Culture

Discovery concerning the nervous system overturns a previous theory

image: From the left: Francois Lallemend and Saida Hadjab (both researchers at the Department of Neuroscience at Karolinska Institutet in Sweden), Yiqiao Wang and Haohao Wu (both PhD students at Karolinska Institutet)

Image: 
Stefan Zimmerman

It appears that when our nervous system is developing, only the most viable neurons survive, while immature neurons are weeded out and die. This is shown in a ground-breaking discovery by researchers at Karolinska Institutet in Sweden. The results indicate that the long-standing neurotrophic theory, which states that chance determines which cells will form the nervous system, needs to be revised.

During the early stages of the development of the nervous system, an excess of neurons is generated. At a certain time, a large portion of these cells then die, which is a necessary step for the proper formation of the nervous system. The process takes about 24 hours and in certain parts of the nervous system roughly half of all neurons disappear.

Researchers have previously believed this has been a random process, in which all cells have had an equal chance of survival. However, researchers from Karolinska Institute have now publishing a study in Nature Communications which shows that cell death instead appears to be controlled by a mechanism that weeds out the less fitted cells.

"The cells that survive are more mature and inclined to form synapses with other nerve cells", says Saida Hadjab, who has coordinated the study together with Francois Lallemend. They are both researchers at the Department of Neuroscience at Karolinska Institutet.

Several years ago, Hadjab and Lallemend noted that the early neurons are different. On the surface of them are receivers of growth factors that stimulate their survival. Hadjab and Lallemend discovered that certain neurons had more of these receivers than others. They started to suspect that cell death is somehow controlled, so that only certain selected cells survived.

They have now conducted with their team a detailed study of individual neurons in the early nervous system in mice and have among other things discovered which genes are active. Their mapping has revealed two distinct molecular patterns that determine the fate of these cells. The cells that are the most capable of growing and forming connections to other neurons survive, while the more immature cells die.

The study has been performed in the peripheral sensory nervous system. Whether cell death is controlled in the same way in other parts of the nervous system remains to be discovered.

"This discovery can help us understand the brain and the development of the nervous system on a different level. Earlier studies have mainly studied the environment surrounding the cell, and neuronal population as homogenous cell type. One has not examined the actual neurons individually, their fitness and how different they are", says Francois Lallemend.

This discovery could potentially be significant to the treatment of different neurological diseases. For example, in the case of Parkinson's Disease, doctors have tried to transplant healthy stem cells in patients, but the majority of cells die shortly after the treatment. It is possible that the treatment could become more successful if the less fitted cells were weeded out before the transplant, so that the patient was only given viable neurons.

Credit: 
Karolinska Institutet

Heart attack patients take longer to call emergency when symptoms are gradual

Sophia Antipolis, 12 September 2019: Heart attack symptoms can be gradual or abrupt and both situations are a medical emergency. That's the main message of research published today in the European Journal of Cardiovascular Nursing, a journal of the European Society of Cardiology (ESC).1

The study found that patients with gradual symptom onset took eight hours to get medical help compared to 2.6 hours for those with abrupt symptoms. A maximum delay of two hours is recommended to get fast treatment and the best outcomes; serious complications and death are more likely beyond this window.2-4

Gradual symptoms begin with mild discomfort that slowly gets worse, while abrupt onset refers to sudden and severe pain from the start. "Both are a medical emergency and require urgent help," said study author Dr Sahereh Mirzaei of the University of Illinois at Chicago, US. "But our study shows that gradual symptoms are not taken seriously."

This was a secondary analysis of a prospective, multicentre study conducted in four US regions. The analysis included 474 patients presenting to the emergency department with acute coronary syndrome (myocardial infarction and unstable angina). Symptom characteristics and time from symptom onset to arrival in the emergency department were assessed using the ACS Patient Information Questionnaire.

