Culture

New research into Alzheimer's disease (AD) suggests that secondary infections and new inflammatory events amplify the brain's immune response and affect memory in mice and in humans - even when these secondary events occur outside the brain.

Scientists believe that key brain cells (astrocytes and microglia) are already in an active state due to inflammation caused by AD and this new research shows that secondary infections can then trigger an over-the-top response in those cells, which has knock-on effects on brain rhythms and on cognition.

In the study, just published in Alzheimer's & Dementia, the journal of the Alzheimer's Association, mice engineered to show features of AD were exposed to acute inflammatory events to observe the downstream effects on brain inflammation, neuronal network function and memory.

These mice showed new shifts in the output of astrocytes and microglia and displayed new cognitive impairment and disturbed 'brain rhythms' that did not occur in healthy, age-matched, mice. These new onset cognitive changes are similar to acute and distressing psychiatric disturbances like delirium, that frequently occur in elderly patients.

Although it is difficult to replicate these findings in patients, the study additionally showed that AD patients who died with acute systemic infection showed heighted brain levels of IL-1β - a pro-inflammatory molecule that was important in causing the heightened immune response and the new onset disruptions seen in the AD mice.

Colm Cunningham, Associate Professor in Trinity's School of Biochemistry and Immunology, and the Trinity Biomedical Sciences Institute, led the research. He said:

"Alzheimer's disease is the most common form of dementia, affecting more than 5% of those over 60 and this distressing, debilitating condition causes difficulties for a huge number of people across the globe. The more we know about the disease and its progression the better chance we have of treating those living with it. We believe our work adds to this knowledge base in a few ways. Primarily, we show that the Alzheimer's-affected brain has a greater vulnerability to acute inflammatory events, even if they occur outside the brain.

Placing this within the context of the slowly evolving progression of AD, we propose that these hypersensitive responses, now seen in multiple cell populations, may contribute to the negative outcomes that follow acute illness in older patients, including episodes of delirium and the accelerated cognitive trajectory that has been observed in patients who experience delirium before or during their dementia."

MIT researchers have created the first fiber with digital capabilities, able to sense, store, analyze, and infer activity after being sewn into a shirt.

Yoel Fink, who is a professor of material sciences and electrical engineering, a Research Laboratory of Electronics principal investigator, and the senior author on the study, says digital fibers expand the possibilities for fabrics to uncover the context of hidden patterns in the human body that could be used for physical performance monitoring, medical inference, and early disease detection.

Or, you might someday store your wedding music in the gown you wore on the big day -- more on that later.

Fink and his colleagues describe the features of the digital fiber in Nature Communications. Until now, electronic fibers have been analog -- carrying a continuous electrical signal -- rather than digital, where discrete bits of information can be encoded and processed in 0s and 1s.

"This work presents the first realization of a fabric with the ability to store and process data digitally, adding a new information content dimension to textiles and allowing fabrics to be programmed literally," Fink says.

MIT PhD student Gabriel Loke and MIT postdoc Tural Khudiyev are the lead authors on the paper. Other co-authors MIT postdoc Wei Yan; MIT undergraduates Brian Wang, Stephanie Fu, Ioannis Chatziveroglou, Syamantak Payra, Yorai Shaoul, Johnny Fung, and Itamar Chinn; John Joannopoulos, the Francis Wright Davis Chair Professor of Physics and director of the Institute for Soldier Nanotechnologies at MIT; Harrisburg University of Science and Technology master's student Pin-Wen Chou; Rhode Island School of Design Associate Professor Anna Gitelson-Kahn, and Professor Anais Missakian, who holds the Pevaroff-Cohn Family Endowed Chair in Textiles at RISD.

Memory and more

The new fiber was created by placing hundreds of square silicon microscale digital chips into a preform that was then used to create a polymer fiber. By precisely controlling the polymer flow, the researchers were able to create a fiber with continuous electrical connection between the chips over a length of tens of meters.

The fiber itself is thin and flexible and can be passed through a needle, sewn into fabrics, and washed at least 10 times without breaking down. According to Loke, "When you put it into a shirt, you can't feel it at all. You wouldn't know it was there."

Making a digital fiber "opens up different areas of opportunities and actually solves some of the problems of functional fibers," he says.

For instance, it offers a way to control individual elements within a fiber, from one point at the fiber's end. "You can think of our fiber as a corridor, and the elements are like rooms, and they each have their own unique digital room numbers," Loke explains. The research team devised a digital addressing method that allows them to "switch on" the functionality of one element without turning on all the elements.

A digital fiber can also store a lot of information in memory. The researchers were able to write, store, and read information on the fiber, including a 767-kilobit full-color short movie file and a 0.48 megabyte music file. The files can be stored for two months without power.

When they were dreaming up "crazy ideas" for the fiber, Loke says, they thought about applications like a wedding gown that would store digital wedding music within the weave of its fabric, or even writing the story of the fiber's creation into its components.

Fink notes that the research at MIT was in close collaboration with the textile department at RISD led by Anais Missakian. Associate Professor Anna Gitelson-Kahn incorporated the digital fibers into a knitted garment sleeve, thus paving the way to creating the first digital garment.

On-body artificial intelligence

The fiber also takes a few steps forward into artificial intelligence by including, within the fiber memory, a neural network of 1,650 connections. After sewing it around the armpit of a shirt, the researchers used the fiber to collect 270 minutes of surface body temperature data from a person wearing the shirt, and analyze how these data corresponded to different physical activities. Trained on these data, the fiber was able to determine with 96 percent accuracy what activity the person wearing it was engaged in.

