CTSI Seminar Series: When Erythrocyte Biology and Mechanics Collide

RedBloodCells3The CTSI Seminar Series for Spring 2014 continues on Tuesday, April 1st with a presentation by Richard Waugh, PhD and James Palis, MD. Drs. Waugh and Palis will be presenting their research in a seminar entitled “When Erythrocyte Biology and Mechanics Collide.”

(UPDATE: For a recap of the presentation, click here.)

Dr. Palis is a Professor in the Department of Pediatrics, Hematology and Oncology at the Medical Center and Dr. Waugh is Chair and Professor in the Department of Biomedical Engineering on River Campus. Dr. Palis and Dr. Waugh are Co-Principal Investigators on a CTSI Incubator award with Michael Bulger, PhD titled “Extensively Self-Renewing Erythroblasts as an Ex-Vivo Source of Human Blood.” In response to the increased blood transfusion need in the United States, their project will explore ways to artificially generate human blood. Click here to read more about their project.

The theme of the Spring 2014 series is “Crossing Elmwood: River Campus-Medical Center Research Collaborations” and will showcase ongoing research collaborations between the University research community and the Medical Center. The series also aims to stimulate new research teams and areas of investigation capitalizing on the existing strength of faculty and programs. The Organizing Committee for the series includes Robert Holloway, MD, MPH, Peter Lennie, PhD, Rob Clark, PhD, Stephen Dewhurst, PhD, Karl Kieburtz, MD, MPH, David Williams, PhD, Richard Waugh, PhD,  and Joanna Olmsted, PhD.

The series takes place on Tuesdays from 12:15-1:15 pm in the Helen Wood Hall Auditorium. You can access the full schedule here. Lunch is provided. Please provide your own beverage. The University of Rochester School of Medicine and Dentistry designates this live educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

CTSI Education Spotlight: David Paul, ART Student

david paulAs a child, I always dreamed of pursuing a career that would combine my interests in science, engineering, business and the arts. After reading the book, Gifted Hands, by Dr. Ben Carson, a Johns Hopkins, neurosurgeon, I knew that medicine would fulfill my interests and allow me to make a lasting impact on my community. Driven to one-day be a physician, I went on to continue my education at Hope College, in Holland, MI; obtaining a B.S. in chemistry. During my time as an undergraduate, I conducted biophysics research in the laboratory of Dr. Brent P. Kreuger at Hope College and was awarded a Cyberinfrastructure Experiences for Graduate Students (NIH-CIEG) Fellowship to study under Dr. Ross Walker at the San Diego Supercomputer Center – University of California, San Diego.

In 2010, I was accepted into the MD program at the University of Rochester School of Medicine and Dentistry. During my first two years of medical school I became increasingly fascinated with the human brain; wanting to know more about it’s function after injury. This prompted a summer research project within the Departments of Neurosurgery, and Brain and Cognitive Sciences at the University of Rochester; where we used anatomical and functional magnetic resonance imagining to characterize the trajectory of visual recovery and cortical plasticity after surgical tumor resection in patients with pituitary tumors that compress the optic nerves. My background in computational methods and biophysics research prepared me to analyze complex neuroimaging data under the supervision of Drs. Bradford Mahon, PhD and G. Edward Vates, MD PhD.

After spending a summer in Dr. Mahon’s lab and shadowing Dr. Vates, a URMC neurosurgeon, my eyes were opened to the plethora of questions that remain unanswered concerning vision loss in pituitary tumor patients. Funding from the CTSI and support from the Academic Research Track Fellowship, in conjunction with the Academic Honors Program in Medical Neurobiology, provided me with an opportunity to answer these question through a dedicated 2-year research fellowship. This spring I will graduate with a masters in Neurobiology and Anatomy and begin the clinical years of my medical education. I am truly grateful to the CTSI for their support of my dreams.

Seminar Recap – Listening through noise: Search for autism biomarkers

anneluebke

Anne Luebke

loisabennetto

Loisa Bennetto

It’s not easy to see signs of autism in a child who is barely walking and talking.

So while doctors who know what to look for can accurately diagnose an autism spectrum disorder when a child is 18 to 24 months old — allowing treatment to begin at the earliest possible stage — the average diagnosis doesn’t come until a child is 4 years old.  Higher-functioning cases aren’t discovered, on average, until a child is 6.

“In order to improve outcomes, we need to be doing a better job at detecting autism earlier,” said Loisa Bennetto, PhD, principal investigator at the Bennetto Lab at the University of Rochester.  “We need to find ways to do this before the language delays in autism really start to take hold.”

According to research findings from Bennetto and colleague Anne Luebke, PhD, one of the first signs may come from the ears.

