Culture

Current vaccination policies may not be sufficient to achieve and maintain measles elimination and prevent future resurgence in Australia, Ireland, Italy, the UK and the US, according to a study published in the open access journal BMC Medicine.

To successfully achieve and maintain measles elimination in these countries in the medium to long term, further country-specific immunisation efforts may be needed in addition to current strategies. Measles elimination has been defined as the absence of endemic measles transmission in a region or other defined geographic area for twelve months or longer.

A team of researchers at the Bruno Kessler Foundation and Bocconi University, Italy used a computer model to simulate the evolution of measles immunity between 2018 and 2050 in seven countries; Australia, Ireland, Italy, Singapore, South Korea, the UK and the US. The authors focused their analysis on countries with a routine two-dose measles vaccination programme and a high primary school involvement rate, but with different demographics and vaccination histories. The aim was to evaluate the effect of possible adjustments to existing immunisation strategies, and to estimate the proportion of people who may remain susceptible to measles in high-income countries over time.

The authors' projections up until 2050 suggest that if current vaccination policies remain unchanged, the proportion of the population susceptible to measles would only remain below 7.5% in Singapore and South Korea, two countries which had high vaccination coverage in the past. Previous research estimated that the proportion of the population that does not have immunity (maximum susceptibility) needs to be 7.5% or less for measles to be eliminated.

In 2018, the proportion of the population susceptible to measles infection in the countries under study ranged from 3.7% in the UK to 9.3% in Italy (the only country where the proportion was found to be higher than 7.5%). In Australia, Ireland, the UK and the US, vaccination from routine programmes would need to continuously cover more than 95% of the population to keep the proportion of susceptible individuals below 7.5% until 2050.

Dr. Filippo Trentini, the first author said: "In recent years, we've witnessed a resurgence of measles cases even in countries where, according to World Health Organisation guidelines, elimination should already have been achieved. This resurgence is due to suboptimal vaccination coverage levels. In Italy, where measles incidents rates were among the highest, the government has made measles vaccination compulsory for children before they enter primary school. We investigated the potential of this and other policies to reinforce immunisation rates in seven high-income countries."

Co-author Dr. Stefano Merler added: "Our results suggest that most of the countries we have studied would strongly benefit from the introduction of compulsory vaccination at school entry in addition to current immunisation programmes. In particular, we found that this strategy would allow the UK, Ireland and the US to reach stable herd immunity levels in the next decades, which means that a sufficiently high proportion of individuals are immune to the disease to avoid future outbreaks. To be effective, mandatory vaccination at school entry would need to cover more than 40% of the population."

In Italy, the fraction of susceptible individuals by 2050 is projected to be 10%, even if coverage for routine vaccination reaches 100%, and additional vaccination strategies targeting both children at school entry and adults may be needed to achieve elimination.

South American fur seal pups with high levels of hookworm infection spend more time in the water, but that's not necessarily a good thing, report Morris Animal Foundation-funded researchers at the University of Georgia.

The team hypothesized the higher infection rates are due to a climate change chain reaction that forces pups' mothers to devote more time to searching for food, rather than providing the pups maternal care that can thwart parasites. The team recently published their study in the journal Ecology and Evolution.

"This was a surprising finding, but it helps us understand the full relationship these parasites have with their hosts, directly and indirectly," said Dr. Mauricio Seguel, a veterinary researcher at the University of Georgia. "More importantly, though, studies like this answer smaller parts of a bigger question: How much do our activities as humans impact animals?"

Hookworm infection is a significant health risk in South American fur seal populations. A separate Morris Animal Foundation-funded study, led by Dr. Seguel, determined more than 20 percent of fur seal pups die from parasitic infections every year.

"It is important to understand these complex associations between animal behavior and disease that can reveal effects of climate change on ocean health" said Dr. Janet Patterson-Kane, Morris Animal Foundation Chief Scientific Officer. "This study shows pups with higher parasite loads and more time in the water as two outcomes of decreased maternal care, but there is more to the story and we are dedicated to discovering what that is."

Dr. Sequel's team studied pups at a fur seal colony on Guafo Island in southwestern Chile, where all pups show some degree of hookworm infection. For four months, researchers captured pups that were 1 to 2 days old and marked them for tracking. The team observed each pup's behavior for at least eight weeks, recording the number of times and in what ways the pups engaged in water activities.

The researchers also took regular blood and fecal samples to measure the level of hookworm infection in each animal. They discovered that pups with higher parasite burdens were far more active in the water than pups with lower levels; playing and swimming, rather than resting by or avoiding it.

Further analysis revealed the animals with higher infection rates spent less time with their mothers. The team believes this could be because warmer ocean temperatures make fish scarcer. Younger, less experienced females then must spend more time searching for food and less time with their offspring. Those pups, in turn, aren't able to feed from their mothers and spend more time in the water; and have weaker immune systems that are less able to clear the parasites.

It is unknown what the implications are for the long-term survival and reproductive success of fur seal populations, given increasing ocean temperatures, higher parasite load, and the extended periods of time mothers spend away from their pups as finding food becomes more challenging. Dr. Seguel's work, with funding from Morris Animal Foundation, is critical to a better understanding of these populations and their ongoing health.

