NEW PARTICLE ACCELERATORS COULD EXPAND USE TO SCIENCE AND INDUSTRY

FROM:  NATIONAL SCIENCE FOUNDATION
Smaller and cheaper particle accelerators?

Scientists developing technology that could expand use for medicine, national security, materials science, industry and high energy physics research
Traditionally, particle accelerators have relied on electric fields generated by radio waves to drive electrons and other particles close to the speed of light. But in radio-frequency machines there is an upper limit on the electric field before the walls of the accelerator "break down," causing it to not perform properly, and leading to equipment damage.

In recent years, however, scientists experimenting with so-called "plasma wakefields" have found that accelerating electrons on waves of plasma, or ionized gas, is not only more efficient, but also allows for the use of an electric field a thousand or more times higher than those of a conventional accelerator.

And most importantly, the technique, where electrons gain energy by "surfing" on a wave of electrons within the ionized gas, raises the potential for a new generation of smaller and less expensive particle accelerators.

"The big picture application is a future high energy physics collider," says Warren Mori, a professor of physics, astronomy and electrical engineering at University of California, Los Angeles (UCLA), who has been working on this project. "Typically, these cost tens of billions of dollars to build. The motivation is to try to develop a technology that would reduce the size and the cost of the next collider."

The National Science Foundation (NSF)-funded scientist and his collaborators believe the next generation of smaller and cheaper accelerators could enhance their value, expanding their use in medicine, national security, materials science, industry and high-energy physics research.

"Accelerators are also used for sources of radiation. When a high energy particle wiggles up and down, it generates X-rays, so you could also use smaller accelerators to make smaller radiation sources to probe a container to see whether there is nuclear material inside, or to probe biological samples," Mori says. "Short bursts of X-rays are currently being used to watch chemical bonds form and to study the inner structure of proteins, and viruses."

Just as important, albeit on a more abstract level, "the goal of the future of high-energy physics is to understand the fundamental particles of matter," he says. "To have the field continue, we need these expensive, large, and complex tools for discovery."

NSF has supported basic research in a series of grants in recent years totaling $4 million, including computational resources. The Department of Energy (DOE) has provided the bulk of the funding for experimental facilities and experiments, and has contributed to theory and simulations support.

"Mori's work is the perfect example of an innovative approach to advancing the science and technology frontiers that can come about when the deep understanding of fundamental laws of nature, of the collective behavior of charged particles that we call a plasma, is combined with state-of-the-art numerical modeling algorithms and simulation tools," says Vyacheslav (Slava) Lukin, program director in NSF's physics division.

Using DOE's SLAC National Accelerator Laboratory, the scientists from SLAC and UCLA increased clusters of electrons to energies 400 to 500 times higher than what they could reach traveling the same distance in a conventional accelerator. Equally important, the energy transfer was much more efficient than that of earlier experiments, a first to show this combination of energy and efficiency using "plasma wakefields."

In the experiments, the scientists sent pairs of electron bunches containing 5 billion to 6 billion electrons each into a laser-generated column of plasma inside an oven of hot lithium gas. The first bunch in each pair was the "drive" bunch; it blasted all the free electrons away from the lithium atoms, leaving the positively charged lithium nuclei behind, a configuration known as the "blowout regime." The blasted electrons then fell back in behind the second bunch of electrons, known as the "trailing" bunch to form a "plasma wake" that thrust the trailer electrons to higher energy.

While earlier experiments had demonstrated high-field acceleration in plasma wakes, the SLAC/UCLA team was the first to demonstrate simultaneously high efficiency and high accelerating fields using a drive and trailer bunch combination in the strong "blowout" regime. Furthermore, the accelerated electrons ended up with a relatively small energy spread.

"Because it's a plasma, there is no breakdown field limit," Mori says. "The medium itself is fully ionized, so you don't have to worry about breakdown. Therefore, the electric field in a plasma device can be pushed to a thousand or more times higher amplitude than that in a conventional accelerator."

Chandrashekhar Joshi, UCLA professor of electrical engineering, led the team that developed the plasma source used in the experiment. Joshi, the director of the Neptune Facility for Advanced Accelerator Research at UCLA is the UCLA principal investigator for this research and is a long-time collaborator with the SLAC group. The team also is made up of SLAC accelerator physicists, including Mike Litos and Mark Hogan; Mori leads the group that developed the computer simulations used in the experiments. Their findings appeared last fall in the journal Nature.

"The near term goal of this research is to produce compact accelerators for use in universities and industry, while a longer term goal remains developing a high energy collider operating at the energy frontier of particle physics," Mori says.