Overall, the median gap between symptoms and arrival at the hospital was four hours. Symptoms came on abruptly in 56% of patients and emerged gradually in 44%. Both women and men sought medical help more quickly when they experienced abrupt pain.

"Nearly half of patients had a slow onset, so this is not uncommon," said Dr Mirzaei. "The symptoms of acute coronary syndrome are non-specific, and interpretation is often challenging for patients. Chest pain, chest discomfort, and chest pressure are warning signs that an artery may be blocked, and patients should call the emergency medical services immediately."

Symptoms were triggered by exertion in more than half (54%) of men with abrupt onset and a diagnosis of ST-elevation myocardial infarction (STEMI). This is a particularly serious type of heart attack requiring rapid restoration of blood flow to blocked arteries. Risky activities included climbing stairs, pulling, pushing, shovelling, heavy gardening, running, and jogging.

"Men with ischaemic heart disease or with multiple risk factors such as hypertension, diabetes, high cholesterol, or family history of heart disease should be aware that chest pain or discomfort after physical effort could be a heart attack," said Dr Mirzaei.

Arrival by ambulance was associated with a shorter interval between the start of pain and hospital arrival. Just 45% of patients called an ambulance, while more than half (52%) used their own transport and 3% were transferred from another hospital. Being uninsured was linked with a longer delay.

Dr Mirzaei said: "Chest pain or discomfort, whether severe and sudden or mild and slow, should not be ignored. Symptoms can also include pain in the throat, neck, back, stomach or shoulders, and may be accompanied by nausea, cold sweat, weakness, shortness of breath, or fear. Call an ambulance straight away; the sooner you get help, the better your prognosis."

Credit: 
European Society of Cardiology

Two studies show promise, safety of proton therapy in the brain in children with cancer

image: A proton treatment room in the Roberts Proton Therapy CEnter

Image: 
Penn Medicine

PHILADELPHIA - From improving outcomes in children with brain cancer to lowering the risk of damage to the brainstem in children with central nervous system tumors, a pair of new studies published today add to the growing body of research showing the potential benefits of proton therapy. The first study, published in Pediatric Blood and Cancer, found that very young children who received proton therapy for medulloblastoma had higher rates of overall survival and recurrence free survival compared to patients who received intense chemotherapy without radiotherapy. The second study, published in Acta Oncologica, showed children with central nervous system tumors who received proton therapy with a newer technique called pencil beam scanning experienced a significantly lower rate of brainstem damage than patients treated with older proton techniques. Both studies were led by Christine Hill-Kayser, MD, an associate professor of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania, a member of Penn's Abramson Cancer Center, and a pediatric oncologist in the Cancer Center at Children's Hospital of Philadelphia (CHOP).

Proton therapy has key differences from traditional photon radiation. Photon radiation typically uses multiple x-ray beams to attack a tumor target but unavoidably deposits radiation in the normal tissues beyond the target, potentially damaging those tissues as the beam exits the body. Proton therapy is an FDA-approved treatment that directs positively charged protons at the tumor, where they deposit the bulk of the radiation dose, with minimal residual radiation delivered beyond the target, potentially reducing side effects and damage to surrounding tissue.

The first study focused on children with newly diagnosed medulloblastoma - a cancer at the base of the skull. Older children - between the ages of four and 18 - with the disease generally receive radiation to the entire brain and spine; however, this treatment can be very toxic to the developing brains of very young children - ages four and younger. The youngest children with this disease thus typically receive intense chemotherapy regimens rather than radiation, but they can often relapse, and previous studies have shown the highest risk of relapse is tied to an area called the posterior fossa - the part of the base of the skull where the tumor is primarily located.

Researchers evaluated 14 young children who received proton therapy following surgery and chemotherapy. They found the five-year rate of overall survival was 84 percent, while the rate of recurrence-free survival was 70 percent. Historical data shows both rates are usually only between 30 and 60 percent in very young patients who do not receive radiotherapy.

