University Times

Researchers to look at benefit of omega-3 in Alzheimer’s

Nutritionists have long endorsed fish as part of a heart-healthy diet, and now some studies suggest that omega-3 fatty acids found in the oil of certain fish, algae and human breast milk also may benefit the brain by lowering the risk of Alzheimer’s disease.

In order to test whether docosahexaenoic acid (DHA), an omega-3 fatty acid, can impact the progression of Alzheimer’s disease, researchers at Pitt’s Alzheimer Disease Research Center (ADRC) supported by the National Institute on Aging (NIA), part of the National Institutes of Health, will evaluate DHA as part of a nationwide clinical trial coordinated by the University of California-San Diego. The trial will take place at 52 sites. Steven DeKosky, director of the ADRC and chair of neurology at Pitt’s School of Medicine, will conduct the study locally.

Researchers primarily will evaluate whether taking DHA over many months slows the progression of both cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease. During the 18-month clinical trial, investigators will measure the progress of the disease using standard tests for functional and cognitive change.

In recent European studies and in the Framingham Heart Study, scientists reported that people with the highest blood levels of DHA were about half as likely to develop dementia as those with lower levels.

Additional information on the study is available by calling Mary Ann Oakley at 412/692-2700 or the NIA’s Alzheimer’s Disease Education and Referral Center at 800/438-4380.

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Social capital can predict student success

Joseph M. Katz Graduate School of Business faculty members Carrie R. Leana, professor of business administration, and Frits K. Pil, associate professor of business administration and research scientist, received the Sloan Industry Studies Best Paper Prize for their research on Pittsburgh Public Schools. Awarded by the Alfred P. Sloan Foundation, the prize recognizes outstanding research in the area of industry studies. Their paper, titled “Social Capital and Organizational Performance: Evidence From Urban Public Schools,” was published in the May-June 2006 issue of Organization Science. The researchers looked at improving student performance by considering the question, “What is it like to work here?”

Leana, the lead author of the paper, and Pil examined internal social capital (relationships among teachers) and external social capital (relationships between the principal and external stakeholders) in 88 Pittsburgh public schools to determine their effects on student achievement. The results of the research indicate that positive relations within the groups (social capital) can predict improved student achievement in mathematics and reading. The researchers concluded the pursuit of improving schools and student achievement has over-emphasized teaching skills and experience, and not given enough attention to social interaction among teachers.

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Teens’ beliefs, smoking linked

The more a high school student overestimates the percentage of people in the general population who smoke cigarettes, the more likely he or she will be to smoke, reports a School of Medicine study published in the current issue of the Archives of Pediatric and Adolescent Medicine.

The study identifies three distinct ways to measure “normative beliefs” involving smoking, each of which it found to be related significantly to adolescents’ likelihood of smoking.

The study found the more a teen perceived that successful and elite people smoke cigarettes or the more he or she overestimated the percentage of smokers in the general population, the more likely that adolescent was to smoke.

Conversely, the more strongly an adolescent perceived that his or her parents or peers disapproved of smoking, the less likely that adolescent was to smoke.

According to the study, 93 percent of high school students overestimated the percentage of people who smoke in the United States. On average, they believed 56 percent of Americans are smokers, while the actual figure is less than half that.

Lead author Brian Primack, assistant professor of medicine and pediatrics at the School of Medicine, said, “Adolescents have important misconceptions about cigarette smoking that can place them at increased risk for smoking.”

More than 1,200 high school students who participated in the study were assigned normative beliefs scores based on their responses to survey items. Students responded whether they agreed or disagreed with statements such as:

“Most successful business people smoke cigarettes at least once a month.”

“My favorite celebrities probably smoke cigarettes at least once a month.”

The students also responded to “perceived disapproval” statements, such as:

“According to my parents, it is very important for me not to smoke cigarettes.”

“According to my friends, it is very important for me not to smoke cigarettes.”

Galen E. Switzer of the School of Medicine was among the study co-authors.

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Immune system off-switch found

School of Medicine researchers have found a fundamental genetic mechanism that shuts down an important gene in healthy immune system cells. The discovery of the mechanism, called a somatic stop-codon mutation, could lead to new therapies against infections, leukemia and other cancers. Results of the study appear in the online journal PLoS ONE, published by the Public Library of Science.

“This kind of loss-of-function mutation can be very dangerous, and it is the first such mutation that has been identified in normal immune cells in blood,” said Bora E. Baysal, assistant professor of obstetrics, gynecology and reproductive sciences.

