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PHILADELPHIA - Chimeric antigen receptor (CAR) T cell therapy has been a game-changer for blood cancers but has faced challenges in targeting solid tumors. Now researchers from the Perelman School of Medicine at the University of Pennsylvania may have an alternative to T cell therapy that can overcome those challenges. Their research shows genetically engineering macrophages - an immune cell that eats invaders in the body - could be the key to unlocking cellular therapies that effectively target solid tumors. The team was able to show these CAR macrophages can kill tumors both in human samples in the lab and in mouse models. They published their proof-of-concept paper in Nature Biotechnology today.

The approach in this study is closely related to CAR T cell therapy, in which patient immune cells are engineered to fight cancer, but it has some key differences. Most importantly, it centers around macrophages, which eat invading cells rather than targeting them for destruction the way T cells do; while T cells are more like a game of Space Invaders, macrophages are like Pac-Man.

Macrophages also have another key difference from T cells in that they are the body's first responders to viral infections. This has historically presented challenges in trying to engineer them to attack cancer, since macrophages are resistant to infection by the standard viral vectors used in gene and cell therapy.

"We have known how to engineer T cells to do this for years, but the fact that macrophages are innately resistant to the viral vectors that we use in our CAR T cells presented a unique challenge, which we show here we were able to overcome," said the study's senior author Saar Gill, MD, PhD, an assistant professor of Hematology-Oncology and a member of Penn's Abramson Cancer Center.

In fact, this anti-viral property carried another unexpected benefit. Macrophages are generally among the first cells to be drawn in by cancer, and they are exploited to help tumors instead of eating them. However, the research team showed that when the viral vector is inserted, not only do these engineered macrophages express the CAR, they also transform into highly inflammatory cells. This transformation allows macrophages to resist being co-opted by tumors.

Researchers say CAR macrophages may also be able to stimulate the rest of the immune system as they attack, potentially opening the door to a greater immune response.

"Finding ways to draw the rest of the body's powerful immune system into the fight would mean an even greater impact than what a cellular therapy can do on its own, so our future research will include efforts to better understand this possibility and how we might be able to exploit it to kill cancer," said the study's first author Michael Klichinsky, PhD, who was a graduate student at Penn while he completed the work. This paper represents the culmination of his graduate career in Gill's lab. Klichinsky and Gill went on to co-found a company, Carisma Therapeutics, based on the CAR Macrophage approach.

CLEMSON, South Carolina -- Metal-organic frameworks (MOFs) are emerging multi-functional materials that are gradually finding their way out of the research labs and into a myriad of real-world applications. For example, MOFs can store dangerous gasses, catalyze chemical reactions, deliver drugs in controlled fashion, and may even be used in rechargeable batteries and solar cells.

A team of researchers from Clemson University's College of Science recently demonstrated that a novel double-helical MOF architecture, in a partially oxidized form, can conduct electricity that potentially makes it a next-generation semiconductor.

The team's findings are described in the paper titled "The Advent of Electrically Conducting Double-Helical Metal-Organic Frameworks Featuring Butterfly-Shaped Electron-Rich π-Extended Tetrathiafulvalene Ligands," which was published on March 18, 2020, as the cover article in Applied Materials & Interfaces, a journal published by the American Chemical Society.

MOFs consist of an array of metal ions connected by organic ligands. Atomically engineered with great precision, they possess highly ordered repetitive units that usually constitute porous structures.

Since the first MOF was constructed over 20 years ago, researchers worldwide have created more than 20,000 different MOFs made with a variety of metals and organic ligands.

According to chemistry associate professor Sourav Saha, most existing MOFs are made of linear or planar ligands. However, Saha and his team introduced a butterfly-shaped, convex ligand into a MOF, which resulted in a novel double helical structure capable of conducting electricity once partially oxidized by guest iodine molecules.

"This butterfly-shaped extended tetrathiafulvalene (ExTTF) ligand has been known to the chemistry community for a while, but it hadn't been incorporated into a MOF before," Saha said. "By introducing it into a double helical MOF, we could create unique S-shaped charge transport pathways that run along the seams of the neighboring strands. When the ExTTF ligands on one side of each double helical strand is oxidized by iodine and those on the other remain neutral, they form intermolecular charge-transfer chains along the seams. Electrons can flow along this pathway in an intermolecular fashion, making the MOF more conductive."

Chemistry graduate student Monica Gordillo in Dr. Saha's research group synthesized the double helical MOF via a solvothermal method, by mixing a zinc salt and the ExTTF ligand in certain proportion. She then heated the mixture in an oven at about 65 degrees Celcius for 24 hours.

"We got these beautiful plate-like orange crystals," Gordillo said. "To achieve this exciting material, we adjusted the conditions of this synthesis, changing the ratio of solvents, ratio of ligands to the metal (zinc) ions and the temperature."

To create a charge transport pathway capable of conducting electricity, she diffused iodine vapor into the porous MOF, causing one strand to become electron deficient while the other remained electron rich.

Electrically conducting MOFs may have some advantages over conventional inorganic semiconductors made from silicon, gallium, or arsenide, which are ubiquitous in logic gates, memory chips, and other electronics applications. For example, conventional semiconductors are synthesized at temperatures between 500 and 1,000 degrees Celsius.

"On the other hand, MOFs can be made in a more energy efficient way than inorganic semiconductors," Saha said. "They can be synthesized anywhere between room temperature and 150 degrees Celsius, while maintaining the highly ordered crystalline structure that conventional semiconductors have."

Saha and his team plan to continue to develop new MOF architectures with different geometries, compositions, and functions that can have applications in future electronics and energy conversion and storage devices.

ANN ARBOR--A small, inexpensive and highly accurate gyroscope, developed at the University of Michigan, could help drones and autonomous cars stay on track without a GPS signal.