"Our study, while small, shows promising outcomes when we use proton therapy to target just the area of surgery in these cases as opposed to radiating the whole brain and spinal areas," said the study's lead author Amardeep Grewal, MD, chief resident in Radiation Oncology at Penn.

The authors say further research is needed given the small cohort.

The second study deals with a new proton technique called pencil beam scanning (PBS), which is more effective at sparing healthy tissue than older proton techniques such as double scattered or uniform scanning. This study evaluated 166 patients with pediatric central nervous system tumors and found that at 24 months, the rate of patients experiencing brainstem tissue damage from PBS proton therapy is 0.7 percent. This is much lower than rates of serious brainstem toxicity historically reported in the literature after treatment with double scattered proton therapy.

"The effect of proton therapy on the brainstem has been a subject of much debate, but our data show that pencil beam scanning proton therapy does not increase the risk compared to conventional photon techniques," said the study's lead author Jennifer Hyatt Vogel, MD, who completed this work while she was a resident at Penn.

The authors say these data warrant further study, especially in high-risk patients and patients who have had prior radiation therapy.

"Regardless of technique, expertise in proton therapy planning and strict adherence to safety constraints is essential, particularly in treatment of tumors near the brainstem," Hill-Kayser said.

Credit: 
University of Pennsylvania School of Medicine

How relapse happens: Opiates reduce the brain's ability to form, maintain synapses

BUFFALO, N.Y. -- Exposure to heroin sharply reduces levels of the protein necessary for developing and maintaining the brain's synapses, a preclinical study by University at Buffalo researchers has found. The development of addiction relapse is directly related to the impact that reductions in this protein, called drebrin, have on specific cells involved in the brain's pleasure-seeking/reward pathways.

The UB research paper, one of the first to trace the pathophysiology of addiction relapse, was published online on Sept. 12 in Nature Communications.

The neurobiology of relapse

"Very few research studies have examined the molecular mechanisms of heroin relapse and there is almost nothing published about the specific cell types that these changes occur in," said David Dietz, PhD, senior author on the paper, chair of the Department of Pharmacology and Toxicology in the Jacobs School of Medicine and Biomedical Sciences at UB and a faculty member in UB's neuroscience program.

"These findings lead us to a better understanding of the neurobiology of relapse to opiates. In combination with other findings, the research will hopefully provide avenues toward treatments that can prevent relapse behaviors."

Most currently available treatments are replacement therapies, none of which address the fundamental changes that occur in addiction and lead to relapse, which remains an intractable issue.

Dietz and his colleagues have focused much of their research on relapse after opiate addiction and withdrawal and the structural plasticity in the brain that they cause. He was recently awarded more than $2 million from the National Institutes of Health (NIH) to continue research on drebrin and other potential targets for treating drug addiction.

Drebrin was of interest because loss of the protein has been previously implicated in brain diseases, such as Alzheimer's disease and Down syndrome.

"Since drebrin is responsible for developing and maintaining synapses, we wondered if it was also involved in addiction to drugs of abuse, ultimately leading to relapse," said Dietz.

In experiments with rodents, the UB team determined that exposure to heroin and morphine reduced drebrin levels in the nucleus accumbens, a key part of the brain's reward pathway.

Synaptic rewiring

The researchers found that opiate exposure causes synaptic rewiring in this part of the brain, as well as a decrease in drenditic spines, the protrusions on neurons that play key roles in neuronal transmission, learning and memory.

"Opiates fundamentally change how the brain communicates with itself," Dietz said.

The researchers found that the reduction in drebrin levels is regulated by changes in how an enzyme called HDAC2 facilitates access to the DNA. In addition, the study demonstrates that these changes occur exclusively in a specific type of cell within the nucleus accumbens, known as D1, which contains medium spiny neurons, the type of cells that make up this part of the reward center.

"Restoring drebrin back to normal levels in these specific brain cells was sufficient to reduce relapse behaviors," said Dietz.

