Breakthrough antibacterial approach could resolve serious skin infections

Like a protective tent over a colony of harmful bacteria, biofilms make the treatment of skin infections especially difficult. Microorganisms protected in a biofilm pose a significant health risk due to their antibiotic resistance and recalcitrance to treatment, and biofilm-protected bacteria account for some 80 percent of total bacterial infections in humans and are 50 to 1,000 times more resistant to antibiotics than simpler bacterial infections.

"In essence, we may have stumbled onto a magic bullet," said David Fox, a Los Alamos National Laboratory researcher on the project. "Through a robust screening strategy, our research team has identified a unique class of materials, known as ionic liquids, which both neutralize biofilm-forming pathogens and deliver drugs through the skin," he said.

"We extended our current capability in antimicrobial platforms with ionic liquids to new heights by partnering with Dr. Mitragotri at UCSB, who is an expert in transdermal drug delivery platforms. The merger made perfect sense," stated Fox.

"In several cases, we found the ionic liquid was more efficacious on a biofilm than a standard bleach treatment and exhibited minimal cytotoxicity effects on human cell lines (unlike bleach). This has excellent prospects for aiding antibiotic delivery to the pathogen through biofilm disruption but, most interestingly, the ionic liquids themselves are quite effective for pathogen neutralization," Fox said.

This work could have especially useful applications for military medical treatments, he noted, where soldiers in the field can be exposed to bacterial infections that are particularly difficult to treat.

Biofilms often persist in the periphery of an actual wound, beneath an intact, healthy skin layer and the difficulty of their treatment is largely due to the outermost layer of the skin, the stratum corneum, being a natural barrier for drug delivery.

"If the bacterial biofilm can be disrupted, delivery of antibiotics is greatly enhanced, and any dispersed pathogens are generally restored to normal antibiotic susceptibility," said Fox. "Further, many bacterial infestations in wounds penetrate under the outer skin layer, the stratum corneum, and deep into the tissue (epidermis and dermis). These materials are able to penetrate through the skin and effectively carry antibiotics to the deepest layers."

"Clearly, the ionic liquids would be of special benefit to our warfighters where exposure to biological agents in hostile environments is likely. Topical application as a prophylaxis or direct treatment to an open wound could buy enough time to reach the proper medical facilities when in an austere environment," he said. Importantly, ionic liquids can be derived from very cheap starting materials that are FDA approved and are extremely stable to high temperatures and pressures, which are necessary traits for commercialization in real-world applications.

In a groundbreaking manuscript appearing this week in the Proceedings of the National Academy of Science, as part of a multi-institutional effort between Los Alamos, University of California Santa Barbara, Dixie State University and Northern Arizona University, researchers explored exploiting ionic liquids both in a concerted effort to combat antibiotic-resistant bacterial biofilms in skin, as well as for topical transdermal drug delivery. The comprehensive strategy resulted in the identification of ionic liquids that are effective at disrupting biofilms, neutralizing pathogens, and enhancing delivery of antibiotic into skin.

Biofilms are a major cause of chronic wounds and wound degeneration. Wounds from infected surgical incisions result in 1 million additional hospital days. Additional causes of bacterial infected wounds include traumatic injuries, as well as diabetic foot ulcers, venous leg ulcers, and pressure ulcers.

The total economic burden of skin disease was estimated to be approximately $96 billion in 2004, and the prevalence and healthcare costs for skin disease have been increasing over the last three decades. Bacterial infections in the skin are among the most common diagnoses in hospital patients, accounting for some 10% of all hospital visits. Staphylococcus aureus infections acquired in hospitals, which account for only 16% of nosocomial infections, are estimated to result in $9.5 billion in extra patient costs and 12,000 deaths annually.

The comprehensive approach is unique in that the team examined a panel of in-house synthesized ionic liquids and enabled the discovery of one ionic liquid, choline-geranate, which showed excellent antimicrobial activity, minimal toxicity to epithelial cells as well as skin, and effective permeation enhancement for drug delivery. Specifically, choline-geranate was comparable with, or more effective than, bleach treatment against established biofilms of Salmonella enterica and Pseudomonas aeruginosa, respectively. In addition, choline-geranate increased delivery of cefadroxil, an antibiotic, by >16-fold into the deep tissue layers of the skin without inducing skin irritation.

