Is it worth explaining the difference between ME and CFS to the public??

[Bob]

I haven't studied them for contradictions, but the ICC does not include some of the symptoms seen in some of the early outbreaks, and I don't recognise some of those symptoms as being a symptom of ME that any of us experience.

Which ones?

I have been looking back over the literature and I see that I have over-stated the differences between historic ME, and what is widely accepted as 'ME' these days. I accept that they are mostly very similar. The historical descriptions have a wide range of symptoms, but so do ME patients when considered together. As far as I remember (unreliable), there were some symptoms in some historic descriptions, which I did not recognise as ME, but I'd have to dig through all the research to find them again.

Well, you posted with such certainty that all ICC-diagnosed patients are from outbreaks areas

Er, no, that was not what I posted.

Then maybe I misinterpreted you, but you seemed to be quite clear that all ICC patients are from outbreak areas:

Bob: "I'm not sure how many patients fitting the ICC would be from outbreak areas these days (not sure if there are any stats), but my guess is that it would be a minority from outbreak areas."

Guido den Broeder: "Nearly all of them, rather. (Criteria are not the disease itself, so it's never 100% but it can be 99%.)"

Chia has done some good research, but his work only applies to a subset of his patients, and he is unable to easily test for viruses in those patients who he treats. (And maybe he is not even able to successfully test for enteroviruses in his entire subset of supposedly infected patients? But I can't remember the details here.)

Best read up on the details, then. Whether the test is easy is irrelevant here, I think, but few tests score 100%. I am satisfied with the 98% he reports.

Could you tell me what "98%" refers to? Is it the number of patients who have enteroviruses, or the patients that test positive for enteroviruses who he successfully treats (i.e. the response rate)? Or something else? Do you have a link you could share?

Hyde is very clear that the evidence for enteroviral infection is only partial, and explains why. He isn't referring to what he calls "Secondary ME", but he is discussing the historic and current inadequacy of viral tests.

What is your point?

My point is that you have been repeatedly stating as a 'fact', that ME is caused by enteroviruses.
But even Byron Hyde doesn't agree that there is enough evidence to know that conclusively, and he is one of the biggest proponents of the enterovirus theory.
A 'belief' or a 'theory' isn't the same as a 'fact'.

Yes, it is very useful to know about all the evidence, and theories, and opinions, but based on the evidence, you are over-stating the case for enteroviruses. People can make up their own minds, if the evidence is presented to them.

Why always this negativity? Evidence is never perfect. Doesn't mean we can't use it.

You have repeatedly been promoting the enterovirus theory as a 'fact'.
But the enterovirus theory is based on partial and inconclusive evidence, as confirmed by Byron Hyde and the anti-viral research that we've been discussing.
If you only have inconclusive evidence for your theories, then it is really unhelpful to promote the theories as 'fact'.

Yes, we need to know about all the evidence, and all the information, and all the theories, because they all help us to further our understanding about the disease. But promoting theory as 'fact' is counter-productive and very frustrating for other members of the forum.
It would be so much more helpful, if you just let us know what your opinions are, and explain why you have come to those opinions, rather than misleadingly stating your opinions as 'facts'.


Casually telling people that you know the cause of ME, and that you know what the treatment for ME is, when in fact you don't, is really frustrating and unhelpful for other members.
As we've now discussed, the antivirals only work on a subset of patients, and have a limited success on that subset of patients. So, taking this into consideration, along with the reasons that Byron Hyde outlined in the quote that I provided, your assertions are not confirmed by the evidence.

I don't believe the Chia confirms your theory either. But I'll look at any evidence you produce.

 

[Guido den Broeder]

The EBV is latent, not so much dormant. It may be immature and not reproduce, but it does not sleep. It effectively takes control of the B-cell, renders it immortal, and makes molecules that perforate the blood-brain-barrier. That is even before the enterovirus comes along.

 

[Bob]

It effectively takes control of the B-cell, renders it immortal, and makes molecules that perforate the blood-brain-barrier.

That's interesting. Do you have any links to this info please?

 

[Guido den Broeder]

I have been looking back over the literature and I see that I have over-stated the differences between historic ME, and what is widely accepted as 'ME' these days. I accept that they are mostly very similar. The historical descriptions have a wide range of symptoms, but so do ME patients when considered together. As far as I remember (unreliable), there were some symptoms in some historic descriptions, which I did not recognise as ME, but I'd have to dig through all the research to find them again.

