OREGON STATE UNIVERSITY

scientific research and advances

Findings about protein could open door to new class of antibiotics

CORVALLIS, Ore. – Researchers have made the first-ever detailed, atomic-level images of a peroxiredoxin, which has revealed a peculiar characteristic of this protein and might form the foundation for a new approach to antibiotics.

Scientists at Oregon State University have used X-ray crystallography, a powerful technique that can reveal structures down to their individual atoms, to study the fundamental nature and behavior of this peroxiredoxin. Their findings were announced today in the journal Structure.

Peroxiredoxin is needed by all cells to help eliminate hydrogen peroxide, a toxin, and in normal cells this process is healthy and valuable. But peroxiredoxins inside bacteria also help provide protection from our immune cells and increase the virulence of bacterial cells that cause infections.

The researchers were able to visualize peroxiredoxin chemistry in action. They found that when it’s restrained and loses its mobility, it also loses its function. And if the normal function is lost, it can lead to cell death.

If a molecule can be found that selectively blocks the motions of peroxiredoxin only in bacterial cells – which the researchers believe may be possible – it could function as an entirely new way to kill those cells. This would leave normal cells undamaged and set the stage for new types of antibiotics.

With the increasing problem of antibiotic resistance to many existing drugs, this approach could have significant value, researchers said. It might also work in synergy with existing antibiotics to improve their efficacy, they said.

“Peroxiredoxins are found in animals, plants, and bacteria, and are proteins that are crucial for cell survival,” said Arden Perkins, the lead author on this study which was done at OSU, in collaboration with Andrew Karplus, a distinguished professor of biochemistry in the OSU College of Science.

“The main function of peroxiredoxins is to eliminate hydrogen peroxide in cells by converting it to water,” Perkins said. “This toxin is a byproduct of normal cell metabolism, and hydrogen peroxide has to be removed so it doesn’t damage the cell. If peroxiredoxin doesn’t do its job, cells will die.”

With the extraordinary images provided by X-ray crystallography, the research also discovered that there are special regions on bacterial peroxiredoxins, different from those found in humans, that could be specifically targeted. If compounds could aim at those targets and selectively shut down the protective function of peroxiredoxin just in bacteria, it would weaken or kill those cells.

“There’s a lot of potential for this to be foundational work, something we can build on to create a new class of antibiotics,” Perkins said. “The key concept is selectively restraining the motions of peroxiredoxins in some cells, inactivating its function and leading to the death of the cells you want to kill.”

In related approaches, Perkins said, the concept may also hold some value against certain non-bacterial pathogens, like those that cause malaria or African sleeping sickness, which increasingly are difficult to treat.

This work, titled Peroxiredoxin Catalysis at Atomic Resolution, was supported by the National Science Foundation, the National Institutes of Health, and the U.S. Department of Energy. It was done in collaboration with the OSU Department of Chemistry and the Wake Forest School of Medicine.

Perkins is now a postdoctoral scholar at the University of Oregon. Karplus is a fellow of the American Association for the Advancement of Science, the world’s largest scientific society, in recognition of his contributions to protein structure determination and for improving the analysis of crystallographic data.

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Andrew Karplus, 541-737-3196

karplusp@science.oregonstate.edu

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Peroxiredoxin
Peroxiredoxin chemistry

System may help treat rare genetic disorder, reduce severe side effects

PORTLAND, Ore. – Researchers at Oregon State University and other institutions have discovered a type of drug delivery system that may offer new hope for patients with a rare, ultimately fatal genetic disorder – and make what might become a terrible choice a little easier.

No treatment currently exists for this disease, known as Niemann Pick Type C1 disease, or NPC1, that affects about one in every 120,000 children globally, and results in abnormal cholesterol accumulation, progressive neurodegeneration and eventual death.

However, a compound that shows promise is now undergoing clinical trials, but it has major drawbacks – the high doses necessary also cause significant hearing loss, requires direct brain injection and causes lung damage.

New findings, published today in Scientific Reports, outline the potential for a nanotech-based delivery system to carry the new drug into cells far more effectively, improve its efficacy by about five times, and allow use of much lower doses that may still help treat this condition without causing such severe hearing loss.

The same system, they say, may ultimately show similar benefits for 50 or more other genetic disorders, especially those that require “brain targeting” of treatments.

“Right now there’s nothing that can be done for patients with this disease, and the median survival time is 20 years,” said Gaurav Sahay, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and corresponding author on the new study.

“The new cholesterol-scavenging drug proposed to treat this disorder, called cyclodextrin or HPβCD, may for the first time offer a real treatment. But it can cause significant hearing loss and requires multiple injections directly into the brain, which can be very traumatic. I’m very excited about the potential of our new drug delivery system to address these problems.”

