Favorite Scientific Paper?

[SteveGrenard]

The abstract states that this is the British Journal of Pharmacology, not the British Journal of Medicine. Both the Lancet and The BMJ have a tradition of open minded publication, placing both sides of the debate in front of their readers. I was not aware that the British J of Pharmacology did also.

I agree that the full paper needs to be read and evaluated. I am not criticising it, I am asking questions or pointing out questions, the answers to which could have possibly skewered the results. I don't know the answers which I why I asked them. In the meantime all we KNOW is what is given in the abstract.

Here is the abstract as it appears in MedLine. Correct me if I am wrong.
We do NOT know what the proofs are: fever, hyperexia, cardiac arrest, tachycardia, flushing, etc. The only proof I found in the historical literature was for Scarlet Fever which correlates with fever and flushing. Or whether any of the proofs include the less well defined effects of belladona which are psychoactive and hallucinogenic.

These results indicate no significance in the proving rate which are both at about 14% for symptoms and 86%, therefore, for nothing.



Br J Clin Pharmacol. 2003 Nov; 56(5): 562-8. Related Articles, Links

Ultramolecular homeopathy has no observable clinical effects. A randomized, double-blind, placebo-controlled proving trial of Belladonna 30C.

Brien S, Lewith G, Bryant T.

Complementary Medicine Research Unit, University of Southampton, Royal South Hants Hospital, Brintons Terrace, Southampton SO14 0YG, UK. s.brien@soton.ac.uk

AIMS: To investigate if ultramolecular homeopathy has any clinical effects. This was assessed using the proving of the homeopathic remedy Belladonna given at an ultramolecular dose (30C), as a model. A proving states that when a homeopathic remedy is given to a healthy person, they will experience symptomatic effects specific to that remedy. If ultramolecular doses are clinically active, the Belladonna 30C group should experience more true Belladonna proving symptoms than the placebo group. METHODS: Healthy subjects (n = 253), aged 18-30 years, took part in this double-blind, randomized placebo-controlled study. Total study duration was 4 weeks. Subjects were randomized before 1 week placebo run-in. They received 2 weeks of treatment intervention (Belladonna 30C or placebo) and were followed up for 1 week. Subjects recorded any symptoms experienced during the total study period on a daily basis using a structured questionnaire. Symptom diaries were analysed blind to determine if each subject had proved or not (based on predefined criteria). The main outcome was the proportion of subjects who had proved in each treatment group. RESULTS: No significant group differences in proving rates were observed [Belladonna provers N = 14 (13.9%); placebo provers N = 15 (14.3%); mean difference -0.4%, 95% confidence interval -9.3, 10.1] based on intention to treat analysis. Primary outcome was not affected by seasonality or the individual's attitude to complementary medicine. CONCLUSION: Ultramolecular homeopathy had no observable clinical effects.

PMID: 14651731 [PubMed - in process]

 

[T'ai Chi]

Ack, one of my favorites is Efron's paper on the bootstrap but I can't seem to find the exact reference.

 

[jj]

That would be Shannon's paper on the Channel Capacity theorem.

 

[JamesM]

Ack, one of my favorites is Efron's paper on the bootstrap but I can't seem to find the exact reference.

Would that be "Bootstrap methods: another look at the jackknife", Ann. Statist., 7, 1-26? By coincidence, I just got out his jackknife/bootstrap monograph from the library.

I found "Assessing Model Fit by Cross-validation" by Hawkins and co-workers, quite thought-provoking, but to anyone not interested in chemometrics or chemoinformatics, it would probably look like the most boring paper ever written.

 

[Matabiri]

That would be Shannon's paper on the Channel Capacity theorem.

That is a brilliant paper.

The one I'm currently sending everyone to read, even though it's nothing to do with what I'm doing, is "Unskilled and Unaware of It: How Difficulties in Recognizing One's Own Incompetence Lead to Inflated Self-Assessments": http://www.apa.org/journals/psp/psp7761121.html

For my own work, my favourite is "The Theory of Sink Strengths" Brailsford and Bullough, Phil. Trans. R. Soc. Lon. 302 (1981) pp 87 - 137, a masterpiece of mathematical simplification.

 

[Rolfe]

Correct me if I am wrong, but doesn't old Sam use cinchona in detectable doses in his first proving?

I'm sorry to be colluding in the hijacking of this thread, but this is exactly what I was referring to in an earlier post - when you say this, the homoeopaths immediately tell you that you don't know what you're talking about.

