University Times

UCIS awarded two GPA grants

The global studies and African studies programs in Pitt’s University Center for International Studies recently received grants from the U.S. Department of Education’s Fulbright-Hays Group Project Abroad (GPA) program.

The global studies program received $85,130 for “Understanding Islam, Through the Egyptian Lens,” which will provide the opportunity for secondary school teachers from Pennsylvania, Ohio and West Virginia to travel to Aswan, Luxor, Alexandria and Cairo to develop curricula related to Africa, Middle East and Islamic studies. Participants will learn through lectures, meetings with educators and community groups, site visits and historical tours about the influence of religion and the impact of the movement of people, colonization and globalization from ancient to contemporary Egypt.

The project will enhance Middle Eastern, African and Islamic studies content in social studies and humanities curricula at the secondary level, establish institutional and peer contacts for continued dialogue and distance-education opportunities and add to Arabic language and area studies instructional resources.

Curricula created by group participants and relevant to Pennsylvania and Ohio secondary education standards will be presented during teacher workshops held throughout 2010 and posted on the global studies web site.

The African studies program received $77,624 for “Summer Curriculum Development Project in Ghana,” which is part of the program’s agenda to promote African studies in the curriculum of K-12 schools in Pittsburgh and surrounding areas. Fourteen teachers and administrators from South Hills school districts will participate in field trips and cultural activities in Ghana and attend lectures on African topics at the University of Ghana.

Following the trip, workshops will be offered to complete curriculum modules and evaluation activities. The modules will be shared online through the African studies web site.

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Biz prof receives funds for conflict research

Laurie Kirsch, professor of business administration in the Katz Graduate School of Business, recently received a National Science Foundation award to explore the triggers of intergroup conflict, or “faultlines,” among stakeholders engaged in cyberinfrastructure projects.

The three-year project, “Collaborative Research: Identifying Faultlines, Circumventing Faultline Eruptions and Mitigating the Effects of Faultlines,” funded by a grant worth approximately $300,000, will study projects being developed by the Global Environment for Network Innovations (GENI), a virtual laboratory for developing experimental infrastructure for computer scientists and network engineers to carry out their experiments.

Kirsch said, “The management of large-scale information technology development projects is challenging, in large part because of their sheer scale, scope and complexity. As a result, this research could have broad application. Understanding how conflict can be anticipated, avoided or mitigated has the potential to positively impact project stakeholders as well as the broader society, which is the ultimate beneficiary of the innovations that GENI may stimulate.”

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UPCI launches breast & ovarian cancer drug trial

The University of Pittsburgh Cancer Institute (UPCI) will be the primary site for a clinical trial of a drug that has been proven in combination treatments to make cancer cells more sensitive to chemotherapy. The new trial will, for the first time, examine the drug ABT-888 as a single agent.

The study primarily will be open to breast and ovarian cancer patients with a BRCA 1 or 2 genetic mutation, but patients with other subtypes of breast, ovarian or prostate cancer may be eligible.

According to the study’s principal investigator, Shannon Puhalla, professor of medicine in the School of Medicine and breast oncologist in the Magee-Womens cancer program, ABT-888 targets the polymerase (PARP) family of enzymes responsible for a wide variety of cellular processes in cancer cells. “Cancer cells have been shown to have increased levels of PARP, which we believe causes resistance to chemotherapies and other cancer treatments,” said Puhalla.

Tumor cells in patients with BRCA mutations are particularly reliant on the mechanism of DNA repair that is inhibited by PARP, she said.

In previous trials in which ABT-888 was used as combination treatment, it appeared to inhibit PARP, making cancer cells more sensitive to chemotherapy. “Our hope with this trial is that patients with BRCA mutations or certain other breast or ovarian cancers may respond to ABT-888 as a single agent,” said Puhalla.

Study co-investigator Merrill Egorin, professor of medicine and pharmacology, said, “This drug is also intriguing because breast cancer patients with BRCA mutations who have exhausted all other therapeutic options may have another treatment to turn to. Other trials also have suggested that ABT-888 may also have fewer side effects than many other therapies.”

The study is part of a National Cancer Institute-funded initiative to develop new therapies to treat cancer more effectively. The program at UPCI is one of 15 in the country.

Early-phase clinical trials are the first step for all new therapeutics; they are designed to evaluate the safety and dosing of novel therapies that have shown promise in earlier animal and preclinical studies.