-- Marlene Cimons, National Science Foundation
Investigators
Warren Mori
Frank Tsung
Viktor Decyk
Russel Caflisch
Michail Tzoufras
Philip Pritchett
Related Institutions/Organizations
University of California-Los Angeles

DOCTORS TRAIN WITH HUMAN PATIENT SIMULATOR

FROM:  NATIONAL SCIENCE FOUNDATION
How robots can help build better doctors
Research seeks to make better 'human patient simulators'

A young doctor leans over a patient who has been in a serious car accident and invariably must be experiencing pain. The doctor's trauma team examines the patient's pelvis and rolls her onto her side to check her spine. They scan the patient's abdomen with a rapid ultrasound machine, finding fluid. They insert a tube in her nose. Throughout the procedure, the patient's face remains rigid, showing no signs of pain.

The patient's facial demeanor isn't a result of stoicism--it's a robot, not a person. The trauma team is training on a "human patient simulator," (HPS) a training tool which enables clinicians to practice their skills before treating real patients. HPS systems have evolved over the past several decades from mannequins into machines that can breathe, bleed and expel fluids. Some models have pupils that contract when hit by light. Others have entire physiologies that can change. They come in life-sized forms that resemble both children and adults.

But they could be better, said Laurel D. Riek, a computer science and engineering professor at the University of Notre Dame. As remarkable as modern patient simulators are, they have two major limitations.

"Their faces don't actually move, and they are unable to sense or respond to the environment," she said.

Riek, a roboticist, is designing the next generation of HPS systems. Her NSF-supported research explores new means for the robots to exhibit realistic, clinically relevant facial expressions and respond automatically to clinicians in real time.

"This work will enable hundreds of thousands of doctors, nurses, EMTs, firefighters and combat medics to practice their treatment and diagnostic skills extensively and safely on robots before treating real patients," she said.

One novel aspect of Riek's research is the development of new algorithms that use data from real patients to generate simulated facial characteristics. For example, Riek and her students have recently completed a pain simulation project and are the first research group to synthesize pain using patient data. This work won them best overall paper and best student paper at the International Meeting on Simulation in Healthcare, the top medical simulation conference.

Riek's team is now working on an interactive stroke simulator that can automatically sense and respond to learners as they work through a case. Stroke is the fifth leading cause of death in the United States, yet many of these deaths could be prevented through faster diagnosis and treatment.

"With current technology, clinicians are sometimes not learning the right skills. They are not able to read diagnostic clues from the face," she said.

Yet learning to read those clues could yield lifesaving results. Preventable medical errors in hospitals are the third-leading cause of death in the United States.

"What's really striking about this is that these deaths are completely preventable," Riek said.

One factor contributing to those accidents is clinicians missing clues and going down incorrect diagnostic paths, using incorrect treatments or wasting time. Reading facial expressions, Riek said, can help doctors improve those diagnoses. It is important that their training reflects this.

In addition to modeling and synthesizing patient facial expressions, Riek and her team are building a new, fully-expressive robot head. By employing 3-D printing, they are working to produce a robot that is low-cost and will be one day available to both researchers and hobbyists in addition to clinicians.

The team has engineered the robot to have interchangeable skins, so that the robot's age, race and gender can be easily changed. This will enable researchers to explore social factors or "cultural competency" in new ways.

"Clinicians can create different patient histories and backgrounds and can look at subtle differences in how healthcare workers treat different kinds of patients," Riek said.

Riek's work has the potential to help address the patient safety problem, enabling clinicians to take part in simulations otherwise impossible with existing technology.

-- Rob Margetta,
Investigators
Laurel Riek
Related Institutions/Organizations
University of Notre Dame

FDA APPROVES FIRST BIOSIMILAR PRODUCT IN U.S.

FROM:  U.S. FOOD AND DRUG ADMINISTRATION
The U.S. Food and Drug Administration today approved Zarxio (filgrastim-sndz), the first biosimilar product approved in the United States.

Biological products are generally derived from a living organism. They can come from many sources, including humans, animals, microorganisms or yeast.

A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product, known as a reference product. The biosimilar also must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

Sandoz, Inc.’s Zarxio is biosimilar to Amgen Inc.’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is approved for the same indications as Neupogen, and can be prescribed by a health care professional for:

patients with cancer receiving myelosuppressive chemotherapy;
patients with acute myeloid leukemia receiving induction or consolidation chemotherapy;
patients with cancer undergoing bone marrow transplantation;
patients undergoing autologous peripheral blood progenitor cell collection and therapy; and
patients with severe chronic neutropenia.

“Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, M.D. “Patients and the health care community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy and quality standards.”

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Obama signed into law in March 2010. The BPCI Act created an abbreviated licensure pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product, called the “reference product.” This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data.

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

The FDA’s approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen. Zarxio has been approved as biosimilar, not as an interchangeable product. Under the BPCI Act, a biological product that that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.

The most common expected side effects of Zarxio are aching in the bones or muscles and redness, swelling or itching at injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome, a lung disease that can cause shortness of breath, difficulty breathing or increase the rate of breathing.