Adding an AI component to the fiber further increases its possibilities, the researchers say. Fabrics with digital components can collect a lot of information across the body over time, and these "lush data" are perfect for machine learning algorithms, Loke says.

"This type of fabric could give quantity and quality open-source data for extracting out new body patterns that we did not know about before," he says.

With this analytic power, the fibers someday could sense and alert people in real-time to health changes like a respiratory decline or an irregular heartbeat, or deliver muscle activation or heart rate data to athletes during training.

The fiber is controlled by a small external device, so the next step will be to design a new chip as a microcontroller that can be connected within the fiber itself.

"When we can do that, we can call it a fiber computer," Loke says.

WASHINGTON, DC - JUNE 3, 2021 -- A new West Health/Gallup survey finds nearly all Democrats (97%) and the majority of Republicans (61%) support empowering the federal government to negotiate lower prices of brand-name prescription drugs covered by Medicare. Overall, 8 in 10 Americans prefer major government action to control prices over concerns about it hurting innovation and competition from the pharmaceutical industry. The results come from a nationally representative poll of more than 3,700 American adults.

While President Joe Biden, Democrats in Congress and former President Donald Trump have called for such negotiation, Republicans on Capitol Hill and the pharmaceutical industry itself have been fiercely opposed to the measure, claiming lower prices would hurt competition and reduce innovation. However, this belief is not widely shared among the American people. According to the survey, less than 20% of all Americans believe Medicare negotiation would hurt innovation or market competition, including a minority of Republicans (39%).

"Americans aren't buying the claim that attempts to reign in drug prices will stifle innovation and devastate the pharmaceutical industry," said Tim Lash, Chief Strategy Officer for West Health, a family of nonprofit and nonpartisan organizations dedicated to lowering healthcare costs to enable successful aging. "These misleading arguments are meant to preserve profits rather than protect patients. The time has come to finally enable Medicare negotiation. Americans are becoming increasing restless for it to happen even if the pharmaceutical companies are not."

If enacted, Medicare negotiation as described in H.R. 3, the Elijah E. Cummings Lower Drug Costs Now Act, is projected to save the federal government, businesses, and workers hundreds of billions of dollars by 2030. According to a new analysis from West Health and its Council for Informed Drug Spending Analysis (CIDSA), private employers could also save $195 billion and workers would see another $98 billion in savings. These savings are in addition to the estimated savings of $456 billion in federal direct spending forecast by the Congressional Budget Office (CBO).

When choosing between the need for major reform in drug pricing and maintaining the status quo, 90% of Americans chose to support reforms, including 96% of Democrats, 88% of Independents and 83% of Republicans. Sweeping support also exists for specific actions including setting limits on out-of-pocket costs for prescription drugs (87% strongly or somewhat supporting) and general healthcare (84%) in Medicare and limiting hospital charges for those with private insurance (83%), and allowing Medicare to negotiate drug prices for all Americans, not just Medicare beneficiaries, is supported by 70% of respondents.

"There is little question that substantial public support exists for more government action when it comes to addressing drug costs," said Dan Witters, Gallup senior researcher. "And while there are differences across the political spectrum, even among Republicans, sentiment for public action is substantial."

Could an over-the-counter health "shot" help fight COVID-19? George Mason University researchers think it just might.

Cell and Bioscience recently highlighted research led by Yuntao Wu and Ramin Hakami in which they examined the potential anti-coronavirus activities of an over-the-counter drink called Respiratory Detox Shot (RDS).

RDS is a remedy containing nine herbal ingredients traditionally used in Eastern medicine to manage lung diseases. The researchers reported that RDS inhibited the infection of target cells by SARS-CoV and SARS-CoV-2 pseudoviruses and by infectious wild-type SARS-CoV-2. Their results suggest that RDS might broadly inhibit respiratory viruses, such as influenza.

SARS-CoV is the viral pathogen causing Severe Acute Respiratory Syndrome (SARS), and its sister virus, SARS-CoV-2, is the pathogen that causes COVID-19. The COVID-19 global pandemic is a major focus of researchers around the world. While effective vaccines have been developed, there is still a need for developing effective treatments. In particular, new variants of the virus are continuously emerging, and some of these variants may make the vaccines less effective.

Ramin Hakami, an Associate Professor in Mason's School of Systems Biology and one of the authors of the study, said that the fact that RDS is a drinkable food supplement is helpful.

"If it proves effective in vivo, it should be a treatment for COVID-19 that is easy to administer," said Hakami, who also works at Mason's National Center for Biodefense and Infectious Diseases. "That's a big plus."

For their study, Hakami, Wu, and Mason researchers Brian Hetrick, Adeyemi A. Olanrewaju, Linda D. Chillin, Sijia He, and Deemah Debbagh worked with Dongyang Yu of Virongy LLC, Yuan-Chun Ma of Dr. Ma's Laboratories Inc., and Lewis A. Hoffman of the World Health Science Organization.

The team screened extracts from approximately 40 medicinal herbs using a SARS-CoV-2 pseudovirus and human lung cells. They also screened for possible anti-SARS-CoV-2 activity of RDS.

