Real-time tracking system developed to monitor dangerous bacteria inside body

Combining a PET scanner with a new chemical tracer that selectively tags specific types of bacteria, Johns Hopkins researchers working with mice report they have devised a way to detect and monitor in real time infections with a class of dangerous Gram-negative bacteria. These increasingly drug-resistant bacteria are responsible for a range of diseases, including fatal pneumonias and various bloodstream or solid-organ infections acquired in and outside the hospital.



"What we have produced is essentially a system that localizes the epicenter of infection and provides real-time tracking of bacterial activity, giving us rapid feedback on how the bacteria respond to antibiotics," says principal investigator Sanjay Jain, M.D., an infectious disease specialist at the Johns Hopkins Children's Center and director of the Center for Inflammation Imaging and Research at Johns Hopkins.


Describing their work in the Oct. 22 issue of the journal Science Translational Medicine, the team says the simplicity, speed and accuracy of the imaging model could change the way dangerous bacterial infections are diagnosed, monitored and treated. Although the work was conducted in mice, the researchers say clinical application in humans could happen quickly, because the system capitalizes on already available imaging devices -- PET scans -- and materials.


"Our approach could quickly and reliably detect infections caused by certain Gram-negative organisms and could speed up diagnosis and treatment by eliminating days-long waits for lab test results," says study co-author Edward Weinstein, M.D., Ph.D., an infectious disease specialist at the Johns Hopkins University School of Medicine. "Perhaps more importantly, the technique can give us critical insights into the basic mechanisms of disease and can help us evaluate the effect of drug therapy quickly."


The new technique, the researchers say, is superior to current imaging tools because it selectively precision-targets a common class of Gram-negative bacteria known as Enterobacteriaceae that includes notoriously virulent germs such as E. coli, Salmonella, Klebsiella, and dozens of other pathogens that can be particularly dangerous in hospitalized people. Some of the germs in the class, the research team notes, could also be used as biological weapons.


Current imaging tools, such as CT, MRI and PET scans, use inflammation as a surrogate to diagnose and monitor infection, the researchers say. Yet inflammation, which is the body's response to infection rather than infection itself, is not specific to bacteria and cannot distinguish true infections from non-infectious inflammation such as inflammation caused by cancer.


The new model emerged from a creative combination of existing PET scan technology -- a sophisticated 3-D visualization system for tumor imaging -- with an ingredient commonly used in sugar-free foods known as sorbitol. The model capitalizes on Gram-negative bacteria's fondness for sorbitol, which they readily soak up. By contrast, other classes of bacteria and other microorganisms, cancer, and human cells do not absorb sorbitol. The researchers hypothesized that converting an already available PET imaging tracer into radio-labeled sorbitol would selectively tag and light up clusters of Gram-negative bacteria inside the body. It did.


When researchers injected mice with the Gram-negative bacterium E. coli in one thigh and harmless dead bacteria in the other thigh, both injections produced inflammation. However, only the cluster of live E. coli attracted the radio tracer and lit up the screen -- a critical feature that let the researchers distinguish the actual bacterial infection from noninfectious inflammation. When the researchers injected one thigh with Gram-negative E. coli and the other thigh with the Gram-positive bacterium Staphyloccocus aureus, the radio tracer lit up only the thigh infected by the Gram-negative organism. In other words, the sorbitol-containing tracer differentiated between bacterial and sterile inflammation, as well as between infections caused by different classes of bacteria. Next, the researchers compared how their modified tracer fared in distinguishing brain inflammation caused by E. coli from cancer-induced brain inflammation. The tracer reliably and predictably lit up E. coli hot spots in the brain but not brain tumor cells.


When serious drug-resistant infections are suspected, the researchers explain, patients are routinely given broad-spectrum antibiotics while waiting -- often for days -- for lab tests to determine the specific organism responsible for the infection and which drugs should be used. Broad-spectrum antibiotics treat many bacteria at once, but their frequent and indiscriminate use has fueled drug resistance in recent years, making many pathogens impervious to common antibiotics.


"Using broad-spectrum antibiotics is not unlike firing a cannonball to kill a fly," says study co-author Alvaro Ordonez, M.D., a fellow in pediatric infectious diseases at the Johns Hopkins University School of Medicine. "While such treatment is clinically justified in patients with serious infections of unknown origin, it promotes bacterial resistance, so the long-term price that both patients and clinicians pay is rather steep."


Knowing quickly which organism is causing a patient's infection and which antibiotic can kill the bacteria could seriously lower that cost, Ordonez adds. This is where the new imaging system could play a critical role. In a separate set of experiments, the investigators showed that their imaging system rapidly captured how bacteria respond to drug treatment in real time. Targeted with the right antibiotic, the dying bacteria produced a visibly and progressively weaker image. By contrast, when bacteria failed to respond to an antibiotic, the strength of the signal remained as intense as ever, heralding treatment failure. Receiving such rapid feedback within hours instead of days could have profound effects on treatment decisions.


"Earlier identification of bacterial drug sensitivity could not only get patients on the mend sooner by giving them the right antibiotic, but in the long run it could save the U.S. health care system billions of dollars in unnecessary drug treatment," Jain says.



Mark Zuckerberg Speaks Mandarin, Blows Everyone’s Mind


zuckerberg-china

Facebook



Think you’re too busy to learn another language? Well, you’re not the CEO of a $205 billion company, and apparently, even this rather demanding job leaves plenty of time to learn some serious Mandarin.


Case in point: the video that Mark Zuckerberg just posted to, yes, Facebook. It shows off his 30-minute Q&A at Tsinghua University in Beijing in which he answered every question exclusively in Chinese.