Bennetto and Luebke shared their research, which was supported by a PILOT grant from the CTSI, at a March seminar in Helen Wood Hall auditorium.

Research

Past studies have shown that children with autism struggle with visual cues.  Their comprehension of a spoken statement is aided less by seeing the speaker’s face than children without an autism spectrum disorder, and they are slower to react to a verbal description when a person is gesturing to them in addition to speaking.

Bennetto and Luebke wanted to find out if their hearing was different as well.

Their research consisted of a hearing in noise test whereby youngsters with and without autism were asked to identify specific phrases over background babble or non-descript broadband noise.

For both the babble and the broadband test, children with autism scored significantly worse.  Researchers performed a similar test with a sequence of musical notes in broadband noise.  Again, children with autism scored significantly worse.

Moreover, children with autism were shown to have reduced otoacoustic emissions (OAEs) at certain frequencies of sound but not all frequencies.

“We saw robust group differences in OAE amplitudes in speech frequency regions,” said Luebke, an associate professor in biomedical engineering and neurobiology and anatomy who specializes in work on the cochlear efferent feedback pathway.

Implications

One of the important implications of the study is that children with autism are actually doubly disadvantaged when it comes to communicating.

“If people without autism have trouble hearing in background noise, seeing the speaker’s lips allows you to do a better job listening.  Kids with autism don’t have that advantage,” said Bennetto.  “So if they also have trouble with hearing in noise as well, then that’s a double problem for them.”

The hearing in noise language tests that Bennetto and Luebke used on the children would not work for newborns or toddlers, who wouldn’t be able to fulfill the call-and-response required.

However, OAE tests are regularly used to measure the hearing of newborns.  So adapting an OAE test to use as an autism indicator could lead to earlier diagnoses — and more proactive treatment.

Said Bennetto: “It’s something that I think we could easily do for toddlers with autism.”

Symposium Recap: Informed Consent Quandaries and New Approaches

nicholassteneck

Nicholas H. Steneck.

Does a doctor need consent before testing an experimental drug on you?  Accessing your medical records for a health study?  Using excess blood collected during your routine health check for a genetic study?

The answer to all of these questions is no — as long as certain requirements are fulfilled.

“The key issue is identification,” said Nicholas H. Steneck, PhD, director of the research ethics and integrity program of the Michigan Institute for Clinical and Health Research at the University of Michigan.  “So as long as I don’t know who you are, I can use your blood.  And under the right circumstances — if you’re not conscious, and the drug is something that might help you in an emergency setting — I can test that on you.”

But the process of patient consent can bring up a handful of ethical quandaries for patients and physicians alike.  The keynote speaker at the 2014 CTSI Symposium, Steneck provided a brief history of the consent process, and discussed some potentially tricky consent situations that researchers can encounter.

“Current consent systems have serious weaknesses — I don’t think I’m telling anybody anything that they don’t know at this point,” said Steneck.  “It’s an area where there’s lots of interesting work to be done and lots of challenges.”

Quandaries

Informed consent was written into law after many controversial studies came to light in the early-to-mid 20th Century.  Fallout from the studies was so explosive that some have become ingrained in popular culture — an Emmy-award-winning HBO movie was made about the Tuskegee syphilis experiments, while a 1989 Billy Joel single references the “children of thalidomide.”

Though the Common Rule was put in to place in 1981, Steneck also touched on several more contemporary examples, including that of a Columbia University professor who in 2001 attempted to measure customer service responses by sending phony letters to hundreds of New York City restaurants alleging food poisoning.

“Can you imagine what happens if you send a letter to a five-star restaurant in New York City saying you got food poisoning?” said Steneck.  “Columbia University was flooded with ‘We’re going to sue you,’ once they found out.  Never a clue on the part of this researcher that he had to get informed consent on that.”

But most breaches aren’t quite so egregious.  Many stem from well-meaning attempts to provide information that isn’t properly understood by subjects.  Consent forms that use overly complicated language are a common culprit.

“How can you turn out a 20-page form written in 12th grade language and say with a straight face ‘We are providing informed consent to our subjects,’” said Steneck.  “It’s a quandary because there are reasons why those forms are that long.  There are reasons you have to include that much information.  What do we do about that?”

Possible approaches

The simplest fix is to improve an informed consent form’s readability.  Creating a consent form that is encompassing yet readable can be a challenge, but using simpler language — less challenging vocabulary words and shorter sentences — can measurably improve understanding.

Steneck showed one consent form that began with a checklist which covered all of the necessary elements.  At the top, it covered the IRB approval, and followed that with the elements of consent, HIPAA notices, options, and record.  Each section was clearly laid out, and every element fit on one page.

Accompanying the one-page consent form in Steneck’s example was an information pamphlet explaining the study, and showing a visual representation of a BioLibrary, which likened it to a traditional library.

