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Engaging Primary Care in Research: Not Always an Easy Task

I am Stella Bing Xin Song, currently a second year student studying pharmacology and psychology at University of Toronto. I was fortunate to be a part of the 2016 Research Opportunity Program (ROP) supervised by Dr. Pascal Tyrrell in the Department of Medical Imaging at University of Toronto. 
My ROP project focused on evaluating the feasibility of using MRI as the primary imaging modality for carotid artery stenosis diagnosis and assessment (not sure what we are talking about? See previous posts here and here). Along with Ginni Ting, a student volunteer in Dr. Tyrrell’s lab, we surveyed physicians in the Niagara region of Ontario to learn about their perspectives on this proposal. Our community partner in this research was Heart Niagara – a fantastic local organization that has been guiding advances in cardiac health education and services since 1977.
Most of the responding physicians saw approximately 2000 or more patients per year. Physicians expressed a variety of care-related decisions for carotid artery stenosis patients, especially for those where diagnosis was less obvious with less than 70% stenosis. Most responding physicians would consider MRI over Ultrasound as the first-line diagnostic imaging modality, because of its ability to detect IPH yielding more pertinent information. IPH is bleeding within the plaques, which causes them to become more vulnerable (see vulnerable plaque). There is a 6 times greater risk of stroke in people with IPH! For those who were reluctant to consider it, they expressed that it was mostly due to their concerns for the relative cost and current wait time for MRI. 

Unfortunately, the response rate for this online survey was very low. Reasons given for the reluctance to participate were that physicians were on a tight schedule and were busy with their patients. Feedback from participants was that the online survey seemed long. Nevertheless, from the responses received, we were able to learn more about physicians’ perspectives of using MRI for carotid artery stenosis diagnosis and assessment.

In the end, it was an exciting and valuable experience to plan out and execute this research project. Most importantly, I had the pleasure to join Dr. Tyrrell’s lab and meet his team. I am grateful for all the help and support which I have received throughout my time at the lab. I look forward to continuing to work as a member of Dr. Tyrrell’s lab.

Stella Bing

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U of T Research Opportunity Program – Clare Sheen

Clare Sheen is an undergraduate student at the University of Toronto, in process of completing her Bachelor of Sciences in Genomics and Microbiology/Molecular Genetics. She was a 2015-6 Research Opportunity Program (ROP) student working on designing the Medical Image Network Enterprise (MiNE) interface for Dr. Pascal Tyrrell from U of T’s Department of Medical Imaging. She is currently a social director on the Life Science Student Network exec team and a volunteer at U of T’s Agrawal Lab where she helps with Drosophila experiments. She continues to seasonally work as a student camp teacher in the summer.

At the Research Opportunity Program (ROP) fair on March 3rd, U of T ROP students from different departments came together to share their research. A mock-up of the MiNE interface was presented in PowerPoint with the goal of increasing user engagement and encouraging the development of a medical imaging research community. Some features of the interface are presented below.

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MiWORD of the day is… Mop-top!

Ahhh, the mop-top! I sigh not because I miss the hairdo but because I miss my hair – all of it. In the mid-60s this hair style was made famous by The Beatles. Don’t know who they are (shame on you!) have a listen here for instruction.


Well the mop-top was made popular because the 4 guys who sported the hairdo were crazy successful musicians from England. Their recording company, Electrical Musical Industries (EMI), was also very happy and successful because of the overwhelming record sales (music was sold to listeners on vinyl records back then).


So, what does any of this have to do with medical imaging? Lots actually. The money generated by record sales enabled the EMI basic science researchers (another division of the company) to work in a prosperous cash-rich environment. One of those researchers was Sir Godfrey Hounsfield, an electrical and computer engineer. 


In 1967, he started his work on what would soon become the first CT scanner. By directing x-ray beams through the body at 1 degree angles, with a detector rotating in tandem on the other side, he was able to measure the attenuation of x-rays. These values were then analysed using a mathematical algorithm and a computer to yield a 2-D image of the interior of the body. The production of CT scanners by EMI started in the early 1970s and their monopoly ended by 1975 when companies like DISCO (not even kidding) and GE entered the arena.


