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Global Health, Immunology, Research, Stanford News

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

Mark DavisThe vaccine field got a major boost today with the announcement that the Bill & Melinda Gates Foundation will invest $50 million in a new collaboration with Stanford’s School of Medicine to speed the development of vaccines for some of the world’s major scourges. The funds will support the new Stanford Human Systems Immunology Center, a multidisciplinary effort led by immunologist Mark Davis, PhD.

In recent decades, efforts to develop vaccines for major killers such as HIV and malaria have been stymied in part by the expense and time involved in conducting large-scale trials, which have often proved disappointing. Through the new initiative, scientists will use advanced immunological tools to better understand how vaccines provide protection and identify the most promising candidates to pursue in clinical trials.

What we need is a new generation of vaccines and new approaches to vaccination

“What we need is a new generation of vaccines and new approaches to vaccination,” said Davis, director of the Stanford Institute for Immunity, Transplantation and Infection. “This will require a better understanding of the human immune response and clearer predictions about vaccine efficacy for particular diseases.”

The 10-year initiative will involve multiple faculty from diverse fields, including medicine, engineering and computer science. It will capitalize on a range of technologies, some of which have been pioneered at Stanford, which can rapidly analyze individual cells and provide a detailed profile of the human immune response, with all of its various components.

“This grant will provide crucial support to Stanford’s world-class scientists as they collaborate with investigators around the globe to assess vaccines against some of the most formidable diseases of our time,” said Lloyd B. Minor, dean of Stanford’s medical school. “The Stanford Human Systems Immunology Center will help the most promising vaccine candidates to move quickly and efficiently from the lab to the front lines of treatment, impacting countless lives.”

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail
Photo of Mark Davis by Steve Fisch

Global Health, Health Policy, In the News, Infectious Disease

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

Barack_Obama_talks_with_Narendra_ModiDuring his three-day visit to India, President Barack Obama issued a joint statement with Indian Prime Minister Narendra Modi praising the “highly successful collaboration” that led to the availability of a newly developed Indian rotavirus vaccine, which is expected to save 80,000 children in India alone each year.

The vaccine was developed with support from the Indo-U.S. Vaccine Action Program, co-chaired since 2009 by Harry Greenberg, MD, senior associate dean for research at the Stanford School of Medicine. Greenberg was the lead inventor of the first-generation vaccine for rotavirus, a severe diarrheal disease that kills between 300,000 and 400,000 children each in the developing world.

“This is the VAP’s biggest accomplishment to date,” Greenberg told me from Taiwan, where he is attending a conference. “The program really helped support the development of a new safe and effective rotavirus vaccine from the start to finish. And it’s the first time ever that a new vaccine was developed in a less developed country by and for that country and became licensed.”

The vaccine initiative, funded by the U.S. Public Health Service and the Indian government, was created in 1987 to help advance the development of new vaccines of importance to India. The NIH manages research grants in the United States for the vaccine program.

“The VAP has been the most successful, continuous program we have with India,” Roger Glass, MD, PhD, director of the NIH’s Fogarty International Center, wrote in an email from India to top NIH officials. “It’s amazing to me that this little research project on rotavirus with Harry Greenberg and George Curlin (former deputy director of NIH’s Division of Microbiology and Infectious Diseases) has turned into a real product that is being launched and will be used.”

A low-cost version of the vaccine, known as Rotavac, is being manufactured in India and was launched into the marketplace on Jan. 23, Greenberg said. It was the result of an unusual team effort involving diverse multinational groups of investigators from 13 institutions seeking to create a vaccine that was not only safe and effective, but also affordable enough for use in India and other low-income countries, Greenberg said. The Indian government is negotiating to purchase the vaccine for public distribution. The vaccine also will compete in the private market against at least two other commercially available vaccines.

In the joint statement, the two world leaders pledged continued support for the vaccine program, and Greenberg, who recently stepped down from his chairmanship, made an argument for now focusing the attention of the vaccine partnership on respiratory syncytial virus (RSV), a potentially serious lung disease that is prevalent in children in India and in other regions as well.

“RSV is an incredibly important pediatric pathogen all over the world, and there is now potential for great progress,” Greenberg said. “I suggested to VAP that it think about RSV as a new target for research. It has a huge public impact and it may well be that there are great advances to be made in the near future. I think that idea resonated with the people. We will see.”

