Brain organoid study highlights potential role of genetic and environmental interaction in autism spectrum disorder

Study illustrates a quicker and less expensive way to explore gene-plus-environment causes of autism spectrum disorder and other conditions

JOHNS HOPKINS UNIVERSITY BLOOMBERG SCHOOL OF PUBLIC HEALTH

Research News

Researchers at Johns Hopkins Bloomberg School of Public Health have shown in a brain organoid study that exposure to a common pesticide synergizes with a frequent autism-linked gene mutation.

The results represent one of the clearest pieces of evidence yet that genetic and environmental factors may be able to combine to disturb neurodevelopment. Researchers suspect that genetic and environmental factors might contribute to the increased prevalence of autism spectrum disorder, a developmental disorder characterized by cognitive function, social, and communication impairments.

The study's use of brain organoids also points the way towards quicker, less expensive, and more human-relevant experimentation in this field when compared to traditional animal studies.

The brain organoid model, developed by the Bloomberg School researchers, consists of balls of cells that are differentiated from human stem cell cultures and mimic the developing human brain. The researchers found in the study that chlorpyrifos, a common pesticide alleged to contribute to developmental neurotoxicity and autism risk, dramatically reduces levels of the protein CHD8 in the organoids. CHD8 is a regulator of gene activity important in brain development. Mutations in its gene, which reduce CHD8 activity, are among the strongest of the 100-plus genetic risk factors for autism that have so far been identified.

The study, which appears online July 14 in Environmental Health Perspectives, is the first to show in a human model that an environmental risk factor can amplify the effect of genetic risk factor for autism.

"This is a step forward in showing an interplay between genetics and environment and its potential role for autism spectrum disorder," says study lead Lena Smirnova, PhD, a research associate in the Department of Environmental Health and Engineering at the Bloomberg School.

Clinically rare as recently as 40 years ago, autism spectrum disorder now occurs in roughly two percent of live births, according to the Centers for Disease Control and Prevention.

"The increase in autism diagnoses in recent decades is hard to explain--there couldn't have been a population-wide genetic change in such a short time, but we also haven't been able to find an environmental exposure that sufficiently accounts for it," says study co-author Thomas Hartung, MD, PhD, professor and Doerenkamp-Zbinden Chair in the Bloomberg School's Department of Environmental Health and Engineering. Hartung is also director of the Center for Alternatives to Animal Testing at the Bloomberg School. "To me, the best explanation involves a combination of genetic and environment factors," says Hartung.

How environmental factors and genetic susceptibilities interact to increase risk for autism spectrum disorder remains mostly unknown, in part because these interactions have been difficult to study. Traditional experiments with laboratory animals are expensive and, especially for disorders involving the brain and cognition, of limited relevance to humans.

Advances in stem cell methods in the past decades have allowed researchers to use human skin cells that can be transformed first into stem cells and then into almost any cell type and studied in the lab. In recent years, scientists have expanded beyond simple lab-dish cell cultures to make cultures of three-dimensional organoids that better represent the complexity of human organs.

For their study, the researchers used brain organoids to model the effects of a CHD8 gene disruption combined with exposure to chlorpyrifos. A group led by co-author Herbert Lachman, MD, professor at Albert Einstein College of Medicine, engineered the cells that make up the organoids to lack one of the two normal copies of the CHD8 gene. This modeled a substantial, but less-than-total, weakening of the CHD8 gene's activity, similar to that seen in people who have CHD8 mutations and autism. The researchers then examined the additional effect of exposure to chlorpyrifos, which is still widely used on agricultural produce in the U.S. and abroad.

"High-dose, short-term experimental exposures do not reflect the real-life situation, but they give us a starting point to identify genetic variants that might make individuals more susceptible to toxicants," says Smirnova. "Now we can explore how other genes and potentially toxic substances interact."

The researchers found that the brain organoids with just one copy of the CHD8 gene had only two-thirds the normal level of CHD8 protein in their cells, but that chlorpyrifos exposure drove CHD8 levels much lower, turning a moderate scarcity into a severe one. The exposure demonstrated clearly how an environmental factor can worsen the effect of a genetic one, likely worsening disease progression and symptoms.

As part of their study, the researchers compiled a list of molecules in blood, urine, and brain tissue that prior studies have shown to be different in autism spectrum patients. They found that levels of several of these apparent autism biomarkers were also significantly altered in the organoids by CHD8 deficiency or chlorpyrifos exposure, and moreso by both.

"In this sense, we showed that changes in these organoids reflect changes seen in autism patients," Smirnova says.

The findings, according to the researchers, pave the way for further studies of gene-environment interactions in disease using human-derived organoids.

"The use of three-dimensional, human-derived, brain-like models like the one in this study is a good way forward for studying the interplay of genetic and environmental factors in autism and other neurodevelopmental disorders," Hartung says.

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"Gene-Environment Interactions in Developmental Neurotoxicity: A Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres" was written by Sergio Modafferi, Xiali Zhong, Andre Kleensang, Yohei Murata, Francesca Fagiani, David Pamies, Helena Hogberg, Vittorio Calabrese, Herbert Lachman, Thomas Hartung, and Lena Smirnova.

The study was funded in part by the Alternatives Research and Development Foundation and the Environmental Protection Agency (R839505).

