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Selasa, 30 Juni 2009

A Tale of Two Suppressed Studies

Let me tell you a story. A big, powerful institution commissioned a report into something important. But the authors ended up writing something that the institution’s leaders couldn’t accept. They found it unpalatable. It went against their orthodox dogmas. So, they suppressed it. It never saw the light of day. It’s the report they didn’t want you to read.

Nice story. But does that mean the report is true? Couldn’t they be smarter than the authors of the report? Is “Commissioned to write a report by a big powerful institution” a qualification you would respect in any other context? Maybe they didn’t want you to read the report because it was just a bit rubbish?

The past couple of weeks has seen two classic texts from the ever-popular genre of Suppressed Reports. There was the World Health Organization study on cocaine that concluded that it isn’t all that harmful. And then there was the Environmental Protection Agency report that was sceptical of global warming. They didn’t want you to read either, so we’re told.

I’m not saying these reports are wrong. I haven’t read either. But it’s odd that their "suppression" has granted them the kind of uncritical attention that they would never have had if they’d just been published normally. How many global warming skeptics take what the Environmental Protection Agency says seriously? Yet when they deliberately don’t say something, they’re all ears. It’s like Catholics taking the Pope’s word as infallible, but only when he doesn’t want them to. It’s the argument from authority in reverse.

A Bad Day in Paris

It was 8th June 2009, my third day in Paris.

After visiting Musée du Louvre, I had sore legs and sat at the cafe table for a while before walking to the Metro station. In order to get back to my hotel, I had to change train at Châtelet. The train from Châtelet to Odéon was so crowded that even 'a can of sardine' is an understatement! It was at about 6.00 p.m. of the peak hours, so I guess I had chosen the wrong time to ride on the Metro.

I was so tired that my alert level was almost zero, if not below. There was an Eastern European lady in front of me kept pushing me on my chest with her shoulder until I almost lost my balance in the train, so I had to hold on to the handle bar very tightly to stay put. I think this is a common trick of a pick pocket on the victims. They try to push you off balance so that your hands are not free to protect your belongings. It already happened on me once in Naples.

When the train reached St. Michel, quite a lot of people had alighted the train but the lady was still pushing on me. Then, when the train door were about to close, she sprinted out of the train. All of a sudden that I realised my wallet was gone! It was replaced by a one-Euro coin. The next Metro station was Odéon, where I wanted to get to, so I alighted the train and went back to the hotel to ask for help at the reception desk.

I called back to Malaysia to cancel all my credit cards that were lost. In fact I lost only two cards but I cancelled four, including the one of the two in my backpack and the one left at home! That left me only one to survive for the remainder of the trip.

I had also lost my identity card, so I asked the receptionist for the direction to the nearest police station. She gave me the address, it was 78 Ru de Bornaparte with a sketched map. After just two blocks away from the hotel, it started to drizzle, so I went back to the hotel again to borrow an umbrella. When I was walking along Ru de Bornaparte in search of the police station, the drizzle turned out to be a downpour. To top it off, there was gusty wind! In addition to that, the lot number along Ru de Bornaparte was getting smaller and smaller than 78. I sensed something wrong and stopped by a gallery to ask for the direction again. Only then I found out the the hotel receptionist gave me the wrong direction!

I had to walk for another 1 km before I arrived at the police station at around 7.00 p.m., my jacket was already quite wet and my socks soaked in water. I approached a young policewoman who wasn't engaged. She recorded down my name and my passport number and asked me to sit down and wait. Minutes later, she came out from a room with a stack of printed form in English for me to fill in. These were to help her in my verbal description of the incidence as she wasn't very fluent in English. When I described the part that my wallet became a one-Euro coin, she cheered. Well, at least she's got some sense of humour and she's quite cute too. That made up a bit of my bad day.






After the report was done, she asked me to wait for another slip that she had to give me to prove that my identity card was lost so that I could get a replacement back in Malaysia. At the same time, she was called for duty on the beat and she passed on the task to another policeman. It wasn't done until about forty-five minutes later! I told the policeman that I was very hungry and he responded with the same answer. All the other people waiting to lodge their reports laughed together. That made up another bit of my bad day.




I decided to treat myself a good meal after all these hassles and went to a nearby restaurant for a main course plus dessert set meal. I had a cheese-baked scallops with rice and a prune tart. On my way back to the hotel, I got lost for another half hour!

Well, after the incidence, I kept the annoyance to the minimal and kept on enjoying the rest of my holidays. So, you see my updates with more photos here.

P.S. I paid my phone bill yesterday for all those international roaming calls and it came out to be almost RM600! I have also got my identity card replacement application done today. I was supposed to pay RM110 for the replacement but it was waived due to the lost through pick-pocketing, not through my own carelessness. I feel like cursing all the pick pockets. Well, they will all need to pay back one day, if not in this life; then after life!