"Our gyroscope is 10,000 times more accurate but only 10 times more expensive than gyroscopes used in your typical cell phones. This gyroscope is 1,000 times less expensive than much larger gyroscopes with similar performance," said Khalil Najafi, the Schlumberger Professor of Engineering at U-M and a professor of electrical engineering and computer science.

Most smartphones contain gyroscopes to detect the orientation of the screen and help figure out which way we're facing, but their accuracy is poor. They're the reason why phones often incorrectly indicate which direction a user is facing during navigation.

It doesn't matter much to a human on the street or behind the wheel, but a driverless car could get lost quickly with a loss of GPS signal. Inside their backup navigation systems, autonomous vehicles currently use high-performance gyroscopes that are larger and much more expensive.

"High-performance gyroscopes are a bottleneck, and they have been for a long time. This gyroscope can remove this bottleneck by enabling the use of high-precision and low-cost inertial navigation in most autonomous vehicles," said Jae Yoong Cho, an assistant research scientist in electrical engineering and computer science.

Better backup navigation equipment could also help soldiers find their way in areas where GPS signals have been jammed. Or in a more mundane scenario, accurate indoor navigation could speed up warehouse robots.

The device that enables navigation without a consistent orienting signal is called an inertial measurement unit. It is made up of three accelerometers and three gyroscopes, one for each axis in space. But getting a good read on which way you're going with existing IMUs is so pricey that it has been out of range, even for equipment as expensive as autonomous vehicles.

The key to making this affordable, small gyroscope is a nearly symmetrical mechanical resonator. It looks like a Bundt pan crossed with a wine glass, made one centimeter wide. As with wine glasses, the duration of the ringing tone produced when the glass is struck depends on the quality of the glass--but instead of being an aesthetic feature, the ring is crucial to the gyroscope's function. The complete device uses electrodes placed around the glass resonator to push and pull on the glass, making it ring and keeping it going.

"Basically, the glass resonator vibrates in a certain pattern. If you suddenly rotate it, the vibrating pattern wants to stay in its original orientation. So, by monitoring the vibration pattern it is possible to directly measure rotation rate and angle," said Sajal Singh, a doctoral student in electrical and computer engineering who helped develop the manufacturing process.

The way that the vibrating motion moves through the glass reveals when, how fast and by how much the gyroscope spins in space.

To make their resonators as perfect as possible, Najafi's team starts with a nearly perfect sheet of pure glass, known as fused-silica, about a quarter of a millimeter thick. They use a blowtorch to heat the glass and then mold it into a Bundt-like shape--known as a "birdbath" resonator since it also resembles an upside-down birdbath.

Then, they add a metallic coating to the shell and place electrodes around it that initiate and measure vibrations in the glass. The whole thing is encased in a vacuum package, about the footprint of a postage stamp and half a centimeter tall, which prevents air from quickly damping out the vibrations.

Irvine, Calif., March 23, 2020 - East Antarctica's Denman Glacier has retreated 5 kilometers, nearly 3 miles, in the past 22 years, and researchers at the University of California, Irvine and NASA's Jet Propulsion Laboratory are concerned that the shape of the ground surface beneath the ice sheet could make it even more susceptible to climate-driven collapse.

If fully thawed, the ice in Denman would cause sea levels worldwide to rise about 1.5 meters, almost 5 feet. With this sobering fact in mind, the UCI and NASA JPL scientists have completed the most thorough examination yet of the glacier and surrounding area, uncovering alarming clues about its condition under further global warming.

The team's assessment is the subject of a paper published today in the American Geophysical Union journal Geophysical Research Letters.

"East Antarctica has long been thought to be less threatened, but as glaciers such as Denman have come under closer scrutiny by the cryosphere science community, we are now beginning to see evidence of potential marine ice sheet instability in this region," said co-author Eric Rignot, chair, Donald Bren Professor and Chancellor's Professor of Earth system science at UCI.

"The ice in West Antarctica has been melting faster in recent years, but the sheer size of Denman Glacier means that its potential impact on long-term sea level rise is just as significant," he added.

According to the study, Denman Glacier experienced a cumulative mass loss of 268 billion tons of ice between 1979 and 2017.

Using radar interferometer data from the Italian Space Agency's COSMO-SkyMed satellite system, the researchers more precisely determined Denman's grounding line, the point at which the ice leaves the land and begins to float in the ocean.

"Differential synthetic aperture radar interferometer data from 1996 to 2018 showed us a marked asymmetry in the grounding line retreat at the ice sheet's land-sea interface," said lead author Virginia Brancato, a postdoctoral fellow with NASA JPL who was a postdoctoral scholar at UCI when the study was conducted.

Denman's eastern flank is protected from retreat by a subglacial ridge. But Brancato said that the western flank, which extends roughly 4 kilometers, is characterized by a deep and steep trough with a bed slope conducive to accelerated retreat.

"Because of the shape of the ground beneath Denman's western side, there is potential for rapid and irreversible retreat, and that means substantial increases in global sea levels in the future," she said.

In December, Nature Geoscience published a paper on the BedMachine Antarctica project led by Mathieu Morlighem, UCI associate professor of Earth system science, which revealed that the trough beneath Denman Glacier extends 3,500 meters below sea level, making it the deepest land canyon on Earth.

The UCI and NASA JPL scientists report in the Geophysical Research Letters paper that the bed configuration of Denman is unique in Antarctica's eastern sector. Other major glaciers, such as Totten and Moscow University, feature prograde beds that slope down in the flow direction, providing some measure of stability, Rignot said.

Tracking the state of the floating extension of Denman Glacier, a 24,000-square-kilometer mass that includes the Shackleton Ice Shelf and Denman ice tongue, will be especially important, he added. The researchers used the German Aerospace Center's TanDEM-X satellite in combination with data from COSMO-SkyMed to assess the melt rate of the floating sea ice, learning that the Denman ice tongue has shed mass at a rate of about 3 meters per year, above average compared to other East Antarctic ice shelves.