Disclosures:

Thomas Hartung, Helena Hogberg, and David Pamies are named inventors on a patent by Johns Hopkins University on the production of mini-brains (also called BrainSpheres), which is licensed to AxoSim, New Orleans, Louisiana, USA. Thomas Hartung, Lena Smirnova, David Pamies, and Helena Hogberg are consultants for AxoSim, New Orleans, and Thomas Hartung is also a consultant for AstraZeneca and American Type Culture Collection (ATCC) on advanced cell culture methods. All other authors declare they have no actual or potential competing financial interests.

 

Antidepressants may improve outcomes in people with diabetes and depression

THE ENDOCRINE SOCIETY

Research News

WASHINGTON--People with diabetes and depression who take antidepressants may have a lower risk of death and of serious diabetes complications, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

People with diabetes face a higher risk of depression, which makes them more likely to die or develop diabetes complications including heart and kidney disease, stroke, eye, and foot problems. Depression makes diabetes complications worse due to stress, body weight changes, and lack of exercise.

"People with depression and diabetes have poorer health outcomes than those with diabetes alone, and regular antidepressant treatment could lower their risk of complications," said study author Shi-Heng Wang, Ph.D., of the China Medical University in Taichung, Taiwan.

"People who adhere to their antidepressants have better diabetes outcomes and quality of life than those with poor adherence," said study author Chi-Shin Wu, M.D., Ph.D., of the National Taiwan University Hospital in Taipei, Taiwan.

The researchers conducted a nationwide retrospective cohort study of 36,276 patients with depression and diabetes to determine if antidepressants could improve diabetes outcomes. They found regular antidepressant treatment was associated with a lower risk of death and heart disease.

Other authors of the study include: Le-Yin Hsu of the National Taiwan University in Taipei, Taiwan; and Yi-Jiun Pan of the China Medical University in Taichung, Taiwan.

The manuscript received funding from the Ministry of Science and Technology, the China Medical University, and the Ministry of Health and Welfare.

The manuscript, "Associations Between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus," was published online, ahead of print.

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Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world's oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at http://www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia.

 

Study: Idea sharing increases online learner engagement

UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN, NEWS BUREAU

Research News

IMAGE: ONLINE LEARNING ENGAGEMENT CAN BE INCREASED BY NEARLY ONE-THIRD BY SIMPLY PROMPTING STUDENTS TO SHARE COURSE IDEAS RATHER THAN PERSONAL DETAILS IN THE FORM OF ICEBREAKERS AND SOCIAL INTRODUCTIONS, SAID... view more 

CREDIT: PHOTO BY GIES COLLEGE OF BUSINESS

CHAMPAIGN, Ill. -- Sharing ideas in an online learning environment has a distinct advantage over sharing personal details in driving learner engagement in massive open online courses, more commonly known as MOOCs, says new research co-written by a University of Illinois Urbana-Champaign expert who studies the intersection of marketing and digital environments.

Online learning engagement can be increased by nearly one-third by simply prompting students to share course ideas in a discussion forum rather than having them share information about their identity or personal motivations for enrolling, said Unnati Narang, a professor of business administration at the Gies College of Business.

With less than 10% of online learners completing courses, and less than 5% participating in course discussions, there's a stark need for online learning platforms to identify and employ strategies that can enhance student engagement, Narang said.

"Engagement levels have tended to be really low in online classrooms simply because students may not ever get the chance to get to know each other in the way they do in an in-person, face-to-face classroom," she said. "A lot of those elements are, quite obviously, lacking in the online learning environment."

Initially, online platforms placed a lot of emphasis on having discussion forums to engage students. But over time, those efforts tended to fizzle out, Narang said.

"Even if a student is posting something, it may never be read by a classmate or by the instructor, which can really demotivate students who are trying to engage in the material," she said.

To determine how to increase learner engagement, Narang and her co-authors analyzed more than 12,000 discussion forum postings during an 18-month period and conducted a field experiment involving more than 2,000 learners in a popular online course offered by a large U.S. university.

"We randomly nudged students to either share something personal about themselves or ideas related to the course," she said. "We thought we were going to see an increase in engagement thanks to the social aspects of identity sharing because there's so much emphasis on it in face-to-face classes for icebreakers and social introductions."

The results indicated that asking learners to share ideas related to the course had a stronger effect on their video consumption and assessment completion, according to the paper.

"We found that the idea of sharing knowledge outperforms identity sharing as well as the control condition of not sharing anything," Narang said. "Across diverse metrics of learner engagement and performance, we found that what learners share plays a big role in enhancing the online learning environment, and they tended to perform 30% better in terms of how many videos they consumed, how many assessments they completed and how they scored on assessments. So there's a distinct advantage to idea sharing in online pedagogy."

For educators, the implications of what the researchers dubbed the "idea advantage" in an era of increased online learning due to the COVID-19 pandemic suggests that identity sharing tends to be superficial and brief, so it's better to push students to engage more on the course content and their ideas about what they're studying, Narang said.

"Just very basic getting-to-know-you introductions that instructors make in a physical classroom - who are you, where you're from, etc. - doesn't really translate into the online learning environment," she said. "There's just too much anonymity to successfully do that when you're in a virtual classroom. The idea posts, on the other hand, tend to be much more elaborate and well-articulated. Students put more time and effort into crafting their answers. On average, an idea-sharing post was 66 words long. But an identity-sharing post tended to be roughly half as long. Students were clearly more invested in ideas than trying to make friends in the online learning environment, thus why the idea advantage is so strong."