Previously: Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial and Trials, and tribulations, of a rotavirus vaccine
Photo courtesy of The White House

Ebola, Events, Infectious Disease, Stanford News

Physician at forefront of Ebola fight: “Ultimate award” is what you get back from survivors

Physician at forefront of Ebola fight: "Ultimate award" is what you get back from survivors

BauschWhen Lassa fever, a cousin of Ebola, was afflicting hundreds of thousands of people in West Africa in the late 90s, Daniel Bausch, MD, MPH & TM, worked with the federal Centers for Disease Control and Prevention in Guinea to set up a laboratory for study and testing of the rodent-borne disease. Unfortunately, the lab lost its international funding in 2003, as it could have proven useful in preventing the Ebola epidemic, which began in a remote village in Guinea just a few hours away, Bausch told a Stanford audience last week.

“I think back that if we had succeeded in keeping this lab going, how different it would have been if we’d been able to just send a sample down the road,” instead of losing valuable time in shipping the samples to Europe for testing, said Bausch, the keynote speaker at a day-long global health conference.

Today, Bausch, an associate professor at the Tulane School of Public Health and Tropical Medicine, is at the forefront of the Ebola fight, treating patients at an Ebola clinic in Sierra Leone that he helped establish and training and recruiting other clinicians. He is also consulting with the World Health Organization in the development and implementation of treatment guidelines and drug and vaccine testing for the disease.

In 1996, Bausch was working with the CDC in the Democratic Republic of Congo, where dozens of miners were being felled by a strange set of symptoms. The source was identified as Marburg virus, a cousin of Ebola that kills more than 80 percent of victims. While the usual course of spread is from one person to the next, these miners were harboring different variants of the virus, suggesting multiple sources, he said. The disease was traced back to the caves where miners unearthed their gold and where they were exposed to bats — the likely reservoir of the virus, Bausch said. He and colleagues published an article on their Marburg investigation in 2006 in the New England Journal of Medicine.

Because of his rare expertise with hemorrhagic fevers, Bausch was called upon early on to help fight in the latest Ebola outbreak, working alongside West African colleagues in Guinea and Sierra Leone who died of the disease.  He said one bright spot in the epidemic is the speed with which scientists have moved forward in developing new treatments and potential vaccines. “In the last six months, we’ve seen a process that’s unprecedented, with accelerated science and the launch of clinical trials that would normally take years,” he said.

And he said he cherishes the experience of seeing patients who have successfully fought off the disease. He showed a photo of a colleague, draped in white protective gear, alongside a young survivor: a smiling boy in striped pants who had lost his father to Ebola.

“That is the ultimate reward… It means something to you – what you get back from (the survivors),” he said.

The Stanford Global Health Research Convening Day was sponsored by Stanford’s Center for Innovation in Global Health.

Previously: Back home from Liberia, Stanford physician continues to help in fight against EbolaEbola: This outbreak is differentStanford physician shares his story of treating Ebola patients in Liberia and Ebola: A look at what happened and what can be done
Photo, of Daniel Bausch and others in Guinea, courtesy of Bausch

Autism, Events, Stanford News

A conversation with autism activist and animal behavior expert Temple Grandin

A conversation with autism activist and animal behavior expert Temple Grandin

Grandin Temple - 560

In the inspiring film, “Temple Grandin,” we learn the remarkable story of a woman born with autism who, as a young child, communicates through screaming and humming, and is given to fist-pumping outbursts of frustration. But Grandin, played brilliantly in the film by Claire Danes, has a rare affinity with animals and a keen sense of their needs. She ultimately becomes a renowned expert in animal behavior, a university professor and a consultant to major U.S. companies.

Grandin, PhD, one of the world’s most famous people with autism, will visit Stanford’s medical school next Wednesday to deliver a talk entitled, “Animals Make us Human.” In anticipation of her presentation, we asked her to answer five questions about the link between autism and animals. Her answers – like this one – offer a window into the world of autism, while providing a sense of Grandin’s character and thought process:

Animal cognition has similarities to autism cognition. Animals are very aware of small, sensory details in the environment. People on the autism spectrum excel at work involving details. SAP, a large computer company, is hiring people on the mild end of the autism spectrum to debug and correct computer programs.

