An epidemic of an easily preventable disease

This is the cost of not getting vaccinated:
http://shine.yahoo.com/channel/parenting/whooping-cough-is-declared-an-epidemic-in-california-1828859/

For Real This Time...

I will not be posting for the next few weeks.  Thanks for reading, and hopefully I'll see you back here sometime in July.

A new avenue in Alzheimer's research?

While most of the work on Alzheimer's has centered around the amyloid hypothesis (or here), another possible set of proteins involved in the disease seems to be yielding promising results:
http://www.sciencedaily.com/releases/2010/05/100525103935.htm

I'm always interested to hear about ideas that don't involve amyloid beta proteins, not because I don't believe they are important to Alzheimer's disease pathology, but I am not convinced that they are the only players in the story (or even the main character).

Sunday Comics

A Letter to Andrew Wakefield

From the ever hilarious "anthropomorphic personification of Science" (a.k.a. Dr. Dean Burnett over at Science Digestive).  The latest in the series addresses the unfortunate case of Andrew Wakefield, the now discredited doctor who started the whole (completely baseless) vaccine and autism scare.  Check out the whole series of "from: Science" letters, which tackle everything from astrology and advertising to chiropracty and homeopathy.  You can start with this one , and of course check out this one (to the anti-vaxxers themselves).

A Fantastic Six Word Memoir

I remember discussing poetry in one of my literature classes as an undergrad.  For some reason, I distinctly remember us talking about how a lot of the power and beauty of poetry derives from brevity.  Thus, one could view truly great poetry as that which says the most using the least amount of words, and a perfection of the art would be summed up by an ability to always find "le mot just".  (This is probably why I am a loquacious scientist, and not a poet... that, and a complete lack of literary talent.)  Anyway, at some point, summing up one's life in 6 words or less became a trendy sort of challenge, a "6 word memoir"so to speak.  I wasn't really aware of this until recently, when I was listening to a talk by Dr. Lyn Clemens of Michigan State University, who ended the talk (which was something of a retrospective of his career) with one of these brief memoirs:

"Followed Dreams, Not Rules, No Regrets."

It seemed fitting to me to share this, since it's graduation season and people are making commencement speeches and looking for good advice to give new grads.

Memory is Not Like Instant Replay

A little bit ago, Slate magazine did a week's worth of articles on the life and work of Elizabeth Loftus, a psychologist who has done more than anyone to show us how imperfect our memories are.  And thankfully so... while it is certainly interesting how she debunked the myth of perfect recall by showing that we can be easily manipulated to remember things differently from how they happened, or even "remember" things that never happened at all, her work has also debunked the idea of "repressed" memories, and helped many wrongly accused victims avoid severe criminal penalties and jail time.  Her work certainly makes one question how much weight eyewitness testimony should be given in legal cases (particularly in the absence of strong corroborating evidence), or, at the very least, it makes a strong case for statutes of limitations...
Check it out...
http://www.slate.com/id/2251883/

This is why science is hard...

Flawed assumptions.  In my last post, I proposed an experiment to test whether or not the flash-lag illusion might be at work in mistaken calls made by baseball umpires (like the one made by Jim Joyce that cost Armando Galarraga a perfect game).  In this, I proposed that a batter running toward first base presents the moving stimulus, and the ball hitting the glove of the firstbaseman (or pitcher as the case may be) represents the instantaneous, or flash, stimulus.  However, it occurs to me that it may be just as likely that an umpire might track the incoming throw, and thus the baseball would be the moving stimulus, while the runner’s foot hitting the base would become the “flash” stimulus.  Since these variables can be so easily reversed, it is likely that the involvement of the flash-lag effect would not necessarily be revealed by any differences in the proportion of errors where the runner was called “safe” versus those where he was called “out”.  What we would need to do is to get umpires who would volunteer to wear head-mounted cameras so that we could know which object they were tracking (or which one they track most often), the runner or the baseball.  Granted, this makes the experiment more difficult, but it is not much different from what was done in this study, which could be claimed as the study that initiated the whole discussion on the potential role of the flash-lag effect in sports officiating.