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Narang's co-authors are Aric Rindfleisch, the John M. Jones Professor of Marketing at the University of Illinois Urbana-Champaign, and Manjit S. Yadav, the JC Penney Chair in Marketing and Retailing Studies at Texas A&M University.

The paper was published in the Journal of Marketing Research.

 

How climate change and fires are shaping the forests of the future

Tracking future forest fires with AI

TECHNICAL UNIVERSITY OF MUNICH (TUM)

Research News

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IMAGE: THE ICONIC LANDSCAPE OF YELLOWSTONE NATIONAL PARK IS CHARACTERIZED BY VAST FORESTS THAT HAVE BEEN UNTOUCHED BY MAN BUT ARE THREATENED BY INCREASING NUMBERS OF FOREST FIRES DUE TO CLIMATE... view more 

CREDIT: R. SEIDL / TUM

Forest fires are already a global threat. "But considering how climate change is progressing, we are probably only at the beginning of a future that will see more and bigger forest fires," explains Rupert Seidl, Professor of Ecosystem Dynamics and Forest Management in Mountain Landscapes at TUM.

In many places, fire is part of the natural environment, and many tree species have become naturally adapted to recurrent fires. These adaptations range from particularly thick bark, which protects the sensitive cambium in the trunk from the fire, to the cones of certain types of pine, which open only due to the heat of fire, allowing a quick regeneration and recovery of affected woodland .

AI is accelerating ecosystem models

"The interaction between climate, forest fires, and other processes in the forest ecosystem is very complex, and sophisticated process-based simulation models are required to take account of the different interactions appropriately," explains Prof. Seidl. A method that has been developed at TUM is using artificial intelligence to significantly expand the field of use of these complex models.

This method involves the training of a deep neural network in order to imitate the behavior of a complex simulation model as effectively as possible. The neural network learns on the basis of how the ecosystem responds to differing environmental influences, but does so using only a fraction of the computing power that would otherwise be necessary for large-scale simulation models. "This allows us to carry out spatially high-resolution simulations of areas of forest that stretch across several million hectares," explains scientist Dr. Werner Rammer.

Forecast for the forests in Yellowstone National Park

The simulations completed by the team of scientists include simulations for the "Greater Yellowstone Ecosystem", which has the world-famous Yellowstone National Park at its heart. This area, which is approximately 8 million hectares in size, is situated in the Rocky Mountains and is largely untouched. The researchers at the TUM have worked with American colleagues to determine how different climate scenarios could affect the frequency of forest fires in this region in the 21st century, and which areas of forest cannot regenerate successfully following a forest fire.

Depending on the climate change scenario, the study has found that by the end of the century, the current forest coverage will have disappeared in 28 to 59 percent of the region. Particularly affected were the forests in the sub-alpine zone near the tree line, where the species of tree are naturally less adapted to fire, and the areas on the Yellowstone Plateau, where the relatively flat topography is mostly unable to stop the fire from spreading.

Climate change is causing significant changes to forest ecosystems

The regeneration of the forest in the region under investigation is at threat for several reasons: If the fires get bigger and the distances between the surviving trees also increase, too few seeds will make their way onto the ground. If the climate gets hotter and drier in the future, the vulnerable young trees won't survive, and if there are too many fires, the trees won't reach the age at which they themselves yield seeds.

"By 2100, the Greater Yellowstone Ecosystem is expected to have changed more than it has in the last 10,000 years, and will therefore look significantly different than it does today," explains Rammer. "The loss of today's forest vegetation is leading to a reduction in the carbon which is stored in the ecosystem, and will also have a profound impact on the biodiversity and recreational value of this iconic landscape."

The potential developmental trends identified in the study are also intended to help visitors to the national park understand the consequences of climate change and the urgency of the climate protection measures. In the next step, the research team will be using AI to estimate the long-term impact of the problems caused by climate change in the forests of Europe.

CAPTION

The way in which increasing numbers of forest fires are changing the landscape over the long term is being studied with the use of AI.

CREDIT

R. Seidl / TUM

 

Chemistry discovery could remove micropollutants from environment

U.S. ARMY RESEARCH LABORATORY

Research News

IMAGE: DR. RONG YE (LEFT), DR. MING ZHAO (CENTER), AND DR. PENG CHENG (RIGHT) AT CORNELL DISCUSS THEIR ARMY-FUNDED RESEARCH THAT IDENTIFIES A NEW CHEMISTRY APPROACH THAT COULD REMOVE MICROPOLLUTANTS FROM... view more 

CREDIT: CORNELL UNIVERSITY

RESEARCH TRIANGLE PARK, N.C. -- Army-funded research identified a new chemistry approach that could remove micropollutants from the environment.

Micropollutants are biological or chemical contaminants that make their way into ground and surface waters in trace quantities.

Using a pioneering imaging technique, Cornell University researchers obtained a high-resolution snapshot of how ligands, molecules that bind to other molecules or metals, interact with the surface of nanoparticles. In doing so, they made an unexpected breakthrough discovery. They determined that by varying the concentration of an individual ligand they could control the shape of the particle it attached too.

This approach could result in an array of daily applications, including developing chemical sensors that are sensitive at a very low level to a specific chemical in the environment.

