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The Innovation of Women in Medicine: A Kean Analysis – The Tower

By Tasha Dowbachuk | Published by September 19th, 2019

On Sept. 11, the American Medical Womens Association (AMWA) held an interest meeting in the Miron Student Center at 11:30 a.m., welcoming students in discovering the mission and values within their organization at Kean University.

The informational event of the organization presented their commitment to promoting excellence in medical communication while providing educational resources in support of women empowerment in medicine.

According to its website, the organization was founded by Dr. Bertha VanHoosen in 1915 in Chicago. The first international organization of medical women was founded in 1919, with the intention of representing women in medicine worldwide.

Informative bulletin board of the American Medical Womens Association.Photo by Tasha Dowbachuk

Today, AMWA provides networking opportunities and in-depth discussions about the future of medicine to anyone who is interested or involved in the medical field. The event was hosted by Vice President Julia CurtisDye, who is majoring in Cell and Molecular Biology, along with the members of the association.

Through the free membership of the campus chapter, members are given the opportunity to participate in national conferences, mentorships, and scholarship benefits by joining the national branch of AMWA through a $35 payment.

I think to give some of our members their first glance of the medical field and helping them get closer to their goals through the memberships, as women in a male-dominated field, is one of our greatest achievements, said CurtisDye. Our job is to connect people to our Kean branch membership for free or connect to the national branch membership under a $35 fee to attend the national conferences, mentorships which cover for your entire undergraduate journey.

Marina Georges, a senior psychology major with a minor in biology, is serving her first year as the President of AMWA this semester. After becoming a member of the chapter, the unification of a sisterhood bond within the organization inspired her to expand and motivate members into pursuing the medical field.

When we bring great minds together, in science, we can bring better public health and hopefully finding cures through the unity within this organization, said Georges. Having that common ground, like a group of strong sisters who support each other, creates something so beautiful for the future of medicine.

The president of AMWA, Marina Georges (left) with Vice president, Julia CurtisDye (right).Photo by Tasha Dowbachuk

The association also provides guidance for admissions processing and preparing for the Medical College Admission Test (MCAT exam).

According to the Princeton Review, the MCAT is a 7.5 hour exam that consists of four sections: Biological and Biochemical Foundations of Living Systems; Chemical and Physical Foundations of Biological Systems; Psychological, Social, and Biological Foundations of Behavior; and Critical Analysis and Reasoning Skills.

We brought in Kean alumni, who shared their experiences in the field and how AMWA helped them in becoming a physician assistant. said Georges.

The academic and social aspects of the association are not restrictive to male students who are interested in joining.

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The Innovation of Women in Medicine: A Kean Analysis - The Tower

CRISPR fix in mice may lead to muscular dystrophy therapy – Futurity: Research News

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The CRISPR gene editing technique may provide the means for lifelong correction of the genetic mutation responsible for Duchenne muscular dystrophy, a new study with mice shows.

Duchenne muscular dystrophy (DMD), a rare but devastating genetic disorder, causes muscle loss and physical impairment. Children with DMD have a gene mutation that interrupts the production of a protein known as dystrophin. Without it, muscle cells weaken and eventually die. Many children lose the ability to walk, and muscles essential for breathing and heart function ultimately stop working.

Research has shown that CRISPR can be used to edit out the mutation that causes the early death of muscle cells in an animal model, says Dongsheng Duan, professor in medical research in the molecular microbiology and immunology department at the University of Missouri School of Medicine and senior author of the paper in Molecular Therapy.

However, there is a major concern of relapse because these gene-edited muscle cells wear out over time. If we can correct the mutation in muscle stem cells, then cells regenerated from the edited stem cells will no longer carry the mutation. A one-time treatment of the muscle stem cells with CRISPR could result in continuous dystrophin expression in regenerated muscle cells.

For the study, researchers explored whether they could efficiently edit muscle stem cells from mice. They first delivered the gene editing tools to normal mouse muscle through AAV9, a virus that the US Food and Drug Administration recently approved to treat spinal muscular atrophy.

We transplanted AAV9 treated muscle into an immune-deficient mouse, says lead author Michael Nance, a MD-PhD program student in Duans lab. The transplanted muscle died first then regenerated from its stem cells. If the stem cells were successfully edited, the regenerated muscle cells should also carry the edited gene.

The researchers reasoning was correctthey found abundant edited cells in the regenerated muscle. They then tested if they could use CRISPR to edit muscle stem cells in a mouse model of DMD. Similar to what they found in normal muscle, the stem cells in the diseased muscle were also edited. Cells regenerated from these edited cells successfully produced dystrophin.

This finding suggests that CRISPR gene editing may provide a method for lifelong correction of the genetic mutation in DMD and potentially other muscle diseases, Duan says.

Our research shows that CRISPR can be used to effectively edit the stem cells responsible for muscle regeneration. The ability to treat the stem cells that are responsible for maintaining muscle growth may pave the way for a one-time treatment that can provide a source of gene-edited cells throughout a patients life.

With more study, the researchers hope this stem cell-targeted CRISPR approach may one day lead to long-lasting therapies for children with DMD.

Additional coauthors are from the University of Missouri, the National Center for Advancing Translational Sciences, Johns Hopkins School of Medicine, and Duke University. The National Institutes of Health, the Department of Defense, the Jackson Freel DMD Research Fund, Hope for Javier, and the Intramural Research Program of the National Center for Advancing Translational Sciences funded the work.

Source: University of Missouri

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CRISPR fix in mice may lead to muscular dystrophy therapy - Futurity: Research News

7 Days in Science September 13, 2019 – Technology Networks

Breakthrough in Preventing Chemotherapy-induced Hair Loss

Scientists have uncovered a novel method that could potentially prevent chemotherapy-induced hair loss, with the use of an ex vivo organ culture model.

Published in:EMBO Molecular Medicine

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Compound Created to Help Reconstruct Myelin in Multiple Sclerosis

Researchers have created a compound, that when tested in mice, was able to promote the reconstruction of the myelin sheath surrounding neuronal axons.

Published in:Glia

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Analytical Science Puts Historical Claims to the Test

The latest analytical techniques available to scientists are being used to confirm the validity of historical artifacts and claims in some cases, and suggest a need for reconsideration in others.

Published in:Eur. Phys. J. PlusRead full story

"Pathobiome" Gives New Angle on Disease

Scientists have presented a novel concept describing the complex microbial interactions that lead to disease in plants, animals and humans. The "pathobiome" concept could be applied to enhance production of many species, such as shrimp, a major aquaculture product globally.

Published in:Trends in Ecology and EvolutionRead full story

A Toast To the Genetic Diversity of Grapes

A research team has deciphered the genome of the Chardonnay grape. By doing so, they have uncovered something fascinating: grapes inherit different numbers of genes from their mothers and fathers.

Published in: Nature PlantsRead full story

When a stroke occurs, the blood supply to parts of the brain is either interrupted, reduced or stopped, depriving the brain of the oxygen and essential nutrients it requires to function. Consequently, brain cells begin to die. In a new study using a mouse model of ischemic stroke, researchers have successfully converted glial cells into new neurons. This may form the basis of a novel gene therapy for stroke treatment.

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Transplant recipients immune systems recognize donor organs as "foreign" and can attack them in a bid to eliminate them from the body. Immunosuppressive drugs can help to minimizethe magnitude of rejection but are not always successful long-term and their use comes with adverse effects of their own. In this article we take a look at the potentialof 3D bioprinting technologies as a way to eliminate the chancesof rejection, by generating organs in the lab from patients' own cells.

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TSE Explores Microplastics What are Microplastics?

Creating Protein Patterns

Credit: Nancy Hernandez, William Hansen and Slava Manichev

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7 Days in Science September 13, 2019 - Technology Networks

Washington People: Gwen Randolph – Washington University School of Medicine in St. Louis

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Immunologist shows that the journey is as important as the destination

Gwendalyn Randolph, PhD, talks in her lab with postdoctoral researcher Rafael Czepielewski, PhD. An immunologist by training, Randolph studies immune cells and how they travel around the body in conditions as diverse as inflammatory bowel and cardiovascular disease.

A few years ago, as immunologist Gwendalyn Randolph, PhD, and postdoctoral researcher Li-Hao Paul Huang, PhD, hashed out a research plan, the two realized they had a problem. They were studying inflammatory bowel disease (IBD), and they needed human participants for a study looking at how fat travels from the intestine to the blood. But they had never done a human study that required more of participants than donating a small amount of blood. Worse, they didnt have a local clinical collaborator since Randolph, the Emil R. Unanue Distinguished Professor of Immunology at Washington University School of Medicine in St. Louis, had just recently arrived in St. Louis from Icahn School of Medicine at Mount Sinai in New York City.

Randolph and Huang started designing a study to be conducted at Mount Sinai, where Randolph still had many collaborators. But to do so, they needed to figure out how the fats would be delivered to participants and brought back to St. Louis for analysis.

First, we were concerned with formulating a fat-rich meal that would be palatable and could be made reproducibly by our colleagues in New York, Huang said. We went to Gwens house, and we prepared a milkshake with ice cream and whole milk and the other ingredients needed for the study including fat molecules that could be traced in the laboratory and we drank it.

The taste test was successful, but luckily, it turned out to be unnecessary. Not long after, Washington University gastroenterologist Matthew Ciorba, MD, approached Randolph and suggested a collaboration. And soon, other School of Medicine faculty members gastroenterologist Parakkal Deepak, MBBS, and nutrition experts Bettina Mittendorfer, PhD, Bruce Patterson, PhD, and W. Todd Cade, PhD signed on as well. Together, they redesigned the study to leverage Washington Universitys prowess in translational medicine. Randolph was only too happy to leave milkshake formulation to the true experts.

The study is nearing completion. It represents a remarkable shift in focus for Randolph, who began her career studying how immune cells travel around the body.

Shes just a fantastic scientist, said Paul Allen, PhD, the Robert L. Kroc Professor of Pathology and Immunology and a collaborator of Randolphs. She used to work on innate immune cells, but then she blossomed out into cardiovascular disease, lipid metabolism, the gut. Its just amazing how she finds these connections between different fields.

Randolph has a long track record of breaking down scientific silos. An immunologist by training, she made a name for herself in cardiovascular and inflammation research by asking questions no one else had thought to ask.

For her, its like solving mysteries, said Melody Swartz, PhD, a professor of molecular engineering at the University of Chicago and a longtime collaborator of Randolphs. She just really cares about science. She is not interested in awards or being the first to publish; she really and truly only cares about figuring out whats going on.

Gwen Randolph, PhD (center), laughs with staff scientist Shashi Bala Kumar (left) and postdoctoral researcher Rafael Czepielewski, PhD.

An accidental scientist

If the stars had aligned just a bit differently, Randolph, who is also a professor of medicine, might never have become a scientist at all. Raised on a maize and cotton farm outside the small town of Hart in the Texas Panhandle, she grew up hoeing weeds and helping with the harvest.

As a teenager, she exhibited a talent for sewing and design that won her awards and trips to New York and Los Angeles. But when she started talking about moving east to study textiles after high school, her parents both descended from generations of Southern farmers hesitated. So instead, she accepted a basketball scholarship to Wayland Baptist University in nearby Plainview, Texas, and enrolled in pre-med courses.

I thought I was going to be a doctor, but in the spring of my first year, I fell in love with histology, Randolph recalled, referring to the microscopic structure of tissues. I can remember sitting in a laundromat, doing my laundry, reading this book on how white blood cells leave the bloodstream and go into tissues, and I was just fascinated. It was very historical, and I remember wondering if anyone was still studying that stuff.

Not many people were, it turned out. Immunologists love to study the immune systems lymph nodes, where cells that have encountered infectious organisms or signs of injury go to alert other cells about the danger in their midst. But immunologists dont tend to spare much thought for the journey immune cells take on their way to the lymph nodes. Once she had the scientific training, Randolph returned to the question that had first piqued her interest what happens en route to the lymph nodes and began to investigate. She was fascinated to learn that lymphatic vessels that connect lymph nodes are far from an inert network of tubing. The vessels dilate or constrict to slow or speed the rate of travel. She showed that the constricting lymphatic vessels leak many signaling molecules into the surrounding tissue, and these signals are captured by other immune cells that, in turn, respond to help regulate immunity. All these functions add up to a pivotal role for the lymphatics in shaping the immune response.

Everyone was throwing away the fatty tissue that is outside of lymph nodes because its boring, Randolph said. But fat is what links all the organs to the various lymph nodes that collect drainage from our tissues, and it turns out all kinds of things are happening in the fat.

That brief textbook passage on histology eventually led Randolph to break down the wall separating lymphatic biology and immunology, and show that how cells and molecules get places is just as important as where theyre going.

Blazing a trail in New York

After two years at Wayland Baptist, Randolph moved to Pennsylvania, where she completed her undergrad studies at Temple University. From there, she moved to the State University of New York, Stony Brook, for graduate school, and then to Rockefeller University and Weill Cornell Medicine for postdoctoral studies.

In New York, while a postdoc at Rockefeller and Weill Cornell, Randolph worked closely with Ralph Steinman, MD, who went on to win the Nobel Prize in Physiology or Medicine in 2011 for his discovery of the dendritic cell the cell type that orchestrates and conducts the immune response.

