Surgical and engineering innovations enable unprecedented control over every finger of a bionic hand

 Prosthetic limbs are the most common solution to replace a lost extremity. However, they are hard to control and often unreliable with only a couple of movements available. Remnant muscles in the residual limb are the preferred source of control for bionic hands. This is because patients can contract muscles at will, and the electrical activity generated by the contractions can be used to tell the prosthetic hand what to do, for instance, open or close. A major problem at higher amputation levels, such as above the elbow, is that not many muscles remain to command the many robotic joints needed to truly restore the function of an arm and hand.

A multidisciplinary team of surgeons and engineers has circumvented this problem by reconfiguring the residual limb and integrating sensors and a skeletal implant to connect with a prosthesis electrically and mechanically. By dissecting the peripheral nerves and redistributing them to new muscle targets used as biological amplifiers, the bionic prosthesis can now access much more information so the user can command many robotic joints at will (video: https://youtu.be/h1N-vKku0hg).

The research was led by Professor Max Ortiz Catalan, Founding Director of the Center for Bionics and Pain Research (CBPR) in Sweden, Head of Neural Prosthetics Research at the Bionics Institute in Australia, and Professor of Bionics at Chalmers University of Technology in Sweden.

"In this article, we show that rewiring nerves to different muscle targets in a distributed and concurrent manner is not only possible but also conducive to improved prosthetic control. A key feature of our work is that we have the possibility to clinically implement more refine surgical procedures and embed sensors in the neuromuscular constructs at the time of the surgery, which we then connect to the electronic system of the prosthesis via an osseointegrated interface. A.I. algorithms take care of the rest."

Prosthetic limbs are commonly attached to the body by a socket that compresses the residual limb causing discomfort and is mechanically unstable. An alternative to socket attachment is to use a titanium implant placed within the residual bone which becomes strongly anchored -- this is known as osseointegration. Such skeletal attachment allows for comfortable and more efficient mechanical connection of the prosthesis to the body.

"It is rewarding to see that our cutting-edge surgical and engineering innovation can provide such a high level of functionality for an individual with an arm amputation. This achievement is based on over 30 years of gradual development of the concept, in which I am proud to have contributed" comments Dr. Rickard Brånemark, research affiliate at MIT, associate professor at Gothenburg University, CEO of Integrum, a leading expert on osseointegration for limb prostheses, who conducted the implantation of the interface.

The surgery took place at the Sahlgrenska University Hospital, Sweden, where CBPR is located. The neuromuscular reconstruction procedure was conducted by Dr. Paolo Sassu, who also led the first hand transplantation performed in Scandinavia.

"The incredible journey we have undertaken together with the bionic engineers at CBPR has allowed us to combine new microsurgical techniques with sophisticated implanted electrodes that provide single-finger control of a prosthetic arm as well as sensory feedback. Patients who have suffered from an arm amputation might now see a brighter future," says Dr. Sassu, who is presently working at the Istituto Ortopedico Rizzoli in Italy.

The Science Translational Medicine article illustrates how the transferred nerves progressively connected to their new hosting muscles. Once the innervation process had advanced enough, the researchers connected them to the prosthesis so the patient could control every finger of a prosthetic hand as if it would be his own (video: https://youtu.be/FdDdZQg58kc). The researchers also demonstrated how the system respond in activities of the daily life (video: https://youtu.be/yC24WRoGIe8) and are currently in the process of further improving the controllability of the bionic hand.

Genes for learning and memory are 650 million years old

 A team of scientists led by researchers from the University of Leicester have discovered that the genes required for learning, memory, aggression and other complex behaviours originated around 650 million years ago.

The findings led by Dr Roberto Feuda, from the Neurogenetic group in the Department of Genetics and Genome Biology and other colleagues from the University of Leicester and the University of Fribourg (Switzerland), have now been published in Nature Communications.

Dr Feuda said: "We've known for a long time that monoamines like serotonin, dopamine and adrenaline act as neuromodulators in the nervous system, playing a role in complex behaviour and functions like learning and memory, as well as processes such as sleep and feeding.

"However, less certain was the origin of the genes required for the production, detection, and degradation of these monoamines. Using the computational methods, we reconstructed the evolutionary history of these genes and show that most of the genes involved in monoamine production, modulation, and reception originated in the bilaterian stem group.

"This finding has profound implications on the evolutionary origin of complex behaviours such as those modulated by monoamines we observe in humans and other animals."