"Professor Peng Chen's work allows for deep insights into molecular adsorption processes, which is important to understand for designing molecular sensors, catalysts, and schemes to clean up micro-pollutants in the environment," said Dr. James Parker, program manager, U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. "This research is also important for designing and engineering stimuli-responsive materials with specialized function that could not be found in regular, bulk materials."

The research, published in Nature Communications, studied interactions of ligands and gained new understanding of the strength, or affinity of ligand adsorption as well as how multiple ligands cooperate, or don't, with each other.

"When the molecule adsorbs on the surface of a nanoscale material, it also actually protects the surface and makes it more stable," said Dr. Peng Chen, the Peter J.W. Debye Professor of Chemistry in the College of Arts and Sciences at Cornell University, who led the research. "This can be utilized to control how nanoscale particles grow and become their eventual shape. And we found we can do this with just one ligand. You don't do any other trick. You just decrease the concentration or increase the concentration, and you can change the shape."

Understanding how ligands interact with the surface of nanoparticles has been a challenge to study. Adsorbed ligands are difficult to identify because there are other molecules in the mix, and nanoparticle surfaces are uneven and multifaceted, which means they require incredibly high spatial resolution to be scrutinized.

A nanoparticle's size and surface structures, or facets, are intrinsically tied to the particle's potential applications. The larger the particle, the more atoms fit inside it, while smaller particles have less available space internally but a greater surface volume ratio for atoms to sit atop, where they can be utilized for processes such as catalysis and adsorption. The different types of structures the atoms and molecules form on these surface facets are directly correlated with the particle's shape.

Army-funded research identifies a new chemistry approach that could remove micropollutants from the environment.

Scientists have used several imaging methods to survey these particles, but until now, they haven't been able to obtain nanometer resolution to really explore the nooks and crannies of the multiple surface facets and quantify the affinity, or strength, of a ligand's adsorption. The research team was able to do just that by employing a method of their own devising called COMPetition Enabled Imaging Technique with Super-Resolution or COMPEITS.

The process works by introducing a molecule that reacts with the particle surface and generates a fluorescent reaction. A nonfluorescent molecule is then sent to bind to the surface, where its reaction competes with the fluorescent signal. The resulting decrease in fluorescence, essentially creating a negative image, can then be measured and mapped with super high resolution.

Using COMPEITS on a gold nanoparticle, the team was able to quantify the strength of ligand adsorption, and they discovered ligand behavior can be very diverse. Ligands, it turns out, are fair-weather friends of a sort, at some sites they cooperate to help each other adsorb, but at other sites they can impair each other's efforts. The researchers also discovered that sometimes this positive and negative cooperativity exists at the same site.

In addition, the researchers learned that the surface density of adsorbed ligands can determine which facet is dominant. This crossover inspired the team to vary the concentrations of individual ligands as a way to tune the shape of the particle itself.

"For us, this has opened more possibilities," Chen said. "For example, one way to remove micropollutants, such as pesticides, from the environment is to adsorb micro-portions on the surface of some adsorbent particle. After it is adsorbed on the surface of the particle, if the particle is a catalyst, it can catalyze the destruction of the micropollutants."

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In addition to ARL, the Center for Alkaline-Based Energy Solutions, an Energy Frontier Research Center of U.S. Department of Energy supported the research.

Visit the laboratory's Media Center to discover more Army science and technology stories

As the Army's national research laboratory, ARL is operationalizing science to achieve transformational overmatch. Through collaboration across the command's core technical competencies, DEVCOM leads in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more successful at winning the nation's wars and come home safely. DEVCOM Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. DEVCOM is a major subordinate command of the Army Futures Command.

 

Swarm of autonomous tiny drones can localize gas leaks

DELFT UNIVERSITY OF TECHNOLOGY

Research News

IMAGE: A SWARM OF TINY DRONES ENTERING A BUILDING IN SEARCH OF A GAS LEAK. THE RESEARCH TEAM USED MODIFIED "CRAZYFLIE " DRONES, WHICH ARE 12 CM IN DIAMETER WEIGHED ONLY 37.5... view more 

CREDIT: MAVLAB/TU DELFT

When there is a gas leak in a large building or at an industrial site, human firefighters currently need to go in with gas sensing instruments. Finding the gas leak may take considerable time, while they are risking their lives. Researchers from TU Delft (the Netherlands), University of Barcelona, and Harvard University have now developed the first swarm of tiny - and hence very safe - drones that can autonomously detect and localize gas sources in cluttered indoor environments.

The main challenge the researchers needed to solve was to design the Artificial Intelligence for this complex task that would fit in the tight computational and memory constraints of the tiny drones. They solved this challenge by means of bio-inspired navigation and search strategies. The scientific article has now been made public on the ArXiv article server, and it will be presented at the renowned IROS robotics conference later this year. The work forms an important step in the intelligence of small robots and will allow finding gas leaks more efficiently and without the risk of human lives in real-world environments.

Autonomous gas source localization

Autonomous gas source localization is a complex task. For one, artificial gas sensors are currently less capable than animal noses in detecting small amounts of gas and staying sensitive to quick changes in gas concentration. Moreover, the environment in which the gas spreads can be complex. Consequently, much of the research in this area has focused on single robots that search for a gas source in rather small, obstacle-free environments in which the source is easier to find.