Baysal and his colleagues tested 180 samples, including blood from healthy individuals and other material from those with childhood leukemia, looking at specific portions of DNA in immune cells known as monocytes, natural killer cells and lymphocytes. These cells are key to the body’s immune response against infection and disease. The investigators found somatic stop-codon mutations in an average of 5.8 percent of crucial portions of genetic material that deliver instructions from DNA, called messenger RNA, in normal blood samples and in a quarter of leukemia samples.

“DNA is the blueprint for all living cells. It carries the genetic code for most biological functions and is passed virtually unchanged from generation to generation,” said Baysal, who also is an associate investigator at Magee-Womens Research Institute. “Harmful alterations in the code — mutations — can produce genetic disorders and play an important role in the development of cancer. Normal cells such as monocytes, lymphocytes and natural killer cells have many mechanisms to recognize and repair mutations, but a stop-codon mutation is a kind of permanent ‘off’ switch that has escaped DNA repair,” he added.

“We believe there is a good biological reason for this. It may allow the cells to survive in a low-oxygen environment, such as where there is cancer or infection,” said Baysal. “It is part of the process for immune cells to ‘armor up’ for battle against cancer cells and other diseases.”

Earlier research on the mutated gene suggests the stop-codon mutation might be part of the programmed adaptive response to oxygen deprivation. This mutation and its location is “unusual because it predicts loss of function, it targets a classical tumor-suppressor gene, and it occurs in (peripheral blood mononuclear cells),” Baysal wrote, adding that the mutation is present at much higher levels in messenger RNA compared to DNA.

“This may give us a tool to modify the immune cells’ survival in a low-oxygen environment, which could help the cells to survive and fight infections and tumors,” said Baysal, calling the mutated gene a potential “therapeutic target.”

The study was funded by the National Cancer Institute.

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Docs support pay for performance

Physician groups that receive “pay-for-performance” incentives linking some compensation to key quality or process measures are more likely to undertake improvement efforts targeting these measures, according to a study published in the May issue of The American Journal of Managed Care. The study also found that physician group leaders broadly support such performance-based pay, but they believe these incentives must be larger than those currently offered by most commercial health plans to drive quality improvements.

The study, led by Ateev Mehrotra, assistant professor at Pitt’s School of Medicine and a policy analyst at RAND Corp., is believed to be the first to examine the relationship between pay-for-performance, or P4P, programs and the use of quality improvement initiatives by physician groups.

Previous studies of P4P programs have shown little, if any, improvement in performance on quality outcomes. In this study, “the relationship we found between pay-for-performance incentives and quality initiatives is important because it could indicate these incentives are having the desired effect. Most health plans have created these incentives because they want physicians to devote more resources to quality improvement,” said Mehrotra. “Though we can’t say definitively that P4P ‘caused’ physician groups to undertake these quality efforts, it is compelling that the majority of physician leaders reported that P4P had a meaningful effect on their groups.” Mehrotra and his colleagues conducted a survey of physician group leaders in Massachusetts, one of the few states where health plans have widely implemented performance incentives and where publicly available reports on quality are available for all physician groups.

With 79 of 100 physician groups interviewed, the researchers found that 89 percent of the groups had a P4P incentive in at least one commercial health plan contract. Most groups had incentives linked to certain preventive care and chronic disease management measures, such as the percentage of eligible patients who received mammography. Seventy-two percent of the physician groups reported at least one ongoing quality improvement initiative focused on these measures.

The most common type of quality improvement initiative was the development of an internal registry and feedback system for physicians about their performance on a given measure. Other efforts included the use of electronic reminders to prompt providers about any missing or appropriate care and group visits for patients with chronic illness.

Among the groups reporting P4P incentives, more than a third reported that the incentives were moderately or very important to the group’s financial performance. But 56 percent reported that the incentive had a moderate or significant effect on the group.

Overall, 77 percent of physician group leaders expressed support for paying physician groups based on their performance on certain quality measures, and 79 percent reported that P4P would lead to quality improvement during the next three years. However, 91 percent reported that the ideal percentage of revenue tied to P4P incentives should be 5 percent or more. At the time of the study, the percentage of total revenue tied to P4P incentives was 2.2 percent for those groups reporting such data.