Why Listeria bacterium is so hard to fight

Listeria is a dreaded bacterium that can be found in both unprocessed and processed foods. Over the last few weeks, 28 persons in Denmark have been infected with Listeria from processed food, sold in supermarkets. 13 have died.

The bacterium is notoriously difficult to fight because it has an almost uncanny ability to adapt to changes in its surroundings, says Associate Professor Birgitte Kallipolitis, University of Southern Denmark. Together with colleagues from the Department of Biochemistry and Molecular Biology, she has published a study, which in details reveals how this extreme ability to adapt takes place.

The researchers tested how Listeria reacts when it is exposed to a number of substances that can normally fight pathogenic bacteria. In the laboratory, Listeria was exposed to antibiotics, bile, salt, acid and ethanol, similar to what it often encounters in food, in the human body and during disinfection.

Listeria is constantly alert

"We knew that Listeria can resist these substances, but we did not quite know how," says Birgitte Kallipolitis.

The researchers discovered that Listeria used a variety of strategies that enabled them to withstand the substances.

"Generally speaking, Listeria must be described as extremely adaptable. It is constantly aware of its surroundings and if the environment changes around it. It reacts instantly and has a number of strategies to withstand threats," says Birgitte Kallipolitis.

The researchers also discovered that listeria is an expert at not attracting unwanted attention from the body's immune system.

"On the one hand, Listeria needs to produce some special proteins that enable it to infect the cells in our body. On the other hand, it must ensure that the body's immune system does not detect these proteins. It is vital for Listeria to keep a balance between producing enough of these proteins but not so many that they are detected by the immune system -- and it masters just that," explains Birgitte Kallipolitis.

When in the lab, the researchers looked at what happened at the microbiological level. It turned out that Listeria started producing some special RNA molecules, when they were exposed to antibiotics, bile, salt, acid and ethanol.

It is all about controlling protein production

"With these RNA molecules the bacteria can adjust how much or how little to produce of various proteins. For example it can downgrade the production of the protein LapB, which it uses to enter our cells. If this production is not downgraded, the bacterium will potentially be detected and fought by the immune system," says Birgitte Kallipolitis.

In other words: Listeria can fine-tune the production of the proteins needed to infect our cells to a point where there is exactly enough to sneak through the immune system's defense, but not so many that they are discovered.

The RNA molecules, produced when Listeria face dangerous environmental changes, also helps Listeria monitor its own cell wall. Antibiotics work by attacking the bacterial cell wall, and when exposed to antibiotics Listeria immediately detects that its cell wall is attacked. This enables it to quickly repair its cell wall -- and thus become ready for combat again.

"We see this production of RNA molecules only when Listeria is exposed to threatening substances in the lab. When there are no threats, Listeria does not produce them. This reveals part of the mechanism behind Listeria´s extreme adaptability," concludes Birgitte Kallipolitis.

The understanding of how Listeria is able to survive antibiotics, the immune system and disinfecting agents is necessary in order to develop effective means against the life-threatening bacteria.

"Only by looking at what the bacteria themselves do to survive, we can become better at fighting their pathogenicity," says Birgitte Kallipolitis.

She and her colleagues are now investigating whether Listeria can be changed into harmless bacteria by removing the RNA molecules.

Tall People Won’t Have to Endure Reclining Airline Seats in the Future



By 2100, New York was enduring an excruciating 70 days a year above 100 degrees (as predicted), so we abandoned it. The other coastal hells, too. Rising sea levels coupled with the inherent seismic instability of living near the boundaries of tectonic plates drove our people inland, leaving the coastlines and engineered seawalls an unpredictable frontier upon which the brave make a living and the destitute subsist, far away from the safety of the megacities. I’ve heard rumors that some six-footers live out there, gulping down great quantities of diseased fish to support the nutritional demands of growing to such an incredible height. They wouldn’t last long in the close confines that house so much of the world’s population.