Interestingly, in the 1960s Dr Allan Cormack of South Africa had also independently showed similar results to Housfield. In the end, Cormack was cited for his math analysis that led to the CT scan and Housfield for its practical development. They shared the Nobel prize in Physics and Medicine in 1979. Cool.

Now for the fun part (see the rules here), using mop-top in a sentence by the end of the day:

Serious: Who would have thought the success of the mop-top Fab Four would be instrumental in the development of the CT scanner?

Less serious: Hey Bob, I went for my head CT scan today and something weird happened. I went in bald and came out with a mop-top! Is that normal?…

Listen to With a Little Help from My Friends from The Beatles to decompress and…

…I’ll see you in the blogosphere.

Pascal Tyrrell


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Causality, Analogy and… Twins?!!!

What a great movie from the eighties. One always thinks of twins as identical or monozygotic. But twins can be dizygotic or fraternal meaning that they develop from two separate eggs and share the same womb. In this case they are more analogous than anything else – as in the movie Twins with Arni and Danny (see the trailer here for a refresher).

In my most recent set of posts I have been talking about Bradford Hill’s criteria for causality – also know as cause and effect (see here for first post). So far we have covered strength, consistency, specificity, temporality, dose-response, plausibility, coherence, and experiment. Today we are going to talk about analogy – the ninth and final criterion.

Again it is an easy one today. Perfect for a Friday. When considering an association for causality one can look for similar relationships and essentially judge by analogy. If causality was shown in similar or analogous evidence to the relationship you’re interested in then this would support your hypothesis. With the effects of acetaminophen (Tylenol) on pain clear to us we would surely be ready to accept similar evidence with another analgesic drug in pain relief.

 
 
Bradford Hill’s criteria wrap-up:

 
None of the nine criteria can bring indisputable evidence for or against your hypothesis of causality and none can be absolutely required. What they can do, with greater or less strength, is to help you decide – is there any other way of explaining the relationship of interest than cause and effect?
 
 
 
 
That’s it! All nine criteria. Now it’s time to try and apply them to a real life example. Let me know how it goes.
 
 
Have a listen to “Ready to Start” by Arcade Fire and…
 
… I’ll see you in the blogosphere.
 
 
Pascal Tyrrell

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MiWORD of the day is… Piezoelectric!

Ah, the super villain Livewire. Not sure she was all that much of a challenge for Superman but there you have it: electricity, spandex, and crazy hair. The perfect foe. I wonder if she will make an appearance in the latest Supergirl TV series?


So, today the MiWORD of the day is piezoelectric. Sounds like a fancy name for a downtown pizzaria – but it’s not. Way back before Roentgen discovered x-rays, Pierre and Jacques Curie in 1877 discovered a phenomenon that occurs when crystals are mechanically distorted by external pressure so that an electrical potential develops between the crystal surfaces: the piezoelectric effect. The term was coined by the brothers from the Greek for “pressure-electricity”. So basically, certain crystals (which include quartz, topaz, tourmaline…) can convert electrical to mechanical energy and vice versa.


Why is this important you ask? Well, because this discovery lead to the development of microphones, earphones, and most importantly for us – ultrasound. Based on the physics of sound and not light, ultrasound captures images by manipulating and analyzing sound waves, very high-frequency sound waves as they bounce off surfaces and echo back to the sender. The idea of getting some kind of image from sound waves was first thought of after the sinking of the Titanic in 1912: detecting submerged icebergs with sound reflection.



A little later, in Austria, two brothers Karl and Friedreich Dussik (do you see a trend here?) transmitted sound waves through a patient’s head in 1937. This and then the development of the SONAR (sound navigation and ranging) in WWII was the ground work needed to launch the field of ultrasonography. It would take, however, 20 years after WWII for ultrasonography to become a commercial reality.







Not only is ultrasound one the oldest medical imaging technologies but it is also an important tool for visualizing soft tissue structures in medical diagnosis, follow up of disease processes and pregnancies. Cool.

