Tech

Despite the numerous benefits associated with patients accessing their medical records, a study by a new Portland State University professor found only 10% of patients utilize the resource.

Researchers expected to find inequities in use and access -- in theory driven by existing digital disparities, those who don't use English as a first-language or communities without access to reliable internet services. However, they were surprised to find that use is unilaterally low. More than 95% of patients recently discharged from a hospital had access to electronic records. But use was disproportionately low across all hospital types.

"This means that there's something there that hospitals could be doing on their own to get more people to use the record," said Sunny Lin, assistant professor in the OHSU-PSU School of Public Health, who led the study. University of California San Francisco Associate Professors Julia Adler-Milstein, Courtney R. Lyles and Urmimala Sarkar also contributed to this research.

Hospitals are financially incentivized by the federal government through the Promoting Interoperability Program to offer patients electronic records -- but only one patient needs to access those records to qualify for continued funding.

"They're not required to actively recruit people to use it," Lin said.

Patient use, however, has its benefits. Lin said studies show patient engagement affects their quality of care and outcomes.

"They're finding patients who are more engaged in their own care, especially after a hospitalization, are able to communicate better with their providers and they have a better idea about what's going on," she said. "They then have better follow up care and as a consequence -- lower readmission."

This paper, Lin said, also speaks to the larger dynamic shift that's occurring within hospital systems. Many systems are exploring supplemental care options to improve patients' outcomes, including food security, housing and drug addiction assistance programming outside the hospital. Offering additional services goes beyond just providing care -- focusing on patient engagement is one facet of the larger picture.

"We're trying to push people to think about if we can do more as a hospital," Lin said. "Should we set that bar a bit higher?"

A recent study found the doctor-patient relationship determined whether or not the patient would actually use the record. Lin said although doctors are expected to do more and more, patient engagement is still key to success. Trusting a provider will further encourage patients to access their records.

"It's a shared responsibility to get people to use their records," she added. "It's about patients actually taking that step but it's also about hospitals making it easy to access."

New research shows that for every £1 invested in pollinator monitoring schemes, at least £1.50 can be saved, from otherwise costly independent research projects.

A research team from the University of Reading and the UK Centre for Ecology & Hydrology is studying how to improve pollinator monitoring in the UK in a cost-effective manner. The preliminary results are presented today at the British Ecological Society's annual meeting in Belfast.

Dr. Tom Breeze, researcher at the University of Reading, who will be presenting the research, said "The study shows that scientifically robust pollinator monitoring schemes, regardless of their size or structure, are cost-effective and add tremendous value to food security and wider scientific research".

Despite the urgent need, monitoring insect pollinators (especially wild bees and hoverflies) has often been considered too expensive to implement at a national scale. This research examines hidden benefits of monitoring schemes. By pooling data and expertise from a wide range of resources, the costs of schemes have been estimated to be between £5,600 for a small volunteer-led scheme collecting basic data and £2.8 million per year for professional monitoring of both pollinating insects and pollination to the UK's crops.

This research combined a series of methods to examine potentially hidden benefits of monitoring schemes, in monetary terms. The authors used a type of statistical method called power analysis to assess how many sites should be sampled to be able to detect a 30% change in insect populations over 10 years, assuming each site was visited by surveyors four times per year. A 30% change was used as a conservative estimate for how pollinator populations may be projected to decrease over the next 10 years, at a rate of 3% per year.

Bioeconomic models were used to estimate the impact of pollinator losses on the yields of insect pollinated crops grown in the UK. These include apples, berries, beans, oilseed rape and tomatoes. The monetary value of the scheme to scientists was estimated by asking leading pollinator researchers across Europe how they would design networks to answer eight research questions about wild pollinators.

The study concluded that these hypothetical monitoring schemes would be cheaper to implement than multiple research projects because administrative and management costs are lower, due to a single centralised network, rather than several, devolved smaller projects.

Dr. Breeze highlights the importance of pollinators in the UK landscape, "Pollinators are vital for our food security but are under threat from landscape and climate changes. Monitoring pollinator populations is vital to understanding the status and trends of these animals and identifying areas where we need to take dedicated action."

It is hoped that this will "protect pollination services to crops and add value as scientific infrastructure", said Dr. Breeze, from the University of Reading.

However, these estimates of the economic benefits of pollination only directly apply to farmers. It is anticipated that, through keeping prices low, they will indirectly provide further value to supermarkets and consumers.

Issues with relying on citizen science monitoring networks are that most volunteers have little experience and may struggle to distinguish between many species in the field. As a result, a network of fully trained professionals could supply higher resolution data.

However, in the UK, there is a strong culture of existing volunteer insect recorders which can be capitalised upon, such as the new Pollinator Monitoring Scheme (PoMS), the Bees, Wasps and Ants Recording Society, the Dipterists Forum and the Bumblebee Conservation Trust.

Dr. Breeze suggested that "A scheme that combines existing pollinator monitoring efforts with additional professional research efforts should be explored as a way to deliver the best of both worlds".

One limitation of the study is that the power analysis cannot distinguish between the relative research quality of different networks. It is assumed that fully professional schemes would add more consistent value to science. Alternatively, volunteer-focussed schemes allow opportunities for public engagement with conservation as well as influencing attitudes to nature and may also provide high quality research.

Dr. Breeze highlighted that governments should consider pollinator monitoring as an excellent investment from both a food security and scientific perspective.

Children in low resourced countries are 100-200 times more likely to die after surgery than children in wealthy countries, according to a first-of-its-kind study published in Anesthesiology.

Two billion of the world's children lack access to safe surgery and anesthesia, and the need for pediatric surgery in low- and middle-income countries is growing, according to lead author Mark Newton, MD, a pediatric anesthesiologist at Monroe Carell Jr. Children's Hospital at Vanderbilt and Director of Anesthesia Global Health and Development in the Department of Anesthesiology.