Concepts are formed from specific examples. To train a dog to always obey the “sit” command, it must be taught in many different locations. If all the dog’s training is done in the living room, the dog may only obey the commands in the living room. To teach a child with autism about road safety, he needs to be taught in many different locations. These similarities between animals and autism apply only to cognition. They do not apply to the emotions. Animals are highly social and emotional creatures.

Her presentation begins at noon in the Clark Center on the medical school campus and will be followed by a book signing at the bookstore at the Li Ka Shing Center for Learning and Knowledge. The talk, sponsored by Stanford’s Department of Comparative Medicine, is free and open to the public. If you’re local and able to attend, I would get there early, as I believe this is going to be one very popular event.

Photo by Rosalie Winard

Global Health, Infectious Disease, Stanford News

Stanford physician shares his story of treating Ebola patients in Liberia

Stanford physician shares his story of treating Ebola patients in Liberia

P1030655For a month, emergency physician Colin Bucks, MD, found himself in the remote, dense jungle of northeast Liberia in the heat of the battle against Ebola. A clinical assistant professor of surgery at Stanford, Bucks was a volunteer with the International Medical Corps at a new tent-like unit hastily built to accept the continuing stream of Ebola patients in the hard-hit West African country.

The facility, a series of low, tin-roofed, concrete buildings, were primitive in design but had very effective methods for controlling infection, including spigots everywhere that dispensed virus-killing doses of chlorine and protective gear for covering the body head to toe. Aside from providing basic care, such as fluid and electrolyte replacement, Bucks said much of his time was spent comforting patients, who were physically isolated from family members because of the threat of infection.

P1030673“In this setting (in West Africa), there is an additional barrier because you have one physical degree of separation, as your head, your hands, your face are completely covered. But that doesn’t preclude the same level of connection to the patient and the same sense of responsibility and care,” said Bucks, who left Liberia Oct. 22 and is now isolated at his home in Redwood City, Calif. “There may be a higher percentage of sad cases because Ebola has a high-case fatality rate, so there is an added burden there. But there is a similarity to working a tough case in rural Liberia to working a tough case in a U.S. critical care unit.”

He said the unit received patients from a nearby hospital, as well as those brought in by makeshift ambulances that might travel as much as eight hours to retrieve ailing victims. “We would get these reports everyday from the ambulance – we have four cases and three flat tires. The roads would be blocked with trees. They would have to drive through dense jungles. The ambulance stories were by far the most riveting.”

Colin Trish PPEBucks said the caregivers at the unit, which included 125 Liberians, were able to save just under half the patients who came in, with each survivor serving as an important ambassador to the community.

“The public health message was blanketing the country, but there was still a lot of fear and misunderstanding,” he said. “People are scared to come to the hospital. People are scared to undergo treatment. It helped every time we had patients discharged as cured.”

Bucks, who is now following recommendations and Stanford requirements to remain in isolation for 21 days, says there is a desperate need for other U.S. volunteers like himself to help contain the spread of the virus. “There needs to be a rational policy that facilitates health-care workers going to and from the U.S. Policy should help this – not impede this. But you need an organized response on West Africa. Otherwise we will be fighting a much bigger battle in the U.S. and around the globe.”

Previously: How to keep safe while operating on Ebola patients, Experience from the trenches in the first Ebola outbreak, Ebola: A look at what happened and what can be done and Dr. Paul Farmer: We should be saving Ebola patients
Photos courtesy of Colin Bucks

Patient Care, Research, Stanford News

Fewer transfusions means better patient outcomes, lower mortality

Fewer transfusions means better patient outcomes, lower mortality

blood transfusionBlood transfusion has been cited by the American Medical Association as one of the top five most overused therapies in the United States. Moreover, studies have shown that when there are fewer transfusions in a hospital setting, patients generally do better, as they’re not exposed to potential transfusion risks.

With that in mind, Stanford Health Care has made a concerted effort since 2009 to effectively reduce the number of patients who receive transfusions. Since that time, patient outcomes have improved, including lower mortality rates and length of stay in the hospital. Moreover, blood costs have been markedly reduced, a new study finds.

