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March 31, 2016

Research Notes

Pittsburgh Health Data Alliance sets first projects

In an effort to solve some of health care’s toughest challenges through the innovative use of technology, UPMC Enterprises will fund the first six projects created under the Pittsburgh Health Data Alliance.

With this funding, Pitt and Carnegie Mellon University (CMU) researchers will develop technologies aimed at reducing patient falls, preventing and monitoring pressure ulcers, improving the accuracy of cancer diagnoses and providing personalized treatment recommendations, among other benefits. The funding will total more than $3 million over the next six months, as the commercial potential of these products is explored further.

The first-funded projects are being developed by the Center for Commercial Applications of Healthcare Data (CCA), led by Michael Becich, chair of the Department of Biomedical Informatics in the School of Medicine, and the Alliance’s CMU-led Center for Machine Learning and Health (CMLH).

Announced last year, the Pittsburgh Health Data Alliance will focus on building new companies that create data-intensive software and services.

The first CMLH project is the Clinical Genomics Modeling Platform, an engine for building precision-medicine models for various diseases and populations. Triage algorithms, for instance, might help to determine if patients with a certain disease should be sent home with monitoring or sent to the intensive care unit. It will be led by two CMU faculty.

The funded CCA projects are:

• MEDIvate, a patient-centered smartphone application that will make it easy for patients to update and share medication lists. Current medications will be added directly to the application from the provider’s electronic medical record or by the patient, ensuring accuracy and reducing medication errors. MEDIvate, led by Philip Empey and James Coons, faculty members in the School of Pharmacy, also will be a personal medication coach, reminding patients to take medications and linking them to key facts and educational videos on demand from pharmacists.

• The Tumor-specific Driver Identification (TDI) System, software that will provide personalized genomic information to cancer clinicians about the genetic drivers of an individual patient’s tumors. Tumor-specific algorithms will be used for real-time mining of genetic “big data” that will enable personalized treatments for cancer patients. TDI also is expected to lead to the discovery of new cancer drivers and may be used by pharmaceutical companies to identify novel drugs. Investigators on this project are Xinghua Lu and Gregory Cooper, biomedical informatics faculty members.

• Fall Sentinel, an automated system that will make it possible for clinical pharmacists to
continuously monitor patients in nursing homes, especially for potential drug-drug interactions that might lead to falls. Nursing home falls are one of the most common and dangerous events for patients, with treatment costing the nation’s health system more than $4 billion each year. The project is led by biomedical informatics faculty member Richard D. Boyce.

• PUMP, aimed at reducing hospital-acquired pressure ulcers, which affect an estimated 3 million patients annually. The monitoring and alert solutions, using wearable devices and hospital bed sensors, will provide real-time documentation of patient repositioning and a process to improve compliance with these preventative measures. J. Peter Rubin, UPMC Professor and Chair of Plastic Surgery, is spearheading this effort.

• ComPACD, or Computational Pathology for Accurate Cancer Diagnosis. This software will aid pathologists in delivering more accurate diagnoses from complex tumor images. Initially, the focus is on breast cancer, where misdiagnosis rates for certain cancers often lead to deadly progression of the disease. The principal investigators are Chakra Chennubhotla and D. Lansing Taylor, faculty members in the School of Medicine’s Department of Computational and Systems Biology.
Based on project results, UPMC Enterprises may provide additional funding and development help in the future.

Social media use linked to depression

The more time young adults use social media, the more likely they are to be depressed, according to research from the School of Medicine.

The findings could guide clinical and public health interventions to tackle depression, forecast to become the leading cause of disability in high-income countries by 2030. The research is published in Depression and Anxiety.

This large, nationally representative study examined associations between use of a broad range of social media outlets and depression. Previous studies on the subject have yielded mixed results, been limited by small or localized samples and focused primarily on one specific social media platform, rather than the broad range often used by young adults.

Said senior author Brian A. Primack, director of the Center for Research on Media, Technology and Health: “Because social media has become such an integrated component of human interaction, it is important for clinicians interacting with young adults to recognize the balance to be struck in encouraging potential positive use, while redirecting from problematic use.”

In 2014, Primack and his colleagues sampled 1,787 U.S. adults ages 19-32, using questionnaires to determine social media use and an established depression assessment tool.

The questionnaires asked about the 11 most popular social media platforms at the time: Facebook, YouTube, Twitter, Google Plus, Instagram, Snapchat, Reddit, Tumblr, Pinterest, Vine and LinkedIn.

On average the participants used social media a total of 61 minutes per day and visited various social media accounts 30 times per week. More than a quarter of the participants were classified as having “high” indicators of depression.