In collaboration with Steinman, Randolph published a paper in Science in 1998 showing that dendritic cells mature from a different immune cell type and that dendritic cells are compelled to migrate to lymph nodes. As part of the study, Randolph grew immune cells in collagen matrices below a layer of cells that line the inner surface of blood vessels. The immune cells passed through the blood vessel cells and migrated upward, toward the rim of the wells. They had presumably climbed through the blood vessel-cell layer in search of lymphatic vessels that would, in a living animal, take them to the lymph nodes. The strong propensity of dendritic cells to migrate to lymph nodes, even when lymph nodes were not part of the experimental setup, fueled her research on lymphatic vessels.

Randolph met her future husband, Hermann Kyrychenko, at an art gallery while on vacation in Prague, and within a year, he moved to New York to be with her. Today, they have two children: Anton, 14, and Athena, 11.

Gwen Randolph relaxes with her husband, Hermann Kyrychenko; son, Anton; daughter, Athena; and the family dog, Lily.

A Ukrainian national by birth who has worked as a translator, a paramedic, an art gallery docent and a martial arts instructor, Kyrychenko did much of the child-raising while Randolph established a lab at Mount Sinai and started exploring the relationship between the lymphatics and other systems of the body, notably the cardiovascular system.

Immune cells known as macrophages help keep blood flowing smoothly by eating up the cholesterol that sometimes collects inside blood vessels. Randolph hypothesized that, after consuming cholesterol, macrophages migrate from the bloodstream through the lymphatics to dispose of the cholesterol, and that problems with the lymphatics could cause the sticky substance to build up, raising the risk of heart attack. This hypothesis proved untrue, but the process of investigating it unveiled other key observations on macrophages, including how much macrophages vary from organ to organ.

What I really like about Gwen is that she goes where the data take her, said Robert Gropler, MD, a professor of radiology who works with Randolph to develop new positron emission tomography (PET) imaging probes designed to detect signs of inflammation and immunity. She maintains an open mind, and because of that, shes a highly innovative scientist. Her real strength is the breadth and depth of her knowledge. She knows not only her own field but other fields well enough to see how they could benefit from collaboration. Shes just a really incredible resource for the university.

Along with her willingness to pursue novel scientific ideas, Randolph has earned a reputation for being willing to stand up for what she believes, especially on issues affecting women and people who arent in positions of power. At Mount Sinai, she helped establish a lactation room after several postdocs in her lab and neighboring labs gave birth, and she realized they had nowhere clean and private to pump milk. She once challenged the dean of the School of Medicine at Mount Sinai to a basketball game both loved the sport to settle a dispute over the schools policy of taking a cut of postdocs career award funding to beef up indirect cost recovery from those awards. The game never happened, but a compromise for the source of the indirect costs was reached, with the departments rather than the investigators covering the required amount. At Washington University, she has continued to voice concerns that touch on social justice.

She will never allow something wrong to happen in front of her eyes without fighting against it, said Miriam Merad, MD, PhD, an immunologist at Mount Sinai who worked with Randolph for many years. It has sometimes been to her detriment to be so vocal. But Gwen will always fight for the cause she believes in.

Finding a scientific home in the Midwest

In 2011, when word began to spread at Mount Sinai that her department was closing, Randolph took a job at Washington University. She resettled her family in Clayton, partly because it was close enough for her to bike across Forest Park to work every day.

I might be the only one from the Panhandle of Texas who ever existed who doesnt like cars, Randolph said. We have a car, but I refuse to drive to work.

In Clayton, she cultivates a varied and thriving vegetable and herb garden. When Huang dropped by her home one afternoon to pick up some reagents he needed in the lab, Randolph treated him to homemade vegetable pizza, marinated cucumbers, basil ice cream That was a bit weird, Huang said and cake with blackberry sauce. Most of the produce for the meal had been harvested from her own backyard.

Just before Randolph moved to St. Louis, a chance conversation at Mount Sinai changed the course of her research.

My graduate student was presenting her research on fat and lymphatics, and one of my colleagues turned to me and joked, There is only one person who is interested in fat and lymphatics other than you: Jean-Frederic Colombel, Randolph said. So I called him up.

Colombel turned out to be a gastroenterologist who specializes in Crohns disease. He introduced Randolph to the peculiar creeping fat that grows up around the intestine near sites of damage in IBD. The fat is associated with strictures in the intestine that can cause bowel obstruction and necessitate emergency surgery. Colombel thought the fat was not just a curiosity but was contributing to the disease. Intrigued, Randolph began collaborating with Colombel to investigate the role of fat and lymphatics in IBD.

I make decisions, and I move forward, and I dont spend a lot of time thinking, Does it make sense to take on this risk? Randolph said. Some doors close, and I open other doors and move forward.

In 2015, she received a prestigious Pioneer Award from the National Institutes of Health (NIH) to study how gut inflammation affects the lymphatic vessels near the intestine. She suspects that inflammatory cells release proteins that cause the vessels to constrict, impeding the flow of immune cells and proteins and contributing to a dysfunctional inflammatory response.

She also suspects that the fat itself is part of the problem. Some of the fat leaves the intestines and travels through the lymphatics to the bloodstream, converting into fatty acids along the way. Some fatty acids are highly inflammatory, so roaming fat could be contributing to the destructive inflammation of the disease.

Although the work is still in its early stages, it could transform our understanding of how IBD develops and progresses, and lead to novel strategies for treating the disease.

She is a completely independent thinker, an innovator, Merad said. Nothing surprises me coming from Gwen. If you told me she has become an astronaut, I would not be surprised. She dares and never looks back.

Immune cells cause cholesterol to be trapped in blood vessels

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Washington People: Gwen Randolph - Washington University School of Medicine in St. Louis

In human cells and mice, a cure for the common cold, Stanford-UCSF study reports – Stanford Medical Center Report

Temporarily disabling a single protein inside our cells might beable to protect us from the common cold and other viral diseases, according to a study led by researchers at Stanford University and University of California-San Francisco.

The findings were made in human cell cultures and in mice.

Our grandmas have always been asking us, If youre so smart, why havent you come up with a cure for the commoncold?said Jan Carette, PhD, associate professor of microbiology and immunology. Now we have a new way to do that.

The approach of targeting proteins in our own cells also worked to stop viruses associated with asthma, encephalitis and polio.

Colds, or noninfluenza-related upper respiratory infections, are for the most part a weeklong nuisance. Theyre also the worlds most common infectious illness, costing the United States economy an estimated $40 billion a year. At least half of all colds are the result of rhinovirus infections. There are roughly 160 known types of rhinovirus, which helps to explain why getting a cold doesnt stop you from getting another one a month later. Making matters worse, rhinoviruses are highly mutation-prone and, as a result, quick to develop drug resistance, as well as to evade the immune surveillance brought about by previous exposure or a vaccine.

In a study published online Sept. 16 inNature Microbiology, Carette and his associates found a way to stop a broad range of enteroviruses, including rhinoviruses, from replicating inside human cells in culture, as well as in mice. They accomplished this feat by disabling aprotein in mammalian cells thatall enteroviruses appear to need in order to replicate.

Carette shares senior authorship with Or Gozani, MD, PhD, professor of biology at Stanford and the Dr. Morris Herzstein Professor of Biology; Raul Andino, PhD, professor of microbiology and immunology at UCSF; and Nevan Krogan, PhD, professor of cellular and molecular pharmacology at UCSF. The lead authors are former Stanford graduate student Jonathan Diep, PhD, and Stanford postdoctoral scholars Yaw Shin Ooi, PhD, and Alex Wilkinson, PhD.

One of the most well-known and feared enteroviruses is poliovirus. Until the advent of an effective vaccine in the 1950s, the virus spelled paralysis and death for many thousands of children each year in the United States alone. Since 2014, another type of enterovirus, EV-D68, has been implicated inpuzzling biennialbursts of a poliolike disease, acute flaccid myelitis, in the United States and Europe. Other enteroviruses can cause encephalitis and myocarditis inflammation of the brain and the heart, respectively.

Like all viruses, enteroviruses travel lightly. To replicate, they take advantage of proteins in the cells they infect.

To see what proteins in human cells are crucial to enteroviral fecundity, the investigators used a genomewide screen developed in Carettes lab. They generated a cultured line of human cells that enteroviruses could infect. The researchers then used gene editing to randomly disable a single gene in each of the cells. The resulting culture contained, in the aggregate, cells lacking one or another of every gene in our genome.

The scientists infected the culture with RV-C15, a rhinovirus known to exacerbate asthma in children, and then with EV-C68, implicated in acute flaccid myelitis. In each case, some cells managed to survive infection and spawn colonies. The scientists were able to determine which gene in each surviving colony had been knocked out of commission. While both RV-C15 and EV-D68 are both enteroviruses, theyre taxonomically distinct and require different host-cell proteins to execute their replication strategies. So, most of the human genes encoding the proteins each viral type needed to thrive were different, too. But there were only a handful of individual genes whose absence stifled both types ability to get inside cells, replicate, bust out of their cellular hotel rooms and invade new cells. One of these genes in particular stood out. This gene encodes an enzyme called SETD3. It was clearly essential to viral success, but not much was known about it, Carette said.

The scientists generated a culture of human cells lacking SETD3 and tried infecting them with several different kinds of enterovirus EV-D68, poliovirus, three different types of rhinovirus and two varieties of coxsackievirus, which can cause myocarditis. None of these viruses could replicate in the SETD3-deficient cells, although all proved capable of pillaging cells whose SETD3-producing capability was restored.

The researchers observed a 1,000-fold reduction in a measure of viral replication inside human cells lacking SETD3, compared with controls. Knocking out SETD3 function in human bronchial epithelial cells infected with various rhinoviruses or with EV-D68 cut replication about 100-fold.

Mice bioengineered to completely lack SETD3 grew to apparently healthy adulthood and were fertile, yet they were impervious to infection by two distinct enteroviruses that can cause paralytic and fatal encephalitis, even when these viruses were injected directly into the mices brains soon after they were newly born.

In contrast to normal mice, the SETD3-deficient mice were completely unaffected by the virus, Carette said. It was the virus that was dead in the water, not themouse.

Enteroviruses,the scientists learned, have no use for the section of SETD3 that cells employ for routine enzymatic activity. Instead, enteroviruses cart around a protein whose interaction with a different part of the SETD3 molecule, in some as yet unknown way, is necessary for their replication.

This gives us hope that we can develop a drug with broad antiviral activity against not only the common cold but maybe all enteroviruses, without even disturbing SETD3s regular function in our cells, Carette said.

Carette and Gozani are members of Stanford Bio-X and the Stanford Maternal & Child Health Research Institute, as well as faculty fellows of Stanford ChEM-H. Gozani is a member of the Stanford Cancer Institute.

Other Stanford co-authors are graduate student Christine Peters; postdoctoral scholar James Zengel, PhD; Siyuan Ding, PhD, instructor in medicine gastroenterology & hepatology; basic life research scientist Kuo-Feng Weng, PhD; former visiting research student Kristi Kobluk, DVM; Joshua Elias, PhD, assistant professor of chemical and systems biology; Peter Sarnow, PhD, professor of microbiology and immunology; Harry Greenberg, MD, professor of gastroenterology and hepatology and of microbiology and immunology; and Claude Nagamine, PhD, DVM, associate professor of comparative medicine.

Researchers at the Chan Zuckerberg Biohub and the VA Palo Alto Health Care System also contributed to the work.

Stanfords departments of Microbiology and Immunology and of Biology also supported the work.

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In human cells and mice, a cure for the common cold, Stanford-UCSF study reports - Stanford Medical Center Report

UCSF Launches Benioff Initiative for Prostate Cancer Research – UCSF News Services

UC San Francisco announced Thursday it will establish the UCSF Benioff Initiative for Prostate Cancer Research, made possible by a $35 million gift from Marc and Lynne Benioff. The new initiative will bring together scientists and physicians who seek to push the boundaries of prostate cancer research and devise new strategies to combat the disease, which remains the most frequently diagnosed cancer among men in the U.S. and the second deadliest.

... We are honoring the memory of Marc's father and all of those who have been lost to prostate cancer by working with the leading experts at UCSF to spare other families the pain of this terrible disease.

Marc and Lynne Benioff

The gift reflects the Benioffs ongoing support of UCSF and commitment to advancing health care in the Bay Area.

This initiative will seek out and better understand the major drivers of prostate cancer and come up with new ways of combating the disease with better therapies, said Alan Ashworth, PhD, FRS, president of the UCSF Helen Diller Family Comprehensive Cancer Center and a member of the new initiatives Executive Committee. This gift will allow us to produce knowledge that will benefit patients and the entire prostate cancer community, and were incredibly grateful to Marc and Lynne for their support.

Prostate cancer has devastated too many families around the world, including our own, said Marc and Lynne Benioff. With this gift, we are honoring the memory of Marc's father and all of those who have been lost to prostate cancer by working with the leading experts at UCSF to spare other families the pain of this terrible disease.

Though prostate cancer claims more than 300,000 lives worldwide each year, the diseases underlying causes and the factors driving the most aggressive, often fatal cases, remain poorly understood.

For patients with metastatic prostate cancer resistant to first-line therapy, the FDA-approved therapies each improve survival by only several months. By investigating the biological pathways that drive prostate cancers to grow and spread, we hope to provide the foundation for developing the next generation of better therapies for this disease, said prostate cancer expert Felix Feng, MD, a UCSF professor of radiation oncology, urology, and medicine, who will serve as the executive director of the new initiative.

According to Feng, the treatment landscape for aggressive prostate cancers stands in stark contrast to the many therapeutic options available for other common forms of cancer including breast, colon and lung cancer for which scientists have developed a range of therapies that target the specific genes, mutations and other molecular drivers that underlie each patients cancer. Such personalized therapies are still largely absent in the realm of prostate cancer.