The pediatric surgery demand in low- and middle-income countries is growing, according to Newton, with children making up more than 50% of the population and up to 85% of those children requiring surgery before their 16th birthday.

"Most low-and middle-income countries have a severe shortage of pediatric surgeons and anesthesiologists," said Newton, Chair of the Department of Anesthesiology at AIC Kijabe Hospital in Kenya, where he lives 10 months out of the year.

"We know from practical experience that pediatric surgical mortality in these settings is high, but we have never been able to prospectively capture this data until now," he said.

In the new study, "Perioperative Mortality in Kenya: A Prospective Cohort Study from 24 Hospitals," Newton and co-authors establish a baseline pediatric perioperative mortality rate for the first time in East Africa and discuss factors associated with mortality.

The data from Africa demonstrates -

Mortality from pediatric surgery in Africa is 100-200 times greater than in a high-income country.

When not using the Safe Surgery Checklist (SSC), mortality increases over 200%.

Surgery on children in Africa during night and weekend hours increases mortality.

Mortality is higher in primary hospitals compared to both secondary and tertiary hospitals.

Newton said he hopes the study will demonstrate the feasibility of collecting perioperative mortality data at scale and illustrate how it can be used to improve pediatric surgical care systems within countries in Africa.

"This study establishes a pediatric perioperative mortality rate for low- and middle-income countries which is 100 to 200 times higher than in high-income countries," Newton said. "It also illustrates how such data can direct quality improvements. For example, we found a link between failure to use the Safe Surgery Checklist and mortality, which can be useful for advocacy, education and enforcement of the use of this patient safety tool."

To establish a baseline pediatric perioperative mortality rate and factors associated with mortality in Kenya, the authors designed a prospective cohort study and measured 24-hour, 48-hour, and 7-day perioperative mortality at 24 Kenyan hospitals.

There were 6,005 cases analyzed, finding cumulative mortality rates of 0.8% at 24?hours, 1.1% at 48?hours, and 1.7% at 7 days postoperatively.

In this sample, the 7-day mortality was more than 100 times higher than in high-resource settings and associated with American Society of Anesthesiologists Physical Status III or more, surgery at night or over the weekend, and not using the Safe Surgical Checklist. Mortality was also higher in primary hospitals compared to secondary or tertiary hospitals.

Newton and James O'Neill, MD, emeritus professor of Pediatric Surgery, have established a fellowship program at AIC Kijabe Hospital that has trained 10 pediatric surgeons and 16 pediatric anesthesiologists, in partnership with the University of Nairobi, from eight different African countries. Many of those trained have gone on to practice as the first pediatric surgeon or pediatric anesthesiologist in their home country.

"These newly trained pediatric surgeons and anesthesiologists are then supported to establish specialty training programs in their own countries," O'Neil said. "They will work as leaders to increase access to surgery for their countries' children and improve surgical outcomes."

A treatment called extracorporeal shockwave therapy (ESWT) is used in patients both human and equine to speed healing of injured tendons and ligaments. Using high-pressure sonic waves, ESWT is thought to increase blood flow to the treated area and has been shown to reduce pain over the short term.

In racehorses, however, masking pain can come with a cost: Overworked minor injuries could lead to major ones or even pose a life-threatening risk to both horse and rider.

For that reason, horse racing authorities have banned the use of ESWT for horses within 10 days of a race or sporting event. But the question of how to enforce this "invisible" therapy remained open. Now a team led by Mary Robinson, director of the School of Veterinary Medicine's Equine Pharmacology Research Laboratory, and lab member Jinwen Chen has found that the practice does in fact leave a trail. In a paper in Equine Veterinary Journal, they report finding potential biomarkers of ESWT that, with further testing, could one day be used to enforce the ESWT ban.

"Because it's not a drug--it's applied to the surface of the skin--it's just not an easy thing to detect," says Robinson. "After a lot of trial and error, our study was able to measure changes in levels of five inflammatory factors, some of which we could detect up to three weeks after the shockwave therapy."

The attempt to find these biomarkers dates back roughly a decade.

"It was Dr. Lawrence Soma, my predecessor, who said the lab was going to have to look at blood-based or urine-based biomarkers to try to detect shockwave therapy," Robinson notes.

To find the fingerprints that ESWT might leave behind, the researchers tested the therapy on 11 horses kept as a study herd at Penn Vet's New Bolton Center. The researchers collected blood samples from the group of horses, composed of Thoroughbreds and Standardbreds, at several times both before and after each received a single dose of ESWT to a leg.

Over the years, the lab investigated a number of potential biomarkers, molecules that would indicate a horse received ESWT. They zeroed in on 10 pro-inflammatory and anti-inflammatory signaling molecules, called cytokines, which they can measure from the blood using a sensitive test called ELISA, short for enzyme-linked immunosorbent assay.

"We looked a week before giving the shockwave therapy to see if there were any changes in the baseline period, due to changes in time of day or anything else, and didn't see anything we could define as significant," Robinson says. "And in the post-shockwave period we went out to three weeks."

They could not detect changes in five of the cytokines they examined following ESWT. But the other five--TNF-?, IL1?, IL-1RA, IL-6, and sTLR2--did respond. Of those, TNF-? levels were significantly increased through the whole of the post-therapy study period, three weeks.

More study is necessary, Robinson emphasizes, before these biomarkers could be used to assess inappropriate use of ESWT in racehorses. For one, the researchers would like to see if measuring these same molecules in horses that are actively training and racing or that have an acute injury might change their results.

For that, she and her colleagues are actively pursuing follow-up studies to look at these biomarkers and other indicators using a biobank of samples from client-owned animals, including injured and active racehorses, treated at New Bolton Center.

