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A Spoonful of Sugar… Makes the Dose-Response Go Around?

An oldie but a goodie! Haven’t heard of Mary Poppins or her spoonful of sugar? Have a peek here for your dose of the classics. In my most recent set of posts I have been talking about Bradford Hill’s criteria for causality. So far we have covered strength, consistency, specificity, and temporality. Today we are going to talk about biologic gradient or dose-response.


This criterion is pretty easy to understand. An increasing amount of exposure increases a risk in question and with a dose-response relationship present, it is strong evidence for a causal relationship!  


Let’s say you think that being out in the sun in a bathing suit causes your skin to suffer a sunburn. So, the exposure is sunlight and the outcome is sunburn. Based on everyone’s experience, it would certainly appear that the longer you stay out in the sun the greater the risk you will suffer a burn! Your parents have been warning you of this for ever.



However, as with specificity, the absence of a dose-response relationship does not rule out a causal relationship.  A threshold may exist above which a causal relationship is present.  


Next time we will talk about the 6th criterion: plausibility.




Watch one of Simon’s Cat earlier clips Cat-Man-Do and see if you can spot the dose-response…


… and I’ll see you in the blogosphere.




Pascal Tyrrell


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All the World’s a Stage

For journalists, authors, bloggers and tweeters, sharing articles has never been easier. Indeed, the public expects to be able to read articles about world events almost in real-time. For example,
the New York Times Twitter account was updated nine minutes ago, and National Geographic tweeted three minutes ago. This expectation of speediness applies equally to scientific advances as it does to international affairs.
As an avid reader of online news, I would be the last to complain about being able to access such a vast amount of information. But there is something particularly noteworthy about information presented by a visible human. Perhaps that explains the persistence of televised news in the age of Twitter. 

Maybe it also explains the popularity of other media sources like TED talks, which often explain complex ideas in an engaging and understandable format. A personal favourite is “The best stats you’ve ever seen” by Hans Rosling. In his talk, Rosling explains the importance of little-known global public health data that shows the progress (or lack thereof) made by different countries over the past few decades. 

A more recent talk on a similar topic is also informative. One would be hard-pressed to find a paper or article that presents the same information with as much clarity and appeal.

In addition to numerous (maybe too numerous?!) TED talks, I have recently experienced the value of human-to-human information transfer. At the beginning of my ROP project in September, I was lucky to be able to hear about previous students’ research in person. I think it helped address the complexity of the work, but also conveyed its importance and the effort that had gone into it. Thanks Kiersten!
I’m not sure if information is generally more effective this way, but it is almost certainly more memorable. In any case, it has definitely worked for the 3.5 million subscribers to CrashCourse’s YouTube channel, where one can learn about anything from astronomy to macroeconomics.
For me, learning more about how researchers give and receive qualitative information to and from their subjects has allowed for a more well-rounded understanding of information transmission in the digital age.  But I think researchers andthe media have a lot to learn from each other. Communication is key for both, so understanding how others best absorb and respond to information can be instrumental.
That’s all for now, Julia!
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Dem Bones Dem Bones Dem Dry Bones

Happy Canadian Thanksgiving!!!

A traditional holiday – originating from the native peoples of the Americas – to celebrate the completion and bounty of the harvest.

This year I am off to Algonquin park for a canoe portage trip with the kids! I will take the time to appreciate some of the successes of our MiVIP program and this blog over the long weekend.

Thanks for being a part of it!

Listen to Dem Bones by the famous Delta Rhythm Boys…

… and I’ll see you in the blogosphere.

Pascal Tyrrell

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Just in the Nick of Time… Causality.

Now that was a great movie: Interstellar. See the trailer here for a refresher. So this movie talked a lot about worm holes – essentially an area of warped spacetime. Theoretically a worm hole could allow time travel. Want to know more? Grab a large coffee and see here. You may be thinking what all this has to do with medical imaging but, believe it or not, I posted about x-rays in space earlier in the blog (see here).

Listen to Hans Zimmer’s – Time from the movie Inception (another great movie) to get into the mood.