Galarraga's Almost Perfect Game and the Flash Lag Illusion

There's been a big sports story that has been getting a lot of press lately.  Armando Galarraga of the Detroit Tigers was on his way to pitching a perfect game, that is, he had pitched 8 and 2/3 innings and hadn't let a single person get on base (no hits, no walks, just 3 batters up and 3 down, every inning).  Philadelphia Phillies pitcher Roy Halladay recently pitched a perfect game against the Florida Marlins, but don't be fooled... his perfect game was only the 20th in the history of Major League Baseball!  (definitely no small feat!)  Galarraga's would have been the 21st perfect game ever, but the 27th batter hit a little infield blooper and was called safe on a very close play by first base umpire Jim Joyce.  In the old days this would have led to a lot of debate that would have lasted for years over "what might have been", or eve "what should have been", but we live in the age of instant replay, and just seconds after the call, the instant replay showed that the runner was actually, and quite clearly, "out".  Just like that, Galarraga had been robbed of his perfect game, by a bad call.  Of course, part of the appeal of this story to the media, and to many of us watching, is the grace and sportsmanship with which all of this has been handled.  Galarraga, for his part, rather than blowing up and screaming, or complaining, simply laughed and shrugged it off, finishing the game and getting the win for his team.  And the umpire, Jim Joyce, rather than making excuses or stubbornly claiming he was right, or that it was a tough call (which it was), owned up to making a mistake and costing Galarraga his perfect game.

Well, I would like to suggest that, grace aside, there is another reason Galarraga was right not to get upset because the blown call may not have been entirely Jim Joyce's fault.  In fact, if anything is to blame, it is our flawed human perception, or perhaps Major League Baseball for not using instant replay or other computer and video asssisted techniques for officiating, but rather relying on human umpires whose perceptions are flawed.  I would like to propose this instance as an excellent example of where having a human umpire will almost invariably lead to bad calls, and hypothesize that the reason for this is a simple visual illusion that most of us are susceptible to.  That's right, Jim Joyce, take solace in the suggestion that (I believe) many umpires may have made the exact same call in your place.  And what is to blame you might ask?  The Flash-lag illusion.
We are all familiar with visual illusions.  They occur when what you perceive in your "mind's eye" doesn't agree with what you see with your actual eyes.  For example, we have all seen images like this one that appear to be moving even though everything in the image is perfectly still.

The flash-lag effect, or flash lag illusion, is a similar illusion in that the brain is "seeing" (perceiving) something different from what is actually there.  Probably the best way to describe it is to say that when you are watching something that is moving, your brain is paying attention to that movement and anticipating where the object will move to next.  In this way, your brain can compensate for the time it takes the "message" of what is being seen to travel from your eyes to your brain by perceiving that the object is slightly leading in front of where it is actually located in time and space.  Normally, this wouldn't be a problem, except when you need to compare something that is moving to something that only happens in an instant.  In the flash-lag effect, you are distracted for a split second by an abrupt, instantaneous event, usually a flash of light, and your brain tries to fill in the information about the moving object that it has missed while being distracted.  As a result you "see" the object leading its actual position, or, you see it moving farther than it actually has.  To help illustrate the point, watch the following YouTube video.  You will see a yellow dot (the "flash") appear, and momentarily block your view of the moving baseball.  After the video plays a couple of times, the still images of each frame will play in slow motion, and you will be able to check and see if the baseball is where you think it is.



(If the illusion worked, it should look like the pitch drops off to the side after the yellow dot because your brain perceived the ball as being closer to you than it really was.  If you need more of a tutorial, check out this page, or this brief video.)
Now that we understand what the flash-lag illusion is, let's try to figure out if it might explain what happened to Jim Joyce in his mistaken call.  It has been proposed that umpires, or rather referees, experience something similar to the flash-lag illusion when they are trying to make a call about  tracking something that is moving and something else that happens in an instant.  For example, in the case of Jim Joyce calling the runner safe at first, he had to be paying attention to the runner's feet moving pretty quickly as they charged toward first base, BUT, he also had to look up for a brief instant to see when Galarraga caught the ball.  This check to see when, or if, the ball was caught could act much like the yellow dot in the example above which would result in Joyce "seeing" the runner's foot lead its actual position, and appear to be over the base before it actually was.