The symptom that you would not recognize is, I mentioned it before, paresis. That is because it only occurs if the enterovirus is a poliovirus.

Could you tell me what "98%" refers to? Is it the number of patients who have enteroviruses, or the patients that test positive for enteroviruses who he successfully treats (i.e. the response rate)? Or something else? Do you have a link you could share?

It (or a similar value) is the percentage that tested positive for enteroviral infection in stomach tissue. In the same study, he and his son (a patient) consistently found low-grade inflammation.

Chia JKS, Chia AY (2008), "Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach"

My point is that you have been repeatedly stating as a 'fact', that ME is caused by enteroviruses.
But even Bryon Hyde doesn't agree that there is enough evidence to know that conclusively, and he is one of the biggest proponents of the enterovirus theory.
A 'belief' or a 'theory' isn't the same as a 'fact'.

Yes, it is very useful to know about all the evidence, and theories, and opinions, but the case for enteroviruses shouldn't be over-stated. People can make up their own minds, if the evidence is presented to them.

Actually, most people are not qualified to do that.

Science consists of both induction (evidence) and deduction (reasoning).

Today, anyone can use a computer and statistical software to produce evidence, and one tends to forget about the second part. But it is just as essential.

If you only have partial and inconclusive evidence for your theories, then it is really unhelpful to promote the theories as 'fact'.

On the contrary, it is the only way. This is known as the scientific method. It is how knowledge progresses. You should embrace it, instead of making petty personal attacks.

We would still think the Earth was flat if Galileo hadn't had the courage to state otherwise, even though he lacked perfect evidence.

Evidence is always incomplete and inconclusive, its presentation always selective. Yet we progress. Because we have the skill to learn from imperfect evidence. Hyde goes on to nonetheless present his model of ME. So do others.
I come from a field of research where the evidence is in fact far less certain than in medicine. Yet we progress.

As we've now discussed, the antivirals only work on a subset of patients, and have a limited success on that subset of patients. So your assertions are not confirmed by the evidence.

You have not provided a source for your claim that antivirals work only on a subset of ME patients and have merely limited succes. The source I gave (Lerner) says otherwise.

 

[Bob]

The symptom that you would not recognize is, I mentioned it before, paresis. That is because it only occurs if the enterovirus is a poliovirus.

That may well be it, thank you. But I can't remember what it was.

Could you tell me what "98%" refers to? Is it the number of patients who have enteroviruses, or the patients that test positive for enteroviruses who he successfully treats (i.e. the response rate)? Or something else? Do you have a link you could share?

It (or a similar value) is the percentage that tested positive for enteroviral infection in stomach tissue. In the same study, he and his son (a patient) consistently found low-grade inflammation.

Chia JKS, Chia AY (2008), "Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach"

Thank you for the reference.
The figure is "82%" for CDC CFS patients and "20%" for healthy controls. These figures are for people who tested positive for Enterovirus VP1 in stomach biopsies (VP = viral capsid protein = a protein from the shell of a virus). The figure for EV RNA was 9/24 (37%) positive in patients. The patient cohort might have been a subset of CFS patients: "CFS patients with chronic abdominal complaints", but the abstract is not very clear about that.
There was not any research into treatments in this particular paper.
http://jcp.bmj.com/content/61/1/43

It's very impressive research, but it doesn't back up your assertions conclusively for a number of reasons:
1. An enterovirus infection might be opportunistic rather than causal.
2. The results might only apply to a subset of patients with abdominal complaints (But I need to see the full paper to confirm this.)
3. There is no info about treatment in this paper.
Also, this research need replicating by other researchers and with more resources.

But it is very interesting, and taken together with Lerner's research, and the Rituximab research, we do seem to be getting somewhere, in terms of treatment.

As we've now discussed, the antivirals only work on a subset of patients, and have a limited success on that subset of patients. So your assertions are not confirmed by the evidence.

You have not provided a source for your claim that antivirals work only on a subset of ME patients and have merely limited succes. The source I gave (Lerner) says otherwise.

Actually, it is Lerner's research that I was thinking of.
I think his research is very impressive, and I wish more resources were made available to follow it up.