The end goal is to keep the sport safe.

"Shockwave therapy is great as long as people rest the horse after using it," she says. "We are concerned that it's being abused in the racehorse industry and that it could potentially result in breakdowns. That's exactly what we're trying to avoid."

By their nature, hospitals are fast-paced environments that can induce some stress in the people who work there. Often, the roles taken on by people saving others' lives are somewhat thankless. For this reason, Penn Medicine's Center for Digital Health created "High Five," a web-based recognition system that enables staff members to easily use social media-style memes and humor to compliment each other on anything from the routine to the extraordinary.

A new study published in NEJM Catalyst Innovations in Care Delivery led by Kathleen Lee, MD, an assistant professor of Clinical Emergency Medicine and director of Clinical Implementation in the Center, showed that this system was adopted by the vast majority of those within the department of Emergency Medicine at the Hospital of the University of Pennsylvania (HUP) -- the first department it was fully integrated into.

"The status quo expectation in many settings in medicine is perfection without recognition, Medical errors can result in harsh consequences, while successes are not often not recognized to the same extent. This imbalance is thought to be a key contributor to clinician burnout," said Lee, who led the research with David Do, MD, an assistant professor of Clinical Neurology, and Ian Oppenheim, MD, a fellow at the Johns Hopkins School of Medicine, who helped to launch "High Five" while he was a resident at Penn Medicine.

The Center for Digital Health -- which studies how things like the internet and other digital technology affect our health -- began exploring whether a web-based platform would be feasible in health care in 2016. The designers believed that making it easy for staff to quickly send out a nice message in a way that is now second instinct to many would increase positive interactions and potentially serve as a tool to combat burnout.

"Keeping it funny and light was us trying to build on what folks already do naturally on social media and via texting," Lee explained. "Humor and levity can organically incentivize folks to connect and support each other. So we thought it made sense to capitalize off of that natural inclination when we were trying to build an opt-in recognition system."

High Five, named for the congratulatory gesture, is usable across multiple devices and easily accessible through a webpage that clinicians could reach as if they were working on electronic health records. Each person can search for and select a colleague from the health system, then pick from a variety of memes or GIFs containing positive phrases that were congratulatory or humorous. The images draw from pop culture or are health-themed and some are the same as memes used commonly on social media. In addition to the images, each message could also be personalized by an accompanying text written by the user. A reply function was also added shortly after launch.

To assess whether the system was actually embraced, Lee and her fellow researchers went back to the first area High Five was introduced, the HUP emergency department, and tracked its use from then (August 2016) to the near-present (June 2019). They found that 88 percent of the residents, attending physicians and nursing staff used the platform in that time, comprising 227 of 259 possible users. Nearly 2,400 messages were sent within the department, with each user sending out an average of about three High Five messages per year.

High Five initially was only a person-to-person connection, but they added a public recognition factor in the middle of 2017 by mounting a monitor that displayed a rotation of the most recent High Fives. After that, the study showed that the average monthly users increased from about 49 to 81 in the emergency department.

Although the platform was intended -- and continues to operate -- as a way to increase peer-to-peer recognition, it could also serve as a tool to measure organizational priorities and goals. The researchers studied over 1,000 messages from between August 2016 and December 2017 and found that 62 percent recognized professional competencies like professionalism, procedural skill, and communication with patients and families. This enables potential real-time positive feedback for staff noted as proficient in areas health systems specifically target.
High Five has expanded since it was launched in 2016 into several different areas at Penn Medicine such as other emergency departments, Women's Health, Pharmacy, and an intensive care nursery, among others. Users now hail from all 20 academic departments within Penn Medicine, and 32 percent of hospital employees have exchanged 28,808 communications expressing courteous interpersonal behaviors, ranging from appreciation and recognition to specific feedback.

Moving forward, the team involved with High Five hopes to expand it across the health system completely, especially with the installment of display monitors.

"We want to continue to partner with departments and groups to help further harness the workplace civility and positivity that High Five enables," Lee said.

University of Otago researchers have discovered how viruses that specifically kill bacteria can outwit bacteria by hiding from their defences, findings which are important for the development of new antimicrobials based on viruses and provide a significant advance in biological knowledge.

Lead researcher Professor Peter Fineran explains that the rise in multi-drug resistant bacteria is leading to the development of alternative therapeutics, including viruses that specifically kill bacteria, called bacteriophages, often referred to as "phages". However, bacteria can become resistant to phages.

Phages are the most abundant biological entities on the planet and are important for global ecosystems, but they can also be used to kill bacterial pathogens. To defend themselves from the phage invasion, bacteria have developed CRISPR-Cas defence systems - immune systems within the bacteria. But the phages have come up with many ways to avoid these bacterial defences.

In the study published today in Nature Microbiology, the team at the University of Otago discovered a widespread method used by phages to hide from bacterial defences. They discovered a "jumbo" phage which, as the name suggests, is very big, with hundreds of genes. This phage is not recognised by CRISPR-Cas defences that would normally cut up the genetic DNA instructions to make many new phages.

PhD student in the Department of Microbiology and Immunology and first author of the study, Lucia Malone says it made the researchers question how this phage escapes recognition.

"We had molecular and genetic evidence for what was happening, but we really needed to see directly inside these tiny bacteria, which if 100 lined up side-by-side would be the width of a human hair," Ms Malone says.

This was made possible using a new spinning disk confocal microscope for high-resolution imaging of live cells - the only one with this capability in New Zealand - that was recently set up by Dr Laura Gumy, a new group leader at the University of Otago.

"When phages infected the bacteria, we could see their DNA was encased by a physical 'shield' and hidden from the CRISPR-Cas defence systems that couldn't gain access," Dr Gumy explains.