To me, this seems like a pretty classic example of the flash-lag illusion.  BUT, in order to support this idea we would have to find a way to test this.  One way might be to go back and examine lots of footage from similar close calls and look at the mistakes that were made.  If the flash-lag effect is at play in these instances, then we would predict that disproportionately more mistaken calls would be in favor of the runner being "safe" rather than being mistakenly called "out".  In a way, this is almost exactly what several researchers have done in examining the errors made by soccer referees when calling offside penalties (1, 2, 3).  Being "offsides" in soccer means being closer to your opponent's goal line than anyone on the other team (aside from the goalie) when your team has the ball, and the ball is also not closer to the goal line than you are.  (It is basically a way to prevent players from "cherry picking" the opponents' goal.)  Two competing explanations for when referees make errors on these calls were the "optical error" hypothesis and the "flash-lag" hypothesis.  In the first case, one would predict that referees would make just as many offsides calls when players were not actually offsides (a "flag" error), as they would miss calls when a player actually was offsides (a "no flag" error).  The flash-lag hypothesis, on the other hand, suggests that referees would make more "flag" errors than "no flag" errors because movement is almost always in the same direction (toward the goal line) in an offsides call. Therefore, the player in question would be perceived to be leading his or her actual position, thus appearing closer to the goal line, and more likely to be called "offsides".  This is exactly what has been found.  The unequal proportion of "flag" to "no flag" errors suggests that the "optical error" hypothesis does NOT explain the majority of mistaken offsides calls, but rather, the disproportionate number of "flag" errors is consistent with the "flash-lag effect".  Of course, this does NOT "prove" that the flash-lag effect is definitely at work, it merely disproves the idea that "optical errors" are the primary cause, and suggests the flash-lag hypothesis as a more consistent alternative. Since this type of analysis does not rule out other possible explanations for why referees might make more "flag errors" than "no flag errors", the researchers can't say for sure whether the flash-lag effect is definitely to blame, or, say, that maybe referees are biased toward wanting to be seen as proactive and authoritative, and thus are more likely to make a call (even if it is the wrong one) rather than not make a call.  Still, it is an interesting hypothesis, with some, if not overwhelming, evidentiary support (see this article for a good description).
It certainly is interesting enough of an idea that I think it would be wothwhile to conduct a similar analysis of close calls (like Jim Joyce's) in baseball to see if we might get similar results.  Additionally, I think that baseball might add a control condition that is lacking in the analysis of offsides penalties in soccer... According to my hypothesis, the instantaneous event of the baseball being caught by the firstbaseman acts as the "flash" stimulus.  But in baseball, runners are not always "thrown out".  In some cases, like when the ball is hit between the pitcher and the firstbaseman, the pitcher fields the ball and then runs over and tries to step on the base before the runner does (so the batter is "run out" or "out run").  This condition is identical to "being thrown out" EXCEPT now, 2 very similar moving objects are being tracked and compared as they move to the same location, rather than one moving object and a "flash" stimulus. I would predict that umpires would make many more mistaken "safe" calls when players are being "thrown out" than when they are "run out", and we could even analyze mistaken calls at first second and third base (and even home plate) to control for the angle of the umpire's view (which would help us also analyze the "optical error" hypothesis).  Sounds like fun... somebody get me Bud Selig on the phone... we've got science to do.

References:

1.Baldo, M., Ranvaud, R., & Morya, E. (2002). Flag errors in soccer games: the flash-lag effect brought to real life Perception, 31 (10), 1205-1210 DOI: 10.1068/p3422

2. Helsen, W., Gillis, B., Weston, M. "Errors in judging 'offside' in association football: test of the optical error versus the perceptual flash-lag hypothesis." (2006). J. Sports Sci. 24(5):521-528.