“This suggests that larger incentives may be necessary to engage more groups,” said Mehrotra. But he noted that other factors also may influence the decision to undertake quality improvements, including the cost and effectiveness of a given quality initiative, a physician group’s operating margin and the size and structure of the group. “We found that larger groups were more likely than smaller groups of independent practitioners to undertake quality improvement initiatives, as were groups that employ a majority of their physicians.”

The study highlighted possibly conflicting views between physician group leaders and practicing physicians. The majority of leaders reported that their groups’ physicians do not view quality as a major problem in health care, despite alarms raised by the Institute of Medicine and other health care experts. In the face of this skepticism, physician group leaders may look to P4P as a way to engage practicing physicians in efforts to improve quality, the researchers concluded.

The study was supported by the Robert Wood Johnson Foundation through a grant to the Massachusetts Health Quality Partners.

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Nicotine enhances pleasure

The smoker puffing away in the corner might be hooked on more than just nicotine. A 15-year study by Pitt researchers suggests that nicotine also enhances the pleasure smokers get from their surroundings when they smoke and creates a psychological link between that amplified satisfaction and cigarettes.

The findings present new ideas about the way nicotine works and the reason people become addicted to cigarettes, said principal investigators Anthony R. Caggiula, chair of psychology; Eric Donny, assistant professor of psychology, and Alan F. Sved, chair of neuroscience, all in Pitt’s School of Arts and Sciences. The ongoing research has yielded more than a dozen academic journal articles. One of the latest appears in the May edition of the journal Neuropsychopharmacology.

Current ideas about cigarette addiction and cessation focus largely on a smoker’s appetite for nicotine, Caggiula said. Psychologically, nicotine is considered a primary reinforcer — something that drives people to engage in and repeat behaviors to acquire the desired substance. Other addictive drugs such as heroin and cocaine, and basic needs such as food and water, fall into the same category.

Without discounting nicotine as a powerful primary reinforcer, Donny said, the Pitt research proposes that nicotine also amplifies the satisfaction smokers get from their environment, from the smell of cigarette smoke to drinking in a favorite bar. This second action of nicotine is known as a reinforcement enhancing effect. Smokers associate the heightened enjoyment with cigarettes and continue smoking to recapture that sensation.

Nicotine’s pleasure-intensifying properties help explain why smoking remains among the hardest habits to overcome despite the well-publicized perils of cigarettes and ample cessation therapies that administer nicotine, Caggiula said.

“If people were just after nicotine,” Caggiula asked, “why don’t they get addicted to it in other ways such as drinking it or shooting it into their arm? But people don’t do those things — they smoke cigarettes. There has to be something else at work here other than just an easy way to get nicotine. We’re not saying that focusing on the physical addiction to nicotine is worthless, but it’s incomplete.”

Donny tested the basic conclusion of nicotine as a reinforcement enhancer in clinical trials. He gave 30 adult smokers cigarettes with nearly all the nicotine removed. Participants smoked the cigarettes for a week or more before their interest in the cigarettes subsided, he said. Considering the absence of nicotine, Donny concluded that the smokers in the study derived pleasure from the act of smoking itself. The results were published in the February edition of the journal Addiction.

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More study needed on family support

Family-oriented psychosocial interventions seem to be beneficial in improving the mental and physical well-being of both patients with chronic illness and their family members, but the results aren’t as robust as researchers had hoped. In a study published in the April issue of Current Directions in Psychological Science, Pitt researchers say more research is needed to improve such interventions.

Prior studies have found that supportive and non-supportive actions by family members are linked with a patient’s emotional well-being, health behaviors, immune function, blood pressure and illness events. When psychosocial and behavioral interventions such as patient education, support groups and cognitive behavioral therapies are integrated into care for chronic illness, the patient’s health is greatly improved.

A patient’s chronic illness also has been shown to impact the psychological and physical wellbeing of the patient’s caregiver. Researchers have attempted to incorporate a family member into the psychosocial component of the patient’s care in an attempt to bolster the effects the interventions have on the patient while also benefiting the caregiver. By looking at a number of published studies on the topic, the current study found that the impact of involving a family member had smaller effects than expected.

“There are volumes of anecdotal evidence about how including a family member in care and psychosocial interventions can improve the mental and physical health of both the patient and family member. For a number of reasons, researchers haven’t been able to demonstrate consistent results across studies,” said Lynn M. Martire of the Department of Psychiatry and Pitt’s University Center for Social and Urban Research. “However, the small effects that have been shown overall make for a compelling argument that we need to carry out well-designed studies that allow us to draw stronger conclusions.”