However, bacteria have another trick up their sleeve. To take over the host, the phages must produce RNA messages that leave this protective compartment. "This is the Achilles heel of these phages and can be destroyed by a special group of CRISPR-Cas defences that recognise RNA messages," Ms Malone says.

Dr Fineran explains the study broadens the knowledge of intricate phage-host interactions and demonstrates that "jumbo" phages are less susceptible to bacterial defence systems than some other phages.

"From a biological perspective, our results provide exciting new insights into how phages evade bacterial defence systems.

"This is important because the rise of the multi-drug resistant bacteria is an issue of global concern, which has led to a renewed interest in using phages as anti-bacterials and jumbo phages may provide excellent therapeutics."

More than 1 million people have died in the 1800 magnitude 5+ earthquakes recorded worldwide since 2000.

Bridges are the most vulnerable parts of a transport network when earthquakes occur, obstructing emergency response, search and rescue missions and aid delivery, increasing potential fatalities.

While engineers have designed structures to withstand destructive natural forces like extreme winds and tornadoes, catastrophic earthquakes such as the 2010 Haiti earthquake (over 310,000 fatalities) or the 2011 T?hoku earthquake in Japan (over 20,000 fatalities) remain a challenge.

To mitigate the impacts of such major earthquakes, a team of researchers at University of Technology Sydney (UTS) have a developed an application for ground anchors as the main seismic resisting system for ultimate protection of bridges against catastrophic earthquakes.

Led by Associate Professor Behzad Fatahi and supported by Mootassem Hassoun (PhD Candidate) at the School of Civil and Environmental Engineering this new application can protect bridges against earthquake levels well above code recommendation.

Despite the stringent design codes enforced globally, and technological advancement in seismic design and protection of structures, more effort is required to lower fatality rates and financial

losses. This is particularly relevant as rapid urbanisation creates higher population concentrations in seismically active zone such as Japan and Indonesia where 230,000 were recorded nationally following a single earthquake in 2004.

Associate Professor Fatahi and his team have developed an advanced three-dimensional computer model to simulate and evaluate the seismic capacity of anchored bridges subjected to some of the world's most catastrophic earthquakes.

Ground anchors are constructed from high tensile capacity steel cables commonly used to support deep excavations in city centres. The cables are light and flexible but can carry tremendous pulling capacity.

They are embedded into the ground behind the bridge, avoiding any effects on the bridge aesthetic looks, and grouted for a certain length in order to secure the anchors into the ground. The proposed ground anchors are passive and flexible, which allows the bridge to expand and shrink during its normal seasonal cycles without cracking.

The benefit of this technology is its low cost and high effectivity: it is cheap yet delivers incredible strength and energy dissipation into the ground - a material that is technically free.

"Our findings prove that bridges restrained with ground anchors have a superior seismic behaviour compared to traditional or even modern bridges with modern seismic protection devices such as viscous dampers," said Associate Professor Fatahi.

This increases the feasibility of bridges with much lighter and economical foundations, and reduced size and cost of safe bridge construction while maintaining - or even increasing - the capacity of the bridge to sustain significant earthquake motions.

The team tested their solution for many high magnitude earthquakes, including the massive 1995 Kobe earthquake in Japan, which damaged nearly 400,000 structures. Their research shows that bridges equipped with the novel ground anchor technology could survive catastrophic earthquakes and remain nearly undamaged while bridges designed using conventional seismic mitigation techniques had collapsed.

Many nations could build or amend earthquake safe bridges at a low cost, as it can also be adopted to retrofit older bridges designed and constructed to previous codes and therefore under-designed against large earthquakes.

Living beings contain their own assembly and operating instructions in the form of DNA. That's not the case with inanimate objects: anyone wishing to 3D print an object also requires a set of instructions. If they then choose to print that same object again years later, they need access to the original digital information. The object itself does not store the printing instructions.

Researchers at ETH Zurich have now collaborated with an Israeli scientist to develop a means of storing extensive information in almost any object. "With this method, we can integrate 3D-printing instructions into an object, so that after decades or even centuries, it will be possible to obtain those instructions directly from the object itself," explains Robert Grass, Professor at the Department of Chemistry and Applied Biosciences. The way of storing this information is the same as for living things: in DNA molecules.

"DNA of Things"

Several developments of the past few years have made this advance possible. One of them is Grass's method for marking products with a DNA "barcode" embedded in miniscule glass beads. These nanobeads have various uses; for example, as tracers for geological tests, or as markers for high-quality foodstuffs, thus distinguishing them from counterfeits. The barcode is relatively short: just a 100-bit code (100 places filled with "0"s or "1"s). This technology has now been commercialised by ETH spin-off Haelixa.

At the same time, it has become possible to store enormous data volumes in DNA. Grass's colleague Yaniv Erlich, an Israeli computer scientist, developed a method that theoretically makes it possible to store 215,000 terabytes of data in a single gram of DNA. And Grass himself was able to store an entire music album in DNA - the equivalent of 15 megabytes of data.

The two scientists have now wedded these inventions into a new form of data storage, as they report in the journal Nature Biotechnology. They call the storage form "DNA of Things", a takeoff on the Internet of Things, in which objects are connected with information via the internet.

Comparable to biology

As a use case, the researchers 3D printed a rabbit out of plastic, which contains the instructions (about 100 kilobytes' worth of data) for printing the object. The researchers achieved this by adding tiny glass beads containing DNA to the plastic. "Just like real rabbits, our rabbit also carries its own blueprint," Grass says.

And just like in biology, this new technological method retains the information over several generations - a feature the scientists demonstrated by retrieving the printing instructions from a small part of the rabbit and using them to print a whole new one. They were able to repeat this process five times, essentially creating the "great-great-great-grandchild" of the original rabbit.