I don’t know Mandarin, so I can’t say how well he spoke. But the audience was decidedly thrilled. The crowd gasped and applauded as soon as he started speaking, and the good vibes appeared to last throughout the chat. Of course, the 21st century’s most fabled boy-genius entrepreneur could probably speak to business school students in pig Latin and still get a rapturous response.


Zuckerberg’s proficiency would appear to be the positive result of one of his annual self-improvement challenges. Every year, Zuckerberg picks a skill or a goal to pursue with extreme focus. This year, the plan was to write one thoughtful thank-you note every day. In 2010, his aim was to learn Mandarin.


The effort seems to have paid off in a whole lot of good will from his audience at Tsinghua, where he said he also just joined the board of the university’s School of Economics and Management. But the ultimate purpose of Zuckerberg’s charm offensive is probably much more ambitious. Right now, Facebook is still banned in China. Maybe next year, his goal will be to get it unblocked. Maybe he can promise the Chinese government a nice thank-you note—written in Mandarin.



China’s Largest Smartphone Maker Vows To Move Online Services Overseas


Hugo Barra. Photo: Ariel Zambelich/Wired

Hugo Barra. Photo: Ariel Zambelich/Wired



In a move that could show the way forward for many Chinese companies hoping to compete in the worldwide tech market, China’s largest smartphone manufacturer, Xiaomi, says it will shift its online services to machines running outside the country.


Hugo Barra, the former Google executive who oversees Xiaomi’s international operation, made the announcement this morning with a post to Facebook, saying the move will affect all oversees users. “In early 2014, we kicked off a massive internal effort to expand our server infrastructure globally,” wrote Barra, who worked on Google’s Android operating system at the U.S. search giant. “This is a very high priority for Xiaomi as we expand into new markets over the next few years.”


He painted the move as a way of improving the speed of its smartphone services in places like India, Indonesia, Malaysia, the Philippines, and Taiwan, while also ensuring that user data is securely stored. In most cases, Xiaomi’s services will run atop overseas installations of Amazon’s popular cloud computing services. But the clear subtext of the announcement is that Xiaomi wants to allay fears that it’s sending user data back to Beijing and potentially sharing it with the Chinese government. “They’re trying to reassure users internationally that their data won’t be in China,” says Adam Segal, a senior fellow for China Studies at the Center for Foreign Relations.


Earlier this week in India, one of the countries where Xiaomi has expanded its operations, the New India Express reported that the Indian Air Force is warning that Xiaomi phones are sending data back to servers in Beijing, and this followed a report from security company FSecure that Xiaomi was grabbing personal smartphone data without permission.


Barra did not respond to a request for comment on the matter, but he has apologized for such data collection in speaking with other news outlets in the past.


For Segal, Xiaomi’s announcement is merely a first step towards convincing overseas users that the company won’t compromise their data. “You’d have to wait to see the details to see how reassured you’d be,” he says. “Even if the servers are outside of China, they could be mirrored back into China. They’ll have to work pretty hard to reassure people.” But he believes this kind of move could provide a template for other Chinese tech companies looking to expand their operations overseas.


Thanks to assumptions that Chinese companies are too close to the Chinese government, the Chinese networking hardware manufacturer Huawei has faced difficulties overseas—with many questioning whether the Chinese government has installed back doors in its hardware—and as Segal points out, the same issues hang over not only Xiaomi but other online Chinese companies, such as WeChat. “We know that the relationship between companies and the government is very close,” Segal says.


There is no hard evidence, he says, that companies are freely sharing data with the government, but the fact of the matter is that many overseas pundits, policy makers, and businesses believe that they do. As Chinese tech companies increasingly move their operations overseas in an effort to capture international dollars, they will have to address these fears. “We haven’t had that many Chinese companies go global yet,” Segal says. “Xiaomi and WeChat are first consumer companies to do so, and this announcement is reflective of a next stage of development.” Chinese e-commerce giant Alibaba recently IPOed in the U.S. but it has yet offer online services Stateside. If it does, Segal says, he suspects it too will do so from local machines.



Our First Look at Android Lollipop and the New Nexus Devices




We had our first hands-on demo of Google’s new version of its Android operating system, Lollipop, this week running on a pair of Nexus devices, the Nexus 6 and Nexus 9. This was a three-for-the-price-of-one demo, with lots to take in. But the bottom line is that this is a great upgrade to Android, and our first impression of the new Nexus devices was that both are really wonderful.


Our favorite thing about both (and Lollipop)? Notifications. They’re simply the best. They have essentially become the centerpiece of the device experience. The way they stack, flow, and get prioritized on the lock screen is a really nice experience. They’re going to save a lot of time.


And then there’s the Nexus 6 display. We didn’t get a chance to fully put it through its paces, but the 6-inch Quad HD AMOLED display packs in 493 ppi and is just stunning to look at. We also liked the way you can just double tap on it now to wake it up, and instantly get to your notifications. This was very… handy.


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Likewise, the ambient display, which lets the device show you notifications in a low power black and white mode, was both effective and useful. Want to make sure a notification rises to the top? We were able to set them up as a priority notification in just a couple of taps, right from the lock screen. It’s great. (You can banish notifications just as easily.)


Another really nice trick is the way Lollipop unlocks based on your face. Android has had this capability for a long time, but now it’s automated. It begins to look for your face as soon as you wake it up. This meant that often, even before you begin to enter your PIN or unlock pattern, the device unlocks and lets you in. It’s super slick.


We’re really excited for all these releases—Lollipop, Nexus 6, and Nexus 9. But really, at a demo you only get to see the best a device and platform has to offer. Stay tuned for a full review in the coming weeks.