I wrote a short summary of homoeopathic methods for a professional journal. In it I made the "mistake" of saying pretty much what Steve just said, for pretty much the same reasons (it makes sense, and it's what the homoeopaths themselves appear to be claiming when you read their more public pronouncements). The response I got was:

Dr [Rolfe]'s letter in the same issue shows that she has not fully understood any writings by homoeopaths she has read. Admittedly, Dr Hahnemann's first experiments with Peruvian bark extract were carried out using material doses (Cullen, 1790), but he gradually reduced the size of the doses used in both proving medicines and treating patients. By 1833 he was recommending that the 30 cH dilution should be used for all provings.

Sigh. Note to self. If you think anything about homoeopathy makes sense, then you almost certainly don't really understand what they're saying.

It was this response that first drew to my attention the essentially mystical nature of the homoeopathic proving. Although it might at one time have been about cinchona producing fever (apparently only in Hahnemann - the effect has never been observed by anyone else and it is postulated that he had an idiosyncratic hypersensitivity reaction to the stuff), and even today in public homoeopaths will refer to using onion to treat colds because chopping an onion makes your eyes water, the reality is very different.

Symptoms reported by provers have little to do with what might be expected from real doses of the substance in question. The following is just a random selection, some going back many years:<UL>
<LI>an unpleasant message makes him deeply sad and depressed
<LI>easily falls asleep when reading
<LI>excessive liability to become pregnant
<LI>excessive trembling of the body, when dallying with females
<LI>after stooping some time, sense of painful weight about the head upon resuming the erect posture
<LI>an itching, tickling sensation at the outer edge of the palm of the hand
<LI>after having written a long time with the back a little bent over, violent pain in the back and shoulder-blades
<LI>dreams which are not remembered - disposition to mental dejection - wakefulness before and after midnight
[/list]A colleague of mine who was informed by some homoeopaths that modern provings are now rigorously scientific and blinded, asked for a reference. He was given this site here. Take a look, Steve. The depth of the new-age mysticism pretty much defies description. It is this sort of meditative and psychological exercise homoeopaths mean when they talk about "provings", and it can be very difficult to design a scientific study to take account of these factors.

Nevertheless, you are criticising a published paper on the grounds of alleged methodological flaws, without having read the full text of the paper. Geni, who has read it, tells you that these concerns are fully dealt with in the complete text, and that when you assume certain precautions were not taken simply because they are not referred to in a short abstract, you are mistaken.

OK, either read the full paper and substantiate your allegations from that, or shut up about it.

Rolfe.

 

[Rolfe]

Treating a group of patients with nausea, vomiting and gastroenteritis with Belladona 30C versus placebo double blinded would be a more rational approach.

Maybe it would. The problem is that it is not a homoeopathic approach, and the homoeopaths categorically reject such studies as "not according to homoeopathic principles".

We are accustomed to thinking of drug A as being an effective treatment for disease B. Therefore a useful way to assess the efficacy of A is to get a bunch of people suffering from B and figure out if more of them get better when given A than when given a placebo. However, this is not how homoeopathy works, and so studies like this are deemed inappropriate by the homoeopaths.

They work on a principle called "individualisation", whereby every patient is assessed individually for all sorts of things - personality traits and incidental unrelated symptoms and all sorts, and then individually matched to what is declared to be their ideal remedy. Thus a group of patients suffering from B might all require different remedies.

Some homoeopaths do recognise something they call the "genus epidemicus", which means that if you are in the middle of an epidemic where everybody has the same thing and you don't have time to individualise everyone, you give them all the same. But they still argue about it.

Arnica is sometimes treated as the "genus epidemicus" for tissue injury. Working on that principle, a double-blind study was done to see if arnica reduced swelling and bleeding post-op for patients having carpal tunnel surgery (chosen because that was a very standardised "injury" to everyone in the group). Oh, and a very similar thing was done using wisdom tooth extraction. Negative results. Dismissed by homoeopaths because of the absence of "individualisation". The concept that arnica is a "specific" for injury and bruising is simply not homoeopathic.

So, try again. This time don't try to assess a single remedy, but "individualised" homoeopathy as an entity in itself. Collect a group of children with asthma. Send them all to the homoeopaths, and let the homoeopaths do whatever they like and prescribe whatever they like. But only half get the actual prescription, the other half get a placebo. Again, no difference. The homoeopaths again bitterly criticise the methodology on various points (some of which are self-contradictory), or else just point to a couple of testimonials and declare that no matter what the scientific study showed, these testimonials are proof of efficacy.

It is against this background that some attention has also been paid to the concept of the proving. This is the assessment of the effect of the proposed remedy on healthy people, which as I pointed out in a post above, is done primarily on solute-free preparations. If anyone could really tell the difference between such a preparation and a placebo, it would provide hitherto unheard-of evidence that such preparations are capable of having physiological effects. The homoeopaths insist that they do.

