Rats, Bad Decisions and Jelloshots

It is an accepted fact of life that alcohol and good decision making have only loose a acquaintance  with one another. Like ships passing in the night, they may meet or they may not. This is true for the momentarily intoxicated but does that propensity for poor choices follow us even after the libations cease? Adolescents who drink alcohol from an early age appear to suffer from impaired decision making skills later in life but the connection is not clear cut as to whether the alcohol lead to that ill advised life choice or if the bad decisions lead to the alcohol.

In an effort to tease out those threads researchers used rats to model behaviour. In this case to entice the rats to consume the alcohol they provided it as part of a “palatable gel matrix” or in common parlance, jelloshots. This allowed the researchers to promote high levels of voluntary alcohol consumption among the adolescent rats. Now to measure the effect of this alcohol on the rats decision making abilities they weren’t able to offer the rats stock market options or the choice of marrying Tony Veitch. To substitute for these sorts of things the rats were give a choice between low risk certain rewards and large but uncertain risky rewards.

Rats that had consumed large amounts of alcohol were biased towards the high risk behaviour even after 3 months without alcohol, or well into maturity. Whereas the control rats displayed behaviour that assessed the risk against the pay-off and went for the more certain rewards. Unfortunately the full study is locked behind a pay wall* so I can’t determine how the study was controlled, how reliable these results are and what they actually tell us about the link between early alcohol abuse and risk taking behaviour later in  life. If anyone has access to this info I’d appreciate it. In the absence of this information it seems as if the alcohol is a significant predictor of risk seeking behaviour independent of the innate predilections of the individual. Or to put it another way:

*Why is the best stuff hidden away? Universal Open Access, your day will come!

TXT Language Redeemed

Working in a laboratory, as I do, abbreviations and acronyms are a way of life. Seriously, if we had to enunciate all of those chemical names, procedures and tests work would grind to a halt. Even so I find myself despising TXT speak, reducing otherwise comprehensible words to single letters, whole sentences becoming a jumble of alphanumeric sequences drives me crazy. And what’s up with “BayB” it’s the same letters in a different order, what do you gain by that?! (Deep Breath)

Even so, perhaps I’m overly harsh on users of this emerging dialect, perhaps we should consider it properly as a new language and users as early adopters deserving of respect for the mental agility it requires. Or at least we shouldn’t stereotype those fluent in  TXT speak as illiterate miscreants with no respect for the English language. A study submitted to the journal Reading and Writing looked 40 subjects in the 12 – 17 age bracket to see if there was a correlation between use of TXTese and poor spelling ability in regular English.

Turns out, there isn’t. In fact those that used more abbreviations tended to be better spellers over all. In direct contradiction of the critics (including me) poor spellers of English also tended to make more mistakes in TXTese (though how this was determined I don’t know).

What does this mean for the future? Will we all descend into a perverted shorthand of truncated words? I doubt it. This new version of English may or may not flourish as time goes on but being a product of necessity due to character limits for SMS I suspect it may very well decline in use again once technology catches up to the ease of other communication methods. Perhaps future linguists will devote treatises to the rise and unfortunate fall of a promising new language. Perhaps not.

Twitter, The End Of The World as I Know It

Alright, up until this point I have viewed the phenomenon known as Twitter to be the vacuous outgrowth of a shallow internet culture and considered it beneath contempt accordingly. That said we should always allow ourselves the opportunity to change our minds with evidence, with this in mind I have been persuaded to give Twitter a try. After only a few hours and having made only a single twat* I still like it better than Facebook.

Hopefully this new tool will help me bring to you, my reader, interesting info in a timely manner. Currently the average time between something coming up on my radar and actually writing about it is approximately 4 weeks. So sign up to follow me and we’ll see where this little experiment takes us, either I will use it constantly giving you a deeper glimpse into my interests and widening yours or it will die the ignominious death of complete abandonment and apathy.

