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Research Roundup
October 21, 2008, Volume 55, No. 9

Optimism Experts Handicap the Presidential Election

A Penn study analyzing the relative optimism of the 2008 presidential and vice presidential candidates has found Barack Obama and John McCain to be equally optimistic and Sarah Palin slightly more optimistic than Joseph Biden.

Researchers have determined that the most optimistic candidates win more than 80% of presidential elections dating back to 1900. How optimism confers this electoral advantage is unclear, but Penn psychologists believe optimistic candidates inspire hope in the electorate and try harder, particularly when faced with a challenge.

The study, conducted by researchers from Penn’s Positive Psychology Center, analyzed speeches given by both presidential candidates at the mid-August Saddleback Forum on Faith and the candidates’ respective convention acceptance speeches to determine levels of optimism.

“Although our initial report suggests this election is too close to call, shifts in optimism and rhetoric over the next few weeks may very well predict which side emerges as the victor,” Stephen Schueller, lead analyst on the project and a doctoral candidate in the department of psychology at Penn, said.

As a group, according to the study, the vice presidential candidates are less optimistic than the presidential candidates, with Senator Biden by far the most pessimistic of the four. In addition, Republican candidates show a higher level of internality when explaining positive events and a lower level of internality when explaining negative events, meaning they accept credit for good events and blame others as the cause for negative outcomes.

While speeches analyzed for the study were scripted, more instances of impromptu speech—such as the debates—can provide additional material to look for shifts and changes in optimism as the election draws.

“The first stage of this multi-part study established baseline optimism ratings for each candidate as of early this month, to be used to gauge and compare optimism levels throughout the remainder of the campaign. Additional stages will include analysis of candidates’ statements on specific issues and events. Analysis will be performed on three dimensions: absolute optimism and pessimism (where does the candidate fall on a numerical scale), comparison between candidates (where does the candidate fall in relation to other candidates) and relative optimism and pessimism (how the candidate compares with the initial baseline figure).

This study is also part of a larger project conducted in partnership with Sensory Logic Inc., a Minneapolis-based company with a proprietary methodology that assesses emotional engagement and focus on a second-by-second basis using facial muscles and combinations of muscle activities.

MsFLASH: NIH Initiative Treatments for Menopause

The University of Pennsylvania School of Medicine is part of a new National Institutes of Health (NIH) initiative to conduct clinical trials of promising treatments for the most common symptoms of the menopausal transition, such as hot flashes and night sweats.

The initiative—Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH)—is led by the National Institute on Aging (NIA) in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Research on Women’s Health (ORWH), all parts of the NIH. The network centers will collectively receive approximately $4.4 million each year of the initiative, which is projected to run for five years. The Penn portion of the five-center study will be led by Dr. Ellen W. Freeman, research professor and co-director of the Human Behavior and Reproduction Unit in Obstetrics and Gynecology at Penn.

Different treatments will be studied for their effectiveness against hot flashes and night sweats in diverse groups of women in trials with either placebo or usual-care control groups. The usual care group does not use a placebo pill. Investigators will also look at possible effects on other symptoms at middle age, including sleep disturbance, mood changes, vaginal dryness, and sexual function. Possible treatments to be studied during the five-year project period include: antidepressants such as paroxetine (Paxil) or escitalopram (Lexapro); paced respiration (slow deep breathing also known as relaxation breathing); yoga; low-dose estradiol patch and low-dose estradiol gel; and exercise programs, both moderate and vigorous.

The target date to start trials is June 2009. The Penn trial aims to recruit approximately 190 women from diverse ethic backgrounds.

“Estradiol is the only FDA-approved treatment for hot flashes at this time,” stated Dr. Freeman. “Researchers have studied other treatments but the studies have been small, often uncontrolled, and results are conflicting.”

Tests for Blocking Progression of Alzheimer’s Disease

Researchers at the University of Pennsylvania School of Medicine are conducting studies on an experimental medication to block nerve damage and inflammation in the brain that can lead to progressive memory loss and behavioral changes in people with Alzheimer’s disease. Current Alzheimer’s disease therapies focus on improving symptoms rather than attacking the root of the disease progression.