The research provides a critical and understudied insight into the mechanisms behind addiction and relapse behaviors, which in combination with future studies may lead to a novel and effective treatment to prevent relapse.

"Our lab is focused on improving our understanding of the neurobiology of addiction and relapse so that we can figure out the best way to target these pathways for future therapeutic use," Dietz said.

Credit: 
University at Buffalo

Only a fraction of the costs of excessive drinking are paid for by alcohol taxes

PISCATAWAY, NJ - The total harm caused by excessive alcohol consumption is a staggering $2.05 per drink in the United States, and, of this, the government ends up paying about 80 cents per drink. However, the federal government and states only bring in about 21 cents per drink on average in alcohol taxes, according to new research in the Journal of Studies on Alcohol and Drugs. This leaves the majority of the cost of alcohol's harms borne by those who don't drink excessively or who don't drink at all.

"The disparity between alcohol-related cost to government and alcohol taxes amounts to a large taxpayer-funded subsidy of excessive drinking and alcohol companies," says senior author Timothy S. Naimi, M.D., M.P.H., of the Boston Medical Center and the Boston University School of Public Health.

Research shows that higher prices on alcohol, often through increased taxes, can lead to less excessive consumption, which in turn reduces a range of alcohol-related harms such as violence, motor vehicle injuries and liver cirrhosis.

"Increasing alcohol taxes could improve public health and reduce the disparity between alcohol-related costs and alcohol taxes in states," says Naimi.

"Policy debates around alcohol taxes have mostly centered on public health benefits, but I think our study might change the focus of the debate somewhat, since it seems fair that those who drink the most and who produce and sell alcohol should cover the costs to society," says study lead author Jason G. Blanchette, J.D., M.P.H., of the Boston University School of Public Health.

To calculate the total amount of federal and state tax per standard drink in each state, Naimi and colleagues analyzed state and federal tax data from 2010. Although the federal government charges a standard excise tax that applies in all states (the equivalent of 5, 4 and 16 cents per drink for beer, wine and distilled spirits, respectively), states can charge up to three additional taxes: specific excise taxes, ad valorem excise taxes, and state general sales taxes.

States may assess any combination of these taxes. In fact, Naimi and colleagues report that four states (Alaska, Delaware, Montana and Oregon) charged only specific excise tax, and no other kind of state tax, on alcohol. Other states and Washington, D.C., applied some combination of specific excise taxes on alcohol plus sales tax and/or ad valorem excise tax.

State and federal specific excise taxes are based on the volume of alcohol sold, not the price, and therefore can erode over time because of inflation. During the past 25 years, state excise taxes have declined by more than 30% on average in inflation-adjusted terms, and federal excise taxes have declined by almost 50% because they were last adjusted for inflation in 1991. Ad valorem excise taxes and state general sales taxes are based on a percentage of the retail price and, therefore, increase in tandem with the purchase price. However, although all states charge specific excise taxes, only a minority of states have ad valorem taxes and not all states apply sales taxes to alcohol.

Accordingly, the study found that specific excise taxes accounted for only one fifth of current tax revenue from alcohol. "All states have specific excise taxes because that was the standard when alcohol prohibition was lifted, but they haven't kept pace with inflation so now they're not worth much now," says Blanchette.

On average, state alcohol taxes brought in an average of 13 cents per drink, the researchers found. Delaware brought in the least (3 cents) and Tennessee brought in the most (27 cents) per drink. Once Naimi and colleagues added in the average amount of federal taxes per drink, the total average tax amounted to 21 cents per drink.

However, this is only a fraction of alcohol-related costs from excessive drinking. "Total alcohol taxes accounted for a median of 26.7% of the economic cost to the government," the authors write, "and 10.3% of the total economic cost of excessive drinking." Total alcohol taxes per drink were compared with cost per drink based on a Centers for Disease Control and Prevention study that included medical costs, costs to the legal and criminal justice systems and lost productivity but did not include "intangible" costs such as pain and suffering.

