Engineers harvest heart's energy to power life-saving devices

Dartmouth engineers develop dime-sized device to capture and convert the kinetic energy of the heart into electricity to power a wide-range of implantable devices.

The heart's motion is so powerful that it can recharge devices that save our lives, according to new research from Dartmouth College.

Using a dime-sized invention developed by engineers at the Thayer School of Engineering at Dartmouth, the kinetic energy of the heart can be converted into electricity to power a wide-range of implantable devices, according to the study funded by the National Institutes of Health.

Millions of people rely on pacemakers, defibrillators and other live-saving implantable devices powered by batteries that need to be replaced every five to 10 years. Those replacements require surgery which can be costly and create the possibility of complications and infections.

"We're trying to solve the ultimate problem for any implantable biomedical device," says Dartmouth engineering professor John X.J. Zhang, a lead researcher on the study his team completed alongside clinicians at the University of Texas in San Antonio. "How do you create an effective energy source so the device will do its job during the entire life span of the patient, without the need for surgery to replace the battery?"

"Of equal importance is that the device not interfere with the body's function," adds Dartmouth research associate Lin Dong, first author on the paper. "We knew it had to be biocompatible, lightweight, flexible, and low profile, so it not only fits into the current pacemaker structure but is also scalable for future multi-functionality."

The team's work proposes modifying pacemakers to harness the kinetic energy of the lead wire that's attached to the heart, converting it into electricity to continually charge the batteries. The added material is a type of thin polymer piezoelectric film called "PVDF" and, when designed with porous structures -- either an array of small buckle beams or a flexible cantilever -- it can convert even small mechanical motion to electricity. An added benefit: the same modules could potentially be used as sensors to enable data collection for real-time monitoring of patients.

The results of the three-year study, completed by Dartmouth's engineering researchers along with clinicians at UT Health San Antonio, were just published in the cover story for Advanced Materials Technologies.

The two remaining years of NIH funding plus time to finish the pre-clinical process and obtain regulatory approval puts a self-charging pacemaker approximately five years out from commercialization, according to Zhang.

"We've completed the first round of animal studies with great results which will be published soon," says Zhang. "There is already a lot of expressed interest from the major medical technology companies, and Andrew Closson, one of the study's authors working with Lin Dong and an engineering PhD Innovation Program student at Dartmouth, is learning the business and technology transfer skills to be a cohort in moving forward with the entrepreneurial phase of this effort."

New disease surveillance tool helps detect any human-infecting virus

A computational method helps scientists examine microbes at a larger, more comprehensive scale than previously possible.

During the Zika virus outbreak of 2015-16, public health officials scrambled to contain the epidemic and curb the pathogen's devastating effects on pregnant women. At the same time, scientists around the globe tried to understand the genetics of this mysterious virus.

The problem was, there just aren't many Zika virus particles in the blood of a sick patient. Looking for it in clinical samples can be like fishing for a minnow in an ocean.

A new computational method developed by Broad Institute scientists helps overcome this hurdle. Built in the lab of Broad Institute researcher Pardis Sabeti, the "CATCH" method can be used to design molecular "baits" for any virus known to infect humans and all their known strains, including those that are present in low abundance in clinical samples, such as Zika. The approach can help small sequencing centers around the globe conduct disease surveillance more efficiently and cost-effectively, which can provide crucial information for controlling outbreaks.

The new study was led by MIT graduate student Hayden Metsky and postdoctoral researcher Katie Siddle, and it appears online in Nature Biotechnology.

"As genomic sequencing becomes a critical part of disease surveillance, tools like CATCH will help us and others detect outbreaks earlier and generate more data on pathogens that can be shared with the wider scientific and medical research communities," said Christian Matranga, a co-senior author of the new study who has joined a local biotech startup.

Scientists have been able to detect some low-abundance viruses by analyzing all the genetic material in a clinical sample, a technique known as "metagenomic" sequencing, but the approach often misses viral material that gets lost in the abundance of other microbes and the patient's own DNA.

Another approach is to "enrich" clinical samples for a particular virus. To do this, researchers use a kind of genetic "bait" to immobilize the target virus's genetic material, so that other genetic material can be washed away. Scientists in the Sabeti lab had successfully used baits, which are molecular probes made of short strands of RNA or DNA that pair with bits of viral DNA in the sample, to analyze the Ebola and Lassa virus genomes. However, the probes were always directed at a single microbe, meaning they had to know exactly what they were looking for, and they were not designed in a rigorous, efficient way.