The Shotgun Approach to Psych Drug Discovery

A foundation is offering to fund research into novel psychiatric medications, we read in the latest Nature Neuroscience:
The Broad Institute in Cambridge, Massachusetts has launched an initiative called ‘PsychHTS’ inviting scientists with ideas and data suggesting novel mechanisms contributing to psychiatric disease to apply for access to the Broad’s infrastructure and expertise for high throughput screening (HTS) of chemical compound libraries.
HTS is a clever technique for discovering new drugs, based on the crude but effective principle of trying hundreds of thousands of different chemicals until you find one which works, by using machines to automatically run the experiments (“assays”) extremely quickly. Hence, “high throughput”. It’s pretty cool.

The Stanley Medical Research Institute wants to use HTS to find new psychiatric drugs. There have been no truly new drugs in psychiatry for a long time: there are dozens of different antidepressants, for example, but they all work (if and when they work) by increasing brain monoamine levels, just like the very first antidepressants, iproniazid and imipramine, discovered in the early 1950s. The same is true of antipsychotics, which all block dopamine D2 receptors, just like the very first, chlorpromazine.

So new drugs for the mind would be great. But how are you going to find them by doing experiments in test-tubes, even if you have 50,000 test-tubes? The mind doesn’t fit in a test-tube. Here’s where the proposal gets a bit iffy:
Readouts may be anything from classical enzymatic reactions ... up to subcellular changes captured by automated high-content imaging. ... ‘Hits’—compounds that affect the assay results in a way that indicates potential usefulness in a psychiatric research context—are automatically retested at several concentrations...
So, the idea is that potential new drugs will be found by measuring how they affect certain cellular processes or chemical pathways. But which ones? Until we know what cellular or protein or enzymatic changes underlie mental illness, we won’t know what to look for. And the whole problem is that we don’t know much about that – if we did we’d have lots of new drugs already.

The article suggests only one route to finding truly novel mechanisms – genetics. In the past few years, there have been many genetic studies trying to find genes which cause mental illnesses. Some of them have identified risk genes which seem to imply new biological pathways. For example, the current orthodoxy is that schizophrenia is caused by abnormalities in the brain’s dopamine system. But the gene most strongly implicated in schizophrenia is called “neuregulin-1”, and it has nothing to do with dopamine. That’s interesting but unfortunately -
Recent genetic studies have indeed suggested new targets, but the identification of specific genetic risk factors remains elusive. The genetic results are themselves variable, often have small effect sizes and need independent replication.
In other words, the genetics evidence is so patchy, that using it as a basis for finding new drugs is like building a house on very shaky foundations. It might stand. But if the genetic links turn out to be spurious, all the subsequent research will have been in vain.

Personally, while I welcome any truly groundbreaking work in psychiatry, I would rather people spend time and money doing better research on the drugs we already have.

ResearchBlogging.orgNature Neuroscience Editorial (2009). Mining chemistry for psychiatry Nature Neuroscience, 12 (7), 809-809 DOI: 10.1038/nn0709-809

Minggu, 28 Juni 2009

American Animated Cartoon Network


The animated cartoon is usually associated with children and of course, kids love this kind of entertainment. However, many

adults are entertained though animation as well. Recently, adults have become the target audience in some animated cartoon

programs. It is not unusual to have a conversation between two adults that include current programs like Family Guy and

Sponge Bob Square Pants.

There are basically four categories in this entertainment genre, basic American, Anime, American Anime and classic. The basic

American animated cartoon includes such memorable programs as Bugs Bunny, Flintstones and Scooby Doo. The changing face of society has left many of these old favorites as cult classic animated cartoons.

Gearing some of the content toward mature audiences is not really a new thing. The older Warner Brothers animated cartoon

would include some jibes and jokes that would go completely over a child's head while providing some entertainment for

parents. Other programs were based on adult shows. For example, the Flintstones animated cartoon was based on Jackie

Gleason's Honeymooners.

Anime is the Japanese style of animated cartoon that has been in circulation for many years. It has become increasingly

popular over the last decade. Anime has been geared for both children and adults. There are several cartoons that are

developed just for children like Pokemon and Digemon Digital Monsters. There are also several adult themed anime cartoons

like Full Metal Alachemist and Inuyasha.

American Anime is the most recent trend in the modern animated cartoon. Shows like Avatar and Martin Mystery and Teen Titans blend the American style of using proper body proportions while adding elements of traditional anime as well. Common

features of the traditional version include oversized eyes and extreme exaggeration of emotion in facial expressions.

Classic animated cartoon styles include Disney and Don Bleuth films. These films are very realistic in style. The animators

are required to study everything about the characters. They even have to know the movement of a cat's tail that is sitting in

the background. The classics like Snow White and The Secret of NIMH are prime examples of this intricate art form.
The animated cartoon has come a long way. You can find entire networks dedicated to this form of entertainment. The Cartoon Network, Nickelodeon and The Disney Channel offer this programming twenty-four hours a day. The Fox network devotes most of its Sunday lineup to the grown-up animated cartoon like Family Guy, The Simpsons and American Dad.

While the animated cartoon will always be closely tied to our experiences with childhood, it is nice to know that we can

still appreciate this form of entertainment as adults.