"We need to collect oceanographic data near Denman and keep an eye on its grounding line," Rignot said. "The Italian COSMO-SkyMed satellite system is the only tool for us to monitor grounding line conditions in this sector of Antarctica, and we are fortunate to have on our team Dr. Brancato, who is skilled in extrapolating the data to give us the precise and up-to-date information we require."

WOODS HOLE, Mass. - Revealing yet another super-power in the skillful squid, scientists have discovered that squid massively edit their own genetic instructions not only within the nucleus of their neurons, but also within the axon -- the long, slender neural projections that transmit electrical impulses to other neurons. This is the first time that edits to genetic information have been observed outside of the nucleus of an animal cell.

The study, led by Isabel C. Vallecillo-Viejo and Joshua Rosenthal at the Marine Biological Laboratory (MBL), Woods Hole, is published this week in Nucleic Acids Research.

The discovery provides another jolt to the "central dogma" of molecular biology, which states that genetic information is passed faithfully from DNA to messenger RNA to the synthesis of proteins. In 2015, Rosenthal and colleagues discovered that squid "edit" their messenger RNA instructions to an extraordinary degree - orders of magnitude more than humans do -- allowing them to fine-tune the type of proteins that will be produced in the nervous system.

"But we thought all the RNA editing happened in in the nucleus, and then the modified messenger RNAs are exported out to the cell," says Rosenthal, senior author on the present study. "Now we are showing that squid can modify the RNAs out in the periphery of the cell. That means, theoretically, they can modify protein function to meet the localized demands of the cell. That gives them a lot of latitude to tailor the genetic information, as needed." The team also showed that messenger RNAs are edited in the nerve cell's axon at much higher rates than in the nucleus.

In humans, axon dysfunction is associated with many neurological disorders. Insights from the present study could accelerate the efforts of biotech companies that seek to harness this natural RNA editing process in humans for therapeutic benefit.

Scientists from Tel Aviv University and The University of Colorado at Denver collaborated with MBL scientists on the study.

Previously, Rosenthal and colleagues showed that octopus and cuttlefish also rely heavily on mRNA editing to diversify the proteins they can produce in the nervous system. Together with squid, these animals are known for strikingly sophisticated behaviors, relative to other invertebrates.

Irvine, Calif., March 23, 2020 - Researchers at the University of California, Irvine have shown that they can give cells a short-term boost of energy through mitochondrial transplantation. The team's study, published today in the Journal of the American Heart Association, suggests that mitochondrial transplantation could one day be employed to cure various cardiovascular, metabolic and neurodegenerative disorders - and even offer a new approach to the treatment of cancer.

"Mitochondria are the engines that drive many activities performed by our cells," said first author Paria Ali Pour, a UCI Ph.D. candidate in biomedical engineering. "If these organelles are mutated or deemed dysfunctional, the clinical manifestations are devastating, so we decided to study the intracellular consequences of mitochondrial transplantation and determine whether it would be a viable method for mitigating these adverse situations and helping patients."

There have been prior attempts to use mitochondrial transplantation in the form of direct injection to the heart muscle in infants with end-stage heart disease, but the UCI study is the first to seek data on the precise outcomes of mitochondrial transplantation at the cellular and subcellular levels. The JAHA article outlines the researchers' successful endeavor to achieve mitochondrial transplantation and how they systematically quantified its ability to boost cellular energy.

For the experiments, Ali Pour first isolated mitochondria by differential centrifugation, followed by transplantation through coincubation. Once the mitochondria had settled in their new host cells, she performed metabolic flux analysis to measure two key parameters: the oxygen consumption rate and the extracellular acidification rate, which provide important information about cellular metabolism and how well the cells are consuming/producing energy. The analyses were conducted at two, seven, 14 and 28 days.

"This is essentially a technique for studying how much oxygen is being consumed and protons emitted, or the total acidification rate, as the mitochondria produce adenosine triphosphate, the fuel for our cells," Ali Pour said. "Metabolic flux analysis is a comprehensive way to evaluate bioenergetics indices - the mechanisms by which cells process nutrients into energy and how well they do this. It helps us understand and make decisions about how mitochondrial transplantation affects cellular bioenergetics and metabolism."

She said the endosymbiosis origin of mitochondria is what inspired their work.

"Billions of years ago, mitochondria were prokaryotic bacteria that came into close contact with our ancestral eukaryotes. At that time, they were completely autonomous - to this day, mitochondrial DNA is separate and different from the genetic code in our cells' nuclei - but now they're semiautonomous," Ali Pour said. "That led us to hypothesize that if cells freely adopted mitochondria ages ago, it should - theoretically - be possible to also achieve this in a directed manner."

Her doctoral adviser and the paper's lead author, Dr. Arash Kheradvar, a UCI professor of biomedical engineering and medicine, said this is exactly what she succeeded in doing. "Paria was able to show in a definitive way, for the first time, that it is possible to control cell bioenergetics by changing the content of the mitochondria in a cardiomyocyte," Kheradvar said.

A key part of the team's experiments was to transplant healthy mitochondria from skeletal muscle cells into cardiomyocytes of a different breed (nonautologous) to focus on questions specifically related to cell bioenergetics. The studies confirmed that cellular bioenergetics improves in the host cells two days after transplantation, but this supercharged state diminishes later on.

"Regarding the viability of mitochondrial transplantation in different cell lines, we've done a lot of variations, including work with skeletal muscle cells, T-cells and cardiomyocytes," Ali Pour said. "We even tested the feasibility of transplanting mitochondria from rat cells to commercially available human cells, in our lab, to see if there's a mechanism that prevents such a procedure; we found that transplanting mitochondria between different species is also possible."