There were significant and linear associations between social media use and depression whether social media use was measured in terms of total time spent or frequency of visits. For example, compared with those who checked least frequently, participants who reported most frequently checking social media throughout the week had 2.7 times the likelihood of depression. Similarly, compared to peers who spent less time on social media, participants who spent the most total time on social media throughout the day had 1.7 times the risk of depression. The researchers controlled for other factors that may contribute to depression, including age, sex, race, ethnicity, relationship status, living situation, household income and education level.

Lead author Lui yi Lin, who will be graduating from the School of Medicine this spring, emphasized that, because this was a cross-sectional study, it does not disentangle cause and effect.

Said Lin: “It may be that people who already are depressed are turning to social media to fill a void.” Conversely, exposure to social media also may cause depression, which could then in turn fuel more use of social media. For example:

• Exposure to highly idealized representations of peers on social media elicits feelings of envy and the distorted belief that others lead happier, more successful lives.

• Engaging in activities of little meaning on social media may give a feeling of “time wasted” that negatively influences mood.

• Social media use could be fueling “Internet addiction,” a proposed psychiatric condition closely associated with depression.

• Spending more time on social media may increase the risk of exposure to cyberbullying or other similar negative interactions, which can cause feelings of depression.

In addition to encouraging clinicians to ask about social media use among people who are depressed, the findings could be used as a basis for public health interventions leveraging social media. Some social media platforms already have made forays into such preventative measures. For example, when a person searches the blog site Tumblr for tags indicative of a mental health crisis — such as “depressed,” “suicidal” or “hopeless” — they are redirected to a message that begins with “Everything OK?” and provided with links to resources. Similarly, a year ago Facebook tested a feature that allows friends to anonymously report worrisome posts. The posters would then receive pop-up messages voicing concern and encouraging them to speak with a friend or helpline.

“Our hope is that continued research will allow such efforts to be refined so that they better reach those in need,” said Primack, who also is assistant vice chancellor for health and society for the Schools of the Health Sciences and a faculty member in medicine. “All social media exposures are not the same. Future studies should examine whether there may be different risks for depression depending on whether the social media interactions people have tend to be more active vs. passive or whether they tend to be more confrontational vs. supportive. This would help us develop more fine-grained recommendations around social media use.”

Additional Pitt authors of the study were Jaime E. Sidani, Ariel Shensa, Ana Radovic, Elizabeth Miller, Jason B. Colditz, Beth Hoffman and Leila M. Giles.

This research was funded by the National Institutes of Health (NIH) and National Cancer Institute (NCI).

Seed grants fund student research participation

The external advisory committee of the Mascaro Center for Sustainable Innovation (MCSI) has awarded four faculty members research seed grants totaling $190,630 for the 2016 academic year. The annual program enables faculty to supplement sustainably focused research with undergraduate, graduate and/or post-doctoral student support.

The recipients are:

• “Pollination in the City: Designing Urban Pollinator Gardens That Are Resilient to Air Pollution” — Tia-Lynn Ashman, faculty member in evolutionary ecology, Department of Biological Sciences, Dietrich School of Arts and Sciences.

• “ß-Ga2O3 Nanoelectronics: A Path to a Sustainable Semiconductor Technology for High Efficiency Electricity Conversion From Renewables” — William Stanchina, faculty member in electrical and computer engineering, Swanson School of Engineering.

• “Desalination of Sequestration and Release of Water in Poly Crystals” — Sachin Velankar, faculty member in chemical and petroleum engineering, Swanson school.

• “A Novel Process for Efficient, Decentralized Ammonia Synthesis: Towards Fertilizer Production With Drastically Reduced Environmental Footprint” — Götz Veser, faculty member in chemical and petroleum engineering, Swanson school.

MCSI developed the research seed grant program to provide faculty with funding that would allow students to participate in high-quality research, teaching, outreach and creative endeavors. The goals of the grants are to provide seed funding to develop ideas leading to external funding; support scholarship in areas where external funding is extremely limited; introduce curricular innovations into the classroom; or encourage community outreach and education.

NCI outstanding investigator named

Patrick Moore, faculty member in the School of Medicine’s Department of Microbiology and Medical Genetics, has received NCI’s Outstanding Investigator Award, including $6.4 million to further his work into the link between viruses and cancer. This NCI grant provides seven years of secured support, giving the investigator freedom from the pressure of ongoing grant competitions.

Moore is the second researcher at the University of Pittsburgh Cancer Institute (UPCI) to receive this recognition.