3. Catteeuw, P., Gillis, B., Wagemans, J., Helsen, W. "Offside decision making of assistant referees in the English Premier League: impact of physical and perceptual-cognitive factors on match performance." (2010) .J. Sports Sci. 28(5):471-481.

More on Autism and Vaccines

An op-ed last week from the LA Times gives some frightening stats and stories about Measles and children dying from such an easily preventable disease.  In a way, the effectiveness of vaccines seems to be partly to blame (with, of course, the whole bogus autism scare bearing most of the blame).  As the author recounts, one parent she had seen in her practice didn't get the MMR vaccine for her child more because she didn't see getting measles (or mumps or rubella) as much of a threat since you never hear of people dying of measles anymore, at least not in the U.S. and other countries with widespread vaccination programs.

Sunday Comics: Who Needs a Wizard?

Who knew that the tin-man was such a deft surgeon... (via See Mike Draw, where you can see some other funny and disturbing cartoons).

Einstein's Brain

NPR has a great little story about Einstein's brain.  As I mentioned in a previous post, Einstein's brain wasn't any bigger than your average brain.  What did differentiate Einstein's brain however was that he had more glia than normal.  Glia (from the Greek for "glue") were originally thought to be nothing more than the cells that hold neurons in place, but more and more we are finding out that glial cells not only moderate (and modulate) neuronal signaling but many of these cells form networks throughout the brain and signal to each other across large distances much like neurons do.  Anyway, check out the story, and, if you want to learn more about Einstein's brain and the crazy journey it has been on since it was removed from the physicist's cranium, check out Driving Mr. Albert by Michael Paterniti.

More on Andrew Wakefield, autism, and inflammatory bowel disease

There is a great correspondence section from an issue of The Lancet in May of 1998 (the same year that Wakefield et al.'s "seminal" paper was published).  The first four pages are contributions from other medical practitioners and researchers pointing out many of the flaws in the report... the most commonly cited being the selection bias I pointed out in my last post.  Also, many take issue with the claims that were made about the MMR vaccine for which the paper only presented very limited anecdotal evidence.  (As I like to say, in experimental science, the plural of anecdote is NOT data).  Anyway, this makes it pretty clear, that many people saw the poorly done science in this paper right from the outset, but the media frenzy, rather than any real or reliable findings, vaulted Wakefield to cult hero status and somehow gave his viewpoint an artificial sense of credibility.  You can read the correspondence here. (and if you don't want to read all of my last post, basically I compared Wakefield and colleagues' selection bias to asking for all of the red M&Ms out of a bag, then looking closely at just those M&Ms and falsely concluding that all M&Ms must be red.)

The Future of Science...

Well, the future of biomedical science at least, is in good hands.  The Scientist has a quick article about the recent BIO convention, and the International BioGENEius Challenge.  This year's winner comes from... right down the hall from me, Raina Jain has spent the past few years working in the lab of Matthias Faulk, a faculty member in the department of Biological Sciences at Lehigh University.  To hear about the types of research projects being tackled by these enterprising high schoolers, one can't help but be impressed, and take comfort that, at least a sizeable group of kids are getting access to high quality science education.  Congrats to all who took part, and to Ms. Jain (the left-most student in the photo) and Dr. Faulk.

The four winners with Allan Jarvis of sanofi-aventis and Paul Hanle, head of the Biotechnology Institute
Image courtesy of The Biotechnology Institute

Read more:The world cup of science fairs - The Scientist - Magazine of the Life Scienceshttp://www.the-scientist.com/blog/display/57452/#ixzz0pnEOb898