The buildup of plaques can trigger inflammation in the brains of people with Alzheimer’s disease (AD). A protein called amyloid beta builds up in plaque deposits and may promote damage to nerve cells. Researchers across the country will test an experimental drug that seeks to stop amyloid beta from binding to a particular receptor in the brain. This receptor, called RAGE, (receptor for advanced glycation endproducts), is believed to prompt an inflammatory reaction and has been linked to several chronic diseases, including Alzheimer’s and diabetes. Dr. Douglas Galasko, professor of neurology at the University of California, San Diego (UCSD), is directing the study. 

The study will recruit 400 volunteers aged 50 and up at 40 sites nationwide, including the University of Pennsylvania School of Medicine. The drug, which has been tested in animals and in preliminary human studies, is being studied in this Phase II clinical trial to determine if it will slow the progressive decline associated with Alzheimer’s disease.

“In addition to monitoring disease progression through cognitive tests, we will examine various biological markers of the disease,” said Dr. Jason Karlawish, local principal investigator and associate director of the Memory Disorders Clinic at Penn. “These include the degree of atrophy (or shrinkage) of the brain as measured by magnetic resonance imaging (MRI), the extent of amyloid buildup in the brain assessed by Positron Emission Tomography (PET) imaging, and levels of amyloid beta and other proteins in blood and spinal fluid.”

Physicians and nurses will monitor the participants during regular visits and measure the severity and progression of the disease using standard tests of functional and cognitive abilities. To ensure unbiased results, neither the researchers conducting the trial nor the participants will know who is receiving the study drug and who is getting the placebo.

Esophageal Cancer Tumor Suppressor

Researchers from Penn’s School of Medicine have identified a key step in the formation—and suppression—of esophageal cancers and perhaps carcinomas of the breast, head, and neck. By studying human tissue samples, they found that Fbx4, a naturally occurring enzyme, plays a key role in stopping production of another protein called Cyclin D1, which is thought to contribute to the early stages of cancer development.

When mutations block production of Fbx4, Cyclin D1 is not broken down, and subsequently contributes to cancer’s advance. Fbx4 acts like a bouncer, stopping trouble before it starts by breaking down Cyclin D1 before it can affect the body.

“Cyclin D1 was identified nearly 20 years ago and after that, it became apparent that it was overexpressed in a high percentage of tumors,” said Dr. Alan Diehl, associate professor of cancer biology at Penn’s Abramson Family Cancer Research Institute. “But its expression didn’t correlate to mutations within Cyclin D1, so we were looking for a protein that regulates accumulation. That’s Fbx4.”

For this study, researchers screened 116 esophageal tumors and found 16 mutations. Their findings were published in Cancer Cell.

The actual mutations researchers found are located within a highly conserved region of Fbx4 that functions like an ‘on switch.’ Mutations within that switch region inhibit activation of Fbx4, which means it can’t trigger destruction of Cyclin D1.

The results are important in that they show how Cyclin D1 becomes so prevalent in tumors. Before, it was thought that Cyclin D1 was present because of a mutation somewhere in the DNA of a cell. Instead, this study shows that Cyclin D1 naturally occurs, but our bodies have created a natural defense mechanism that breaks it down before cancer develops. “When Fbx4 is inactivated, it permits the accumulation of its target, Cyclin D1,” said Dr. Diehl.

While it remains important to define the cause of the initial mutations, this study provides researchers with a better understanding of the early stages of cancer, which is crucial to finding a way to reverse the process.

Co-authors are Drs. Hiroshi Nakagawa and Anil K. Rustgi from the department of genetics; Dr. Olena Barbash, Ms. Petia Zamfirova and Mr. Douglas I. Lin from the Abramson Family Cancer Research Institute; and Drs. Xiangmei Chen, Ke Yang and Fengmin Lu of Peking University Health Center in China.


Almanac - October 21, 2008, Volume 55, No. 9