In this approach, the HPβCD drug is attached to an extraordinarily small, nanotech-sized lipid particle that can carry it into cells, where it helps to flush out cholesterol. Researchers were surprised to discover, however, that the carrier itself also helped address the problem, while working in synergy with the drug it carries to greatly increase its effectiveness.

This should allow use of much lower dosages, Sahay said, and possibly an easier delivery through intravenous injection, instead of brain injection. In the form currently used, only 0.2 percent of the drug is able to cross the blood brain barrier.

In previous research with the HPβCD drug in animal models, the treatment did slow the progression of this disease, but did not reverse it. The disease focuses its damage on liver and brain cells.

In their report, researchers noted that this type of drug delivery system has several advantages, including prolonged circulation times, the ability to incorporate multiple drugs with different mechanisms of action, and a variety of “targeting ligands” that can help cross the blood brain barrier.

The researchers have also partnered with Dr. Edward Neuwelt at the OHSU Blood Brain Barrier Program, who has pioneered temporary opening of the blood brain barrier in humans to access drugs to the brain. They are also working leaders in the NPC disease field to translate these findings in-vivo.

“Taken together, nanocarriers can serve as a platform that can effectively deliver small molecules, genes and perhaps imaging agents for treatment and diagnosis of a wide variety of other rare lysosomal storage disorders,” the researchers wrote in their conclusion.

This research was supported by the OSU College of Pharmacy, OSU Venture Development Funds, AACP New Investigator Award, Birmingham Fellowship and Wellcome Trust Seed Award. Collaborating researchers were from the University of Birmingham, Oregon Health & Science University, and Newcastle University.

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Gaurav Sahay, 503-346-4698

sahay@ohsu.edu

Research outlines cellular communication processes that make life possible

CORVALLIS, Ore. – Researchers have discovered a mechanism of intercellular communication that helps explain how biological systems and actions – ranging from a beating heart to the ability to hit a home run – function properly most of the time, and in some scenarios quite remarkably.

The findings are an important basic advance in how cell sensory systems function. They shed light on the poorly-understood interaction between cells - and they also suggest that some of the damage done by cancer cells can be seen as a “failure to communicate.”

The work was reported today in Proceedings of the National Academy of Sciences by physicists from Oregon State University and Purdue University, done with support from the National Science Foundation and the Simons Foundation.

Scientists have long known that cells have various types of sensory abilities that are key to their function, such as sensing light, heat, nerve signals, damage, chemicals or other inputs.

In this process, a chemical stimulus called ATP functions as a signaling molecule, which, in turn, causes calcium levels in a cell to rise and decline, and tells a cell it’s time to do its job – whether that be sending a nerve impulse, seeing a bird in flight or repairing a wound. These sensing processes are fundamental to the function of life.

“We’ve understood for some time the basics of cellular sensory function and how it helps a cell respond to its environment,” said Bo Sun, an assistant professor of physics in the College of Science at Oregon State University, and a corresponding author on this study.

“The thing is, individual cells don’t always get the message right, their sensory process can be noisy, confusing, and they make mistakes,” Sun said. “But there’s strength in numbers, and the collective sensory ability of many cells working together usually comes up with the right answer. This collective communication is essential to life.”

In this study, researchers helped explain just how that works for animal cells.

When cells meet, a small channel usually forms between them that’s called a gap junction. On an individual level, a cell in response to ATP begins to oscillate, part of its call to action. But with gap junction-mediated communications, despite significant variability in sensing from one cell to another, the sensitivity to ATP is increased. Oscillation is picked up and becomes more uniform.

This interactive chatter continues, and a preponderance of cells receiving one sensation persuade a lesser number of cells reporting a different sensation that they must be wrong. By working in communication and collaboration, most of the cells eventually decide what the correct sensory input is, and the signal that gets passed along is pretty accurate.

With this accuracy of communication, cells in a heart chamber collectively decide to contract at the appropriate time, and blood gets pumped, dozens of times a minute, for a lifetime. Neuron cells send accurate signals. Photoreceptor cells see clearly.

This research was done with fibroblast cells, which are used in wound healing, but the results should apply to many cellular sensing mechanisms, researchers said.

Cancer cells, by contrast, are poor communicators. This study showed that they resist this process of collective communication, and when enough of them are present, the communicative process begins to lessen and break down. This may be at least one of the ways in which cancer does its biologic damage.

“These processes of collective sensory communication are usually accurate, but sometimes work better than others. Mistakes are made,” Sun said. “Even so, this process makes life possible. And when everything goes just right, the results can be remarkable.”