Joe Brown

Joe Brown is WIRED’s Deputy Editor. He wrote this this morning.

Most of us moved late in the twenty-first century, after the famines and population growth made rural or even suburban life untenable, a trend sociologists began to observe late in the Twentieth. The scrubbers keep our air safe from the antibiotic-resistant bacteria and the massive fans stir up a cool breeze; you barely notice the combination of the outside temperature and the radiant heat of millions of densely packed bodies. You can choose air conditioning for half of the day—I can’t sleep without it at night—but there’s not enough juice for a full 24. Our towers, topped with solar cells and stacked stories of ultracapacitors, soar far above the clouds. It’s so much cooler up here.

The middle of America is still our Breadbasket. Breadbasket haha, only rich people get bread. It’s more like the Algae-and-Solar-Farmbasket. The robots live there, loading onto electrified rails great vats of nutrient-rich sludge harvested from stinking pools that used to have names like Iowa. Kansas. Ne-bras-ka. Fat cables stacked next to the tracks pump power from the photovoltaic arrays out to the walls, constantly pumping to keep the oceans at bay.

There used to be plush, padded chairs in airplanes, and everyone got one. Passengers used to lounge around, drinking free juice of tomato and watching TV.

Life here is predictable and safe. There is no crime and plenty of food from the faucet. Though our ancestors used to commute—actually leave their homes and work in completely different buildings!—we never have to leave our units. The companies who gave us telepresence once boasted that they could keep cars off the roads; now nobody owns cars, and few people use roads. There’s no need for such excess, and besides, working from home lets us consume fewer calories, the only currency we worry about anymore.

A very few people have to travel, and they take planes. It is supposed to be miserable: hundreds of poor souls crammed standing inside a metal tube for hours on end. There used to be plush, padded chairs in airplanes, and everyone got one. Passengers used to lounge around, drinking free juice of tomato and watching TV. And because that wasn’t luxurious enough, there was a whole other section devoted to being even more comfortable. Huge chairs, hot food, servants. Haha, their utensils were probably made of gold or petroleum-based plastic or something.

With such a plush experience, it’s no wonder that people used to spend much of their precious vacation time on planes, so accustomed to luxury that reclining seats were considered a right rather than a privilege.

At least we take up less room these days. In the mid-21st century parents started realizing that their children would have better lives if they were smaller. Small changes in diet from a young age had massive effects on a person expected to live efficiently. Height, once seen as an attractive quality became, like so many other vestiges of uncivilized life, superfluous, and we awakened to the beauty of miniaturization. Fashion websites started featuring sustainably sized people shown next to small objects for scale. A woman next to a fire hydrant. A man riding a dog.

Eventually the gene pool responded, and average heights dropped by six inches in 25 years: a mirror-like reflection of the 19th century’s planetary growth spurt. By taking up even just a little less space, we could fit more of our kind on our wilting planet. Nature.

The other day I was watching a historical internet feed where a group of six-footers complained about space on an airplane, one of the older ones that had seats. One tried to recline into the personal space of another—oh no, you’re close to me!—and then, when he stopped her chaise’s descent, she doused him with an entire container of fresh water. (This is an old custom that required he pay $100 to an Ebola patient.) What a waste! But imagine the life back then: free tomato juice and peanuts, so much water that you could just throw it around, and a freewheeling charitable spirit that stretched across the globe. With such excess, it’s no wonder we ended up where we are, but who can blame them? 2014 must truly have been the golden age of flying.

Vote for Eruptions in the 3 Quarks Daily Science Prize

I’m not usually great with self promotion, but my post “So You Think Yellowstone Is Going to Erupt” was nominated (with 85 science articles from all over the spectrum) for the 2014 3 Quarks Daily Science Prize. If you have a moment, head over a cast a vote for my post to move onto the final rounds. You have until Monday September 1 at 11:59 PM EDT to cast your vote. Thanks!

How We Can Get Submarines to Travel at Supersonic Speed

Axisymmetric ventilated supercavitation: ventilation increases and cavitation index decreases from top to bottom.