For the study, they pretreated cells with diluted RDS and then infected the cells in the presence of RDS for four to six hours. After infection, they cultured cells in the absence of RDS and then quantified the cells to determine if viral infection was inhibited at 48 and 72 hours.

Subsequently, the researchers used the Biomedical Research Lab on Mason's Science and Technology Campus to confirm the in vitro efficacy of RDS against infectious SARS-CoV-2 virus.

[The] study revealed that RDS contains very potent ingredients that can destroy the infectivity of SARS-CoV, SARS-CoV-2, and influenza A virus, even at very low dosages, said Wu, a professor in Mason's National Center for Biodefense and Infectious Diseases and a study co-author. In addition, the investigators have demonstrated that RDS is effective against the SARS-CoV-2 variants in vitro.

Hetrick, a PhD student in biosciences working on the study, said that the discovery was a happy surprise for him. It would be great if there are safe and effective herbal drugs available for the management of COVID-19 in the future.

Hakami is currently conducting in vivo animal studies to build on the in vitro discovery that RDS may be used as a SARS-CoV-2 treatment. He is testing RDS using K18-hACE2 transgenic mice that will be infected with SARS-CoV-2. Depending on the results, Dejia Harmony, the sponsor of the above pre-clinical trial, may seek FDA approval to begin human clinical trials.

"This study points to the possibility of using a readily available, over-the-counter herbal beverage to provide protection against SARS-CoV-2 and influenza A infections," said Ali Andalibi, senior associate dean in Mason's College of Science. "It will also be quite interesting to see if RDS shows activity against other respiratory viruses."

WOODS HOLE, Mass. -- Plastics are everywhere. From cell phones to pens and cars to medical devices, the modern world is full of plastic-- and plastic waste. New research from scientists at the Marine Biological Laboratory (MBL) Ecosystems Center found that some of that plastic waste has been accumulating in salt marshes for decades. The study was published in Environmental Advances.

Salt marshes are the link between the land and open ocean ecosystems, and -- in a way --between urban environments and the wild ocean. Microplastics (plastic particles smaller than 5 millimeters) tend to float on the water surface, but salt marshes fill and empty with the tides, so particles that would normally float get trapped within branches and roots and settle into the marsh soil.

Sediments accumulate in the salt marsh layer after layer, like tree rings, keeping an historical record of sedimentation within the ecosystem. "By accumulating sediments, they are keeping a record in time," says Javier Lloret, MBL research scientist and co-first author on the paper.

Globally, scientists estimate that about 8 million tons of plastic enter the ocean each year. But until now, there's been no estimation of the amount of that plastic that gets trapped in salt marsh ecosystems.

By taking core samples of the marsh sediment at six different estuaries in the Waquoit Bay system on Cape Cod, as well as New Bedford, Mass., harbor, the researchers were able to trace the abundance of microplastics dating back decades in areas with very contrasted degrees of land use.

"As you go into the past, the amount of microplastics you find decreases clearly," says Lloret. "The amount of microplastics you find in sediments is related to the population numbers... but also the amount of plastic that people use."

"Waquoit Bay is the perfect salt marsh system to study plastic pollution because we can contrast one area that is almost pristine... with another area that is highly impacted by human activity," says Rut Pedrosa-Pàmies, also an MBL research scientist and co-first author on the paper. "We found a broad range of plastic pollution."

The researchers focused on two types of microplastic pollution: fragments (from the breakdown of larger plastic pieces) and fibers (thread-like plastics which tend to shed from clothing and fishing gear). They found that fragment pollution increased both through time and with urbanization. The more populated the area surrounding the collection site, the more plastic fragments the researchers observed.

One surprise in the data was that microplastic concentration in the sediments wasn't linear as urbanization grew. Up to 50% development, the concentration of microplastic fragments was relatively unchanged, but once the land was occupied at 50%, the number of microplastics grew exponentially.

"Just a few people in the surrounding area is not going to change much, but when urban uses occupy more than 50% of the land, the number of microplastics goes crazy," says Lloret.

The microplastic fibers didn't have the same relationship with urbanization. "Even in the more pristine areas that don't have urbanization, we find fiber plastic pollution" says Pedrosa-Pàmies.

The researchers believe the fragments have a local origin (people using and disposing of plastics where they live) whereas fibers can be transported long distances by air or by water from large-scale urban areas.

"When we started, we didn't know if microplastics were an issue here on Cape Cod, or not. No one had analyzed the marsh sediments on Cape Cod for microplastics before," says Lloret.

Now that the scientists have shown there is microplastic pollution in New England salt marshes, the next step is to gain further insight. How are those particles arriving in the ecosystem? What are the sources? How are they impacting the ecosystem and the food web of the organisms that live there?

"There are still a lot of unanswered questions," says Pedrosa-Pàmies. "This is the first step for management, too."

MADISON, Wis. -- If you're wearing gold jewelry right now, there's a good chance it came from an illegal mining operation in the tropics and surfaced only after some rainforest was sacrificed, according to a team of University of Wisconsin-Madison researchers and alumni who studied regulatory efforts to curb some of these environmentally damaging activities in the Amazon.

The researchers, including UW-Madison geography Professor Lisa Naughton, investigated mining-related deforestation in a biodiverse and ecologically sensitive area of the Peruvian Amazon to see whether formalizing and legalizing these mining operations might curb some of their negative effects.