Consider a baseball player trying to get a hit, which Ted Williams once called “the hardest single thing to do in sport.” A major league pitcher hurls a 93 mile-per-hour fastball, low but possibly a strike. 

The photoreceptor cells in the batter’s eyes see the pitch coming. Some cells see it as a curve in the dirt, and some mistake it for a changeup, a slower pitch. But the majority of the cells come to the correct conclusion, it’s a fastball at the knees, and they spread the word. After extensive communication between all these cells, a conclusion is reached and the correct message is sent to neurons in the brain.

The brain cells, in turn, send a strong signal through nerves to muscles all over the batter’s body, the shoulders, legs, and especially arms. The signals arrive and once again a collaborative process takes place, deciding what the message is and how to react. Calcium ions in muscle cells are triggered and a brutally fast-but-accurate response is triggered, swinging the bat. This entire process, from the ball leaving the pitcher’s hand to contact with the bat, takes less than half a second.

On a perfect day – the cellular debate over what pitch was coming was sufficiently short-lived, the timing exact, the muscle contractions just right – the ball explodes off the bat and sails over the center field fence.

On a more realistic day – since the best hitters in the world only succeed 3 times out of 10 – the ball bounces weakly to the second baseman for an easy out. This in turn triggers the collective groans of 30,000 disappointed fans. But the heart has cellular communication that continues to guarantee its normal beating, and the player lives to bat another day.

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Bo Sun, 541-737-8203

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ATP model
ATP signaling molecule

Important advance made with new approach to “control” cancer, not eliminate it

PORTLAND, Ore. – Researchers have created a new drug delivery system that could improve the effectiveness of an emerging concept in cancer treatment – to dramatically slow and control tumors on a long-term, sustained basis, not necessarily aiming for their complete elimination.

The approach, called a “metronomic dosage regimen,” uses significantly lower doses of chemotherapeutic drugs but at more frequent time intervals. This would have multiple goals of killing cancer cells, creating a hostile biological environment for their growth, reducing toxicity from the drug regimen and avoiding the development of resistance to the cancer drugs being used.

A system just published in Chemistry of Materials by a group of researchers from Oregon and the United Kingdom offers an even more effective way to deliver such drugs and may be able to greatly improve this approach, scientists say. Further testing is needed in both animals and humans for safety and efficacy.

“This new system takes some existing cancer therapy drugs for ovarian cancer, delivers both of them at the same time and allows them to work synergistically,” said Adam Alani, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on the new study.

“Imagine if we could manage cancer on a long-term basis as a chronic condition, like we now do high blood pressure or diabetes. This could be a huge leap forward.”

This approach is still in trial stages, Alani said, but shows promise. In some prior work with related systems in animal tests, OSU and collaborating researchers have been able to completely eradicate tumors.

Total remission, Alani said, may be possible with metronomic dosage, but the initial goal is not only to kill cancer cells but to create an environment in which it’s very difficult for them to grow, largely by cutting off the large blood supply these types of cells often need.

Most conventional cancer chemotherapy is based on the use of “maximum tolerable doses” of a drug, in an attempt to completely eliminate cancer or tumors. In some cases such as ovarian cancer, however, drug-free intervals are needed to allow patient recovery from side effects, during which tumors can sometimes begin to grow again or develop resistance to the drugs being used.

The types of cancers this approach may best lend itself to are those that are quite complex and difficult to treat with conventional regimens based on “maximum tolerable dose.” This includes ovarian, sarcoma, breast, prostate, and lung cancers.

One example of the new metronomic regimen, in this instance, is use of two drugs already common in ovarian cancer treatment – paclitaxel and rapamycin – but at levels a tenth to a third of the maximum tolerable dose. One drug attacks cancer cells; the other inhibits cancer cell formation and the growth of blood vessels at tumor sites.

The new system developed in this research takes the process a step further. It attaches these drugs to polymer nanoparticles that migrate specifically into cancer cells and are designed to release the drugs at a particular level of acidity that is common to those cells. The low doses, careful targeting of the drugs and their ability to work in synergy at the same time appeared to greatly increase their effectiveness, while almost completely eliminating toxicity.
“Our goal is to significantly reduce tumors, slow or stop their regrowth, and allow a person’s body and immune system time to recover its health and natural abilities to fight cancer,” Alani said. “I’m very optimistic this is possible, and that it could provide an entirely new approach to cancer treatment.”

This research was supported by OSU, the Medical Research Foundation of Oregon, and the AACP New Pharmacy Faculty Research Award Program. It was done in collaboration with researchers from the Oregon Health & Science University, Pacific University, and Kingston University in the United Kingdom.