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Pre-op tests aid thyroid surgery options

Knowing prior to surgery whether a patient’s thyroid cancer harbors a specific gene mutation leads to tailored treatments and improved outcomes, according to School of Medicine research recently presented at the American Association of Endocrine Surgeons annual meeting.

According to Linwah Yip, surgical oncologist at the UPMC Multidisciplinary Thyroid Center, malignant thyroid tumors can contain a mutation in a gene known as BRAF, and BRAF-positive cancers are more likely to recur. “For that reason, using genetic testing to establish BRAF status prior to surgery has important implications for the type and extent of surgery the patients need,” she explained. “BRAF-positive thyroid cancer patients should have the entire thyroid gland removed instead of having a partial thyroidectomy.”

Yip and her colleagues reviewed 206 papillary thyroid cancer cases, of which 106 were BRAF-positive and 100 were BRAF-negative. In 19 percent of the cases, the surgical plan would have changed if BRAF status had been determined prior to surgery.

Yip said patients with a BRAF mutation face a more aggressive disease, which is why testing the tumor for gene mutations is important.

“In the past, we’ve proven that this mutation is 100 percent predictive of thyroid cancer. Through genetic testing, we can ensure patients receive the right operation the first time, reducing recurrences and additional surgeries,” said Yip.

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Study finds drinkers’ minds wander unaware

A new Pitt study suggests that a moderate dose of alcohol increases mental wandering and at the same time disrupts a person’s ability to realize his or her mind has wandered.

“Lost in the Sauce: The Effects of Alcohol on Mind Wandering,” appears in this month’s issue of Psychological Science.

The study provides the first evidence that alcohol impacts an individual’s ability to realize his or her mind has wandered, suggesting impairment of a psychological state called meta-consciousness. These findings suggest that distinct processes are responsible for causing a thought to occur, as opposed to allowing its presence to be noticed.

Pitt psychology professor Michael Sayette; Erik Reichle, chair of Pitt’s cognitive program in psychology, and a researcher from the University of California-Santa Barbara studied a group of men, half of whom had consumed alcohol and half of whom had been given a placebo.

After 30 minutes, the participants began reading a portion of Tolstoy’s “War and Peace” from a computer screen. If they caught themselves zoning out — having no idea what they had just read or thinking about something other than the text — they pressed a key on the keyboard. They also were prompted at intervals to see if they could be “caught” with their minds wandering before they realized it themselves.

Researchers found those who had consumed alcohol were “mind wandering” without realizing it about 25 percent of the time – more than double that of those who had not consumed alcohol.

But as far as “catching themselves” zoning out, those who had been drinking were no more likely to do so than the other group even though they would have had many more opportunities to catch themselves because they zoned out more frequently.

Sayette said, “Researchers have known for a while that alcohol consumption can interfere with our limited-capacity powers of concentration. But this ‘double-whammy’ may explain why alcohol often disrupts efforts to exercise self-control, a process requiring the ability to become aware of one’s current state in order to regulate it.”

These findings have potentially important implications for understanding the disruptive effects of alcohol.

For example, the observation that alcohol increases mind wandering suggests another reason why alcohol makes driving dangerous: Drunk drivers may lose track of what they are doing. Moreover, the finding that alcohol reduces meta-consciousness may explain why people drive when they are drunk. With a reduced ability to assess their current state, intoxicated people may fail to realize how intoxicated they are and thus inadequately appraise the danger of driving.

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Gender, sepsis death risk linked

Differing biological response to infection between men and women may explain higher death rates among older men who are hospitalized with community-acquired pneumonia (CAP). The findings, published online in the Critical Care Medicine journal, may have important implications for understanding sex differences in life expectancy.

Sachin Yende, professor in the School of Medicine’s Department of Critical Care Medicine and corresponding author of the study, said, “Our study found that men with CAP were less likely to survive after an infection compared to women and this was not explained by differences in demographics, health behavior, chronic health conditions or quality of care.”

Measurement of blood levels of inflammatory indicators, coagulation indicators and fibrinolysis indicators suggested that men generate a stronger inflammatory and coagulation response and, perhaps, break up blood clots more quickly than women in response to infection. The differences, Yende said, may explain the reduced short-term and long-term survival rates.

