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October 13, 2016

Research Notes

Early Zika vaccines effective in newborn mice

Two vaccines against Zika virus developed at the School of Medicine have conveyed immunity from female mice to pups conceived weeks after the mother’s vaccination.

When challenged with Zika virus within a week of their birth, both vaccines protected the pups against neurological damage better than pups with no maternal-conferred immunity. The results are published online now and scheduled for the November issue of EBioMedicine.

Said senior author Andrea Gambotto, surgery faculty member in the School of Medicine: “We’ve not only developed a promising vaccine candidate to move toward larger preclinical and, eventually, human clinical trials, but also a delivery format that would be inexpensive to produce and distribute to hundreds of thousands of people.”

Zika is a virus spread primarily through the bite of an infected mosquito of the Aedes species. When a pregnant woman is infected, the virus can pass to her fetus, which can damage the developing baby and cause severe neurological birth defects, including microcephaly, or an abnormally small head.

One of the two vaccines uses a “microneedle array” to deliver the vaccine just below the surface of the skin through tiny crystals that dissolve after being affixed to the skin by a Band-Aid-like patch. The technology was co-invented by Louis D. Falo, chair of the school’s Department of Dermatology and co-author of the study.

The other vaccine uses the traditional needle delivery format and adenovirus, a type of common cold virus, to present Zika antigens to the immune system to induce immunity.

Both vaccines used proteins on the “envelope,” or outer shell, of the virus as the antigen to prime the immune system so it can quickly recognize and fight off the actual virus. This approach has worked to develop West Nile, yellow fever and dengue vaccines.

Three groups of female mice, with five mice per group, were immunized with either one of the two vaccines or a saline solution with no vaccine for the control group. Two weeks after the initial vaccination, the mice received a booster of the same vaccine they originally received.

Blood tests were performed at vaccination and every two weeks afterward. The mice showed immunity against Zika two weeks after immunization with the adenovirus Zika vaccine and six weeks after immunization with the microneedle array Zika vaccine.

Five weeks after initial immunization, the female mice were mated with unvaccinated males. Because mice do not develop microcephaly, giving the mothers Zika while pregnant would be unlikely to affect the pups. So the researchers waited until one week after the pups were born and then exposed them to Zika. All of the pups from the mothers immunized with adenovirus Zika vaccine and half of the pups from the mothers who received the microneedle array vaccine survived infection. Only 12.5 percent of the pups from mothers in the unimmunized control group survived.

Furthermore, all of the control group pups showed signs of neurological damage, including loss of balance, muscle weakness and hind-limb paralysis. Five out of six of the microneedle array group pups also exhibited neurological issues, though they weren’t as severe as the control group’s symptoms. None of the adenovirus vaccine pups showed significant neurological problems.

Although the adenovirus Zika vaccine definitely performed better in this study, Gambotto said it was used as a proof-of-principle vaccine in mice to quickly develop and test whether the envelope protein antigen would work in a mouse model. It wouldn’t work well in humans because the vast majority of us have already had adenovirus colds so our immune systems would simply neutralize the vaccine and not develop proper Zika antibodies.

“We decided to move forward with the microneedle array Zika vaccine and have since developed a promising, second-generation vaccine,” said Gambotto.

“We are hopeful, now that Congress has approved the $1.1 billion bill to provide funding for Zika prevention and research, that we’ll be able to do larger-scale studies to evaluate and develop this vaccine for possible human clinical trials.”

Additional Pitt researchers on this study were Eun Kim, Geza Erdos, Shaohua Huang and Thomas Kenniston.

UPMC and the Department of Surgery provided funding for the study.

earPitt, Allergan investigate tinnitus persistence

Nearly 50 million Americans suffer from tinnitus, an audiological and neurological condition most frequently characterized by ringing in the ears when no actual noise is present, but little is known about the physiology underlying the condition. Allergan, a global pharmaceutical corporation, and Pitt have agreed to a research partnership to help understand the molecular and cellular mechanisms that sustain tinnitus once it has developed.

Thanos Tzounopoulos, endowed chair in auditory physiology, faculty member in otolaryngology and member of the auditory research group in the School of Medicine, will lead the research.

Tzounopoulos has spent the past eight years working on projects funded by the U.S. Department of Defense (DOD) and the American Tinnitus Association that focused on determining the mechanisms that lead to the triggering — rather than maintenance — of tinnitus. His team found that exposure to excessive noise in mice caused a reduction in a potassium channel activity.