Their study, published June 2 in the journal Environmental Research Letters, was co-authored by a group including UW-Madison alumnae Nora Álvarez-Berríos, now studying land-use and climate impacts at the International Institute of Tropical Forestry, and Jessica L'Roe, now a geography professor at Middlebury College.

The team focused on an area around the Tambopata National Reserve in Peru from 2001 to 2014. During this time period, Naughton says, demand for gold rose, roads penetrated the region and mining surged. In turn, mining-related deforestation rose by almost 100,000 acres over their study period.

"Because the gold is in the sediment scattered under the forest floor, to extract the gold, you have to remove the forest and dig," Álvarez-Berríos says. "You have to cut a lot of the forest and excavate sensitive waterways."

While these mining operations are often called "artisanal" or "small-scale," in aggregate they are very destructive. In many countries they operate outside the law, and millions of people are involved across the tropics. Álvarez-Berríos says the typical first step to reducing the environmental impact of artisanal mining is bringing it under governmental oversight, formalizing the activity. That way, local agencies can manage the impacts and protect both ecologically sensitive areas and the economic well-being of poor mine workers.

"Peruvian authorities, like authorities in other gold-rush sites, have given up on trying to stop gold mining. They're trying to confine it and contain it," L'Roe says. "Most of the studies about formalization are mainly about trying to help the poor, or make it more fair for the poor. Seldom, almost never, as far as we can tell, have these formalization projects been assessed for their environmental impact. So that's what we were looking at."

During their study period, local agencies issued provisional titles to miners to conduct their operations safely. After receiving a provisional title, miners would, in theory, undergo a series of environmental impact and compliance assessments before they started work.

But, as L'Roe says they found, the regulation process took a long time. Many miners simply took their provisional title as a green light to start mining, and never went through with the environmental impact assessments. Over their study period, no mining operations made it through the full compliance process, and as such they found little evidence for improved environmental outcomes in formalized mining areas.

To assess environmental outcomes, the team used satellite imagery analysis to see how much of the forest had been cut down, as compared to areas without formalized mining regulations.

Naughton says while formalizing mining has the potential to decrease environmental damage, it needs enforcement and regulations that match the local context. Formalization without environmental impact assessment or enforcement could just encourage more damaging and dangerous mining, or the expansion of these operations under the pretense that what they're doing is legal.

But gold rushes are exactly what they sound like, Naughton says: rushed. They're fast, and slow formalization processes with many steps and provisions and impact assessments often cannot keep up with the pace of extraction.

"To sort out in a fair way who owns what land, with what rights, that is a slow process," Naughton says. "This gold rush is explosive. By the time you have well-regulated and transparent public land and property rights, the forest will be gone."

The team plans to go back to Tambopata to present its results to local stakeholders. Many members of the community are already aware of the problems with mining formalization but have not had a chance to systematically study the environmental consequences. The three co-authors hope their study will set a precedent for monitoring formalization interventions in Tambopata and other tropical sites losing forest to mining. They are already sharing results and methods with colleagues concerned about gold mining impacts in Colombia, Brazil and Bolivia.

"We'll go back to our study site and share the results -- but in a humble way because folks there know that it hasn't worked well, and they know the problems," says Álvarez-Berríos. "So, yes, it's important to share it with that group of stakeholders and experts, but maybe even more important is to share the results and our methods and design for studying this problem with folks working in the many, many other areas where there's uncontrolled small-scale gold mining and where formalization efforts are being launched with best intentions."

A University of Birmingham-led study of over a thousand dental professionals has shown their increased occupational risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK.

The observational cohort study, published today (3 June 2021), in the Journal of Dental Research, involved 1,507 Midland dental care practitioners. Blood samples were taken from the cohort at the start of the study in June 2020 to measure their levels of antibodies against SARS-CoV-2, the virus that causes COVID-19.

The team found 16.3% of study participants - which included dentists, dental nurses and dental hygienists - had SARS-CoV-2 antibodies, compared to just 6% of the general population at the time. Meanwhile, the percentage of dental practice receptionists, who have no direct patient contact, with SARS-CoV-2 antibodies was comparable to the general population, supporting the hypothesis that occupational risk arose from close exposure to patients.

The study also found ethnicity was also a significant risk factor for infection, with 35% of Black participants and 18.8% of Asian participants having SARS-CoV-2 antibodies, compared to 14.3% of white participants.

Blood samples were taken from participants three months later, in September 2020, when dental practices in England had re-opened with enhanced PPE and infection control measures in place, and once again in January 2021, six months after the start of the study, during the second wave of the pandemic when healthcare workers were being vaccinated.

The results showed that of those who had previous COVID-19 infection, over 70% continued to have SARS-CoV-2 antibodies both at three months and six months later, and they were at a 75% reduced risk of re-infection with the virus.

The study also demonstrated the immunological impact of COVID-19 vaccination, with 97.7% of those without previous infection developing an antibody response at least 12 days after their first Pfizer vaccine. In those with evidence of previous infection, the antibody response was more rapid and higher in magnitude after a single dose of the Pfizer vaccine.

Furthermore, none of the cohort with a level of SARS-CoV-2 antibodies greater than 147.6 IU/ml in their blood tested positive for COVID-19 throughout the six-month period from the first to the final blood tests.

First author Dr Adrian Shields, of the University of Birmingham's Institute of Immunology and Immunotherapy, said: "Understanding what an antibody test result means to an individual with respect to their risk of infection is essential to controlling the pandemic.