Next, the team plans to investigate whether the internalized mitochondria establish signaling with the cell's nucleus and whether they'll be adopted by the host on a long-term basis.

"We took a very cautious and fundamental approach with this project, because these cellular procedures, as a potential biotherapy, can have unknown and possibly grave consequences," Kheradvar said. "We didn't want to rush into human experimentation without knowing all of the potential ramifications in terms of safety and efficacy. Although we have a few hypotheses, nobody firmly knows what's happening when these mitochondria are introduced inside the cell - or whether there will be side effects. There are a lot of unanswered questions that need to be addressed."

Tsukuba, Japan - Mammals experience rapid eye movement (REM) and non-REM (NREM) sleep. While the hypothalamus and brainstem are known to be a critical regulators of sleep, the precise mechanism is not fully understood. New work in mice has found that a widely distributed network of neurotensinergic neurons regulates NREM sleep, which also implicates a critical role of the neuropeptide neurotensin.

A normal sleep architecture is crucial for physical and cognitive health, and disruption of REM/NREM sleep can therefore have serious consequences. While several brain areas including the hypothalamus are known to be essential for NREM sleep, comparatively little is known about how the brainstem controls NREM sleep. Previous work has found that a subregion of the brainstem, the sublaterodorsal tegmental nucleus (SubLDT), regulates both REM and NREM sleep. Researchers at the University of Tsukuba therefore targeted this area to identify NREM sleep-promoting neurons, and found that a wide network of neurotensin-producing neurons is involved in NREM sleep regulation. The article was published in Current Biology last month.

"Using microarray analyses, we measured the expression levels of several genes in the mouse SubLDT," says Associate Professor Yu Hayashi, corresponding and last author of the study. "A subset of these SubLDT neurons had a high, selective expression of the gene Nts, which encodes the neuropeptide neurotensin. Artificial activation of these SubLDT neurons promoted NREM sleep, which confirmed the role of Nts-expressing neurons in NREM sleep."

NREM sleep-promoting neurons were also found in three other brainstem structures that have not previously been proven to be involved in sleep regulation (the dorsal deep mesencephalic nucleus, periaqueductal gray, and medial vestibular nucleus). Neurons in these regions also expressed Nts. Furthermore, direct administration of neurotensin itself induced NREM sleep-like brain activity.

"Our findings not only provide insights about brainstem involvement in NREM sleep promotion, but also highlight the key role of neurotensin," says Mitsuaki Kashiwagi, first author. "It will be interesting to see whether Nts-expressing neurons contribute to the co-ordination between sleep and other known functions of neurotensin signaling, such as pain and metabolism. The response of Nts-expressing neurons also differed according to the time of day, so the influence of the circadian rhythm on these neurons should be studied."

More broadly, these results could tell us something about the evolution of the complex sleep architecture of mammals. Future work could examine whether similar Nts¬-expressing neurons are also present in vertebrates, which do not experience REM and NREM sleep.

LOS ALAMOS, N.M., March 20, 2020 -- Researchers at Los Alamos National Laboratory are reinventing the mirror, at least for microwaves, potentially replacing the familiar 3-D dishes and microwave horns we see on rooftops and cell towers with flat panels that are compact, versatile, and better adapted for modern communication technologies.

"Our new reflectors offer lightweight, low-profile alternatives to conventional antennas. This is a potential boon for satellites, where minimizing weight and size is crucial," said Abul Azad, of the MPA-CINT group at Los Alamos National Laboratory. "The panels could be easily incorporated onto surfaces of buildings or terrestrial vehicles as well."

Most reflectors are reciprocal: in the case of a bathroom mirror, for example, if you can see someone reflected in it, they can see you too. The new reflector design breaks reciprocity, effectively turning it into a one-way mirror.

The flat-panel reflector can be controlled electronically, which means its characteristics can be reconfigured on the fly. This opens the window for beam steering, customized focusing, and other functions that are difficult to achieve with conventional antenna designs. Miniaturized versions could improve chip-based circuitry by ensuring that signals go only to the intended components and don't lead to inadvertent signals in other parts of the circuit, a problem that chip designers often have to worry about.

The reflectors are composed of an array of finely structured electronic components on a planar surface. Applying signals to the components allows the 2-D reflector to perform much like a 3-D antenna, and in some cases do things no conventional antenna could do. This sort of a device is known as a "metasurface" because its characteristics can be electronically changed to act in different ways without modifying the physical shape of the surface.

By applying electrical signals to the reflector components, the researchers managed to modulate the metasurface to control the direction and frequency of reflected light. The nonreciprocal response of the reflector can help prevent antennas from picking up echoes from their outgoing broadcasts and protect delicate circuitry from powerful, potentially damaging incoming signals.

"We have demonstrated the first dynamic metasurface capable of achieving extreme non-reciprocity by converting microwaves into plasmons, which are electric charge waves on the reflector's surface," said Diego Dalvit, of the T-4 group at Los Alamos. "This is key to controlling the way the reflectors function."

The new Los Alamos reflector platform opens exciting opportunities in various applications, including adaptive optics that can account for distortions that disrupt signals, one-way wireless transmission, and novel antenna designs.

A range of information is collated through a simple framework that will help marine scientists to design more accurate experiments that will better help them understand the projected impact of global warming on marine life.

Understanding the consequences of rising carbon dioxide (CO2) levels and global warming for marine life requires complex experiments that can assess the responses of biota to different environmental scenarios. Experiments need to be able to precisely represent future CO2 levels and temperature if they are to accurately predict the potential impact on different species throughout the world's oceans.

Nathan Geraldi, Carlos Duarte and colleagues at KAUST's Red Sea Research Center recently noted that some published marine research papers did not match up to the CO2 level predictions outlined in the reports from the Intergovernmental Panel on Climate Change (IPCC). This prompted the team to investigate further.