He is leader of the UPCI cancer virology program, holding The Pittsburgh Foundation Chair in Innovative Cancer Research. With his research partner and wife, Yuan Chang, Moore has identified two different viruses that cause Kaposi sarcoma and Merkel cell carcinoma.

The award will fund Moore’s research in three key areas:

• Understanding the mechanism by which the virus that causes Merkel cell carcinoma turns normal cells into cancer.

• Investigating unusual ways that the virus causing Kaposi sarcoma makes oncoproteins.

• Identifying new ways to find viruses that cause cancer in humans.

Recently, the Moore-Chang lab found a new mechanism that cancer viruses use to regulate how cells translate RNA into proteins and developed an assay to discover a class of viruses called polyomaviruses.

Said Moore: “I am hopeful this research will help provide new insights into methods to reliably determine the role of viruses in human cancers and to uncover new common cancer pathways that are at work in both infectious and noninfectious tumors.”

Pregnancy, heart disease study funded

Researchers at Magee-Womens Research Institute (MWRI) were awarded a four-year $3.7 million grant from the American Heart Association (AHA) Go Red for Women Research Network to examine whether certain pregnancy-related blood vessel changes can uncover mechanisms of later-life cardiovascular disease (CVD) in women, identify women at highest risk and guide new interventions to help them.

The causes of heart disease, which damages the inner walls of the blood vessels and can lead to spasms and decrease blood flow to the heart muscle, known as microvascular dysfunction, are unclear, noted principal investigator Carl Hubel, faculty member in obstetrics, gynecology and reproductive sciences in the School of Medicine and MWRI investigator. During pregnancy, profound metabolic and cardiovascular changes occur, putting extra stress on a woman’s body and requiring the heart and blood vessels to work harder. Researchers believe that studying these cardiovascular changes may reveal early mechanisms of CVD.

Said Hubel: “This grant is an important next step for our research team in the ongoing assessment of using pregnancy as a lens to understand CVD in women throughout the life span. Microvascular dysfunction is a devastating public health challenge because almost two-thirds of women who die suddenly of coronary heart disease have had no previous symptoms. We hope to build on the research of our previous studies by identifying mechanisms of CVD in women that are unmasked or perhaps affected by adverse pregnancy outcomes. By examining these relationships, we aim to discover early heart disease risks in women as well as the causes.”

Four other centers make up the AHA Go Red for Women Research Network with Magee: Johns Hopkins University School of Medicine; Columbia University Medical Center; University of California-San Diego; and New York University Medical Center.

Anxiety disengages  prefrontal cortex

For some people, anxiety is just a bad, passing feeling, but for others, anxiety rules their day-to-day lives, even taking over the decisions they make.
Pitt researchers have discovered a mechanism for how anxiety may disrupt decision making. In the Journal of Neuroscience,they report that anxiety disengages a region of the brain called the prefrontal cortex (PFC), which is critical for flexible decision making. By monitoring the activity of neurons in the PFC while anxious rats had to make decisions about how to get a reward, the scientists observed that anxiety leads to bad decisions when there are conflicting distractors present and that bad decisions under anxiety involve numbing of PFC neurons.

The data indicates that anxiety has a selective effect on neuronal activity that supports decision making, says Bita Moghaddam, the lead author of the study and a faculty member in the Dietrich School of Arts and Sciences’ Department of Neuroscience. Up to now, scientists mostly have studied anxiety in animal models in the context of fear and measured how brain cells react to a threatening situation. But human anxiety is devastating because it can interfere with nearly all aspects of daily life including decision making, Moghaddam says.

Pitt researchers studied this aspect of anxiety by monitoring the activity of a large number of neurons as rats made decisions about which choice was most optimal for receiving a reward. The researchers compared behavior and neuronal activity in two groups: one group that had a placebo injection and another that got a low dose of an anxiety-inducing drug.

As with many people who suffer from anxiety but go through day-to-day life and make decisions, the anxious rats completed the decision-making task and, actually, did not do too badly. But they made far more mistakes when the correct choice involved ignoring distracting information.

“We have had a simplistic approach to studying and treating anxiety. We have equated it with fear and have mostly assumed that it over-engages entire brain circuits. But this study shows that anxiety disengages brain cells in a highly specialized manner,” Moghaddam says.

Perhaps, down the line, this better understanding of the brain mechanics behind anxiety and decision making, she says, could lead to better treatment of anxiety in people and, subsequently, better outcomes in the treatment of psychiatric disorders.

Small shift boosts college access

In 2007, the College Board — the nonprofit corporation that administers the SAT — instituted a new score-sending policy intent on increasing college applications and improving college matches for low-income students. The new policy doubled the number of courtesy SAT score reports from four to eight and allowed the reports to be used at any time during the test taker’s high school career.