A study conducted by Steneck’s team showed that separating these two steps can create a high level of understanding — 89 percent of participants scored perfectly when asked about their level of comprehension.

“The idea here is we do the informing process separate from the consenting process,” said Steneck.  “But it’s a change.  The process of moving the understanding outside the consent form, I understand is a risky one.  It’s a risky one for the people who are responsible for assuring that we’re following the Common Rule.”

Under current conditions, this type of separation isn’t ideal.  A participant could potentially file a lawsuit and claim that they never received the informational pamphlet.

It’s here where an electronic consent form could potentially bridge the gap, but that can create other obstacles, such as added costs, privacy concerns and logistical issues such as the need to sterilize an iPad every time a new participant uses it.

Regardless, the informed consent process needs to be improved, said Steneck.

“As in all areas, researchers need to get on top of this, administrators need to get on top of this, before somebody else gets on top of it and tells us what we have to do,” he said.

*

The 2014 CTSI Symposium, which took place on March 13, was titled “Ethics in Research: Consent Quandaries,” and was hosted by Dr. Carl T. D’Angio, Professor of Pediatrics and Medical Humanities & Bioethics at the School of Medicine and Dentistry.  To view the Symposium in its entirety, click here.

CTSI Seminar Series: Listening through noise: Search for Autism biomarkers

Autism_Awareness_RibbonThe CTSI Seminar Series for Spring 2014 continues on Tuesday, March 25th with a presentation by Anne Luebke, PhD and Loisa Bennetto, PhD. Drs. Luebke and Bennetto will be presenting their research in a seminar entitled “Listening through noise: Search for Autism biomarkers.” Dr. Luebke is an Associate Professor in the Departments of Biomedical Engineering and Neurobiology and Anatomy at the Medical Center. Dr. Bennetto is Chair and Associate Professor in the Department of Psychology on River Campus. The research done in the Bennetto Lab is broadly directed at examining the neurocognitive bases of developmental disabilities, with the ultimate goal of understanding how atypical neurocognitive development relates to deficits in social-communication functioning as well as everyday difficulties with adaptive functioning. The goal of the Luebke lab is to understand the role of cochlear outer hair cells in hearing and hearing loss both at the molecular and at the systems level. Specifically, they are interested in agents that block or enhance the action of receptors on outer hair cells of the cochlea, which enhance hearing and decrease hearing loss.

The theme of the Spring 2014 series is “Crossing Elmwood: River Campus-Medical Center Research Collaborations” and will showcase ongoing research collaborations between the University research community and the Medical Center. The series also aims to stimulate new research teams and areas of investigation capitalizing on the existing strength of faculty and programs. The Organizing Committee for the series includes Robert Holloway, MD, MPH, Peter Lennie, PhD, Rob Clark, PhD, Stephen Dewhurst, PhD, Karl Kieburtz, MD, MPH, David Williams, PhD, Richard Waugh, PhD,  and Joanna Olmsted, PhD.

The series takes place on Tuesdays from 12:15-1:15 pm in the Helen Wood Hall Auditorium. You can access the full schedule here. Lunch is provided. Please provide your own beverage. The University of Rochester School of Medicine and Dentistry designates this live educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Symposium Recap: Informed Consent in Community Participatory Research

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Cindi Lewis

Not only were researchers selling the blood of study participants to Satanists, but they were using the profits to buy new vehicles, which they’d brazenly drive to follow-up visits.

At least, that was the rumor going around at some trial sites of the HIV prevention trials network, an example taken from Woodsong and Karim 2005 American Journal of Public Health publication.

“We kind of laugh at it now, but it was serious,” said Cindi Lewis, a PhD candidate in the CTSI’s Translational Biomedical Science Program. “The people really thought that ‘blood money’ was somehow involved here, and they were superstitious about it, and they were not going to participate.”

While researchers regularly spend time educating participants on the front end of their studies, informed consent can be a moving target which requires regular follow-up throughout the duration of a trial. That’s especially true when dealing with communities that may be less developed, less educated, or more vulnerable — communities wherein rumors or distrust may spread more readily among participants.

Speaking at the 2014 CTSI Symposium, Lewis outlined a continuum of strategies that researchers can employ to ensure that study participants are giving fully informed consent throughout the duration of a study, which can help prevent rumors like the one mentioned above from spreading.

“Typically, people sometimes like to think about the informed consent as a fixed point in time when you bring people in, and then the trial goes on,” said Lewis. “But it’s really a dynamic process.”

Pre-enrollment

Lewis, who has worked on several research projects centered on HIV trials, spoke about the informed consent process in three phases: pre-study enrollment, enrollment, and the continuation of the study, as based on Woodsong and Karim’s proposed framework to improve informed consent in target communities.