In future studies, Dr. Seguel and his team hope to learn more about fur seal pup swimming behavior and how less or more time in the water positively or negatively impacts pup health.

Strict policies traditionally embraced by Asian nations to discourage illicit drug use are beginning to change, with a few nations adopting alternative approaches while other nations are taking an even harder line against drugs, according to a new RAND Corporation report.

Thailand is on the forefront of Southeast Asian nations that are reconsidering longstanding policies, moving to adopt greater harm reduction, approving the use of medical cannabis and easing restrictions on the traditional use of the substance kratom.

Meanwhile, some other nations -- most visibly represented by the Philippines -- are adopting even harsher policies on illicit drugs, including violent repression of drug distribution and use.

"Asian nations have long espoused the goal of a drug-free society, imposing harsh criminal penalties and even the death penalty on those involved with illicit drugs," said Bryce Pardo, lead author of the report and a policy analyst at RAND, a nonprofit research organization. "So it is surprising to see some Asian nations begin to go in a different direction and consider more-progressive policies."

The RAND report also dissects China's role as a focal point in the global supply of fentanyl, a powerful synthetic opioid that is responsible for a growing number of fatal drug overdoses in the U.S.

The report outlines the rapid rise of the drug industry in China, where there are now more than 5,000 pharmaceutical manufacturers and hundreds of thousands of chemical companies. While the industry is a leading source of many legitimate chemicals and pharmaceutical ingredients, its growth has made it easier for some companies to avoid regulations.

China's central government has promised to crack down on fentanyl manufacturers, but enforcement of such policies is typically done at the provincial level, where there is little infrastructure in place to regulate the drug and chemical industries.

"China's leaders recognize that they have a problem and appear committed to seeking solutions," Pardo said. "But it is unlikely that they can contain the illicit production and distribution of fentanyl in the short term because enforcement mechanisms are lacking. Producers are quick to adapt, impeding Chinese law enforcement's ability to stem the flow to global markets."

Thailand's shift from harsh drug policies toward evidence-based treatment and reduced punishment appears to be motivated by the heavy burden previous policies have had on its prison system and an alarming increase in disease transmission related to needle-sharing.

In 2016, about 70 percent of Thailand's 320,000 prisoners were incarcerated for drug offences, including many for consumption-related violations. The nation has begun to move toward voluntary outpatient treatment and has experimented with needle-exchange programs to address disease transmission.

The report notes that the illicit production and use of opioids and amphetamine-type substances are the greatest concern across Asia. There also are reports of rising trafficking and use of new psychoactive substances and ketamine.

But one challenge facing Asian nations is a shortage of reliable information about drug use, which is key to assessing the size of the problem and judging the influence of policies.

"As in many countries, there is tremendous imprecision in the data available on the prevalence of drug use in Asia and the amount of money spent on these substances," said Beau Kilmer, a co-author of the report and co-director of the RAND Drug Policy Research Center. "Policy shifts are occurring and these data gaps will make it difficult to evaluate the consequences of these changes in the near and longer term."

May 15, 2019 - We all know plants need nutrients, especially nitrogen and phosphorus. To give crops a boost, they are often put on fields as fertilizer. But we never talk about where the nutrients themselves come from.

Phosphorus, for example, is taken from the Earth, and in just 100-250 years, we could be facing a terrible shortage. That is, unless scientists can find ways to recycle it.

Scientists at Tel Hai College and MIGAL Institute in Israel are working on a way to make phosphorus fertilizer from an unlikely source -- dairy wastewater.

Additionally, they are taking the element from the wastewater with another unlikely character. They are using the leftovers that comes from making clean drinking water, which contain the element aluminum.

"The material left after purification, called aluminum water treatment residue, is normally taken to a landfill to be buried," says Michael "Iggy" Litaor, who led this work. "We changed this material by mixing it with dairy wastewater rich with phosphorus and organic matter. We then found it can be just as good as common fertilizers."

The benefits of the practice could go beyond recycling the element. Putting too much of the commercially available fertilizers on fields can hurt the quality of water nearby.

"Phosphorus is an important nutrient needed by most crops," Litaor explains. "However, it is a non-renewable resource. If we continue with the current rate of use, what we have may be depleted in 100 to 250 years. There are also side-effects of too much fertilizer. Hence, scientists around the world are searching for simple and affordable ways to recycle the element without lowering crop yield."

In their study, Litaor and his team mixed the aluminum water treatment residue with dairy wastewater. Dairy wastewater comes from washing cow udders before milking and from cooling cows during hot summer days. It is high in phosphorus because of detergents used while cleaning the sheds that house the cows as well as runoff from cows' urine.

What allows the mixture to become fertilizer is the magic of chemistry. Reactions occur between the phosphorus, aluminum, and organic matter that result in it being a possible fertilizer.

Litaor and his team then put the potential fertilizer on lettuce to see how well it worked. They found it did just as well as common fertilizers.

"This experiment clearly showed that we can use aluminum refuse to recapture phosphorus from dairy wastewater and use it as fertilizer," he says. "We showed that the water treatment residue can take phosphorus from the wastewater and put it in soil that doesn't have much phosphorus. This may offset somewhat the mining of this non-renewable resource."