NBC Dateline: Vaccines and Autism Edition

The other night, Dateline had a special about Andrew Wakefield, the man who started the whole anti-vaccine movement.  In the latest in a string of events that can only be described as the complete discreditation of Dr. Wakefield, the general medical council in the UK has struck his name from their register, a move equivalent to revoking his license to practice medicine.  Dateline did a pretty good job with the issue, and it is worth watching if you aren't too familiar with the supposed "controversy" (you can check it out below).
 I really do think the whole thing is such a shame.  I understand why people want to believe in Wakefield's claims, because he offers hope for an otherwise hopeless situation, and he seems so genuine and sympathetic, I almost want to believe him myself.  But there are 2 things (mainly) that prevent me from taking him at his word...
First, as you can see in the video, there were a few issues with potential conflicts of interest... Wakefield was being paid (about $750,000 U.S.) by lawyers who were bringing a civil case against MMR vaccine manufacturers.  Also, he held a patent for a treatment to be used either in place of MMR, or in children who had an adverse or unsuccessful reaction to MMR.  Thus, it was in Wakefield's financial interests to present a story that MMR was either dangerous in some way, or, ineffective.  Having these financial interests is not necessarily bad in and of itself, but what bothers me is that they were never disclosed... at least not until after they were exposed by Brian Deer's investigative reporting.  All scientific journals have a form you have to fill out if your manuscript has been accepted, and most, if not all of them, ask you to disclose "ANY POTENTIAL conflicts of interest".  In my experience, honest scientists put down anything and everything they think might even be remotely considered a conflict of interest, and they usually list ALL of their sources of funding regardless. Which is why Wakefield's excuse that the lawyers were paying him for another study, and that he used the money for research only doesn't excuse him in my mind.  These things should have been reported initially to the editors of the Lancet, by Wakefield himself, in the interest of transparency and full disclosure.  I believe that any scientist worth his or her salt would do so, and thus, I can't help but to find Wakefield's behavior to be deceitful.  But even if he didn't know better because he was more of a clinician than a researcher, there is a much more convincing reason to disregard Andrew Wakefield's claims, and that is bad science.

This is my second major point of contention, and for me, it is far more important than character issues.  If you take a look at the original paper from the Lancet (now retracted) you can see that there is a very large disconnect from what the study showed and what Wakefield is claiming.  First, Wakefield and his colleagues only examined 12 children, which is a very small sample size for a disease that affects anywhere from 1 in 110 to 1 in 150 children in western countries.  Ignoring the size of the sample, however, there is also a glaring selection bias in this study in that ALL of the children in the experimental group were selected based on the fact that they had been previously diagnosed with autism-like symptoms, AND, they had come to the Royal Free Hospital with gastrointestinal complaints.  After examining the patients for bowel inflammation, the researchers found that the autistic patients, who had been admitted complaining of gastrointestinal symptoms, did have signs of inflammation in the large intestine.  Go figure.  It's kind of like selectively removing all the red M&Ms from a bag of M&Ms, then taking a closer look at them, and concluding that all M&Ms must be red.  And, in fact, the authors of the manuscript say as much in the discussion: "We describe a pattern of colitis and ileal-lymphoidnodular hyperplasia in children with developmental disorders. Intestinal and behavioural pathologies may have occurred together by chance, reflecting a selection bias in a self-referred group..." (emphasis added)
The point is, at the time, this paper presented a small set of observations that suggested an hypothesis that can be paraphrased like this: "swollen lymph nodes, or other inflammatory processes in the intestinal tract may be related to autism pathogenesis".  In fact, that is how the scientific community took it, and since 1998, many studies have disproved this hypothesis (a couple of which can be found here and here).  And since Wakefield tried to extend beyond this hypothesis to implicate vaccines as causing autism, several groups set out to test this idea as well, and it has also been disproved (here and here for just a couple examples).  Ultimately, the problem here is that Wakefield is treating his hypothesis as if it were proven fact, and the end result is that children may not be getting much needed vaccines and Wakefield is exploiting parents of autistic children by selling them snake oil (or a pipe dream) and accepting their money for his books, lectures, etc.
I plan to post a more thorough review of the evidence at some later point, as well as an examination of all of the various permutations of the anti-vax hypotheses (thimerosol, etc.) but for now, here's the Dateline video...

(Click here to watch the whole episode)

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Quote for the day

"We didn't send you to Washington to make intelligent decisions.  We sent you to represent us."
          - Kent York, a Texas pastor, to Rep. Bill Sarpalius (D-TX)