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Adam Alani, 503-346-4702

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Cancer therapy
Cancer therapy

OSU research funds reach second consecutive record of $336 million

CORVALLIS, Ore. – Oregon State University research funding reached $336 million in the fiscal year that ended June 30 – a second consecutive year of record-breaking growth and an increase of more than 60 percent over the past decade.

In 2006, the university garnered $209 million from state, federal and private-sector sources. Since then, OSU has received research revenues totaling more than $3 billion. In the last year, Oregon State researchers brought in $27 million more from all sources than they did in 2015, a 15 percent increase in competitive federal grants and an overall 9 percent increase.

OSU accounts for more research funding than nearly all of the state’s comprehensive public universities combined.

“Our researchers deserve all the credit for this amazing accomplishment,” said Cynthia Sagers, Oregon State vice president for research. “They have stepped up to the challenge of securing research funds that support our programs and our students, and create an impact on Oregon, the nation and the world.”

Through salaries, student stipends and expenditures, Oregon State research generates an annual societal and economic impact of about $762 million in the state and globally, based on an assessment conducted in 2015 by ECONorthwest.

Ongoing projects funded last year include:

  • Shannon Lipscomb at OSU-Cascades in Bend, an associate professor in the College of Public Health and Human Sciences, is leading a four-year, $1.5 million project funded by the U.S. Department of Education to train teachers to work with children exposed to trauma such as abuse, neglect, parental mental illness or parental substance abuse.
  • With grants totaling $227,000 from the Simons Foundation, Angelicque White and Laurie Juranek in the College of Earth, Ocean, and Atmospheric Sciences, are collaborating with scientists from the University of Washington, MIT, the University of Hawaii and the University of Southern California on a research project in the remote North Pacific Ocean. Preliminary results suggest that changes in the ratios of nitrogen, carbon and other nutrients lead to distinct shifts in microorganisms, affecting climate and the growth of plants and animals that live in the sea.
  • With a $2 million grant from the U.S. Army, Joseph Beckman, distinguished professor in the Linus Pauling Institute and the College of Science, is developing a potential ALS treatment cased on copper ASTM. He has demonstrated that this compound in mice can halt the progression of what is also known as Lou Gehrig’s disease.
  • With a $1.4 million grant from the Walmart U.S. Manufacturing Innovation Fund, the College of Engineering has been developing improvements to plastic injection molding processes and investigating the use of biopigments for digital printing on fabric. The aim in both initiatives is to increase manufacturing competitiveness by reducing waste and boosting energy efficiency.

 OSU researchers undertook projects to study and manage forests, coastal waters and other natural resources; to protect human health by identifying new treatments for infectious diseases; and to support communities and businesses by solving problems in food, energy and water systems.

Scientists are developing new ways to deliver education in the STEM fields — science, technology, engineering and math — and tracking the performance of students learning English as a second language.

Success, Sagers added, is due in part to collaborations among researchers across disciplines in areas such as robotics, marine sciences and information technologies.

“Working with people outside one’s own field can lead to real advances in knowledge and innovation,” Sagers said. “We’re seeing progress in unmanned aerial systems for agriculture, forestry and infrastructure inspections, in genetic testing to understand disease and improve food security, and in software for environmental monitoring and crop improvements.”

Research results are finding their way into businesses, fueling economic growth. For example, two newly formed companies — Agility Robotics and e-MSion, Inc. — have grown out of OSU labs with help from the Oregon State University Advantage program and RAIN, the Regional Accelerator and Innovation Network.

Agility Robotics is developing the second generation of a bi-pedal robot with funding from the federal Defense Advanced Research Projects Agency, or DARPA. E-MSion is driven by an advance in mass spectrometry, a workhorse technology in research labs worldwide. The company aims to transform this high-end research tool into an easy-to-use appliance and hire 20 to 30 employees within five years.

Among funds received in 2016 were the following:

  • $5.3 million from the Agricultural Research Foundation for projects to enhance the productivity and sustainability of food and ornamental crops across the state
  • $2.8 million from the National Oceanic and Atmospheric Administration for the Cooperative Institute for Marine Resources Studies, focusing on undersea eruptions, fisheries and acoustic techniques for monitoring marine mammals and other animals
  • $1.2 million for the Long Term Ecological Research program at the H.J. Andrews Experimental Forest, emphasizing environmental responses to climate change
  • $3 million for design and bid preparation for two to three new regional class coastal research vessels
  • $1 million from Oregon BEST for 17 sustainability projects in wood science, engineering and agriculture
  • 11 NSF CAREER Awards to jumpstart research programs by young researchers in engineering, computer science, physics, chemistry and statistics
  • 35 grants over $1 million, for projects ranging from biomass fuels for the Northwest and plant genetics to changing Arctic and North Atlantic Ocean conditions, aquaculture, nutrition, pharmaceuticals, STEM education and health risks of air pollution

Funds provided by federal agencies increased over what was received in 2015 from the Department of Commerce, up 72 percent; Department of Energy, up 69 percent; Department of Defense, up 39 percent; and Department of Health and Human Services, up 30 percent. Total federal funding grew from $185 million last year to more than $212 million in 2016.

