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November 20, 2014

Research Notes

Datasets for public health analyses inconsistent

Commercially available datasets containing a wealth of information about food and alcohol establishments differ significantly, raising concerns about their reliability as sources of information that could be used to set public policy or conduct scientific research, according to a Graduate School of Public Health investigation.

The analysis, funded by the Aetna Foundation, was presented at the American Public Health Association’s (APHA) annual meeting. It examined systematic differences in two commercially available datasets when they were used to determine the relationship between neighborhood socioeconomic characteristics and the density of food and alcohol establishments.

Said lead investigator Dara Mendez of epidemiology: “If we’re making decisions about setting public policy to improve public health — such as incentives for grocery stores that offer fresh produce in economically depressed areas — then we need to be making these decisions based on accurate data to back up the need for such incentives. Our study found that relying on just one of these commercially available datasets likely wouldn’t provide robust information.”

There are numerous data-sets available for a fee that give detailed information about food and alcohol establishments across the U.S. Typically, these datasets are purchased by companies that use them for marketing purposes.

Mendez and her team used two different commercially available datasets containing information about food and alcohol establishments in Allegheny County, which includes Pittsburgh. The information was divided into the 416 distinct census tracts in the county as a means to define neighborhoods. Each census tract consists of an average of 4,000 people.

Both of the datasets showed that the density of alcohol outlets increased as neighborhood poverty increased. However, the datasets differed when it came to grocery stores. One showed that as poverty increased, the number of grocery stores increased. The other showed no association.

“This is a perplexing disagreement that likely comes down to the datasets using different classification systems and also not accurately capturing all the information. For example, because we are familiar with Allegheny County, my team was able to determine that some of the key grocery stores in our area were not included,” said Mendez. “However, if we were doing a similar analysis for a city we were not familiar with, we likely wouldn’t catch the discrepancy and could come to an inaccurate conclusion.”

The Aetna Foundation funded the study as part of a larger grant to public health to study the potential influence of living in stressful neighborhoods on the health of African-American mothers and their babies.

Additional researchers on this study included Anthony Fabio and Kevin H. Kim of Pitt and a faculty member from Duke University.


Cyber dating abuse common among teenagers

Two in five teens surveyed experienced cyber dating abuse, which involves the use of technology to control, harass, threaten or stalk another person in the context of a dating relationship, in the previous three months, according to a Children’s Hospital study that appears online in Pediatrics.

The study is the first about cyber dating abuse among a group of young people who are using school-based health services, said senior investigator Elizabeth Miller, pediatrics faculty member in medicine and chief of the Division of Adolescent and Young Adult Medicine at Children’s Hospital.

Done in collaboration with the California Adolescent Health Collaborative of the Public Health Institute, California School-Based Health Alliance and Futures Without Violence, the study was conducted at eight school-based health centers in California where students receive confidential clinical health services, including annual checkups, sports physicals and birth control. The study, conducted during the 2012-13 school year, assessed those ages 14-19 for exposure to cyber dating abuse, adolescent relationship abuse, sexual behavior and care-seeking for sexual and reproductive health.

Key findings showed 41 percent of teens reported experiencing this form of abuse within the last three months, with more females than males reporting such victimization. Most commonly, their partners used technology including mobile apps, social networks, texts or other digital communication to repeatedly contact them to see where they were and who they were with.

Said Miller: “These findings underscore that cyber dating abuse is an emerging concern. We need to support prevention efforts that increase education about the many different forms of abuse in adolescent relationships, and to encourage parents, teachers, coaches and others to talk to young people about what healthy relationships look like.”

As in previous research examining this form of abuse, the researchers found that teens exposed to cyber dating abuse were more likely to also experience other forms of physical and sexual dating abuse, such as being slapped, choked or made to have sex by a dating partner, and also non-partner sexual assault.  Additionally, greater exposure to cyber dating abuse was associated with less contraceptive use among adolescent girls.