Says Naimi, "the bottom line is that current alcohol taxes, even considering all types of tax including general sales taxes, don't come close to covering alcohol-related costs."

Credit: 
Journal of Studies on Alcohol and Drugs

Teens with opioid use disorder may benefit from medication treatment

PISCATAWAY, NJ - Although the effectiveness of medications to treat adults with opioid use disorder has been well established, there has been little research about how -- or even if -- such treatment works in adolescents.

Now, a new review of the literature suggests that, in addition to adults, adolescents with severe opioid use disorder can be treated with one of three medications: methadone, buprenorphine (Subutex/Suboxone) or extended-release naltrexone (Vivitrol). The study was published in the latest issue of the Journal of Studies on Alcohol and Drugs.

"In 2017, 900 adolescents started misusing opioid pain relievers each day," the authors write. In addition to abusing prescription medication, some of these teens "initiate heroin use because of its ready availability, lower cost, and strong potency."

"Adolescents with severe opioid use disorder may benefit from a medication as part of a larger comprehensive treatment plan," says lead author Deepa R. Camenga, M.D., M.H.S., of the Yale School of Medicine. Further, "parents should try to consult with an addiction psychiatry or medicine specialist to see if there are additional treatments that may benefit their child."

In their research, Camenga and colleagues searched the scientific literature for investigations of the effects of medication in the treatment of opioid use disorder in adolescents. They identified 14 reports, published between 1973 and 2018. The number of adolescents in each study ranged from just a handful to several hundred.

Overall, the researchers report that the dangers of untreated opioid use disorder "far outweigh the risks" of treatment with methadone, buprenorphine, or naltrexone. However, few adolescents receive such therapy: Only about 2 to 5 percent of adolescents with an opioid use disorder receive treatment with one of these medications, compared with 12 to 26 percent of adults.

In general, methadone, buprenorphine and extended-release naltrexone improved the number of adolescents who remained in treatment, decreased opioid use, and led to more abstinence. But, the authors say, "research is still needed to understand the optimal treatment duration and how to retain adolescents in treatment."

The medications do have their challenges. For methadone, the authors say, the use of these medications needs to be closely monitored due to known side effects with high doses, including slow breathing and sedation, as well as heart rhythm problems. Further, methadone needs to be administered by a federally certified opioid treatment program, which can cause difficulty for adolescents who don't have transportation to such locations. Also, adolescents must receive special dispensation to receive it, and there is the risk that methadone itself can be abused.

Unlike methadone, buprenorphine can be administered on an outpatient basis. However, teens may need the oversight of an adult to help ensure the medication is taken properly and not misused.

For naltrexone, one challenge to treatment is that patients have to go through detoxification before starting treatment. Also, naltrexone may increase the risk of opioid overdose if a patient begins using opioids again once the medication wears off. Nonetheless, extended-release naltrexone is given by injection once a month and doesn't require the frequent visits of methadone or the oversight of buprenorphine.

However, there is a very limited number of health care professionals who treat teens with opioid use disorder. "There is a great need to improve adolescents' access to medications for the treatment of OUD and to increase workforce capacity to care for these adolescents," the authors conclude.

In a commentary that accompanies the review, a group of researchers led by Rachel Gonzales-Castaneda, Ph.D., M.P.H., of UCLA, writes that, because relapse occurs in more than half of the adolescents treated for opioid use disorder with standard approaches, alternatives such a treatment with medication may need to be considered. However, they add that researchers lack information on how medical treatment may interact with other mental or physical disorders, or their treatments, and that much more research is needed that addresses the needs of the adolescent population with opioid disorder.

In a second commentary, Noel Vest, Ph.D., of the Stanford University School of Medicine, and Keith N. Humphreys, Ph.D., of the Veterans Affairs Palo Alto Health Care System in California, sound a cautious tone about the use of medication to treat opioid use disorder in adolescents.