Data were gathered from the multicenter Genetic and Inflammatory Markers of Sepsis (GenIMS) study. The study included 2,320 subjects, with a mean age of 64.9 years, 1,136 of whom were men. All were enrolled when they were admitted to emergency departments at 28 academic and community hospitals.

The men were sicker on admission, more likely to be smokers and to have at least one chronic health condition such as cardiac disease or cancer. Severe sepsis occurred in 31 percent of the subjects. Of these, about half had severe sepsis on their first day of hospitalization.

Men had a higher risk than women of death at 30 days (7 percent vs. 4.5 percent), 90 days (11.4 percent vs. 8.6 percent) and one year (21 percent vs. 16 percent). “Even compared to women with an equivalent illness severity, men were more likely to die,” Yende noted.

Derek C. Angus, chair of critical care medicine and principal investigator of the study, said, “Our results suggest that immune response to infection may be an important target for interventions to reduce sex disparities in the outcomes of infections.”

The GenIMS researchers hope to identify whether certain changes in the genes for key inflammatory molecules are associated with the risk of developing pneumonia (the most common cause of sepsis), and the risk of progression to severe sepsis, septic shock, organ dysfunction or death.

In a paper published online on April 3 in the Federation of American Societies for Experimental Biology Journal, GenIMS researchers led by Yende and Angus found that people with certain gene variations associated with higher levels of macrophage migration inhibitory factor, an innate immune response regulator, were less likely to die following CAP.

“Macrophage migration inhibitory factor is a molecule that plays an important role in inflammation and has been shown to worsen outcomes in animal models of sepsis.

“Our results are intriguing in light of these findings and as other research groups are trying to design human studies to block this molecule in sepsis,” said Yende. In future work, the researchers will continue to examine relationships between sex and gene variations in CAP, sepsis and survival.

GenIMS is supported in part by the National Institute of General Medical Science with additional support from GlaxoSmithKline and Diagnostic Products Corp.

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Army funds SCRR brain injury, trauma research

The U.S. Army has awarded Pitt’s Safar Center for Resuscitation Research (SCRR) more than $1 million for the next three years. A consortium of three centers was selected for special research on the management of blast-induced brain injury and polytrauma. The other centers selected are the Walter Reed Army Institute of Research and the University of Maryland.

In addition to Patrick Kochanek, SCRR director and professor in the departments of critical care medicine, pediatrics and anesthesiology, Pitt’s research team includes Hulya Bayir of critical care medicine, Edward Dixon of neurosurgery, Valerian Kagan of the Center for Free Radical and Antioxidant Health and Robert Garman of neuropathology.

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Pitt-CMU gets NSF funds for learning center

The National Science Foundation has awarded Pitt and Carnegie Mellon University a five-year, $25 million grant to establish the Pittsburgh Science of Learning Center (PSLC), which will sponsor research into how people learn and develop technologies and teaching approaches that will foster high academic achievement.

The PSLC is one of three learning centers that the NSF is funding at this time. The others will be housed at Boston University and jointly at the University of Washington and Stanford University.

The co-directors of PSLC are Pitt computer science professor Kurt VanLehn, senior scientist in Pitt’s Learning Research and Development Center, and Kenneth R. Koedinger, professor of human-computer interaction and psychology at Carnegie Mellon.

PSLC’s core will be its LearnLab, where education researchers can create, run and analyze experiments on how people learn.

LearnLab will address what has long been a dilemma for education researchers: Experiments conducted in the artificial confines of the laboratory produce results and innovations that are not transferable broadly to schools, while studies conducted in classrooms have tended to be controlled less rigorously and may not provide sufficiently trustworthy results.

LearnLab scientists initially will use two high school math courses, two college science courses and three college language courses (Chinese, French and English as a second language) as a basis for their research.

PSLC will invite schools in the Pittsburgh area and across the country to participate as “research schools” and serve much as research hospitals do for medical research.

LearnLab, in conjunction with the schools, aims to enable learning scientists to conduct research that is as rigorous as traditional laboratory studies and test their results in real classroom settings to improve student achievement. LearnLab will build an infrastructure for conducting school-based studies by establishing streamlined procedures, troubleshooting common problems and creating methods for researchers without computer programming experience to employ computer learning technologies.

In addition to being a center for research in education, LearnLab also will be a repository for education data.