Swarms of tiny drones

"We are convinced that swarms of tiny drones are a promising avenue for autonomous gas source localization", says Guido de Croon, Full Professor at the Micro Air Vehicle laboratory of TU Delft. "The drones' tiny size makes them very safe to any humans and property still in the building, while their flying capability will allow them to eventually search for the source in three dimensions. Moreover, their small size allows them to fly in narrow indoor areas. Finally, having a swarm of these drones allows them to localize a gas source quicker, while escaping local maxima of gas concentration in order to find the true source."

However, these properties also make it very hard to instill the drones with the necessary artificial intelligence for autonomous gas source localization. The onboard sensing and processing is extremely limited, excluding the type of AI algorithms that make self-driving cars autonomous. Moreover, operating in a swarm brings its own challenges, since the drones need to be aware of each other for collision avoidance and collaboration.

Bio-inspired Artificial Intelligence

"Actually, in nature there are ample examples of successful navigation and odor source localization within strict resource constraints.", says Bart Duisterhof, who performed the research for obtaining his MSc thesis at TU Delft. "Just think of how fruitflies with their tiny brains of ~100,000 neurons infallibly locate the bananas in your kitchen in the summer. They do this by elegantly combining simple behaviors such as flying upwind or orthogonally to the wind depending on whether they sense the odor. Although we could not directly copy these behaviors due to the absence of airflow sensors on our robots, we have instilled our robots with similarly simple behaviors to tackle the task."

In particular, the tiny drones implement a new "bug" algorithm for their navigation, termed "Sniffy Bug". As long as no drone has sensed any gas, the drones spread out as much as possible over the environment, while avoiding obstacles and each other. If one of the drones senses gas at its location, it communicates this to the others. From that point on, the drones will collaborate with each other to find the gas source as soon as possible. Specifically, the swarm then performs a search for maximal gas concentration with an algorithm termed "particle swarm optimization" (PSO), with each drone being a "particle". This algorithm was originally modelled after the social behavior and motion of bird flocks. It has each drone moving based on its own perceived highest gas concentration location, the swarm's highest location, and an inertia in its current moving direction. As a search strategy, PSO has the advantage that it only requires measuring the gas concentration, and not the gas concentration gradient or wind direction. Furthermore, it allows the swarm to ignore local maxima that may occur in complex environments.

The path to real-world applications

"This research shows that swarms of tiny drones can perform very complex tasks.", adds Guido, "We hope that this work forms an inspiration for other robotics researchers to rethink the type of AI that is necessary for autonomous flight."

The development of this type of technology to a fully functioning product still requires further work. For instance, the current work does not yet tackle moving in three dimensions to locate gas sources at a height. Furthermore, the robustness of navigation should also be improved before deploying the drones in a real emergency scenario.

However, the current work is very promising. The developed algorithms are not only useful for detecting gas leaks in buildings, but also for scientific missions such as detecting methane on Mars or economical use such as the early detection of diseases or pests in greenhouses.

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More information

Scientific article:

Sniffy Bug: A Fully Autonomous Swarm of Gas-Seeking Nano Quadcopters in Cluttered Environments, by B.P. Duisterhof, S. Li, J. Burgués, V.J. Reddi, and G.C.H.E. de Croon, accepted at IEEE/RSJ International Conference on Intelligent Robots and Systems 2021 (IROS 2021). - Preprint available at the Arxiv: https://arxiv.org/abs/2107.05490

Video at: https://youtu.be/hj_SBSpK5qg

Video playlist: https://www.youtube.com/playlist?list=PL_KSX9GOn2P-J5qh90Y-9fw2ODcxYtFap

More information at: http://mavlab.tudelft.nl/

 

Personalised 3D printed knee implant could help thousands of arthritis sufferers

UNIVERSITY OF BATH

Research News

IMAGE: THE BESPOKE IMPLANT PRESERVES THE EXISTING JOINT AND CAN BE USED AT AN EARLIER STAGE OF ARTHRITIS, BEFORE A KNEE REPLACEMENT IS NEEDED. view more 

CREDIT: UNIVERSITY OF BATH

Pioneering 'printed metal' procedure to create bespoke treatment for early knee osteoarthritis set to be trialled in the UK following MHRA approval.

• World's first 3D printed high tibial osteotomy (HTO) device and procedure developed at University of Bath given approval for UK trials
• Bespoke titanium alloy HTO implants that fit perfectly are designed to reduce discomfort for knee osteoarthritis patients
• Sophisticated 3D scanning aims to make surgery quicker and safer
• New TOKA process could make earlier intervention possible - saving patients decades of pain before surgery becomes viable

Intro

A groundbreaking new treatment that uses 3D printed implants and that could bring relief to tens of thousands of knee osteoarthritis sufferers has received approval to be trialled in UK patients, following a virtual "in-silico" trial that demonstrated its safety.

The personalised early knee osteoarthritis treatment, developed by engineers at the University of Bath's Centre for Therapeutic Innovation (CTI), uses state of the art 3D metal printing technology to make personalised medical-grade titanium-alloy plates that perfectly fit every patient.

The TOKA (Tailored Osteotomy for Knee Alignment) treatment improves the operative procedure and fit of high-tibial osteotomy (HTO) plates used to realign a patient's knee, making them more stable, comfortable and better able to bear weight than existing generic plates. The technique also simplifies HTO surgery, making operations quicker and therefore safer.

The HTO plates have already been safety tested virtually, in a computer-based trial using CT scan data from 28 patients. The in-silico clinical trial, the first in the world to demonstrate the safety of an orthopaedic device, modelled the stresses that would be exerted on the bespoke plates and showed that they would be comparable in safety to the standard treatment.

