderful thoughtfulness and graciousness in the posts I have read. I believe I can promise that I will remain as level headed I am capable. Thank you all for giving me the opportunity to read what you say and post my own thoughts.
Blessings.
Revday

 

[dmarie4301]

Revday! Totally understand your feelings. This gets a bit wearing on our spirit at the double decade mark. I want so much to live, but find myself wishing I were dead too. Strange tug of war inside. Good thing I have kids that still need me on a consulting basis. Plus, I dont believe in suicide

Anyway, this second study is questionable and at this point we are waiting to hear what Dr. Judy Mikovits makes of it. Dr. Nancy Klimas warned us there would be ups and downs as reasearch is sorted out....so do not despair. I despaired for two days. Now I need to rest and get my spirit back. It aint over til the fat lady sings, as they say and there's much more research to be done to make any real conclusions.

Take good care....I hope you get this message!


Donna

 

[guest]

I can relate so much to most people here. I'm very disappointed too. However I'm quite sure that within the next 3 months we can draw a much better conclusion and know the exact reason why the studies differed. Maybe there is more about XMRV or viruses than we know right now or maybe it isn't. Anyways I'm excited.

 

[Marco]

It was the posts suggesting there was something amiss in the scientists' motives or integrity I was talking about. I'm too tired to keep repeating myself !! See Garcia's post - it's more balanced and much better written than mine.....

Hi KFG

There has been a lot of good discussion here around the scientific method and the issue of whether or not we can 'trust' the researchers. I don't believe, in this case, that its the scientists' integrity that's being questioned.

A number of posters have spoken knowledgeably about the scientific method suggesting a science background, possibly even as active researchers. That being the case, they must also be aware that science does not proceed in a vaccum. The context within which science takes place is also important and the commissioning and funding of research should adhere to the same principles of objectivity as the science itself.

When the WPI study was published there was considerable debate on this forum regarding our hopes and fears for future replications studies. Posters were anxious that anyone undertaking research into XMRV and ME should be aware of the 'political' backgroud to ME, specifically on the issue of the cohorts selected for study. Many of us believed that only a prospective study of Canadian defined subjects was likely to replicate WPI's findings. Dr Bell's involvement (albeit possibly in a minor role) in the current study is to be welcomed in this respect.

It has been stated that the current study was funded by the MRC, yet a written response to a parliamentary question published in December made no mention of a study investigating XMRV in ME. It is a matter of record that ME researchers have criticised the current composition of the MRC committee on the funding of research into ME and many well designed studies into biomedical causes of ME have been refused funding while studies into psychosocial hypotheses appear to have flourished. The most glaring being the PACE/FINE trials.

So when and why did the MRC's attitude change to biomedical research? When was this study proposed, evaluated and recommended for funding?

Perhaps the MRC decided that the WPI findings were sufficiently convincing that to ignore them was no longer tenable. Perhaps they felt that the Imperial College study was sufficiently flawed that nothing could be deduced from its results and that they could do a better job?

I'm sure the researchers, particularly Dr Bell, were glad to receive any funding, even if the level of funding (unknown) and time constraints meant that they had to compromise on issues such as the patient cohort, stored v fresh blood draws, time taken to culture samples etc, issues which in retrospect may have been crucial to detecting XMRV or not.

On the other hand, MRC's research programme is on record. The MRC and the Department of Work and Pensions have invested heavily in the PACE/FINE trials with an obvious expectation that the proposed 'therapies' will be rolled out in some form. Irrefutable evidence of the presence of XMRV as a causal agent in ME would hardly be welcome at this stage, not only as regards rolling out the PACE programme but also when the MRC's prior research programme is considered.

So, it is entirely possible if not probable, that the researchers in this case, have genuinely attempted to find XMRV, using the best methods available to them, and have failed to do so for reasons that have nothing to do with their integrity or failures of proper scientific methodology. Perhaps they were just 'insufficiently funded' to find it.

Whatever the scientific merits of the study (which I am not qualified to comment on, but others have noted issues that question the likelihood of their methods being able to detect XMRV) the study was clearly commissioned and completed in what seems to be a very short timeframe in comparison to the WPI study and without any apparent transparency as to the funding process.