* Someone with an ego the size of mine will never “Tweet”

Backing Up Evolution

I’ve said it before and no doubt I’ll say it again but we know science works because it makes predictions that we can then measure against the universe and determine if the models we have created to describe it are accurate or not. One of the more successful models is the theory of evolution by natural selection. A criticism levelled against the theory of evolution by detractors is the claim that new information can not be introduced into the system, only taken away. This is actually false but lets consider how we might tackle this question scientifically

First, the underlying assumption here isn’t unreasonable, let’s explore it. The accepted mechanism of introducing change in an organism, change that natural selection can then act upon, is mutation. Mutations involve a mistake in the copying of an organism’s DNA, this might consist of a change in a single base of a gene (an insertion of an extra base, deletion of an existing base or swapping one base for another) or it might involve large stretches of DNA. The basic principle that is relevant here is the same, a change is made to the blueprints of life in our cells.

As you might expect there are many more ways of being wrong than there are of being right, any random change is more likely to introduce a defect in the complicated machinery of life than it is to create an improvement (bearing in mind that “improvement” is a value judgement that really cannot be applied here but don’t focus on the wrong part of the story). So on the surface it would seem that random change is very definitely a bad thing, mutations would likely lead to loss of gene function, and by extension, loss of information and specifically death of the individual.

How might evolution get around such a problem? One solution would be to make copies of critical genes, this way is one copy is damaged through mutation the other can still function and produce a viable organism. The “spare” gene would then be free to mutate and the resulting gene may be selected for or against by natural selection (or human breeders).

If you have been reading closely you will have picked up on our prediction, the genomes of organisms should contain copies of various genes that allow mutations to occur without harming the individual that accumulates them. It turns out this is exactly what we find.  A recent study found a significant amount of redundancy in the genome of Zebrafish which allows mutations to occur in genes critical to development without lethal consequences to the fish.

The researchers intentionally gave mutagens to populations of Zebrafish and looked for changes in fish morphology indicative of mutations. In particular they created a mutation that lead to the loss of most of the fish’s scales, similar to that of Mirror Carp. The mutation was traced to a gene critical to normal development, further investigation revealed that the gene existed as a redundant pair, only one of which being required for normal development.

It is tempting to talk about this phenomenon in terms of intention, the gene was duplicated so that it could mutate and provide raw material for evolution. This is a mistake however, evolution can not move towards any putative desired future state. the genes that are duplicated in this way will be random and the mutations that affect the genes will be equally random, there are likely many genes in the Zebrafish that are not duplicated and would cause death to the individual if they were to change. This does not detract from the fact that a proposed mechanism for introducing new information into an organisms genome has proven correct.

Science is Awesome.

Beware the Demons!!!!!*

Catching up on blogs from over the weekend this one on the Center For Inquiry blog particularly stood out in the category of conspicuous displays of crazy. Beware of demons in your Halloween treats. I try not to do posts that are just “Look at this other Blog” but this one was too good.

*And all those exclamation marks, you notice? Five? A sure sign of someone who wears his underpants on his head.’ — Terry Pratchett,Maskerade

Can Torture Ever Be Justified?

I don’t think I would be going out on too much of a limb if I observed that most of us find the idea of torture to be repellent. As social creatures it is natural for us to shy away from inflicting harm on our fellows, empathy stays our hand when ruthlessness might otherwise help us achieve our personal goals. This holds true both in normal social interactions and in the extreme situations of conflict. It requires a significant expenditure of effort for us to overcome our inbuilt aversion to causing pain.

Even so torture can be rationalised as being for the “greater good” such as in the hypothetical situation which illustrates when torture might be a reasonable recourse known as the “ticking time bomb” scenario. In this case it is supposed that a terrorist has planted a bomb in a populated area, the terrorist is captured but the authorities have not been able to ascertain the location of the bomb which might go off at any time killing hundreds or possibly thousands of innocent people. If the terrorist refuses to co-operate, so the logic goes, it is then not only permissible to resort to torture to extract the information it might even be obligatory in order to prevent greater harm.

This situation however contains a hidden assumption that if untrue leaves the entire argument moot, namely, torture leads to accurate information. If this assumption is false then the justification falls apart. Last week in the journal Trends in Cognitive Sciences Shane O’Mara argued exactly this point. The main thrust of O’Mara’s argument asserts that prolonged stress causes changes in the brain that make it difficult for the subject to accurately recall memories and make the implantation of false memories and confabulation more likely.

False memories can be laid down when a subject incorporates what they are told into their own memory as if it actually happened when it did not. Simple repetition of information can induce false memories in normal subjects, assuming that it does not also happen in stressful situations is not  particularly reasonable.