"Our study has taken the first steps in defining the level of antibody in a persons' blood necessary to protect them from infection for six months. Furthermore, by comparing the antibody levels we have found in dentists to those contained in widely available reference material produced by the World Health Organization, we hope the protective level we found can be easily confirmed and compared by other laboratories."

Corresponding author Professor Thomas Dietrich, of the University of Birmingham's School of Dentistry, adds: "Critically, only 5.3% of the cohort developed an antibody response that exceeded this threshold of 147.6 IU/ml following the first wave of the UK pandemic. This suggests that natural infection alone is unlikely to generate meaningful, durable herd immunity."

Co-corresponding author Iain Chapple, Professor of Periodontology at the University of Birmingham and Consultant in Restorative Dentistry at Birmingham Community Healthcare Trust, adds: "Dental professionals are thought to be at high risk of exposure to SARS-CoV-2 because they routinely operate within patients' aerodigestive tract and regularly carry out aerosol-generating procedures that result in the production of airborne particles.

"Through our research, we have clearly shown that dental professionals were at increased occupational risk of exposure to SARS-CoV-2 prior to the new PHE guidance on PPE. The occupational health measures that have been put in place in general dental practice as a consequence of COVID-19 appear to remove that increased risk, however, this will need to be thoroughly investigated to see if they have successfully interrupted transmission of SARS-CoV-2 and other respiratory viruses."

Co-corresponding author Professor Alex Richter, also of the University of Birmingham, said: "This is the first time the occupational risk of exposure to a potentially fatal respiratory virus has been studied in a large dental cohort.

"It is important that we now progress our research to ensure we have an understanding of how people are protected from re-infection with COVID-19 following natural infection and vaccination.

"The nature and duration of immunity in these cohorts will be critical to understand as the COVID-19 pandemic progresses, particularly with respect to the efficacy of vaccination strategies -single-dose, multiple-doses, vaccine combinations - and in relation to novel viral variants of concern."

For decades, researchers have debated whether the buildup of certain electrical activities in the brain indicates that human beings are unable to act out of free will.

Experiments spanning the 1960s and 1980s measured brain signals noninvasively and led many neuroscientists to believe that our brains make decisions before we do--that human actions were initiated by electrical waves that did not reflect free, conscious thought.

However, a new article in Trends in Cognitive Science argues that recent research undermines this case against free will.

"This new perspective on the data turns on its head the way well-known findings have been interpreted," said Adina Roskies, the Helman Family Distinguished Professor and professor of philosophy at Dartmouth College, who co-wrote the article. "The new interpretation accounts for the data while undermining all the reasons to think it challenges free will."

The debate over free will centers mostly around research from the 1980s that used electroencephalograms to study brain activity. The EEG-based research measured when electrical signals begin to build in the brain relative to when a person is aware of their desire to make a movement. The averaged data described a ramp before movement that became known as the "readiness potential," or "RP."

The 1980s research, conducted by neurophysiologist Benjamin Libet, contended that if the readiness potential was evident prior to a person having a conscious thought about moving, free will could not be responsible for either the buildup of electrical signals or the subsequent movement.

According to the research team, this part of Libet's logic was based on a premise that is likely false.

"Because the averaged readiness potential reliably precedes voluntary movement, people assumed that it reflected a process specifically directed at producing that movement. As it turns out, and as our model has shown, that is not necessarily the case," said Aaron Schurger, an assistant professor of psychology at Chapman University who co-wrote of the article.

The article highlights new research using computational modeling that indicates that the standard interpretation of the readiness potential should be reassessed, particularly for its relevance to the question of free will.

The study points to findings that suggest that the readiness potential--the pre-movement buildup of activity--reflects the neural activity that underlies the formation of a decision to move, rather than the outcome of a decision to move.

"These new computational models account for the consistent finding of the readiness potential without positing anything like an RP in individual trials. The readiness potential itself is a kind of artifact or illusion, one which would be expected to appear just as it does given the experimental design, but doesn't reflect a real brain signal that begins with the RP onset or is read out by other areas," said Roskies.

The article also highlights several challenges to the idea that the readiness potential causes humans to act: difficulty distinguishing the readiness potential from other electrical signals in the brain; the presence of a readiness potential when tasks do not involve motor activity; and "noise" in analyses which makes it difficult to confirm whether the readiness potential always predicts movement.

False positives, in which readiness potential is observed but fails to initiate movement, and inconsistencies in the amount of time between the buildup of the brain waves and movement also complicate the understanding of the connection between the electrical activity in the brain and free will.

Finally, the article emphasizes the philosophical aspects of attempting to address the problem of free will with brain data.

Pengbo Hu at Pomona College and Joanna Pak from Chapman University, also contributed to this paper.

Known as nature's own sonar system, echolocation occurs when an animal emits a sound that bounces off objects in the environment, returning echoes that provide information about the surrounding space.

While echolocation is well known in whale or bat species, previous research has also indicated that some blind people may use click-based echolocation to judge spaces and improve their navigation skills.

Equipped with this knowledge, a team of researchers, led by Dr Lore Thaler, of Durham University, UK, delved into the factors that determine how people learn this skill.

Over the course of a 10-week training programme, the team investigated how blindness and age affect learning of click-based echolocation. They also studied how learning of this skill affects the daily life of people who are blind.