The ability to forward additional reports to college admissions offices produced significant ripple effects for thousands of low-income students, says a recent analysis produced by researchers at the School of Education, with colleagues from Harvard University and the College Board.

Said Lindsay C. Page, a lead researcher on the analysis as well as research methodology faculty member in the School of Education and a research scientist in the Learning Research and Development Center: “SAT score sending is a subtle but key component of the college application process that is often underappreciated. Limited score sending translates into fewer, or fewer successful, college applications. In turn, this decreases the likelihood of prospective students being admitted to a college that represents a sound match for their academic qualifications, which has a profound impact on their chances of postsecondary success.”

The analysis focused on test takers who took the SAT between 2007 and 2009 and then followed their collegiate progress through the 2014-15 academic year. The researchers found that in the years following the policy change, low-income students were 10 percent more likely to send at least eight score reports to college admissions offices. The likelihood of a student enrolling in college in the fall semester after high school graduation grew by nearly 5 percent. The change also contributed to the up-to-3 percent increase of low-income students earning a bachelor’s degree. Additionally, the researchers found that the policy change increased the likelihood that a lower-income student with a higher SAT score generally will apply to more selective institutions.

With these findings, the analysis contributes to a growing body of national education literature that shows that small interventions in the application process can shift postsecondary outcomes for lower-income students. Collectively, said Page, the analysis results prove that small steps add up to postsecondary access and success.
“Given the low cost and subtle nature of the policy change itself, impacts of this magnitude were surprising,” said Page. “Our findings reveal that the less-than-optimal aspects of the college-selection process for low-income students can be partially remedied with relatively small nudges and tweaks.”

To investigate the policy shift’s outcomes, the researchers focused their analysis on whether the additional score reports increased three factors: the volume of score sending; college attendance; and college completion. The team used a differences-in-differences analytic estimation strategy to investigate the policy’s impact on the three factors. The strategy measured the change outcomes for lower-income students before and after the introduction of the enhanced score-sending policy and compared this change to that occurring among other student economic demographic groups.

In the analysis, the term “low-income students” refers to test takers who were eligible for the College Board’s SAT fee-waiver program. To qualify for the program, test takers or their guardians must have met predefined income guidelines or other special circumstances specified by the national school lunch program. The majority of students using SAT fee waivers belonged to traditionally underrepresented communities.

The analysis relied on data held by the College Board, including SAT scores as well as gender and racial demographic information. This information was merged with college attendance records — whether and where students enrolled in college — from the National Student Clearinghouse.

Autoimmune disease linked to gut imbalance

An imbalance in the reciprocal relationship between common gut bacteria and certain immune cells can set the stage for the development of autoimmune inflammation, according to a study conducted by researchers at the School of Medicine and Children’s Hospital, who published their findings in Immunity.

Scientists have known bacteria and other microorganisms, or microbiota, drive the development of the immune system in the intestine, noted senior investigator Jay Kolls, pediatrics faculty member in medicine and director of the Richard King Mellon Foundation Institute for Pediatric Research at Children’s Hospital.

In particular, segmented filamentous bacteria (SFB) play a critical role in the production of T-helper (Th) immune cells that make interleukin-17, which is a signaling molecule that promotes inflammation. According to the researchers, these Th17 immune responses have been implicated in many human autoimmune diseases, including arthritis, multiple sclerosis and inflammatory bowel diseases.

Said Kolls: “Because many infectious agents are introduced into the body through the intestine and certain bacteria are essential for proper intestinal function, there is intense interest in understanding the role of the gut microbiome in health and disease. Our study demonstrated these Th17 cells in turn control the gut’s SFB burden, and disruptions in the balance between them can have important consequences.”

For the study, the team engineered mice lacking the receptor for IL-17 in cells of the gastrointestinal tract, preventing the molecule from binding to the cells and blocking IL-17 signaling. That led to an overgrowth of SFB in the gut. Further testing showed that the absence of IL-17 signaling triggered other intestinal immune defects, creating an environment in which IL-17 could cause intestinal inflammation.

“These results show us the yin-yang relationship between SFB and Th17 cells,” Kolls said. “As SFB goes up, more Th17 cells are produced to hold the bacteria in check. Without the influence of IL-17 signaling, SFB overgrows. These findings could have a tremendous impact on our understanding of how intestinal and autoimmune disorders develop, and also could point us to new ways to treat these diseases.”

The Pitt team included Pawan Kumar, Leticia Monin, Patricia Castillo, Waleed Elsegeiny, William Horne, Taylor Eddens, Amit Vikram, Misty Good, Kyle Bibby and Ronald C. Montelaro. Colleagues from the University of North Carolina-Chapel Hill and Albany Medical College also contributed.