What they needed was a computational method for designing probes that could provide a comprehensive view of the diverse microbial content in clinical samples, while enriching for low-abundance microbes like Zika.

"We wanted to rethink how we were actually designing the probes to do capture," said Metsky. "We realized that we could capture viruses, including their known diversity, with fewer probes than we'd used before. To make this an effective tool for surveillance, we then decided to try targeting about 20 viruses at a time, and we eventually scaled up to the 356 viral species known to infect humans."

Short for "Compact Aggregation of Targets for Comprehensive Hybridization," CATCH allows users to design custom sets of probes to capture genetic material of any combination of microbial species, including viruses or even all forms of all viruses known to infect humans.

To run CATCH truly comprehensively, users can easily input genomes from all forms of all human viruses that have been uploaded to the National Center for Biotechnology Information's GenBank sequence database. The program determines the best set of probes based on what the user wants to recover, whether that's all viruses or only a subset. The list of probe sequences can be sent to one of a few companies that synthesize probes for research. Scientists and clinical researchers looking to detect and study the microbes can then use the probes like fishing hooks to catch desired microbial DNA for sequencing, thereby enriching the samples for the microbe of interest.

Tests of probe sets designed with CATCH showed that after enrichment, viral content made up 18 times more of the sequencing data than before enrichment, allowing the team to assemble genomes that could not be generated from un-enriched samples. They validated the method by examining 30 samples with known content spanning eight viruses. The researchers also showed that samples of Lassa virus from the 2018 Lassa outbreak in Nigeria that proved difficult to sequence without enrichment could be "rescued" by using a set of CATCH-designed probes against all human viruses. In addition, the team was able to improve viral detection in samples with unknown content from patients and mosquitos.

Using CATCH, Metsky and colleagues generated a subset of viral probes directed at Zika and chikungunya, another mosquito-borne virus found in the same geographic regions. Along with Zika genomes generated with other methods, the data they generated using CATCH-designed probes helped them discover that the Zika virus had been introduced in several regions months before scientists were able to detect it, a finding that can inform efforts to control future outbreaks.

To demonstrate other potential applications of CATCH, Siddle used samples from a range of different viruses. Siddle and others have been working with scientists in West Africa, where viral outbreaks and hard-to-diagnose fevers are common, to establish laboratories and workflows for analyzing pathogen genomes on-site. "We'd like our partners in Nigeria to be able to efficiently perform metagenomic sequencing from diverse samples, and CATCH helps them boost the sensitivity for these pathogens," said Siddle.

The method is also a powerful way to investigate undiagnosed fevers with a suspected viral cause. "We're excited about the potential to use metagenomic sequencing to shed light on those cases and, in particular, the possibility of doing so locally in affected countries," said Siddle.

One advantage of the CATCH method is its adaptability. As new mutations are identified and new sequences are added to GenBank, users can quickly redesign a set of probes with up-to-date information. In addition, while most probe designs are proprietary, Metsky and Siddle have made publicly available all of the ones they designed with CATCH. Users have access to the actual probe sequences in CATCH, allowing researchers to explore and customize the probe designs before they are synthesized.

Sabeti and fellow researchers are excited about the potential for CATCH to improve large-scale high-resolution studies of microbial communities. They are also hopeful that the method could one day have utility in diagnostic applications, in which results are returned to patients to make clinical decisions. For now, they're encouraged by its potential to improve genomic surveillance of viral outbreaks like Zika and Lassa, and other applications requiring a comprehensive view of low-level microbial content.

The CATCH software is publicly accessible on GitHub. Its development and validation, supervised by Sabeti and Matranga, is described online in Nature Biotechnology.

Huge cavity in Antarctic glacier signals rapid decay

Thwaites Glacier.

A gigantic cavity -- two-thirds the area of Manhattan and almost 1,000 feet (300 meters) tall -- growing at the bottom of Thwaites Glacier in West Antarctica is one of several disturbing discoveries reported in a new NASA-led study of the disintegrating glacier. The findings highlight the need for detailed observations of Antarctic glaciers' undersides in calculating how fast global sea levels will rise in response to climate change.