State appropriations for land grant funding — money that supports work in agriculture, wood products, engineering and other fields —increased by $7 million, from $61 million in 2015 to $68 million in 2016. Funds are being used to hire experts to work with farmers, ranchers and others on issues from water quality and disease control to food safety and value-added manufacturing.

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Cynthia Sagers, 541-737-0664

cynthia.sagers@oregonstate.edu

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shipprofile
New research vessel

 

Robert Tanguay

Zebrafish research


ATRIAS, a two-legged robot created at Oregon State University, ambles down the sideline at Reser Stadium, home of Beaver football. (Photo courtesy of Oregon State University)
Bipedal robot

 

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https://youtu.be/q8TCAClYais 

 

High resolution downloadable video:

http://bit.ly/2c4Ta7b

Swiss needle cast disease intensifies in the Oregon Coast Range

CORVALLIS, Ore. — Over the last decade, a fungal disease known as Swiss needle cast has intensified within the Douglas-fir forests of the Oregon Coast Range, according to the most recent scientific surveys.

Results from aerial analyses in 2015 indicate a slight expansion, 0.6 percent, in the affected area over 2014, but it remains the most significant threat to Douglas-fir plantations in western Oregon, says David Shaw, Oregon State University forest health specialist in the College of Forestry. Shaw is director of the Swiss Needle Cast Cooperative at Oregon State, which leads efforts to understand the disease and determine how best to manage it.

Symptoms of the disease, which is native to the Northwest, have spread as much as 30 percent in one year. Caused by a fungus that reduces the growth of Douglas-fir trees, it now affects over 590,000 acres of trees in Oregon, an area more than four times larger than what was found when surveying began in 1996. The annual economic loss has been estimated at $128 million.

The fungus, Phaeocryptopus gaeumannii, doesn’t kill trees outright, but the annual growth of the most infected stands can be reduced up to 50 percent. Application of fungicides is generally not recommended. Where the disease is severe, researchers suggest planting species other than Douglas fir, such as western hemlock, western redcedar and Sitka spruce.

Scientists have reported the results in Forests, a professional journal, of two decades of aerial surveys conducted by the Oregon Department of Forestry. Researchers in the U.S. Forest Service and the Weyerhaeuser Corporation co-authored the report.

“Sustained growth losses over the previous 20 years have resulted in millions of dollars in lost timber and tax revenues,” said Gabriela Ritokova, lead author and assistant director of the Swiss Needle Cooperative. “In many cases, mid-rotation stands in the hardest hit areas have remained in an unproductive state, with managers hoping for a reprieve in disease levels.”

The pathogen disperses as tiny spores that land on Douglas-fir needles and plug needle openings that normally carry air and water into and out of the tree. Like a clogged drain, the needle loses the ability to function. Infected trees can be visually identified from the air because, in the spring, they turn slightly yellow in contrast to the deep green of healthy trees. While unaffected Douglas-fir trees often retain needles for three years or more, needles on infected trees may fall off in two years or less.

Standard forest management practices neither increase nor decrease the severity of the disease, researchers said.

“The start of the epidemic is thought to be partially the result of planting Douglas-fir that originated from seed sources outside the area being planted,” said Ritokova, who is also a faculty research assistant at Oregon State.

“The correlation between disease severity and climate factors, such as spring moisture and warm winter temperatures, raises the question of a link between disease expansion and climate change. Those factors, in combination with lots of Douglas fir and with large springtime fungal spore production, have us where we are now.”

In addition to conducting aerial flights over the Coast Range, Ritokova and her colleagues have been monitoring fungus infection in 10- to 23-year-old Douglas-fir trees in the western Cascades. Samples from 590 trees analyzed in 2001, 2006 and 2011 show that Swiss needle cast is present but, with few exceptions, is of limited concern.

Swiss needle cast was first discovered among Douglas-fir trees planted in Switzerland in the early 20th century.

The research was carried out by the Swiss Needle Cast Cooperative, a consortium of OSU, U.S. Forest Service, Bureau of Land Management, Oregon Department of Forestry, Stimson Lumber, Starker Forests, Cascade Timber Consultants and Weyerhaeuser Corporation. The cooperative recently completed installation of a research and monitoring plot network across western Oregon and southwest Washington to enable scientists to study disease abundance, growth impacts and climate.