“Professionals should take cyber dating abuse seriously and actively ask teens if they are being monitored, threatened or sexually coerced by their partner using technology-based communication,” added Miller. “Given the prevalence of cyber dating abuse in this sample of adolescents, we recommend that relationship abuse prevention education include cyber dating abuse and that such education and counseling be integrated into health assessments in clinical settings.”

Pitt collaborators with Miller on the study were Rebecca Dick, Heather L. McCauley and Kelley Jones.

The study was supported by the National Institute of Justice, Office of Justice Programs, Department of Justice.


Blood test could reduce antibiotic use

A new blood biomarker test that indicates whether bacteria are the cause of a patient’s lung infection now is being studied at UPMC Presbyterian, launching a national multicenter trial. The information could help doctors decide when to prescribe antibiotics and possibly reduce overuse of the drugs, which can lead to antibiotic-resistant strains of bacteria.

According to principal investigator David T. Huang, faculty member in critical care medicine and emergency medicine, patients who go to hospital emergency departments (ED) with coughs and breathing difficulties could have pneumonia, bronchitis, asthma, chronic obstructive pulmonary disease or even congestive heart failure.

Said Huang: “Doctors prescribe antibiotics more often than they would like to because it can be really hard to tell if a patient has a lung infection or a non-infectious disease. Also, viral infections look very much like bacterial infections, and X-rays typically cannot distinguish between the two. This study will examine whether a novel biomarker can help doctors make more informed decisions about using antibiotics.”

School of Medicine faculty members Aaron Brown, emergency medicine, and Franziska Jovin, medicine, will lead the study in the ED and hospital.

More than 1,500 lung infection patients will be needed to complete the Procalcitonin Antibiotic Consensus Trial (ProACT), which eventually will be expanded to include approximately 10 other sites across the country.

Patients diagnosed in the ED with a lung infection and who are not critically ill will be asked to join ProACT. If they agree, patients will be randomly assigned either to get the usual care alone or to also have a blood test to measure the level of the protein procalcitonin, which previous Swiss studies have shown is high with bacterial infection and low with viral infection. The result and a recommendation about antibiotic use will be available within an hour to the treating ED physician. If the patient is admitted to the hospital, follow-up procalcitonin levels will be checked and made available to the treating hospital physician. The research team will call study patients twice within 30 days of the ED visit to check on their health status and the period of antibiotic use, if any.

“The final decision to use or not use antibiotics is up to the doctor, who also will be taking into account the patient’s medical history and other factors,” Huang said. “My hope is that we’ll find that patient outcomes are just as good, while antibiotic use declines.”

ProACT is funded by a $5 million, five-year grant and a one-year trial planning grant, from the National Institute of General Medical Sciences, part of the National Institutes of Health (NIH).


New method to treat high-saline water

Developing a method to use waste heat from thermoelectric plants to treat high-saline water from hydrofracturing and other processes is the focus of a Department of Energy (DOE) grant recently awarded to researchers at the Swanson School of Engineering. “Development of Membrane Distillation Technology Utilizing Waste Heat for Treatment of High Salinity Wastewaters” was funded with a $496,000 grant from the DOE National Energy Technology Laboratory (NETL), with an additional $157,000 in funding from Pitt.

Principal investigator is Radisav Vidic, chair of the Swanson school’s Department of Civil and Environmental Engineering. Co-PI is Vikas Khanna, department faculty member. The grant was funded through the DOE’s fossil energy crosscutting research program.

Vidic and his group will target two goals to solve a mutual problem: utilizing low-grade waste heat in existing large scale power generation and gas transport systems, and developing a low-cost treatment of waste water produced from fossil-based resources and CO2 storage.

Said Vidic: “The typical coal- or natural gas-powered electric plant produces a tremendous amount of low-grade heat and energy as a by-product, but capturing and using it is not cost-effective. Similarly, hydrofracturing and carbon sequestration produces water with high salinity, which is too costly to recycle and is typically disposed as waste. We intend to explore whether a membrane distillation technology can be adapted to utilize this waste heat to treat these wastewaters in a cost-effective manner.”