In collaboration with Peter Wipf, faculty member in the Department of Chemistry, the team discovered a highly potent and selective potassium channel activator that can prevent the development of tinnitus.

“Due to the structural relationship of this compound to the FDA-approved anticonvulsant drug retigabine, which has considerable side effects, there is a significantly enhanced probability that this activator will gain regulatory approval,” said Tzounopoulos.

The new project with Allergan will use two-photon in vivo imaging in mice to explore the cortical areas and the specific cell types that are different in mice with established tinnitus. Once cell-specific tinnitus-related differences are discovered, the researchers will perform experiments to identify the specific molecular changes that mediate these differences. “We believe that understanding these mechanisms will lead to the development of drugs and therapies for eliminating tinnitus after it becomes permanent,” said Tzounopoulos.

Faculty receive NIH early career awards

Two faculty members received awards from the National Institutes of Health (NIH) aimed at early career investigators who demonstrate the potential for innovative research.

William R. Stauffer, neurobiology faculty member in the School of Medicine and a Brain Institute member, received an NIH Director’s New Innovator Award, given to support “exceptionally creative new investigators who propose highly innovative projects,” according to NIH.

Stauffer will study how the brain processes rewards and how we make choices. This aspect of brain function is critical to our interpretation of the world around us; consequently, deficits are reflected in disorders such as depression, schizophrenia and obsessive-compulsive disorder. He will perform his studies in non-human primate research models using novel behavioral techniques, electrophysiology and optogenetics, which uses light to control genetically modified cells.

Matthew D. Neal, faculty member in surgery and critical care medicine in the School of Medicine, was selected for a Maximizing Investigators’ Research Award by NIH’s National Institute of General Medical Sciences (NIGMS). The award, which is part of a pilot program, is designed to give promising independent early-career investigators flexibility and stability, “thereby enhancing scientific productivity and the chances for important breakthroughs,” according to NIGMS.

Neal will investigate the function of platelets in blood clotting during trauma. His long-term goal is to develop therapies that can be more effective in preventing excessive bleeding in traumatic injuries, as well as preventing the subsequent development of blood clots, a major problem in trauma patients.

First retrievable vascular stent funded by DOD

Researchers at the Swanson School of Engineering and the UPMC Division of Vascular Surgery were awarded a four-year, $2.5 million contract from the DOD for further development of a retrievable stent to treat noncompressible hemorrhages, a major cause of mortality among servicemen and women, as well as civilian gunshot victims.

Said Bryan W. Tillman, vascular surgery faculty member in the School of Medicine and principal investigator: “A well-known principle of first aid for bleeding is to apply pressure to the bleeding site. Unfortunately, for injuries within the chest and abdomen, this maneuver is not effective, and death rates exceed 80 percent due to massive bleeding in a very short time.”

The proposal, “A Rapid, Temporary Stent for Hemorrhagic Injuries of the Torso,” allows for refinement of a novel stent that can be rapidly placed by nonvascular physicians with minimal training. The system uses radiofrequency tags similar to the microchips used to identify pets. A handheld device is used by physicians to help place the tagged stent in a blood vessel, simplifying positioning and replacing bulky and often unavailable X-ray equipment.

“The absence of immediate vascular expertise and X-ray imaging on the battlefield or even in some hospitals remains a major obstacle to treat hemorrhages,” Tillman said. “What is needed is a way to rapidly control massive bleeding until a patient can be transported to a proper medical facility or to a properly equipped vascular hybrid room.”

As the first fully retrievable vascular stent, the proposed device can be removed at the time of permanent repair by vascular surgeons with dedicated imaging equipment. A prototype of the stent was developed and successfully tested by UPMC as a part of the DOD application for funding.

“This device will be used to save the lives of critically wounded soldiers until they can be transported to a major medical facility,” Tillman said.

“We expect that this same technology also will be used in trauma bays when vascular expertise or state-of-the-art hybrid operating suites are not immediately available to rescue civilian patients with life-threatening traumatic injuries of the liver and large vessels.”

Other researchers involved, all faculty members in the Swanson school, are Youngjae Chun, industrial engineering/bioengineering; William Clark, mechanical engineering and materials science; and Sung Kwon Cho, mechanical engineering and materials science.