Confabulation is the involuntary creation of false memories in response to questioning when the frontal lobe of the brain is impaired. The subject believes what they are saying and so is not lying but the information may not be accurate in any meaningful way. Events from the subject’s past and imagination can be jumbled together without the ability to tell the difference between them, when or if they happened. As prolonged stress can have negative effects on the frontal lobe confabulation could be a real danger in torture situations.

In addition the subject will also be conditioned that while they are talking the extreme interrogation techniques are stopped, thus talking represents safety. There is no extra inducement to truthful speech. In this situation there is no immediate method of ascertaining the truth of the subject’s words and so as long as the subject continues to talk further interrogation is not necessary.

Given these objections and certainly in the absence of reliable data to refute these points the justification for the use of torture simply dissipates. I for one find this information very reassuring.

Disgust or Anger?

The ability to recognise the emotional states of those around us is a very useful tool which allows us to act appropriately in social situations. If this ability is impaired then it could lead to inappropriate reactions when dealing with others, this in turn could land us in hot water. An impairment like this has been suggested to explain the behaviour of delinquents, though it is unlikely to be a sole cause of antisocial behaviour.

A study published recently lends support to this hypothesis, published last month in the journal of  Child and Adolescent Psychiatry and Mental Health (or CAPMH for short, catchy) the study looked at 24 Japanese young adults that were serving time in correction facilities (in Japan). Simply put the researchers compared these so-called delinquents with a control batch of young people (matched for age and gender), in the ability to correctly match an emotion to a facial expression. Six basic emotions were represented with 8 different pictures each, so participants had to match a total of 48 pictures.

The emotions covered were anger, disgust, fear, happiness, sadness, and surprise, the prediction was that the incarcerated subjects would have difficulty interpreting some facial expressions and that this difficulty would skew the subjects towards misidentifying expressions as anger. This in fact did happen, the delinquent subjects actually identified disgust as anger more than the control group.

This interesting result is lessened in it’s impact somewhat due to the fact that the control group also made this mistake a large percentage of the time. This predilection in the delinquents however is an insight into how certain personalities might perceive some social situations as being more hostile than they really are. These personalities are also marked by being quick to anger and experiencing more intense anger than others so recognising how this occurs can be useful information in diffusing these situations and possibly diagnosis of individuals who might otherwise be labelled as simply “difficult”.

Simon Singh Granted Permission to Appeal,

This just in (sort of), for those following the unfortunate case of the British Chiropractic Association suing columnist and author Simon Singh for libel, Singh has just been granted the right to appeal original ruling on the meaning of his article. For those not aware of all of this see here for a rough run down of the back story.

See Jack of Kent’s blog for the legalese, thanks to The Lay Scientist for the breaking news.

Natural Health Expo(sed)?

Driving around Hamilton the past few weeks I couldn’t help but notice the signs sprinkled around the city for the “Natural Health Expo” which is to take place here this week end. As I perused the website for this event yesterday I was disturbed by the large number of anti-scientific “treatments” that will be showcased. Like my co-blogger Grant who has already posted on this, I was troubled by the amount of misinformation that will be leveled directly at consumers.

As I was pondering how to answer the bewildering array of AltMed that will be promoted I checked my email and found a great little article just published in Chiropractic & Osteopathy (made available through the open access publisher BioMed Central).

The paper, “Why do ineffective treatments seem helpful? A brief review” written by Steve E Hartman, looks at how practitioners and patients can fool themselves into thinking that ineffective medical interventions actually work. An excellent example of Evidence Based Medicine 101, Steve covers the cognitive biases that hinder our ability to draw logical conclusions in the medical sphere such as the Post Hoc, Ergo Propter Hoc logical fallacy, confirmation bias and cognitive dissonance. Also covered are explanations of how it can seem that a treatment has been directly responsible for improvement in a patient’s condition when it may not  have been.

The paper touches on disease natural history, which simply refers to how a particular malady might be expected to progress without treatment. Self limiting diseases such as colds, headaches and fatigue can be expected to get better on their own . If a patient is taking a treatment at the time, the treatment (rather than their own immune system) might erroneously be given the credit.