During the pre-enrollment process, it’s vital for researchers to observe and interact with the community that they are going to be studying. This means spending time at community gatherings, such as town hall meetings or church services.

If possible, the researcher should attempt to form a partnership with individuals or groups that are already working to provide services to their community. By doing so, a researcher can form a community advisory board that truly has its finger on the pulse of the population.

“Sometimes when we look at the composition of community advisory boards, they’re not truly representative of our population,” said Lewis. “This is where, in the beginning, selecting an adequately representative community advisory board — people who are really connected to the community and are going to hear these rumors, these things that aren’t on the surface — is very important.”

An informed community advisory board can provide valuable insight into community response as the study progresses. It can also help researchers understand what suspicions may be inherent within a community from the outset, especially as the team moves into the second phase.

Enrollment

Though researchers need to be careful about satisfying the requirements set by the federal government and internal review boards, a creative approach to the informed consent process can help.

Lewis highlighted an example from the Carraguard Microbicide trial held in South Africa in which the research team created an image of a study participant that they named “Serena.” In early mockups, she was wearing a bandana, but as they moved through the pre-enrollment phase and learned more about their community, Serena evolved into a woman with long, curly hair. The image was meant to depict a community member and to make potential participants feel more at ease with the notion of joining the study.

Additionally, one piece of study documentation featured a visual representation of the concept of randomization, which featured a mixed group of people with pair of dice in the foreground. This helped to get the concept across to a population that may have struggled with the clinical definition.

The enrollment phase is also a good time to be proactive about addressing misconceptions — which could serve to cloud the minds of participants as the study progresses and effectively negate informed consent.

In the HIV vaccine trial group led by URMC’s Dr. Michael Keefer, Lewis is working with the group to develop materials that clearly depict key vaccine messages in the hopes of improving trial participants’ understanding of the information provided to them. For example, the fact that HIV and AIDS cannot be contracted through a vaccine — a common misconception — needs to be well-emphasized.

Continuation of study

Throughout the study period, researchers need to follow-up with the community to ensure that they remember what the study is about to begin with.

“Maybe they have an understanding right at the point where they come in to the trial,” said Lewis. “But if the trial goes on for 2 years, and I ask you 6 months down the road to tell me something about this trial and you knew nothing, but you’re still enrolled in the trial, can we really say, ethically, that this person is informed?”

Proactive efforts and steady follow-ups can help keep the participants informed. They can’t, however, prevent the emergence of every piece of misinformation. In the example referenced earlier, researchers had to work quickly to dispel the notion that they were selling the collected blood to Satanists, even limiting the amount they used the vehicles that they’d supposedly purchased with the “blood money.”

But through a concerted effort — which starts in the pre-enrollment period and continues through the end of the study and beyond — researchers can get a handle on rumors like this one, helping to ensure that their study participants are truly informed.

*

The 2014 CTSI Symposium, which took place on March 13, was titled “Ethics in Research: Consent Quandaries,” and was hosted by Dr. Carl T. D’Angio, Professor of Pediatrics and Medical Humanities & Bioethics at the School of Medicine and Dentistry.  To view the Symposium in its entirety, click here.

CTSI Seminar Series: Progress toward noninvasive vision correction

knox huxlinThe CTSI Seminar Series for Spring 2014 continues on Tuesday, March 18th with a presentation by Krysten Huxlin, PhD and Wayne Knox, PhD. Drs. Huxlin and Knox will be presenting their research in a seminar entitled “Progress toward noninvasive vision correction.” Dr. Huxlin is Professor in the Departments of Ophthalmology, Neurobiology & Anatomy, Brian & Cognitive Sciences and the Center for Visual Science. Dr. Knox is the Associate Dean of Education and New Initiatives and Professor in the Departments of Optics and Physics and Visual Sciences. Click here to learn more about their research collaboration.

The theme of the Spring 2014 series is “Crossing Elmwood: River Campus-Medical Center Research Collaborations” and will showcase ongoing research collaborations between the University research community and the Medical Center. The series also aims to stimulate new research teams and areas of investigation capitalizing on the existing strength of faculty and programs. The Organizing Committee for the series includes Robert Holloway, MD, MPH, Peter Lennie, PhD, Rob Clark, PhD, Stephen Dewhurst, PhD, Karl Kieburtz, MD, MPH, David Williams, PhD, Richard Waugh, PhD,  and Joanna Olmsted, PhD.

The series takes place on Tuesdays from 12:15-1:15 pm in the Helen Wood Hall Auditorium. You can access the full schedule here. Lunch is provided. Please provide your own beverage. The University of Rochester School of Medicine and Dentistry designates this live educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.