This is the background to these papers on the proving of belladonna 30C, and it's not much use to come along and say, well, they should have done an efficacy trial on sick patients. That wasn't the purpose of the experiment. The purpose of the experiment was to see if there was any evidence for the homoeopaths' claims that belladonna 30C has detectable effects on healthy people.

Now, we all know that the word limit on abstracts is pretty tight. In order to assess a paper fully, and in particular to see if there are any methodological flaws, it is necessary to read the whole thing. Steve has chosen to assume that there are methodological flaws in Geni's favourite paper, simply because not every i was dotted or t crossed in the abstract. I'm still waiting to hear him substantiate this accusation from an assessment of the full paper.

Rolfe.

 

[SteveGrenard]

Rolfe misquotes, LIES and misattributes by saying:

Nevertheless, you are criticising a published paper on the grounds of alleged methodological flaws, without having read the full text of the paper. Geni, who has read it, tells you that these concerns are fully dealt with in the complete text, and that when you assume certain precautions were not taken simply because they are not referred to in a short abstract, you are mistaken.

1.To this Mr Rolfe, I say YOU are mistaken.

2. To this, I say NEVERTHELESS I am doing nothing of the kind.

3. To this, I say I am not criticizing this paper.

4. To this, I say I am asking questions which may or may not lead to criticism of this paper, the answers to which nobody here can apparenbtly give in spite of their highly credulous acceptance of the findings in abstract.

Is that clear enuf for you sir?

oh, and to this:

4. Geni does not admit he read the paper only the abstract. If he has read the paper he can answer my questions.
The statements he made could be obtained from the abstract. He said it is available online to subscribers. He did not say he was a subscriber.

I am asking my medical library to order me a full text today and I should have it in a few days.

Please do try and refrain from personally lying about my intentions and deliberately NOT properly reading what I wrote, changing the words to suit whatever your opinions are instead of the facts. This is not the first time you have fabricated misinformation about my intentions. Join the club of people like Hoyt who are much better at it than you are.

You do yourself no favors by using the skeptic liars trick of fabricating intentions not specified in what your target has written. Instead you heap ridicule upon yourself for doing so.

 

[Rolfe]

Rolfe misquotes, LIES and misattributes....

Huh? If we're getting into who is lying and misattributing and not properly reading what people write, might I submit:

Rolfe:

I assume you have read the full paper since it is your favorite scientific paper of all time

Nowhere did I even suggest it was anywhere close to being my favourite scientific paper of all time. I have not yet decided which paper to submit in response to T'ai Chi's interesting question.

Now, I interpreted Steve's statement

I guess this means this study refuting homeopathy is garbage.

as criticism of the paper. Steve now says:

I say I am not criticizing this paper.
....
Please do try and refrain from personally lying about my intentions and deliberately NOT properly reading what I wrote, changing the words to suit whatever your opinions are instead of the facts.

Well. if that statement wasn't criticism, I don't know what it was.

I'm still quite baffled as to why you're so het up about this paper. It's perfectly normal for people with some interest in a subject to refer to abstracts available on the Internet, taking it as a given that the full study does support what is asserted in the abstract. On the other hand, if one intends to criticise the methodology of a paper, one does that because there is a clear flaw evident. Such a flaw may indeed be evident in an abstract, but if it is not, it is not sufficient to say, it is possible that reading the full paper might reveal a flaw. It is necessary actually to read the paper and then point out the flaw.

Now, Steve, if you're accusing Geni of not actually having read his declared favourite paper, I think that's something you ought to take up with him.

And if you think that reading the full text will reveal a flaw, then carry on. When you've found it, I'll be as interested as everyone else to hear about it and discuss it.

Rolfe.

 

[Rolfe]

Hi,

What is your favorite scientific paper?

(by that I mean a paper, published in a respected peer-reviewed scientific journal)

This is a very interesting question. I have a few papers I'm constantly referring to, but often this is because of defects in the paper - for example a 2001 offering in the Veterinary Record which demonstrated conclusively (in the Results section) that all the feline leukaemia tests currently on the market are rubbish, then went on in the Discussion to say how good the tests were! And an earlier one in the same journal which declared that an analytical instrument was useful for diagnostic purposes without presenting a single fact in the entire five pages to substantiate that assertion. (A classic case of a flaw not appreciable from the abstract, but very clear once one reads the full text.)

But a favourite should be because it's good, I think. And an all-time favourite should have something more to commend than just being another standard-recipe trial of something. There are a lot of papers which show quite nicely that a certain treatment does or doesn't give good results, or a certain test is or is not useful for diagnosing a certain condition, and good though they are, they're almost ten a penny.