According to Vidic, membrane distillation technology doesn’t require high temperatures to separate brine from water and can function between approximately 70-80 degrees Celsius (160-180 degrees Fahrenheit). The first phase of the research would include developing the technology in the lab using two processes — direct contact membrane distillation, which is the simplest form, and vacuum membrane distillation — to recover clean water from the salty brine. Systems analyses also will be performed to determine the availability and quantity of useful thermal energy from coal and natural gas power plants in Pennsylvania, Ohio and West Virginia, as well as from natural gas and CO2 compression facilities. This will enable the researchers to determine the economic viability of the treatment process.

In theory, the residual salts and other materials then could be stored in a landfill or disposed of by deep well injection, and the recovered clean water could, for example, be used in place of fresh water in hydrofracturing and other power-related systems or for irrigation.

Said Khanna: “Fresh water is a finite resource and so we need to examine the water footprint of the energy industry as a whole, which is very water-intensive. Although the technology may ultimately be cost-prohibitive for power utilities, it could be practical for private industry to develop and build near power plants, creating a win-win situation. Most importantly, we hope to create a more sustainable solution for two distinct yet related problems — waste heat and waste water.”


How the tiger beetle visualizes prey

Speed is an asset for a predator — except when that predator runs so fast that it essentially blinds itself.

The tiger beetle, relative to its size, is the fastest creature on Earth. Some of these half-inch-long beetles cover about 120 body lengths per second (at about five miles per hour). The fastest human can do about five body lengths. To take the sprinting gold from the tiger beetle, a person would have to hit 480 miles per hour.

But the tiger beetle has a problem. At peak speeds, everything becomes a blur. It can’t gather enough light with its eyes, and vision is compromised. It can still perceive the pursued but not clearly.

Daniel Zurek, a postdoctoral researcher in Nathan Morehouse’s lab in the Department of Biological Sciences in the Dietrich School of Arts and Sciences, is looking into how the tiger beetle’s speed-related vision issues correlate with when it opens and closes its mandibles in pursuit of supper.

Is it just guessing, hoping that its jaws are ready to crush prey when it inevitably catches up?

No, Zurek wrote in a new paper published in Biology Letters.

Said Zurek: “We’re asking in what situations do the mandibles open and close. (The beetles are) trying to catch something, so they want to be sure that their jaws are open and close on contact.” But, he added, in their obstacle-riddled habitat, it’s probably not a good idea to keep them open all the time, lest the mandibles snag something, delaying the beetle and permitting the prey to escape.

“Is it a matter of distance (to prey), the size (the prey) appears on the retina, the projected time to collision? There are lots of variables,” he said.

Using a dummy piece of prey (a plastic bead on a string), Zurek let the beetles give chase and recorded their hunting efforts in super slow-motion. As the beetle begins to catch up to the escaping dummy prey, the contracting image of the prey as perceived by the beetle begins to expand, which is the cue for the beetle to open its jaws, Zurek found. And as the image begins to recede, the jaws close.

This research, Zurek said, reveals a novel and potentially widespread mechanism for how behavioral decisions can be made based on visual “rules” in dynamic situations, where both the observer and the target are moving.


FDA approves personalized blood test to predict transplant rejection

A personalized blood test to predict the likelihood of organ rejection in children with liver or intestine transplants has received Food and Drug Administration (FDA) approval. Researchers at Children’s Hospital developed the test to determine a personalized rejection-risk index with cell-based technology.

Cellular rejection affects half of all transplant recipients in their lifetime. If unchecked, rejection can lead to progressive loss of function of the transplanted organ. Therefore, predicting whether rejection will occur is an essential part of the recipient’s care, and has been an unmet need until recently. A biopsy is used to detect ongoing rejection, but this surgical procedure cannot predict rejection.