Many others have raised genuine concerns about the MRC's process of funding research into ME. To share these concerns doesn't make you a conspiracy theorist.

Does it advance the science to discuss these contextual issues? Probably not. There are further studies to come and, when properly executed, negative results are as valid as positive from a scientific perpective. But neither does it advance the science to ignore the context. Negative results lose their neutrality when used as weapons by those with vested interests.

PS - KFG. Please do not feel that I have any issues with what you have said. I just feel it is necessary to remember that science, like any other activity, takes place in an enviroment that to a greater or lesser extent is 'political'. I also apologise if the 'tone' of this post causes concern. Tone is easily misconstrued in this medium. We're all in this together.

 

[Quilp]

Hi folks,

Bob has informed me that there's some confusion about permission to repost the Malcolm Hooper note. While he tries to resolve the permission to repost issue, I will snip the quote out of his (and others) posts.

Thanks.

ETA: if permission is granted I will restore it!

Any news on this Robin ? For those that didn't see this post, let me tell you that I did, but given the sensitivities referred to above I will not go into detail. However it stretched beyond the modus operandi that normally prevails when scientists disagree on a particular topic. Scathing ? Plenty of it ! A modicum of diplomacy ? In very short supply.
Why is this important ? Well contrast his comments with that of Dr Charles Shepherd when the first study results were announced; I don't think there has every been such a wide polarisation of views within those that are fighting our cause. What makes this so unusual is that the fallout seems to have extended to the other side too. Look at Reeves and the CDC. Again speculation might not be helpful, but I think most of us are satisfied with the supposition that Reeves didn't move sideways because he wanted to.
Where does this leave us ? Well I cannot ever see us going back to October 7th 2009. Look what happened after the De Frietas debacle; things didn't get better for us they got worse; the psychiatric lobby built whole empires with our illness as their foundations. I can scarcely countenance the possibility that this could happen again, but we have to face facts. Who would want to work in this field ever again if we failed ?
But XMRV has been found, and from cohorts all over the world; and the worlds leading virologists are working on this. They 'didn't flinch' when the first UK study came out; they are sure; they know.
Judy has talked of pharmaceutical companies being involved and therapeutics in six months time. Cort on an earlier post has alluded to a rumour that the CDC are 'finding something'.
Einstein once said that 'God doesn't play dice' in reference to quantum mechanics. In quantum mechanics two particles can be at different places at the same time. You can be right and wrong at the same time. Is somebody playing dice with us ? While others play dice we have an illness that is very real. It is organic, biological, physical. It has nothing to do with abnormal illness beliefs, or being depressed. We have known the truth for decades and suffered for it. We know the truth is there, and I believe that many others on both sides of the arguments know it too. It cannot be a question of IF, it is only a question of when.
The stakes have never been higher,all the protagonists are at the table and ready to roll their dice. But this isn't quantum mechanics, there will be winners and losers, careers elevated and shattered.
Everybody in the casino has come to watch; deathly sounds of silence seep into the ambient air; a sharp intake of breath. Lets Roll.

Fingers crossed xxx

 

[Gerwyn]

Hi KFG

There has been a lot of good discussion here around the scientific method and the issue of whether or not we can 'trust' the researchers. I don't believe, in this case, that its the scientists' integrity that's being questioned.

A number of posters have spoken knowledgeably about the scientific method suggesting a science background, possibly even as active researchers. That being the case, they must also be aware that science does not proceed in a vaccum. The context within which science takes place is also important and the commissioning and funding of research should adhere to the same principles of objectivity as the science itself.

When the WPI study was published there was considerable debate on this forum regarding our hopes and fears for future replications studies. Posters were anxious that anyone undertaking research into XMRV and ME should be aware of the 'political' backgroud to ME, specifically on the issue of the cohorts selected for study. Many of us believed that only a prospective study of Canadian defined subjects was likely to replicate WPI's findings. Dr Bell's involvement (albeit possibly in a minor role) in the current study is to be welcomed in this respect.