We recognize that prostate cancer is a heterogeneous disease, said Rohit Bose, MD, PhD, a UCSF assistant professor of anatomy, medicine and urology, and a genitourinary medical oncologist who will serve on the Executive Committee of this initiative. There are all kinds of prostate cancer, and each patients disease is unique. Relying on a single magic bullet to stop all forms of the disease is a tall order.

So far, the science has lagged behind this growing recognition that prostate cancer is a complex disease that demands a variety of individualized therapeutic approaches. But Feng, Ashworth and Bose believe the Benioffs gift will catalyze the kind of bold, collaborative research that could transform the field, beginning with research on the basic biology and genetics of the disease.

Among its many objectives, the initiative will recruit new research faculty to UCSF, fund high-risk high-reward projects, develop cutting-edge resources for its investigators, and build teams of research fellows mentored by UCSF faculty members. This gift leverages the Benioffs long-standing support of prostate cancer research and care in the Department of Urology, where they have funded the development of new diagnostic tools and innovative therapeutic approaches, as well as the recruitment of leading physicianscientists, under the leadership of Peter Carroll, MD, MPH.

The initiative has already charted an ambitious agenda. Within five years, they hope to identify new molecular drivers of aggressive prostate cancer and understand why these lead to specific cancer features. Within this timeframe, they also hope to develop new therapeutic approaches to target these drivers, and eventually launch clinical trials that benefit patients who dont respond to existing treatment regimens.

Marc and Lynne Benioff have a long history of supporting health care and scientific research in the Bay Area. Since 2005, the couple has pledged more than $400 million to UCSF, including $200 million to support the Benioff Childrens Hospitals in San Francisco and Oakland and$50 million to launch the UCSF Benioff Childrens Hospitals Preterm Birth Initiative in partnership with the Bill and Melinda Gates Foundation. Of this total giving, they allocated $15 million to UCSF Benioff Childrens Hospital Oakland to address the acute shortage of mental health services for children and adolescents in Oakland and the East Bay. The Benioffs recently donated $25 million to launch the UCSF Benioff Center for Microbiome Medicine to accelerate the development of microbe-based therapies. They also recently donated $30 million to launch the UCSF Benioff Homelessness and Housing Initiative, which researches the causes of homelessness to identify evidence-based solutions.

About UCSF:The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.UCSF Health, whichserves as UCSFs primary academic medical center, includestop-ranked specialty hospitalsandother clinical programs,and has affiliations throughout the Bay Area.

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UCSF Launches Benioff Initiative for Prostate Cancer Research - UCSF News Services

Lancet Commission Lists Three Tools for Effectively Zapping Malaria – News18

The Lancet Commission on Malaria Eradication which recently published its report states that eradication of the mosquito-borne disease is possible by 2050. The commission, however, warns that while over 100 countries have managed to eradicate malaria, a chance of resurgence and re-establishment is still possible.

According to the Lancet Commission, in India, the malaria vector, Anopheles stephensi, has a suitable environment for breeding which means incidence of the disease in urban areas is quite high.

Notably, in 2017, there were a total of 219 million malaria cases in 86 countries, a decline from 262 million cases, and 839,000 malaria deaths in 2001. Out of the 219 million cases reported in 2017, 9.6 million were in India.

According to the Lancet commission, three important tools are necessary in the worlds attempt at eliminating malaria by 2050. These include rapid diagnostic tests, artemisinin-based combination therapy, and long lasting insecticide-treated nets.

Apart from these, IT, molecular methods for diagnosis and surveillance, and a new drug for Plasmodium vivax malaria will act as catalysts for eradication as well.

India follows the recommendations of World Health Organization (WHO)'s Global Technical Strategy for Malaria to eradicate the mosquito-borne disease. However, improper waste management, lack of municipal water supply infrastructure, etc, results in breeding facilitation of the Anopheles mosquito.

The out of pocket (OOP) burden, according to the commission is undesirable, forcing families to forego necessary care and causing medical impoverishment.

According to the Commission, India must invest a lot more in making malaria prevention and treatment tools more affordable and accessible for its citizens.

Speaking about the same, Dr Shailja Singh, Associate Professor at Special Centre for Molecular Medicine, JNU, says, that generalised policies will not work in case of India because the nation in itself is so diverse, and so are the Plasmodium parasites that affect its people.

According to her, to achieve complete eradication, firstly, a large scale surveillance to capture the diverse nature of malaria in India is needed. Secondly, a mass campaignlike in the case of poliocan also help in eradication processes.

The Lancet Commission further notes that eradication of the mosquito will not only reduce mortality, but will also be a financial win for nations, as according to a WHO report, it will result in an estimated gain in GDP of USD 238 billion, which would be a lot higher than the cost of eradicating itUSD 35 billion.

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Medical Bioinformatics Market 2017 Global Forecasts Analysis, Company Profiles, Competitive Landscape and Key Regions 2030 – Rapid News Network

Bioinformatics involves the development and application of novel informatics techniques in the field of biology. It improves the methods of storing, organizing, retrieving and analyzing biological data. Major activity in bioinformatics is to develop software tools in order to generate useful biological knowledge database. In molecular biology, bioinformatics techniques such as signal processing allow extraction of useful results from large amount of raw data. In the field of genetics it helps in sequencing, annotating genomes and to observe mutations. Bioinformatics study acts a biological literature and developmental data bank for biology related data.

Similarly, biomedical informatics is an emerging discipline which defines the study of inventions and implementation of structures, algorithms to improve communication, understanding and managing the medical information. The National Center for Toxicological Research (NCTR) conducts research in bioinformatics and chemo informatics. The bioinformatics tools were created for analysis and integration of genomics, proteomics, metabolomics datasets and transcriptomics.

The growth of global medical bioinformatics market is driven by increasing initiatives and funding, use of bioinformatics in drug discovery and biomarkers. The market is expected to offer opportunities with the introduction and adoption of upcoming technologies such as cloud computing and other sequencing technologies. The global medical bioinformatics market can be segmented by tools approved from Food and Drug Administration (FDA) or European Federation for Medical informatics (EFMI) for further research process.

Medical Bioinformatics market is based on the tools, application and end users.

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The global medical bioinformatics market can be segmented based on types of tools and the list of bioinformatics tools approved by FDA are as follows: Array Track: DNA microarray data management, mining, analysis, and interpretation software Estrogenic Activity Database (EADB): Comprehensive set of estrogenic activity data Endocrine Disruptor Knowledge Base (EDKB): Scientific resources for estrogen and androgen activity of potential endocrine disruptor chemicals Decision Forest: Novel pattern-recognition method for analysis of data from microarray experiments, proteomics research, and predictive toxicology AtBioNet: Integrated PPI (protein-protein interaction) Network Analysis Tool for Systems Biology and Biomarker Discovery Mold2: Software that generates molecular descriptors from two-dimensional structures NCTR Liver Cancer Database (NCTRlcdb): Database of 999 chemicals with assigned liver-toxicity classifications to facilitate the construction of cleaner and better carcinogenicity models approved by FDA and other organizations SNPTrack: Integrated solution for the management, analysis, and interpretation of genetic association study data Microarray/Sequencing Quality Control (MAQC/SEQC): Project to develop microarray quality control metrics and thresholds

The global medical bioinformatics market can be segmented by application as follows: Molecular Medicine Personalized Medicine Preventive Medicine

The global medical bioinformatics market can be segmented by end user as follows: Pharmaceutical Companies Hospitals Academic institutes Universities

Medical bioinformatics market is segmented into five major regions: North America, Europe, Latin America, Asia Pacific, and Rest of World. North America leads the market followed by the European nations in terms of revenue. Globally, the medical bioinformatics market growth is expected to increase with the demand in development of generic drug development and mode of sequencing the genes in order to have prevalence from various diseases. In 2015, Department of Biomedical Informatics was inaugurated at Harvard Medical School. This was initiated in order to bring quantitative methods and technological development to biomedicine engineering research. According to Harvard Medical School, Department of Biomedical Informatics (DBMI) and research associates planned to break the wall of autism by detecting the disorder in newborns using the same standard of testing device used to check for hearing impairment. According to Food and Drug Administration, collaboration with National Center for Toxicological Research has driven the demand and use of bioinformatics tools such as predicting patient-specific treatment outcomes with in silico tools. Latin America and Asia Pacific regions are anticipated to be the emerging markets in the global medical bioinformatics market during the forecast period. The effective guidelines from EFMI reports the promotion of high standard application and development in medical bioinformatics. Increase in patient population base and rising disease incidences in the Asia Pacific region is expected to fuel the use of bioinformatics tools for research and tests, which is projected to propel the demand in global medical bioinformatics market in the forecast period.

The key players in the global medical bioinformatics market develop bioinformatics tools, and software which is used in drug designing, sequencing methods. Some of the top players in the global medical bioinformatics market are Optra HEALTH, Affymetrix, Inc., Thermo Fisher Scientific Inc., Illumina, Inc., QIAGEN, Paraxel, Station X and others.

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The report offers a comprehensive evaluation of the market. It does so via in-depth qualitative insights, historical data, and verifiable projections about market size. The projections featured in the report have been derived using proven research methodologies and assumptions. By doing so, the research report serves as a repository of analysis and information for every facet of the market, including but not limited to: Regional markets, technology, types, and applications.

The study is a source of reliable data on: Market segments and sub-segments Market trends and dynamics Supply and demand Market size Current trends/opportunities/challenges Competitive landscape Technological breakthroughs Value chain and stakeholder analysis

The regional analysis covers: North America (U.S. and Canada) Latin America (Mexico, Brazil, Peru, Chile, and others) Western Europe (Germany, U.K., France, Spain, Italy, Nordic countries, Belgium, Netherlands, and Luxembourg) Eastern Europe (Poland and Russia) Asia Pacific (China, India, Japan, ASEAN, Australia, and New Zealand) Middle East and Africa (GCC, Southern Africa, and North Africa)

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

Highlights of the report: A complete backdrop analysis, which includes an assessment of the parent market Important changes in market dynamics Market segmentation up to the second or third level Historical, current, and projected size of the market from the standpoint of both value and volume Reporting and evaluation of recent industry developments Market shares and strategies of key players Emerging niche segments and regional markets An objective assessment of the trajectory of the market Recommendations to companies for strengthening their foothold in the market

Note:Although care has been taken to maintain the highest levels of accuracy in TMRs reports, recent market/vendor-specific changes may take time to reflect in the analysis.

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Medical Bioinformatics Market 2017 Global Forecasts Analysis, Company Profiles, Competitive Landscape and Key Regions 2030 - Rapid News Network

UoM scientists’ breakthrough for cancer hair-loss – The Mancunion

Hair-loss during chemotherapy for cancer patients could soon become a thing of the past, thanks to new breakthrough research at The University of Manchester.

Scientists from the Centre for Dermatology Research, based in Manchester, have been working on reducing arguably one of the most psychological source of distress in cancer therapy induced hair-loss.

Taxanes, substances that widely used as chemotherapy agents in treating patients with lung or breast carcinoma, are believed to induce hair-loss as a powerful side-effect.

Research conducted by Doctor Talveen Purba and his colleagues, is believed to have found a way to prevent hair follicles from being damaged by the chemical taxanes, in the process of treating the malign formation in the body.

As the scientists explained in the journal EMBO Molecular Medicine, they have explored the proprieties of CDK4/6 inhibitors a new class of drug. These are presumed to block cell division and are medically approved as being the future in chemotherapy.

The lead coordinator of the study, Dr Talveen Purba stated that even though it might seem counter-intuitive at first, they found that DK4/6 inhibitors can be used temporarily to halt cell division without promoting additional toxic effects in the hair follicle.

Dr Purba further explained that when they bathed human scalp hair follicles in a CDK4/6 inhibitors solution they became less affected by the effects of taxanes. It analysed that the most vulnerable to taxanes were the specialised dividing cells which are located at the very base of the hair follicle, and the stem cells from which they arise. For that reason, they started an investigation on how to protect these particular cells from undesired chemotherapy effects but in such a way that malign cells are still eradicated successfully.

Their ultimate goal for the future is to develop externally applicable medicines that will complement existing preventive approaches for cancer treatment-induced hair loss.

Dr Purba emphasised the importance of this study, as there are still uncertainties when it comes to why some people lose more hair than others while in chemo treatment, and why some drug combinations produce more damage than others. This study is aimed at revealing those aspects as well.

He added: We need time to further develop approaches like this to not only prevent hair loss but promote hair follicle regeneration in patients who have already lost their hair due to chemotherapy.

The researchers behind the study highlighted the fact that more exploration in the topic area is desperately needed in this field of cancer research, which is currently highly underfunded. Patients, too, have been impatiently waiting for a pharmacological breakthrough when it comes to chemo-induced hair damage as they feel that hair-loss, especially in women, affects them the most.

The study has recently attracted a vast amount of attention, with many people eager to hear the outcomes.

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UoM scientists' breakthrough for cancer hair-loss - The Mancunion

Shafqat Mahmood against politics in education sector – Business Recorder

KARACHI: Federal Minister for Education and Professional Training, Shafqat Mahmood here on Wednesday called upon all stakeholders to play their role in turning education sector into free of politics with major focus on up-gradation of standard and quality of the courses and training offered to the children and youth of the country.

Inaugurating the National Institute of Virology at the Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), University of Karachi, he said said the government was trying to unite all provinces on one point of education as this sector should be free from politics.