If this method of making fertilizer were to become widely practiced, Litaor sees the possibility of building plants next to dairies with lots of cattle. This would give a large supply of phosphorus. A company could bring in the leftovers from water treatment systems to produce fertilizer. It could be used by large farms or sold to others.

He says the next step in this research is to look at the use of water treatment leftovers that contain iron, because many soils also lack this element. The scientists must also show that no unwanted material such as hormones and antibiotics are in the fertilizer.

"I also want to find an investor who will support us taking this idea to the marketplace," he adds. "After many years of research on phosphorus in wetlands, streams, and rivers, I decided to look for an efficient means to recycle the element using wastes we were already producing."

ANN ARBOR, Mich. - Thousands of emergency medicine physicians gather this week at the Society for Academic Emergency Medicine Annual Meeting in Las Vegas, Nevada. According to SAEM, it is the largest forum for the presentation of original education and research in academic emergency medicine.

The emergency medicine team at Michigan Medicine is well represented at the conference. Here are some highlights:

Keynote address: Firearm injury

This year's keynote address was presented by Rebecca Cunningham, M.D., a professor of emergency medicine at Michigan Medicine and director of the Centers for Disease Control and Prevention-funded University of Michigan Injury Prevention Center.

Cunningham, along with Garen Wintemute, M.D., M.P.H., presented Firearm Injury: Facts, Myths, and a Public Health Path Forward.

"Firearm violence is a major public health problem," says Cunningham, associate vice president for research-health sciences at U-M. "In fact, firearm injuries are the second leading cause of death among children one to 18 years old and the leading cause of death among children 14 to 17 years old."

In April 2018, she received a $5 million grant from the National Institutes of Health to create the Firearm-safety Among children & Teens Consortium (FACTS). In November 2018, FACTS launched a new website with free access to data on the issue of gun violence, as well as training for health care providers and others.

The keynote address focused on gun safety, a term Cunningham hopes more people will start using.

"People always use the term gun control when talking about gun safety, but that's not what I'm talking about here," Cunningham says. "We're talking about an injury prevention issue. We want to prevent injury, while respecting Second Amendment rights."

Cunningham and Wintemute provided an overview of firearm violence, data on how firearm injuries compare to other forms of injury and death in patient populations, and ways for their fellow physicians to begin researching and screening for gun violence in their own clinical settings.

"Through research and science we were able to reduce the amount of children and teens dying in motor vehicle accidents, even though there are more cars on the road today," Cunningham says. "I believe we can apply the same scientific principles to firearm violence and reduce the number of children dying from guns."

Plenary session: Reducing over-testing in the emergency department

The meeting's plenary session includes the top six abstracts selected by the SAEM19 Program Committee.

One of this year's plenary session abstracts was research presented by Keith Kocher, M.D., M.P.H., an assistant professor of emergency medicine at Michigan Medicine.

The abstract, titled Emergency Care Quality Imaging Benchmarks in a Statewide Collaborative: Estimated Excess and Associated Spending, included other Michigan Medicine experts Benjamin Bassin, M.D., Michaelina Bolton, M.D., James Pribble, M.D., Nicole Sroufe, M.D., Bradley Uren, M.D., and Michele Nypaver, M.D.

In the study, the research team highlights opportunities to safely reduce over-testing in emergency departments using data from the Michigan Emergency Department Improvement Collaborative (MEDIC), a physician-led statewide quality network connecting a diverse set of unaffiliated emergency departments with the goal of improving quality and reducing low-value emergency care throughout the state of Michigan. Estimates of excess imaging were calculated based on Achievable Benchmark of Care, a method for determining quality improvement targets across a population.

"The emergency department is an essential care setting, treating over 145 million annual visits in the United States across a wide range of patient populations," says Kocher, a member of the University of Michigan Institute for Healthcare Policy and Innovation. "Therefore, the emergency department setting represents the ideal venue to implement practice improvement efforts to ensure high-quality care, informed by the best available evidence."

Across the collaborative, the team found substantial variation in amounts of performed imaging and the potential to avoid 1,519 head computed tomography (CT) scans for minor head injury, 3,308 chest x-rays for children with asthma, bronchiolitis or croup, and 4,254 CT scans for suspected pulmonary embolism in 2017 alone.

"The estimated spending on these excess tests ranged from $3.59 to $5.02 million," Kocher says. "We show that there is the opportunity to avoid low-value imaging in the emergency department and in turn, create significant health care savings."

Awards

In addition to giving the keynote address, Cunningham received this year's SAEM Excellence in Research Award.

According to SAEM, the award honors a SAEM member who has made outstanding contributions to emergency medicine through the creation and sharing of new knowledge. Recipients are chosen based on their research accomplishments, training and mentorship of other investigators, and recognition, such as peer review journal positions, awards they have received and more.

"I am humbled and honored to receive this award from the Society for Academic Emergency Medicine," says Cunningham, who will become interim vice president for research at U-M on June 1. "As an emergency medicine physician and academic researcher, my goals have consistently aligned with those of SAEM: we both strive to improve care for acutely ill and injured patients by advancing research and education.