The research team is led by Rakesh Sindhi, surgery faculty member in the Division of Transplantation and co-director, pediatric transplantation, at the Hillman Center for Pediatric Transplantation at Children’s. The researchers began work on this test system in late 2006. The technology was licensed by Pitt to Plexision, a Pittsburgh-based biotech company, for development.

Pleximmune, as the test is named, predicts acute cellular rejection with an accuracy approaching or exceeding 80 percent under a variety of conditions. This performance has been established in a study involving more than 200 children who received liver or intestine transplants at Children’s.

Said Sindhi: “A common theme in every encounter with our patients is an assessment of whether that child is at risk for rejection and whether this risk will be affected by the planned treatment. It is hoped that the information from such personalized blood tests will improve clinical decision-making and benefit patients in the long run.”

Sindhi is the inventor of the technology on which this test system is based. Pitt holds equity in the company; Sindhi has an unpaid consulting relationship with the company.


Source of creativity: Near or far?

It’s commonly believed that creativity is a process that involves connecting ideas and building on the past to create something new. But is it better to think outside the box, using unrelated concepts to get the creative juices flowing, or to build on something more closely related to the problem one is trying to solve?

In a paper published in Design Studies, recent graduate Joel Chan and his mentor Christian Schunn, senior scientist at the Learning Research and Development Center, along with a researcher from Carnegie Mellon University, have collected surprising evidence that nearer is better.

Said Chan, the lead author, who earned his PhD from Pitt this summer and now is a postdoctoral fellow at CMU: “For people needing fresh inspiration for a problem, these findings imply that you shouldn’t just go off and talk to random people or read things totally unrelated to your problem. These might yield novel ideas, but not necessarily … useful and novel ideas.”

Chan and Schunn, a faculty member in psychology, collected data through OpenIDEO, a web-based, crowd-sourced innovation platform intended to help people address a wide range of social and environmental problems such as human rights violations and job growth for youth.

The team began collecting data from OpenIDEO’s “inspiration phase,” during which individuals posted descriptions of solutions to problems similar to those posited by new solution seekers. Subsequent to the inspiration phase, contributors moved on to posting more concrete, increasingly detailed solutions to the specific problem at hand. Then, OpenIDEO experts created a shortlist of what they saw to be viable creative solutions to the problem. The process took up to 10 weeks. Other similar studies, Chan said, have looked at the creative process over a much shorter period of time. Also, he added, “in our study we had more than 350 participants and thousands of ideas. Creativity studies typically have many participants solve ‘toy’ problems or observe few participants solving real problems. In our study we had both, lending greater strength to our conclusions.”

The team collected its data at the conclusion of the OpenIDEO process. They then entered it into an algorithm to determine whether an idea was near to or far from the posted problem. This algorithm first was vetted against human judgments and proved to be quite good at determining idea distance. Then, the outcomes of the model proved adept at predicting the OpenIDEO experts’ shortlist and found that the vast majority of ideas that made the list were closely related to the posted problem, Schunn said.

“Instead of seeing a bigger effect of far inspirations,” Chan said, “I saw that ideas built on source ideas more closely related to the problem tended to be selected more often. And I saw the same pattern across 12 very different problems, ranging from preventing human rights violations to fostering greater connectedness in urban communities to improving employment prospects for young people.”

Schunn added that “we chose to look at a variety of problems to find out if there is a consistent pattern, and there is. And we can use this algorithm as a tool for a variety of problems, to identify the ideas that are ‘close’ and direct people to look at them.”

In short, Chan said, “My overall theory is that creative ideas more often come from accumulating many small insights, stretching the boundaries just a bit at a time.”


Preventing colon cancer through anti-inflammatories

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protect against the development of colorectal cancer by inducing cell suicide pathways in intestinal stem cells that carry a certain mutated and dysfunctional gene, according to a new study led by researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine. The findings were published online in the Proceedings of the National Academy of Sciences.