Rediscover Bugs Bunny, Superman, Batman, Dexter and other cartoons characters

Turner Broadcasting' Cartoon Network Channel is perhaps one of the most appreciated cable television for children. It was launched in 1992 in United States. This channel has gained the audience with its considerable library of animations. Here are some of the most popular cartoons, many of them as reviewed on Cartoon-secrets.com - some of them inherited from generation to generation and the other newer: Tom and Jerry, Scooby-Doo, The Flintstones, Dexter's Laboratory, Power Puff Girls, Codename: Kids Next Door, Courage the Cowardly Dog, The Grim Adventure of Billy & Mandy, Foster's Home for Imaginary Friends, Camp Lazlo.

- Tom and Jerry are the legendary cat-mouse pair, responsible for some of the most funny and unforgettable scenes of animation. They have delighted and gained more and more fans along time and won seven awards.
- Scooby-Doo's shows are numerous. They evolved along time through more and more inspired series on the stream with the latest scientific conquests in the field of computers. However, they have preserved their ace, the mistery waiting to be revealed, the creepy atmosphere, suspense, thrills and harrowing adventures; this is what gave the charms to this cartoon and gained its fans forever.

- The Flintstones, Fred and Wilma, and their neighbours the Rubbles, Barney and Betty, the town of Bedrock, vehicles propelled by the driver's feet, Dino, the dog-dinosaur and the adventures of the Stone Age transformed into a modern atmosphere. Nothing new and still, so fresh every time you see them.
- Dexter's Laboratory. This cartoon series is about a boy genius, a junior scientist called Dexter, his passion for scientific discoveries and disgust for girly� feelings, weaknesses; Dexter's older sister Dee Dee is exactly the opposite, but together they form an A team that gives delightful moments to the audience.
- Johnny Bravo with his Elvis-like appearance, his bulging biceps, and overflowing ego are only a few of the qualities this mama's boy has. He makes you laugh and you somehow adore him although you hate everything that he does. In fact he is his own worst nightmare wherever he goes.

- The Powerpuff Girls. Three supernatural superhero girls created with a secret ingredient by Professor Plutonium in a laboratory near Townsville fight against bad guys. A mayor, too small to be good and candies as fuel for super-heroines, and this is just part of the story.
- Codename: Kids Next Door. Five 10-year-old tenacious kids fight to preserve the innocence of the childhood which is permanently endangered by the world of adults which is always ruled by implacable rules. Besides the drama you can easily laugh and enjoy their mustard or sweets based weapons.
- Courage the Cowardly Dog describes the isolated life of a very timid, timorous and scared dog which has to fight against horrifying monsters to protect himself and his owners, especially Muriel who is very devoted to her dog, while her husband Eustace scares the poor dog all the time and enjoys it.
- Foster's Home for Imaginary Friends. Children create imaginary friends which give them the needed help to pass over the obstacles and misfortunes of life. However there is a time when that created hero is no longer wanted so he has to retire somewhere, and that's what Foster's home is for.
- Camp Lazlo. The camp where the Bean Scouts spend their summer is a place where rules are observed and the nature is a temple. Everything was in an orderly fashion until Lazlo appeared. For more cartoons and information please see our other resources on Cartoon-secrets.com

Anime warriors


A Mighty Fortress with insulation walls.
There were anime warriors and pictures of dragons within the Manga and Fantasy drawings.
Listening to the audio book online allows you to enter the underground shelter while jamming to techo beats.

Still recovering from the dragons' fire attack, Helena along with Jean-Gaël and the rest of the Orchestra sought protection in an underground shelter And what a indomitable garrison it was. Helena's underground escort, Jean-Gael, excitedly explained how they were safe from evil creatures since the walls were heavily insulated. The underground shelter had safeguards and full reinforcement for security. But his sense of pride and security was shortly lived upon knowing the capture and death of some comrades during the dragon attack...

Fresh online audio book that's a musical tale with fantasy drawings an adventure soundtrack with techno. Manga drawings have adapted to the modern age and evolved to graphic drawings and pictures of dragons, wolves, and horses that are lifelike

Like a typical anime warrior, Helena, a young virtuoso is destined to a heroic fate...
Accompany her on her journey to decode the gathering of the "Vision" as well as her fate.
Watch the video on youtube by going to: http://www.youtube.com/watch?v=9S3PTVexk-Y...

On Psychiatric Cool

At Somatosphere, "Liz Oloft" (heh) writes about the dilemmas of "coming out" as a user of psychiatric meds while being an academic who researches them: Prozac In The Closet.

Liz is a social scientist, while I'm a card-carrying neuroscientist, but like her I also take antidepressants while studying them, and I identify strongly with her thoughts.

One sentence in particular struck a chord -
Depending on who you ask ... to engage in Lacanian psychoanalysis for neurotic problems of living might be cool, to take an antidepressant for depression without psychotherapy is less cool, and to take a cocktail for bipolar might be even less so (although bipolar disorder may be more legitimate than depression because it seems to be more widely accepted as a “real biological disease”).
This is something which isn't much talked about, but it's absolutely true. Some mental illnesses are just cooler than others. Cool is a famously elusive concept, maybe undefinable. Either you got it or you don't. But some diagnoses certainly have more of it than others. From most cool to least the pecking-order seems to be:
1. "Issues" – problems of living and/or "stress", rather than illness
2. "Physical" conditions with psychiatric symptoms, such as thyroid problems and PMT
3. Anxiety, phobias, panic attacks
4. Substance abuse & addiction
5. Bipolar disorder (manic-depression)
6. Eating disorders
7. Unipolar depression
8. "Personality Disorders"
9. Schizophrenia
This list is, of course, subjective - "cool" inherently is – and it goes without saying that I’m not endorsing this hierarchy, just reporting it as I perceive it. I’m no slave to cool as a glance at my iTunes library would verify.