He pointed out that the government would steadily enforce a unified education system in the country to mitigate class differences between rich and poor classes.

The Minister for Education and Professional Training mentioned that the federal education ministry was working on many projects to enhance the quality of learning in all faculties and that the federal government has allocated Rs.59 billion for the higher the education sector.

The government was said to had taken major step towards introducing a uniform syllabus in the country.

With the regard to Virology Lab inaugurated by him, Shafqat Mahmood expressed his pleasure that a world class institution was focused towards understanding the causes of the viral diseases and expressed his confidence that it will play a key role in the prevention and treatment of viral disease in the country.

Emergence of several viral diseases in the last two decades, such as Dengue hemorrhagic fever, Zika, Chikungunya, and Congo fever has challenged the existing healthcare system of the country, he said appreciating that the virology research center was the first of its type using state-of-the-art technologies conduct scientific investigation on viral and other diseases.

On the occasion Vice-Chancellor University of Karachi Prof. Dr. Khalid Mehmood Iraqi, Prof. Dr. Atta ur Rahman, Chairman of the Prime Ministers National Task Force on Science and Technology, Director ICCBS Prof. Dr. Muhammad Iqbal Choudhary, and Chairman H.E.J. Foundation Aziz Latif Jamal also expressed their views.

Prof. Atta ur Rahman said that significant investments worth billions of rupees were being made in a multitude of projects related to the industry, agriculture, artificial intelligence, nanotechnology, industrial biotechnology, space sciences etc.

Prof. Khalid Mehmood Iraqi said that establishment of this world class institute was a key step forward towards the capacity building in the field of virology in Pakistan.

He pointed out that the building of the new institute was equipped with most modern tools, and facilities for frontier research in this important field of virology.

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Shafqat Mahmood against politics in education sector - Business Recorder

Education should be free from politics, says Shafqat Mahmood – The News International

Education should be free from politics, says Shafqat Mahmood

While inaugurating the National Institute of Virology at the Dr Panjwani Centre for Molecular Medicine and Drug Research (PCMD), Karachi University, on Wednesday, Federal Minister for Education and Professional Training Shafqat Mahmood said the government was trying to unite all provinces on one point of education as this sector should be free from politics.

He said the government would steadily enforce a unified education system in the country to mitigate class differences between rich and poor classes. He informed the participants that the federal education ministry was working on many projects to enhance the quality of education in all faculties of education.

The federal government had allocated Rs59 billion for the higher education sector, he said, adding that government had taken a major step towards introducing a uniform syllabus in the country.

On the occasion, Karachi University Vice-Chancellor Prof Dr Khalid Mehmood Iraqi, Prof Dr Atta ur Rahman, chairman of the Prime Ministers National Task Force on Science and Technology, Director ICCBS Prof Dr Muhammad Iqbal Choudhary, and Chairman HEJ Foundation Aziz Latif Jamal were also present.

I am pleased that a world-class institution to work on understanding the causes of the viral diseases has been inaugurated today, which I am confident will play a key role in the prevention and treatment of viral disease in the country, he said while talking about the newly established research centre.

The emergence of several viral diseases in the last two decades, such as dengue haemorrhagic fever, Zika, Chikungunya and Congo fever, had challenged the existing healthcare system of the country, he said.

The virology research centre, the first of its type, owned the state-of-the-art technologies for cutting-edge instruments to conduct scientific investigation on viral and other diseases. Addressing the audience, Prof Atta ur Rahman said significant investments worth billions of rupees were being made in a multitude of projects related to the industry, agriculture, artificial intelligence, nanotechnology, industrial biotechnology, space sciences etc.

Talking about the prominence of the ICCBS, he said that this internationally renowned research establishment owned four major aspects, which included its quality faculty, uppermost trained technicians, bright students, and public-private partnership.

Prof Khalid Mehmood Iraqi said that establishment of this world-class institute was a key step forward towards the capacity building in the field of virology in Pakistan. He pointed out that the state-of-the-art building of the new institute was equipped with most modern tools and facilities for frontier research in this important field of virology.

Prof Iqbal Choudhary said that the virology research centre, the first of its type, owned the state-of-the-art technologies for cutting-edge instruments to conduct a scientific investigation on viral and other diseases to contribute knowledge policy and practise and engage in capacity development for improved public health in Pakistan.

He said one the highest prevalence of hepatitis in Pakistan was causing considerable mortality and morbidity to people, and adversely affecting the national economic revival. Polio, non-existing in the world, had become a matter of national esteem for Pakistan, he said.

A message of Nadira Panjwani, chairperson of Dr Panjwani Memorial Trust, was read out by an official. In her message, she welcomed the federal minister and other participants in the ceremony, and said that the establishment of the virology research centre was yet another milestone for her organisation. It was, by all means, an essential need for the countrys healthcare infrastructure, she added.

Saman Aziz Jamal, in her speech, said that the HEJ Foundation had established three world-class science institutions at the ICCBS, apart from providing continuous help to the HEJ scientists, as well as establishing several industry-related laboratories. The most recent contribution of the foundation was the establishment of the Latif Ebrahim Jamal Nanotechnology Research Institute to be inaugurated soon, she maintained.

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Education should be free from politics, says Shafqat Mahmood - The News International

Towards a universal flu vaccine – Scientific American

Flu shots can be hard to sell to the public. Even a run-of-the-mill influenza infection can be debilitating to otherwise healthy people, and lethal to those who are elderly or frail, so vaccinations are important. The problem is that flu vaccines deliver inconsistent performance. In a good season, were up to 60% effectiveness, but in bad, mismatched years it can be as low as 10% or 20%, says Barney Graham, deputy director of the Vaccine Research Center at the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.

Current flu vaccines provide protection only against the strains they have been matched to, so a universal flu vaccine that provides broader protection against most influenza viruses has been a long-standing dream. The 2009 swine-flu pandemic, which caught the public-health community off guard and claimed the lives of as many as half-a-million people worldwide, gave the issue new urgency.

The 2009 pandemic made it obvious and clear that we didnt have good enough solutions for influenza vaccines, says Graham. We knew the virus, but we werent able to make enough vaccine quickly enough. More-effective manufacturing is one solutionbut a single inoculation that protects against both seasonal and emerging strains would have much greater impact.

Fortunately, the timing of the pandemic coincided with great progress in the development of technologies for investigating the human response to influenza. Around 2008 or 2009, people started finding a few broadly neutralizing antibodies against the influenza virus, says Ian Wilson, a structural biologist specializing in vaccine development at Scripps Research Institute in La Jolla, California. Once people started looking, many more were discovered.

Now, around 100 years after the Spanish flu pandemic of 1918 that killed about 50 million people, multiple universal-vaccine programmes are demonstrating promise in both preclinical and clinical testing. But it remains to be seen whether any will ultimately deliver the broad protection that clinicians seek.

Peter Palese, a microbiologist at the Icahn School of Medicine at Mount Sinai in New York City, believes that todays flu vaccines come in for too much criticism. They are fairly good vaccines but theyre not perfect, he says. The main problem, he adds, is that they elicit a focused immune response against a moving target.

Humans are affected by two main types of influenza. Influenza A and B can both contribute to seasonal flu, but some influenza A subtypes preferentially infect animal hosts. Sometimes these subtypes abruptly acquire the ability to infect humans, leading to pandemics such as the one in 2009. Each year the seasonal flu vaccine is designed to cover two strains each of influenza A and B, based on the publichealth communitys best informed guess about which strains will be dominant that year.

Every influenza virus is studded with hundreds of molecular structures formed by a multifunctional protein called haemagglutinin. Haemagglutinin helps the virus to bind and penetrate host cells. It comprises a bulky head attached to the virus by a slender stalk. Most of the immune response is targeted at the head because it is highly exposed, but there is also evidence that the head contains features that preferentially elicit a strong antibody response.

There are structured loops, and antibodies easily recognize loops that stick out like that, explains James Crowe, director of the Vanderbilt Vaccine Center in Nashville, Tennessee. Unfortunately, these immunodominant elements are also highly variable between strains.

Influenza A viruses are particularly diverse. They are classified by numbers based on the subtype of haemagglutinin (H) protein and a second viral protein known as neuraminidase (N), with even greater strain variation observed among those subtypes. For example, the 2009 pandemic arose from a new strain of the H1N1 subtype. The extent of haemagglutinin variability means that poor strain selection can leave recipients largely unprotectedand even a good vaccine offers limited protection against future strains. In two years, the virus can change again so we can get re-infected and get disease, says Palese.

Further complicating the quest for a universal flu vaccine is the fact that our immune system is strongly biased by its earliest encounters with influenza through a phenomenon called imprintingor, as it has been dubbed, original antigenic sin. This means that individuals have a strong antibody response to viruses with molecular features shared by the strain encountered during their first exposure, but they essentially start from scratch when exposed to distantly related strains for the first time. Its not that you cannot see the second virusits just like youre a baby and youre seeing it for the first time, says Crowe.

Imprinting is a double-edged sword because early exposure to the right strain could theoretically produce far-reaching and vigorous protection in response to vaccination. But if a childs first influenza encounter is with a relatively unusual or atypical strain, vaccination might prove less effective in terms of rousing broadly protective immunity.

A vaccine that focuses the immune response on a more stable target on the virus could overcome the problem of viral diversity. Researchers have known that such targets existed for decades. In 1983, Palese and his colleagues determined that the haemagglutinin stalk domain is so similar between strains that antibodies can recognize specific physical features, known as epitopes, of haemagglutinin proteins from multiple influenza subtypes. Unfortunately, the stalk is something of an immunological wallflower, overshadowed by the influence of the head. We have engineered epitopes into the stalk and the same epitopes into the head, and we get a much better response to epitopes in the head, says Palese. But immunity can still emerge naturally in some cases, and a series of stalk-specific antibodies were isolated from human donors in 2008 and 2009.

More recently, several research groups have devised multiple vaccine strategies for selectively provoking a stem-specific response. Grahams team at NIAID, for example, undertook a painstaking process of protein engineering a standalone version of the stem from an H1 influenza virus. It took us about seven or eight years to engineer it and stabilize it enough to maintain the right surfaces and structures, says Graham. The researchers subsequently generated nanoparticles displaying multiple copies of these engineered stems and showed1 that these could generate strong protection against entirely different subtypes of influenza A, such as H5at least in animal models. This vaccine design is now undergoing a phase I clinical trial and could in principle confer protection against many of the most prominent pandemic virus subtypes. A newer haemagglutinin stem construct developed by NIAID could lead to even broader protection against the remaining subtypes.

Palese and Florian Krammer, a virologist who is also at Mount Sinai, have developed an alternative approach to stimulating stemspecific immunity. They have generated multiple influenza viruses with chimaeric haemagglutinin proteins in which the same stalk domain is paired with various exotic head domains from virus subtypes that primarily infect birds and are therefore unlikely to trigger an imprinting-biased response in humans. If you then revaccinate with a vaccine that has the same stalk but a completely different head, the immune memory against the stalk could be boosted, explains Krammer.

This approach uses the entire virus particle, creating the potential to elicit parallel immune recognition of other influenza antigens. On the basis of promising evidence of crossprotection against diverse influenza A subtypes in animals, the Mount Sinai team is now conducting phase I trials to explore the vaccines safety and effectiveness in humans.

Inspired by the discovery of cross-protective stalk antibodies in the wild, several research groups have been casting the net wider to find more such molecules. We use all kinds of donorspeople who are actively sick, people who have recovered from avian influenza, or well go to other countries to find donors with exposure to unusual strains, says Crowe. After isolating the antibody-producing B cells from these individuals, researchers can comprehensively profile the specific influenza targets that elicit a natural immune response and identify antibodies that might have broad infectionneutralizing capabilities.

These studies have revealed that even in the variable head domain of haemagglutinin there are structural elements that are consistent across influenza subtypes. In 2012, researchers at Scripps and Janssens Crucell Vaccine Institute in Leiden, the Netherlands, identified2 an antibody called CR9114, which exhibited unprecedented breadth of recognition. That could actually bind to both influenza A and influenza B, says Wilson, who helped characterize the antibody. This antibody is now being used to identify target epitopes on haemagglutinin that can be exploited to achieve far-reaching virus neutralization for both prevention and treatment.

In some cases these searches have revealed unexpected vulnerabilities in the virus. Haemagglutinin normally assembles into highly stable complexes of three closely coupled molecules, but Crowe and Wilson discovered3 this year that these trimers occasionally open up to expose a weak point to which antibodies can bind, potentially thwarting infection by a wide range of influenza A viruses. This trimer interface is a whole new universal flu epitope, and everybodys going crazy about it, says Crowe. Its not even clear how it works, but it clearly works in animals.

Much of the variability between influenza viruses is only skin deep. Probe more deeply within the virus particle and you find greater similarity in the essential proteins. These are beyond the reach of antibodies but they can be recognized by T cellsan element of the immune system that can target and eliminate influenza-infected cells, which present peptide signatures of their viral intruders.

So far, antibodies have been the primary focus of the vaccine community because they represent a crucial first line of defence against circulating virus particles, but T cells provide critical protection by containing infection once it is under way. People get exposed and infected every two or three years on average, says Sarah Gilbert, who heads vaccine development at the University of Oxfords Jenner Institute, UK. The vast majority of these infections are either asymptomatic or mild, she says, and the reason is that people have a T-cell response thats strong enough to protect them.