Between 2009 and 2013, the number of red blood cell units transfused annually at Stanford Health Care fell almost 24 percent – from 29,472 to 22,991. At the same time, mortality rates and length of stays decreased overall among hospital patients. The decline occurred despite the fact that the volume of patients receiving treatment was higher and patients came in with more complex medical problems, according to the researchers, led by Lawrence Goodnough, MD, a professor of pathology and medicine and director of the hospital’s transfusion service.

Goodnough helped implement a program that uses the hospital’s electronic medical record system to alert clinicians to blood-use guidelines and relevant medical literature whenever they request a transfusion. The physician is asked to explain the reason for the transfusion, prompting him or her to reconsider whether it is also needed. As a result, the overall percentage of patients transfused dropped from 21.9 percent in 2009 to 17 percent in 2013, the researchers reported.

The researchers more closely analyzed outcomes for 3,622 patients transfused before implementation of the system and some 10,500 patients who received transfusions after the change. In this group, mortality rates fell from 5.5 percent to 3.3 percent. Patients also spent less time in the hospital (down from 10 to 6.2 days) and were less likely to be readmitted within 30 days.

In the process, the hospital has saved some $1.62 million annually in costs over each of the four years, not including indirect costs, such as patient testing and administration of blood, the researchers calculated.

A similar 2011 study conducted at Lucile Packard Children’s Hospital Stanford found that the automated alerts saved the children’s hospital 460 unnecessary red blood cell transfusions and $165,000 in one year, while patients who needed transfusions still received them.

“For health care institutions, improved blood utilization is accompanied by improved quality of care as measured by decreased patient exposure to unnecessary red blood cell transfusions, decreased blood transfusion-related costs and improved patient outcomes,” authors of the latest study, which appears in the current issue of the journal Transfusion, concluded.

Previously: Stanford Hospital trims use of blood supplies and New issue of Stanford Medicine magazine asks, What do we know about blood?
Related: Against the flow: What’s behind the decline in blood transfusions?
Illustration by Jonathon Rosen

Ebola, Events, Global Health, Infectious Disease

Experience from the trenches in the first Ebola outbreak

Experience from the trenches in the first Ebola outbreak

512px-Ebola_virus_emNoted infectious disease expert Donald Francis, MD, PhD, was “a quiet doctoral student” at Harvard when he was called in to fly into the remote bush of southern Sudan in 1976 to help with one of the world’s first documented outbreaks of Ebola. The federal Centers for Disease Control and Prevention dispatched him for a two-week assignment that stretched into two months, as he saw villages demolished by the virus and helped bury some 274 bodies, he told a group of 70 science writers earlier this week in San Francisco.

Like today’s epidemic in West Africa, most people who contracted the disease were caregivers, either at home or at the make-shift tent hospital, or people assisting at funerals, where bodies were literally dripping with blood, he said. A single drop contains many thousands of viral particles, so all it took was a simple scratch of the nose with a contaminated finger to become infected.

Remarkably, none of his team members became infected, though they took risks, including storing viral samples in unsafe vials, and flying in and out of the treatment area when they were supposed to be in quarantine, he said.

Unlike today’s epidemic, the outbreak burned itself out because it took place in the remotest of areas.

“This was a very good place to control an outbreak – very rural, very isolated,” said Francis, co-founder and executive director of Global Solutions for Infectious Diseases.

Francis is the former director of the CDC’s AIDS Laboratory Activities and was among the first to suggest that AIDS was caused by an infectious agent. He has worked in epidemics around the world and helped eradicate smallpox from Sudan, India and Bangladesh before he became involved in the AIDS epidemic.

But his early work was in Ebola. During that first outbreak in Sudan, his five-member team worked with local nurses, some of whom were sickened by the virus but recovered. “I had patients who were so sick that the whole skin of their feet would slough off,” he said. And though the survivors were in a weakened state, losing as much as 20 percent of their body weight, they were determined to continue caring for their fellow villagers, he said.

He said today’s epidemic in West Africa presents a number of “worrisome challenges,” as it is occurring in a part of the world beset by political and social chaos.

“You have social chaos, socio-economic lack of resources, and hospitals that are just set up for transmission of the virus,” he said.