New mechanism for integrity of capillaries uncovered

Researchers from the School of Medicine and Children’s Hospital have uncovered a new mechanism governing the integrity of capillaries, the smallest branches of the circulatory system. The study was published in Cell Reports.

Capillaries are lined by endothelial cells, which can maintain a water-tight barrier to prevent leakage of fluid from the bloodstream into surrounding tissue. However, under certain conditions, these cells can be stimulated to induce a rapid but temporary increase in the leakiness of this barrier. This allows fluid and immune cells to exit the bloodstream and accumulate in tissue leading to a condition known as “edema,” a cornerstone of the body’s inflammatory response.

While this acute increase in permeability is important for normal inflammation, it can cause more harm than good if left unchecked. In a broad range of conditions, from acute hypersensitivity responses such as a bee sting reaction or asthma attack, to brain swelling in trauma patients, excessive capillary leakiness can become life threatening.

A lack of knowledge about how endothelial cells regulate permeability has resulted in current therapies being mostly supportive in nature, directed at overcoming the consequences of edema and inflammation. This study highlights the unexpected role for an enzyme, MALT1, in mediating endothelial permeability initiated by several key inflammatory stimuli.

To study the role of MALT1, researchers used a mouse model that mimicked a state of septic shock, a life-threatening inflammatory condition that can lead to excessive fluid accumulation in the lungs. Mice genetically deficient in MALT1 enzymatic activity were protected from this fluid accumulation, demonstrating the crucial role of MALT1 activation in increasing leakiness of the endothelial barrier.

Said Linda McAllister-Lucas, pediatrics faculty member in the School of Medicine, chief of the Division of Pediatric Hematology/Oncology at Children’s Hospital and a senior author of the study: “Armed with this new knowledge, we can now begin to think about how targeting MALT1 might be an effective strategy for curtailing excessive acute capillary leakiness in a range of clinical scenarios.”

The research group is focused on compounds that were used several decades ago in the field of psychiatry but only recently discovered to inhibit MALT1 effectively.

Said Peter Lucas, faculty member in pathology and pediatrics in the School of Medicine and the study’s co-senior author: “It’s particularly exciting to contemplate how an old class of pharmaceuticals, the phenothiazines, might be quickly repurposed for use in an entirely new therapeutic arena: the treatment of acute edema.”

The authors consider their current work as a “proof-of-principle” that pharmacologic MALT1 inhibition might have therapeutic benefit in conditions associated with capillary leak such as sepsis, trauma or allergic/hypersensitivity reactions.

The work was supported primarily by a grant from the National Heart, Lung and Blood Institute.

Micro drone swims human body

Fifty years after the release of the iconic science-fiction movie “Fantastic Voyage,” researchers are beginning to launch fleets of tiny swimming robots inside the human body, with biomedical applications. These super-small submarines have the potential to navigate the body less invasively and with more maneuverability than some current surgical and medical procedures. However, the ability to accurately control the movement of these robots remains the focus of many studies.

Because there isn’t enough room at the micro and nano scales to include motors, actuators or batteries, researchers are exploring methods of directing the robot movement by using electromagnetic fields, interacting with biological and chemical fuels within the body or even harnessing bacteria and hitching a ride. For Sung Kwon Cho, mechanical engineering and materials science faculty member in the Swanson school, the answer seems to be an arrangement of strategically positioned tiny bubbles and an acoustic field.

The National Science Foundation (NSF) awarded Cho a three-year, $724,691 grant for research into the development of a micro swimming drone that can be located and controlled inside the human body through ultrasound waves. When the sound waves pass through gaseous bubbles implanted in the drone, Cho and his team can propel it forward and change its direction. By adding a few more bubble-filled tubes, the drone will be able to follow a user-defined, three-dimensional path.

Said Cho: “We have already proven that our design works in two-dimensional space. By placing a bubble of air in a cylinder and passing a sound wave through it, the excited air moves in a three-dimensional space. Longer tubes respond to lower frequencies and shorter tubes respond to higher frequencies. Not only can we propel the robot forward, but we can change direction, too. There are many ways to apply this design to three-dimensional space, and the grant will fund our research into optimizing the robot for practical applications.”

Cho’s method of acoustically exciting micro bubbles within the robot has several advantages over previously proposed designs. Most clinics are equipped with ultrasound systems, so ultrasound-driven robots could be easily integrated into the existing medical infrastructure. Furthermore, Cho’s proposed robot is less bulky, cheaper and more compatible with the human body than other designs.