Scientists have long known from animal studies and clinical trials that use of NSAIDs, such as aspirin and ibuprofen, lowers the risk of developing intestinal polyps, which can transform into colon cancer. But they have not known why, said senior investigator Lin Zhang, faculty member in Medicine’s Department of Pharmacology and Chemical Biology and UPCI, a partner with UPMC CancerCenter.

Added Zhang: “Our study identifies a biochemical mechanism that could explain how this preventive effect occurs. These findings could help us design new drugs to prevent colorectal cancer, which is the third leading cause of cancer-related deaths in the country.”

The research team performed experiments in animal models and examined tumor samples from patients who had taken NSAIDs and those who hadn’t. They found that NSAIDs activate the so-called death receptor pathway, which selectively triggers a suicide program in intestinal stem cells that have a mutation in the APC gene that renders the cells dysfunctional. Healthy cells lack the mutation, so NSAIDs cause them no harm. In that manner, the drugs instigate the early auto-destruction of cells that could lead to precancerous polyps and tumors.

“We want to use our new understanding of this mechanism as a starting point to design better drugs and effective cancer prevention strategies for those at high risk of colon cancer,” Zhang said. “Ideally, we could harness the tumor-killing traits of NSAIDs and avoid possible side effects that can occur with their chronic use, such as gastrointestinal bleeding and ulcers.”

The research team included lead author Brian Leibowitz and Jian Yu of UPCI and the Department of Pathology, as well as others from UPCI and the School of Medicine, Sichuan University INCELL Corp. and Indiana University School of Medicine.

The project was funded by NIH and the American Cancer Society.


Blood thinner dabigatran found to cause more bleeding

Patients with atrial fibrillation who take the blood thinner dabigatran are at greater risk for major bleeding and gastrointestinal bleeding than those who take warfarin, according to a study by researchers at the Graduate School of Public Health.

The findings, based on Medicare claims data and published in JAMA Internal Medicine, indicate greater caution is needed when prescribing dabigatran to certain high-risk patients.

Atrial fibrillation, an arrhythmia in which the heart’s upper chambers irregularly contract, can send tiny clots from the heart to the blood vessels in the brain, explained the study’s senior author Yuting Zhang, faculty member and director of the Pharmaceutical Economics Research Group in Public Health’s Department of Health Policy and Management. For that reason, these patients often are prescribed a blood thinner to limit clot formation with the aim of preventing strokes.

“Dabigatran was introduced in 2010 and, at the time of approval, it was the only available alternative to warfarin,” Zhang said. “Warfarin dosing can be tricky and regular monitoring with blood tests is required, so doctors and patients were glad to have a drug that was easier to manage. But some recent studies suggest that dabigatran is associated with a higher risk of bleeding.”

To investigate that possibility, the study’s first author, Inmaculada Hernandez, and the team looked back at pharmacy and medical claims data from 2010 and 2011 in a random national sample of Medicare beneficiaries. They tracked 1,302 dabigatran users and 8,102 warfarin users to see whether they experienced bleeding episodes, classifying the events as major, such as intracranial bleeding or gastrointestinal bleeding requiring a hospital or emergency room stay, or minor, such as gastrointestinal bleeding that was treated on an outpatient basis, or nosebleeds.

They also looked more closely at bleeding episodes in four high-risk subgroups: those who were 75 and older; African Americans; those with chronic kidney disease, and those with seven or more co-existing medical problems.

Medicare data showed that the incidence of major bleeding was 9 percent and of any bleeding was 32.7 percent in the dabigatran group and 5.9 percent and 26.6 percent, respectively, in the warfarin group.

In other words, dabigatran users were 58 percent more likely to have a major bleed and 30 percent more likely to have any kind of bleed than those taking warfarin. African Americans and patients with chronic kidney disease using dabigatran were about twice as likely to have a major bleed as those taking warfarin. In addition, dabigatran users were more likely than warfarin users to experience gastrointestinal or vaginal bleeding, or blood in the urine, joints or sputum. However, the dabigatran group had a lower risk for bleeding in the brain.