But I still don't understand the hypothetical relationship between Herpes viruses, and enteroviruses. There's no mention of enteroviruses in Lerner's paper.

In Lerner's 2010 study, 75% of his 'Group A' CFS patients responded to treatment with valacyclovir and/or valganciclovir. The results do seem very impressive, despite 25% of 'Group A' not responding to treatment.
In his 'Group B' (also CFS patients), the response to treatment was disappointingly 'small', and I can't see any details for how many 'Group B' patients responded.
As far as I can tell, Lerner only treated patients who tested positive for the Herpes virus, in which case the combination of 'Group A' and 'Group B' was still a subset of his CFS patients. I can't see any details stating what proportion of his CFS patients made up this subset.
http://www.co-cure.org/Lerner.pdf

Extra info re Lerner's study:
'Group A' CFS patients had the herpes viruses: EBV, HCMV, and HHV6, in
single or multiple infection without coinfection.
'Group B' CFS patients were similar to Group A, but with coinfections:
tick-borne Borrelia burgdorferi, Babesia microti, Anaplasma phagocytophila, and/or adult rheumatic fever.

 

[Bob]

The third issue, that I changed my mind about, was not a 'retraction', because I didn't make a statement in the first place. I had raised a point of discussion, and clearly gave my opinions, re the differences/similarities of the ICC to some old descriptions of 'ME'. I'm still not sure about the differences/similarities between the ICC and some of the old descriptions, but I can now see that I may have made too much of the differences, based on some of the literature that I have just had a look at. The points of discussion that I raised are still valid, but I don't know if they have as much importance as I originally thought.

Guido, I think you have misunderstood the issues that I raised. I never have a problem when people make mistakes, or get in a muddle, or misunderstand stuff. Of course there's no problem with that: It's all part of having a discussion, and I'm always getting details wrong. But I do find it frustrating when people repeatedly make assertions, as if they are stating conclusive factual information, but then it turns out that they are just expressing their opinions. I think that irritates many people, not just me.

If you only have partial and inconclusive evidence for your theories, then it is really unhelpful to promote the theories as 'fact'.

On the contrary, it is the only way. This is known as the scientific method. It is how knowledge progresses.

That's not correct at all. The scientific method is to hypothesise, and then to carry out research in order to prove or disprove the hypothesis. Stating opinions as 'fact' is absolutely not the scientific method. In fact, it's the opposite.

As for making "petty personal attacks", I'm sorry that's how my comments have been perceived. I was just trying to point out why I find your assertions very frustrating and unhelpful. I probably went about it in the wrong way, and I should have had more patience. So I apologise if I have offended you.

Evidence is always incomplete and inconclusive, its presentation always selective. Yet we progress. Because we have the skill to learn from imperfect evidence. Hyde goes on to nonetheless present his model of ME. So do others.

I agree with that, philosophically speaking. But, practically speaking, it's not exactly the case: Using a simple example; all scientists agree that the world is round(ish), these days.

I agree that we learn from imperfect evidence, but my issue is how you have presented inconclusive evidence as conclusive evidence that supports your theory, when it doesn't.

 

[Guido den Broeder]

A hypothesis is merely the manner in which we present theory as fact.

Note that a theory cannot be proven, only disproven. Obviously, I will therefore never present evidence as conclusive proof. All I said was that I was satisfied.

What is important here, is that a lot of testing has already taken place over the years. Since research, too, is always imperfect, the resulting evidence needs to be evaluated in order to establish its value. There is a whole set of tools again to do just that.

The 82% in Chia, 2008 is just one of the tests in that study. The article also gives the results of other tests showing enteroviral material, partly in different patients. It adds up. Lerner's Group B will simply need treatment for Lyme etc.

 

[Nielk]

A hypothesis is merely the manner in which we present theory as fact.

Note that a theory cannot be proven, only disproven. Obviously, I will therefore never present evidence as conclusive proof. All I said was that I was satisfied.

What is important here, is that a lot of testing has already taken place over the years. Since research, too, is always imperfect, the resulting evidence needs to be evaluated in order to establish its value. There is a whole set of tools again to do just that.

The science of disease is not hypothesis nor theory. If one has a heart attack, then that's exactly what is happening... there is no hypothesis or theory...just hard cold fact.