Axisymmetric ventilated supercavitation: ventilation increases and cavitation index decreases from top to bottom. Cavitation and Bubbly Flows Research Group , University of Minnesota

Chinese researchers say they are developing technology that would allow submarines to travel more than 750 mph. That’s faster than commercial aircraft fly, and yes, it is possible.

The technology is called supercavitation, and it’s been around for decades. The idea is to increase the speed of an object like, say, a submarine or torpedo by creating a bubble around it, reducing drag as it moves through the water. The nose of the vehicle typically is designed to create the bubble, and gas often is used to shape the bubble. The Soviets used this trick on the Shkval torpedo in the 1960s and ’70s; it was capable of 230 mph but for no more than a few miles.

Obviously, the concept is proven. But there are practical problems. “The devil is in the details,” says Dr. Roger Arndt, a University of Minnesota professor who works with the university’s terrifically named Cavitation and Bubbly Flows Research Group.

One of the stickiest wickets is steering a submerged craft that has little in the way of control surfaces in the water. A traditional submarine is controlled by a rudder, much like a conventional boat. Steering a supercavitating vessel requires having control planes pierce the bubble, producing great drag. These planes also would be under tremendous force and pressure at speed, and would need to be extraordinarily strong.

Another challenge: High speeds (for underwater travel) are required to maintain the bubble, perhaps around 45mph, though it would depend greatly on the size and design of the ship. It’s tricky just to reach a speed where a bubble can be created in the first place. So even if the Chinese researchers, at Harbin Institute of Technology’s Complex Flow and Heat Transfer Lab, have made a breakthrough in supercavitation, the limits of standard underwater propulsion will hold them back—especially if they want to make a real submarine. An underwater rocket capable of giving a supercavitating vessel long range doesn’t exist yet. Building a small torpedo is one thing, building a submarine capable of crossing the Pacific is quite another.

A wedge-shaped fin partially piercing a supercavity. Note the partial cavity forming from the leading edge of the fin.

A wedge-shaped fin partially piercing a supercavity. Note the partial cavity forming from the leading edge of the fin. Cavitation and Bubbly Flows Research Group , University of Minnesota

The Chinese researchers told the South China Morning Post they have developed a liquid membrane that tackles both issues. Continuously sprayed on, it would reduce drag and help get the vessel up to speed. The membrane could allow various amounts of friction to be applied to different sides of the ship, creating a steering effect. “By combining liquid-membrane technology with supercavitation, we can significantly reduce the launch challenges and make cruising control easier,” Professor Li Fengchen says.

Details on the new developments are scarce, however. “It’s a quantum leap to making a supersonic submarine,” says Arndt. “What they’re showing doesn’t give an inkling of what technology they’ve got.”

Whatever the Chinese team does have in pocket, it’s not the only one working on the idea of underwater supersonic travel. Arndt says Iran and Russia are among the many countries doing research, along with the American crew at the University of Minnesota. “Everybody is getting in on the act.”

So it may be a while before you clamber into a submarine for a quick trip to Shanghai, but the idea isn’t too far fetched, either.

Predictive Analytics: Potential Cure for What Ails the American Economy?



The way we hire and manage employees in America is fundamentally broken. Not only are unemployment rates still high in most cities, but approximately 32 percent of the current unemployed population has been unemployed for seven months or longer. Many people believe these long term unemployed workers no longer fit in today’s workplace, but they are wrong. To combat this issue the White House just unveiled new legislation for getting America back to work with the recent signing of the Workforce Innovation and Employment Act. Key to this initiative is taking action against the human biases and “skills gap” separating many unemployed workers from the companies that could hire them. As part of the President’s initiative, 300 corporations have pledged to change hiring practices that discriminate against the long term unemployed, enabling qualified individuals to get back to work.

They key vehicle for making that change? Predictive analytics.

It’s now recognized that the use of predictive analytics can surface powerful conclusions from disparate data sources that can, in turn, serve as the catalyst to foster change in business culture, improve hiring and management practices, and enable more Americans to find gainful employment in fulfilling roles. In my own experience at Evolv, just one of the harmful hiring biases we’ve used predictive analytics to debunk is that “People who haven’t worked recently aren’t viable candidates.” Our technology platform looked across millions of data points on employees across our customer network to prove that the long term unemployed perform no worse than those without an extended jobless spell and have empowered our clients (including several of the companies that supported this week’s legislation) to hire those candidates using a predictive score based on this same technology. We hope this finding in particular helps that 32 percent get that interview, that call back – that chance to show employers that they too, can be great additions to a team.