Said Hernandez: “These findings indicate that physicians should be cautious when prescribing dabigatran, particularly to African Americans and patients with kidney impairments. Also, the incidence of gastrointestinal bleeding was high in all the subgroups, so we recommend doctors explain to patients how to detect it so that it can be treated promptly.”

Zhang said: “We plan to examine 2012 data to monitor the risk of stroke for patients on dabigatran, which is the primary indication for taking the blood thinner. It’s possible that for some patients a greater reduction in the risk of stroke will outweigh the higher risk of bleeding with dabigatran compared to warfarin.”

Other co-authors were Seo Hyon Baik of public health and a researcher from La Paz University Hospital in Madrid.

The project was funded by the Commonwealth Foundation for Public Policy Alternatives and the Agency for Healthcare Research and Quality.


Pitt researchers get early-career Komen breast cancer awards

Among the Susan G. Komen organization’s recent early-career breast cancer research awards were three awards to Pitt researchers to investigate breast cancer biology, screening, risk reduction and treatment.

• $450,000 went to Rachel Jankowitz, a clinical faculty member in medicine’s Division of Hematology/Oncology, to conduct clinical trials to determine the efficacy of using tamoxifen, anastrozole (an aromatase inhibitor) and fulvestrant in the tumor tissue of women newly diagnosed with invasive lobular carcinoma, a type of breast cancer about which little is known and which often is treated in the same manner as invasive ductal carcinoma, rather than as a unique subtype.

• $180,000 went to Sreeja Sreekumar, a postdoctoral associate in the Oesterreich Lab of medicine’s Department of Pharmacology and Chemical Biology, to better understand the action of the estrogen receptor in invasive lobular carcinoma in order to provide better targeted therapies in this little understood type of breast cancer.

• $200,000 in continued funding was awarded to Adrian Lee, faculty member in the molecular genetics and developmental biology program, to investigate the therapeutic potential of combining drugs that target the insulin-like growth factor 1 receptor (IGF-1R) with chemotherapy to treat triple negative breast cancer.


$4.2 million grant from NIH continues cancer studies among Chinese

Cancer epidemiologist Jian-Min Yuan, Arnold Palmer Endowed Chair in Cancer Prevention, has been awarded a five-year grant of more than $4.2 million from the National Cancer Institute to continue two studies examining how environmental and lifestyle exposures and genetics have affected the incidence, mortality and age-related outcomes of cancer in more than 81,000 Chinese men and women.

Yuan, associate director for cancer control and population sciences at the University of Pittsburgh Cancer Institute (UPCI) and co-leader of UPCI’s cancer epidemiology and prevention program, is the principal investigator of the Shanghai Cohort Study and the Singapore Chinese Health Study. For the two population-based prospective studies, researchers examine cancer and other major health outcomes by evaluating blood, urine and other samples collected from participants for more than 25 years. These studies already have yielded important findings about the causes and prevention of cancer and have led to chemoprevention trials underway in the U.S.

Said Yuan: “We anticipate that the two Asian study groups will become even more scientifically valuable over the next five years as the younger members of these groups get older and have a greater risk of developing cancer, thereby increasing the number of pre-disease, biomarker-based research opportunities.”

With the new award, Yuan and his collaborators hope to add 2,700 new cancer cases over the next five years. They also hope to:

• Gather data to maintain and enhance the two Asian study databases, including follow-up for cancer, non-cancer and death outcomes; maintenance of the biorepositories, and management of the databases.

• Conduct in-person and telephone interviews among participants to update exposure and medical information.

• Collect blood and urine samples from participants with cancer diagnoses.

• Engage in collaborative research projects of the NCI and the Asia Cohort Consortium.

—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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