"I look forward to partnering with organizations like SAEM as we continue our work to translate research that has the greatest impact on emergency care."

Patrick Carter, M.D., an assistant professor of emergency medicine at Michigan Medicine, was one of the recipients of this year's SAEM Young Investigator Award.

According to SAEM, the award recognizes those SAEM members who have demonstrated commitment and achievement in research during the early stage of their academic career. Recipients are chosen based on several criteria, but mainly their academic and research accomplishments, including grant awards.

SonoGames

Robert Huang, M.D., the associate director of clinical ultrasound and clinical ultrasound fellowship director at Michigan Medicine, is one of the lead organizers of SonoGames, an ultrasound educational event that takes place on the last day of the Annual Meeting.

According to SAEM, SonoGames is a national ultrasound competition in which residents demonstrate their skills and knowledge of point-of-care ultrasound in an exciting and educational format. They compete in front of hundreds of spectators in hopes of bringing home the SonoCup to their residency program.

"Typically about 80 teams from 80 different residency programs compete and faculty come to support and watch," Huang says. "We will have our own team of residents, Mitch Odom, Christ Hebert and Vivian Lam, competing this year."

The Houston Astros' José Altuve steps up to the plate on a 3-2 count, studies the pitcher and the situation, gets the go-ahead from third base, tracks the ball's release, swings ... and gets a single up the middle. Just another trip to the plate for the three-time American League batting champion.

Could a robot get a hit in the same situation? Not likely.

Altuve has honed natural reflexes, years of experience, knowledge of the pitcher's tendencies, and an understanding of the trajectories of various pitches. What he sees, hears, and feels seamlessly combines with his brain and muscle memory to time the swing that produces the hit. The robot, on the other hand, needs to use a linkage system to slowly coordinate data from its sensors with its motor capabilities. And it can't remember a thing. Strike three!

But there may be hope for the robot. A paper by University of Maryland researchers just published in the journal Science Robotics introduces a new way of combining perception and motor commands using the so-called hyperdimensional computing theory, which could fundamentally alter and improve the basic artificial intelligence (AI) task of sensorimotor representation -- how agents like robots translate what they sense into what they do.

"Learning Sensorimotor Control with Neuromorphic Sensors: Toward Hyperdimensional Active Perception" was written by computer science Ph.D. students Anton Mitrokhin and Peter Sutor, Jr.; Cornelia Fermüller, an associate research scientist with the University of Maryland Institute for Advanced Computer Studies; and Computer Science Professor Yiannis Aloimonos. Mitrokhin and Sutor are advised by Aloimonos.

Integration is the most important challenge facing the robotics field. A robot's sensors and the actuators that move it are separate systems, linked together by a central learning mechanism that infers a needed action given sensor data, or vice versa.

The cumbersome three-part AI system--each part speaking its own language -- is a slow way to get robots to accomplish sensorimotor tasks. The next step in robotics will be to integrate a robot's perceptions with its motor capabilities. This fusion, known as "active perception," would provide a more efficient and faster way for the robot to complete tasks.

In the authors' new computing theory, a robot's operating system would be based on hyperdimensional binary vectors (HBVs), which exist in a sparse and extremely high-dimensional space. HBVs can represent disparate discrete things -- for example, a single image, a concept, a sound or an instruction; sequences made up of discrete things; and groupings of discrete things and sequences. They can account for all these types of information in a meaningfully constructed way, binding each modality together in long vectors of 1s and 0s with equal dimension. In this system, action possibilities, sensory input and other information occupy the same space, are in the same language, and are fused, creating a kind of memory for the robot.

The Science Robotics paper marks the first time that perception and action have been integrated.

A hyperdimensional framework can turn any sequence of "instants" into new HBVs, and group existing HBVs together, all in the same vector length. This is a natural way to create semantically significant and informed "memories." The encoding of more and more information in turn leads to "history" vectors and the ability to remember. Signals become vectors, indexing translates to memory, and learning happens through clustering.

The robot's memories of what it has sensed and done in the past could lead it to expect future perception and influence its future actions. This active perception would enable the robot to become more autonomous and better able to complete tasks.

"An active perceiver knows why it wishes to sense, then chooses what to perceive, and determines how, when and where to achieve the perception," says Aloimonos. "It selects and fixates on scenes, moments in time, and episodes. Then it aligns its mechanisms, sensors, and other components to act on what it wants to see, and selects viewpoints from which to best capture what it intends."

"Our hyperdimensional framework can address each of these goals."

Applications of the Maryland research could extend far beyond robotics. The ultimate goal is to be able to do AI itself in a fundamentally different way: from concepts to signals to language. Hyperdimensional computing could provide a faster and more efficient alternative model to the iterative neural net and deep learning AI methods currently used in computing applications such as data mining, visual recognition and translating images to text.

"Neural network-based AI methods are big and slow, because they are not able to remember," says Mitrokhin. "Our hyperdimensional theory method can create memories, which will require a lot less computation, and should make such tasks much faster and more efficient."