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Gabriela Ritokova, 541-737-3826, gabriela.ritokova@oregonstate.edu; Dave Shaw, 541-737-2845, dave.shaw@oregonstate.edu

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Swiss needle cast

Swiss needle cast

Swiss needle cast symptoms from the air, near Tillamook photo Rob Flowers ODF

FirNeedle

Subduction zone earthquakes off Oregon, Washington more frequent than previous estimates

CORVALLIS, Ore. – A new analysis suggests that massive earthquakes on northern sections of the Cascadia Subduction Zone, affecting areas of the Pacific Northwest that are more heavily populated, are somewhat more frequent than has been believed in the past.

The chance of one occurring within the next 50 years is also slightly higher than previously estimated.

The findings, published this week in the journal Marine Geology, are based on data that is far more detailed and comprehensive than anything prior to this. It used measurements from 195 core samples containing submarine landslide deposits caused by subduction zone earthquakes, instead of only about a dozen such samples in past research.

The work was done by researchers from Oregon State University, Camosun College in British Columbia and Instituto Andaluz de Ciencias de la Tierra in Spain. The research was supported by the National Science Foundation and the U.S. Geological Survey.

“These new results are based on much better data than has been available before, and reinforce our confidence in findings regarding the potential for major earthquakes on the Cascadia Subduction Zone,” said Chris Goldfinger, a professor in the College of Earth, Ocean and Atmospheric Sciences at OSU, and one of the world’s leading experts on tectonic activity of this subduction zone.

“However, with more detailed data we have also changed somewhat our projections for the average recurrence interval of earthquakes on the subduction zone, especially the northern parts. The frequency, although not the intensity, of earthquakes there appears to be somewhat higher than we previously estimated.”

The Cascadia Subduction Zone runs from northern California to British Columbia, and scientists say it can be roughly divided into four segments. There have been 43 major earthquakes in the past 10,000 years on this subduction zone, sometimes on the entire zone at once and sometimes only on parts of it. When the entire zone is involved, it’s believed to be capable of producing a magnitude 9.1 earthquake.

It’s been known for some time, and still believed to be accurate, that the southern portions of the subduction zone south of Newport, Oregon, tend to rupture more frequently – an average of about every 300-380 years from Newport to Coos Bay, and 220-240 years from Coos Bay to Eureka, California.

The newest data, however, have changed the stakes for the northern sections of the zone, which could have implications for major population centers such as Portland, Tacoma, Seattle and Vancouver, B.C.

A section of the zone from Newport to Astoria, Oregon, was previously believed to rupture on average about every 400-500 years, and that average has now been reduced to 350 years. A section further north from Astoria to Vancouver Island was previously believed to rupture about every 500-530 years, and that average has now been reduced to 430 years.

The last major earthquake on the Cascadia Subduction Zone – pinpointed in time because it caused a tsunami that raced all the way across the Pacific Ocean to Japan – occurred in January, 1700, more than 315 years ago.

“What this work shows is that, contrary to some previous estimates, the two middle sections of the Cascadia Subduction Zone that affect most of Oregon have a frequency that’s more similar than different,” said Goldfinger, who directs the Active Tectonics and Seafloor Mapping Laboratory at OSU.

Based on these findings, the chances of an earthquake in the next 50 years have also been slightly revised upwards. Of the part of the zone off central and northern Oregon, the chance of an event during that period has been changed to 15-20 percent instead of 14-17 percent. On the furthest north section of the zone off Washington and British Columbia, the chance of an event has increased to 10-17 percent from 8-14 percent.

The study also increased the frequency of the most massive earthquakes, where the entire subduction zone ruptures at once. It had previously been believed this occurred about half the time. Now, the data suggest that several partial ruptures were more complete than previously thought, and that complete ruptures occur slightly more than half the time.

“Part of what’s important is that these findings give us more confidence about what’s coming in our future,” Goldfinger said.

“We believed these earthquakes were possible when the hypothesis was first developed in the late 1980s. Now we have a great deal more certainty that the general concern about earthquakes caused by the Cascadia Subduction Zone is scientifically valid, and we also have more precise information about the earthquake frequency and behavior of the subduction zone.”

Based in part on the growing certainty about these issues, OSU has developed the Cascadia Lifelines Program, an initiative working with Pacific Northwest business and industry to help prepare for the upcoming subduction zone earthquake, mitigate damage and save lives. Many other programs are also gaining speed.

The new measurements in this research were made with cores that showed the results of massive amounts of sediments released by subsea landslides during a subduction zone earthquake – a catastrophic event beneath the sea as well as on land. New technology is helping researchers to actually simulate these underwater landslides, better understand their behavior, and more accurately identify the “turbidite” or sediment layers they leave behind.