It has been stated that the current study was funded by the MRC, yet a written response to a parliamentary question published in December made no mention of a study investigating XMRV in ME. It is a matter of record that ME researchers have criticised the current composition of the MRC committee on the funding of research into ME and many well designed studies into biomedical causes of ME have been refused funding while studies into psychosocial hypotheses appear to have flourished. The most glaring being the PACE/FINE trials.

So when and why did the MRC's attitude change to biomedical research? When was this study proposed, evaluated and recommended for funding?

Perhaps the MRC decided that the WPI findings were sufficiently convincing that to ignore them was no longer tenable. Perhaps they felt that the Imperial College study was sufficiently flawed that nothing could be deduced from its results and that they could do a better job?

I'm sure the researchers, particularly Dr Bell, were glad to receive any funding, even if the level of funding (unknown) and time constraints meant that they had to compromise on issues such as the patient cohort, stored v fresh blood draws, time taken to culture samples etc, issues which in retrospect may have been crucial to detecting XMRV or not.

On the other hand, MRC's research programme is on record. The MRC and the Department of Work and Pensions have invested heavily in the PACE/FINE trials with an obvious expectation that the proposed 'therapies' will be rolled out in some form. Irrefutable evidence of the presence of XMRV as a causal agent in ME would hardly be welcome at this stage, not only as regards rolling out the PACE programme but also when the MRC's prior research programme is considered.

So, it is entirely possible if not probable, that the researchers in this case, have genuinely attempted to find XMRV, using the best methods available to them, and have failed to do so for reasons that have nothing to do with their integrity or failures of proper scientific methodology. Perhaps they were just 'insufficiently funded' to find it.

Whatever the scientific merits of the study (which I am not qualified to comment on, but others have noted issues that question the likelihood of their methods being able to detect XMRV) the study was clearly commissioned and completed in what seems to be a very short timeframe in comparison to the WPI study and without any apparent transparency as to the funding process.

Many others have raised genuine concerns about the MRC's process of funding research into ME. To share these concerns doesn't make you a conspiracy theorist.

Does it advance the science to discuss these contextual issues? Probably not. There are further studies to come and, when properly executed, negative results are as valid as positive from a scientific perpective. But neither does it advance the science to ignore the context. Negative results lose their neutrality when used as weapons by those with vested interests.

PS - KFG. Please do not feel that I have any issues with what you have said. I just feel it is necessary to remember that science, like any other activity, takes place in an enviroment that to a greater or lesser extent is 'political'. I also apologise if the 'tone' of this post causes concern. Tone is easily misconstrued in this medium. We're all in this together.

I agree Marco science does not operate in a vacuum and the application of the method is influenced by social constructs.I,m a bit worried why people cant see flaws in this The design produced unfalsifiable conclusions because it used controls which had endogenous retrovirus expression many times normal.We dont know therefore whether it was lack of sensitivity of the test, misdiagnosis or absence of XMRV, problems with drawing blood, thawing rates or a number of minor methodological issues.These are the basic generic standards of study design.If this was a drug trial with cost implications for the state people would be queing up to rip it to shreds

 

[Gerwyn]

A number of people have, very adroitly, alluded to the use of the scientific method .At its heart it is very simple , occurance of a phenomena , quetions raised about a phenomena ,evaluation of evidence relating to phenomena, explanatory hypothesis and methods devised to test hypothesis usually, experimental or predictive there are others,. the test methodoly must be constructed to actively disprove the hypothesis. Ifthe hypothesis cannot be disproved over time it develops into an accepted theory of approximate truth to a cetain level of probability.can somone tell me where the science was in the british studies according to these criterea.The active attempt to disprove hypothesis is what makes science science no other activity does this.If we lose this approach we have the global warming scenarine final point sudies must be prospective.If you look backwards like a meta analysis different statistical treatments of the same data will reach diffeent conclusions as our psycho friends now so well when reviewing pace/get trials etc

 

[Adamskitutu]

From Angela Kennedy:

PERMISSION TO REPOST

My response to "Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome" in 'Retrovirology 2010'

http://www.retrovirology.com/content/7/1/10

(This response is awaiting moderation by retrovirology - it was submitted 15 February 2010)

What were the characteristics of the patient cohort?