“The proposed drone has many potential medical applications,” said Cho, “including local treatment of tumors; removal of fatty deposits on blood vessel walls; break[ing] or removal of blood clots, kidney stones and liver stones; cleaning of burnt or wounded tissue; attack[ing] and removal of parasites; removal of tar in the lungs; and drug delivery.”

The drone will be tested under hydrodynamic conditions similar to living organs, including tests inside fish. The fish selected have transparent tissue, allowing the researchers to observe the drone’s movement unobstructed.

Pitt co-principal investigators are Kang Kim, faculty member in medicine and bioengineering, and Nitin Sharma, faculty member in mechanical engineering and materials science.

NSF’s National Robotics Initiative is providing funding.

Senior tennis playerHealthy lifestyle shortens end-of-life disability

Leading a healthy lifestyle not only extends one’s lifespan, but also shortens the time that is spent disabled.

An analysis of a quarter-century of data by scientists at the Graduate School of Public Health and their colleagues nationwide revealed that older adults with the healthiest lifestyles could expect to spend about 1.7 fewer years disabled at the end of their lives, compared to their unhealthiest counterparts. The study results were published in the Journal of the American Geriatrics Society.

Said senior author Anne B. Newman, chair of the Department of Epidemiology in Public Health and Katherine M. Detre Professor of Population Health Sciences: “The duration of the disabled period near the end of one’s life has enormous personal and societal implications, ranging from quality of life to health care costs.”

Newman and her colleagues examined data collected by the Cardiovascular Health Study, which followed 5,888 adults for 25 years. All of the participants were aged 65 or older and were not institutionalized or wheelchair-dependent when they enrolled.

The participants reported or were assessed for various lifestyle factors, including smoking habits, alcohol consumption, physical activity, diet, weight and their social support system. The researchers took into account and adjusted results for such factors as participants’ age, sex, race, education, income, marital status and chronic health conditions.

Across all the participants, the average number of disabled years directly preceding death — years when the person had difficulty eating, bathing, toileting, dressing, getting out of bed or a chair, or walking around the home — averaged 4.5 years for women and 2.9 years for men.

For each gender and race group, those with the healthiest lifestyle (those who were nonsmokers of a healthy weight and diet and getting regular exercise) lived longer and had fewer disabled years at the end of their lives. For example, a white man in the healthiest lifestyle group could expect to live 4.8 years longer than his counterpart in the unhealthiest group, and at the end of his life, he’d likely spend only two of those years disabled, compared to 3.7 years for his unhealthy counterpart.

Lead author was Mini E. Jacob, who completed this project during her Pitt doctoral studies and currently is at Boston University School of Public Health and Harvard medical school. Additional authors are from the University of Washington; Seattle Veterans Affairs Medical Center; Florida International University; Stanford University; University of California-Davis Medical Center; and New York Academy of Medicine.

This research was supported by the National Institute on Aging, NIH, the National Institute of Neurological Disorders and Stroke and the University of Pittsburgh Claude D. Pepper Older Americans Independence Center.

Pitt joins vaccine surveillance network

Medical doctor injecting a vaccine into the arm of a patientChildren’s Hospital will join a group of academic medical centers nationwide that survey for communicable diseases in children and evaluate vaccine effectiveness. The data collected and studies conducted, led by School of Medicine faculty, will help detect emerging disease outbreaks and be used to make health policy decisions regarding vaccination and investment in drug development.

Through a $5 million, five-year grant from the U.S. Centers for Disease Control and Prevention (CDC), Children’s will become a New Vaccine Surveillance Network (NVSN) site and collect information on respiratory and gastrointestinal viruses circulating in Allegheny County.

Said John V. Williams, pediatrics faculty member and principal investigator of the new NVSN site: “There are few or no effective antivirals for these viruses, and therefore vaccination is the most promising intervention. Active disease surveillance is necessary to establish the effectiveness of existing vaccines and provide the data needed to guide policymakers and pharmaceutical industries in the development of new vaccines. We intend to provide that critical information.”

Acute respiratory illnesses are caused by viruses that include respiratory syncytial virus, human metapneumovirus and influenza, and may interfere with normal breathing. Acute gastroenteritis is caused by viruses including rotavirus and can cause diarrhea and dehydration.

Said Marian Michaels, pediatrics and surgery faculty member and co-principal investigator of the new NVSN site: “Together these are the leading causes of disease among children in the U.S. and globally. These infections can require hospitalization and can be deadly. They also are quite costly, both in terms of treatment as well is indirect costs, including parental leave from work.”