"All other known forms of storage have a fixed geometry: a hard drive has to look like a hard drive, a CD like a CD. You can't change the form without losing information," Erlich says. "DNA is currently the only data storage medium that can also exist as a liquid, which allows us to insert it into objects of any shape."

Hiding information

A further application of the technology would be to conceal information in everyday objects, a technique experts refer to as steganography. To showcase this application, the scientists turned to history: among the scant documents that attest to life in the Warsaw Ghetto during World War II is a secret archive, which was assembled by a Jewish historian and ghetto resident at that time and hidden from Hitler's troops in milk cans. Today, this archive is listed on UNESCO's Memory of the World Register.

Grass, Erlich and their colleagues used the technology to store a short film [https://www.youtube.com/watch?v=yqcLlTbSXUg] about this archive (1.4 megabytes) in glass beads, which they then poured into the lenses of ordinary glasses. "It would be no problem to take a pair of glasses like this through airport security and thus transport information from one place to another undetected," Erlich says. In theory, it should be possible to hide the glass beads in any plastic objects that do not reach too high a temperature during the manufacturing process. Such plastics include epoxides, polyester, polyurethane and silicone.

Marking medications and construction materials

Furthermore, this technology could be used to mark medications or construction materials such as adhesives or paints. Information about their quality could be stored directly in the medication or material itself, Grass explains. This means medical supervisory authorities could read test results from production quality control directly from the product. And in buildings, for example, workers doing renovations can find out which products from which manufacturers were used in the original structure.

At the moment the method is still relatively expensive. Translating a 3D-printing file like the one stored in the plastic rabbit's DNA costs around 2,000 Swiss francs, Grass says. A large sum of that goes towards synthesising the corresponding DNA molecules. However, the larger the batch size of objects, the lower the unit cost.

SEATTLE -- Dec. 9, 2019 -- What if a metal that's already used to repair broken bones, straighten teeth and keep arteries from clogging could also be used to stop your cancer from spreading?

New findings published Dec. 9 in Nature Biomedical Engineering from scientists at Fred Hutchinson Cancer Research Center show for the first time that a piece of small, thin metal mesh loaded with cancer-fighting immune cells shrinks tumors in preclinical models of ovarian cancer.

"Cell therapies to fight cancer have had great success in blood cancers but haven't worked well with solid tumors," said lead author Dr. Matthias Stephan, a faculty member in the Fred Hutch Clinical Research Division. "Our findings take a significant step toward making cell therapies effective against solid tumors by showing that a thin metal mesh loaded with T cells engineered to fight ovarian cancer cleared tumors in 70% of the treated mice."

Solid tumors, including cancers of the breast, ovary and pancreas, have a variety of tactics to hide from and fight back against cancer-killing immune cells like CAR (chimeric antigen receptor) T cells. Simply injecting anti-cancer cells has not worked; they don't reach the tumor or if they do reach the cancerous cells, they tire out in trying to kill them and are then shed from the body.

Stephan designs materials that are safe in the body and can carry cancer-fighting cells to tumors. "In addition to minimizing side effects in patients, our ultimate goal is to make T-cell therapies faster and cheaper to make, and easier to deliver to patients." he said.

In a step toward that goal, Stephan's latest study loaded CAR T cells targeting ovarian cancer onto a porous, mesh-like metal film and then placed the film on tumors.

"This is not just a passive delivery device," Stephan said. "It's a release platform that triggers an expansion of CAR T cells that can overcome defenses that tumors make against the immune cells."

The researchers used thin, nearly translucent metal films made by Monarch Biosciences (MonarchBio), which helped fund the project. The films are 10 micrometers thick, which is 1 millionth of a meter, or about seven times thinner than the average width of a human hair. Made of nickel titanium, the film can safely be implanted within the body and is used in other medical devices.

Viewed under a powerful microscope, the film has minuscule spaces that can be configured into different patterns. The spaces can be filled with drugs or other liquids and then implanted in the body, where the liquids ooze out and find their targets.

Stephan and his colleagues wanted to see if the films could hold T cells and deliver the cancer-fighting cells to tumors.

"We needed to find a pattern of the film that would work well for T cells," Stephan said. "The pattern needed to be small enough where the cells would not fall between the cracks and not too small so that the T cells would feel too cramped and wouldn't be able to move."

They found that a pattern with straight lines resembling a top-down view of a maze worked best with the T cells. They coated the metal film with a combination of materials that allow the CAR T cells to grow and expand once they're in the body.

The Fred Hutch team loaded the film with CAR T cells programmed to seek out a marker for ovarian cancer cells, called ROR1. The engineered cells were placed on both sides of the film and were then absorbed into the middle of the material.

"It's like a piece of bread spread with marmalade on both sides," Stephan said. "The metal film is the bread, and then we put CAR T cells on both sides of it and then they soak into the middle too."

Using lab models of ovarian cancer, the researchers implanted films loaded with CAR T cells on the tumors. The T cells moved out of the film and gravitated near the tumor. Within 10 days, the tumors disappeared in all mice. Within 20 days, 70% of the mice remained tumor-free.

The approach -- if confirmed by more studies and clinical trials -- could eventually be used to treat diseases such as pancreatic and ovarian cancer, where tumor growth could be kept in check by implanting the film over it.

In another experiment reported in the same paper, the Fred Hutch researchers found that a tube-like version of the film soaked with CAR T cells kept tumors from growing into the tube. This approach could be used in cancers that cause obstruction of the airways or the digestive system, such as lung cancer or pancreatic cancer, or esophageal cancer, where stents are used to restrain tumors from interfering with swallowing.

"We focused on CAR T cells in the current experiment, but I could see this approach working with T cell receptor therapies, natural killer cells and other types of immune cells that target cancer," Stephan said.