Specifically, they write that teens treated with methadone "may end up taking the medication for half a century or more" and that the risks of such lengthy treatment are unknown. Further, they suggest that the treatment retention noted in the review does not necessarily equate to patients refraining from drugs or alcohol.

Last, diagnosing an adolescent poses complications. "[I]t can be challenging to determine whether 16-year-olds are truly dependent on Vicodin if they have been frequenting parties in which they are among many teenagers who consume the drug," Vest and Humphreys write.

Credit: 
Journal of Studies on Alcohol and Drugs

Opioid treatment for teens? Medications can help

New Haven, Conn. -- Teens who misuse prescription or illicit opioids might benefit from opioid treatment medications, according to a new study led by a Yale researcher.

An estimated 900 adolescents started to misuse opioid painkillers every day in 2017, and some of them turned to cheaper and more potent illegal opioids like heroin. Yet little is known about the effectiveness of opioid medications -- the recommended treatment for adults with opioid use disorder -- in teens who are younger than 18.

The research team, led by assistant professor of emergency medicine at Yale School of Medicine Deepa Camenga, M.D., searched the scientific literature for studies examining the effect of opioid treatment medications on teens. Their review suggested that teens with severe opioid use disorder can be treated with the medications.

While there were only 14 reports identified between 1973 and 2018, they all favored treatment with one of the three medications for opioid use disorder: methadone, buprenorphine, or naltrexone.

The studies revealed that these medications increased the number of teens who remained in treatment, decreased their use of opioids, and increased abstinence, the researchers said.

"Adolescents with severe opioid use disorder may benefit from a medication as part of a larger comprehensive treatment plan," said Camenga. Only 2%-5% of teens with an opioid use disorder receive medication treatment.

The dangers of leaving opioid addiction untreated far outweigh the risks of the medications, they noted. More research is needed to determine how long teen patients should receive medication treatment, and how to keep them in treatment, the researchers said.

"Parents should try to consult with a healthcare provider, and if they are able, an addiction psychiatry or addiction medicine specialist, to see if medications may benefit their child," Camenga said. The authors emphasized the need to improve teens' access to treatment and the capacity of providers to care for this population.

Credit: 
Yale University

Cell-mostly internet users place privacy burden on themselves

A new report from the Media, Inequality and Change (MIC) Center -- a joint project of the Annenberg School for Communication at the University of Pennsylvania and the School of Communication and Information at Rutgers University -- details the kinds of online privacy tradeoffs that disproportionately impact cell-mostly internet users, who are likely to be Black, Hispanic, and/or low-income.

Researchers Jan Fernback and Gwen Shaffer facilitated focus group discussions with 79 people in Philadelphia and Long Beach, California all of whom rely on their phones to go online. Through participant observation, the researchers also gained insight into the most popular apps for cell-mostly internet users and how much time they spend engaging with them.

Tanya, a 30-something African American woman who lives in Philadelphia, refuses to fill out online applications for jobs or credit cards. She doesn't own a computer and exclusively uses her phone to go online.

Shelly, a formerly homeless woman in her 50s who lives in Philadelphia and doesn't use a computer, is afraid to make purchases on her cell phone, in fear of having her information stolen.

Karla, another Philadelphia woman in her 50s who lives in transitional housing, worries about data collection by social media platforms. However, without a car or cash, posting to Facebook is a necessity to remain in touch with her family.

Jazmin, a Hispanic woman who lives in Long Beach, voiced similar concerns about social media platforms. In fact, she deleted Facebook from her phone after hearing about the company's repeated privacy violations, but ultimately installed it again.

The sentiments expressed by these cell-mostly internet users are not unique. Nearly all study participants shared stories of relinquishing their data privacy, which the researchers consider to be a basic human right, in exchange for the ability to access online services and platforms. Many people shared anecdotes about forgoing opportunities in an attempt to maintain data privacy.