In general, eliciting a truly protective T-cell response entails reawakening memory T cells that were formed in the aftermath of a previous exposure. Gilberts team uses a crippled vaccinia virus that can infect human cells and that synthesizes two different immunitystimulating influenza proteins but is incapable of further replication. With a single dose, we saw a boost in pre-existing T-cell responses of between eight- and tenfold in humans, says Gilbert. She adds that the target proteins are 90% identical across influenza A viruses, offering the potential for broad protection against pandemic strains.

Gilberts vaccine is undergoing two phase II trials under the guidance of Vaccitech, a company she co-founded in Oxford. A potent T-cell response also seems to contribute to the apparent cross-protection offered by a replication- defective flu vaccine from FluGen, based in Madison, Wisconsin, which has reported success in a recent phase II clinical trial.

Even with several promising series of human trials under way, the road to the clinic remains fraught with difficulties. Mice are often used for early studies of vaccine preclinical development but Palese points out that they are not a natural reservoir for the influenza virus. Many researchers therefore quickly switch to using ferrets to test their vaccine candidates, because they are broadly susceptible to influenza and are physiologically more like humans in that ferrets have a longer respiratory tract than mice. Both species are short-lived, however, making it difficult to study the effects of a vaccine over many rounds of influenza exposure.

Gilbert has started working on pigs in collaboration with the Pirbright Institute near Woking, UK. This long-lived species could serve as both a useful test case and an important beneficiary for vaccines. The upper respiratory tract of the pig is very similar to the human and they tend to get infected with the same viruses, she says. And there is a need for flu vaccines in pigsthe 2009 H1N1 pandemic virus is thought to have come from pigs.

Krammer has also used pigs as a model but says their large size makes them difficult to use routinely in research. Moreover, he is hesitant about drawing too many conclusions from any animal model: You can use them to down-select candidates and for safety, but with universal influenza vaccines, the ultimate animal model is Homo sapiens.

The ultimate proof for any flu vaccine is protection against disease in clinical trials. But for a putative universal vaccine, such testing is more complicated. A growing number of groups are using human challenge trials, in which healthy volunteers are deliberately exposed to a particular influenza strain after vaccination. This approach allows for faster trials with smaller cohorts and defined exposure conditionslowering the trial costand it also allows researchers to hand-pick the viruses they wish to protect against.

But challenge trials also have their critics. Its not a natural infection. You have to inoculate people with a million or even ten million virus particles, says Krammer, and it doesnt seem to work like a natural infection. These trials also leave out very young and very old people, which are the groups most vulnerable to flu.

Another problem is that the US Food and Drug Administration still requires a real-world trial before giving approval, and these are difficult and costly. They require thousands of participants to ensure that a sufficient number of people are exposed to flu, and they must span several seasons to demonstrate efficacy against multiple virus strains or subtypes.

Many academic researchers say that even embarking on a clinical trial can pose a nearly insurmountable challenge, because it requires access to sophisticated production facilities that meet the high bar of good manufacturing standards. Even if its a simple construct, were talking about at least a year to make it and a cost of approximately US$1 million to $2 million, says Krammer. A few major companies such as GlaxoSmithKline and Janssen have made these investments, but obtaining that much funding from either public or private bodies is far from easy. Gilbert struggled for five years to obtain funding before launching her company, which raised the capital needed to bring her labs vaccine programme into phase II trials.

More investment may be on the way. In the past few years, both NIAID and the US Biomedical Advanced Research and Development Authority have prioritized the development of a universal vaccine, and the Bill & Melinda Gates Foundation has joined forces with governmental and non-governmental organizations to form the Global Funders Consortium for Universal Influenza Vaccine Development.

The vaccines now being developed promise much broader protection than current seasonal shots but fall well short of being truly universal. The World Health Organization (WHO) still sees considerable value in such vaccines, and has called for a vaccine that prevents severe disease from all forms of influenza A by 2027, which would prevent pandemics. But Krammer points out that seasonal influenza B infections can also inflict a serious death toll, and both he and Palese have focused their sites on true universality. I think the WHO is making the bar too low, says Palese. We really should be trying to aim high.

Universal protection need not entail eliminating all traces of influenza virus but simply providing sufficient immunity to minimize the symptoms of infection. Even achieving that more modest goal will probably require a multipronged attack. Stem antibodies contribute to protection but are probably not sufficient for very potent protection, says Crowe. They would be just part of the scheme.

Indeed, Gilbert is exploring the potential of a broader immunological assault that melds the Mount Sinai groups chimaeric stem vaccine with her teams vaccinia technique. At least in mice, she says, combining these two approaches was better than either alone.

A greater understanding of the human immune system and its response to infection could inform smarter vaccination strategies. In May 2019, the US National Institutes of Health awarded $35 million to an international team of researchers to profile the immunity of young children in the years after their initial exposure to influenza, providing the deepest insights yet into the imprinting process.

Their findings could help vaccine designers figure out the best way to rewire the immune system while it remains malleable. And that, says Crowe, could be a game-changer. You could envision doing a universal vaccination as your first exposure, with beneficial imprinting for the rest of your life, he says.

Michael Eisenstein is a science writer in Philadelphia.

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Towards a universal flu vaccine - Scientific American

Arizona: The New Frontier in Technology and Health Care – SPONSOR CONTENT FROM ARIZONA COMMERCE AUTHORITY – Harvard Business Review

From the irises in our eyes to the shape of our ears to our fingerprints, no two humans on eartheven identical twinsare alike. So when our bodies become sick or injured, applying a one-size-fits-all, trial-and-error treatment for whatever ails us may be a good solution for a majority of patients, but it is not the best for all of them.

Enter personalized medicine. This revolutionary medical model is pushing the boundaries of traditional practice by creating new, precise treatments; reducing the need for expensive tests; and flagging risk factors that enable earlier diagnoses for everything from cancer to asthma to Alzheimers. Researchers in Arizona are at the forefront of this innovation, which combines genetic research, molecular profiling, nanotechnology, and other cutting-edge medical practices.

Across the states private sector and public universities, work is being done on a number of fronts to diagnose and treat cancer patients with methods tailored to their individual needs in the most effective way. At the University of Arizonas (UA) Bio5 Institute, biotech engineers have created a tiny pillbox that floats through the bloodstream, andon cuedelivers medicine to cancerous cells, avoiding healthy ones. Researchers at startup GT Medical Technologies Inc. of Tempe developed a tinysmaller than a square inchcollagen tile that can deliver radiation to tumor cells that were missed by surgery. Celgenes Abraxane is made in Arizona. The injectable drug treats pancreatic, breast, and certain types of lung cancers.

Just as important, cancer diagnostic tools are the subject of much research in Arizona. Arizona State University is home to the Virginia G. Piper Center for Personalized Diagnostics, which uses a plasmid repository to develop early warnings for those at risk of major illnesses. Tucson-based tumor profiling company HTG Molecular Diagnostics technology allows the genetic profiling of a tumor using a much smaller sample of the tumor than is required by traditional technology. Roche Tissue Diagnostics (formerly Ventana Medical Systems, founded by UA pathologist Dr. Thomas Grogan) provides more than 250 cancer tests through state-of-the-art automated testing. In addition to diagnostics, the company works with pharmaceutical companies to find relevant therapies for the patients its diagnosed. Caris Life Sciencess services include molecular profiling for genetics and pathology for early detection of cancer and other complex diseases. This global companys Life Sciences primary lab and the Caris Research Institute are located in Phoenix, which it calls the ideal location for a continuous service laboratory because of the predictable weather patterns and limited exposure to extreme weather events and natural disasters.

Arizona has also become ground zero for Alzheimers research. This important study is a collaborative effort of public and private institutions working together to decode the genetic makeup of patients, delay the onset, treat the symptoms, and save lives. The Arizona Alzheimers Consortium member institutions include Arizona State University, Barrow Neurological Institute, Mayo Clinic Arizona, Banner Sun Health Research Institute, the Translational Genomics Research Institute (TGen), the University of Arizona, and Banner Alzheimers Institute. The Barrow Neurological Institute at St. Josephs Hospital is home to cutting-edge imaging technology and clinical and research partnerships with world-class neurologists and neurosurgeons. Banner Sun Health Research Institute hosts the National Institutes of Health-designated Arizona Alzheimers Disease Center in the retirement community of Sun City. The consortium, through more than 5,000 publications and 1,000 research grants, has proposed new Alzheimers treatments, supported research through data-sharing and collaboration, and facilitated $1.5 billion in investments in Alzheimers research.

It has been said often in the [Arizona State House] Health Committee, the brain that will cure Alzheimers will be an Arizona brain, said Arizona State Representative Heather Carter.

Another stellar example of the importance of public-private collaboration in advancing personalized medicine is Phoenix-based TGen, a nonprofit research institute that began in 2002 with $100 million from Arizona public- and private-sector investors. TGen researchers work on employing genetic discoveries to develop smarter diagnostics and targeted therapies. Today, the TGen biomedical campus is an integral piece of a statewide bioscience initiative with faculty who contribute to biomedical discoveries and the quality of health care for Arizona residents.

While clinicians and researchers in Arizona continue to achieve medical breakthroughs in personalized medicine, information technology professionals at many of these same institutions are advancing telemedicinethe delivery of health care through inexpensive portable devices that allow patients to conduct their own lab tests and download results.

The Mayo Clinic first rolled out its stroke telemedicine program in Arizona in 2007. Neurologists trained in blood vessel conditions, along with neurosurgeons and neuroradiologists, work as a team with emergency medicine doctors and staff at remote sites to treat stroke patients. The stroke telemedicine program is now on Mayo campuses in Florida and Minnesota and treats over 1,500 patients annually at 28 remote hospital sites. Banner Health Systems, called a trendsetter with a robust history employing this technology by HealthLeaders, connects with patients and bedside care teams across the state to monitor best practices and measure clinical outcomes.

Medical records, too, can be accessed with ease, thanks to telemedicine. GlobalMed, based in Scottsdale, provides access anywhere to patient data and medical images. Their hardware, software, and cloud solutions are used in 55 countries.

Education in telemedicine, which started as a pilot program at the University of Arizona College of Medicine in 1995, is now part of the curriculum that provides services, distance learning, informatics training, and telemedicine technology assessment capabilities to cities and towns across the state. Recognized as one of the premier programs at the college, its received numerous awards at the national level for its research and innovations. UA is also the home of the Southwest Telehealth Resource Center, which works with organizations in five states to coordinate technology and other resources for telemedicine programs. ASUs Project HoneyBee, Northern Arizona Universitys Center for Bioengineering Innovation, and NAUs Health Research Institute are also working on developments in telemedicine.

If the recent announcement by Mesa startup Myndshft is any indication of the future of telemedicine, expect phenomenal growth. Two Arizona residents founded the company, which specializes in blockchain and artificial intelligence in health care, in 2015. It expects to grow its staff to 100 by the end of 2019.

The concentration of biotech innovators in Arizona means the state is well ahead of the game in both personalized medicine and telemedicine. Arizona medical experts, researchers, entrepreneurs, designers, and manufacturers all are key players in developing new devices and facilitating these advancements to improve health care outcomes for those not just in the state but also around the world.

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Arizona: The New Frontier in Technology and Health Care - SPONSOR CONTENT FROM ARIZONA COMMERCE AUTHORITY - Harvard Business Review

Federal Education Minister to open virology center at ICCBS – Business Recorder

KARACHI: Federal Minister for Education and Professional Training, Shafqat Mahmood will inaugurate on Wednesday the state-of-the-art Virology Research Center, a component of the International Center for Chemical and Biological Sciences (ICCBS) of University of Karachi (KU).

Director ICCBS, Prof. Dr. Muhammad Iqbal Choudhary in an announcement here Tuesday said that the virology center works under the auspices of Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), KU.

The ceremony was said to be also addressed by Prof. Dr. Atta ur Rahman, Chairman of the Prime Ministers National Task Force on Science and Technology and Vice-Chancellor University of Karachi Prof. Dr. Khalid Mehmood Iraqi.

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Federal Education Minister to open virology center at ICCBS - Business Recorder

Breakthrough in bid to prevent hair loss in cancer patients – The London Economic

A breakthrough has been made in preventing hair loss in cancer patients.

Doctors say that losing their hair while undergoing chemo adds to the distress of breast cancer patients.

Taxane-based chemotherapy drugs are an important tool for fighting cancer, but their toxicity damages hair follicles and can cause permanent hair loss.

To try and prevent hair loss, University of Manchester researchers have exploited a newer class of targeted cancer drugs.

The so-called CDK4/6 inhibitors block the division of cancerous cells while limiting the damage to hair follicles.

Study lead author Dr Talveen Purba said: Although at first this seems counter-intuitive, we found that CDK4/6 inhibitors can be used temporarily to halt cell division without promoting additional toxic effects in the hair follicle.

When we bathed organ-cultured human scalp hair follicles in CDK4/6 inhibitors, the hair follicles were much less susceptible to the damaging effects of taxanes.

Researchers hope this approach could lead to new treatments to prevent chemotherapy-induced hair loss, which can be traumatic for cancer patients.

They added patients have waited too long to see real breakthroughs in hair loss prevention because this field of cancer treatment is lamentably under-funded.

In the first stage of the research, Dr Purbas team examined exactly how hair follicles responded to taxane chemotherapy.

They found that the specialised dividing cells at the base of the hair follicle were critical for producing hair.

They also discovered that the area most vulnerable to the chemotherapy side effects was the stem cells which hair grows from.

Dr Purba added: We must protect these cells most from undesired chemotherapy effects but so that the cancer does not profit from it.