When I suffered from my Crohn's disease which is an inflammation in the Ileum, I can clearly see the inflammation on
a colonoscopy test. It is clear cut there and therefore anti-inflammatory medications help.

So far with ME/CFIDS/CFS, science has not progressed to the point that there is clear cut proof of a causing agent.
You might say that it is a enterovirus and others say it is a retrovirus. Many scientists or doctors think that it is
a neurological disease whereas others believe it is an immune problem affecting B cells.

Right now it is still in the theories stage but, this can change at any point where science can prove that one of these theories is true.

Of course theories can be proven true. What do you call Science and Mathematics?

 

[Bob]

A hypothesis is merely the manner in which we present theory as fact.

Not so. Please consult a dictionary.

Obviously, I will therefore never present evidence as conclusive proof. All I said was that I was satisfied.

Making what appear to be factual statements about the cause and treatment of ME, but on close inspection are found to be unsupported opinions, is very confusing for everyone else reading this thread. We all want treatments and we all want to know what the cause is, and so making such statements draws our attention to such comments. You've caused me a load of work to show that you didn't have the evidence to back up your claims.

Not only that, but, frustratingly, you haven't once admitted an error in anything that you've said, even though I've demonstrated that your assertions were not supported by the evidence, or were just inaccurate.

If you've got any actual evidence to demonstrate why your assertions are correct, then I'm very open minded, and would love to see that evidence, and to change my mind.

What is important here, is that a lot of testing has already taken place over the years. Since research, too, is always imperfect, the resulting evidence needs to be evaluated in order to establish its value. There is a whole set of tools again to do just that.

Yes, of course the research needs to be interpreted. That's what I've tried to do this thread.

The 82% in Chia, 2008 is just one of the tests in that study. The article also gives the results of other tests showing enteroviral material, partly in different patients. It adds up. Lerner's Group B will simply need treatment for Lyme etc.

Yes, it does all add up, and it's all very impressive research.
But Chia has found enterovirus shell proteins (VP1) in 82% of a subset of CFS patients. And that doesn't even prove that there is a causal relationship in any of the subset.
And Lerner has successfully treated 75% of a subset of CFS patients. (I don't know what the percentage of CFS patients as a whole is, but it will obviously be less than 75%.)
So neither of those studies confirm that ME is either caused by an enterovirus or successfully treated with antivirals, which is what you misleadingly stated earlier in the thread.
Although, they are obviously very interesting and helpful pieces of research which need to be followed up.

And if ME is caused by an enterovirus, I still don't understand why Lerner's treatment is for herpes viruses. To me, that suggests that there could be a disorder of the immune system, leading to opportunistic infections, or that herpes viruses could be causing an immune system disorder. Even the Rituximab research paper, which was discussed earlier, demonstrated that Rituximab reduces plasma copy numbers of a herpes viruses (EBV), and not an enterovirus. I wonder, if there is no treatment available for enteroviruses? Anti-viral treatment for enteroviruses would be an interesting research project.

 

[Guido den Broeder]

What I have told here about herpes and enteroviruses as cause and trigger is not something I invented just the other day. This model of ME was put forward before everyone went CFS (see Hyde, 1990).

The science of disease is not hypothesis nor theory. If one has a heart attack, then that's exactly what is happening... there is no hypothesis or theory...just hard cold fact.

Really? There are no theories about alcohol, obesity, blood pressure, tobacco, stress, exertion, and so on?

When I suffered from my Crohn's disease which is an inflammation in the Ileum, I can clearly see the inflammation on a colonoscopy test. It is clear cut there and therefore anti-inflammatory medications help.

You can see the CNS inflammation from ME when you open up the spine or the brain. The only drawback is that this will kill you but hey, if you really want to be sure. It was done with monkeys way back in the 1950s.
Chia 2008 shows that the inflammation is also commonly present in the stomach; other researchers found it in the muscles as well.

I seem to recall years ago a neurologist or perhaps my ME doctor told me that CNS injury can activate B-cells and generate autoantibodies.

Possibly, but in ME it starts the other way around.

 

[Tally]

Really? There are no theories about alcohol, obesity, blood pressure, tobacco, stress, exertion, and so on?

You are mixing up "theory" as used by laymen and "theory" as used by scientists. Examples you mentioned are scientific hypothesis, not scientific theories.