The Children’s site of the NVSN has three aims:

• To evaluate the effectiveness and impact of current or upcoming vaccines and other proactive disease prevention strategies, then analyze the results to inform pediatric vaccine-related policies;

• To assess the burden of acute gastroenteritis and acute respiratory illness by voluntarily enrolling children seen at the hospital, along with healthy children enrolled at well-child visits, and perform laboratory tests to confirm or rule out viral infection; and

• To gain new insights into the evolution and transmission of pediatric diseases, the impact of vaccines on targeted and vulnerable populations and the socioeconomic and microbiological factors potentially relevant to public health interventions.

The NVSN has been funded by the CDC since 2000, becoming a core component of national influenza surveillance.

Additional Pitt investigators at the new NVSN site are Robert Hickey, Judith Martin, Bala Goundappa and Heather Eng.

Early hot flashes could predict  heart disease

Women who experience hot flashes and night sweats earlier in life are more likely to die from cardiovascular disease (CVD) when compared to women with later onset menopausal symptoms, according to research from the School of Medicine published in Menopause.

Up to 80 percent of women experience menopausal symptoms, particularly hot flashes and night sweats, at some point during the menopause transition.

The research indicates that early onset of menopausal symptoms is associated with dysfunction of the endothelium, which is the lining of blood vessels. Endothelial dysfunction was measured by assessing flow-mediated dilation (FMD), a noninvasive ultrasound measure of how well the vessel dilates in response to pressure on the wall of the blood vessel.

Rebecca Thurston, psychiatry faculty member in the School of Medicine, and her colleagues investigated associations between menopausal symptoms and risk for CVD complications among postmenopausal women participating in the National Heart, Lung and Blood Institute’s women’s ischemia syndrome evaluation study. A total of 254 postmenopausal women with signs and symptoms of ischemic heart disease were evaluated, and researchers found those who had hot flashes before age 42 were more likely to have lower FMD, suggesting adverse endothelial changes, as well as higher mortality from heart disease.

“While more work needs to be done to confirm our findings,” Thurston said, “our research could, one day, help us predict the midlife women who might be at increased risk for cardiovascular disease so that we proactively target these women for early prevention strategies.”

PInCh awards $450K for health care ideas

A total of $450,000 in funding was awarded to innovative projects that address problems in health care at the Pitt Innovation Challenge (PInCh) finals event. Three projects gained $100,000 each in funding, and six others received $25,000.

The challenge, in its third year, was sponsored by the Clinical and Translational Science Institute (CTSI), the Office of the Provost and the Innovation Institute.

This year’s contestants were asked to submit proposals in response to the question: “What is your bold solution to a vital health problem?” After two rounds, 14 teams were invited to compete at the final pitch event, with six teams in the $100,000 category and eight teams in the $25,000 category.

The $100,000 awards went to:
• Neurogel: An injectable solution containing a regenerative matrix that promotes healing of damaged nerve tissue.

• Esophagel: A minimally invasive treatment for Barrett’s esophagus, a condition which, if left untreated, can lead to esophageal cancer.

• CardioTrak: A novel peptide that can deliver radioisotopes specifically to heart muscle, thus reducing the amount of radiation absorbed by the body during cardiac stress tests.

The $25,000 awards went to:

• Aeronics Inc.: A portable device that uses novel porous materials to store medical oxygen at low pressure in a standard 12-ounce aluminum can.

• Emotion Prosthetics: A wearable device called Purrr that intuitively detects stress and noninvasively counters it through stimulating cranial nerves.

• EyeCures: A new generation of eye drops using antibody technology to allow current advanced biological drugs to act on the surface of the eye.

• I-HITS: An individualized hand motion tracking system that allows stroke patients and therapists to monitor and improve rehabilitation.

• VasoMag: A novel engineered biodegradable metallic vascular stent technology.

• Ventriculo-Amniotic Shunt for Fetal Aqueductal Stenosis: A device to drain excess fluid from the fetal brain and prevent progressive brain injury during pregnancy.
Finalist and semifinalist videos can be viewed on the PInCh website.

Evidence-based cancer treatments encouraged

Evidence-based treatment pathways implemented by UPMC 15 years ago to guide cancer care have become integral to ensuring that each patient receives the most up-to-date course of treatment specific to his or her cancer.