MINNEAPOLIS - Vertigo is a form of severe dizziness that can result in a loss of balance, a feeling of falling, trouble walking or standing, or nausea. There is more than one type of vertigo, each with a different cause, and sometimes requiring different treatment. Now a proof-of-concept study has found that special goggles that measure eye movements during an episode of vertigo may help more accurately diagnose which type of vertigo a person has. The study is published in the May 15, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Vertigo can be a disabling condition, so an accurate diagnosis is important to effectively treat and stop the vertigo as soon as possible," said study author Miriam S. Welgampola, MD, PhD, of the University of Sydney in Australia and a member of the American Academy of Neurology. "Observing a person's eye movements during an episode can help make the diagnosis, but people don't always have an episode when they are at the doctor's office."

For the study, researchers gave participants a pair of video-oculography goggles that record the uncontrolled eye movements that accompany vertigo.

The study involved 117 people who had been previously diagnosed with one of three conditions that cause vertigo. Of the group, 43 people had Meniere's disease, an inner ear disorder that can affect hearing and balance, 67 had vestibular migraine that can cause vertigo but may not cause a headache, and seven had benign paroxysmal positional vertigo, one of the most common causes of vertigo, where a person's head movements trigger the episodes.

Researchers taught each participant how to use the goggles to record video of their eye movements at home whenever they had a vertigo episode. Eye movements that accompany vertigo are repetitive and uncontrolled, and the eyes can move side to side, up and down or around in circles.

For the majority of people with Meniere's disease who had fast horizontal eye movements, the goggles were able to diagnose the type of vertigo accurately with a sensitivity of 95 percent and a specificity of 82 percent. Sensitivity is the percentage of actual positives that are correctly identified as positive. Specificity is the percentage of negatives that are correctly identified. By comparison, audio tests for Meniere's disease have both a sensitivity and specificity of 91 percent.

The patterns of eye movements were more mixed for those with vestibular migraine. However, up and down, repetitive, uncontrolled eye movements had a high specificity of 93 percent, but a low sensitivity of 24 percent.

For those with benign paroxysmal positional vertigo, the sensitivity was 100 percent and the specificity was 78 percent.

"While further studies are needed in larger groups, providing people with a pair of goggles that they can easily use at home to record eye movement has the potential to help with vertigo diagnosis not only by a neurologist in a clinic, but also by physicians in an emergency room and physicians diagnosing patients remotely as well," said Welgampola.

Limitations of the study include that some participants did not feel well enough to wear the goggles when experiencing vertigo. Additionally, others did not wear them when they thought their vertigo was too mild. Also, some medications taken for vertigo may have influenced eye movement.

More studies are needed in larger groups of people.

Blood tests that track the amount of tumor DNA can - after only one month of drug therapy - detect how well treatment is working in patients with skin cancer, a new study finds.

Led by researchers from NYU School of Medicine and Perlmutter Cancer Center, the study takes advantage of the nature of cancer cells, which die and are replaced by new cells continuously as part of aggressive cancer growth. Tumor cells burst as they die, spilling their DNA into the bloodstream, where it can be measured by tests, enabling improved diagnosis and better targeting of treatment based on each individual tumor's DNA.

For the new study, researchers traced circulating tumor DNA or ctDNA for the cancer gene BRAF, a gene that plays a key role in many melanomas, the most deadly form of skin cancer. In the United States, more than 7,200 individuals are expected to die from metastatic melanoma in 2019, with BRAF mutations playing a role in nearly half of such diagnoses, according to the Skin Cancer Foundation.

"Our study offers firm evidence that tracking this genetic information may be helpful in identifying patients whose cancers shrink and who survive longer as a result of a particular drug regimen," says senior study investigator David Polsky, MD, PhD, the Alfred W. Kopf, MD, Professor of Dermatologic Oncology at NYU Langone Health.

For the study, being presented at the 2019 American Society of Clinical Oncology annual meeting on June 1 in Chicago, researchers analyzed blood samples from 345 male and female patients with stage III or IV melanoma, which had already spread from the skin to other organs, and who had BRAF mutations.

These patients could not be treated surgically and were part of a larger group of patients participating in a clinical trial of the drugs dabrafenib and trametinib, designed to target BRAF-mutated cancers.

Among the study’s key findings was that the tumor’s BRAF mutation could be detected by the new blood test in 93 percent of the patients before treatment started. In addition, the research team found that BRAF ctDNA levels were no longer detectable after one month of therapy in the 40 percent of patients who had a positive clinical outcome after targeted therapy (as measured by an average survival time of 28 months). By contrast, the 60 percent of patients who did not respond as well still had detectable ctDNA levels, and survived for an average of just 14 months.

Polsky and his colleagues say this test appears to be more revealing than the current standard test, which measures lactate dehydrogenase (LDH), an enzyme often elevated by melanoma, because fluctuations in LDH often do not accurately predict treatment success or failure.

The typical method of identifying disease progression for these melanoma patients is through CT scans every three months, but Polsky says the blood test in the current study, noted as the largest BRAF detection rate in patients' blood to date, suggests it may be helpful to doctors because these tests can be done more frequently and efficiently, and results could be available within a few days.