For this approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name for this product should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products. While the FDA has not yet issued draft guidance on how current and future biological products marketed in the United States should be named, the agency intends to do so in the near future.

U.S.-EU HAVE SUCCESS FIGHTING ANTIMICROBIAL RESISTANCE

FROM:  U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

US and EU progress in fight against antimicrobial resistance

International collaboration critical for combating global health crisis

The U.S. Department of Health and Human Services (HHS) and the European Commission released today the first progress report of the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR).  The report renews the commitment of U.S. and European Union (EU) health authorities to pursue specific goals in their joint battle against antimicrobial resistance, a complex, dynamic and multi-faceted concern not bound by borders.  The report also summarizes the advancements made during the first TATFAR implementation period of 2011-2013.

TATFAR was created following the 2009 U.S.-EU presidential summit with the goal of improving cooperation between the U.S. and the EU in three key areas: (1) appropriate therapeutic use of antimicrobial drugs in medical and veterinary communities, (2) prevention of health care- and community-associated drug-resistant infections, and (3) strategies for improving the pipeline of new antimicrobial drugs.

“The partnership offers a unique perspective to tackle antimicrobial resistance worldwide,” said Jimmy Kolker, HHS Assistant Secretary for Global Affairs.  “We hope that the positive outcomes of this partnership will serve as a global model as we continue to work on this critical issue.”

TATFAR identified and adopted 17 recommendations for collaborations between the U.S. and the EU. Implementation of the recommendations has been carried out through increased communication, regular meetings, joint workshops, and the exchange of information, approaches, and best practices.  Moving forward, one new and 15 existing recommendations will serve as the basis for partner agencies in the U.S. and the EU to focus on areas where common actions can deliver the best results in prevention and control of antimicrobial resistance. In 2013 it was decided to renew TATFAR for another two-year term.

“Antimicrobial resistance is a priority of the European Commission, and international cooperation is key in addressing this serious cross border and global health threat.  I am positive that our renewed commitment to TATFAR can make a tangible contribution in the area of global health security,” said John F. Ryan, Acting Director for Public Health in the European Commission.

Notable outcomes of TATFAR activities during 2011-2013 include:

Adoption of procedures for timely international communication of critical events that might indicate new resistance trends with global public health implications;
Publication of a report on the 2011 workshop, “Challenges and solutions in the development of new diagnostic tests to combat antimicrobial resistance” to the TATFAR website; and Joint presentations to the scientific community to increase awareness about the available funding opportunities on both sides of the Atlantic.
Studies estimate that drug-resistant infections result in at least 25,000 deaths in 29 countries in Europe and 23,000 deaths in the U.S. every year.  In addition to the toll on human life, antimicrobial-resistant infections add considerable and avoidable costs to health care systems.  Antimicrobial resistance costs the EU and the U.S. billions every year in avoidable health care costs and productivity losses.

In the U.S. and in the EU, significant progress in reducing specific types of infections has been made.  However, the global problem of antimicrobial resistance continues to escalate. Therefore, the original mandate of the taskforce that ran through 2013 has been extended for at least two additional years.

Forthcoming publications from the taskforce during 2014 that will provide a foundation for specific joint collaborative actions include:

A report summarizing the strategies hospitals in the U.S. and EU should include as part of their programs to improve antimicrobial prescribing practices;
A joint publication summarizing the existing methods for measuring antimicrobial use in hospital settings;
A joint publication describing the need for new vaccines for healthcare-associated infections (HAIs); and
A joint publication comparing the results of the U.S. and EU point prevalence surveys, which are used to estimate the burden of HAIs in each population.

OTEZLA APPROVED BY FDA TO TREAT ADULT ACTIVE PSORIATIC ARTHRITIS

FDA NEWS RELEASE

For Immediate Release: March 21, 2014
Media Inquiries: Morgan Liscinsky, 301-796-0397, morgan.liscinsky@fda.hhs.gov 
Consumer Inquiries: 888-INFO-FDA

FDA approves Otezla to treat psoriatic arthritis

The U.S. Food and Drug Administration today approved Otezla (apremilast) to treat adults with active psoriatic arthritis (PsA).

PsA is a form of arthritis that affects some people with psoriasis. Most people develop psoriasis first and are later diagnosed with PsA. Joint pain, stiffness and swelling are the main signs and symptoms of PsA. Currently approved treatments for PsA include corticosteroids, tumor necrosis factor (TNF) blockers, and an interleukin-12/interleukin-23 inhibitor.

“Relief of pain and inflammation and improving physical function are important treatment goals for patients with active psoriatic arthritis,” said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “Otezla provides a new treatment option for patients suffering from this disease.”

The safety and effectiveness of Otezla, an inhibitor of phosphodieasterase-4 (PDE-4), were evaluated in three clinical trials involving 1,493 patients with active PsA. Patients treated with Otezla showed improvement in signs and symptoms of PsA, including tender and swollen joints and physical function, compared to placebo.