What does it mean for one thing to be higher on the list than other? Amongst much else it means - that people are more comfortable talking about it and being in the presence of it; that people will tend to prefer it as a diagnosis for themself or a loved-one; and that it's easier to think of "cool" people who have it. And, simply, it means it that it’s easier to “come out” as having it.

Some of the rankings may surprise at first glance. If you read the textbooks, you'd think that bipolar disorder is generally speaking "worse" than unipolar depression. And in many ways it is. But it's still cooler, I think. Cobain sang about "Lithium", the quintessential treatment for mania, not "Imipramine". Hendrix sang "Manic-Depression", not "Depression". Lots of cool, or at any rate famous, people, are bipolar, or are widely believed to be. By contrast, try to think of a famous unipolar depressive, and you'll come up with Winston Churchill with his Black Dog and... who else?

The key factor behind psychiatric coolness seems to be the degree to which a problem is seen as internal to the self. There's little shame in being "stressed" due to things that happen to you, because then the problem is external. You're "normal", it's the situation that's screwed up.

Likewise, as Liz says, bipolar disorder is in an important way cooler than depression, because it's seen a closer to being a "physical” illness that happens to you, like a thyroid problem. That’s as opposed to a weakness or failure of you as a person, which is the most damaging and most persistent stigma of unipolar depression.

The one apparent exception is schizophrenia, which is profoundly stigmatized despite being widely viewed as a biological disease. But isn't this because schizophrenia is seen as a disease that disturbs the self, leaving someone merely "mad" or "insane", no longer responsible for their actions and therefore no longer really a person?

How Far Off Is Mind-Reading?


PopSci.com has a somewhat enthusiastic article about the possibility of using fMRI to "uncover your private thoughts"- Mind-Reading Tech May Not Be Far Off.
Neuroscientists are already able to read some basic thoughts, like whether an individual test subject is looking at a picture of a cat or an image with a specific left or right orientation. They can even read pictures that you're simply imagining in your mind's eye. Even leaders in the field are shocked by how far we've come in our ability to peer into people's minds. Will brain scans of the future be able to tell if a person is lying or telling the truth? ... While we aren't there yet, these possibilities have dramatic social, legal and ethical implications.
But what do we mean by "mind-reading"? I guess what most people mean by the term is being able to tell what someone is thinking, being able to "hear" their private thoughts. A stereotypical fictional "telepath" can get inside their targets minds and tell exactly what's going through them.

Sadly, what most fMRI "mind-reading" experiments have done is rather less impressive. they've shown that it's possible to tell whether someone is thinking about one thing as opposed to a second thing. But only if you already know what both things are, and only if you have already "read" the pattern of neural activity that corresponds to each one.

So, you could scan someone while they are thinking about, say, cats, and then again while they are thinking about dogs. From that, you could work out whether they are thinking about cats or dogs at any given point in time (here's how). If they were thinking about anything else, you'd have no idea what it was, or worse, you'd think it was either a cat or a dog. A lion, for example, would probably activate many of the same pathways that a cat does.

The great majority of "mind-reading" studies are like this. It's still pretty cool, but it's no telepathy. Is there any prospect of true "mind-reading"? In other words, could you read a mental state without knowing what you were looking for in advance?

Maybe. The parts of the brain concerned with visual processing happen to be arranged in a relatively straightforward way,which means that there are predictable relationships between visual stimuli and the areas of the brain that are activated when looking at them. Reports have claimed that it's possible to infer which picture someone is looking at out of a large set (1) and even to reconstruct the image that someone is looking at based purely on the visual cortex activity (2,3). For a good explanation of the last paper, which attracted a lot of attention, see Neurophilosophy.

Such studies come closer to true "mind-reading", but thus far the technique only works with vision. Even assuming that the same areas of the brain light up when you're thinking about something (visual imagery) compared to when you're looking at it (visual perception), the best this method could achieve would be to tell what picture was in someone's head at a given time. In ten years it might be possible to put someone in a scanner and tell, straight off the bat, that they were picturing a small white dog. But if you wanted to know what they were thinking about that dog, you'd be out of luck.

To truly read someone's mind you would need to understand how every brain state relates to every mental state. In other words, you would need to know how the brain allows us to think. At the moment, we really have no ide about that, so true mind-reading remains over the horizon.

Edit: I must be telepathic because I just saw that Mind Hacks covered a new study about mind reading a few hours ago: I know where you are secretly attending! Yet again, it involves the visual cortex.

Sabtu, 27 Juni 2009

I'm Back!

I have just arrived in Kuching via Malaysia MH1 from London to Kuala Lumpur and transferred to MH2532 from Kuala Lumpur to Kuching. It was a very fruitful 3-week trip in terms of photography but somewhat disastrous in Paris! I'll keep on updating on the places I have visited on this blog. Please stay tuned!