They outline several shortcomings in current scientific knowledge. Although some data exists for the impact of rising CO2 and accompanying warming in the oceans, it is stored in disparate locations and is not accessible through a central database. Further, the IPCC figures for CO2 levels and predicted temperature rises relate predominately to the atmosphere and land surface, rather than to marine environments. Overall, the oceans grow warmer slower than the land, and this should be factored into "future ocean" studies. Also, the IPCC regional projections currently exclude the polar regions, despite the fact that the Arctic is now warming faster than the global average.

"Predicting the responses of marine organisms to future ocean conditions remains challenging, but it is necessary to inform potential risks and impacts," says Duarte. "Experiments mimicking the conditions expected in the future are often used to quantify and assess these responses. However, the Achilles heel of this approach is that the experimental variables are often poorly informed, resulting in misrepresentations."

"There is currently no straightforward way for researchers to select future levels of CO2 and temperature when running experiments on marine life," explains Geraldi. "Current and future conditions in any given region are variable and depend on many factors. Knowing that researchers need to simplify the natural variability, we wanted to provide a framework that would guide them in selecting appropriate CO2 and temperature levels for their studies."

Warming predictions depend on CO2 emissions, and local conditions--for example, geochemistry and vegetation type--can impact CO2 levels for a given area. However, it is very expensive for individual research teams to continuously monitor local and regional CO2 levels.

The KAUST team focused on coral reef regions as a case study for their framework, largely because their responses to global change have been extensively studied in recent years. "Coral reefs are seen as the 'canary in the coal mine' in terms of reflecting impacts of warming and ocean acidification on marine lifeforms," notes Geraldi.

The team assimilated data from the IPCC reports, together with detailed information gathered from studies on coral reefs around the world. The resulting datasets will enable researchers to select more accurate CO2 predictions for their given region at any specific point in the next hundred years. The team also summarized current uncertainties in CO2 emission trajectories and highlighted the challenges of predicting the sensitivity of different ecosystems and organisms to ocean acidification and warming.

If used widely, the team anticipates that their framework will provide a strong base to help improve the robustness and reproducibility of the growing body of research in different marine environments.

"The strength of our framework is its simplicity, but this is also a limitation given that both temperature and CO2 vary across space and time," says Geraldi. "Under optimal conditions, researchers would have the resources to characterize local fluctuations in these variables so that experiments can mimic local conditions. Ultimately, new studies can feed into databases and improve predictions still further."

The team also notes that their framework could feasibly also be applied to terrestrial and freshwater ecosystems.

New research reveals rising rates of liver cancer around the world, despite advances aimed at preventing the disease. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS).

To obtain trends and estimates of liver cancer by age, sex, region, and cause, Xingdong Chen, MD, PhD, of Fudan University in China, and his colleagues examined 1990-2017 data from the Global Burden of Disease Study pertaining to 195 countries and territories.

Globally, liver cancer cases diagnosed before the age of 30 years decreased from 17,381 in 1990 to 14,661 in 2017, but they increased in people aged 30-59 years and 60 years and older from 216,561 and 241,189 in 1990 to 359,770 and 578,344 in 2017, respectively. When applying age adjustments (to allow populations to be compared when the age profiles of the populations are different), the team found that the incidences of liver cancer diagnosed before age 30 years and from 30-59 years decreased in both sexes, whereas in older adults, rates increased in males and remained stable in females. Compared with women, men had a more dramatic increase in liver cancer diagnosed at aged 60 years and older and a milder decrease in cases diagnosed at 30-59 years.

Decreases seen in younger adults were largely ascribed to hepatitis B vaccinations (since the hepatitis B virus can cause liver cancer) and were consistent in most regions except in developed countries, in which liver cancer rates increased irrespective of sex and age. Liver cancer caused by non-alcoholic fatty liver disease, or buildup of fat in the liver, increased by the greatest magnitude in most regions.

"Our findings suggest the lack of attention for older people in current liver cancer prevention efforts and highlight the emerging concern of obesity as a risk factor for liver cancer," said Dr. Chen. "Liver cancer prevention strategies in both developing and developed countries should be tailored and updated."

In a recent paper in the open-access journal Neotropical Biology and Conservation, a group of Brazilian scientists from the Federal University of Viçosa (Brazil) published ten different defensive behaviours for the False Coral Snake (Oxyrhopus rhombifer), seven of which are registered for the first time for the species. One of these is reported for the first time for Brazilian snakes.

Evolution shaped anti-predator mechanisms in preys, which can be displayed either with avoidance or defensive behaviours. The current knowledge about such mechanisms are still scarce for many snake species, but it is constantly increasing over the last years. These data are helpful for better understanding of the species ecology, biology and evolution.

The False Coral Snake (O. rhombifer) is a terrestrial snake species with a colouration like the true coral snake. The species has a wide geographic distribution, occurring in Argentina, Paraguay, Uruguay, Bolivia and all Brazilian biomes. Among its previously known anti-predator mechanisms, this species has already shown cloacal discharge, body flattening, struggling, erratic movements and hiding the head.

However, these behaviours were only a small part of what this species is capable of doing to defend itself! In November 2017, a juvenile male captured in the Atlantic Forest of southeastern Brazil was observed under laboratory settings, where the scientists would simulate a predation attempt with an increasing threat level.

"We released the snake on to the laboratory bench and let it notice our presence. The animal remained motionless at first, then performed a pronounced dorsoventral flattening of the anterior part of the body, raised its tail, adopted an S-shaped posture, raised the first third of the body and performed brief body vibrations. Then we approached the snake, which remained with the same posture and body vibrations. When we touched the animal (not handling), it remained with the S-shaped posture, keeping the first third of the body elevated and the dorsoventral flattening (however, less accentuated) and started to display erratic movements, false strikes and locomotor escape. When handled, the snake only struggled," shares the lead scientist Mr. Clodoaldo Lopes de Assis.