Comment:
Immediate questions that spring to mind relate to the patient cohort and whether they were similar enough to the patient cohort in the Lombardi et al project.

The Lombardi et al research cohort apparently met criteria for 'ME/CFS' as identified by Carruthers et al, in addition to Fukuda et al. which has been demonstrated to select patients with post-exertional malaise and fatigue, sleep dysfunction, pain, clinical neurocognitive, and clinical autonomic/ neuroimmunoendocrine symptoms (Jason et al).

Furthermore, the WPI give this information about their patient cohort in their supporting online material:

"Their diagnosis of CFS is based upon prolonged disabling fatigue and the presence of cognitive deficits and reproducible immunological abnormalities. These included but were not limited to peturbations of the 2-5A synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as measured by standard diagnostic assyas) and elevated cytokines particularly interleukin-6 and interleukin-8. In addition to these immunological abnormalities, the patients characteristically demonstrated impaired exercise performance with extremely low VO2 max measured on stress testing..." (www.sciencemag.org/cgi/content/full/117905/DC1)

The Erlwein et al project selected a rather different patient cohort:

""Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness".

In any British subsequent research to Lombardi et al, unless the patient cohort selected was similar enough to that in the Lombardi research, it is premature to believe XMRV is not present in the 'CFS' population in Britain.

Ongoing neglect of the importance of establishing a possible ‘CFS’ patient population in Britain, clinically and in research settings, using the Canadian Guidelines, is preventing the development of knowledge that might help extremely ill and disabled people, diagnosed with 'CFS', known to be here in Britain.

**I am therefore interested if the authors are aware of any serious attempts to identify such a population in Britain, or taking part in such attempts themselves. **

The problems I have briefly outlined here do not fully express the range and depths of problems with regard to: the identity of an accurate ‘CFS’ population; the instabilities of ‘CFS’ criteria per se; the faulty concepts of ‘medically unexplained’ or ‘functional‘ and relation to ‘psychogenic‘ explanations for somatic illness; the vagaries of criteria that claim to facilitate a ‘diagnosis of exclusion’; and the psychogenic dismissal of serious organic dysfunction of patients given a ’CFS’ diagnosis, problems that have happened for many years.


REFERENCES

Carruthers, B. et al (2003) “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols” Journal of Chronic Fatigue Syndrome, Vol. 11(1), pp 7 - 115.

Jason LA, Torres-Harding SR, Jurgens A, Helgerson J. “Comparing the Fukuda et al. Criteria and the Canadian Case Definition for chronic Fatigue Syndrome”. Journal of Chronic Fatigue Syndrome 12(1):37-52, 2004


Angela Kennedy

 

[faith.hope.love]

Very interesting! Thanks for the update.

 

[Katie]

Good response from the WPI, reasoned, well mannered and polite. I'd actually like them to put this cohort question to bed with a list of the patients, for example...

Patient #0001 - ME 22 years, symptoms blah blah blah, other illnesses, IBS etc.
Patient #0002 - ME 13 years....


On the response to the study I think that's an appropriate response.

 

[Gerwyn]

http://www.wpinstitute.org/news/news_current.html

In The News


February 18, 2010: WPI is aware of the recent UK study that was unable to detect the presence of XMRV in any CFS patient samples. Although researchers at the WPI were not involved in this project, our work in XMRV continues with researchers around the world. We look forward to the results of studies which replicate the methods used in the original research described in the journal Science in October, 2009.
View more...

Information Regarding XMRV Studies

1. The authors of the Science paper established the existence of XMRV as an infectious human blood borne retrovirus for the first time in blood of patients diagnosed with Chronic Fatigue Syndrome (CFS). Previous studies had established the presence of XMRV sequences and protein in human prostate tissue.