Kamis, 25 Juni 2009

Are 1 in 64 Kids Autistic?

Quite possibly, yes. In the last post I discussed the interesting background to a new paper about the prevalence of autism in British children, Prevalence of autism-spectrum conditions: UK school-based population study. Here's some more about the study itself.

The authors, Simon Baron-Cohen et al from the University of Cambridge, set out to assess the prevalence of “autistic spectrum conditions” in the county of Cambridgeshire, England, by sampling all of the school children aged 5 to 9 years during 2003-2004.

The most recent major study examining the prevalence of autistic spectrum conditions in Britain was Baird et al (2006), who reported a prevalence of about 1 in 86. But Baron-Cohen et al point out that this may have been too low, since Baird only looked for autism in children who were already on the government's “Special Educational Needs (SEN)” register of children with difficulties in school. If there were autistic children who were doing OK in school, or at least well enough to get by without attracting concern, they’d have been missed.

So, Baron-Cohen’s team first wrote to every school in Cambridgeshire (162 of them) and asked them to report how many of their children had been diagnosed with an autism-spectrum condition.
79 schools replied and reported 83 children diagnosed out of 8824 total, or 1 in 106 children – pretty close to Baird et al's in 2006.

But those were only the kids who had already got a diagnosis. In order to try to find undiagnosed cases, they then sent questionnaires to the parents of 11,635 children. The questionnaires included a screening form developed in Cambridge called the CAST, which asks parents about various aspects of their child’s behaviour (“Does s/he come up to you spontaneously for a chat?” “Does s/he like to do things over and over again, in the same way all the time?” Etc.)

The authors invited all of the kids who scored highly on the CAST to a face-to-face assessment to confirm whether they really had the condition. The end result was that out of 3373 kids whose questionnaires were returned, 11 were judged (in the opinion of the research team) to have an autism-spectrum condition which had never been previously diagnosed.

What does this mean? Well, good question. All it strictly means is that 11 out of 3373 children had undiagnosed autism. However, because not all of the children who scored highly on the CAST agreed to be interviewed, the authors estimate that the true figure was probably more like 22. That compares to 33 out of those 3373 whose parents reported already diagnosed autism. (Actually it was 41 reported, but only an estimated 33 were declared “confirmed”. See page 503 if you’re sceptical of this fudge, but it seems kosher to me.)

The bottom line: for every 3 children with a diagnosis, 2 others went undiagnosed. Since about 1 in 100 children have diagnosed autism, that makes 1 in 64 children with autistic spectrum conditions in total.

But this relies on some assumptions. In particular, this only works if you assume that the parents of autistic children were no more or less likely to complete the CAST questionnaire, and no more or less likely to agree to a face-to-face interview, than parents of the non-autistic kids.

However, it could well be that the parents of autistic children were already concerned that there was “something wrong” with their child and wanted to get a professional opinion, so they were keen to take part – that would mean that this study overestimated the rate of undiagnosed autism. On the other hand, it could equally well be that the autistic children were less likely to get included in the study. Maybe they just didn't want to go along to the interview with a stranger. In which case, the rate of autism would be underestimated.

Because only 29% of parents did the questionnaire and even then only about 60% of the children who scored high came up for the face-to-face, the potential for bias is great. Unfortunately, there is no way of knowing which way the bias operates. The authors acknowledge these concerns and admit that their estimates are not exact.

But this is still an important study. Even if you assume that the data were extremely biased towards finding autistic children there were still 11 cases of undiagnosed autism out of about 11,000 kids aged 5-9, compared to 83 diagnosed, which means that at an absolute minimum 1 in 9 children with autism of that age are undiagnosed. And the true figure is likely to be a lot higher, maybe 2 in 5 as the paper claims.

On this blog I've often been skeptical of claims that mental illness is extremely common. But I can easily believe that 1 in 64 children has a significant autism spectrum-condition, and that some cases go undiagnosed in primary school. While we still don't know the exact numbers, and these will always be somewhat arbitrary since they depend upon the chosen diagnostic, about 1 in 50 sounds about right. Certainly, the idea that autism is an extremely rare condition affecting more like 1 in 2000, as was believed twenty years ago, is out of date.

ResearchBlogging.orgBaron-Cohen, S., Scott, F., Allison, C., Williams, J., Bolton, P., Matthews, F., & Brayne, C. (2009). Prevalence of autism-spectrum conditions: UK school-based population study The British Journal of Psychiatry, 194 (6), 500-509 DOI: 10.1192/bjp.bp.108.059345

Rabu, 24 Juni 2009

Autism, the Media, and "1 in 58" - the story continues

It was about this time two years ago that my faith in the British media died. It had never been in the best of health, but up until then I believed that the (non-tabloid) newspapers were written by professionals trying to find out and communicate the truth as best they could.

Journalists might be wrong, I thought, but they did their best to ensure that they weren't. And they might have a bad habit of focussing on sensational stories that "sold papers", but such stories would at least be accurate. A career in journalism was something that strongly appealed to me.