Amongst ten recorded behaviour types only three were among those already registered for this species. Since defensive responses in snakes decrease as body size increases, juveniles exhibit a broader set of defensive behaviour than adults. Because of that, some types of behaviour described in this study might be explained either by physical constraints or stage of development of the individual.

Some types of behaviour resemble the ones of true coral snakes of the genus Micrurus, a group of extremely venomous snakes. Thus, this similarity may be linked with the mimicry hypothesis between these two groups, where harmless false coral snakes take advantage of their similar appearance to the true coral snakes to defend themselves.

Another type of anti-predation mechanism shown -- body vibrations -- is yet an unknown behaviour for Brazilian snakes and has been recorded for the first time. This type of behaviour is difficult to interpret, but could represent a defensive signal against non-visually orientated predators.

Finally, defensive strategies of the specimen differed according to the threat level imposed: starting from discouraging behaviour up to false bites, erratic movements and locomotor escape."O. rhombifer may be capable of recognising different threat levels imposed by predators and adjusting its defensive behaviour accordingly," highlights Mr. Clodoaldo Lopes de Assis.

"Through such simple laboratory observations we can get a sense of how Brazilian snakes are yet poorly known regarding their natural history, where even common species like the false coral snake O. rhombifer can surprise us!" Mr. Clodoaldo Lopes de Assis adds in conclusion.

The ability to accurately monitor drug levels and biological molecules inside patients in real time has remained largely elusive.

Most of the implantable monitors invented so far rely on high tech and expensive detectors such as CT scans or MRI. Using ultrasound - which is cheap and portable - as a means to track a disease state as in response of a tumour to a new drug or the risk of a heart attack with the rise of a diagnostic protein called troponin has always been more a Blue Sky than reality.

Now Melbourne, Australia researchers have developed the first biosensor that can be used in vivo, inside a body, able to emit signals that can be detected by common ultrasound scanners.

The technology - published today in the journal ACS Sensors - has been granted an international provisional patent.
The team led by Dr Simon Corrie and Dr Kristian Kempe, from the ARC Centre of Excellence in Bio-Nano Science and Monash University in Australia, has developed a nanoparticle that alters its stiffness in response to pH changes in the body, with these changes picked up by ultrasound.

To date ultrasound imaging uses what is a called a contrast using gas-filled microbubbles. However according to Dr Corrie these last only 10-20 minutes making long term tracking within a body impossible.

The new technology which was developed with colleagues at Monash University and the Baker Heart and Diabetes Institute, can be inserted deep into the tissues and measure biomarkers such as, pH (as a measure of whether a tumour is shrinking following chemotherapy) and in the near future more complex markers such as oxygen (as an indicator of stroke injury) or disease-related proteins.

According to Dr Corrie the advantage of the technology is that, eventually, it will be able to be "read" by "something as simple as a mobile phone which can currently record ultrasound, making it able to monitor patients in remote areas, without the need for big hospital labs," he said.

The technology has been tested in an animal model to detect changes in pH levels. It will now be tested in an animal models of disease to determine whether it can accurately monitor rapidly changing pH levels, initially focussing on cancer and stroke. The goal, according to Dr Corrie, is to give clinicians the power of being able to have a patient sit in a chair and, as they are infusing the drugs, using commonly available ultrasound to monitor drug levels or organ response in real-time, adjusting dosages as a function of the patient's needs.

The world's animal distribution map will need to be redrawn and textbooks updated, after researchers discovered the existence of 'Australian' species on Christmas Island.

The University of Queensland's Professor Jonathan Aitchison said the finding revises the long-held understanding of the location of one of biology and geography's most significant barriers - the Wallace line.

"The Wallace line - named after its discoverer Alfred Russel Wallace - delineates major biological division separating the species with Asian origins from those with Australasian ones," Professor Aitchison said.

"It runs along the narrow seaways separating Bali from Lombok, and Borneo from Sulawesi.

"To the west are the tigers, elephants, rhinoceroses and orang-utans of Eurasia and to the east, the marsupials and monotremes that are synonymous with Australia."

Working 1000 kilometres west of the conventional trace of Wallace line, on Christmas Island, Professor Aitchison and his colleagues, Dr Jason Ali from the University of Hong Kong and Professor Shai Meiri from the University of Tel Aviv, noted species with Australasian origins.

"Unexpectedly, half of Christmas Island's land mammal and land reptile species - two rats, two skinks and one gecko - have a genetic heritage to Australia's side of the divide," Dr Ali said.

"It was a highly surprising discovery.

"The ancestors of these species would have most likely have been washed over on uprooted trees of vegetation mats and transported in by a major oceanic current known as the Indonesian Throughflow.

"The Indonesian Throughflow is part of the global heat conveyor belt, and follows deeper waters that delineate the Wallace line.

"It's caused by the westernmost Pacific Ocean surface topography being slightly higher than its Indian Ocean counterpart.

"That's right - it's a little mind-bending - but the 'sea-level' varies slightly in different parts of the world."

Professor Aitchison said the species' journey must have occurred within the last five million years, as this is when Christmas Island emerged to form a new landmass.

"Christmas Island existed as a coral atoll from about 40 to 17 million years ago," Professor Aitchison said.

"But in response to a tectonics phenomenon originally described by Darwin, it subsided beneath the ocean surface and disappeared.

"It re-surfaced only five million years ago thanks to some flexing tectonic plates - 300 to 350 kilometres to the south of where it is now located - from then on land plants and animals could begin to establish new populations.

"Christmas Island is a strange and unique place, not just because of its geological history, but also its biological history.

"We're excited to see what other weird and wonderful discoveries are ahead."

Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.