"If further testing proves successful, monitoring blood samples for BRAF could give us an early indication of whether or not we need to adjust a patient's treatment plan," says Polsky, dermatologist and director of the pigmented lesion service at NYU Langone.

Researchers next plan to test the efficacy of monitoring patient blood samples over longer periods of time, such as several months. They also hope to open a clinical trial to determine whether treatment decisions based on these test results improves patient survival.

A University of Bristol academic has succeeded where countless cryptographers, linguistics scholars and computer programs have failed - by cracking the code of the 'world's most mysterious text', the Voynich manuscript.

Although the purpose and meaning of the manuscript had eluded scholars for over a century, it took Research Associate Dr. Gerard Cheshire two weeks, using a combination of lateral thinking and ingenuity, to identify the language and writing system of the famously inscrutable document.

In his peer-reviewed paper, The Language and Writing System of MS408 (Voynich) Explained, published in the journal Romance Studies, Cheshire describes how he successfully deciphered the manuscript's codex and, at the same time, revealed the only known example of proto-Romance language.

"I experienced a series of 'eureka' moments whilst deciphering the code, followed by a sense of disbelief and excitement when I realised the magnitude of the achievement, both in terms of its linguistic importance and the revelations about the origin and content of the manuscript.

"What it reveals is even more amazing than the myths and fantasies it has generated. For example, the manuscript was compiled by Dominican nuns as a source of reference for Maria of Castile, Queen of Aragon, who happens to have been great aunt to Catherine of Aragon.

"It is also no exaggeration to say this work represents one of the most important developments to date in Romance linguistics. The manuscript is written in proto-Romance - ancestral to today's Romance languages including Portuguese, Spanish, French, Italian, Romanian, Catalan and Galician. The language used was ubiquitous in the Mediterranean during the Medieval period, but it was seldom written in official or important documents because Latin was the language of royalty, church and government. As a result, proto-Romance was lost from the record, until now."

Cheshire explains in linguistic terms what makes the manuscript so unusual:

"It uses an extinct language. Its alphabet is a combination of unfamiliar and more familiar symbols. It includes no dedicated punctuation marks, although some letters have symbol variants to indicate punctuation or phonetic accents. All of the letters are in lower case and there are no double consonants. It includes diphthong, triphthongs, quadriphthongs and even quintiphthongs for the abbreviation of phonetic components. It also includes some words and abbreviations in Latin."

The next step is to use this knowledge to translate the entire manuscript and compile a lexicon, which Cheshire acknowledges will take some time and funding, as it comprises more than 200 pages.

"Now the language and writing system have been explained, the pages of the manuscript have been laid open for scholars to explore and reveal, for the first time, its true linguistic and informative content."

An innovative use of instruments that measure the ocean near Antarctica has helped Australian scientists to get a clearer picture of how the ocean is melting the Antarctic ice sheet.

Until now, most measurements in Antarctica were made during summer, leaving winter conditions, when the sea freezes over with ice, largely unknown.

But scientists from IMAS and the CSIRO, supported by ACE CRC, the ARC-funded Antarctic Gateway Partnership and the Centre for Southern Hemisphere Oceans Research (CSHOR), developed a novel mission that allowed year-round measurements to be collected near the Totten Glacier, a fast-melting glacier in East Antarctica.

They used instruments known as ARGO floats that are typically designed to drift with ocean currents and measure ocean temperature and salinity profiles.

For this mission, however, the floats were designed to "park" on the sea floor between profiles so they stayed in the region and did not drift away, and vital data collected during ice-covered winter months were stored and uploaded via satellite later in ice-free conditions.

The study published in the journal JGR Oceans revealed for the first time that deep water driving melting at the base of the Totten Glacier is warmer and in a thicker layer during winter and autumn than during spring and summer.

Lead author Alessandro Silvano, from IMAS, said this means the Totten Glacier might melt more rapidly in winter than summer, and that summer measurements might under-estimate the flow of warm water to the ice shelf.

"We had a nervous wait during the first winter, wondering if the floats would survive the icy winter conditions after being parked on the rough sea floor for long periods," he said.

"When spring arrived and the sea ice started to melt we were very excited to see that the floats returned and transmitted the winter data.

"We immediately noticed that the ocean was warmer in autumn and winter than found in our previous summer measurements.
"The new measurements confirm that this part of East Antarctica is exposed to warm ocean waters that can drive rapid melt, with the potential to make a large contribution to future sea level rise.

"The floats also provided new measurements of ocean depth in the region, revealing a deep trough that allows warm water to approach the glacier year-round," Mr Silvano said.

CSIRO co-author Dr Steve Rintoul from CSHOR said the new measurements of ocean depth, temperature and salinity will help improve models used to predict the Antarctic's contribution to sea level rise.

"Crashing sensitive oceanographic instruments into the sea floor isn't generally recommended," he said.

"But these results show that profiling floats can be used in novel ways to measure the ocean near Antarctica, a critical blind-spot in the global ocean observing system.

"Much work remains to be done and more measurements are needed to assess the vulnerability of the ice shelf to changes in the ocean, including in the ocean beneath the floating Totten Glacier.

"New technologies, like the autonomous underwater vehicle (AUV) recently acquired by the University of Tasmania, will be needed to fill this gap," Dr Rintoul said.