He said Ebola “can be controlled, but once it becomes so broad (as is currently the case), you lose that capability.” He expressed little hope that the current epidemic could be contained anytime soon: “I expect it will play out very badly for at least a year.”

Previously: Ebola: A look at what happened and what can be done,  Dr. Paul Farmer: We should be saving Ebola patients, Ebola panel says 1.4 million cases possible, building trust key to containmentShould we worry? Stanford’s global health chief weighs in on Ebola and Biosecurity experts discuss Ebola and related public health concerns and policy implications
Photo by CDC/ Dr. Frederick A. Murphy

Ebola, Events, HIV/AIDS, Infectious Disease, Public Health, Stanford News

Dr. Paul Farmer: We should be saving Ebola patients

Dr. Paul Farmer: We should be saving Ebola patients

The photo says it all: A very slender, ailing man sits on the floor with his head bent, completely alone in the dark in what used to be an Ebola treatment center in West Africa.

Paul Farmer, MD, PhD, the brilliant physician and humanitarian, flashed the photo on a screen to a rapt Stanford audience last Friday to show the emaciated state of health care systems in West Africa, incapable now of treating the most basic ailments.

Every time someone dies, it’s a failure to diagnose and deliver the imperfect tools we have

“The primary determinant of outcomes is the strength of health care systems. And if this is what ETU’s (Ebola Treatment Units) look like, there are going to be a lot of fatalities,” he told the crowd of some 400 people at Stanford’s Graduate School of Business. “We should be saving most of these patients. Every time someone dies, it’s a failure to diagnose and deliver the imperfect tools we have.”

But this vast inequity in care need not exist, said Farmer, MD, PhD, a Harvard professor. He pointed to examples from his own experience, in which he and the group he co-founded, Partners in Health, helped build robust health systems in Haiti and more recently, Rwanda, saving thousands of lives.

Farmer started working in Haiti while he was a student at Harvard Medical School nearly 30 years ago. In 1998, during the peak of the AIDS epidemic there, he established the HIV Equity Initiative, which relied on community health workers to visit the homes of patients daily to check on their status and ensure that they took their antiretroviral and/or tuberculosis medications. The approach proved remarkably successful, as people rose from their deathbeds to return to normal, functioning lives.

More recently, after the 2010 quake in Haiti, his group helped to build a medical center and teaching hospital in rural Haiti; he showed a photo of the modern, expansive new facility to the Stanford audience, which applauded the work.

“This is what I think of for rural Liberia, rural Sierra Leone,” he said. “This is not rocket science. Just think what we could do if we had a lot of help with systems and partners. It just requires sticking with some of these problems for a long time.”

Previously: Ebola panel says 1.4 million cases possible, building trust key to containmentExpert panel discusses challenges of controlling Ebola in West Africa, Should we worry? Stanford’s global health chief weighs in on Ebola and Biosecurity experts discuss Ebola and related public health concerns and policy implications

Medical Education, Medical Schools, Stanford News, Videos

Stanford students design "enrichments" for lions, giraffe and kinkajou at the San Francisco Zoo

Stanford students design "enrichments" for lions, giraffe and kinkajou at the San Francisco Zoo

My job took me to the zoo.

It was a rather unorthodox assignment for a medical writer, but one of our faculty at Stanford medical school was teaching a rather unorthodox class at the San Francisco Zoo. A dozen Stanford sophomores signed up to spend two intensive weeks there learning about animal welfare and behavior and designing “enrichments” to make life more interesting for the lions, a giraffe and a kinkajou at the zoo.

These included a “Poop Shooter” to lob animal poop into the lion’s cage, a urine-soaked scratcher for a lone giraffe and a “Robo-Flower” to automatically dispense smoothies to the kinkajou, a tree-dwelling rainforest mammal that looks like a cross between a squirrel and a raccoon.

“Zoo animals have pretty good welfare already,” said Stanford’s Joseph Garner, PhD, an associate professor of comparative medicine who helped design and lead the class. “So it’s not about fixing things. It’s about how we can turn this animal on a little. How can we help the keepers manage the animal and improve the experience for guests.”