Researchers expected to find some gaps between ice and bedrock at Thwaites' bottom where ocean water could flow in and melt the glacier from below. The size and explosive growth rate of the newfound hole, however, surprised them. It's big enough to have contained 14 billion tons of ice, and most of that ice melted over the last three years.

"We have suspected for years that Thwaites was not tightly attached to the bedrock beneath it," said Eric Rignot of the University of California, Irvine, and NASA's Jet Propulsion Laboratory in Pasadena, California. Rignot is a co-author of the new study, which was published in Science Advances. "Thanks to a new generation of satellites, we can finally see the detail," he said.

The cavity was revealed by ice-penetrating radar in NASA's Operation IceBridge, an airborne campaign beginning in 2010 that studies connections between the polar regions and the global climate. The researchers also used data from a constellation of Italian and German spaceborne synthetic aperture radars. These very high-resolution data can be processed by a technique called radar interferometry to reveal how the ground surface below has moved between images.

"[The size of] a cavity under a glacier plays an important role in melting," said the study's lead author, Pietro Milillo of JPL. "As more heat and water get under the glacier, it melts faster."

Numerical models of ice sheets use a fixed shape to represent a cavity under the ice, rather than allowing the cavity to change and grow. The new discovery implies that this limitation most likely causes those models to underestimate how fast Thwaites is losing ice.

About the size of Florida, Thwaites Glacier is currently responsible for approximately 4 percent of global sea level rise. It holds enough ice to raise the world ocean a little over 2 feet (65 centimeters) and backstops neighboring glaciers that would raise sea levels an additional 8 feet (2.4 meters) if all the ice were lost.

Thwaites is one of the hardest places to reach on Earth, but it is about to become better known than ever before. The U.S. National Science Foundation and British National Environmental Research Council are mounting a five-year field project to answer the most critical questions about its processes and features. The International Thwaites Glacier Collaboration will begin its field experiments in the Southern Hemisphere summer of 2019-20.

How Scientists Measure Ice Loss

There's no way to monitor Antarctic glaciers from ground level over the long term. Instead, scientists use satellite or airborne instrument data to observe features that change as a glacier melts, such as its flow speed and surface height.

Another changing feature is a glacier's grounding line -- the place near the edge of the continent where it lifts off its bed and starts to float on seawater. Many Antarctic glaciers extend for miles beyond their grounding lines, floating out over the open ocean.

Just as a grounded boat can float again when the weight of its cargo is removed, a glacier that loses ice weight can float over land where it used to stick. When this happens, the grounding line retreats inland. That exposes more of a glacier's underside to sea water, increasing the likelihood its melt rate will accelerate.

An Irregular Retreat

For Thwaites, "We are discovering different mechanisms of retreat," Millilo said. Different processes at various parts of the 100-mile-long (160-kilometer-long) front of the glacier are putting the rates of grounding-line retreat and of ice loss out of sync.

The huge cavity is under the main trunk of the glacier on its western side -- the side farther from the West Antarctic Peninsula. In this region, as the tide rises and falls, the grounding line retreats and advances across a zone of about 2 to 3 miles (3 to 5 kilometers). The glacier has been coming unstuck from a ridge in the bedrock at a steady rate of about 0.4 to 0.5 miles (0.6 to 0.8 kilometers) a year since 1992. Despite this stable rate of grounding-line retreat, the melt rate on this side of the glacier is extremely high.

"On the eastern side of the glacier, the grounding-line retreat proceeds through small channels, maybe a kilometer wide, like fingers reaching beneath the glacier to melt it from below," Milillo said. In that region, the rate of grounding-line retreat doubled from about 0.4 miles (0.6 kilometers) a year from 1992 to 2011 to 0.8 miles (1.2 kilometers) a year from 2011 to 2017. Even with this accelerating retreat, however, melt rates on this side of the glacier are lower than on the western side.

These results highlight that ice-ocean interactions are more complex than previously understood.

Milillo hopes the new results will be useful for the International Thwaites Glacier Collaboration researchers as they prepare for their fieldwork. "Such data is essential for field parties to focus on areas where the action is, because the grounding line is retreating rapidly with complex spatial patterns," he said.