From wikipedia:
"In modern science, the term "theory" refers to scientific theories, a well-confirmed type of explanation of nature, made in a way consistent with scientific method, and fulfilling th criteria required by modern science. Such theories are described in such a way that any scientist in the field is in a position to understand and either provide empirical support ("verify") or empirically contradict ("falsify") it. Scientific theories are the most reliable, rigorous, and comprehensive form of scientific knowledge,in contrast to more common uses of the word "theory" that imply that something is unproven or speculative."

But all we are doing here is discussing semantics and flexing our brain muscles. It is well known how many medical researches with what results need to be done for something to be accepted as a cause and as a cure. That has yet not been done with ME/CFS. I think the Phoenix Rising's article "Once Is Not Enough" does a good job of explaining this http://phoenixrising.me/archives/12124

 

[Guido den Broeder]

I have been a scientist for nearly half a century.

As so often, Wikipedia is wrong. And so is the Phoenix Rising article.

 

[Ember]

I think it's fair to point out that a number of hypothetical statements on this thread sound like statements of fact. The ones about CFS are less likely to be challenged though. At the beginning of this thread I read that “there is no such thing as CFS, other than a misnomer for ME and a misdiagnosis for unfortunate people with 'CF.'

In your summary, you seem to concur, Bob, with this theory: “So the current 'CFS' criteria do not define an actual disease.” However, no CFS definition has been retracted, and with 10% undiagnosed even by Dr. Hyde's standards, nobody is in a position to make such a statement, one that could affect large numbers of patients. This statement too is based on partial knowledge and inconclusive evidence.

Notice that the description of the new Complex Chronic Disease Clinic in Vancouver includes both ME and CFS:

This clinic is for people who suffer from a group of complex chronic diseases which include but are not limited to:

• Myalgic Encephalomyelitis
• Chronic Fatigue Syndrome
• Fibromyalgia Syndrome
• Lyme disease (http://www.bcwomens.ca/Services/HealthServices/complex-chronic-disease-clinic/default.htm).

 

[Ember]

Whether CCC should be used to define 'CFS' or 'CFS/ME' or 'ME', is a legitimate argument to have, but I think that people should be careful to separate this argument from the argument about whether CCC should be used at all. It's very confusing when people start having arguments over the use of CCC without totally clarifying their perspective and their use of the terms 'ME' and 'CFS' from the outset. Often what seems like a huge argument can just boil down to a different and casual use of the terms 'ME' and 'CFS'.

I'm very interested in finding out more about the history of 'ME', and how the 'ME' definitions are different to what the CCC describes.

In much of this thread, reference to the “CCC CFS criteria” has gone unchallenged. But as you know, it would seem more accurate to characterize the CCC as ME criteria. Dr. Carruthers writes in last month's Journal of Iime, “The results of Jason et al’s studies have confirmed that the Canadian Definition of ME/CFS had clearly separated cases who have ME...from those who have CFS....” In an interview with Cort, Marj van de Sande has explained that the term 'CFS' in ME/CFS was used solely for its familiarity in the US:

The draft of the Canadian Consensus Criteria (CCC) used the name “myalgic encephalomyelitis” (ME). However, we changed it to ME/CFS because a member of the panel felt that some American patients were not familiar with the name ‘ME’. At the time we did the CCC, we didn’t have plans to do another definition in the future. In retrospect, it did serve as a good transition period.

It may be useful to note too that the ICC moves toward making ME exclusionary for CFS: “Individuals meeting the International Consensus Criteria have myalgic encephalomyelitis and should be removed from the Reeves empirical criteria and the National Institute for Clinical Excellence (NICE) criteria for chronic fatigue syndrome.” Wouldn't promoting the ICC, the next generation definition to the CCC, be a useful part of any action plan?

 

[Bob]

I think it's fair to point out that a number of hypothetical statements on this thread sound like statements of fact. The ones about CFS are less likely to be challenged though. At the beginning of this thread I read that “there is no such thing as CFS, other than a misnomer for ME and a misdiagnosis for unfortunate people with 'CF.'

In your summary, you seem to concur, Bob, with this theory: “So the current 'CFS' criteria do not define an actual disease.” However, no CFS definition has been retracted, and with 10% undiagnosed even by Dr. Hyde's standards, nobody is in a position to make such a statement, one that could affect large numbers of patients. This statement too is based on partial knowledge and inconclusive evidence.