However, participants lacked a clear understanding of how near-constant mobile internet use, including dependence on internet-connected apps, potentially compounds other inequalities that exist in their lives. Rather, study participants generally seemed resigned to their status as having little power and minimal social capital.

"Our findings shed light on the added dangers to information privacy that lower-income, cell-mostly internet users face, and how those dangers shape their online behaviors," Fernback said.

All individuals are vulnerable to security breaches, identity fraud, system errors, and hacking. But economically disadvantaged individuals who rely exclusively on their mobile phones to access the internet are disproportionately exploited through leakier phone models, lack of knowledge about phone security practices, and attitudes of resignation with regard to their agency over their own data. Such users are also more open to governmental surveillance if they participate in programs for low-income individuals and families or live in subsidized housing.

"The smartphone-dependent people we interviewed typically did not own a computer, and many lacked stable housing and relied on public services," said Shaffer. "Unfortunately, members of disadvantaged populations are frequent targets of data profiling by retailers hoping to sell them cheap merchandise or bait them into taking out subprime loans. They may be charged higher insurance premiums or find their job applications rejected. Ultimately, the inequities they experience off-line are compounded by online privacy challenges."

The researchers argue that privacy is a public good and a fundamental value in a democratic society. In fact, it is a requirement of basic human dignity. Because of the sheer ubiquity of digitized data compiled on individuals who rely on cell phones to access the internet, the need for privacy should be elevated from a personal liberty and legal right to a matter of social justice. Data privacy is not a luxury for those who cannot afford to invest the time, resources, and effort required to actively protect one's digital assets.

This study underscores the need for U.S. citizens, lawmakers, and activists to further consider the grassroots impact of data privacy and security and includes sets of recommendations at the policy, individual, and consumer advocacy levels. Understanding the symbiotic relationship between the material nature of mobile technology and the social construction of technology is a key means to safeguarding privacy in our increasingly digital lives.

The report is entitled "Cell Phones, Security and Social Capital: Examining How Perceptions of Data Privacy Violations among Cell-Mostly Internet Users Impact Attitudes and Behavior" and is available here.

Credit: 
University of Pennsylvania

Predictable eSports: Amateurs and professionals sit differently on a chair

image: The experiment involved a total of 19 players, including 9 professionals and 10 amateurs, who were asked to play Counter-Strike: Global Offensive (CS: GO) for 30 to 60 minutes.

Image: 
Skoltech

A group of scientists from Skoltech's Computational and Data-Intensive Science and Engineering Center (CDISE) won the Best Paper Award at the prestigious 5th IEEE Internet of People conference (IoP 2019) for their research in artificial intelligence which helped them find a connection between an eSports player's movements and skill level. Their research findings show that machine learning methods help accurately predict a player's skill level in 77% of cases.

In just a few years, eSports that has its roots in video games for schoolkids has evolved into a full-fledged industry with professional teams, coaches, and huge investments. Like in any other sport, an eSports player can be a professional or an amateur, and telling one from another is essential for optimizing the training process.

Master's students from the Skolkovo Institute of Science and Technology (Skoltech), Moscow, Moscow Institute of Physics and Technology (MIPT) and the State University of Aerospace Instrumentation (SUAI), St. Petersburg, led by Skoltech professors, Andrey Somov and Evgeny Burnaev, looked for a connection between the proficiency and body movements of an eSports player seated on a chair.

"We assumed that there could be a link between a player's body movements and skill level. Also, it was interesting to look at the players' response to various game events, such as kills, deaths or shootings. We suspected that professional players and beginners would react differently to the same event," explains the first author of the study and Skoltech master student, Anton Smerdov.

The experiment involved a total of 19 players, including 9 professionals and 10 amateurs, who were asked to play Counter-Strike: Global Offensive (CS: GO) for 30 to 60 minutes. Their skills were evaluated in game hours, similarly to pilots, whose skills are assessed in flight hours. The data were collected using an accelerometer and a gyroscope embedded in the chair.