"Understanding the details of how the ocean melts away this glacier is essential to project its impact on sea level rise in the coming decades," Rignot said.

The paper by Milillo and his co-authors in the journal Science Advances is titled "Heterogeneous retreat and ice melt of Thwaites Glacier, West Antarctica." Co-authors were from the University of California, Irvine; the German Aerospace Center in Munich, Germany; and the University Grenoble Alpes in Grenoble, France.

Laughter may be best medicine -- for brain surgery

Illustration showing how an electrode was inserted into the cingulum bundle.

Neuroscientists at Emory University School of Medicine have discovered a focal pathway in the brain that when electrically stimulated causes immediate laughter, followed by a sense of calm and happiness, even during awake brain surgery. The effects of stimulation were observed in an epilepsy patient undergoing diagnostic monitoring for seizure diagnosis. These effects were then harnessed to help her complete a separate awake brain surgery two days later.

The behavioral effects of direct electrical stimulation of the cingulum bundle, a white matter tract in the brain, were confirmed in two other epilepsy patients undergoing diagnostic monitoring. The findings are scheduled for publication in the Journal of Clinical Investigation. Videos of the effects of cingulum bundle stimulation are available, with the patient's identity obscured.

Emory neurosurgeons see the technique as a "potentially transformative" way to calm some patients during awake brain surgery, even for people who are not especially anxious. For optimal protection of critical brain functions during surgery, patients may need to be awake and not sedated, so that doctors can talk with them, assess their language skills, and detect impairments that may arise from resection.

"Even well-prepared patients may panic during awake surgery, which can be dangerous," says lead author Kelly Bijanki, PhD, assistant professor of neurosurgery. "This particular patient was especially prone to it because of moderate baseline anxiety. And upon waking from global anesthesia, she did indeed begin to panic. When we turned on her cingulum stimulation, she immediately reported feeling happy and relaxed, told jokes about her family, and was able to tolerate the awake procedure successfully."

Outside of use during awake surgery, understanding how cingulum bundle stimulation works could also inform efforts to better treat depression, anxiety disorders, or chronic pain via deep brain stimulation.

Previous investigators have reported that direct electrical stimulation of other parts of the brain can trigger laughter, but the demonstration that anti-anxiety effects observed with cingulum bundle stimulation can provide meaningful clinical benefits make this study distinct, says senior author Jon T, Willie, MD, PhD, who performed the surgeries reported in the paper. He is assistant professor of neurosurgery and neurology at Emory University School of Medicine.

Additional Emory authors include Joseph Manns, PhD, Cory Inman, PhD, graduate student Sahar Harati , Nigel Pedersen, MD, Daniel Drane, PhD, and Rebecca Fasano, MD. Authors who are now at Mount Sinai in New York City are Ki Sueng Choi, PhD, Allison Waters, PhD and Helen Mayberg, MD, all previously at Emory.

Lying under the cortex and curving around the midbrain, the cingulum bundle has a shape resembling a girdle or belt -- hence its Latin name. The area that was a key to laughter and relaxation lies at the top and front of the bundle. The bundle is a logical target because of its many connections among brain regions coordinating complex emotional responses, Willie says.

The location of cingulum bundle stimulation is distinct from other brain locations that process reward, such as ventral striatum, which has been targeted for the treatment of depression and addiction. Because the cingulum bundle is a crossroads for white matter connecting several lobes, Willie and his team may be affecting widespread networks throughout the brain.

Willie says the locations of initial electrode placement were chosen in order to record brain activity and locate the onset of the first patient's seizures. The electrode initially used to stimulate the cingulum bundle was inserted into the brain in a way that was different than standard, he says. The unique trajectory was necessary because of the first patient's previous surgeries; the approach was from the rear (see illustration), leading to a broader extent of cingulum bundle being sampled and therefore accessible for electrical stimulation.

The JCI paper says that cingulum bundle stimulation "immediately elicited mirthful behavior, including smiling and laughing, and reports of positive emotional experience."

"The patient described the experience as pleasant and relaxing and completely unlike any component of her typical seizure or aura," the authors write. "She reported an involuntary urge to laugh that began at the onset of stimulation and evolved into a pleasant, relaxed feeling over the course of a few seconds of stimulation."