There are of course the real greats. Krebs' first description of the citric acid cycle. Watson, Crick and Franklin and the double helix. And I'm sure every field has its own. But I think T'ai Chi wants something personal.

So I'm going with the paper I referred to while I was doing my PhD, as "the paper I wish I'd written".

Robertshaw, D. & Taylor, C. R. (1969) Sweat gland function of the donkey (Equus asinus). J. Physiol., 205, 79-89.

I'm chagrined to find that the paper is missing from the relevant file, so I can't refer to it. However, quoting from my thesis,

This work demonstrated that heat-induced sweating was mediated entirely by local sympathetic nervous stimulation and was abolished in decentralised skin, that humoral adrenaline alone (either by infusion or stimulated in vivo by insulin-induced hypoglycaemia) would cause sweating even in decentralised skin, and that both neural and humoral mechanisms were involved in exercise-induced sweating, which could only be abolished by decentralisation of the skin and adreno-medullary denervation together, not by either procedure alone.

My admiration was drawn by the authors' very precise definition of the question to be answered, and their elegant and well-conceived experimental protocol to answer the question.

Actually, "paper I wish I'd written" is a really hypocritical thing to say. I couldn't possibly have done this work, because it meant doing things to donkeys which, while not cruel at the time, undoubtedly meant that they would have had to be put down after the experiment. I'm a big enough hypocrite to be unable to imagine doing this to a donkey myself, but to admire intellectually the way others have done this to answer a scientific question which was central to my own work.

Rolfe.

 

[geni]

Here is the abstract as it appears in MedLine. Correct me if I am wrong.
We do NOT know what the proofs are: fever, hyperexia, cardiac arrest, tachycardia, flushing, etc. The only proof I found in the historical literature was for Scarlet Fever which correlates with fever and flushing. Or whether any of the proofs include the less well defined effects of belladona which are psychoactive and hallucinogenic

Use of royal we here. I'm sitting here with the paper on screen in frount of me. The symptoms tested for were those that homeopaths claim would turn up in a proving (plus another 5 test symptoms and two for internal consistancy). People in both groups proved. There was no significant difference between the groups.

 

[Rolfe]

In the meantime all we KNOW is what is given in the abstract.

I now have a copy of the full paper.

I'm trying to address Steve's concerns specifically. First, he very reasonably enquired whether the subjects were blinded as to what they might be taking (that is, did they or did they not know that Belladonna was the preparation under examination).

Subjects were blinded to the placebo run-in phase and that the medication was Belladonna 30C.

So, they didn't know that the study was about Belladonna. This seems to refute one possible criticism. If they didn't know it was Belladonna, they could hardly go and look up Belladonna to see which of the listed symptoms they were supposed to be experiencing. (The other part of that sentence refers to the fact that all participants were given the placebo for a week, before half of them were switched to the homoeopathic preparation. It appears that the subjects were led to believe that they might be taking the homoeopathic preparation right from the beginning.)

I wish I could reproduce large sections of the paper, because it is well put together and a great deal of attention is paid to statistical validity and effectiveness of the blinding, as well as some constructive discussion of possible inadequacies in the methodology and the authors' reasons for nevertheless standing by their conclusions. However, I'd probably get banned for breaching copyright rules, so forget it.

However, maybe I'll get away with reproducing one section, as it refers directly to Steve's comments.

The proving questionnaire

The primary outcome was based on a proving response as identified by the proving questionnaire (PQ). The PQ (see Table 1) contained 12 statements with an 'open' section for subjects to record other symptoms. These statements included: (i) five true Belladonna symptoms selected from valid homeopathic reference source (Schroyens, F. (1999) Synthesis. London: Homeopathic Book Publishers.); (ii) five false symptoms; and (iii) two statements for internal consistency. Symptoms recorded in the 'open' section were coded as true of false [according to the same reference].

Table 1 Symptoms used in the proving questionnaire
-----------------------------------------------------------------
True Belladonna symptoms
1. My lips are inflamed
2. I have experienced shooting, tearing pains in my lower limbs, that are made better by walking
3. I had an unusual dry racking cough after 11 pm
4. I have a sinking and rising sensation in my head
5. My pupils are unusually dilated, especially when I feel hot

False Belladonna symptoms
1. I enjoyed listening to my favourite music station today
2. My ears feel as if they are frozen, regardless of the weather
3. I have had an unusual fear of crowds
4. I have a stitching pain in my fingertips when I grasp something
5. Everything tastes bitter except for water

Two statements for internal consistency
1. My lips feel like they have shrunk
2. I have disliked all music today

The data were analysed blind to according to pre-determined criteria to assess whether an individual had "proved" for Belladonna according to the homoeopaths' own theories and methods, that is they had demonstrated the symptom pattern believed to be associated with Belladonna according to Schroyens. During the run-up week, when everybody got the placebo, 7 out of 105 in the control group and 8 out of 101 in the "got Belladonna the following week" group proved. During the two weeks of the actual trial, 15 of the placebo group proved, while only 14 of the Belladonna group proved.