The findings are published in the journal PLOS ONE.

The study involved blind and sighted participants between 21 and 79 years of age who trained over the course of 10 weeks. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life.

Both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training. Somewhat surprisingly, in some cases sighted people even performed better than those who were blind.

Importantly, however, neither age nor blindness was a limiting factor in participants' rate of learning or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing.

Overall, the results suggest that the ability to learn click-based echolocation is not strongly limited
by age or level of vision. This has positive implications for the rehabilitation of people with vision loss or in the early stages of progressive vision loss.

Currently, click-based echolocation is not taught as part of mobility training and rehabilitation for blind people. There is also the possibility that some people are reluctant to use click-based echolocation due to a perceived stigma around making the required clicks in social environments.

Despite this, the results indicate that blind people who use echolocation and people new to echolocation are confident to use it in social situations. The potential barriers relating to perceived stigma are perhaps much smaller than previously thought.

Dr. Lore Thaler, in the Department of Psychology at Durham University, said "I cannot think of any other work with blind participants that has had such enthusiastic feedback."

"People who took part in our study reported that the training in click-based echolocation had a positive effect on their mobility, independence and wellbeing, attesting that the improvements we observed in the lab transcended into positive life benefits outside the lab. "

"We are very excited about this and feel that it would make sense to provide information and training in click-based echolocation to people who may still have good functional vision, but who are expected to lose vision later in life because of progressive degenerative eye conditions."

The human brain continues to surprise us with its capabilities for complex learning strategies and the neuroplasticity to alter its very structure to better process information from its senses.

The work was funded by a grant of the Biotechnology and Biological Sciences Research Council United Kingdom, and a grant from the Network for Social Change.

Clinical trials published in high-profile medical journals rarely report on income or other key sociodemographic characteristics of study participants, according to a new study that suggests these gaps may create blind spots when it comes to health care, especially for disadvantaged populations.

The study, publishing June 2 in JAMA Network Open, analyzed 10 per cent of 2,351 randomized clinical trials published in New England Journal of Medicine, JAMA, The BMJ, The Lancet and Annals of Internal Medicine between Jan. 1, 2014 and July 31, 2020.

The most commonly reported sociodemographic variables were sex and gender (in 98.7 per cent of trials) and race/ethnicity (in 48.5 per cent). All other sociodemographic data, such as income, literacy or education level, language or housing status were reported in less than 15 per cent of the trials.

"Randomized trials can only work for everyone if they include everyone," said Dr. Aaron Orkin, a researcher and Emergency Physician at St. Joseph's Health Centre of Unity Health Toronto who led the study. "The results of randomized trials affect everybody because they determine how we promote health and how we diagnose and treat disease.

"If trials don't report on the characteristics of the people being studied, there is no way to know that the study's findings will apply to all populations. Trials can only serve populations made vulnerable by social and economic policies if they are included."

The research found that education level or literacy was reported in 14.3 per cent of studies examined, 5.9 per cent reported income or socioeconomic status and 4.6 per cent included participants based on a social determinant of health, such as health insurance or employment status which are social factors that impact health. Of the 237 studies examined, only six (2.5 per cent) reported gender. No studies reported non-binary gender descriptors.

Dr. Orkin used the rollout of the COVID-19 vaccine as an example to explain why these findings are important. Public health officials now know that communities who are most vulnerable to COVID-19 tend to also be those who face the most barriers in terms of access to vaccines.

"In Ontario, Manitoba and elsewhere, data on race, ethnicity, income and occupation were collected with cases of COVID-19, and this has informed the vaccine rollout," noted Dr. Andrew Pinto, a Scientist at the MAP Centre for Urban Health Solutions of St. Michael's, who co-led the study and was a co-author. "We need to ensure data on these important social determinants of health are included in COVID-19 treatment and vaccine studies as well," he noted.

Similarly, recently, including women in cardiovascular trials after years of exclusion has led to the discovery that women have different heart disease symptoms and pathologies - something that was not known until women were included in randomized clinical trials about the disease.

"People who face discrimination or disadvantages should have confidence that research being done to benefit them is inclusive," said Dr. Nav Persaud, a scientist at MAP and co-author on the paper.

The authors argue that experiences and outcomes of a disease across cultures, races, income levels, living situations, genders, and other variables will be different. Studying a disease and its treatment in limited groups ultimately limits its applicability.

The authors hope to use the initial information reported in this study to focus on reporting of social determinants in trials in specific disease areas and to change standards in conducting research.

"Trials like the ones we studied have a great impact on clinical guidelines and often determine what gets funded. Inclusivity from the start is essential," Dr. Pinto said.

MINNEAPOLIS - Deep brain stimulation continues to be effective in people with Parkinson's disease 15 years after the device is implanted, according to a study published in the June 2, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Researchers found that compared to before deep brain stimulation, study participants continued to experience significant improvement in motor symptoms, which are symptoms that affect movement, as well as a reduction in medications 15 years later.

Parkinson's disease can progressively affect speech, walking and balance due to a gradual reduction of a chemical in the brain called dopamine. Parkinson's symptoms of muscle stiffness, tremor and slowness of movement can be treated with a medication call levodopa that temporarily restores dopamine. However, that process of rising and falling levels of dopamine throughout the day can cause dyskinesia, a side effect of medication that may include twisting, swaying or head bobbing.