However, even with plenty of data to back up conclusions like this, many people fear and resist the use of big data and predictive analytics in employment practices. Images of robot recruiters with a marked lack of empathy or a dystopian society like the one in George Orwell’s “1984” come to mind. While much of the public conversation focuses on very real problems associated with big data (think NSA), the technology and political spheres have a tremendous opportunity to join forces to solve real human problems.

What’s missing from the current conversation is practical dialogue about how predictive analytics can be the catalyst for impactful partnerships between policy makers and businesses – for example how big data provides insights that destroy stereotypes when it comes to hiring. We are beyond simply “hacking” societal problems and must move toward progressive and actionable steps to change the way we conduct business on a larger scale. The technology industry must partner with America’s leaders to apply innovation to outdated processes that harm our economy’s growth, e.g. leaving millions of Americans out of meaningful work.

Some organizations are already doing great work connecting data science to social good. Kaggle is empowering data scientists to solve for challenges like decoding the human brain, classifying forest categories or predicting survival in disasters. Code for America enables skilled technologists to utilize their skills to impact their local governments by updating outdated sites and creating apps to meet community needs. Even academia has partnered with technology for impactful problem solving; Eric & Wendy Schmidt’s Data Science for Social Good Summer Fellowship is currently incubating its first class of do-good data scientists. But there is much more to be done.

Placing hope in predictive analytics isn’t just blind optimism, however. For example companies who use big data and predictive analytics to alter their management practices can significantly and simultaneously improve the health of their business. In the case of Xerox, one of the companies actively engaged in the push to hire the long-term unemployed, data showed that their prior practice of hiring based on previous work experience in a similar role didn’t necessarily predict success in that candidate’s new job at Xerox. When they opened up new doors for candidates who would previously never have gotten to interview based upon their resume, Xerox then hired more people who were better suited to their job and reduced attrition rates by 20 percent, allowing the company to pocket the otherwise wasted money connected with those who left shortly after onboarding and put workers in best suited roles.

Xerox’s example is just one of the many surrounding how technology and business have worked to impact a societal problem — the possibilities are endless. How can we in business, government and technology work together to solve more human problems — and at greater volumes? Predictive analytics is at once the platform and the catalyst. I hope other leaders look at this week’s report and act. Find ways to use today’s predictive technology capabilities to actively hire candidates who have nontraditional backgrounds but who can also prove (via other signals not found on a resume) that they can and will be successful in the job — especially those who have been unemployed for a long period of time. Using predictive analytics in this way, we can help make better decisions and change the way we work in this country for better.

Carl Tsukahara is responsible for marketing and product strategy at Evolv.

‘The Shift’: BYO Brings a Big Challenge to the Software Community



There was a time not too long ago when web sites and web applications prescribed directions on how each should be sourced to be properly viewed and utilized. For example, on many sites there was a banner that would proclaim that this application or website should be viewed using a certain browser and a specific version of that browser.

Over the past 10 years those banners have slowly disappeared. Instead, we are now faced with “The Shift,” where users dictate how they want to use the applications and websites. Evidence of “The Shift” can be seen across the enterprise, from BYOD (Bring Your Own Device) to BYOBI (Bring Your Own Business Intelligence). While a seemingly small change, “The Shift” can pose a giant challenge for the software community.

In the good old days, software developers had to create, test and validate that their application or website worked on a prescribed browser. The responsibility was on the user to then ensure they had the right browser and only accessed the app or website using the proper source. This meant the software developers’ and testers’ task was relatively simpler, having to only design programs for a well-defined, finite combination of target browsers. Unfortunately, those days are gone.

Today applications and websites live in a very competitive space. They have to not only work on a range of browsers, in varying versions, but also through any mobile platform (which includes device, OS, browser and network combinations) that the user selects. If the applications or websites do not function to the user’s expectation in any of these various combinations, they can easily be lost to competitors.