 


 


 

 





Now for the fun part (see the rules here), using piezoelectric in a sentence by the end of the day:

Serious: Mom went for her ultrasound today. Told me that I am going to have a little baby sister! She had to wait a while to have her scan because the piezoelectric transducer was on the fritz – again.


Less serious: Hey Bob, do you remember a pizza place on Electric Avenue in Calgary? Piezoelectric something or other? All closed down now. What a shame…



Listen to Electric Avenue from Eddy Grant to decompress and…

…I’ll see you in the blogosphere.

Pascal Tyrrell

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Back to Basics… Midpoint Thoughts from an ROP Student

Reaching new heights? (Source: NYT)

Through the ‘Research Opportunity Program‘ (ROP) for second year students at U of T, I have been working on a project about physicians’ willingness to use MRI as the front-line diagnostic imaging technology for carotid stenosis patients. For a description see here.

After a recent discussion with Dr. Tyrrell (my supervisor), and as I approach the midpoint of my ROP project, I thought it would be a good idea to review some of my background knowledge of carotid stenosis from my work in the Fall term. Having a certain amount of independence while working on this project has been a great experience, but it also means I am responsible for keeping track of my own learning.


So, during the first week of January, I took out my notes, my Physiology textbook, and several articles in order to compile what I have learned so far and highlight areas that need further review.

Review in process!

Begrudgingly, I’ll admit that this ‘self-directed’ review process has shed new light on the usefulness of midterms in other courses. However, I still prefer this project-based review format. It has allowed me to review necessary information to make sure that it is fresh in my mind. Now I feel more prepared to begin the second half of the project. I’m looking forward to a major meeting this month and all the other exciting parts of the project to come.


Julia Robson

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Prison Experiments and Causality? Whoops!

Guard or inmate? Who would you like to be?

In my most recent set of posts I have been talking about Bradford Hill’s criteria for causality (see here for first post). So far we have covered strength, consistency, specificity, temporality, dose-response, plausibility, and coherence. Today we are going to talk about experiment – the eighth criterion. 


This is an easy one (and it’s a Friday… Perfect!). Can the condition of the association of interest be altered (prevented or ameliorated) by an appropriate experimental / semi-experimental regimen? If so, then this would lend support to the notion of causality. 


That’s it. Now consider the infamous Stanford Prison Experiment that has etched its place in history, as a notorious example of the unexpected effects that can occur when psychological experiments into human nature are performed.The experiment was a study of the psychological effects of becoming a prisoner or prison guard. The experiment was conducted at Stanford University on August 14–20, 1971, by a team of researchers led by psychology professor Philip Zimbardo using college students. Needless to say the experiment got out of hand and participants were harmed in the research process. Whoops! Not good.


The Stanford Prison Experiment led to the implementation of rules to preclude any harmful treatment of participants. Before they’re implemented, human studies must now undergo an extensive review by an research ethics board or institutional review board.

 

You may be able to show causality by an experimental regimen but at what cost? Be careful and think about research ethics before you leap into an experiment.

 

Watch the trailer to the movie about the Stanford Prison Experiment to get a better idea of what I am talking about and…


… I’ll see you in the blogosphere!




Pascal Tyrrell

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Coherence, Causality… and Space – Time?

Warp speed ahead!

In my most recent set of posts I have been talking about Bradford Hill’s criteria for causality (see here for first post). So far we have covered strength, consistency, specificity, temporality, dose-response, and plausibility. Today we are going to talk about Coherence – the seventh criterion. 


The association should be compatible with existing theory and knowledge.  In other words, it is necessary to evaluate claims of causality within the context of the current state of knowledge. What concessions do we have to make in order to accept a particular claim of causality? Too much, too little, or just right?









As with the issue of plausibility, research that disagrees with established theory and knowledge are not automatically false.  They may, in fact, force a reconsideration of accepted beliefs and principles.

In his Special Theory of Relativity, Einstein states two postulates:


1- The speed of light (about 300,000,000 meters per second) is the same for all observers, whether or not they’re moving.


