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Thursday 31 January 2008

ON A LIGHTER NOTE...

Someone was asking on a forum the other day about the best treatment for crows' feet. I don't know, but I think it would be very difficult to catch one and try it out. I suggest that any crows having difficulty walking should consider flying instead.

Do people choose their jobs, or do their jobs choose them? I love the name of the BBC's whaling correspondent.

SCIENCE, SLEEP AND SSRIs

In an earlier post, I mentioned that I have narcolepsy with cataplexy, which is a very odd condition, and becomes odder all the time. One of the recent discoveries about it involves the identification of orexin producing cells in the hypothalamus, and their depletion in narcolepsy. Hence there is a diagnostic test which involves a lumbar puncture to take a sample of cerebro-spinal fluid and analyse it for orexin concentration. In narcoleptics, the level is either abnormally low, or undetectable.

I was very worried about having the test. Notwithstanding the unpleasantness of the test itself, it has taken me more than half my life to find a sympathetic neurologist who would agree that my symptoms might be narcolepsy with cataplexy, and the diagnostic validity of this test is taken to be so strong that I was terrified the outcome. What if the orexin count was not low? It would leave me wondering if my symptoms were psychiatric all along, and perhaps my neurologist would think that too.


Photograph by MegElizabeth

Anyway, I needn't have worried. I was honest with my neurologist about my apprehension, and he said that whatever the outcome, he felt strongly that something neurological was going on, and that nothing would alter his standard of care to me. You can see why I didn't want to lose him! As it turned out, my orexin levels were, as he put it, "barn door abnormal".

I take modafinil for the narcolepsy, and venlafaxine for cataplexy at the moment, although I used to take prozac for the latter. Over at Ben Goldacre's brilliant Bad Science blog, there's a discussion going on about the quality of research into the effectiveness of selective seratonin re-uptake inhibitors, SSRIs, like prozac. Most particular to the confusion as to their effectiveness seems to be the selective reporting of positive trials, and mis-reporting of some that had less favourable results. Venlafaxine is a selective seratonin-norepinephrine reuptake inhibitor (SNRI), and I don't know how well its trials and their fair publication compare.

One thing that is always interesting about psychoactive drugs is that there are high variations from individual to individual in their effect, dosage and efficacy. They also seem to act differently for different conditions. For example, fluoxetine (prozac), when prescribed for depression, usually takes a couple of weeks to start taking effect. When I was prescribed it for cataplexy, the effect was within 48 hours. It seems to me that it must be acting through different channels in each case. The human nervous system is an enigmatic and complex machine, and I don't think our current understanding is adequate to explain these differences. It is interesting, for instance that Parkinson's patients can develop secondary narcolepsy, and exhibit the full range of narcolepsy and cataplexy symptoms, although the primary defect is in the dopamine system. Recent research has seemed to indicate that REM sleep behaviour disorder (RBD) is strongly associated with later development of Parkinson's Disease, unless it is associated with narcolepsy, in which such a progression is not expected.

It all makes me wonder whether depression is really a single illness at all, when it has many different triggers (and none) and manifests itself differently from person to person in its extent, prognosis and response to treatment. When the brain and its workings are so difficult to understand, then any medical trial has the problem that even in the patient group, we may not be comparing like with like. Faced with the difficulties in trials of comparing an active drug accurately with placebo, and the added difficulty of comparing placebo to no treatment at all, the possibility that very similar symptoms may arise from different organic mechanisms within the study group makes any inferences very tricky indeed.

I'm not arguing against trials - on the contrary, I think we need to know far more. But we also need to better understand the nature and origin of the illnesses before we can make hard pronouncements. We need well organised, well reported trials, but we also need to be willing to challenge all underlying assumptions openly and honestly, and not censor or prejudice any possible debate.

Wednesday 23 January 2008

AN INTERESTING MATHEMATICS PUZZLE

Well, this is the first time I've tried to put any maths into my blog, and I can tell you for sure I'll have to learn a lot more about how to do all the typesetting and stuff before trying again!!! Hats off to the clever folks who do it all the time.

I wanted to share a puzzle that I tackled some while ago now, when I was doing my first undergraduate year in mathematics. It was satisfying in one way, but remained always rather unsatisfying in another.