The large amounts of additional data, researchers say, has helped refine previous work, fill holes in the data coverage, and also to rule out other possible causes of some sediment deposits, such as major storms, random landslides or small local earthquakes.

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About the OSU College of Earth, Ocean, and Atmospheric Sciences: CEOAS is internationally recognized for its faculty, research and facilities, including state-of-the-art computing infrastructure to support earth/ocean/atmosphere observation and prediction. The college is a leader in the study of the Earth as an integrated system, providing scientific understanding to complex environmental challenges.

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Chris Goldfinger,541-737-9622

gold@coas.oregonstate.edu

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Oregon samples
Sampling sites

Lack of pharmacy access sends some patients back to the hospital

PORTLAND, Ore. – Hospital readmissions, a $17 billion annual problem, are higher in rural, remote or smaller communities that sometimes have significantly less access to pharmacies, according to a study published today that was one of the first to examine this issue.

Researchers at Oregon State University and Oregon Health & Science University found that the average number of readmissions from rural areas was 15.3 percent, compared to 14.7 percent for their urban counterparts where the days and hours a person could find an open pharmacy were much higher.

Unplanned hospital readmissions are such a serious national problem that recent changes in federal law are penalizing hospitals that have high readmission rates. It can be a problem with various groups: older adults; people who have several medical conditions; those taking multiple medications; and people who have difficulty adhering to their medication regimen.

The study was done in Oregon with census data of patients over 65, studying 507 pharmacies and 58 hospitals. It was supported by the OHSU Layton Alzheimer Disease Center, which is funded by the National Institutes of Health.

“It’s a huge burden both on a patient and our medical system when they have to be readmitted to a hospital,” said David Lee, an assistant professor in the OSU/OHSU College of Pharmacy, and senior author on a new study in the Journal of the American Pharmacists Association.

“The modern pharmaceutical profession is increasingly being recognized as an important partner in health care, and as its services continue to expand it will help even more. This research shows that pharmacy access can help people from going back to the hospital. For older populations who often find hospital experiences quite exhausting, that’s extremely important to their overall health.

“The sooner a person gets out and stays out of a hospital, the better off they usually will be.”

In some rural areas of Oregon, Lee noted, a person might have to drive 100 miles or more to find a pharmacy. In one of Oregon’s rural communities there is a single pharmacy that’s open 54 hours a week; by comparison, in some major urban areas a person might be able to find multiple pharmacies that collectively are open more than 3,800 hours a week.

These challenges of availability, distance and convenience to professional pharmaceutical products, service and counsel are a problem, researchers said. Another interesting corollary to the issue, they said, is identification of what have been called “pharmacy deserts” even within major urban areas, such as Chicago.

“Large, urban, predominantly white communities usually have a lot of pharmacies and access,” said Sarah Bissonnette, lead author on this study and an OSU postdoctoral fellow. “But in some lower socioeconomic areas even within cities, it’s much more difficult to find an open pharmacy.”

If more conventional pharmacies are not economically viable, the researchers said, a possible remedy to the problem is growth and improvement of what’s called “telepharmacy,” or mail-order services that are carefully backed up by personal advice, monitoring and counsel from professional pharmacists.

Improved hospital discharge medication counseling has been shown to increase adherence to use of new or changed medications, the study indicated. And some hospitals around the country have also taken it upon themselves to open community and 24-hour pharmacies in an attempt to reduce readmission rates.

Nonadherence to medication usage ranges from 25-50 percent in the United States, depending on the disease state, and is associated with increased illness and death, the study noted.  Causes can include adverse side effects, insurance coverage, costs, education levels, cognition and pharmacy access.

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David Lee, 503-494-2258

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Teens who smoke daily are more likely to report health complaints

CORVALLIS, Ore. – As fewer teens overall take up smoking, those who do smoke daily are reporting more health complaints than in years past, a new study indicates.

“Teens who smoke report significantly higher levels of health complaints than nonsmoking teens, and we found that this gap has widened over the years, even as the overall prevalence of teen smoking has dropped,” said Marc Braverman a professor, lead author and Extension specialist in the College of Public Health and Human Sciences at Oregon State University, who worked with collaborators in Norway.

“Some adolescents smoke as an attempt to cope with their health problems, and that subgroup may represent a growing proportion of teen smokers, as fewer teenagers are taking up smoking for social reasons.”

The researchers believe it is the first time that this shifting relationship between daily smoking and health complaints in adolescence has been reported. The results were published recently in the journal Nicotine and Tobacco Research.

Smoking is on the decline among adults and adolescents in most places around the world, which is very welcome news, said Braverman, whose research expertise includes smoking prevention and tobacco control policy.