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Aflatoxin interventions studied

Felicia Wu, professor in the Department of Environmental and Occupational Health, is a member of a team of researchers from around the world who received a $2.7 million Gates Foundation grant to assess aflatoxin interventions in Mali, Kenya and Uganda.

Aflatoxin, produced by a food-borne fungus, is a very potent natural liver carcinogen found in corn, peanuts, pine nuts, pistachios and almonds.

Wu will be the lead investigator for a project focused on assessing the interventions’ cost-effectiveness and feasibility.

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Study rules may exclude some patients, affect outcomes

Findings from clinical studies used to gain Food and Drug Administration approval of common antidepressants are not applicable to most patients with depression, according to a report led by the Graduate School of Public Health (GSPH).

Published in the May issue of the American Journal of Psychiatry, the study suggests only a small percentage of people with depression qualify for these studies, and those who do not qualify often are treated with the same medications but may suffer poorer clinical outcomes.

As part of the National Institute of Mental Health-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project — the largest study of the treatment of depression conducted in the United States — researchers compared symptoms and outcomes in depressed patients who met phase III study inclusion criteria to those who did not.

Phase III studies for antidepressants determine the effectiveness of the drug in comparison to a placebo. The inclusion criteria for these studies are not standardized nor subject to federal guidelines, resulting in some variation from study to study in the profile of eligible patients. Typically excluded are patients with milder forms of depression, who might be more likely to respond to a placebo drug, and those who may have chronic depression or additional illnesses or psychiatric and/or medical conditions.

After assessing 2,855 patients treated with citalopram, a commonly prescribed selective serotonin reuptake inhibitor for mood disorders, study authors concluded that fewer than one in four, or 22.2 percent, of the patients met the usual criteria for inclusion in phase III antidepressant trials.

The study’s lead author, Stephen Wisniewski, professor of epidemiology and co-director of the GSPH Epidemiology Data Center, said, “Only a small percentage of depressed patients in our study would have qualified for inclusion in phase III efficacy trials of depression drugs. This raises major concerns about whether results from traditional phase III studies can be generalized to most people with depression, who also often suffer from anxiety, substance abuse and other medical and psychiatric problems.”

When Wisniewski and colleagues further assessed how well patients did on treatment, they found that those who met the eligibility criteria for phase III trials had better outcomes, including higher remission rates, less severe side effects and serious adverse events. The depression remission rate in the patients who met the criteria was 34.4 percent, compared to 24.7 percent in the ineligible group. Additionally, the drug response rate also was higher in the eligible group: 51.6 percent compared to 39.1 percent of the ineligible group.

“Results from research studies suggest more optimistic outcomes than may exist for real-world patients receiving treatment for depression,” said Wisniewski.

Although phase III eligibility criteria could be changed to include a broader population of patients, Wisniewski cautioned that this could come at the cost of more serious side effects in patients who have additional health conditions. These patients may not be able to tolerate the drugs being tested.

Instead, he suggests medical care providers who treat patients with depression use their professional judgment by noting that most phase III findings are based on patients who may be very different than those under their care.

The study was funded by the National Institute for Mental Health. Among the study co-authors was Michael Thase, psychiatry professor in the School of Medicine and director of WPIC’s Division of Mood, Anxiety and Related Disorders.

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GSPH research grants awarded

Four GSPH researchers recently were awarded $20,000 in Computational and Systems Models in Public Health pilot grants. The GSPH program was initiated in 2008 by Dean Donald S. Burke.

This year’s awardees and their projects are:

• Stephanie R. Land, biostatistics, for “Social Networks and Tobacco Use in First-Year College Students”;

• Stephen B. Thomas, Philip Hallen Professor of Community Health & Social Justice and director, Center for Minority Health, Department of Behavioral and Community Health Sciences, for “Developing an Agent-Based Model to Assess Racial Differences in Medical Discrimination, Social Support and Trust”;

• Janice C. Zgibor, professor in the Department of Epidemiology and director of evaluation at the University of Pittsburgh Diabetes Institute, for “Application of the Archimedes Model to Estimate Clinical Outcomes and Cost-Effectiveness in Diabetes Treatment and Prevention Research,” and

• Yuting Zhang, Health Policy and management, for “Fill the Gap: Modeling Total Medicare Spending Among the Elderly.”

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