Patients treated with Otezla should have their weight monitored regularly by a healthcare professional. If unexplained or clinically significant weight loss occurs, the weight loss should be evaluated and discontinuation of treatment should be considered. Treatment with Otezla was also associated with an increase in reports of depression compared to placebo.

The FDA is requiring a pregnancy exposure registry as a post-marketing requirement to assess the risks to pregnant women related to Otezla exposure.
 
In clinical trials, the most common side effects observed in patients treated with Otezla were diarrhea, nausea, and headache.  

CDC REPORTS ON FIGHT AGAINST POLIO IN PAKISTAN AND AFGHANISTAN

FROM:  CENTERS FOR DISEASE CONTROL AND PREVENTION 

Progress and Challenges Fighting Polio in Pakistan and Afghanistan
Not reaching every child jeopardizes progress and risks re-introduction in other parts of the world

Both Pakistan and Afghanistan saw an overall decrease in wild poliovirus (WPV) cases from January – September 2013 compared with the same time period in 2012 according to data published in the Morbidity and Mortality Weekly Report (MMWR) released today by the Centers for Disease Control and Prevention (CDC).  Since 2012, transmission of indigenous WPV has been limited to three countries: Afghanistan, Pakistan, and Nigeria.  Results for Nigeria will be released in December.

Both countries still face significant challenges in reaching unvaccinated children.  Afghanistan is fighting a polio outbreak in the Eastern Region while Pakistan continues to see polio increases in the conflict-affected Federally Administered Tribal Areas (FATA), where there is a ban on polio vaccination, and in security-compromised Khyber Pakhtunkhwa Province. The potential risk of transmission to other countries highlights the need for strong ongoing global efforts to eradicate this disease.

“Although there have been setbacks, we are making progress towards global polio eradication,” said CDC Director Dr. Tom Frieden, M.D., M.P.H. “There is encouraging progress in Afghanistan, but, as long as transmission is uninterrupted in Pakistan and Nigeria, the risk for spread to other countries continues because polio anywhere presents a threat of polio everywhere."

In Afghanistan, confirmed cases of WPV dropped from 80 in 2011 to 37 in 2012.  The downward trend continues for 2013 with only eight cases confirmed during January–September 2013, compared with 26 during the same period in 2012.  All eight polio cases in 2013 were in the Eastern Region and originated from the wild poliovirus in Pakistan.

This week Afghanistan achieved a significant milestone - 12 months without any recorded cases of wild poliovirus in the traditionally polio-endemic provinces of Kandahar and Helmand, long recognized as Afghanistan's epicentres of polio.  This unprecedented progress is an endorsement of the effectiveness of the polio eradication programs and their implementation in the Southern Region.    

akistan reported a decrease from 198 WPV cases throughout the country in 2011 to 58 in 2012 in selected areas.  Fifty-two cases were reported during January–September 2013, compared with 54 cases during the same period in 2012.   However, because of additional cases since September, 2013 Pakistan has now surpassed the 2012 numbers, thus reversing the downward trend.   Eighty-four percent of cases reported since January 2012 occurred in the FATA and Khyber Pakhtunkhwa Province.

Approximately 350,000 children in the FATA have not received polio vaccines during immunization campaigns conducted since mid-2012 because local authorities have banned vaccination. In other areas of Pakistan, polio vaccination teams have encountered increased security threat-levels, hindering immunization programs.  Further multi-pronged efforts to reach children in conflict-affected and security-compromised areas will be necessary to prevent WPV re-introduction into other areas of Pakistan and other parts of the world.  This situation requires all countries to take additional public health actions to strengthen detection and strengthen protection by enhancing polio surveillance programs and intensifying vaccination efforts.

WEST NILE VIRUS AND TRANSFUSIONS

FROM:  CENTERS FOR DISEASE CONTROL AND PREVENTION 
Fatal West Nile Virus Infection Following Probable Transfusion-Associated Transmission—Colorado, 2012
CDC Media Relations
404-639-3286

Starting in 2003, the U.S. blood supply has been screened for West Nile virus.  Since then, approximately 3,500 West Nile virus-infected units have been removed from the blood supply and only 12 cases of transfusion-associated transmission of West Nile virus have been identified. This report describes the first probable case of transfusion-associated West Nile virus infection in which the donation was negative by individual nucleic acid testing on initial screening. The case occurred in an immunosuppressed patient who was likely more susceptible to infection at very low concentrations of West Nile virus in the transfused blood product. Transfusion-associated West Nile virus infections are rare.  However, healthcare providers should consider West Nile virus disease in any patient with compatible symptoms who has received a blood transfusion during the 28 days before the onset of illness.  Possible cases should be promptly reported to the blood collection agency and public health authorities