This combined with the overlapping arenas of the placebo effect and regression to the mean can be a powerful confounding factor when treatments are not being considered in light of scientifically controlled settings. The placebo effect is referred to frequently in common culture but regression to the mean is a less well known entity for the layman. Steven does a good job of explaining the concept, essentially people experience a variety of different intensities in their symptoms. Also they will tend to seek medical help when the symptoms become severe, knowing that the severity of the symptoms will tend to cluster about a mean value it is likely that whether treatment is sought or not the patient’s condition will tend to get better.

Thus the patient will feel relief and attribute that relief to what ever modality they are using at the time. Practitioners are not immune to these effects either and will in their practice see time and again that patients are getting better after their pet therapy is applied. In which case they will feel justified in proclaiming it works in the absence of confirming studies (or even in the face of disconfirming evidence).

The one aspect that I felt was missing from the paper, although it may have been obliquely implied, is the role of prior plausibility in evaluating treatments. Many modalities that will be on offer at the Natural Health expo are not only unusual they fly in the face of currently understood science. Scientific plausibility is our compass, without it we can become lost in the wilderness of fanciful ideas without any method of discerning the way forward. This concept is what separates Science Based Medicine from simply Evidence Based Medicine. The former takes the plausibility of a treatment into account when deciding the threshold of evidence needed before it can be considered effective. The later only measures outcomes and so is less able to distinguish true effects from chance outcomes.

Consider the following scenario: I claim to be able to influence the outcomes of coin tosses by virtue of what I had for breakfast on a particular day. If I have eggs then tails with predominate, lettuce produces more heads. Now without considering the plausibility of the setup we could run a trial, perform statistical analysis and find that my predictions are correct. But given that there is no good reason to suspect that my diet can influence a coin toss the positive is more likely to be because of chance than because of a real effect. In this case then a higher standard of evidence would need to be achieved than if I had said I could alter the probabilities be sticking a piece of gum to one side.

All-in-all though this a very nice paper and my complaint is a small one, given the probable readership of the journal the inclusion of plausibility may even have alienated those that might otherwise have been receptive to the other points presented. I recommend reading it for yourself, it is a very easy and informative read.

Legitimate Use of Magnets in Therapies

I have to say I cringe every time I see an advertisement for some magnet based item that promises health benefits. I’ve ragged on these Magnet Therapies before but today I’d like to cover one of the ways that magnets are legitimately being used to treat medical problems. A couple of months ago a study was published in the The Journal of the American College of Cardiology: Cardiovascular Interventions (a mouthful huh?) that detailed the use of magnetic nanoparticles and an externally applied magnet in guiding cells inside the body to a site of injury.

Specifically the study attempted to tag a particular type of stem cell, Endothelial Progenitor Cells (EPCs), with iron oxide superparamagnetic* nanoparticles. This was rather simply achieved by the addition of the particles to the growth medium of the cells. The cells then took up the particles via endocytosis. Once this was done they injected the cells into rats whose carotid artery had been damaged by angioplasty. A magnet was then applied to the outside of the rat to attract the tagged cells to the site of the damage. This technique showed a 5-fold increase in cells attaching to the damaged area compared to not using the magnet.

The difficulty of getting the cells to the right place without the magnet is due to the rapid blood flow past the injury. Imaging being swept down a fast flowing river with the goal of grabbing onto the river bank at a particular spot, not that easy, if there are thousands of you doing it some will manage but most will be carried right past. The addition of the magnet is like throwing a rope out to the hapless swimmers, once they get that helping hand they can then clamber onto the bank on their own. The EPCs will naturally attach themselves to places where damage is evident but under the high flow rates in arteries this process is inefficient.

This technique is specifically tailored to helping repair damage caused by angioplasty and it is hoped that it’s use might reduce the occurrence of Restenosis, or the re-narrowing of arteries after they have been widened by the angioplasty procedure. Even so, the guidance of the cells by magnetic field has obvious applications for other types of stem cell therapies as well as targeting drugs and gene therapies to specific organs of areas of the body.

Magnets are awesome.

*This sounds like a good name for a cheesy super hero, Superparamagnetic Powers Activate!.