Now, we have been talking about Bradford Hill’s criteria for causality and today we are addressing the fourth one: temporality. The exposure of your association of interest should always precede in time the outcome.  If factor “A” is believed to cause a disease,  then factor “A” must necessarily always precede the occurrence of the disease. So for example the act of smoking (or being exposed to second-hand smoke) must precede the development of lung cancer for the relationship to be considered causal. This is the only absolutely essential criterion (out of nine).

Easy one, right? Next time I will be talking about biological gradient.


I am not sure you need time to decompress today as it has not been too taxing… but listen to Bonnie Raitt Nick of Time anyway…

… and I’ll see you in the blogosphere.

Pascal Tyrrell

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Be More Specific… Or It May Not Be Causal?!!!

Well, if you are relaxed and heading nowhere in particular then I guess you probably won’t be too concerned with showing causality either. In our past few posts we have been discussing Bradford Hill’s criteria for determining causality (see Strength and Consistency for a refresher). If you are stressed out already, have a listen to “Come the morning” from an up and coming Canadian artist from Winnipeg, Manitoba – Sebastian Owl – before reading on.



Today we will talk about the third of the nine Hill criteria: Specificity

 
When considering the specificity of the association of interest, we wish to establish whether a single putative cause produces a specific effect. When specificity of an association is found, it provides additional support for a causal relationship.  But keep in mind that very often the effect under investigation may have more than one cause. So the absence of specificity in no way negates a causal relationship. This criterium of Hill’s is considered to be the least important and can often be over-ruled in the case of multi-causal relationships.


Next, post we will talk about the oh-so-important criterium: temporality.



If you are nowhere in particular then you are not being specific to your whereabouts – right? Anyway, why don’t you watch this great Film festival short by Mason Cardiff, Nowhere in particular, to decompress and…




… I’ll see you in the blogosphere.




Pascal Tyrrell
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Consistent Associations May Be Causal Ones…?

Do you remember the Rain Man movie with Dustin Hoffman and Tom Cruise? Great movie that introduced Savant Syndrome to theater audiences all over the world. The savant syndrome is a rare condition in which persons with autistic disorder or other mental disabilities have extraordinary skills that stand in stark contrast to their overall handicap. There is a very interesting documentary on Kim Peeks who was the inspiration for the movie here. Anyway, last post we talked about strength – one of Bradford Hill’s criteria for causation (see here for a refresher). Today we will talk about consistency, a good qualifier for the often obsessive and ritualistic behaviors of autistic savant persons.




An association between two entities is consistent when results are replicated in multiple studies in different settings using different methods. So if a relationship is causal, we can expect to find it consistently in different studies and among different populations.  This implies that many studies need to be done before meaningful statements can be made about any causal relationship.








A great example of this is the long debated causal relationship between smoking cigarettes and lung cancer. It took hundreds, if not thousands of highly technical studies and many, many publications before a definitive conclusion could be made that cigarette smoking increases the risk of cancer and in a causal manner (see here for a statement from the CDC Surgeon General).  


So be consistent in your smoking cessation and you will consistently avoid the risk of lung cancer…


Next post we will tak about Bradford’s third criterium: specificity.




Relax listening to the very eighties styled theme music to Rain Man and…


… I’ll see you in the blogosphere.




Pascal Tyrrell

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Causality and Who’s Running Up That Hill?

Yes, back to the eighties. They were my high school and undergrad years – so very memorable! This song – Running Up That Hill – by Kate Bush was her first great hit from that time.


So, why was she running up that hill you ask? Well, it was because she had finally come to realize the importance of establishing the minimal conditions needed to establish a causal relationship between two entities, of course! Somewhat like the story of Archimedes who leapt from his bath yelling “Eureka” in excitement having discovered a law of physics that would later become the building block to fluid mechanics (see Archimedes principle).






In 1965 (no, I was not born yet – but just!), Austin Bradford Hill a British medical statistician proposed minimal conditions needed to establish a causal relationship between two entities. These later became know as the Hill’s Criteria. Very often people get the relationship of association confused with that of causality. See my previous post Rebel Without a Cause for some insight on when an association can be considered as cause and effect.