Given that I'm constantly being told that if only I'd take 30C Belladonna myself, I'd immediately be convinced of the validity of homoeopathy because of the unmistakable symptoms I'd feel, I don't find this result very impressive. Or rather, I do find it quite impressive in debunking the assertion.

Yes, one can quibble round the edges of all this, and the authors do that themselves. But this final quote from the Discussion rather says it all.

This study has raised a number of questions. Proving studies form the basis for homeopathic prescribing, yet these data have not provided evidence for the existence of a homeopathic effect using a commonly prescribed remedy. It could therefore be suggested that the central tenets that underlie homeopathy are not valid, i.e. the concept of provings and ultradilutions, which has considerable implications in terms of homeopathic practice.

Quite.

I see why Geni likes this. It's a murderously difficult study to design, but the authors have put a great deal of effort both into designing a scientific trial, and into satisfying the rather different criteria of the homoeopathic establishment. Even they themselves are not claiming perfection in every detail, nevertheless they put up an excellent defence of their ultimate conclusions.

Rolfe.

 

[Prester John]

Can't say i really have a favourite paper. The SHOT report is quite interesting tho' (Serious Hazards of Transfusion - yearly report ) with some good case reports and general interesting information.

http://www.shot.demon.co.uk/


The site doesn't seem to have the latest report tho'.

 

[wipeout]

Consistent Resolution of Some Relativistic Quantum
Paradoxes by Robert B. Griffiths

http://arxiv.org/abs/quant-ph/0207015

 

[Rolfe]

The one I'm currently sending everyone to read, even though it's nothing to do with what I'm doing, is "Unskilled and Unaware of It: How Difficulties in Recognizing One's Own Incompetence Lead to Inflated Self-Assessments": http://www.apa.org/journals/psp/psp7761121.html

That was a good read, Matabiri. Structured way of demonstrating that common accusation - "he's so ignorant he doesn't even realise how little he knows."

From the Introduction:

We argue that when people are incompetent in the strategies they adopt to achieve success and satisfaction, they suffer a dual burden: Not only do they reach erroneous conclusions and make unfortunate choices, but their incompetence robs them of the ability to realize it. Instead, like Mr. Wheeler, they are left with the mistaken impression that they are doing just fine.

Oh dear, methinks we're straying back to the homoeopaths again.

Rolfe.

 

[Matabiri]

That was a good read, Matabiri. Structured way of demonstrating that common accusation - "he's so ignorant he doesn't even realise how little he knows."

However, I strongly disagree with their "experts" that

'If a kid asks where rain comes from, I think a cute thing to tell him is 'God is crying.' And if he asks why God is crying, another cute thing to tell him is 'probably because of something you did.'"'

is funny to the tune of 9.6 out of 10.

Maybe my humour is incompetent.

 

[Rolfe]

However, I strongly disagree with their "experts" that

'If a kid asks where rain comes from, I think a cute thing to tell him is 'God is crying.' And if he asks why God is crying, another cute thing to tell him is 'probably because of something you did.'"'

is funny to the tune of 9.6 out of 10.

Maybe my humour is incompetent.

Well, be fair, it was out of 11, not 10. But I still agree with you, it's seriously unfunny. I thought maybe my opinion was skewed because I'm not Amercian, though.

Humour is such a subjective thing that I'm not convinced it was such a great choice for a part of the study. But on the other hand, maybe that made it perfect - just go with the expert assessments and ignore your own opinions.

Rolfe.

 

[T'ai Chi]

Would that be "Bootstrap methods: another look at the jackknife", Ann. Statist., 7, 1-26? By coincidence, I just got out his jackknife/bootstrap monograph from the library.

Yes, that is the one. Of course there are much more recent articles that develop bootstrap methods, but I always enjoy reading the originals.

 

[LFTKBS]

LFTKBS's favorite study, hands down.

Electron Band Structure in Germanium, My Ass

 

[Rolfe]

LFTKBS's favorite study, hands down.

Electron Band Structure in Germanium, My Ass

Rolfe (who still has a very similar set of data in a very old notebook, referring to a so-called "glucose tolerance curve").