Tragedy in the UK

Last week I presented the safety study for the Gardasil qHPV vaccine, after this a reader remarked that it was a relief to see as she was concerned by a story she had read. It revolved around the unfortunate case of a UK school girl who died shortly after receiving a vaccine. As the full story does not yet seem to have been covered adequately by local news I thought I would cover the salient points here.

Firstly there are two competing HPV vaccines in the world market, Gardasil produced by Merk and Cervarix made by GalaxoSmithKline (GSK).  Here in New Zealand we have opted for the Merk version of the vaccine while the UK uses GSK’s product. Cervarix immunizes against the HPV strains 16 and 18 which are implicated in development of cervical cancer while Gardasil also covers strains 6 and 11 which cause genital warts.

Thus the first point to be made in relation to New Zealand readers is that the vaccine this young girl was exposed to is not the same one that is being given to our population.

To summarize the facts about this case, as reported by TimesOnline on the 29th of September, 14 year old Natalie Morton died in hospital on the afternoon of the 28 of September. Preceding her death by several hours was her injection of the GSK HPV vaccine Cervarix, this proximity in time is the only evidence that linked the vaccine to the girl’s death.

Late on the 29th the news that Natalie had a “serious underlying medical condition” was reported in the Guardian. At this point it was still unclear (to the public) whether the vaccine was in any way related to Natalie’s death. Health officials were however preparing to continue the vaccinations that had been put on hold following Natalie’s perceived complications.

By the 2nd of October the full story was clear, as covered in Medical News Today, Natalie’s death was revealed to have been caused by a previously undiagnosed and apparently asymptomatic malignant tumour in her chest. The tumour was described as having heavily infiltrated her heart and gone into her left lung. The HPV vaccine was officially cleared of any causitive agency in her death, in fact according to Dr Caron Grainger, Joint Director of Public Health for NHS Coventry and Coventry City Council, it could have happened at any point.

This story, if the end had been less definitive, could have been a very powerful anecdote against the use of HPV vaccines, as comments both within and about the early news stories reveal. Some with a vested interest of discrediting vaccines will undoubtedly still try to use it as such, already there are attempts to label the cause of death as fiction.  This shows a deeply unsettling conspiracy mindset as well as disrespect to Natalie and her family in trying to use her tragic tale to further their own agenda.

Evolution – The Story of Life

I was sitting at my computer this morning wondering if I would suddenly be inspired with a topic to write about or whether I would resort to my default setting of abject sloth. Then inspiration did strike, in a way, my copy of “Evolution – The Story of Life” arrived by courier. Written by Douglas Palmer and illustrated by Peter Barrett this is a fantastic large format hardcover book that takes you on a trip through the history of life on planet Earth. From the appearance of single celled organisms, through the proliferation of forms during the Cambrian period and finishing up with the life we see around us today.

Beginning with introductory information explaining what evolution is as well as briefly covering the history of the theory, the time scales involved, taxonomy, fossils and how it all comes together this book will be accessible reading for anyone.

The book is beautifully illustrated throughout, touching upon each major stepping stone from the beginning to the present day. Every turn of the page brings a new vista with examples of flora and fauna typical of each age and location depicted. Below the impressive artwork is a brief description of the area and life shown as well as an information box showing a representation of the distribution of the continents at the time compared with how the particular location is situated today. Rounding out the informative package are photographs of actual fossils from the period.

I was particularly taken with the Cladograms that show how the species of animals are related. The major levels of the tree of life each have their own cladograms; Metazoa, Tetrapoda, Mammalia and certainly not forgetting Primates.  These fantastic illustrations provide a great overview of the interrelatedness of species and are a fascinating read.

Finally the book ends with a “Species listing”, an A-Z of the species depicted in the book featuring pictures of plants, animals and fossils. Each entry gives the time period the life form lived, it’s place within the tree of life, a brief description and the reference to were it can be found in the earlier pages of the book.

At the back of the book can be found a condensed timeline of the geological and evolutionary history of our planet. In addition all of the artwork in the book is reproduced side by side to show a continuous panoramic view of the story of life.

I think I say without too much exaggeration that this book is truly a masterpiece and a great addition to any collection. Highly recommended.