Researchers in the Organic Photonics and Nano-optics goup at the Laboratory of Organic Electronics have developed optical nanoantennas made from a conducting polymer. The antennas can be switched on and off, and will make possible a completely new type of controllable nano-optical components.

Plasmons arise when light interacts with metallic nanoparticles. The incident light sets off a collective oscillation, a unified forwards and backwards motion, of the electrons in the particles. It is this collective oscillation that is the plasmon. Metallic nanostructures and their ability to shape light on a scale of nanometres are studied by many research groups around the world for use in, for example, biosensors and energy conversion devices, and to reinforce other optical phenomena. Other potential fields of use include miniature medical equipment and windows that control the amount of light and heat admitted to or emitted from a building.

In an article in Nature Nanotechnology, scientists from Linköping University present optical nanoantennas, made from a conducting polymer instead of a traditional metal, such as gold or silver. In this case, they used a variant of PEDOT, which is a widely used polymer in many other areas, including thermoelectrics and bioelectronics.

"We show that light can be converted to plasmons in nanostructures of the organic material", says Magnus Jonsson, leader of the Organic Photonics and Nano-optics group at the Laboratory of Organic Electronics.

It is, however, not electrons that create plasmons in the conducting polymer, but polarons. A polymer consists of a long chain of connected atoms and in the conducting polymer that the researchers have worked with, it is positive charges along the polymer chain that are responsible for the electrical conductivity. Together with associated chain distrorions these positive charges form polarons, which start collective oscillations when light is incident on the nanostructure.

"Our organic antennas can be transparent to visible light while reacting to light at somewhat longer wavelengths, making them interesting for applications such as smart windows", says Magnus Jonsson.

The researchers initially carried out theoretical calculations and used simulations to design experiments, which they were subsequently able to carry out. Shangzhi Chen, doctoral student in the group, has managed to produce billions of tiny nanometre-sized disks of the organic conducting material on a surface. These small disks react to light and act as tiny antennas.

The researchers have shown that both the diameter and the thickness of the disks determine the frequency of light to which they react. It is thus possible to control this wavelength by changing the geometry of the disk. The thicker the disk, the higher the frequency. They are also hoping that they can increase the range of wavelengths to which the nanoantennas react by changing the polymer used.

Another innovation they have explored is the ability to switch the organic nanoantennas on and off, which is difficult with conventional metals. The material manufactured in the laboratory is initially in an oxidised state, and the nanoantennas are switched on.

"We have shown that when we reduce the material by exposing it to a vapour, we can switch off the conduction and in this way also the antennas. If we then reoxidise it using, for example, sulphuric acid, it regains its conductivity and the nanoantennas switch on again. This is a relatively slow process at the moment, but we have taken the first steps and shown that it is possible", says Magnus Jonsson.

"While this is basic research, our results make possible a new type of controllable nano-optical components that we believe can to be used for many applications."

In a new study published today in Nature Climate Change, scientists show how specific wave patterns in the jet stream strongly increase the chance of co-occurring heatwaves in major food producing regions of Northern America, Western Europe and Asia. Their research finds that these simultaneous heatwaves significantly reduce crop production across those regions, creating the risk of multiple harvest failures and other far-reaching societal consequences, including social unrest.

Lead author, Dr Kai Kornhuber from the University of Oxford's Department of Physics and Colombia University's Earth Institute, said: 'Co-occurring heatwaves will become more severe in the coming decades if greenhouse gases are not mitigated. In an interconnected world, this can lead to food price spikes and have impacts on food availability even in remote regions not directly affected by heatwaves.

'We found a 20-fold increase in the risk of simultaneous heatwaves in major crop producing regions when these global scale wind patterns are in place. Until now this was an underexplored vulnerability in the food system. We have found that during these events there actually is a global structure in the otherwise quite chaotic circulation. The bell can ring in multiple regions at once and the impacts of those specific interconnections were not quantified previously.'

Western North America, Western Europe and the Caspian Sea region are particularly susceptible to these atmospheric patterns that get heat and drought locked into one place simultaneously where they then affect crops production yields.

Dr Dim Coumou, co-author from the Institute for Environmental Studies at VU Amsterdam, said: 'Normally low harvests in one region are expected to be balanced out by good harvests elsewhere but these waves can cause reduced harvests in several important breadbaskets simultaneously, creating risks for global food production.'

Dr Elisabeth Vogel, co-author from Melbourne University, said: 'During years in which two or more summer weeks featured the amplified wave pattern, cereal crop production was reduced by more than 10% in individual regions, and by 4% when averaged across all crop regions affected by the pattern.'

Dr Radley Horton, co-author from the Lamont-Doherty Earth Observatory at Colombia University, said: 'If climate models are unable to reproduce these wave patterns, risk managers such as reinsurers and food security experts may face a blind spot when assessing how simultaneous heat waves and their impacts could change in a warming climate.'

The scientists conclude that a thorough understanding of what drives this jet stream behaviour could ultimately improve seasonal predictions of agricultural production at the global scale and inform risk assessments of harvest failures across multiple food-producing regions.

Bacteria and the viruses that infect them are engaged in a molecular arms race as ancient as life itself. Evolution has equipped bacteria with an arsenal of immune enzymes, including CRISPR-Cas systems, that target and destroy viral DNA. But bacteria-killing viruses, also known as phages, have devised their own tools to help them outmaneuver even the most formidable of these bacterial defenses.

Now, scientists at UC San Francisco and UC San Diego have discovered a remarkable new strategy that some phages employ to avoid becoming the next casualty of these DNA-dicing enzymes: after they infect bacteria, these phages construct an impenetrable "safe room" inside of their host, which protects vulnerable phage DNA from antiviral enzymes. This compartment, which resembles a cell nucleus, is the most effective CRISPR shield ever discovered in viruses.