Today we will talk about the first of the nine Hill criteria: Strength


– The strength of an association is defined as the size of a given association as measured by appropriate statistical tests.  The stronger the association, the more likely it is that the relation between the two entities of interest is cause and effect.  For example, the more highly correlated hypertension is with smoking, the stronger is the relation between the exposure, smoking, to the outcome, hypertension. Though we cannot be sure of the direction of the relationship (this will be achieved when we discuss Temporality) – as hypertension could hypothetically lead subjects to smoke – we can certainly decide that the strength of the association observed supports our argument of causation.


Look at that, we have completed the first criterium all ready! Next we will look at Consistency.




Have a listen to “Strength Of A Women” by Shaggy to recover from today’s fun and…


… I’ll see you in the blogosphere.




Pascal Tyrrell

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Kiersten Thomas – Summer 2015 ROP at UofT: Another great student experience… part deux!

Kiersten Thomas – ROP summer 2015

Hello, I’m one of Professor Pascal Tyrrell’s summer ROP students and a second year Immunology Specialist student at the University of Toronto. I have just completed my summer research project investigating the cost-effectiveness of using MRA to evaluate asymptomatic carotid artery stenosis. 


I learned a lot and had an amazing time conducting research with Dr. Eli Lechtman and my ROP partner Indranil Balki. Using TreeAge Pro to create and analyse decision trees, we demonstrated that the additional information gained from an MRA/IPH scan increases the effectiveness of MRA when imaging carotid artery stenosis. 


Our research suggests that the additional information of the presence of intraplaque hemorrhage (IPH) would lead to better patient care, reducing long-term stroke risks. This means that MRA/IPH can be cost-effective or even dominant when compared to the current imaging strategy that uses standard ultrasound as a first-line imaging modality, for evaluating all degrees of asymptomatic carotid artery stenosis. Take a look at my timeline to see some of the highlights of my summer!


Thank you Dr. Pascal for this wonderful summer. 


Kiersten Thomas

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Indranil Balki – Summer 2015 ROP at UofT: Another great student experience!

Indranil Balki – ROP Summer 2015

 

I am one of Dr.Pascal’s 2nd year ROP students at the University of Toronto.  This summer, I had an amazing experience into the realm of research working with my partner Kiersten Thomas, mentor Dr. Eli Lechtman, and supervisor Prof. Pascal Tyrrell. This timeline-cum-infographic highlights some of the especially memorable moments of this journey.
Our main project was focused on constructing a computer simulation to model the effect of choosing either MRI or US as a first line imaging modality to diagnose and treat patients with Carotid Artery Disease. This project involved comprehensive literature search, discussions with experts (including the “Trip to Cambridge”), learning computer software and presentations!
Our team’s models’ main finding was that MRI can be both more effective and no more costly than US as a first line diagnosing tool in measuring carotid artery disease.
 

Thanks to Dr. Pascal for allowing me to share my experience on his blog and I hope you enjoy the read!
 
 
Indranil Balki
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Another Reason Why a Brain Boo-Boo Is Bad.

Rostam Rashidkhani – YSP 2015



Rostam Rashidkhani is a grade 12 International Baccalaureate student at the Toronto French School and he was a Meds – Youth Summer Program student with me this summer.

Rostam is intrigued by the sciences and enjoys biology, chemistry, and physics in school. He has participated in a number of University of Toronto summer programs and is looking forward to University life!


This summer Rostam looked at what causes brain problems after traumatic brain injury and how best to detect these changes with MRI. Recent brain imaging studies, including those in former professional football players, indicate that persistent brain inflammation after a single moderate head injury or repeated milder traumatic brain injury may be very common, may contribute to cognitive problems. More importantly, the chronic brain inflammation related to traumatic brain injury may be treatable. Looking for chronic traumatic brain inflammation with followup MR may be a way to reduce cognitive impairment.

Well done, Rostam!



Enjoy the read and…

… see you in the blogosphere,

Pascal Tyrrell