The team hope their work will help to develop externally applicable medicines to slow cell division in the scalp hair follicles to reduce hair damage.

Such medicines could complement and enhance existing preventive approaches including scalp cooling devices.

The researchers highlighted that more work is desperately needed in the field to deliver real breakthroughs for cancer patients and to find out why some suffer greater hair loss than others.

Dr Purba said: Despite the fact that taxanes have been used in the clinic for decades, and have long been known to cause hair loss, were only now scratching the surface of how they damage the human hair follicle.

We need time to further develop approaches like this to not only prevent hair loss, but promote hair follicle regeneration in patients who have already lost their hair due to chemotherapy.

The study was published in the EMBO Molecular Medicine.

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Breakthrough in bid to prevent hair loss in cancer patients - The London Economic

Study signals new era of precision medicine for children with cancer – The Institute of Cancer Research

Image credit: Pixabay.

A new study has shown the power of genetic testing to pick out the best drugs for children with cancer to extend and improve their lives signalling a new era of precision medicine for young patients.

The pilot including more than 200 children found that half had gene mutations that are targetable by adult cancer drugs that are either available as standard treatment or via clinical trials.

Although few children on the study went on to receive adult drugs, those who did receive targeted therapies had significant benefits.

But the study also laid bare the regulatory and funding barriers to children receiving the newest drugs, as only 7 per cent of those with targetable mutations were able to access the appropriate adult drug.

The study was led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and offered genetic testing of tumours to children as part of a clinical trial. Some 20 additional hospitals around the UK participated by sending childrens biopsies in for testing.

The research ispublished in the European Journal of Cancer today (Thursday) and was primarily funded by the parent-led charity Christophers Smileand the NIHR Biomedical Research Centreat The Royal Marsden and The Institute of Cancer Research (ICR).

Researchers used a gene panel test to read the DNA sequence of 91 genes that drive cancers growth and spread from 223 childrens tumour biopsies looking for potentially targetable mutations.

Solid tumours such as those of the brain, central nervous system, bone and muscle are rare but have much worse survival rates than childrens blood cancers such as leukaemia. Surgery is often not possible and treatment is limited to blunt instrument chemotherapies.

The researchers first validated the panel test, showing it to be than more than 99 per cent sensitive at picking up the 91 mutations, even with just 50 nanograms of DNA which is around 1,000 times less than the weight of a grain of table salt.

Using the test, they found 51 per cent of tumour samples tested had mutations that could be targeted by adult cancer drugs.

The most common potentially treatable mutations were in the genes ATRX, CDKN2A and CTNNB1 which were each found in 12 childrens tumours. MYCN mutations were found in 11 tumours and PI3K3CA mutations in 10 tumours.

Three children had BRAF gene mutations which are common in melanoma skin cancers and can be treated using a combination of the drugs dabrafenib and trametinib.

Using these melanoma drugs, one of the children had their brain tumour held in check for 13 months before developing resistance. Another was on the drug for nine months with no progression of disease. The third child couldnt tolerate the combination but had a response to dabrafenib for 15 months.

We are building a new state-of-the-art drug discovery centre to develop a new generation of drugs that will make the difference to the lives of millions of people with cancer.

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But there are still challenges to overcome, since the majority of children with targetable mutations didnt receive adult drugs because there was no trial available for the drug in children, they were unable to access the drug on the NHS or they were too ill to receive an experimental treatment by the time they were tested.

For eight of the patients, there were samples available at diagnosis and after treatment and in six of those, testing revealed that the cancer had acquired new mutations as it evolved in response to treatment. That highlights the need to take an additional biopsy at relapse to search for targetable mutations.

For 12 of the children, the researchers were also able to test for cancer gene mutations in DNA released from tumours into the bloodstream from a blood sample. They found blood tests picked up almost all of the mutations found in the tumour, and in some cases they also found extra mutations which were not detected in the tumour region biopsied.

In future work the researchers will use serial blood tests to monitor how tumours evolve in response to therapies which will be particularly useful in hard-to-biopsy tumours.

Additionally, for children with brain tumours, the researchers are now looking at using samples of cerebral-spinal fluid to find drug targets. Although lumbar punctures are invasive, they are less so than a brain biopsy.

Study author Dr Sally George, Clinical Research Fellow at the ICR and Consultant Paediatric Oncologist at The Royal Marsden, said:

Children deserve the very best cancer treatments, so they can live as long as possible and as well as possible. We desperately need better, more intelligently designed treatments which can give children longer with their families with fewer side effects.

By testing tumours for specific gene mutations, we have shown its possible to identify new smarter, kinder treatment options for children, which may potentially give these patients much longer with their families after conventional therapies have failed.

But our study also exposes the desperately frustrating barriers that children still face in receiving new treatments barriers which lie in the regulations controlling how drugs for children are developed and approved.

Study leader Professor Louis Chesler, Professor of Paediatric Cancer Biology at the ICR, and Consultant at The Royal Marsden, said:

Our study has demonstrated that we have the scientific knowledge and technology to get children access to state-of-the-art testing and treatments. And because our testing currently only assesses a focused set of well-known and clinically meaningful mutations, it is more practical, faster and more cost-effective than looking at the whole genome.

In future, I want to be able to treat more children whose tumours have these targetable mutations with better drugs, as currently not all children have access. But gathering the molecular data is the first practical step to making this possible. This data, and more that we are continuing to collect, will be good evidence to more clearly guide use of the most appropriate drug for each child.

It is also very important that we extend very robust and detailed testing to children at time of diagnosis, so we can more accurately classify and treat these cancers in the first place. We will also be looking at the utility of the approaches for detecting cancer relapse, a very important area where we currently have few tools to anticipate what treatments may be required with adequate time to do so.

September gives us a chance to highlight the incredible research that goes on at the ICR, but we continue to work tirelessly with our parent charity partners all year round to keep making the discoveries that we hope will one day defeat childrens cancer.

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Dr Mike Hubank, Head of Clinical Genomics at The Royal Marsden and Reader in Translational Genomics at the ICR, said:

The next steps for testing will be to look at using liquid biopsies to detect targetable tumour mutations without having to rely on invasive biopsies to get the information.

Our early results, presented here, show that we can detect more mutations in blood than we do in conventional biopsies. It is probably in the blood that we get a more complete picture of the whole tumour, and not just the small part of the tumour that was removed for testing. Blood-based testing will also allow us to monitor tumour response to treatment and may be able to detect relapses early, offering the possibility of finely tuned, personalised treatments in the future.

Karen Capel is the founder and trustee of UK childrens cancer charity Christophers Smile, who funded the development of the test. Karen and her husband Kevin have campaigned tirelessly to improve the treatment for children with cancer after their son Christopher died from medulloblastoma in 2008. Karen said:

When our son died there was no biological information available to doctors about individual childrens tumours. There is an urgent unmet need to provide new treatments for those children diagnosed with the most aggressive and hard-to-treat cancers.

This test Professor Chesler and colleagues at the ICR developed is a first for children. We believe gene sequencing is the key foundation stone in enabling personalised medicine, and it will help to bring new treatments for children a step closer.

Building on the foundations of the sequencing test, blood tests could provide critical information for any child from diagnosis throughout their treatment and into remission opening the door for additional, continued or changed treatments. We are determined to fight for these liquid biopsies to become standard of care at the earliest opportunity.

As well as the main funding from Christophers Smile and the NIHR, the study was also supported by Children with Cancer UK, Cancer Research UK, Abbies Fund,Rosetrees Trust, the KiCa Fund, Rocheand The Brain Tumour Charity.

The Royal Marsden Cancer Charity supports Dr Sally Georges work, and funds Dr Mike Hubanks work through a generous donation from Her Highness Sheikha Jawaher Bint Mohammed Al Qasimi of Sharjah. The Royal Marsden Cancer Charity also funds The Royal Marsdens Oak Paediatric Drug Development Unit.

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Study signals new era of precision medicine for children with cancer - The Institute of Cancer Research

U-M obesity experts available to comment on complexity of overcoming national epidemic – University of Michigan News

EXPERTS ADVISORY

A national dialogue about fat shaming and other aspects of obesity has been touched off in recent days by late-night television host James Corden, and his response to comments by fellow television host Bill Maher.

Corden, who openly discussed his own struggle with being overweight, referenced research from a University of Michigan team in a monologue that has gone viral on social media.

In addition to the researchers behind that study, many other U-M scientists, health care researchers and clinicians work to understand the risk factors that contribute to obesity, the roots of weight issues at the molecular and genetic level, and the outcomes from weight-loss strategies ranging from exercise to bariatric surgery.

These experts are available to comment to media:

Kim Eagle

Kim Eagle, M.D. A cardiologist and co-director of the U-M Frankel Cardiovascular Center, co-led the 2016 study that Corden mentioned on his show. Using data from Massachusetts, it found that childhood obesity rates were highest among public schoolchildren living in the poorest areas, and that racial and ethnic differences in childhood obesity rates went away when family income was factored in (more information).

Eagle also leads Project Healthy Schools, a partnership between Michigan Medicine and community organizations aimed at reducing childhood obesity through in-school action.

Contact: Michigan Medicine Department of Communication, 734-764-2220

Martin Myers

Martin Myers Jr., M.D., Ph.D. Cordens monologue also referenced the importance of leptin, a hormone involved in metabolism and obesity. Leptin is the focus of work by Myers, a Medical School professor who is the director of MDiabetes, which brings together members of the U-M research community who study metabolism and diabetes.

His research focuses on the processes that enable the body to respond normally to insulin, and how problems in these pathways contribute to the development of insulin resistance and diabetes. His laboratory specifically concentrates on the crucial role played by nerve centers in the unconscious part of the brainwhat Myers calls glycemic control centersthat regulate the bodys ability to respond to insulin.

Contact: Michigan Medicine Department of Communication, 734-764-2220

Katherine Bauer

Katherine Bauer, Ph.D., M.S., assistant professor of nutritional sciences at the School of Public Health, is an epidemiologist whose research focuses on how social factors such as families and schools influence childrens nutrition and growth. Her work has specifically focused on the harms of family weight talk and teasing, and she is currently studying how blame directed at parents of children of higher weight impacts families.

Contact: kwbauer@umich.edu

Kendrin Sonneville

Kendrin Sonneville, assistant professor of nutritional sciences at the School of Public Health, is a registered dietitian, behavioral scientist and public health researcher whose research focuses on the prevention of eating disorders among children, adolescents and young adults. She uses a weight-inclusive framework to study how to promote health and well-being without inadvertently increasing body dissatisfaction, disordered eating and weight stigma.

Weight stigma and fat-shaming are pervasive across society, including within health care settings, Sonneville said. Weight stigma harms people with larger bodies and should not be used as a health promotion tool.

Contact: 734-763-8789, kendrins@umich.edu

Randy Seely

Randy Seeley, Ph.D., director of the Michigan Nutrition Obesity Research Center, oversees an effort to bring together U-M researchers focused on prevention and treatment of obesity at all levels. It is one of only 12 obesity research centers funded by the National Institutes of Health. Seeleys own work at the Medical School focuses on understanding the way the metabolism changes after bariatric surgery.

Contact: Michigan Medicine Department of Communication, 734-764-2220

Ling Qi

Ling Qi, Ph.D. The complicated relationship between obesity, metabolism and the immune system is the specialty for Qi, a professor of physiology at the Medical School. Qis team recently used a discovery about this relationship to spur mice to produce more insulin (more information).

Contact: Michigan Medicine Department of Communication, 734-764-2220

Amir Ghaferi

Amir Ghaferi, M.D., M.S. is a bariatric surgeon and health care researcher at Michigan Medicine and VA Ann Arbor Healthcare System. He directs the Michigan Bariatric Surgery Collaborative, which pools data from obesity-related surgery programs at 42 Michigan hospitals to fuel improvements in care, research and evidence-based decision tools to help people with obesity decide if bariatric surgery is the best option for them.

Contact: Michigan Medicine Department of Communication, 734-764-2220

Huda Akil

Huda Akil, Ph.D., a neuroscientist who co-directs the Molecular and Behavioral Neuroscience Institute, recently published findings about the roots of overeating deep in the brain. She and her colleagues discovery, made in mice, shows that the brain has molecules that act as both brakes and a gas pedal to govern eating, and explored how the two interact (more information).

Contact: Michigan Medicine Department of Communication, 734-764-2220

Roger Cone

Roger Cone, Ph.D. is director of the U-M Life Sciences Institute and vice provost and director of the U-M Biosciences Initiative. He is an obesity researcher who studies how the brain controls body weight and regulates energy balance. His lab has identified how two key receptors in the brain affect energy balanceand the receptors central roles in disease cachexia, anorexia nervosa and the most common cause of syndromic obesity in humans. His labs findings have served as the basis for developing setmelanotide, a new drug to treat syndromic obesity.