A medical imaging technique known as PSMA PET/CT that provides detailed body scans while detecting levels of a molecule associated with prostate cancer could help doctors better tailor treatments for their patients, by determining the extent of disease spread at the time of diagnosis, a randomised controlled trial involving 300 patients in Australia published in The Lancet journal has found.

The approach combines two imaging technologies - positron emission tomography (PET) and computed tomography (CT) - and is almost one third more accurate than standard imaging at pinpointing the spread of prostate cancer throughout the body. PSMA PET/CT proved to be 92% accurate compared with only 65% accuracy with standard imaging.

Although the study did not assess whether the scans had any effect on patient survival, the researchers say this approach could improve outcomes by helping doctors decide whether to offer a localised treatment, such as surgery or radiotherapy, or to use more advanced treatments to treat the whole body if the cancer has already spread.

Costs associated with PET/CT vary by geographical area and the researchers caution that a full economic analysis will be critical for determining the feasibility of widespread use. Nevertheless, they recommend a review of current clinical guidelines and for PSMA PET/CT to replace the use of conventional imaging where possible for men with high risk prostate cancer.

Prostate cancer is commonly treated by surgery to remove the prostate or intensive radiotherapy to target the tumour. If there is a high risk the cancer may have spread to other parts of the body, patients may be offered medical imaging - typically CT and bone scans - to help doctors determine if additional treatments are needed.

Study lead Professor Michael Hofman of the Peter MacCallum Cancer Centre, Australia, said: "Taken together, our findings indicate that PSMA-PET/CT scans offer greater accuracy than conventional imaging and can better inform treatment decisions. We recommend that clinical guidelines should be updated to include PSMA PET/CT as part of the diagnostic pathway for men with high risk prostate cancer." [1]

Researchers sought to investigate if a molecular imaging approach could help doctors better define the extent of disease at the time of diagnosis. This approach involves giving patients a radioactive substance that detects a molecule called Prostate Specific Membrane Antigen (PSMA), which is found at high levels on prostate cancer cells. They then undergo a PET/CT scan. The CT scan produces detailed images of the body's organs and structures, while the PET scan lights up areas where PSMA is present at high levels, indicating the presence of prostate cancer cells.

The study involved 300 men recruited to ten sites across Australia. All of the men had been diagnosed with prostate cancer, confirmed by tests on prostate tissue samples, and were deemed to be at high risk of having aggressive disease. The men were randomly assigned to receive either conventional CT and bone scans (152 patients) or PSMA-PET/CT (148 patients). Men then swapped over and were given the scans using the alternative imaging arm unless more than three sites of cancer spread were detected on the initial scans (18 patients). A low number of men dropped out of the study or follow up information was not available for them (five patients). The remainder were given a second round of medical imaging at their six month follow-up appointment. The results of these scans were used to confirm tumour spread, in addition to biopsies and change in blood tests.

Overall, the researchers found the PSMA-PET/CT scans were much more accurate than conventional CT and bone scans at detecting cancer spread (92% vs 65%). This is because the new technique was better at detecting small sites of tumour spread. Conventional imaging failed to detect that the cancer had spread in 29 patients, giving a false negative result. By comparison, PSMA-PET/CT gave false negative results in just six patients. Furthermore, fewer men had false positive results obtained with the new technique (2 with PSMA-PET/CT and 9 with conventional imaging).

Patients who underwent PSMA-PET/CT scans had fewer ambiguous results than conventional imaging (7%, 11/148 patients vs 23%, 35/152 patients).

Both imaging techniques involve exposure to radiation but the dose associated with PSMA-PET/CT was less than half that associated with conventional imaging (8.4mSv vs 19.2mSv).

PSMA-PET/CT scans had greater impact on the way patients' disease was managed, with 28% having their treatment plans changed after the scans (41/147) compared with 15% following conventional imaging (23/152).

When PSMA-PET/CT was given at the second round of imaging after conventional imaging, disease management plans were still changed in more than a quarter of cases (39/146, 27%). When conventional imaging was used at the second round, however, just 5% of patients had their treatment plans changed (7/135 patients).

Professor Declan Murphy, senior author, said, "Around one in three prostate cancer patients will experience a disease relapse after surgery or radiotherapy. This is partly because current medical imaging techniques often fail to detect when the cancer has spread, which means some men are not given the additional treatments they need. Our findings suggest PSMA-PET/CT could help identify these men sooner, so they get the most appropriate care." [3]

Associate Professor Roslyn Francis, co-author, of the University of Western Australia, said: "Costs associated with PSMA-PET/CT vary in different regions of the world but this approach may offer savings over conventional imaging techniques. A full health-economic analysis will help to determine the cost effectiveness of introducing PSMA-PET/CT, both from a patient and a healthcare perspective"

Some patients in the study had undergone further tests to confirm the spread of disease, which involved removing tissue from their pelvic lymph nodes. This is acknowledged as the most reliable test for assessing the stage of prostate cancer disease spread. The researchers caution that as not all patients underwent the procedure, it may lead to an overestimation in the sensitivity of PSMA-PET/CT scans at detecting smaller tumours. However, as patients had been randomly assigned to their groups, the researchers conclude that their study provides robust comparative data.

Writing in a linked Comment article, Professor Caroline Moore, University College London (who was not involved in the study), said: "Introduction of novel imaging into routine practice requires careful assessment of the potential burden to both individuals and to society, taking into account changes in treatment which can result. The proPSMA authors have planned an economic analysis of the potential effect of replacing conventional staging with PSMA-PET, which will be crucial in assessing the feasibility of widespread use of PSMA PET-CT in men being considered for radical treatment for high-risk prostate cancer."

The world expects some teenagers to become criminals. These "troublemakers" are taken away from everything and everyone they know. The State places them in children's homes, often far from family and friends.

"Care-leavers from children's homes live with more layers of vulnerability. They can be more vulnerable than youth growing up in poor families", says Prof Adrian van Breda. He is a researcher at the Department of Social Work, University of Johannesburg, South Africa.