"In our experiments, these phages didn't succumb to any of the DNA-targeting CRISPR systems they were challenged with. This is the first time that anyone has found phages that exhibit this level of pan-CRISPR resistance," said Joseph Bondy-Denomy, PhD, assistant professor in the Department of Microbiology and Immunology at UCSF. Bondy-Denomy led the research team that made the discovery, which is detailed in a paper published Dec. 9, 2019 in the journal Nature.

The Hunt for DNA That CRISPR Can't Cut

To find CRISPR-resistant phages, the researchers selected viruses from five different phage families and used them to infect a common bacteria that had been genetically engineered to deploy four different Cas enzymes, the DNA-cutting component of CRISPR systems.

These CRISPR-fortified bacteria emerged victorious against most of the phages they faced off against. But two jumbo phages -- so named because their genomes are five to 10 times larger than the genomes of the most well-studied phages -- were found to be impervious to all four CRISPR systems.

The researchers decided to put these jumbo phages to the test and probe the limits of their CRISPR-resistance. They exposed them to bacteria outfitted with a completely different type of CRISPR, as well as bacteria equipped with restriction-modification systems -- a DNA-cleaving enzyme that's more common than CRISPR (restriction systems are found in about 90 percent of bacterial species, whereas as CRISPR is present in only about 40 percent) -- but which can only target a limited number of DNA sequences. The results were the same as before: petri dishes littered with the exploded remains of phage-infected bacteria.

"It was really surprising because we engineered the bacteria to massively overproduce components of the immune system, but none of them could cut the phage DNA. These phages were resistant to all six bacterial immune systems tested. No other phage even comes close," said Bondy-Denomy.

Jumbo phages, it seemed, were virtually indestructible. But test tube experiments suggested otherwise -- jumbo phage DNA was, in fact, as vulnerable to CRISPR and restriction enzymes as any other DNA. The CRISPR resistance that was observed in phage-infected cells had to be the result of something the viruses were producing that interfered with CRISPR. But what?

Anti-CRISPRs were an obvious culprit. These proteins, first discovered by Bondy-Denomy in 2013, are potent CRISPR inactivators encoded in some phage genomes. But when the researchers analyzed the jumbo phage genome sequences, anti-CRISPR genes were nowhere to be found. Plus, every known anti-CRISPR can only disable specific CRISPR systems, whereas jumbo phages were resistant to every antiviral enzyme thrown at them. Whatever was protecting jumbo phage DNA had to be based on some other mechanism.

Found: An Impenetrable CRISPR Shield

Microscope-based experiments finally revealed what was happening. When these jumbo phages infect bacteria, they build a spherical compartment in the middle of the host cell, which keeps antiviral enzymes at bay and provides a "safe room" for the viral genome to replicate.

This compartment, it turns out, was identical to one first discovered in 2017 by UCSD Professor Joe Pogliano, PhD, and UCSF Professor David Agard, PhD, both of whom are co-authors of the new study. Though these researchers previously demonstrated that the phage genome replicated in this nucleus-like shell, nobody knew until now that the shell also serves as an impenetrable shield against CRISPR and other DNA-dicers.

Still, many questions about the shell and the viruses that build it remain unanswered, including fundamental details about the protein from which the shell is constructed.

"This was one of many hypothetical proteins that was found when these phages were sequenced. It seems like it's unique to phages, but it's not common. It's not even found in some closely related phages. We also don't know what the protein structure looks like at the atomic level," said Bondy-Denomy.

But the shell's protein building blocks aren't the only mystery that Bondy-Denomy and his colleagues are eager to tackle. While the researchers were monitoring phage-infected bacteria under the microscope, they noticed something unusual: while the phage's safe room is being assembled, a process that takes about 30 minutes, its genome remains at the site where it was injected into the host cell. During this time, the phage genome would seem to be vulnerable to any antiviral enzymes floating around the host cell. But somehow, the genome remains intact while the safe room is under construction.

"We think some kind of pre-shell is protecting the injected DNA early on. It's like an armor that's shed once the shell is finally assembled. But we don't know what that armor is," said Bondy-Denomy, who is eager to figure out how these phages protect themselves from CRISPR at every step of the viral life cycle.

The researchers also discovered that the shell isn't as impenetrable as the initial experiments suggested. With some clever engineering, the study's lead author Senén Mendoza, a graduate student in the Bondy-Denomy lab, found a way to bypass the nucleus-like shield by attaching a restriction enzyme to one of the viral shell proteins. This Trojan horse strategy allowed the DNA-dicing restriction enzyme to sneak into the shell as it was being assembled and chop up the phage genome inside of what was supposed to be an immunity-free zone, which allowed the bacteria to survive.

This experiment is especially exciting to the researchers because it shows that there are in fact ways that the "impenetrable" safe room can be breached. And given that bacteria and phages are always finding new ways to sabotage one another's defenses, Bondy-Denomy believes that scientists will eventually find that bacteria are already armed with the tools needed to break through or bypass this nucleus-like compartment.

"We're looking for ways that bacteria get around the shell. There's no way this is the be-all and end-all in this fight," said Bondy-Denomy. "Maybe there are bacteria that fuse an immunity enzyme to a phage protein and finds its way into the shell. Or maybe bacteria steal a phage gene and use it against the phage. I think we'll eventually find that bacteria have come up with lots of ways to fight against phages that build these shells, and we'll probably be surprised by how they do it."

A new study by scientists from The Nature Conservancy (TNC), the University of Bristol and flood analytics company Fathom, seeks to answer an important question related to flooding in the United States - pay now to protect undeveloped areas that are likely to flood in the future or allow developments to go ahead and pay for damage when it occurs.

The paper, published today in the journal Nature Sustainability has identified 270,000 square kilometres of land - an area roughly the size of Colorado - in floodplains where conservation would be an economically sound way to avoid future flood damages.