Professor Richie Gill, from the Centre for Therapeutic Innovation, says: "Knee osteoarthritis is a major health, social and economic issue and does not receive as much attention as it should. A quarter of women over 45 have it, and about 15 percent of men, so it's a significant burden that many live with.

"Knee replacement is only useful for end-stage osteoarthritis, so you can be in pain and have to live with a disability for a long time, potentially decades, before it's possible. We hope that the new TOKA process we've developed will change that."

Knee osteoarthritis patients undergoing TOKA will undergo a 3D CT scan of their knee, before a personalised 3D printed surgical guide and plate, both shaped to their tibia (shin) bone is created. The surgical guide simplifies the surgery, and is designed to improve surgical accuracy.

The process also sees the first implementation of 3D printed screw threads into the HTO plates, meaning they can be optimally positioned to help secure them against the bone.

Trials to begin once clinical centres reopen for elective surgery

When clinical centres return to carrying out elective surgery, expected later this year, the trials will begin. Hospitals in Bath, Bristol, Exeter and Cardiff will take part in a randomised control trial to compare patient outcomes with an existing generic HTO procedure.

Tests of the TOKA technique have already begun in Italy, where so far 25 patients received new personalised HTO plates as part of a trial at the Rizzoli Institute in Bologna.

High Tibial Osteotomy (HTO) surgery realigns the knee joint by making a cut to the tibia (shin bone) and opening a small gap, which needs to be stabilised by a metal plate. This realignment moves the loading to a less 'worn' part of the knee. Patient outcomes depend on how accurately the cut is made and the gap opened.

Prof Gill adds: "The HTO surgery has a long clinical history and it has very good results if done accurately. The difficulty surgeons have is achieving high accuracy, which is why we have created the TOKA method, which starts with a CT scan and digital plan.

"3D printing the custom knee implant and doing the scanning before operating means surgeons will know exactly what they'll see before operating and where the implant will go."

"In addition to a surgeon being able to precisely plan an operation, a surgical guide (or jig) and a plate implant, each personalised to the patient, can be 3D printed automatically based on the scanning data.

"Importantly this type of treatment relieves the symptoms of knee osteoarthritis while preserving the natural joint."

The pre-planning element greatly simplifies surgery and could cut the time on the operating table from two hours to around 30 minutes.

The work to date and UK trial is supported and funded by Versus Arthritis UK. The in silico trial has been published in Communications Medicine.

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New evidence of an anomalous phase of matter brings energy-efficient technologies closer

UNIVERSITY OF CAMBRIDGE

Research News

Researchers have found evidence for an anomalous phase of matter that was predicted to exist in the 1960s. Harnessing its properties could pave the way to new technologies able to share information without energy losses. These results are reported in the journal Science Advances.

While investigating a quantum material, the researchers from the University of Cambridge who led the study observed the presence of unexpectedly fast waves of energy rippling through the material when they exposed it to short and intense laser pulses. They were able to make these observations by using a microscopic speed camera that can track small and very fast movement on a scale that is challenging with many other techniques. This technique probes the material with two light pulses: the first one disturbs it and creates waves - or oscillations - propagating outward in concentric circles, in the same way as dropping a rock into a pond; the second light pulse takes a snapshot of these waves at various times. Put together, these images allowed them to look at how these waves behave, and to understand their 'speed limit.'

"At room temperature, these waves move at a hundredth of the speed of light, much faster than we would expect in a normal material. But when we go to higher temperatures, it is as if the pond has frozen," explained first author Hope Bretscher, who carried out this research at Cambridge's Cavendish Laboratory. "We don't see these waves moving away from the rock at all. We spent a long time searching for why such bizarre behaviour could occur."

The only explanation that seemed to fit all the experimental observations was that the material hosts, at room temperature, an "excitonic insulator" phase of matter, which while theoretically predicted, had eluded detection for decades.

"In an excitonic insulator, the observed waves of energy are supported by charge neutral particles that can move at electron-like velocities. Importantly, these particles could transport information without being hindered by the dissipation mechanisms that, in most common materials, affect charged particles like electrons," said Dr Akshay Rao from the Cavendish Laboratory, who led the research. "This property could provide a simpler route toward room-temperature, energy-saving computation than that of superconductivity."

The Cambridge team then worked with theorists around the world to develop a model about how this excitonic insulating phase exists, and why these waves behave in this way.

"Theorists predicted the existence of this anomalous phase decades ago, but the experimental challenges to see evidence of this has meant that only now we are able to apply previously developed frameworks to provide a better picture of how it behaves in a real material," commented Yuta Murakami, from the Tokyo Institute of Technology, who collaborated on the study.

"The dissipationless energy transfer challenges our current understanding of transport in quantum materials and opens theorists' imaginations to new ways for their future manipulation," said collaborator Denis Gole�, from the Jozef Stefan Institute and University of Ljubljana.

"This work puts us a step closer toward achieving some incredibly energy-efficient applications that can harness this property, including in computers." concluded Dr Rao.