In a review of the scientific literature, Pitt researchers found that in 70 studies that compared a family-oriented psychosocial intervention to usual medical care alone, the family-oriented interventions had a small but promising effect on the emotional well-being of the patient and family member.

A second literature review of 12 studies that compared patient-oriented psychosocial interventions to family-oriented interventions showed varying results, based on a number of factors, including disease, gender and type of intervention.

The researchers say these findings suggest that future research into family interventions should attempt to target interactions that promote or derail healthy behaviors and incorporate strategies from family caregiver interventions.

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2 Pitt centers receive alcohol study grant

Researchers from the Pittsburgh Adolescent Alcohol Research Center and from the Center for Rural Health Practice at Pitt-Bradford have received a $900,000 grant to fund a three-year study on the use of alcohol among adolescents.

The grant was awarded by the National Institute on Alcohol Abuse and Alcoholism, a unit of the National Institutes of Health.

“This grant will help to support the establishment of the Northwest Pennsylvania Adolescent Alcohol Research Cooperative (NPAARC),” said Lorraine Ettaro, interim director of the Center for Rural Health Practice and co-principal investigator on the grant. “The goal of the cooperative is to develop the capacity of primary health care systems in the region to conduct research addressing underage drinking.”

In collaboration with practitioners, adolescents and parents, researchers from the two centers will be developing and evaluating the effectiveness of a computer-assisted clinical decision support system.

Primary care providers play a vital role in identifying, intervening and referring underage drinkers to treatment, Ettaro explained, but only a small proportion of the providers consistently engage in routine screening, intervention and referrals for adolescents who use alcohol. She said that prior research has identified various barriers to providers’ involvement in routine substance use screening, education and referrals of adolescents.

In rural areas, additional factors may further impede identification, treatment and referral for adolescent alcohol use, she said. Ettaro indicated that research is needed to develop a better understanding of these barriers and novel approaches for addressing them.

These monies also will enable area rural health care systems to assess the extent of underage drinking in the region and develop capacity for intervening with this problem, Ettaro explained.

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PSC aids weather forecasting model

Pittsburgh Supercomputing Center (PSC) technology is aiding the National Oceanic and Atmospheric Administration (NOAA) in an experiment to improve forecasting of severe storms.

A major goal of the 2007 NOAA hazardous weather testbed (HWT) spring experiment is to assess how well “ensemble” forecasting — a computationally demanding approach — works to predict thunderstorms, including the supercells that spawn tornados.

It is the first time ensemble forecasts, multiple runs of the same forecast model (to measure the uncertainty inherent in weather forecasts), are being carried out at the spatial resolution at which storms occur. It also is the first time ensemble forecasts are being carried out in real time in an operational forecast environment.

The project forecasts require more than 100 times more computing daily than the most sophisticated National Weather Service operational forecasts.

Collaborators in the experiment are the NOAA storm prediction center, the Center for Analysis and Prediction of Storms (CAPS) at the University of Oklahoma-Norman; the NOAA National Severe Storms Laboratory in Norman; LEAD (Linked Environments for Atmospheric Discovery), an NSF large information technology research grant program; TeraGrid Science Gateway, and the National Center for Supercomputing Applications in Illinois.

To implement CAPS’ daily forecast runs on PSC’s Cray XT3 using the WRF (Weather Research and Forecast) model, PSC coordinated the implementation of a dedicated link to a supercomputer at the University of Oklahoma, which post-processes the data. PSC also optimized the model and routines to speed processing.

Each night, from April 15 until June 1, CAPS transmits weather data to the PSC’s Cray XT3, which runs a 10-member ensemble (10 runs of the model) in addition to a single higher-resolution WRF run, in time to produce a forecast for the next day by morning. The forecast domain extends from the Rockies to the East Coast, two-thirds of the continental United States.

The ensemble runs are at four-kilometer horizontal resolution, with the single WRF forecast at two kilometers. A scientific objective is to assess the value of ensemble forecasts in relation to the higher-resolution forecast, and the XT3 and a high-bandwidth link to Oklahoma make it possible to do both of these demanding runs daily under real-time constraints.

University of Oklahoma meteorologist Kelvin Droegemeier, who directs LEAD, said: “Ensembles open up a new array of interpretative capabilities to forecasters analyzing how good the forecast is. With ensembles, you’re not only forecasting the weather, you’re forecasting the accuracy of the forecast.”