2. In the Science paper, the presence of XMRV in well-characterized patients with CFS was established using multiple technologies:

a) PCR on nucleic acids from un-stimulated and stimulated white blood cells;
b) XMRV protein expression from stimulated white blood cells;
c) Virus isolation on the LNCaP cell line; and
d) A specific antibody response to XMRV.

3. The authors of the two UK studies did not attempt to replicate the WPI study. Replication requires that the same technologies be employed. The WPI sent reagents and information to several groups of researchers in an effort to support their replication studies. Neither UK study requested positive control blood, plasma or nucleic acids from the WPI.

4. The collection, preparation and storage of DNA were completely different between the Science and UK papers. The latter studies do not show data on blood harvesting or storage. Nor do the studies disclose the quantity of isolated cells. Insufficient number of cells analyzed may result in failure to detect a low copy virus like XMRV, regardless of the sensitivity of the assay. Neither UK study provides detail to allow interpretation of how many white blood cells were analyzed.

5. Patient population selection may differ between studies.

6. The UK authors were unable to detect XMRV, even though 4% of healthy individuals were found to be infected in the US. Japanese scientists detected XMRV in 1.7% in healthy blood donors in Japan. The two previously identified human retroviruses have distinct geographical distributions.

7. Perhaps the most important issue to focus on is the low level of XMRV in the blood. XMRV is present in such a small percentage of white blood cells that it is highly unlikely that either UK studys PCR method could detect it using the methods described. Careful reading of the Science paper shows that increasing the amount of the virus by growing the white blood cells is usually required rather than using white blood cells directly purified from the body. When using PCR alone, the Science authors found that four samples needed to be taken at different times from the same patient in order for XMRV to be detected by PCR in freshly isolated white blood cells. More importantly, detection methods other than PCR showed that patients whose blood lacks sufficient amount of XMRV detectable by PCR are actually infected. This was proven by the isolation of viral proteins and the finding of infectious XMRV isolated from the indicator cell line LNCaP. The authors of the Retrovirology paper admit that their neutralization assay did not detect bacterially expressed XMRV gag and that positive control sera was needed to validate their assay. The WPIs monoclonal antibodies specifically and sensitively completed the immune response demonstrating the assays sensitivity and specificity for XMRV envelope.

Simply stated the only validated reliable methods for detecting XMRV in CFS patients, to date, are the methods described in Science. Failure to use these methods and validated reagents has resulted in the failure to detect XMRV. A failure to detect XMRV is not the same as absence of this virus in patients with CFS.




Post Script Admin Feel Free to retitle or Move Joy

They are more or less the same points I made with the exception of the controls I wonder if someone has the ability to let them know about the high levels of expressed endogenous retros in the illnesses in the control group I,m sorry but i don,t know how to do it

 

[Abraxas]

Thanks joyscobby. So the new info on the WPI's website today is exactly what Ladybugmandy posted yesterday (# 242)

 

[natasa778]

exactly what Gerwyn has been saying.

Gerwyn for president!!!

 

[julius]

I have been thinking about the question of cohort selection and have found a way to rule it out as a possible confounding factor.

We know the VIP tests are about 50% positive in the UK. And what is the 'cohort' of people getting that test? A bunch of people who think they probably have CFS. Not well defined at all. In fact, you really can't get a more loosely defined 'cohort'.

So, how could the UK researchers pick a cohort with ZERO positives? I can only think of two possibilites;

1) Random Chance.
But the probability of this is so infinitesimally small, it is just not worth considering. With an almost random sampling of possible CFS patients being 50%+, it seems impossible that a cohort picked according to any definition would be ZERO in two separate studies. Really, it's not even worth considering. I'm no statistician, but I feel comfortable guessing that it has less than .001% probability.

or

2) Before they did their studies, the UK teams tested the CFS patients and kicked out any who tested positive. Then did the study using only negatives. I really don't think they did this, but it's the only other way it could happen.

 

[julius]

They are more or less the same points I made with the exception of the controls I wonder if someone has the ability to let them know about the high levels of expressed endogenous retros in the illnesses in the control group I,m sorry but i don,t know how to do it

Gerwyn,

judym @wpinstitute.org
(I put a space before the @)