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Reference:

Hope M. Bretscher et al. 'Imaging the coherent propagation of collective modes in the excitonic insulator Ta2NiSe5 at room temperature', Science Advances (July 2021). DOI: 10.1126/sciadv.abd6147

 

Cocoa bean DNA testing offers path to end slavery and child labour in chocolate industry

Research shows low-cost DNA biomarker technique can trace cocoa from a specific farm to the chocolate bar in your hand

UNIVERSITY OF BATH

VIDEO: MICHAEL ROGERSON DISCUSSES THE DNA RESEARCH AND ITS IMPLICATIONS FOR THE CHOCOLATE INDUSTRY view more 

CREDIT: UNIVERSITY OF BATH PRESS OFFICE/MICHAEL ROGERSON

A new method of DNA testing on cocoa beans could revolutionise the chocolate industry, offering consumers greater reassurance about the origins and ethics of their beloved confectionery, and giving the global cocoa industry a precision tool to help end slavery and child labour.

Researchers from the University of Bath, University of the West of England, and Surrey Business School have proven a low-cost method which compares DNA in chocolate products to the cocoa when it is farmed. This means cocoa can be reliably traced back from an individual chocolate bar to the specific farms which cultivated the cocoa in it, a major advance on current fairtrading, certification and sustainability practices.

"This has the potential to revolutionise sustainability in a market rife with environmental destruction and human misery in that firms will now be able to buy from a specific set of known farms which have approved labour and environmental standards and to prove that their chocolate is made with that cocoa," said Michael Rogerson, researcher at the University of Bath School of Management.

"And activists, NGOs, and governments, will be able to prove that the chocolate bar you buy in your local supermarket contains cocoa grown on farms which abuse the environment or employ child or forced labour. We know consumers care about this - but they need accurate, reliable information to make ethical choices," Rogerson said.

Rogerson said the research team had developed a method where the DNA sampling would cost around £5 per farm, putting this well within the reach of the $78 billion cocoa supply industry, and government and NGO foreign aid budgets.

"It would cost a tiny fraction of the industry's revenues to build such a database in Ghana and Ivory Coast, which is the source of more than 70% of the world's cocoa production. There are an estimated 2.2 million child labourers working on farms in West Africa and reports suggest the problems are worsening despite promises made by large chocolate producers," he said.

Rogerson said the research team's interviews of chocolate and cocoa industry stakeholders along the whole supply chain revealed a certain 'fatalism' about the child labour issue and a sense it was too great a problem to tackle.

The interviews also showed third-party ethical certification and labelling was regarded primarily as a marketing ploy, easily understood by consumers, considered desirable, but ultimately in need of improvement to be meaningful.

"What we are offering industry is a way to break out of that fatalism, and consumers the reassurance that when they pick an 'ethical' product that it is genuinely ethical. We could also see third-party certifiers like Fairtrade or the Rainforest Alliance strengthening their offering and credibility with this," he said.

Rogerson said the difficulty of tracing cocoa from farms to the end product was at the heart of the issue. The majority of the world's cocoa is collected by small-scale traders and taken to larger trading facilities, where vast quantities are traded on international markets. Tracing beans back to the farm of origin is a challenge due to the number of different parties aggregating and mixing crops early in the supply chain. He said current certification systems, while laudable in their intent, were not addressing the core issues.

"And this is not a new issue. During our research we found reports that in 1905 Cadbury investigated claims of abuses on cocoa plantations on the islands of São Tomé and Príncipe, in Central Africa. The industry has known of the problems for over 100 years, and not yet found a viable solution to trace cocoa through supply chains, perhaps until now," he said

Biomarkers - biochemical 'barcodes' extracted from plant DNA - offer a way to resolve this issue, Rogerson said.

Biomarkers are unique indicators of a plant and the particular environment in which it plant is grown. Biomarkers in cocoa beans are sufficiently hardy that they can survive the industrial processes used in chocolate making, allowing for the identification of individual cocoa farm beans from a mixture of different origins in final products.

Biomarkers are produced by isolating DNA at cocoa farms, enabling the creation of a database of those markers specific to each farm. Further biomarkers can be taken from the location of cocoa fermentation as these also have unique signatures. Once a database has been created with sufficient samples, chocolate bought anywhere in the world can be traced back to farms of origin. This enables a chocolate producer, or even a customer given access to the right technology, to know precisely where the cocoa in their chocolate comes from.

Rogerson said the solution had been proven in a small pilot study but the approach would need operationalization at scale, something the chocolate industry could accomplish, given the will or incentive to act.

"If the method can be scaled effectively there can be no excuses for continued abuses within chocolate supply chains. Claims that farms are too widespread or remote, or that the trading of cocoa through various intermediaries makes it impossible to trace become suddenly empty. I would like the chocolate industry and governments to honestly face this ethical challenge - we have developed a tool they can deploy in that fight," he said.

Notes to editors

* For further information please contact Tony Roddam at the University of Bath press office on +44 7971 500460 or press@bath.ac.uk

The University of Bath is one of the UK's leading universities both in terms of research and our reputation for excellence in teaching, learning and graduate prospects.

The University is rated Gold in the Teaching Excellence Framework (TEF), the Government's assessment of teaching quality in universities, meaning its teaching is of the highest quality in the UK.

In the Research Excellence Framework (REF) 2014 research assessment 87 per cent of our research was defined as 'world-leading' or 'internationally excellent'. From developing fuel efficient cars of the future, to identifying infectious diseases more quickly, or working to improve the lives of female farmers in West Africa, research from Bath is making a difference around the world. Find out more: http://www.bath.ac.uk/research/

Well established as a nurturing environment for enterprising minds, Bath is ranked highly in all national league tables. We are ranked 6th in the UK by The Guardian University Guide 2021, and 9th in The Times & Sunday Times Good University Guide 2021 and 10th in the Complete University Guide 2021. Our sports offering was rated as being in the world's top 10 in the QS World University Rankings by Subject in 2021.