Deep brain stimulation controls motor symptoms from Parkinson's disease with electrodes that are placed in certain areas of the brain. The electrodes are connected to a device placed under the skin in the upper chest. The device controls the electrical impulses.

"Deep brain stimulation benefits seem to last for several years but not enough data have been available to show that these effects are still present more than 15 years after surgery," said study author Elena Moro, MD, PhD, of the Grenoble Alpes University in France and a Fellow of the American Academy of Neurology. "We wanted to know if people with Parkinson's disease continue to benefit from this treatment. It is exciting to report that our study found in the long run, deep brain stimulation continues to be effective in people with Parkinson's disease."

For the study, researchers identified 51 people who had a deep brain stimulation device implanted at the university hospital. The average age for diagnosis of Parkinson's disease was 40. The average age for device implantation was 51. Study participants had the device an average of 17 years.

Researchers reviewed data for each participant on movement problems, quality of life, medication and scores on tests that measure the severity and progression of Parkinson's disease.

Researchers found that when comparing data on participants before having a device implanted to data 15 years later, the amount of time participants experienced dyskinesia was reduced by 75%.

Researchers also found the amount of time spent in an "off state," when medication was no longer working well, was reduced by 59%. Also, the use of medications to control dopamine levels was reduced by 51%.

Researchers found few side effects of having the stimulation for 15 years and such side effects were mostly manageable.

"Our study also found that despite the natural progression of Parkinson's disease and the worsening of some symptoms that become resistant to medications over the years, participants still maintained an overall improvement in quality of life," said Moro. "Future studies should continue to examine the benefits of deep brain stimulation over longer periods of time and in larger groups of people."

A limitation of the study was that many of the people who had deep brain stimulation at the hospital were not available for study 15 years later, either because researchers were no longer able to contact them or because they had died. It is possible that the people in the study may have been healthier than those not included, meaning the results may not fully reflect the experience of all people using deep brain stimulation.

What The Study Did: Researchers investigated the effect of real-time continuous glucose monitoring on glycemic control among patients with insulin-treated diabetes.

Authors: Andrew J. Karter, Ph.D., of Kaiser Permanente in Oakland, California, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2021.6530)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Individuals at higher risk of developing pancreatic cancer could be identified earlier using machine learning (ML) techniques which would result in a greater number of patients surviving the disease, suggests a new study published in PLOS ONE.

The study was led by the London School of Hygiene & Tropical Medicine (LSHTM) and funded by the UK charity Pancreatic Cancer Research Fund (PCRF).

It used UK electronic health records for more than 1,000 patients aged 15-99 years who were diagnosed with pancreatic cancer between January 2005 and June 2009.

The researchers examined numerous symptoms and health statuses recorded by a GP among patients up to two years before the cancer diagnosis. They then developed an algorithm which 'learnt' how to distinguish patients who went on to develop pancreatic cancer from those who didn't.

The algorithm was then used to identify those at high risk of developing pancreatic cancer just from GP records.

Using this technique, 41% of patients under the age of 60 were identified as high risk, up to 20 months prior to diagnosis. Over 72% of people who went on to be diagnosed would have been successfully identified as high risk (sensitivity) whilst 59% of people who did not develop cancer were correctly identified as low risk (specificity). Results were similar for patients over 60, with 43% identified at 17 months, with 65% sensitivity and 57% specificity.

The team estimates that combining their algorithm with simple blood and urine tests which could potentially detect pancreatic cancer, currently under investigation, could result in 30 older and 400 younger patients per cancer being identified as 'potential patients'. This could lead to the earlier diagnosis of around 60% of all pancreatic cancer tumours.

The authors acknowledge that further work is required to confirm, refine and evaluate the potential use of these findings in practice.

Dr Ananya Malhotra, co-lead author from the London School of Hygiene & Tropical Medicine, said: "Each year, 460,000 people worldwide are diagnosed with pancreatic cancer, and only around 5% of those diagnosed survive for five years or more. This low survival is because patients are usually diagnosed very late. Recent progress has been made in identifying biomarkers in the blood and urine, but these tests cannot be used for population screening as they would be very expensive and potentially harmful due to the psychological distress of excess testing.

"Although preliminary, this study offers some hope for a new early diagnosis for pancreatic cancer which until now remains elusive."

Previous research has highlighted conditions associated with pancreatic cancer diagnosis such as jaundice, abdominal pain and new-onset diabetes. Whilst these new results are consistent with these findings, this approach is a step-change from these previous studies because the team examined whether it is possible to predict future pancreatic cancer based on the presence of a combination of symptoms or abnormalities more than 12 months before diagnosis, ignoring late-stage symptoms.

The case-control study used anonymised electronic health records from primary care linked to cancer registrations. Cases were comprised of 1,139 patients, aged 15-99 years, diagnosed with pancreatic cancer between January 2005 and June 2009. Each case was age-, sex- and diagnosis time-matched to four non-pancreatic (cancer patient) controls. Disease and prescription codes for the 24 months prior to diagnosis were used to identify 57 individual symptoms, with models then trained to predict patients who later developed pancreatic cancer.

The algorithm's greatest potential is within a multiple-testing model where pancreatic cancer is one of several malignancies of interest. Another important finding was the relative importance of diabetes, over time-varying symptoms, in predicting later pancreatic cancer diagnosis, which is consistent with previous research.