He authored the study Patterns of criminal activity among residential care-leavers in South Africa.

"For most, the children's home is the very 'last stop'. Their grandmothers are not providing foster care, they are not placed in foster care with other families, and not adopted. Some are moved from one foster placement to the next. Often, behavioural issues contributed to them being placed in a children's home."

Fragile statistics

In Australia, for example, 27% of care-leavers reported contact with police and 11% had been found guilty of a crime since turning 18 (Note 1). And in Sweden, 37% of male care-leavers went on to serious crime, compared to 5% of the general population (Note 2).

"Often, youth in children's homes lack healthy family connections. This may make them more vulnerable than poor teenagers. A poor teenager can still have healthy relationships with their parents, siblings and extended family. Family connections are a potent form of 'social capital'," adds Van Breda.

"The young person who grows up in care in this study, entered care on average at age 12. Most of them do have family, but their relationships with family became fragmented and thin. Sometimes, they were moved into care to protect them from their family.

"When care-leavers move out of a children's home, they often do not have the networks and skills to help them navigate into employment. A child who grows up in a poor community with their family may have far more social capital," he says.

Kieren, year 1 after leaving the children's home

Kieren (not his real name) lives with his parents. He got caught with drugs and had a fight with his mom. She called the police. After spending a few days in jail, he stopped dealing cannabis. He says that he "can just be triggered", "like a ticking timebomb". He agrees that he never learnt to deal with his anger at the children's home.

Kieren was interviewed five times during the study, at yearly intervals.

Unusual results from South Africa

Contrary to what we might expect, the majority of care-leavers in Van Breda's South African study do not engage in criminal activities. Instead, about three quarters (73%) say that they didn't engage in any criminal activities. They each took part in two or more annual interviews up to 5 years after leaving a children's home.

This encouraging result is despite a sudden stop in State support when the care-leaver turns 18. To them, this means no further housing and no further support for training and education. It is also despite a 55.2% unemployment rate among 15-24 year olds in 2019, according to Statistics SA.

The small study engaged with 100 young people leaving the children's homes in three South African provinces. They represent the racial diversity of the country.

They were recruited into the study just before leaving the children's home, between 2012 and 2016. By the end of 2018, 51 young people had given two or more in-depth annual interviews to research field workers. In total the study included 163 interviews with these 51 care-leavers.

The hungry, sleepy 10%

The second group in the study is the 10% who say that they engaged in one minor incident of crime after leaving care. This group stays out of serious trouble with the law.

"Some of these incidents were people who were hungry and stole food. Or they stole money to buy food. Others did not have a place to live. They would go to sleep at a vacant site or house because they needed shelter. They would be found and arrested for trespassing. These incidents of criminal activity are often survival-driven," says Van Breda.

Kieren, year 2 after leaving the children's home

Kieren spent nine months in juvenile prison after the previous interview. In prison, he saw a gang member "trying to hit on this guy. I know this guy from a long time. And I could not let him down like that."

So he stabbed the gang member in the neck. The gang member was in hospital for about a week. The police beat Kieren up "very badly".

The more violent 17%

The third group is the 17% who self-report more serious incidents of criminal activity in two or more years after leaving care.

These incidents are more frequent and more violent than the second group. They are more likely than the second group to come into conflict with the law and to spend at least one day in jail.

It is this third group that Kieren (not his real name) belongs to in the study. He is an unusual interviewee in the study, because he is the only one to serve a long prison sentence.

"This group told us about significantly more incidents of violence. They were usually unarmed, though, and the victims seldom needed medical care. The violent incidents decrease slightly over time," says Van Breda.

"They were holding and selling stolen goods and doing it more frequently as time went on. Most said that they dealt in drugs and used every year. Some stole, but a bit less frequently over time, and the monetary value was usually low."

Kieren, Year 3

Kieren is still living with his caregivers. He got into an argument and reflects "because I have a short temper I just switched." He went to prison for assault and was released two months later. He is still smoking cigarettes and cannabis, but not drinking, not stealing. He is holding and dealing stolen electronics and drugs.

Kieren, Year 4

The research field worker interviews Kieren in prison where he on trial for murder. He lived with a relative, until he assaulted a man and was charged with attempted murder.

Kieren, Year 5

The research field worker interviews Kieren in jail through a glass screen via a phone. He is serving a life sentence for the murder of the relative he had lived with.

What happens to care-leavers in Africa?

Globally, little research exists about crime committed by care-leavers. In Africa, little research has been done about care-leavers in general, says Van Breda.

"Statistics about crime committed by care-leavers in the global north exists. But often we don't know what is actually happening. What criminal activities do the care leavers engage in? How often do these happen? Is it a once-off exploratory thing that any young person might do, or is it continuous over time and increasing in frequency or severity? This study offers more insight on what is going on in this area, by collecting both numerical and narrative data.

"We think is it important to understand how to help care-leavers find their way successfully into young adulthood. Understanding this very vulnerable group can teach us how to better support other vulnerable young people transitioning into adulthood," says Van Breda.

Van Breda is a founding member of the Africa Network of Care-Leaving Researchers (ANCR). The researchers in ANCR collaborate online to research how young people in Africa transition out of alternative care.

Vulnerability across generations

"It is now more than 20 years after democracy in South Africa, a developing country that was colonised by the global north. Vulnerability and trauma in families continues to run along race and gender lines. This includes access to quality health care and education, access to social security, opportunities to learn a trade and find jobs.

"Black African youth and women are significantly more vulnerable than other young people. Existing State interventions do not fully address these vulnerable groups."

Van Breda concludes: "Young people under 30 is a fast-growing section of the South African population. Because of this, we need to understand how to better support care-leavers from children's homes and foster care. Juveniles need that support before they have to make their own way into the world."