The course in question was a rather gentle introduction to some topics in number theory, and the lecturer wanted to encourage us to experiment and learn for ourselves a bit, so as well as the compulsory assignments we did each week, he set a weekly "challenge problem", which was optional. Whereas the assignment tested that we had understood the course and could apply what we had learned, the "challenge" was intended to go some way beyond the course itself. The lecturer gave the added incentive that he would keep a record of the challenge problem solutions he received, and at the end of the semester there would be a prize for the best student.

Initially, about eight or so students submitted solutions, but it tailed off quickly, and by about half way through the semester, the only students still submitting solutions were myself and another student. This carried on until the final lecture, when we both waited expectantly for the winner to be announced. Instead, however, he said that he was still unable to separate us, and so he was launching a final challenge for everyone to think about over the Christmas break. He said he would wipe the slate clean, and, regardless of how many, if any at all, of the previous challenges had been completed, the person who delivered the correct answer, with proof, soonest after Christmas would win the challenge prize. Should he receive more than one correct answer, the prize would go to the student whose solution was the most elegant.

What he then handed out read as follows:

CHRISTMAS CHALLENGE

The following Christmas teaser was set by Dr J Brownowski in the New Statesman and Nation, 24th December, 1949:

Find the smallest natural number which is such that if the digit on the extreme left is transferred to the extreme right, the new number formed is one and a half times the original number


He also gave a hint, without which I am sure that I would not have been able to solve it. I had a solution by the soonest date, and so did two others. One turned out to be wrong. The other was also correct, and had been submitted by the same student with whom I had been neck-and-neck all along. Since the lecturer still could not separate us, he finally announced us as joint winners.

I said at the beginning that the process was satisfying, and this was partly of course the pleasure of winning, but also because I had in doing so undertaken some puzzles, including this one, that I would never have thought I could solve previously. The dissatifaction, though, was entirely with my solution to this last problem. My initial approach, using the hint, was fine, and led to a most general solution. However, the second half, which was in order to find the lowest possible solution has always seemed inelegant, and I've wondered whether there was a better way of finding the answer. I hope that I've eluded to the part I mean enough, since my own solution, in the graphic is, I hope, too small to read, and those who want to try it themselves can avoid enlarging it.

The hint, was, in ROT13,
vasvavgr qrpvznyf


Monday 7 January 2008

BAD SCIENCE

Perhaps I've just had too good a Christmas, and my normal bad temper is on rebound, or perhaps some things are just remarkably annoying. I usually make a point of not watching programmes like "The Wright Stuff" on UK Channel 5, but my other half is off work with the 'flu today, and put it on.

As the programme went to an advertisement break, the teaser question we were left with was:

In what year was MRSA first discovered?
a) 1880
b) 1950
c) 1980

It's often possible to answer these questions on a psychological basis rather than actual knowledge; they are almost always designed to surprise. Now, I don't mind the intellectual superiority that people intend to show by asking these kinds of questions, as long as the answer is actually correct, and illuminates the subject in some way. However, it was all too easy to predict that the given answer would be - and indeed was - 1880.

Since MRSA is methycillin-resistant Staphylococcus Aureus, it doesn't take a genius to suppose that MRSA cannot have been discovered until after methycillin was developed. This was by Beecham, in 1959. It was first reported in the UK in 1961 that certain Staphylococcus Aureus had been found to be resistant to methycillin.

The bacterium itself was discovered in 1880. It resides perfectly normally on human skin, nose, throat and the colon, and doesn't necessarily indicate the presence of infection. It usually responds to methycillin, among other antibiotics.

Why does this wind me up so much? Because what it does to the watching population is give the impression that MRSA has been around for over 100 years, and has not been a problem until now. I think the average viewer may conclude that all the recent concern is merely scaremongering, and will also find the conflict with what they thought previously will add to a sense that science is not to be trusted, and that scientists change their advice according to political expediency.

Staphylococcus Aureus in itself is not a worry. MRSA is a big concern. It may well have been caused to thrive today by continued overuse of antibiotics. It is very hard to see how we can get back from this position, but disinformation is unlikely to help.