The authors suggest that this new way to modulate neuronal circuits might have played a role in the Cambrian Explosion -- known as the Big Bang -- which gave rise to the largest diversification of life for most major animal groups alive today by providing flexibility of the neural circuits to facilitate the interaction with the environment.

Dr Feuda added: "This discovery will open new important research avenues that will clarify the origin of complex behaviours and if the same neurons modulate reward, addiction, aggression, feeding, and sleep."

Liquid safety cushioning technology

The discovery that football players were unknowingly acquiring permanent brain damage as they racked up head hits throughout their professional careers created a rush to design better head protection. One of these inventions is nanofoam, the material on the inside of football helmets.

Thanks to mechanical and aerospace engineering associate professor Baoxing Xu at the University of Virginia and his research team, nanofoam just received a big upgrade and protective sports equipment could, too. This newly invented design integrates nanofoam with "non-wetting ionized liquid," a form of water that Xu and his research team now know blends perfectly with nanofoam to create a liquid cushion. This versatile and responsive material will give better protection to athletes and is promising for use in protecting car occupants and aiding hospital patients using wearable medical devices.

The team's research was recently published in Advanced Materials.

For maximum safety, the protective foam sandwiched between the inner and outer layers of a helmet should not only be able to take one hit but multiple hits, game after game. The material needs to be cushiony enough to create a soft place for a head to land, but resilient enough to bounce back and be ready for the next blow. And the material needs to be resilient but not hard, because "hard" hurts heads, too. Having one material do all of these things is a pretty tall order.

The team advanced their work previously published in the Proceedings of the National Academy of Sciences, which started exploring the use of liquids in nanofoam, to create a material that meets the complex safety demands of high-contact sports.

"We found out that creating a liquid nanofoam cushion with ionized water instead of regular water made a significant difference in the way the material performed," Xu said. "Using ionized water in the design is a breakthrough because we uncovered an unusual liquid-ion coordination network which made it possible to create a more sophisticated material."

The liquid nanofoam cushion allows the inside of the helmet to compress and disperse the impact force, minimizing the force transmitted to the head and reducing the risk of injury. It also regains its original shape after impact, allowing for multiple hits and ensuring the helmet's continued effectiveness in protecting the athlete's head during the game.

"An added bonus," Xu continued, "is that the enhanced material is more flexible and much more comfortable to wear. The material dynamically responds to external jolts because of the way the ion clusters and networks are fabricated in the material."

"The liquid cushion can be designed as lighter, smaller and safer protective devices," said associate professor Weiyi Lu, a collaborator from civil engineering at Michigan State University. "Also, the reduced weight and size of the liquid nanofoam liners will revolutionize the design of the hard shell of future helmets. You could be watching a football game one day and wonder how the smaller helmets protect the players' heads. It could be because of our new material."

In traditional nanofoam, the protection mechanism relies on material properties that react when it gets crunched, or mechanically deformed, such as "collapse" and "densification." Collapse is what it sounds like, and densification is the severe deformation of foam on strong impact. After the collapse and densification, the traditional nanofoam doesn't recover very well because of the permanent deformation of materials -- making the protection a one-time deal. When compared to the liquid nanofoam, these properties are very slow (a few milliseconds) and cannot accommodate the "high-force reduction requirement," which means it can't effectively absorb and dissipate high-force blows in the short time window associated with collisions and impacts.

Another downside of traditional nanofoam is that, when subjected to multiple small impacts that don't deform the material, the foam becomes completely "hard" and behaves as a rigid body that cannot provide protection. The rigidness could potentially lead to injuries and damage to soft tissues, such as traumatic brain injury (TBI).

By manipulating the mechanical properties of materials -- integrating nanoporous materials with "non-wetting liquid" or ionized water -- the team developed a way to make a material that could respond to impacts in a few microseconds because this combination allows for superfast liquid transport in a nanoconfined environment. Also, upon unloading, i.e., after impacts, due to its non-wetting nature, the liquid nanofoam cushion can return to its original form because the liquid is ejected out of the pores, thereby withstanding repeated blows. This dynamic conforming and reforming ability also remedies the problem of the material becoming rigid from micro-impacts.

The same liquid properties that make this new nanofoam safer for athletic gear also offer a potential use in other places where collisions happen, like cars, whose safety and material protective systems are being reconsidered to embrace the emerging era of electric propulsion and automated vehicles. It can be used to create protective cushions that absorb impacts during accidents or help reduce vibrations and noise.