The project was funded by NIH and Children’s Hospital.

2 get oncology research awards

School of Nursing faculty member Grace Campbell and postdoctoral fellow Marci Nilsen have received research career development awards from the Oncology Nursing Society Foundation. These awards support oncology research training and mentorship of recent PhD graduates to best position them for research careers.

Campbell, who earned her PhD at Pitt in 2013, was awarded the grant for her proposal “Quantifying the Functional Impact of Neurotoxic Chemotherapy: Automated Gait Assessment.” She plans to use a Microsoft Kinect camera to explore gait and mobility changes during and after neurotoxic chemotherapy. For this work, Campbell will be mentored by Marjorie A. Skubic of the University of Missouri Schools of Engineering and Computer Science.

Nilsen, a 2013 PhD nursing graduate, will be mentored by Heidi Donovan, Pitt nursing faculty member, and Jonas T. Johnson, the Dr. Eugene N. Myers Professor and Chairman of the Department of Otolaryngology in the School of Medicine. Her project is “Promoting Communication and Symptom Management of Persons With Head and Neck Cancer and Caregivers.” The goals of this research program are to identify long-term survivorship needs and design a behavioral intervention to promote communication and symptom management on the part of such cancer patients and their family caregivers.

Pitt analyzes rise in state overdoses

Drug-overdose deaths in Pennsylvania increased 14-fold in the last 35 years, with rates climbing especially fast in relatively young white women, according to researchers from the Graduate School of Public Health.

The analysis is the first to examine in detail accidental overdose deaths over time in Pennsylvania and suggests potential targets for public health intervention and law enforcement efforts. It was published in PLOS ONE.

Said co-author Donald S. Burke, dean and UPMC-Jonas Salk Chair of Global Health: “Our latest analysis reveals that drug overdoses are the biggest problem facing our nation in terms of years of life lost — more than car crashes or cancer or HIV — and we as a society need to work together  to solve it.”

Pennsylvania ranks in the top 20 states for overdose mortality, the leading cause of accidental death in the U.S.

Using the Mortality and Population Data System, a repository and retrieval system for detailed death data from the National Center for Health Statistics housed at Pitt, the researchers broke down 1979-2014 overdose deaths in Pennsylvania by sex, age and race. The team started with 1979 because changes in reporting cause of death make it impossible to make comparisons with previous years. The most recent year for which data are available is 2014.

Overdose deaths were concentrated around the counties of southwestern Pennsylvania, those surrounding Philadelphia and those in northeast Pennsylvania near Scranton. Philadelphia County leads, but Allegheny County is close behind with rates rapidly increasing since the mid-1990s.

The age group of 35-44 had the greatest increase in rate of overdose deaths, growing almost 22-fold since 1979, but the 25-34 age group seems to be overtaking the older group, with the highest overdose death rate in 2014.

The overdose death rate for white men peaks between ages 25 and 44; for black men, it peaks between ages 45 and 65, indicating different racial patterns in drug use. A national survey showed higher prevalence of cocaine and nonmedical painkiller use among white adults, compared with a higher prevalence of crack cocaine use among black adults. Also, a study of heroin use among patients entering substance abuse treatment centers indicates a shift to predominantly white users in the last 50 years.

Accidental overdose rates are higher in men than in women; however, women saw a more dramatic increase, particularly from 2010 to 2014. High overdose death rates for women also spanned a longer age range of 25-54 for white women and 35-64 for black women, compared to the U.S. average peak in ages 45-54.

Said lead author Lauren C. Balmert, a graduate student researcher in the Department of Biostatistics: “This seems to indicate a more prolonged period of concern for overdoses in Pennsylvania women. Previous research has shown that women are more prone to having accelerated progression from their first drug use to substance abuse and often enter into treatment programs with more severe dependence than men.”

Compounding matters, most women who enter substance abuse treatment programs also are responsible for children and tend to be more reliant on public insurance, factors that the researchers say could affect a woman’s decision to enter or remain in a drug rehabilitation program.

Said co-author Jeanine M. Buchanich, deputy director of the Center for Occupational Biostatistics and Epidemiology: “Many of these findings are applicable to other states as well. Our county-level findings provide possible avenues for targeting interventions to areas and people with the highest drug overdose mortality.”

Other contributors were senior author Gary M. Marsh, public health; co-authors Janice L. Pringle, pharmacy; and a member of the Allegheny County Office of the Medical Examiner.

The research was supported by Pitt.

—Compiled by Marty Levine



The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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