Hi Ember, it wasn't helpful to discuss my post directly after your first paragraph. It makes it look like you are accusing me of trying to make hypothetical statements sound like statements of fact.

In the post that you've highlighted, I was clearly discussing opinions and theories, from a variety of sources.
And the specific sentence, that you highlighted, was used in the context of describing a theory. I think it's very clear in that post, that I'm not certain about any of it, but was involved in a process of exploring the issues.

However, having said that, I would be a little surprised if Fukuda diagnoses a single discrete disease, because it just defines a set of symptoms. If more than one unknown disease has similar symptoms which are described by Fukuda, then Fukuda doesn't define a single disease.

Edit:
And, as I highlighted earlier, a patient only needs to have fatigue, pain, headaches and sleep problems to be diagnosed with 'CFS'. That doesn't seem like a sophisticated description of a discrete disease to me.

 

[Bob]

Wouldn't promoting the ICC, the next generation definition to the CCC, be a useful part of any action plan?

Just so you know, the ICC hadn't been published when a large part of this thread was created.

 

[Guido den Broeder]

The CCC 2003 are criteria for chronic ME. The disease does not always become chronic.

 

[Ember]

Hi Ember, it wasn't helpful to discuss my post directly after your first paragraph. It makes it look like you are accusing me of trying to make hypothetical statements sound like statements of fact.

In the post that you've highlighted, I was clearly discussing opinions and theories, from a variety of sources.
And that specific sentence that you highlighted was written as part of a description of a theory, and I think it's clear in that post, that I'm not certain about any of it.

However, having said that, I would be a little surprised if Fukuda diagnoses a single discrete disease, because it just defines a set of symptoms. If more than one unknown disease has similar symptoms which are described by Fukuda, then Fukuda doesn't define a single disease.

Edit:
And, as I highlighted earlier, a patient only needs to have fatigue, pain, headaches and sleep problems to be diagnosed with 'CFS'. That doesn't seem like a sophisticated description of a discrete disease to me.

I tried to be careful with my words, Bob. I called your post a summary, said you seemed to concur with an earlier post and identified your statement as a theory. I was trying to point out that a hypothetical statement can sound like a fact and that some such statements (particularly ones about CFS) tend to go unchallenged, despite their being based on partial knowledge and inconclusive evidence.

I appreciate your care in writing that you “would be a little surprised if Fukuda diagnoses a single discrete disease.” I think such careful wording is important. So far, of course, CFS is defined as a syndrome, not as a disease. I find it encouraging to see that the new Vancouver clinic is identifying both ME and CFS patients.

Thanks, by the way, for pointing out that the ICC hadn't been published when a large part of this thread was created. You're right in assuming that I hadn't noticed when the thread jumped back a year...

 

[Bob]

Guido, if you've got any information that I'm not aware of, that supports your assertions, then I'd be happy to review it, and to change my opinions where appropriate. So far, you haven't presented me with any information that supports your assertions that ME is caused by a enteroviruses, and that ME is successfully treated with antivirals (Although, I acknowledge that Lerner has treated some patients who test positive for a herpes virus). I'd be very interested to see any research that I'm not aware of.

Chia's study of a subset of CFS patients doesn't prove a cause, although his research is impressive. It's a shame that there aren't better anti-virals available, which are able to treat enteroviruses. Is there any enterovirus research that indicates causality?

Lerner has managed to treat 75% of CFS patients who test positive for herpes viruses (and who don't have other co-infections), and it would be interesting to see this research carried out on a large scale. I believe that Lerner uses valacyclovir and/or valganciclovir.

It's interesting that Ampligen might be getting the go-ahead by the FDA - This is another area of research that is worth keeping an eye on.

What I have told here about herpes and enteroviruses as cause and trigger is not something I invented just the other day. This model of ME was put forward before everyone went CFS (see Hyde, 1990).

It sounds like an interesting 'model'. It's a shame you are unable to provide us with links to information about this model of disease, so we can all find out about it, if we want to. You've still not properly explained why herpes is involved in this model. And you've not answered any of my repeated questions about your model, which is a shame.

 

[Guido den Broeder]

I am under no obligation to answer your questions. You will just have to read the book.

My effort to teach something ends here.