Another purpose that might not be as evident is the role liquid nanofoam can play in the hospital setting. The foam can be used in wearable medical devices like a smartwatch, which monitors your heart rate and other vital signs. By incorporating liquid nanofoam technology, the watch can have a soft and flexible foam-like material on its underside and help improve the accuracy of the sensors by ensuring proper contact with your skin. It can conform to the shape of your wrist, making it comfortable to wear all day. Additionally, the foam can provide extra protection by acting as a shock absorber. If you accidentally bump your wrist against a hard surface, the foam can help cushion the impact and prevent any harm to the sensors or your skin.

Gene mutation may explain why some don't get sick from COVID-19

 People who contract COVID-19 but never develop symptoms -- the so-called super dodgers -- may have a genetic ace up their sleeve. They're more than twice as likely as those who become symptomatic to carry a specific gene variation that helps them obliterate the virus, according to a new study led by UC San Francisco researchers. 

The paper, published July, 19, 2023 in Nature, offers the first evidence that there is a genetic basis for asymptomatic SARS-CoV-2. The research helps to solve the mystery of why some people can be infected without ever getting sick from COVID-19. 

The secret lies with the human leukocyte antigen (HLA), or protein markers that signal the immune system. A mutation in one of the genes coding for HLA appears to help virus-killing T cells identify SARS-CoV-2 and launch a lighting attack. The T cells of some people who carry this variant can identify the novel coronavirus, even if they have never encountered it before, thanks to its resemblance to the seasonal cold viruses they already know. The discovery points to new targets for drugs and vaccines.

"If you have an army that's able to recognize the enemy early, that's a huge advantage," explained the study's lead researcher, Jill Hollenbach, PhD, MPH, professor of neurology, as well as epidemiology and biostatistics, and a member of the Weill Institute for Neurosciences at UCSF. "It's like having soldiers that are prepared for battle and already know what to look for, and that these are the bad guys." 

The mutation -- HLA-B*15:01 -- is quite common, carried by about 10% of the study's population. It doesn't prevent the virus from infecting cells but, rather, prevents people from developing any symptoms. That includes a runny nose or even a barely noticeable sore throat. 

UCSF researchers found that 20% of people in the study who remained asymptomatic after infection carried at least one copy of the HLA-B*15:01 variant, compared to 9% of those who reported symptoms. Those who carried two copies of the variant were far more likely -- more than eight times -- to avoid feeling sick.

Leveraging a national marrow donor database

Researchers suspected early on that HLA was involved, and fortunately a national registry existed that contained the data they were looking for. The National Marrow Donor Program/Be The Match, the largest registry of HLA-typed volunteer donors in the U.S., matches donors with people who need bone marrow transplants

But they still needed to know how the donors fared against COVID-19. So, they turned to a mobile app developed at UCSF, called the COVID-19 Citizen Science Study. They recruited nearly 30,000 people who were also in the bone marrow registry and tracked through the first year of the pandemic. At that time, vaccines were not yet available, and many people were undergoing routine COVID testing for work or whenever they were potentially exposed.

"We did not set out to study genetics, but we were thrilled to see this result come from our multidisciplinary collaboration with Dr. Hollenbach and the National Marrow Donor Program," said Mark Pletcher, MD, MPH, a professor of epidemiology and biostatistics at UCSF.

The primary study group was limited to those who self-identified as white because the final set of study respondents did not have enough people in it from other ethnic and racial groups to analyze.

Researchers identified 1,428 unvaccinated donors who tested positive between February 2020 and the end of April 2021, before the vaccines were widely available and when it still took many days to get back test results.

Of these, 136 individuals remained asymptomatic for at least two weeks before and after testing positive. Only one of the HLA variants -- HLA-B*15:01 -- had a strong association with asymptomatic COVID-19 infection, and this was reproduced in two independent cohorts. Risk factors for severe COVID-19, like being older, overweight and having chronic diseases like diabetes did not appear to play a role in who remained asymptomatic.   

"We are proud to partner on research that has the potential to leverage a long-term public investment in building the national registry to help cure diseases and improve our ability to avoid future pandemics," said Martin Maiers, vice president of research at the National Marrow Donor Program/Be The Match.

To figure out how HLA-B15 managed to quash the virus, Hollenbach's team collaborated with researchers from La Trobe University in Australia. They homed in on the concept of T-cell memory, which is how the immune system remembers previous infections. 