Vanderbilt University paleontologists are looking into the evolutionary origins of the whistles and squeaks that dolphins and porpoises make - part of the rare echolocation ability that allows them to effectively navigate their dark environment.

The team, one of the first in the world to examine the ability's origins, used a small CT scanner to look inside a 30-million-year-old ear bone fossil from a specimen resembling Olympicetus avitus. This member of the toothed whale family, in a branch that died out before modern dolphins and porpoises appeared, lived in what is now the state of Washington. The CT scan revealed cochlear coiling with more turns than in animals with echolocation, indicating hearing more similar to the cloven-hoofed, terrestrial mammals dolphins came from than the sleek sea creatures they are today.

"The simple theory is that there was one origin for echolocation in dolphins, and we'd find it in their 30-million-year-old ancestor," said Rachel A. Racicot, who completed the research as a visiting scholar at Vanderbilt. "Now, we believe it didn't evolve just once in this lineage, but more than once and in more than one lineage - at least in xenorophids, which are extinct, and somewhere along the line to the Odontoceti crown group that still survives."

Because echolocation is useful for navigating dark waters, natural selection likely came into play with its development in the branch that survived, she said. The findings appear May 15 in The Royal Society journal Biology Letters.

Racicot will join Vanderbilt's Earth and Environmental Sciences Department after spending a year working in Germany. Her co-author, Assistant Professor of Earth and Environmental Sciences Simon A.F. Darroch, installed the CT scanner, which works the same way as those used in medicine and allows for internal examination of fossils without damaging them.

Learning echolocation's origins also can help preserve modern creatures that use it, Darroch said, by understanding how they're perceiving sound from ship engines, oil drills and other machinery. Confusion over those sounds may be causing mass stranding events, and solving the mystery could lead to methods of discouraging species such as the vaquita, a small porpoise on the brink of extinction in the Gulf of California, away from boats and nets.

"If we develop correlates for the shapes of the inner ear and how that corresponds to hearing frequencies, we can extrapolate those methods without capturing animals and bombarding them with sounds that don't work," Darroch said.

First, according to Racicot and Darroch, paleontologists will have to find and scan a much larger sampling of all the toothed whale group's ancestors and those of rare modern species.

In a records review of 290 people at risk for Alzheimer's disease, scientists at Johns Hopkins say they have identified an average level of biological and anatomical brain changes linked to Alzheimer's disease that occur three to 10 years -- some even more than 30 years -- before the disease's first recognizable symptoms appear.

"Our study suggests it may be possible to use brain imaging and spinal fluid analysis to assess risk of Alzheimer's disease at least 10 years or more before the most common symptoms, such as mild cognitive impairment, occur," says Laurent Younes, Ph.D., professor and chair of the Department of Applied Mathematics and Statistics at The Johns Hopkins University. A report of their findings was published online April 2 in Frontiers in Aging Neuroscience.

Younes cautions that brain changes vary widely in people, and that their research findings reflect an average level of such changes in a small group of research subjects. As a result, he says, the scientists cannot yet use them to draw any precise conclusions about brain changes in individual people. Nor, they say, are there any drug or other interventions yet known to slow or stop the disease process even if risk is identified early. But the work, he adds, could lead eventually to a test to determine an individual's relative risk for Alzheimer's disease and to guide the use of treatments when and if they are developed.

For the study, the scientists reviewed medical records collected from 290 people age 40 and older by the National Institutes of Health and the Johns Hopkins University School of Medicine as part of the BIOCARD project, an effort to develop predictors of cognitive decline. It is currently directed by Johns Hopkins neurologist Marilyn Albert, Ph.D.

Most of the 290 people had at least one first degree relative with dementia of the Alzheimer's disease type, putting them at higher than usual risk.

As part of the BIOCARD studies, scientists collected cerebrospinal fluid and performed MRI brain scans of study participants every two years between 1995 and 2005. They also conducted five standard tests of memory, learning, reading and attention annually from 1995 to 2013.

Because all 290 participants were cognitively normal when the study began, the scientists were able to track various biological and clinical features associated with Alzheimer's disease in the years leading up to the appearance of symptoms. By the time of their last appointment with the BIOCARD project, 209 study participants remained cognitively normal, and 81 were diagnosed with mild cognitive impairment or dementia due to Alzheimer's disease.

In the 81 people who developed cognitive problems or dementia, the Johns Hopkins team found subtle changes in cognitive test scores 11 to 15 years before the onset of clear cognitive impairment. They also found increases in the rate of change of a protein called Tau, which has long been considered a marker of Alzheimer's disease, in cerebrospinal fluid an average of 34.4 years (for t-tau, or total Tau) and 13 years (for a modified version called p-tau) before the beginning of cognitive impairment.

The online complaint system used by web giants like Google and Twitter is a 'Wild West' with evidence of abuse by complainants, according to a new study from Queen Mary University of London.

Despite this, the UK government is considering promoting similar systems to underpin parts of future web regulation, and the researchers believe this raises questions for its effectiveness.

Over one year, they observed more than 1 billion URLs being complained about, primarily with the intent of removing content.