As a test of her mood and thought processes, the researchers tested how the first patient viewed faces and whether she interpreted them as happy, sad or neutral. Cingulum bundle stimulation shifted her view of faces so that they were interpreted as happier. This effect, called "affective bias" is known to correspond with the reduction of depressive symptoms, and suggests a potential use of cingulum stimulation in treating depression.

The two other patients that underwent cingulum stimulation and behavioral testing did not undergo awake surgery for epilepsy treatment. Upon stimulation, they both also smiled and reported mood elevation and pain relief, and at higher levels of current, experienced laughter. During stimulation, one of the later patients took tests of attention, memory and language and performed normally, except for delayed verbal recall on a list-learning task.

The researchers envision cingulum bundle stimulation as potentially applicable to surgery for brain tumors, as well as epilepsy.

"We could be surer of safe boundaries for removal of pathological tissue and preservation of tissue encoding critical human functions such as language, emotional, or sensory functions, which can't be evaluated with the patient sedated," Bijanki says. "In addition, although substantial further study is necessary in this area, the cingulum bundle could become a new target for chronic deep brain stimulation therapies for anxiety, mood, and pain disorders."

The research was supported by the American Foundation for Suicide Prevention (YIG-727 0-015-13), the National Center for Advancing Translational Sciences (UL1TR002378, KL2TR002381), the National Institute of Neurological Disease and Stroke (R21NS104953, K08NS105929, R01NS088748, K02NS070960) and the National Institute of Mental Health (K01MH116364).

Interesting Facts about Airports, Airlines and Air Traveling.

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1. All International Airline Pilots speak English.

2. Flights longer than 8 hours require 3 pilots (1 captain and 2 first officers) to rotate flying duties. Flights longer than 12 hours require 4 pilots (1 captain and 3 first officers). They usually fly 3-4 hour shifts.

3. Each airline pilot flying the aircraft, eats a different meal to minimize the risk of all pilots on board being ill.

4. The height requirement for Flight Attendant is for safety reasons, making sure that all flight attendants can reach overhead safety equipment.

5. An air traveler can lose approximately 1.5 liters of water in the body during a three-hour flight.

6. The reason why the lights are turned out during takeoff and landing Is for your eyes to adjust to lower levels of light.

7. The World's largest Airline in terms of Fleet Size is Emirates airline  (United Arab Emirates) with 744 aircraft and 121 aircraft on order.

8. The largest passenger plane is the Airbus 380 - nearly 240 feet long, almost 80 feet high, and has a wingspan of more than 260 feet. The double-decker plane has a standard seating capacity of 555 passengers for Emirates airline.

9. The Internet/On-Line check-in was first used by Alaskan Airlines in 1999.

10. The world's Largest Airport is Kansai International Airport, Osaka, Japan (as of 2011). By 2019 Al Maktoum International Airport in Jebel Ali, Dubai, United Arab Emirates is planned to be the largest airport in the world.

11. The airport with the longest runway in the world is Qamdo Bangda Airport in the People’s Republic of China with 5.50 kilometers in length.

12. Singapore Airlines spends about $700 million on food every year and $16 million on wine alone. First class passengers consume 20,000 bottles of alcohol every month and Singapore Airlines is the second largest buyer of Dom Perignon champagne in the world.

13. KLM of Netherlands stands for Koninklijke Luchtvaart Maatschappij (meaning Royal Dutch Airlines).

14. KLM is the worlds' oldest airline established in 1919.

15. QANTAS - Australia's national airline, originally stood for Queensland and Northern Territories Air Service.

16. QANTAS is the world's second oldest airline established in 1920.

17. QANTAS still has the world's best safety record with no crashes.

18. Virgin Atlantic lists catering as their third biggest expense, after fuel and maintenance.

19. In one year, British Airways passengers consume: 40.5 tons of chicken, 6 tons of caviar, 22 tons of smoked salmon, 557,507 boxes of chocolate and 90 thousand cases (9 liter cases) of sparkling wine.

20. Keeping the blinds open while take off and landing is for the passengers to spot any fire in the wings or to spot any vehicles in the tarmac so they could alert the crew.

21. Instruction to fasten the seat belts and to make the seat upright while take off and landing is primarily for the safety of the passengers.
But it also stabilizes the centre of gravity of the aircraft and helps controlling the plane.