Such lands, described as '100-year' floodplains, are areas of land that have a greater than one percent chance of flooding in any given year, or a greater than 26 percent chance of flooding during a 30-year period.

Kris Johnson, TNC's Deputy Director of Agriculture for North America, who co-authored the paper, said: "In these areas, we found that investing a dollar to protect these floodplains today could save at least five dollars in potential future flood damages.

"The study also tells us it would make even more economic sense to acquire and protect areas with a five percent or greater chance of flooding each year, or so-called 20-year floodplains.

"Not only would investing now to conserve undeveloped lands in floodplains likely save tens of billions of dollars in avoided flood damages but protecting these lands would also provide a host of additional benefits for habitat, wildlife, water quality and recreation, further strengthening the economic rationale for floodplain conservation."

Oliver Wing, a flood risk scientist and researcher at the University of Bristol's School of Geographical Sciences, who also co-authored the paper, added: "Our work has shown that projected socio-economic changes alone in the United States could almost double annual flood losses by the end of the century.

"One way to prevent this is to simply ensure that development occurs in lower-risk lands. We found that an area of land larger than that of the United Kingdom may be cheaper to purchase today than it would be to cover the costs of future damages to potential developments.

"We quantify, for the first time, the value of natural floodplain conservation to mitigating flood loss and find tracts of land in every one of the lower 48 states where this is a cost-effective strategy."

The Bristol team, made up of hydrologists and flood mappers who came up with the analysis used to determine the findings of the research, also found that while the conservation of undeveloped, flood-prone areas would be broadly effective across the nation, it is likely to be particularly beneficial in the Southwest, the eastern Great Lakes, the Appalachians, and areas where population growth is anticipated in areas at risk of flooding.

This information will be used by TNC and - the researchers hope - planners and decision-makers across the US to inform conservation strategies which consider the potential costs of permitting unabated development in risky areas.

So far, 2019 has been the wettest year on record in the lower 48 US States, and flooding has been particularly widespread and destructive.

Flooding is among the most common of natural disasters, and it is the most-costly with average flood losses in the US increasing steadily to nearly $10 billion annually. Meanwhile, the American taxpayer-backed National Flood Insurance Program is in record debt at nearly $25 billion.

A team of molecular and structural biologists from Nanyang Technological University, Singapore (NTU Singapore) have found a potential new route to disabling respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) after elucidating the structure of one of its key components.

RSV and HMPV are two closely related viruses causing severe and life-threatening respiratory diseases such as pneumonia and bronchiolitis in premature babies and infants, the elderly, and anyone with a weak immune system.

According to UNICEF, pneumonia killed a child somewhere in the world every 39 seconds in 2018, but there are no vaccines or effective antiviral therapies against it.

As they infect human cells, HMPV and RSV commandeer the cell's machinery to make copies of themselves. To initiate the process, special proteins released by the virus interact with each other to make distinct protein complexes.

Writing in Nature, Dr Julien Lescar from NTU's School of Biological Sciences and his team report how they have used cryo-electron microscopy to image the molecular structure of one of these large complexes, an enzyme called HMPV L:P polymerase.

Cryo-electron microscopy uses an advanced electron-scanning microscope, which can image a cryogenically frozen sample down to the sub-nanometre range, about ten times smaller than a strand of human DNA or one million times smaller than the width of a human hair.

The NTU images captured the enzyme at a resolution of 3.7 Angstrom, or 0.37 nanometres. Based on these two-dimensional pictures, the team then built three-dimensional computer models of the proteins' L:P molecular structures.

Analysis of these model structures revealed key sites for molecules to interact at, offering new targets for designing antiviral molecules against both viruses.

Dr Lescar, who is a Principal Investigator at the NTU Institute of Structural Biology, said with this detailed structural knowledge, researchers can now hope to develop inhibitors that disrupt the enzymatic activities of HPMV L:P protein and potentially block infection by the virus.

"We hope that our work will help researchers in pharma and academia around the world to design much needed therapies for difficult viral infections that often lead to antibiotic-resistant bacterial infections," said Dr Lescar, an Associate Professor at NTU's School of Biological Sciences.

Since the HMPV proteins they studied are essentially unchanged through evolution and very similar to those of RSV and other virus species belonging to the Pneumorivridae family, the scientists hope that inhibitors developed against HPMV could also work against a broad spectrum of viruses involved in respiratory diseases, and inform similar quests against other viral diseases.

The motions of plasmas may be notoriously difficult to model, but they can be better understood by analysing what happens when protons are scattered by atoms of hydrogen. In itself, this property is characterised by the size of a particular area surrounding the atom, known as its 'cross section'. In new research published in EPJ D, Anthony Leung and Tom Kirchner at York University in Canada used new techniques to calculate the cross sections of atoms which have been excited to higher energy levels. They analysed the behaviour over a wide range of impact energies.

Since a huge amount of energy is released when ions and atomic nuclei combine, the duo's efforts are of particular importance to the field of nuclear fusion. Among those interested parties will be the International Thermonuclear Experimental Reactor (ITER) project, which relies upon accurate plasma modelling in its continuing developments of feasible fusion reactors. The collision process has been modelled through a wide variety of theoretical techniques in the past, but widespread discrepancies have remained between their results. In calculating the cross sections of hydrogen atoms in their first and second excited states, and for impact energies between 1 and 300keV, Leung and Kirchner's results validate some of these previous conclusions. At the same time, they reveal continuing discrepancies in other models.

The researchers calculated their cross sections through a mathematical approach similar to those used in some previous studies, but which was more adaptable to intermediate-energy problems. Leung and Kirchner's work could bring about important advances in physicists' understanding of how plasmas behave, and may even advance our understanding of how they can be used to realise an abundant source of clean energy.