That’s the conclusion of a recent University of Pittsburgh Cancer Institute (UPCI) analysis showing the high physician compliance rate with the pathways, a standardization concept borrowed from the manufacturing sector.

The analysis, presented at the American Society for Radiation Oncology 2016 annual meeting, found that UPMC CancerCenter physicians nearly always complied with the standard, evidence-based treatment pathways or presented an acceptable alternative to a review panel of their peers.

Said lead author Brian Gebhardt, a third-year resident in the UPCI radiation oncology residency program: “Research and clinical trials are continuously yielding new and better cancer treatments, but it can take time for treatment protocols to be updated and, even then, physicians may be unfamiliar with rapid advances in treatment. Our treatment management process, called Clinical Pathways, is updated as often as necessary to ensure that our patients receive the best care. We set treatment protocols according to national guidelines, published literature and institutional experience, and then evaluate each option based on efficacy, toxicity and cost, in that order.”

UPMC CancerCenter physicians enter their treatment decisions into the online Clinical Pathways support tool that is integrated with patient electronic medical records. Sometimes for a specific cancer, there is only one type of treatment recommended, but often there is more than one evidence-backed option. If the physician wants to provide a treatment recommendation not compliant with the pathways, the tool launches a peer-review process that usually yields a ruling within two days.

Gebhardt and his colleagues evaluated 6,965 treatment decisions entered in 2015 across 22 UPMC CancerCenter sites and found that 91.3 percent followed the Clinical Pathways recommendation. In 605 decisions (the remaining 8.7 percent), the physician wanted to pursue a different treatment protocol than was recommended. Those cases were sent to peer review for evaluation. More than 99 percent were approved.

The reasons for an off-pathway treatment were: The patient was in poor health and an aggressive approach was not warranted (53.2 percent); the patient was doing better than expected on standard treatment and wanted more aggressive treatment (17.1 percent); the financial burden of treatment was too great (1 percent); the patient refused standard treatment (13.8 percent); or the physician didn’t agree with the Clinical Pathways-recommended treatment for some other reason (14.9 percent).

“Since less than 1 percent of the treatment decisions were ultimately rejected following peer review, we believe that we’ve hit upon a really positive, efficient method to widely disseminate the latest cancer treatment options throughout our UPMC CancerCenter sites,” said Gebhardt. “The peer-review process is a strong way to encourage compliance and ensure consistent, high-quality care across a large network.”

Additional UPCI authors were Sushil Beriwal and Dwight E. Heron.

PT or surgery for rotator cuff tears?

bad pain in shoulder of senior manRotator cuff tears are one of the most common injuries seen by orthopaedic surgeons, resulting in 30 percent of all visits to orthopaedic surgeons and over 150,000 surgical procedures per year in the United States. The preferred initial treatment is six-12 weeks of physical therapy (PT), but 25-50 percent of those cases still require surgery. Researchers at the Swanson school received a $2.79 million award from NIH to develop diagnostic methods to determine whether PT or surgery is the most effective initial treatment.

Principal investigator of the five-year study is Richard E. Debski, bioengineering faculty member and co-director of the Orthopaedic Robotics Laboratory. Co-principal investigators are James J. Irrgang, chair of the Department of Physical Therapy in the School of Health and Rehabilitation Sciences and vice chair of clinical outcomes research in the Department of Orthopaedic Surgery, and a colleague from the University of Texas Health Science Center.

Said Debski: “Rotator cuff injuries are one of the most common injuries for people aged 40-70, and can be caused by an injury but often occur simply from wear and tear as we age. Over the age of 50, chances increase that 40-50 percent of people have a tear and many don’t know it. Although physical therapy is the first preferred treatment, most patients still require surgery, which prolongs recovery time and increases costs. Our goal is to utilize new methods to perform a biomechanical analysis to determine whether a patient is more suited for PT or surgery, and thereby improve overall recovery.”

Over the first two years, Debski and his group plan to enroll 100 patients with isolated full thickness tears of the supraspinatus tendon, the most basic tear. The biomechanics analysis will measure shoulder motion and tear size before and after physical therapy. The study will use a new technology, a biplanar X-ray system, to provide quantitative measurements of shoulder motion during activities of daily living. The group also will track the tear size longitudinally out to one year. The long-term goal is to perform a clinical trial to determine whether the predictions make a difference in treatment outcomes.

—Compiled by Marty Levine

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