What happened on July 8th 2007 was that The Observer printed a front-page article so demented that I’ve never been able to take that newspaper at face value since. And if you can't trust The Observer, which sat on my family's breakfast table every Sunday since before I can remember, you can't trust any of them (at least, I can’t.)

The article was about autism, and it claimed to be a report on a new research study carried out at Cambridge by the famous Professor Simon-Baron-Cohen. The upshot was that Baron-Cohen’s team had found the rate of autism to be 1 in 58 children, much higher than the previous study from a few years earlier, which found a rate of about 1 in 86. Furthermore, The Observer said, two of the team, “world experts” in autism, thought that this “dramatic rise” (i.e. a rise of 50% in a few years!) might be something to do with the much-maligned MMR vaccine.

The original article no longer exists on the Observer’s website, but the WayBack Machine has it.

It was pulled after Ben Goldacre, amongst many others (including Baron-Cohen and even the Government), criticized the piece vociferously and it was, eventually, replaced by an unsatisfactory “clarification”. Goldacre’s take on things was chronicled in a astonishing series of articles (1, 2, 3, 4, et al.) which revealed some horrific journalism, including, amongst much else, attributing opinions to people who didn’t hold them and failing to reveal conflicts of interest. If for some reason you’re not already a Goldacre fan, read those posts, and you’ll see what all of the fuss is about. But you need to know one other thing – he is literally the only journalist in the country who does what he does.

The most damning criticism at the time, however, was that the research in question could not possibly have found an increase in autism rates, let alone a “big surge”, a “dramatic rise”, or an “upward trend”. The new research, quite deliberately, used more extensive assessment criteria than previous studies. It was specifically designed to find the highest possible estimate. So only a fool would try to compare it to other sets of data and see this as evidence of rising rates. Also, even if there had been a real increase, it couldn’t have been because of MMR, because the kids in both studies will have had the MMR vaccine. The oldest kids in the Baird et al study of 9-10 year olds were born in 1991, a few years after MMR was introduced, while the youngest in the Baron-Cohen study were born in 2000, when MMR uptake was, if anything, lower, thanks to the MMR-autism scare.

Now, two years after The Observer’s “scoop”, the research is finally out in the British Journal of Psychiatry: Prevalence of autism-spectrum conditions: UK school-based population study. I’ll be examining this paper in detail in the next post, but here’s what you need to know if you remember the story from 2007:

The paper doesn’t mention the Observer affair but it’s obvious that the authors had the article in mind while they were writing up their results. They repeatedly emphasise that their prevalence estimate cannot be compared to previous ones. They make it very clear (to the point of seeming a bit stilted) that they believe that the apparent rise in prevalence of autism over time is due to better detection and diagnosis, rather than a real “epidemic”. And they do not mention MMR – not that they had any reason to, of course. The highest estimate they arrive at, which they say is probably somewhat too high but close enough, is 1 in 64 children. 1 in 58 doesn’t appear in the paper.

What’s most interesting about the paper is who wrote it. The author list includes Simon Baron-Cohen (obviously) and Fiona Scott. The Observer named Scott as an MMR-autism theorist, something she strongly denied, in 2007. However, fascinatingly, Carol Stott is not an author, although she receives a massive acknowledgement at the end of the paper – “Carol Stott was a member of the research team throughout the main phase of the study and contributed to the coordination and running of the study, data management and data collection. She also made valued contributions to team discussions.” On the basis of this, she clearly had a right to be listed as an author – but wasn’t. We can only assume that she chose not to be, because if the other authors had left her off the list without her permission they would have been guilty of a serious breach of trust.

Carol Stott, you’ll remember, played a role in the Observer autism story. Unlike Fiona Scott, she does (or at least did in 2007) believe that MMR is linked to autism, and she had very close links with Andrew Wakefield as well as displaying a, er, penchant for the scatological in some bizarre emails to journalist Brian Deer. (Goldacre does say he “genuinely warmed to her, and she regrets that many people have fallen into entrenched positions on MMR on both sides” though, so she’s not all bad!)

So, questions remain. How did the preliminary research get leaked in 2007? What happened to make 1 in 58 become 1 in 64? What’s the deal with Stott? We don’t know. But we do know a bit more about autism thanks to this paper, and in the next post I’ll be discussing that.

[BPSDB]

Sabtu, 20 Juni 2009

On Anonyminity

You'll probably have heard about the "outing" of formerly anonymous blogger Night Jack, a British policeman. Night Jack went to court in an attempt to prevent The Times newspaper from publishing his identity, but the judge ruled against him. His award-winning blog, http://nightjack.wordpress.com/, has been taken down; I don't know if this is going to be permanent.

Lawyer Jack of Kent has a typically lucid and detailed legal commentary on the case, but as a fellow anonymous blogger, I believe that this is an issue which goes beyond British law.

I write anonymously because it allows me to write things that I otherwise couldn't. I could write under my own name, as many excellent bloggers do. However, the content of Neuroskeptic would not be the same.

Broadly speaking, my "neutral" coverage of science news would remain (like this), and my criticism of journalists probably also would (like this). However, I don't feel that my more "critical" writing about science - like this - would be possible without anonymity.