The researchers looked at T cells from people who carried HLA-B15 but had never been exposed to the SARS-CoV-2 virus, and found these cells still responded to a part of the novel coronavirus called the NQK-Q8 peptide. They concluded that exposure to some seasonal coronaviruses, which have a very similar peptide, called NQK-A8, enabled T cells in these individuals to quickly recognize SARS-CoV-2 and mount a faster, more effective immune response. 

"By studying their immune response, this might enable us to identify new ways of promoting immune protection against SARS-CoV-2 that could be used in future development of vaccine or drugs," said Stephanie Gras, a professor and laboratory head at La Trobe University. 

'Stunning' discovery: Metals can heal themselves

 

Scientists for the first time have witnessed pieces of metal crack, then fuse back together without any human intervention, overturning fundamental scientific theories in the process. If the newly discovered phenomenon can be harnessed, it could usher in an engineering revolution -- one in which self-healing engines, bridges and airplanes could reverse damage caused by wear and tear, making them safer and longer-lasting.

The research team from Sandia National Laboratories and Texas A&M University described their findings today in the journal Nature.

"This was absolutely stunning to watch first-hand," said Sandia materials scientist Brad Boyce.

"What we have confirmed is that metals have their own intrinsic, natural ability to heal themselves, at least in the case of fatigue damage at the nanoscale," Boyce said.

Fatigue damage is one way machines wear out and eventually break. Repeated stress or motion causes microscopic cracks to form. Over time, these cracks grow and spread until -- snap! The whole device breaks, or in the scientific lingo, it fails.

The fissure Boyce and his team saw disappear was one of these tiny but consequential fractures -- measured in nanometers.

"From solder joints in our electronic devices to our vehicle's engines to the bridges that we drive over, these structures often fail unpredictably due to cyclic loading that leads to crack initiation and eventual fracture," Boyce said. "When they do fail, we have to contend with replacement costs, lost time and, in some cases, even injuries or loss of life. The economic impact of these failures is measured in hundreds of billions of dollars every year for the U.S."

Although scientists have created some self-healing materials, mostly plastics, the notion of a self-healing metal has largely been the domain of science fiction.

"Cracks in metals were only ever expected to get bigger, not smaller. Even some of the basic equations we use to describe crack growth preclude the possibility of such healing processes," Boyce said.

Unexpected discovery confirmed by theory's originator

In 2013, Michael Demkowicz -- then an assistant professor at the Massachusetts Institute of Technology's department of materials science and engineering, now a full professor at Texas A&M -- began chipping away at conventional materials theory. He published a new theory, based on findings in computer simulations, that under certain conditions metal should be able to weld shut cracks formed by wear and tear.

The discovery that his theory was true came inadvertently at the Center for Integrated Nanotechnologies, a Department of Energy user facility jointly operated by Sandia and Los Alamos national laboratories.

"We certainly weren't looking for it," Boyce said.

Khalid Hattar, now an associate professor at the University of Tennessee, Knoxville, and Chris Barr, who now works for the Department of Energy's Office of Nuclear Energy, were running the experiment at Sandia when the discovery was made. They only meant to evaluate how cracks formed and spread through a nanoscale piece of platinum using a specialized electron microscope technique they had developed to repeatedly pull on the ends of the metal 200 times per second.

Surprisingly, about 40 minutes into the experiment, the damage reversed course. One end of the crack fused back together as if it was retracing its steps, leaving no trace of the former injury. Over time, the crack regrew along a different direction.

Hattar called it an "unprecedented insight."

Boyce, who was aware of the theory, shared his findings with Demkowicz.

"I was very glad to hear it, of course," Demkowicz said. The professor then recreated the experiment on a computer model, substantiating that the phenomenon witnessed at Sandia was the same one he had theorized years earlier.

Their work was supported by the Department of Energy's Office of Science, Basic Energy Sciences; the National Nuclear Security Administration and the National Science Foundation.

A lot remains unknown about the self-healing process, including whether it will become a practical tool in a manufacturing setting.

"The extent to which these findings are generalizable will likely become a subject of extensive research," Boyce said. "We show this happening in nanocrystalline metals in vacuum. But we don't know if this can also be induced in conventional metals in air."

Yet for all the unknowns, the discovery remains a leap forward at the frontier of materials science.

"My hope is that this finding will encourage materials researchers to consider that, under the right circumstances, materials can do things we never expected," Demkowicz said.

Sandia National Laboratories is a multimission laboratory operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy's National Nuclear Security Administration. Sandia Labs has major research and development responsibilities in nuclear deterrence, global security, defense, energy technologies and economic competitiveness, with main facilities in Albuquerque, New Mexico, and Livermore, California.