Contact: U-M Life Sciences Institute Communications, 734-615-6228

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U-M obesity experts available to comment on complexity of overcoming national epidemic - University of Michigan News

Bioinformatics Services Market Development Analysis 2017-2025 – Rapid News Network

Perpetual expansion of application areas of biotechnology in the fields, such as, disease diagnosis and forensic research is attracting the attention of health care professionals. Bioinformatics is used for management, storage, and standardization of information obtained from research and development in biotechnology, life sciences, and biopharmaceutical industries. The global bioinformatics services market has experienced tremendous growth in the past decade due to factors such as advancement in technology, expanding application of information technology in health care, and increasing demand for data management tools in life sciences and biotechnology research sectors. Major factors influencing the growth of this market are increasing research and development activities in the field of biotechnology, drug discovery, and biopharmaceuticals. In addition, increase in government initiatives also boosts the growth of the biotechnology market globally. Bioinformatics is widely used in research and development in the biotechnology and biopharmaceutical industries. Research and development activities involve significant investments and thus, small and medium-sized companies face difficulties in investing on analytical software. In order to reduce the cost of research and development process, manufacturers are focusing on development of web-based software solutions, wherein researchers need to make marginal investment in analytical software. In addition, web-based analytical software does not require large storage or data handling capacity. Thus, owing to the mentioned factors, demand for web-based analytical software is expected to rise in the near future. Therefore, web-based offerings in bioinformatics show potential growth opportunities for players operating in this market. Bioinformatics techniques demand skilled manpower to derive accurate results. Installation and upgrade to sophisticated tools or platforms in clinical laboratories demand for high investment in training of the staff so that they can efficiently use the systems. Lack of skilled personnel is a key factor restricting the adoption of sophisticated and high-end biotechnology processes.

The global bioinformatics services market can be segmented based on service type, application, end-user, and region. In terms of service type, the bioinformatics services market can be categorized into sequencing services, database and management services, data analysis services, and other services. Bioinformatics has eased the process of data analysis with various technological applications. Manufacturers are offering various services in order to overcome the shortage of skilled personnel in using bioinformatics tools and platforms. Data analysis is one of the vital operations performed by the bioinformatics service industry. High-end tools, such as, microarrays have been introduced to cater to the rising demand for customized data analysis. In terms of application, the bioinformatics services market can be classified into preventive medicine, molecular medicine, gene therapy, drug development, and others. Based on end-user, the bioinformatics services market can be segmented into academic and research institutes, pharmaceutical and biotechnology companies, hospitals and clinics, and others.

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In terms of region, the global bioinformatics services market can be divided into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America is projected to continue its dominance in the global bioinformatics services market owing significant R&D expenditure, greater acceptance of technology advancements, and increase in investments for technological innovations in bioinformatics. Rise in drug discovery and development, coupled with increase in government initiatives toward funding of small and start-up companies in the biotechnology and life sciences industry, is a major factor expected to drive the bioinformatics services market in North America during the forecast period. The bioinformatics services market in major countries of Asia Pacific, such as India and China, is expected to grow rapidly during the forecast period. Government initiatives to boost the biotechnology sector is a prime driver of the bioinformatics services market in the region. Moreover, availability of skilled and qualified manpower at low cost, government support in setting up of manufacturing units, strategic acquisitions of local players, and currency difference benefits are expected to attract global bioinformatics manufacturers to Asia Pacific.

Key players operating in the global bioinformatics services market are Agilent Technologies, IBM Life Sciences, Qiagen N.V., Illumina Inc., Eurofins Scientific, Bruker Daltonics Inc., Perkinelmer Inc., Accelrys Inc., Life Technologies Corporation, and CD Genomics.

The report offers a comprehensive evaluation of the market. It does so via in-depth qualitative insights, historical data, and verifiable projections about market size. The projections featured in the report have been derived using proven research methodologies and assumptions. By doing so, the research report serves as a repository of analysis and information for every facet of the market, including but not limited to: Regional markets, technology, types, and applications.

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The study is a source of reliable data on: Market segments and sub-segments Market trends and dynamics Supply and demand Market size Current trends/opportunities/challenges Competitive landscape Technological breakthroughs Value chain and stakeholder analysis

The regional analysis covers: North America (U.S. and Canada) Latin America (Mexico, Brazil, Peru, Chile, and others) Western Europe (Germany, U.K., France, Spain, Italy, Nordic countries, Belgium, Netherlands, and Luxembourg) Eastern Europe (Poland and Russia) Asia Pacific (China, India, Japan, ASEAN, Australia, and New Zealand) Middle East and Africa (GCC, Southern Africa, and North Africa)

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

Highlights of the report: A complete backdrop analysis, which includes an assessment of the parent market Important changes in market dynamics Market segmentation up to the second or third level Historical, current, and projected size of the market from the standpoint of both value and volume Reporting and evaluation of recent industry developments Market shares and strategies of key players Emerging niche segments and regional markets An objective assessment of the trajectory of the market Recommendations to companies for strengthening their foothold in the market

Note:Although care has been taken to maintain the highest levels of accuracy in TMRs reports, recent market/vendor-specific changes may take time to reflect in the analysis.

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Bioinformatics Services Market Development Analysis 2017-2025 - Rapid News Network

Global trends in antimicrobial resistance in animals in low- and middle-income countries – Science Magazine

Livestock antibiotic resistance

Most antibiotic use is for livestock, and it is growing with the increase in global demand for meat. It is unclear what the increase in demand for antibiotics means for the occurrence of drug resistance in animals and risk to humans. Van Boeckel et al. describe the global burden of antimicrobial resistance in animals on the basis of systematic reviews over the past 20 years (see the Perspective by Moore). There is a clear increase in the number of resistant bacterial strains occurring in chickens and pigs. The current study provides a much-needed baseline model for low- and middle-income countries and provides a one health perspective to which future data can be added.

Science, this issue p. eaaw1944; see also p. 1251

The global scale-up in demand for animal protein is the most notable dietary trend of our time. Since 2000, meat production has plateaued in high-income countries but has grown by 68%, 64%, and 40% in Asia, Africa, and South America, respectively. The transition to high-protein diets in low- and middle-income countries (LMICs) has been facilitated by the global expansion of intensive animal production systems in which antimicrobials are used routinely to maintain health and productivity. Globally, 73% of all antimicrobials sold on Earth are used in animals raised for food. A growing body of evidence has linked this practice with the rise of antimicrobial-resistant infections, not just in animals but also in humans. Beyond potentially serious consequences for public health, the reliance on antimicrobials to meet demand for animal protein is a likely threat to the sustainability of the livestock industry, and thus to the livelihood of farmers around the world.

In LMICs, trends in antimicrobial resistance (AMR) in animals are poorly documented. In the absence of systematic surveillance systems, point prevalence surveys represent a largely untapped source of information to map trends in AMR in animals. We use geospatial models to produce global maps of AMR in LMICs and give policy-makersor a future international panela baseline for monitoring AMR levels in animals and target interventions in the regions most affected by the rise of resistance.

We identified 901 point prevalence surveys from LMICs reporting AMR rates in animals for common indicator pathogens: Escherichia coli, Campylobacter spp., nontyphoidal Salmonella spp., and Staphylococcus aureus. From 2000 to 2018, the proportion of antimicrobial compounds with resistance higher than 50% (P50) increased from 0.15 to 0.41 in chickens and from 0.13 to 0.34 in pigs and plateaued between 0.12 and 0.23 in cattle. Global maps of AMR (available at resistancebank.org) show hotspots of resistance in northeastern India, northeastern China, northern Pakistan, Iran, eastern Turkey, the south coast of Brazil, Egypt, the Red River delta in Vietnam, and the areas surrounding Mexico City and Johannesburg. Areas where resistance is just starting to emerge are Kenya, Morocco, Uruguay, southern Brazil, central India, and southern China. Uncertainty in our predictions was greatest in the Andes, the Amazon region, West and Central Africa, the Tibetan plateau, Myanmar, and Indonesia. Dense geographical coverage of point prevalence surveys did not systematically correlate with the presence of hotspots of AMR, such as in Ethiopia, Thailand, Chhattisgarh (India), and Rio Grande do Sul (Brazil). The highest resistance rates were observed with the most commonly used classes of antimicrobials in animal production: tetracyclines, sulfonamides, and penicillins.

The portfolio of antimicrobials used to raise animals for food is rapidly getting depleted, with important consequences for animal health, farmers livelihoods, and potentially for human health. Regions affected by the highest levels of AMR should take immediate actions to preserve the efficacy of antimicrobials that are essential in human medicine by restricting their use in animal production. In some middle-income countries, particularly in South America, surveillance must be scaled up to match that of low-income African countries that are currently outperforming them despite more limited resources. Policy-makers coordinating the international response to AMR may consider sparing African countries from the most aggressive measures to restrict access to veterinary drugs, which may undermine livestock-based economic development and rightfully be perceived as unfair. However, in regions where resistance is starting to emerge, there is a window of opportunity to limit the rise of resistance by encouraging a transition to sustainable animal farming practices. High-income countries, where antimicrobials have been used on farms since the 1950s, should support this transitionfor example, through a global fund to subsidize improvement in farm-level biosafety and biosecurity.

The main article presents a map of antimicrobial resistance in animals in low- and middle-income countries where sales of veterinary antimicrobials remain largely unregulated. In this image, broilers are seen roaming freely outside of a family-owned farm in Kitwe, Zambia. [Photo: S. Jetha]

The global scale-up in demand for animal protein is the most notable dietary trend of our time. Antimicrobial consumption in animals is threefold that of humans and has enabled large-scale animal protein production. The consequences for the development of antimicrobial resistance in animals have received comparatively less attention than in humans. We analyzed 901 point prevalence surveys of pathogens in developing countries to map resistance in animals. China and India represented the largest hotspots of resistance, with new hotspots emerging in Brazil and Kenya. From 2000 to 2018, the proportion of antimicrobials showing resistance above 50% increased from 0.15 to 0.41 in chickens and from 0.13 to 0.34 in pigs. Escalating resistance in animals is anticipated to have important consequences for animal health and, eventually, for human health.

Antimicrobials have saved millions of human lives, yet the majority (73%) are used in animals raised for food (1). The large and increasing use of antimicrobials in animals is both an enabler and a consequence of the global scale-up in demand for animal protein. Since 2000, meat production has plateaued in high-income countries but has grown by 68%, 64%, and 40% in Africa, Asia, and South America, respectively (2). The transition to high-protein diets in low- and middle-income countries (LIMCs) has been facilitated by the global expansion of intensive animal production systems, in which antimicrobials are used routinely to maintain health and productivity (3). A growing body of evidence has linked this practice with antimicrobial-resistant infections not just in animals but also, in some cases, in humans (46). Although the majority of emerging infectious disease events have been associated with drug-resistant pathogens of zoonotic origins (7), antimicrobial resistance (AMR) in animals has received comparatively less attention than in humans.

In LMICs, trends in AMR in animals are poorly documented. Colombia is currently the only country that has publicly available surveillance data on AMR in animals (8). As in high-income countries, antimicrobials are used in LMICs to treat animals and as surrogates for good hygiene on farms. However, in LMICs, AMR levels could be exacerbated by lower biosecurity, less nutritious feed, and looser regulations on veterinary drugs (9). Conversely, in LMICs, AMR levels may also be reduced by less meat consumption and limited access to veterinary drugs in rural areas. Few studies have attempted to disentangle the effect of those factors and, thus far, expert opinion has prevailed over an evidence-based assessment of AMR in LMICs (10).

In 2017, The World Health Organization (WHO) called on its member states to reduce veterinary antimicrobial use (11, 12). Coordinating the global response to AMR requires epidemiological data to assess trends in AMR across regions. In human medicine, the WHOs Global Antimicrobial Resistance Surveillance System (GLASS) (13) has encouraged the adoption of a harmonized reporting framework, but there is no comparable framework for AMR in animals. Scandinavian countries have been at the forefront of monitoring AMR in animals, and Europe and the United States have adopted similar systems (14). However, in LMICs, similar surveillance systems are nascent at best, and building a globally harmonized surveillance system could take a long time. The challenge posed by AMR requires immediate action, and thus alternatives to systematic surveillance are needed to guide intervention based on the best evidence currently available.

In LMICs, point prevalence surveys are a largely untapped source of information with which to map trends in AMR in animals. Generating resistance maps from these surveys presents several challenges. First, surveys often differ in protocol, sample size, and the breakpoints used for antimicrobial susceptibility testing. Harmonizing these variations is a first step toward improving comparability. Second, because AMR affects many organisms, indicator organisms should be identified; the foodborne pathogens listed by the WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) are an ideal starting point (15). Third, because the problem of AMR affects many drug-pathogen combinations, it is difficult to communicate with policy-makers. Introducing composite metrics of resistance may help when summarizing global trends. Finally, the interpolation of epidemiological observations from data-rich regions to data-poor regions is inherently uncertain and could be improved using factors associated with AMR.

Species distribution modeling can identify such associations for predictive mapping, and the development of ensemble geospatial modeling (16) has helped to improve their accuracy.

In this study, we address these challenges to mapping AMR in animals in LMICs at 10-km resolution using point prevalence surveys of common foodborne pathogens. The maps summarize current knowledge and provide policymakers, or any future international panel (17), a baseline with which to monitor AMR levels in animals and to target interventions across regions.

We identified 901 point prevalence surveys reporting AMR rates in animals and food products in LMICs. Our analysis focused on resistance in Escherichia coli, Campylobacter spp., nontyphoidal Salmonella spp., and Staphylococcus aureus. The number of published surveys on resistance to these pathogens in LMICs increased from three in 2000 to 121 in 2018 and peaked at 156 per year in 2017. However, the number of surveys conducted during that period was uneven across regions (Fig. 1A): surveys from Asia (n = 509) exceeded the total for Africa and the Americas (n = 415). The number of surveys per country was not correlated with gross domestic product (GDP) per capita (Fig. 1B).

(A) Publications by continent. (B) Publications per capita versus GDP per capita; each country is designated by International Organization for Standardization (ISO3) country code.