I'm an academic at a junior stage of my career. Some of the targets of my (implicit and explicit) criticism are people and organizations who might well play a part in that career. Quite simply, I don't want to go on record criticizing them, for obvious reasons of self-interest.

Perhaps this just makes me a bit of a coward, but I prefer to think about it in a more philosophical light. Often when we say or write something, two things happen in parallel. We are doing something in the social world, and we are asserting a proposition.

If I were to say to someone "Your wife is having an affair", I would be doing something momentous, something that might well be very painful and damaging. This is why we don't say things like that lightly - even if they are true. We value tact. Yet at the same time, my statement is true (or false), just like any other statement of fact, and it remains true (or false) whether or not I say it.

As a society, we recognize that it's sometimes desirable to allow people to assert things without having to worry about the consequences of their words as a social act. This is why we have anonymous feedback forms, anonymous comment boxes, anonymous witnesses (in some cases). It's also why we don't regard an election as fair and open if it doesn't have a secret ballot.

And in science, we have anonymous peer review. In order for a paper to be published, it must first be subjected to the criticism of one or more experts on the topic in question, writing anonymously. The anonymonity is fundamental because it allows them to criticize the research as harshly as necessary without having to worry about the consequences. Few people want to go on record as criticizing someone else's work, especially as most scientific fields are sufficiently narrow that peer reviewers personally know the authors of most of the papers they have to critique. Yet someone has to do the dirty work of criticism.

So anonymous peer review is valued in science as a way of facilitating objectivity, something otherwise in short supply, because scientists are people with careers and reputations to uphold. At the risk of giving too much dignity to a mere blog, I see Neuroskeptic as a continuation of this review process once papers have been published. Scientific debate shouldn't be hampered by concerns about careers and reputations, although scientists being only human, it is - anonymous comment is one way of getting closer to the ideal of pure objectivity.

All of that said, anonyminity is not all roses. It's open to abuse. Someone could persue a vendetta against a rival by making apparantly objective, anonymous criticisms that were in fact motivated by nothing more than self-interest. This occasionally happens during the process of peer review - a reviewer might trash a manuscript just because they just don't like the results, or because they are planning to publish the same results and they want to do so first. And an anonymous blogger could exploit their status for similar reasons. I would like to think that I have never personally criticized anyone who is acting in good faith, which includes the vast majority of academics. I try to stick to criticising ideas, not people. But of course, I would say that.

So anonymous writing has to be seen for what it is - something that has the potential to be more objective than on-the-record statements, but with no guarantee that it in fact is. Caveat lector, as always.

[BPSDB]

Selasa, 16 Juni 2009

Anime Shippuuden: Naruto Shippuuden

Naruto Shippuuden is the story of Naruto Uzumaki, in the original animated TV series Naruto. This is based on the Japanese comic created by the famous Japanese manga artist, Mashashi Kishimoto. The TV series gained much popularity through out the world that different companies broadcast it through different languages after the translation. It has become the most popular series in the world with its amazing hand-drawn animated graphics. It is also much attractive with its special effects. It also contains some annoying flash backs through out the episodes, which is considered as the huge deal of anime goodness by the people through out the globe. Anime Shippuuden is the online free anime website which is providing more than 500 anime series and movies for the people of different continents. All the episodes of Naruto Shippuuden are now available through anime shippuuden.com.

Naruto Shippuuden has 220 episodes, among which the first 134 episodes are based on the manga of Mashashi Kishimoto. The episodes which followed the first 134, are the fillers. The Naruto Shippuuden story is about the older and a still more matured Uzumaki Naruto, who is in a quest to save his friend, Uchiha Sasuke from the grips of a snake like creature (shinobi) called Orochimaru. Naruto Shippuuden is a fifteen year old boy, who always shows his physical abilities, strength, speed and other techniques. He is sported in new out fit, and shows his intelligence and sometimes the cunningness too, wherever required. He is a loud, hyper active adolescent ninja or shinobi, who is always in a search for the recognition and the approval by others. He also want to become the �~Hokage’, Hokage is the strongest person and the leader of the people who lives in the village.

Naruto Shippuuden goes back to the village of Konoha, and works hard to make his dream come true to become the Hokage of the village. Naruto is aware that it is not an easy thing to become the Hokage. Again he has to face a group of more dangerous enemies called Akatsuki. These new enemies all belong to the organization of shinobies. The whole story of these 220 episodes is character driven and casuality is incorporated through out the series when the characters reciprocate the past actions and relationships. The destinies of the characters are much intertwined with each other.

Why Anime and Naruto Can Be a Good Moral Guide For Children?

I am not recommending all anime shows, but there are some examples that can actually be a good moral guide. The first thing to keep in mind is that the Japanese Anime series is designed simply to be entertainment. However, The Naruto series, shown on the cartoon network is the example I recommend for parents concerned about the morals contained in the programs.

I am not recommending letting your children watch the Naruto anime series without any supervision. There are some characters that should be left out, but none of them prevent the show from getting a Y7 rating. My first warning is to stay away from the episodes with the character known as "Pervy Sage."

There are also some violence scenes. Understandably, this may be an issue for some parents. The show centers around a young man training to be a ninja so he can protect his home village. The combat scenes are essential to the story, but they are not very realistic. The ninjas are portrayed as the good guys.