“It’s like if you lived in the same room your whole life. We want to change it up, keep it fresh and interesting – something novel,” said student Jennifer Ren.

For Floyd the giraffe, the students shook things up a bit by building a scratcher soaked in female giraffe urine to make it appealing to him. Instead of lurking in a corner of his paddock near the female enclosure, Floyd ventured out into his large pad to explore his new toy, where he was a lot more visible to zoo-goers.

“The giraffe is one of the largest and strongest animals on the planet, so building something that he is not going destroy in 30 seconds is a real challenge,” Garner said.

For the lions, the students adapted a conveyor-belt system to periodically shoot giraffe poop into the lion’s cage, where the male lion in particular found the aromatic pellets extremely interesting.

“Lions lie around all day watching and waiting. But when the zoo put the enrichment in, it was like somebody just flipped a switch,” Garner said. “The male lion was up and about and smelling and searching for the giraffe droppings, and performing all of this wonderful lion behavior.”

The students took their assignments very seriously, videotaping the animals’ responses and designing charts and graphs to measure the results, which they presented at a zoo ceremony last Friday in which they were celebrated for their contributions.

The students said they came away with a whole new perspective on zoos and wildlife behavior, as well as a gratifying sense of having designed something to improve the animals’ lives.

Previously: How horsemanship techniques can help doctors improve their art
Photo in featured entry box by Norbert von der Groeben

Behavioral Science, In the News, Sleep, Stanford News

"Sleep drunkenness" more prevalent than previously thought

"Sleep drunkenness" more prevalent than previously thought

sleep_drunkennessA phenomenon known as “sleep drunkenness” may be more prevalent than previously thought, affecting as many as 1 in 7 adults, Stanford researchers report in a new study. That means as many as 36 million Americans experience this potentially problematic sleep condition, in which they are awakened suddenly in a confused state and may be prone to inappropriate behavior, poor decision-making, or even violence.

In interviews with nearly 16,000 adults aged 18 to 102, the researchers found that within the previous year, 15.2 percent had experienced the condition, also known as confusional arousal, with more than half saying they had at least one episode a week.

Stanford psychiatrist and sleep expert Maurice Ohayon, MD, DSc, PhD, said he was surprised at the extent of the problem and particularly the length of time that people reported feeling confused and disoriented following a sudden awakening, whether at night or from a daytime nap.

“I was thinking maybe 30 seconds, a minute or two minutes,” Ohayon told me. “When you ask people, 60 percent said it lasted more than 5 minutes. And one third said it was 15 minutes or more. A lot of things can happen in that time.

“The concern is that people in a job of security, such as engineer, may misjudge the situation because their memory is impaired. Their judgment is not taking into account the environment around them, so they will probably have a bad response. The response will not be adapted to the environment,” said Ohayon, a professor of psychiatry and behavioral sciences and the study’s first author.

He noted that the 1979 Three Mile Island nuclear disaster, the worst nuclear incident in U.S. history, was exacerbated in part by poor decision-making on the part of an engineer who had been awakened suddenly from a nap. He also cautioned that airline pilots, who may nap during a break, may not be efficient for 5 or 10 minutes after being awakened and should take their time before resuming control of an aircraft.

Among those who are most prone to the condition are those with sleep disorders, such as sleep apnea or those who sleep less than 6 hours or more than 9 hours a night, as well as people with certain psychiatric disorders, such as major depression, anxiety and alcohol dependence, the researchers found. Ohayon said he was surprised to discover a strong link between the condition and the use of antidepressants, which likely modify sleep architecture and may contribute to a greater incidence of the condition. Though there is a common perception that people who take sleep medications to help them fall asleep may be confused when they wake up, that was not found to be the case, he said.

More than a third of the people in the study who experienced confusional arousal also said they had hallucinations, and 14.8 percent reported sleep-walking, sometimes accompanied by violent behavior.

“People during confusional arousal can become violent because they are awakened suddenly,” Ohayon said. “They are not happy. They are confused. They may feel aggression toward their partner or the people who have awakened them.”

He said people who experience frequent episodes of confusional arousal should consult with a physician for evaluation and possible treatment. And he urged further study of the problem, which has received little scientific attention.

The study appears in the August 26 issue of the journal Neurology.

Photo by katiecooperx

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