2- Anyone moving at a constant speed should observe the same physical laws.


Putting these two ideas together, Einstein realized that space and time are relative — an object in motion actually experiences time at a slower rate than one at rest. Although this may seem absurd to us, we travel incredibly slow when compared to the speed of light, so we don’t notice the hands on our watches ticking slower when we’re running or traveling on an airplane. Scientists have actually proved this phenomenon by sending atomic clocks up with high-speed rocket ships. They returned to Earth slightly behind the clocks on the ground. 


Not convinced? Watch Einstein’s Time is an Illusion for addtitional insight.


Still not convinced? That’s OK. Often fundamental changes to basic concepts of a scientific discipline take time for people to understand and adopt as a belief. This is referred to a paradigm shift. 


Bottom line is that the cause-and-effect interpretation of your data should not seriously conflict with the generally known facts of the base of knowledge in your field of study – but there is wiggle room here!




Watch the movie trailer for Coherence to confuse you even more and…


… I’ll see you in the blogosphere.




Pascal Tyrrell

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Ethics Schmethics?

 

Today, it may seem obvious that the first step of any research project should be to complete a proposal for ethics review. But why do we need ethical standards? While helping to complete an ethics form for a project I’m working on, I wondered if scientists perhaps made more ‘progress’ before ethical considerations became commonplace. Even if this was the case, research is certainly better now, when institutions and procedures protect patients’ and research subjects’ rights. 

It also seems that scientific research in the 18th and 19th centuries tended to be somewhat more haphazard than it is now, and almost certainly less ethical. For example, Dr. Edward Jenner tested his smallpox inoculation hypothesis for the first time on an eight-year-old
boy in 1796, with little preliminary understanding and no certainty that the patient would not be severely harmed.

Scientists were often fairly independent, acting based on their own curiosity to advance knowledge. Fortunately, research standards have evolved significantly since then. Ethics have been a major part of the transition, as ethical standards help to ensure that scientific research does not cause harm to researchers or subjects. The shocking Stanford Prison Experiment, just one example, shows that physical and psychological damage can occur if study participants’ rights are not upheld through ethics. College students with no criminal record were asked to play the role of prisoners and prison guards, the ‘guards’ became brutal and cruel, while the ‘prisoners’ became stressed and depressed. The experiment was terminated early, after only six days.

Fortunately, much has changed since the emergence of modern science in the 20th century. The current structure of research, including working in teams and undergoing peer review, helps to ensure a high standard of practice. Nevertheless, ethical issues in science remain. Researchers who work with human participants can become quite focused on the minutiae of their work, so Research Ethics Boards have an important mediating role. They provide an experienced, unbiased viewpoint that weighs the potential benefits of the research against any harm that may come to participants. Even if an ethical review sometimes slows the pace of scientific progress, it provides an essential foundation and structure for research, to the benefit of participants and researchers alike.  





Julia Robson
2nd year student at U of T
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Plausibility, My Dear Watson!

Or was that “Elementary, my dear Watson”? I always get those confused…


Anyway, in my most recent set of posts I have been talking about Bradford Hill’s criteria for causality (see here for first post). So far we have covered strength, consistency, specificity, temporality, and dose-response. Today we are going to talk about plausibility – the sixth criterion. An easy one at that.


For plausibility to exist we need the association of interest to agree with currently accepted understanding of pathological/ biological/ physical processes. In other words, there needs to be some theoretical basis for the association we are considering. While we hope to avoid spurious associations, at the same time, relationships that disagree with current understanding is not necessarily false; they may, in fact, be a needed challenge to accepted beliefs and principles.


 As Sherlock Holmes advised Dr. Watson, ‘when you have eliminated the impossible, whatever remains, however improbable, must be the truth.’


Next time we will talk about the 7th of nine criteria: coherence.




Don’t remember who Sherlock Holmes is? See the trailer to Robert Downey‘s rendition of Sir Arthur Conan Doyle‘s famous detective here and…




… I’ll see you in the blogosphere,


Pascal Tyrrell