But as smoking rates decline, reducing them further becomes more challenging. Some tobacco researchers believe that the remaining smokers tend to be more “hard-core” smokers, who have been smoking for long periods and either do not wish to quit or believe they would not be successful if they tried, he said.

“Many public health officials are asking what kinds of new strategies might be needed to reduce smoking prevalence, to say, the low single digits, and what kinds of resources that might require,” Braverman said.  “Some smokers are more addicted to or dependent on cigarettes than others.”

Understanding the links between health and smoking among teens will help public health officials determine better smoking cessation strategies for that age group, particularly those who smoke on a daily basis, Braverman said.

For the study, researchers used data from the Health Behavior in School-Aged Children Study, an international collaborative project sponsored by the World Health Organization that began in the 1980s and currently includes 43 countries. Surveys of 11-, 13- and 15-year-olds are conducted every four years in participating countries.

The researchers examined smoking behavior and health problems among 15-year-olds in Norway over five waves of the survey, from 1993-94 to 2009-10. They focused on Norway in part because that country experienced dramatic declines in smoking rates over that time period, which allows for investigation of how smoking populations have changed, Braverman said.

As part of the survey, the students were asked about their smoking behavior and how often they experienced subjective physical and psychological health complaints such as headache, stomachache, backache, dizziness, irritability, nervousness, feeling “low” and sleep difficulties.

In addition to the changes in health complaints over time, the researchers found important differences in health complaints related to gender. Girls, in general, reported more health complaints than boys, but the difference between the sexes was significantly larger among smoking teens than nonsmoking teens. In particular, girls who smoked daily reported higher levels of health complaints than any other subgroup, Braverman said.

The data collected did not allow for an explanation of the reason for the finding, but the study raises concerns that adolescent girls might be at especially high risk for health problems associated with smoking, he said.

If teens are smoking as a coping mechanism for physical or psychological problems, they may be at greater risk for dependence and addiction than their peers who are smoking because of peer or social influences, Braverman said.

“And for those teens who smoke to cope with health problems, getting them to stop will likely require different strategies and more intensive intervention efforts than those that are commonly used,” Braverman said. “A ‘stop smoking’ media campaign probably won’t be enough.”

Co-authors of the study include Robert Stawski of OSU; Oddrun Samdal of the University of Bergen;    and Leif Edvard Aarø  of the Norwegian Institute of Public Health. Braverman’s work on the study was funded in part by a grant from the OSU Division of International Programs.

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Marc Braverman, 541-737-1021

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OSU researchers fix calculation error in study on fracking and human health

CORVALLIS, Ore. – A 2015 Oregon State University study that linked natural-gas fracking to increased air pollution and heightened health risks has been corrected by its authors.

The corrected article still concludes that natural gas extraction contributes polluting chemicals known as polycyclic aromatic hydrocarbons (PAHs) to the air, but at levels that would not be expected to increase lifetime cancer risk above the EPA threshold.

The researchers measured levels of airborne PAHs near several Ohio hydraulic-fracturing sites in 2014. PAHs have been linked to increased risk of cancer and respiratory diseases.

In their March 2015 article, published in the journal Environmental Science and Technology, the researchers reported that PAH pollution from fracking could put a person living in the study area at a greater than a one-in-a-million risk of developing cancer during his or her life. One in a million is the threshold set by the U.S. Environmental Protection Agency for unacceptable cancer risk.

The authors retracted the article on June 29, 2016, after they found an error in a complicated spreadsheet used to calculate the concentrations of various PAH chemicals in the air.

The researchers redid the calculations and submitted a corrected version of the article, which was published on July 11, 2016. It finds that the estimated risk for the maximum exposure to fracking-related PAH pollution in the study area is 0.04 in a million—well below the EPA’s threshold.

Steve Clark, OSU’s vice president for university relations, said the mistake came to light as the researchers were crunching numbers from a current project. In the process, he said, they discovered a similar calculation error in a 2014 study of PAH pollution of air and water during the 2010 Deepwater Horizon oil spill, which also was published in Environmental Science and Technology.

That article too was retracted on June 29, and the corrected article was published online on July 8.

“In both cases the researchers were using a complicated, multi-linked spreadsheet to analyze large quantities of data,” said Clark. “The error was an honest mistake that unfortunately slipped through the peer-review process. Our researchers knew they couldn’t let it stand, so they stepped forward and corrected the error.”  

The coauthors of the Ohio fracking study include OSU researchers Kim Anderson (College of Agricultural Sciences) and Laurel Kincl (College of Public Health and Human Sciences), and Erin Haynes of the University of Cincinnati. Anderson also coauthored the Deepwater Horizon study.

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