One of the common strategies developers and testers now deploy to maintain a competitive edge is to rely on application usage analytics. From these analytics, information can be gathered on the distribution of use and can then be applied to target development and testing for specific browser versions and mobile platforms. Frequently analytics reports show heavily concentrated use on a few select popular mobile platforms and a long tail of usage distribution among others. However, making decisions on concentrating development and testing efforts only on the heavily used mobile platforms is dangerous. This could leave out select groups of users — like early adopters who may be moving to a new device or laggards who tend to linger on older devices.

Usage analytics also may not reflect any external events that could affect the market. A new product introduction such as Samsung Galaxy S5 or an iPhone 6 can shift usage dramatically to new devices, and software versions. Most developers and testers are not aware of upcoming releases of devices, OS updates, browser changes and other elements that are critical to their users. Even if there is a level of awareness, not everyone has the means and abilities to procure all of these ahead of time to test and validate their applications. This can inhibit the success of an application or website based on its potentially lowered useability and overall compatibility.

So what is the right strategy to release relevant and configurable applications amidst “The Shift”? In order to reach the comprehensive market of consumer, developers and testers need to use a multi-pronged approach to research their target devices, OS and browsers. An increase in cognitive analysis on the developer level needs to go into this rather than a dependency on product managers or business analysts to prescribe target web and mobile platforms.

A new global product roadmap needs to be created by enterprises to ensure changes that are external to the enterprise are captured and planned for. A good understanding of device, OS, browser and network changes and when they are planned, is essential preparation. Once this information is known, testing in those new mobile platforms should be planned either before the release either using real mobile platforms or emulation (only when it is not available). Combining this with a better insight into current usage analytics will help ready apps for user consumption.

Raj Rao is VP and global head of Software Quality at NTT DATA.

Meet the Rebels in These Awesome New Hunger Games Posters

If there’s anything fans of The Hunger Games know, it’s that advertising is propaganda with a nicer name. So in promoting the film franchise’s next installment, Mockingjay—Part 1, it is appropriate that the marketing onslaught look and feel like the message war that plays out as Katniss Everdeen (Jennifer Lawrence) and her fellow Panem revolutionaries rally to take on the Capitol.

The latest installment is a series of slick “Rebel Warriors” posters. Readers of Mockingjay will remember Katniss, having been rescued from the Hunger Games arena at the end of Catching Fire, was taken to the underground enclave of District 13 to lead Panem’s revolt. These Rebel Warriors posters depict the soldiers and film production crew who join Katniss after she vows to lead the revolution as the Mockingjay (as seen in the film’s first trailer). There’s Cressida (Game of Thrones’ Natalie Dormer), the propaganda documentary director; Gale (Liam Hemsworth), Katniss’ longtime friend and fellow Capitol-hater; Messalla (Evan Ross), Cressida’s assistant; Boggs (Mahershala Ali), Katniss’ bodyguard of sorts; and Castor (Wes Chatham) and Pollux (Elden Henson), who—if their characters follow the book—are brothers and Cressida’s cameramen.

The posters are something of a tide-shift in Mockingjay’s marketing. These images are being released after a series of in-universe (and super-creepy) promos like the “together as one” TV address from President Snow (Donald Sutherland) and images of Panem’s “Heroes.” And, following the way the rebels respond to the propaganda from the Capitol in the books, the posters are coming on the heels of a video showing that Beetee (Jeffrey Wright) interrupted one of Snow’s addresses to announce “the Mockingjay lives” and after a series of Capitol billboards appeared to be vandalized with Mockingjay graffiti in various cities. Clearly, the latest marketing push is all about showing how the rebels are hacking their way to a revolution.

This is the point where the line between marketing and symbolism from the Hunger Games meet. Just as the lead-up to Catching Fire was littered with “Capitol Couture” and Victory Tour ads, this one evokes the guerrilla tactics the rebels might use to spread the word that fire is catching. Cue up a four-note whistle and put three fingers in the air.

The Hunger Games: Mockingjay—Part 1 hits theaters Nov. 21.