SciBlogs

The Sciblogs website has now gone live! What is Sciblogs? Sciblogs is an exciting initiative by the Science Media Centre an “…inde­pen­dent source of expert com­ment and infor­ma­tion for jour­nal­ists cov­er­ing sci­ence and tech­nol­ogy in New Zealand.”, the Science Media Centre was set up by the Royal Soci­ety of New Zealand and is now venturing into the Blogging arena.

Essentially the site is a collection of science blogs from around New Zealand making it easy to find the work of scientists and science writers. Even before it began it was the largest such site in New Zealand and it will get bigger. I find the opening of this site especially exciting as I am one of the freshly minted Scibloggers myself. So head on over there and check out the best of science writing that New Zealand has to offer, and me.

If you want to always be up to date with new Sci­blogs posts you can sub­scrib­e via RSS or email or by fol­low­ing our Twit­ter feed.

As I said Sciblogs plans to grow over time, that means new bloggers. If you think this would be an opportunity that you’re interested in contact Sciblogs here.

Gardasil Post-licensure Study

Last month the Post-licensure safety study for Gardasil (the HPV vaccine) was released. The study focused on the reports of adverse events as reported to the VAERS database by the manufacturer, doctors and patients or caregivers. Much has been made by detractors of the vaccine about the serious alleged side effects that have struck young women given the course of injections. These allegations have been supported by referring to the VAERS database itself so if they are valid they should be upheld by this study.

Of the 12,424 reports that VAERS received in the 2.5 year period following implementation of the vaccine, 772 (6.2%) were classified as “serious”, the total number of vaccine doses distributed in this period was 23 million. The category of “serious” was defined according to the FDA regulatory definition of an adverse event that “is life threatening; results in death, permanent disability, congenital anomaly, hospitalization, or prolonged hospitalization; or necessitates medical or surgical intervention to preclude one of these outcomes”.

It must be noted at this point that the VAERS database cannot determine causality, the events reported merely have to occur after vaccination takes place. Therefore anything that happens to a patient in this time frame that someone thinks might be related to the vaccine may be entered. I point this out only to remind that while we may be looking at vaccine safety life does go on, accidents happen and co-incidences occur. The point of a study such as this is to determine if these events are occuring at a frequency higher than what we would expect in the normal population. In other words, is there really a correlation between these events and the vaccine or is is simply a statistical fluke.

The study looked into each type of adverse report in detail and attempted to answer the above question, does the rate of reporting exceed that which would be expected in the general population? In almost all cases the answer appears to be “No”, the exceptions to this were reports of syncope (fainting) and venous thromboembolic events (blood clots), this finding will certainly be followed up in future studies. Curiously one of he more prominent adverse effects that has been concerning many on both sides of the debate, Guillain-Barre´ Syndrome was not found to occur more than expected.

Guillain-Barre´ Syndrome is an auto-immune condition that can be brought on by vaccines but also by normal infections. The syndrome is caused when the immune system is stimulated by an antigen but then starts to target the body’s own nervous system, it usually exhibits as an ascending paralysis noted by weakness in the legs that spreads to the upper limbs and the face along with complete loss of deep tendon reflexes. As vaccines are made to induce an immune reaction the link between vaccines and the syndrome is biologically plausible and not controversial in the medical community.

The study concludes favourably but cautiously, as scientific studies are wont to do:

Vaccination with qHPV has the potential to decrease the global morbidity and
mortality of HPV-associated diseases, including cervical cancer. After hepatitis B vaccine, which can prevent liver cancer, qHPV is only the second vaccine licensed with an indication to prevent cancer. The postlicensure safety profile presented here is broadly consistent with safety data from prelicensure trials. Because VAERS data must be interpreted cautiously and cannot generally be used to infer causal associations between vaccines and AEFIs, postlicensure monitoring will continue, and identified signals may be
evaluated using epidemiologic observational studies.

The full study can be found here, a summary of the study here and a comprehensive discussion of the study here.

Harriet’s Toolbox

Harriet Hall of the Science Based Medicine Blog gave a talk at the Skeptic’s Toolbox workshop at the University of Oregon in August. The power point slides for this talk are now up on the Skeptics Toolbox website for all of us to benefit from. Head over there and check it out, the talk was titled “Tooth Fairy Science and Other Pitfalls: Applying Rigorous Science to Messy Medicine.” and is full of info and humour. Highly recommended.