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A star in a distant galaxy blew up in a powerful explosion, solving an astronomical mystery

Giant explosion in space illuminates thousand-year mystery

TEL-AVIV UNIVERSITY

Research News

IMAGE: HUBBLE SPACE TELESCOPE COLOR COMPOSITE OF THE ELECTRON-CAPTURE SUPERNOVA 2018ZD AND THE HOST STARBURST GALAXY NGC 2146 view more 

CREDIT: NASA/STSCI/J. DEPASQUALE; LAS CUMBRES OBSERVATORY

Dr. Iair Arcavi, a Tel Aviv University researcher at the Raymond and Beverly Sackler Faculty of Exact Sciences, participated in a study that discovered a new type of stellar explosion - an electron-capture supernova. While they have been theorized for 40 years, real-world examples have been elusive. Such supernovas arise from the explosions of stars 8-9 times the mass of the sun. The discovery also sheds new light on the thousand-year mystery of the supernova from A.D. 1054 that was seen by ancient astronomers, before eventually becoming the Crab Nebula, that we know today.

A supernova is the explosion of a star following a sudden imbalance between two opposing forces that shaped the star throughout its life. Gravity tries to contract every star. Our sun, for example, counter balances this force through nuclear fusion in its core, which produces pressure that opposes the gravitational pull. As long as there is enough nuclear fusion, gravity will not be able to collapse the star. However, eventually, nuclear fusion will stop, just like gas runs out in a car, and the star will collapse. For stars like the sun, the collapsed core is called a white dwarf. This material in white dwarfs is so dense that quantum forces between electrons prevent further collapse.

For stars 10 times more massive than our sun, however, electron quantum forces are not enough to stop the gravitational pull, and the core continues to collapse until it becomes a neutron star or a black hole, accompanied by a giant explosion. In the intermediate mass range, the electrons are squeezed (or more accurately, captured) onto atomic nuclei. This removes the electron quantum forces, and causes the star to collapse and then explode.

Historically, there have been two main supernova types. One is a thermonuclear supernova -- the explosion of a white dwarf star after it gains matter in a binary star system. These white dwarfs are the dense cores of ash that remain after a low-mass star (one up to about 8 times the mass of the sun) reaches the end of its life. Another main supernova type is a core-collapse supernova where a massive star -- one more than about 10 times the mass of the sun -- runs out of nuclear fuel and has its core collapsed, creating a black hole or a neutron star. Theoretical work suggested that electron-capture supernovae would occur on the borderline between these two types of supernovae.

That's the theory that was developed in the 1980's by Ken'ichi Nomoto of the University of Tokyo, and others. Over the decades, theorists have formulated predictions of what to look for in an electron-capture supernova. The stars should lose a lot of mass of particular composition before exploding, and the supernova itself should be relatively weak, have little radioactive fallout, and produce neutron-rich elements.

The new study, published in Nature Astronomy, focuses on the supernova SN2018zd, discovered in 2018 by Japanese amateur astronomer Koihchi Itagaki. Dr. Iair Arcavi, of the astrophysics department at Tel Aviv University, also took part in the study. This supernova, located in the galaxy NGC 2146, has all of the properties expected from an electron-capture supernova, which were not seen in any other supernova. In addition, because the supernova is relatively nearby - only 31 million light years away - the researchers were able to identify the star in pre-explosion archival images taken by the Hubble Space Telescope. Indeed, the star itself also fits the predictions of the type of star that should explode as an electron-capture supernovae, and is unlike stars that were seen to explode as the other types of supernovae.

While some supernovae discovered in the past had a few of the indicators predicted for electron-capture supernovae, only SN2018zd had all six - a progenitor star that fits within the expected mass range, strong pre-supernova mass loss, an unusual chemical composition, a weak explosion, little radioactivity, and neutron-rich material. "We started by asking 'what's this weirdo?'" said Daichi Hiramatsu of the University of California Santa Barbara and Las Cumbres Observatory, who led the study. "Then we examined every aspect of SN 2018zd and realized that all of them can be explained in the electron-capture scenario."

The new discoveries also illuminate some mysteries of one of the most famous supernovae of the past. In A.D. 1054 a supernova happened in our own Milky Way Galaxy, and according to Chinese and Japanese records, it was so bright that it could be seen in the daytime and cast shadows at night. The resulting remnant, the Crab Nebula, has been studied in great detail, and was found to have an unusual composition. It was previously the best candidate for an electron-capture supernova, but this was uncertain partly because the explosion happened nearly a thousand years ago. The new result increases the confidence that the historic 1054 supernova was an electron-capture supernova.

"It's amazing that we can shed light on historical events in the Universe with modern instruments," says Dr. Arcavi. "Today, with robotic telescopes that scan the sky in unprecedented efficiency, we can discover more and more rare events which are critical for understanding the laws of nature, without having to wait 1000 years between one event and the next."

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Dr. Arcavi is a member of the Global Supernova Project, and makes use of the Las Cumbres telescope network to study rare transient phenomena like supernovae, neutron star mergers, and stars torn apart by black holes.

Link to the original article: https://www.nature.com/articles/s41550-021-01384-2