Dr Laura Woods, study senior author from the London School of Hygiene & Tropical Medicine, said: "Using machine learning techniques we developed a risk score for pancreatic cancer diagnosis in order to identify patients for whom biomarkers might detect the disease at an early and treatable stage. After further work this approach could be applied in the primary care setting and has the potential to be used alongside a non-invasive biomarker test to increase earlier diagnosis. This would result in a greater number of patients surviving this devastating disease."

Maggie Blanks, Pancreatic Cancer Research Fund's Chief Executive Officer, said: "Using machine learning to help improve earlier diagnosis is truly novel and we're extremely pleased that this pilot study has shown to have strong potential. We're looking forward to seeing where this research leads, as earlier diagnosis will be a game-changer for improving survival for patients."

The authors acknowledge limitations of the study including the poor specificity of the models arising principally from the use of cancer patients as controls that are not representative of the general population.

The research team is seeking further funding to develop this pilot study into a full investigation.

All the cells of an organism share the same DNA sequence, but their functions, shapes or even lifespans vary greatly. This happens because each cell "reads" different chapters of the genome, thus producing alternative sets of proteins and embarking on different paths. Epigenetic regulation--DNA methylation is one of the most common mechanisms--is responsible for the activation or inactivation of a given gene in a specific cell, defining a secondary cell-specific genetic code.

Researchers led by Dr. Modesto Orozco, head of the Molecular Modelling and Bioinformatics lab at IRB Barcelona, have described how methylation has a protein-independent regulatory role by increasing the stiffness of DNA, which affects the 3D structure of the genome, thus impacting gene activation. Present work reveals a cryptic mechanism connecting epigenetic footprinting and gene programming, which can help us to better understand development, ageing and cancer.

"The new model organism and the theoretical analysis framework that we have developed and published are really innovative and we hope they will facilitate research projects undertaken by many laboratories around the world studying DNA methylation and its impact on gene expression," explains Dr. Orozco, also an ICREA Academia Fellow and Professor of the University of Barcelona (UB).

3D structure and gene expression

The DNA inside the cell is folded and structured in a 3D manner to maintain its correct organisation and preservation. When a gene has to be "read", DNA unfolds in this region, allowing access to the cellular machinery. Therefore, the 3D structure increases or decreases accessibility to a gene, conditioning whether that gene will produce the protein it encodes for, or not. For this study, the Molecular Modelling and Bioinformatics group used next-generation sequencing methods and molecular simulations to model the whole genome structure.

"Using these techniques, we observed that we could recapitulate the characteristic distribution of DNA methylation seen in mammalian genomes, and we confirmed our earlier in vitro result on the relationship between 3D structure, DNA flexibility, and methylation, showing that this also occurs in vivo," explains Dr. Isabelle Brun Heath, director of the Experimental Bioinformatics Laboratory and codirector the study.

Autistic people's ability to accurately identify facial expressions is affected by the speed at which the expression is produced and its intensity, according to new research at the University of Birmingham.

In particular, autistic people tend to be less able to accurately identify anger from facial expressions produced at a normal 'real world' speed. The researchers also found that for people with a related disorder, alexithymia, all expressions appeared more intensely emotional.

The question of how people with autism recognise and relate to emotional expression has been debated by scientists for more than three decades and it's only in the past 10 years that the relationship between autism and alexithymia has been explored.

This new study, published in the Journal of Autism and Developmental Disorders, uses new techniques to explore the different impacts of autism and alexithymia on a person's ability to accurately gauge the emotions suggested by different facial expressions.

Connor Keating, a PhD researcher in the University of Birmingham's School of Psychology and Centre for Human Brain Health, is lead author of the study. He says: "We identified that autistic people had a specific difficulty recognising anger which we are starting to think may relate to differences in the way autistic and non-autistic people produce these expressions. If this is true, it may not be accurate to talk about autistic people as having an 'impairment' or 'deficit' in recognising emotion- it's more that autistic and non-autistic faces may be speaking a different language when it comes to conveying emotion".

In the study, 31 autistic and 29 non-autistic participants were asked to identify emotions from a series of moving images made up of dots representing the key dynamic points of a facial expression - a little bit like the dots used to translate human movement into CGI animation. The images were displayed at a range of emotional intensities by varying the amount of movement in each expression, and at a variety of speeds.

The team found that both autistic and non-autistic participants had similar recognition capabilities at different speeds and intensities across all the emotions shown, except for one particular aspect - the autistic group were less able to identify angry expressions produced at normal speed and intensity. These represented the sorts of angry expressions that might be encountered in everyday life.

"When we looked at how well participants could recognise angry expressions, we found that it was definitely autistic traits that contribute, but not alexithymic traits," explained Connor. "That suggests recognising anger is a difficulty that's specific to autism."

A key trait that the team found was specific to participants with alexithymia was a tendency to perceive the expressions to be intensely emotional. Interestingly though, people with alexithymia were more likely to give higher correct and incorrect emotion ratings to the expressions. To give an example, those with alexithymia would rate a happy expression as more intensely happy and more intensely angry and sad than someone without alexithymia.

Connor explains: "One idea is that people with alexithymia are less able to gauge the intensity of emotional expressions and are more likely to get confused about which emotion is being presented."

He adds: "Everyone will know or meet somebody with autism at some point in their lives.By better understanding how people with autism perceive and understand the world we can start to develop training and other interventions for both autistic and non-autistic people to overcome some of the barriers to interacting successfully."