In LMICs, from 2000 to 2018, the proportion of antimicrobial compounds with resistance higher than 50% (P50) increased from 0.15 to 0.41 in chickens and from 0.13 to 0.34 in pigs and plateaued between 0.12 to 0.23 in cattle (Fig. 2). Those trends were inferred from the average yearly increase in P50 (1.5%/year for chickens and 1.3%/year for pigs), weighted by the number of studies published each year (supplementary materials).

Proportion of antimicrobial compounds with resistance higher than 50% (P50) is shown. Solid lines indicate statistically significant (5% level) increases of P50 over time; shading indicates the number of surveys per year relative to total number of surveys per species.

In LMICs, resistance levels showed considerable geographic variations (see Fig. 3A and fig. S1 for country-level indexes). Regional hotspots (P50 > 0.4) of multidrug resistance were predicted in south and northeast India, northeast China, north Pakistan, Iran, Turkey, the south coast of Brazil, Egypt, the Red River delta in Vietnam, and the areas surrounding Mexico City and Johannesburg. Low P50 values were predicted in the rest of Africa, Mongolia, and western China. On the basis of maps of animal densities (fig. S2), we estimate that across LMICs, 9% [95% confidence interval (CI), 5 to 12%] of cattle, 18% (95% CI, 11 to 23%) of pigs, and 21% (95% CI, 11 to 28%) of chickens were raised in hotspots of AMR in 2013. For chickens, the percentage of birds raised in hotspots of resistance in each country exceeded the global average in China [38% (95% CI, 24 to 46%)], Egypt [38% (95% CI, 22 to 55%)], and Turkey [72% (95% CI, 41 to 81%)]. We also identified regions where AMR is starting to emerge by subtracting P50 from P10 (the proportion of antimicrobial compounds with resistance higher than 10%; Fig. 3C). In Kenya, Morocco, Uruguay, southern and eastern Brazil, central India, Iran, Chile, and southern China, the difference between P10 and P50 was high (>0.5), indicating that these regions are emerging AMR hotspots. Conversely, established hotspots of AMR where the difference between P10 and P50 was low (<0.1) included northeastern China, West Bengal, and Turkey.

(A) P50, the proportion of antimicrobial compounds with resistance higher than 50%. (B) 95% confidence intervals on P50 (supplementary materials). (C) Difference in the proportion of antimicrobials with 10% resistance and 50% resistance. Red areas indicate new hotspots of resistance to multiple drugs; blue areas are established hotspots. Maps are available at resistancebank.org.

The accuracy of the P50 maps (Fig. 3B) reflects the density of surveys for a region as well as the ability to associate the geographic distribution of P50 with environmental covariates using geospatial models (supplementary materials). All geospatial models had limited accuracies (areas under the curve, 0.674 to 0.68), but all identified the travel time to cities of 50,000 people as the leading factor associated with the geographic distribution of P50. Minimum annual temperature and percentage of irrigated land were also positively associated with P50 but had less influence (table S1).

Uncertainty in the map of P50 was high (95% CI > 0.3) in the Andes, the Amazon region, West and Central Africa, the Tibetan plateau, Myanmar, and Indonesia. Dense geographical coverage of surveys (>4 point prevalence surveys/100,000 km2) did not systematically correlate with high P50 values (Ethiopia; Thailand; Chhattisgarh, India; and Rio Grande do Sul, Brazil).

The highest resistance rates were observed in the most commonly used classes of antimicrobials in animal production (Fig. 4): tetracyclines, sulfonamides, and penicillins (1). Among antimicrobials considered critical to human medicine (18), the highest resistance rates were found for ciprofloxacin and erythromycin (20 to 60%) and moderate rates were found for third- and fourth-generation cephalosporins (10 to 40%). Other critically important antimicrobials, such as linezolid and gentamicin, were associated with lower resistance rates (<20%). AMR trends in LMICs were in agreement with the trends reported in Europe and the United States (14, 19) for tetracyclines, sulfonamides, and third- and fourth-generation cephalosporins, but differences also exist for quinolones and aminoglycosides.

Shown are resistance rates and number of surveys (n) by region. Transparency levels reflect sample sizes for each animal-pathogen combination (for drug acronyms, see supplementary text, protocol S1).

In E. coli and Salmonella spp., quinolone resistance in LMICs (20 to 60%) was comparable with European levels [59.8 to 64% (14)], but gentamycin resistance was higher in LMICs (5 to 38%) than in Europe (2.4 to 8.9%). The reverse situation was observed when comparing LMICs and the United States, where quinolone resistance is low (2.4 to 4.6%) and gentamycin resistance higher [22.1% and 41.3% for Salmonella and E. coli, respectively (19)]. In LMICs, high resistance in third- and fourth-generation cephalosporins in E. coli was high (~40%). Resistance to carbapenems was low in all host species in LMICs, as previously reported in animals (20). Asia and the Americas currently have the highest rate of colistin resistance (~18 to 40%).

In Campylobacter spp., in LMICs, the highest resistance rates were found for tetracycline (60%) and quinolones (60%). Tetracycline resistance was also the highest among all animals in the United States [49.1 to 100% (19)], but lower for quinolones in chickens (20%). Resistance to erythromycin was moderate (<30%) in LMICs but higher than in high-income countries (0.3 to 22% in the United States and 0 to 21.6% in Europe), indicating that erythromycin resistance genes [e.g., erm(B)] could be spreading more commonly on mobile genetic elements in LMICs.

Finally, for S. aureus, resistance rates across all antimicrobials were higher in Asia than in other regions. The highest rates were found for penicillin (40 to 80%), erythromycin (20 to 60%), tetracycline (20 to 60%), and oxacillin (20 to 60%). For S. aureus, unlike other pathogens, resistance rates among antibiotics (except for penicillin) varied greatly by region. Comparisons with high-income countries are limited, as few European countries reported resistance in S. aureus in 2016, and susceptibility testing was typically restricted to methicillin-resistant S. aureus, which has considerable variation in prevalence [0% in Irish cattle and chickens to 40 to 87% in Danish pigs (14)].

In most high-income countries, AMR has been monitored in animals for over 10 years (14). Here, we used point prevalence surveys to conduct a global assessment of the trends in AMR in animals in LMICs. A singular challenge in the epidemiology of AMR is to synthetize a problem involving multiple pathogens and compounds across different regions. We therefore introduced a summary metric of resistance, P50, which reflects the ability of veterinarians to provide effective treatment solutions. On the basis of the evidence assembled, P50 increased in LMICs from 0.15 to 0.41 (+173%) in chickens and from 0.13 to 0.34 (+161%) in pigs and plateaued between 0.12 and 0.23 in cattle. Rapid increases in AMR in chickens and pigs are consistent with the intensification of livestock operations for these species compared with cattle (21). The main consequence of those trends is a depletion of the portfolio of treatment solutions for sick animals. This loss has economic consequences for farmers because affordable antimicrobials are used as first-line treatment (22), and this could eventually be reflected in higher food prices.

The number of surveys supporting this first assessment is limited (n = 901) and heterogeneous across countries (fig. S3A). However, it enables us to draw inferences on large-scale trends in AMR (Fig. 3A). Globally, the percentage of animals raised in hotspots of AMR was limited (<20%), with the notable exception of chicken production in upper- to middle-income countries such as Turkey (72%) and Egypt (38%). These countries are also the first- and third-largest per-capita consumers of antimicrobials in human medicine among LMICs (23).

The largest hotspots of AMR in animals were in Asia, which is home to 56% of the worlds pigs and 54% of the chickens. In Asia, targeted interventions such as legislative action and subsidies to improve farm hygiene could reduce the need for antimicrobials in animal production (1), thereby preserving important drugs for human medicine and the treatment of sick animals. We identified hotspots for the emergence of AMR including central India and Kenya, where resistance to multiple drugs has appeared but not yet reached 50% (Fig. 3C). In these regions, meat consumption is still low and animal production is gradually intensifying. Here, there may be a window of opportunity to contain AMR by imposing strict hygiene standards in newly built farms. This approach could reduce the risk of the spread of resistant pathogens such as mcr-1carrying E. coli (6) that have emerged in regions where intensive meat production has been facilitated by enormous quantities of veterinary antimicrobials (1).

In Africa, resistance maps reveal the absence of major AMR hotspots, except for the Johannesburg metropolitan area. This suggests, on the basis of the regions surveyed, that Africa probably bears proportionately less of the current global burden of AMR than high- and upper- to middle-income countries. Policy-makers coordinating an international response to AMR might therefore spare Africa from the most aggressive measures, which may undermine livestock-based economic development and rightfully be perceived as unfair.

In the Americas, where the number of surveys was limited (Fig. 3B), the observed low AMR levels could reflect either good farming practices (low antimicrobial use) or the absence of surveys conducted in the areas most affected by AMR. Considering that Uruguay, Paraguay, Argentina, and Brazil are net meat exporters (2), it is of concern that little epidemiological surveillance of AMR is publicly available for these countries. Many low-income African countries have more point prevalence surveys per capita than middle-income countries in South America. Globally, the number of surveys per capita was not correlated with GDP per capita, suggesting that surveillance capacities are not solely driven by financial resources.

In this study, we stacked predictions from geospatial models to map P50 and P10 in LMICs. The moderate accuracy of these models reflects the challenge of associating the spatial distribution of AMR with environmental and socioeconomic factors (24). AMR in animals may be driven by factors known to influence antimicrobial use in humanssuch as cultural norms, the presence of drug manufacturers in the national market, or the density of health professionals (25)that could not be easily mapped from publicly available sources of information. The leading factor associated with the spatial distribution of P50 was the travel time to cities (26). Ease of access to providers of veterinary drugs may drive AMR, and hotspots appear to correspond to peri-urban environments where large farms supply affluent city dwellers. We also found a positive association between P50 and temperature. Evidence for a link with temperature in animals is less established than in humans (27), but it has been suggested that high temperature causes stress and conflicts in animals, thus increasing the risk of wounds that require preventive antimicrobial treatment (28). Finally, in Asia, 74% of P50 hotspots corresponded to areas previously identified for their projected increase in antimicrobial use (fig. S4). The relative influence of antimicrobial use on the spatial distribution of P50 was limited to 3.8% (table S1), but this association should be treated with caution given the scarcity of original data on antimicrobial use in LMICs (29).

We identified diverging patterns of resistance across combinations of pathogens and drugs. For S. aureus, geographic differences in AMR levels could be explained by sublineages carrying different SCCmec cassettes that are specific to certain regions (30). Of greater concern for public health is the presence of resistance to third- and fourth-generation cephalosporinscritically important antimicrobials for human medicineon all continents. In addition, the high levels of colistin resistance found in Asia suggest that regional spread may have been driven by plasmid-mediated resistance (6), as well as by the widespread use of this cheap antimicrobial. The recent Chinese ban on colistin (31), if enforced, may improve the situation. However, globally, progress may be undermined by the large quantities of colistin still used, including in some high-income countries. For quinolones, in LMICs, E. coli and Campylobacter had resistance levels comparable with European levels but considerably higher than in the United States, where quinolones were banned in poultry in 2005. Conversely, for Salmonella and E. coli, LMICs had substantially higher resistance to gentamycin than in Europe, where this compound is banned for use in poultry and cattle (32). These findings suggest that regional restrictions on the use of specific compounds are associated with lower AMR rates.

The uncertainty associated with interpolation of resistance rates is captured with confidence interval maps (Fig. 3B). However, there are additional sources of uncertainty. First, insufficient geographic coverage may lead to inaccurate spatial predictions, and local variations in AMR may not reflect ground truth. In this study, we attenuate the risk of overfitting geospatial models to local outliers using spatial cross-validation. Second, temporal variation in AMR over the period 20002018 was not accounted for. As more surveys become available, spatiotemporal, model-based geostatistics approaches could help to overcome this limitation. Third, in slaughterhouse surveys, most did not perform molecular typing longitudinally throughout the different processing stages, which would have enabled us to assess potential cross-contamination. Although cross-contamination may generally affect AMR rates, in the absence of international benchmarking, it is unknown whether it could systematically bias our result in any single country. Finally, our analysis raises renewed concerns about the pace of increase of AMR in animals, but it is beyond the scope of this study to draw conclusions about the intensity and directionality of transfer of AMR between animals and humans, which should be further investigated using robust genomics methods (33).

Point prevalence surveys are imperfect surrogates for surveillance networks. However, in the absence of systematic surveillance, maps have been useful to guide interventions against other diseases of global importance, such as malaria (34). In human medicine, point prevalence surveys of AMR in hospitals have generated snapshots of AMR across regions (35).

This initial assessment outlines three global priorities for action. First, our maps show regions that are poorly surveyed and where intensified sampling efforts could be most valuable. Second, our findings clearly indicate that the highest levels of AMR in animals are currently found in China and India. These countries should take immediate actions to preserve antimicrobials that are essential in human medicine by restricting their use in animal production. Third, high-income countries, where antimicrobials have been used on farms since the 1950s, should support the transition to sustainable animal production in LMICsfor example, through a global fund to subsidize improvements in farm-level biosafety and biosecurity (36).

T. P. Van Boeckel, J. Pires, R. Silvester, C. Zhao, J. Song, N. G. Criscuolo, M. Gilbert, S. Bonhoeffer, R. Laxminarayan, R code for: Global trends in antimicrobial resistance in animals in low- and middle-income countries, Zenodo (2019). doi:10.5281/zenodo.3354324

A. Getis, J. K. Ord, The analysis of spatial association by use of distance statistics, in Perspectives on Spatial Data Analysis (Springer, 2010), pp. 127145.

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