They investigated the nature of various types of complaints that are issued to many web companies, also including Vimeo and Bing, which now allow any third party to file complaints. To date, there is little evidence regarding how these complaint procedures are handled, how successful they are, or who they are targeted against and by whom.

The study, which will be presented at The Web Conference 2019, shows that the top ten complainants dominate the entire system and generate hundreds of millions of complaints, or 41 per cent of all notices, mostly about copyright.

The majority of these are generated by a tiny set of hypergiants including Fox, NBC and copyright pursuit specialists Rivendell that issue complaints widely.

However, that leaves a large number of organisations sending a small number of complaints (fewer than 100) as the majority of senders just send a few notices, leaving a small minority to send a very large number.

Some complainants do not seem to take much care when sending complaints as they often send repeat complaints again and again, send complaints for URLs that do not exist, or send complaints for content already taken down.

For those receiving the complaints, this creates a huge overhead of sifting through these non-existent URLs and potentially crowds out smaller senders of complaints because of the sheer volume to deal with.

Dr Gareth Tyson, co-author of the study from Queen Mary University of London, said: "As the web grows, it is unclear how sustainable this complaint model is and at the moment it resembles something like the Wild West. It is unclear how effectively small organisations could handle this approach. Should the UK government, and other governments around the world, be adopting a similar system to underpin web regulation, or thinking of new approaches and tools to support the web? The answer is not yet clear."

It is also often the same websites that are repeatedly targeted as the top 1 per cent of sites accumulate 63 per cent of complaints. However, the researchers found this is very unstable because some complainants suddenly send aggressive bursts of complaints which then cease soon after.

Most of these include well know pirate video portals such as gorillavid, daclips, movpod, googlevideo.com (part of YouTube) and the website piratebay which is a BitTorrent portal.

The efficacy of these complaints vary a lot with many websites just ignoring them, while some tend to remove content and almost 20 per cent of all websites do not even have live domains anymore.

Although previous studies have looked at copyright notices, the researchers generalise across a number of different complaint types including defamation and court orders.

For the first time, they also show the dynamics between complainants and websites who generate negative attention from those people sending complaints.

Damilola Ibosiola, lead author of the study and a PhD candidate from Queen Mary University of London, said: "People often assume that the only reason content gets blocked is because an intermediate party like a government censors it. In reality, however, there is a huge ecosystem of organisations constantly exchanging complaints about the activities of others. This has far reaching implications for how the world wide web is structured, yet it is rarely seen."

Dr Gareth Tyson added: "Our study also sheds light on the efficacy of these various regulatory practices, and highlights both the use and misuse of web complaint mechanisms. We hope that the findings can lead to a better regulatory structure surrounding the takedown of illegal material from the web, and a better idea of what works. Importantly, we also hope that this can be used by those people generating complaints to better streamline their activities to avoid overwhelming recipients with many erroneous complaints."

Surface engineering of nanocarriers devotes considerable contribution to the field of biomedicine ranging from drug delivery to theranostic. Conventional chemical/physical approaches trend to use PEG functionalization, morphological control, and lipid modification, which allow nanocarriers participate various tasks in complex biological conditions. Although the in-vivo performance of nanocarries was improved by using these aforementioned methods, nanocarriers still suffer from drug delivery barrier caused by immune clearance, resulting in a low therapy efficacy. Furthermore, synthetic components of nanocarriers with undesired biocompatibility and biotoxicity also limits their biomedical applications. It is highly needed to develop biomimetic nanocarriers for the current drug delivery systems.

Recently, increase interest inspires that coating cell membranes on the surface of nanocarriers as a promising strategy can help address these issues. Cell membranes isolated from red blood cells are considered as the coating materials on the surface of nanocarriers. This novel bioimimetic hybrid system combines synthetic materials and naturally biological components, which breaks through the traditional concept of nanocarrier. By directly inheriting biological components of cell membrane (proteins, lipids, antigens), nanocarriers successfully achieve the immune-evasion and prolong the circulation time in the blood stream. To pursue functional diversity, some other cells, such as platelets, immune cells, cancer cells, and bacterium, contribute their membranes to cover nanocarriers for versatile properties (Image), including bioadhesion, target recognition, or deep tissue penetration. Compared with synthetic carriers, cell membrane-covered nanocarriers obviously improve their biocompatibility and get great efficiency to perform drug delivery, bioimaging, phototherapy, and detoxification. These above advantages indicate that cell membranes-inspired delivery systems will play an important role in the next-generation nanomedicine with extensive medical applications.

Prof. Junbai Li at Beijing National Laboratory for Molecular Sciences, CAS Key Lab of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry?Chinese Academy of Sciences, heads an expertise biomaterial team that develop a series of cell membrane-camouflaged nanocarriers for cancer therapy ranging from drug delivery to photothermal therapy as well as photodynamic therapy. A recent review article published in National Science Review, Prof. Junbai Li's group reviews recent progress of cell membranes-covered nanoparticles from biomaterials perspective, and demonstrate their unique advantages and highlight relevant biomedical applications. The appearance of this review will help researchers of interdisciplinary science to understand cell membrane coating materials, and further promote the development in this field.