Frequently the episodes that center around Naruto's training involve some tests. Naruto and his companions often misunderstand the nature of these tests. They think they are tests of their combat prowess, instead of tests showing more important traits like teamwork, honesty, mercy, and the ability to get along with others.

Now we come to the moral issues. Most importantly, this show contains deeply spiritual elements that most American made cartoons lack. Honor and duty are recurring themes in the series.

Even though the Naruto episodes can be a good moral guide, parents should take care not to substitute these shows for one on one time with their children. Naruto is a good choice for morality relative to most American cartoons. However, parents should not plant their kids in front of the TV thinking this will teach them what they need to know. That responsibility will always begin with the parents themselves.

Animated film is very good for children under five who are still present from the parents that the film does not educate or adult movies because movies like that can affect the development of the child's life and we as parents should be more selective in choosing programs for we children do not want .You if not the children we will not moral?

Aripiprazole, Dopamine, and Well-Being - Science or Selling Point?

Suppose you were a drug company, and you've invented a new drug. It's OK, but it's no better than the competition. How do you convince people to buy it?

You need a selling point - something that sets your product apart. Fortunately, with drugs, you have plenty of options. You could look into the pharmacology - the chemistry of how your drug works in the body - and find something unique there. Then, all you need to do is to spin a nice story to explain how the pharmacological properties of your drug make it brilliant.On an entirely unrelated note, aripiprazole (Abilify) is an antipsychotic marketed in the US by Bristol Meyers-Squibb. A Cochrane meta-analysis finds that it's about as good as any other antipsychotic in terms of efficacy and side effects. As good, but no better. However, uniquely, aripiprazole is a D2 receptor partial agonist. Other antipsychotics work by blocking D2 receptors in the brain, switching them off (full antagonism). Aripiprazole also blocks D2 receptors, but it activates them slightly in the process (partial agonism).

Is that a good thing? A paper just published says yes - The relationship between subjective well-being and dopamine D2 receptors in patients treated with a dopamine partial agonist and full antagonist antipsychotics. The research in question was funded, by the way, by Bristol Meyers-Squibb. Let's see if it holds up.

The authors got 22 patients with schizophrenia who were taking an established antipsychotic, either olanzapine or risperidone. These are both D2 antagonists. Incidentally, neither of them is made by Bristol Meyers-Squibb. 11 of the patients were switched to aripiprazole, while 11 stayed on their original drug. There was no blinding, and no randomization. (The dose of aripiprazole was randomized, although still unblinded, but the assignment to aripiprazole itself wasn't).
Lo and behold, the patients who switched reported improved "well-being". Because there was no randomization and no blinding, and because the outcome was entirely subjective, this could be entirely explained as a placebo effect (or an experimental demand effect.) Especially when you consider that the patients were most likely convinced to take part in the study by being told that aripiprazole would make them feel better than their original drug.

That's not all, though. They also did some brain scanning, using PET to measure D2 receptor occupancy. On average aripiprazole blocked more D2 receptors than the other antipsychotics, which is what you'd expect, as it has a very high affinity for that receptor. But it's a partial agonist, remember - it binds to D2 receptors without switching them "off" entirely.

The paper suggests that this is a good thing because it doesn't make people feel horrible, which is what normally happens when you block almost all of someone's D2 receptors (they're rather important). By switching on the receptors as well as blocking them, it makes you feel OK.
Nice story, and scientifically it's not unreasonable. And as you can see on this plot, in the non-aripiprazole patients (triangles), D2 occupancy in the ventral striatum was negatively correlated with well-being, but in the aripiprazole patients (circles), it wasn't.

Great - except that the range of D2 occupancies in the aripiprazole group is so narrow that no correlation would be apparent even if there was one. The occupancies in the aripiprazole group are all extremely high, 80-95%. There's just no room for a correlation to appear. (Think about it this way - in children, age is strongly correlated with height, but if you only looked at a bunch of 7 year olds, you wouldn't know that.) This is high-school statistics.

This scatter-plot is in fact exactly what you'd expect assuming that a) aripiprazole strongly blocks D2 receptors, and makes people feel awful, just like any other strong D2 blocker and b) the placebo effect made some of the aripiprazole group feel (or at least say that they feel) a bit better than they otherwise would.

You'll note also that the aripiprazole group reported feeling no better than the other antipsychotic group, and that the single most miserable patient was on aripiprazole. The paper concludes on an optimistic note -
The present data suggests that aripiprazole may be associated with early and sustained improvement in subjective well-being, notwithstanding the very high D2 occupancy. This may be related to its partial agonist profile at D2 receptors.
I leave it to the reader to evaluate this claim, and to consider how likely we are to progress in our understanding of the brain when so much of the research is funded by organisations with a direct financial interest in certain theories.

[BPSDB]

ResearchBlogging.orgMizrahi, R., Mamo, D., Rusjan, P., Graff, A., Houle, S., & Kapur, S. (2009). The relationship between subjective well-being and dopamine D2 receptors in patients treated with a dopamine partial agonist and full antagonist antipsychotics The International Journal of Neuropsychopharmacology, 12 (05) DOI: 10.1017/S1461145709000327