"We then cut the data into 3-minute sessions, assuming that 3 minutes were enough to understand the player's behavior and obtain a sample big enough for algorithm learning," Smerdov added.

The patterns extracted from each session were used to evaluate the players' behavior and check how intensively and how often they moved or turned around along each of the three axes and leaned back in the chair. A total of 31 patterns were obtained for each player, and 8 most important features were defined using statistical techniques. Machine learning methods were then applied to the key features. The popular Random Forest method displayed the best performance, correctly determining the player's skill level from a 3-minute session in 77% of cases. Also, the results showed that professional players move around more often and more intensively than beginners, while sitting perfectly still during shootings and other game events.

Launched within the Skoltech Introduction to Internet of Things course and Skoltech Cyber Academy initiative, this research project is being further developed at the Head Kraken eSports start-up, benefiting from the grants provided by Skoltech's STRIP program and the Russian Foundation for Basic Research (RFBR).

The team led by professors Andrey Somov and Evgeny Burnaev has been studying eSports players' psycho-emotional state and physical reactions to the game using sensors and machine learning methods since 2018. The data collected and analyzed include pulse, skin resistance, gaze direction, hand movements, environmental data (temperature, humidity, CO2 level), game telemetry, and other parameters.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Gene therapy helps functional recovery after stroke

image: This is an image of neurons (red) that were converted from glial cells using a new NeuroD1-based gene therapy in a stroke-injured mouse brain.

Image: 
Chen Laboratory, Penn State

A new gene therapy turns glial cells--abundant support cells in the brain--into neurons, repairing damage that results from stroke and significantly improving motor function in mice. A paper describing the new therapy, which uses the NeuroD1 gene, appears online in the journal Molecular Therapy. Once further developed, this NeuroD1-based gene therapy could potentially be used to treat stroke, which is a leading cause of disability in the U.S., with 800,000 new stroke patients every year.

"The current treatment for stroke has a narrow time window, typically within a few hours after the occurrence of stroke," said lead author Yuchen Chen, a postdoctoral fellow at Penn State. "Many patients cannot receive the treatment in time and as a result, often suffer from permanent disability caused by irreversible neuronal loss. There is an urgent need to develop a new therapy to regenerate new neurons and restore lost brain functions among stroke patients."

The human brain has approximately 86 billion neurons. While mini-strokes can be tolerated, moderate stroke involving the loss of billions of neurons leaves detrimental effects that do not spontaneously recover.

"So, the critical question that is still unanswered in the neuroregeneration field is how can we regenerate billions of new neurons in a patient's brain after stroke?" said Gong Chen, professor of biology and Verne M. Willaman Chair in Life Sciences at Penn State and leader of the research team. "The biggest obstacle for brain repair is that neurons cannot regenerate themselves. Many clinical trials for stroke have failed over the past several decades, largely because none of them can regenerate enough new neurons to replenish the lost neurons."

Gong Chen and his team pioneered a new approach to regenerate functional neurons using glial cells, a group of cells surrounding every single neuron in the brain that provide essential support to neurons. Unlike neurons, glial cells can divide and regenerate themselves, especially after brain injury.

"I believe that turning glial cells that are already present in the brain into new neurons is the best way to replenish the lost neurons," said Gong Chen. "These glial cells are the neighbors of the dead neurons in the brain and are likely to share the same ancestral cellular lineage."

Gong Chen's team previously reported that a single genetic neural factor, NeuroD1, could directly convert glial cells into functional neurons inside mouse brains with Alzheimer's disease, but the total number of neurons generated was limited. The research team believed that this limited regeneration was due to the retroviral system used to deliver NeuroD1 to the brain. In the current study, the research team used the AAV viral system, which is now the first choice for gene therapy in the nervous system, to deliver NeuroD1 into mouse motor cortex that had suffered from stroke.

Many neurons die after stroke but surviving glial cells can proliferate and form a glial scar in the stroke areas. The AAV system was designed to express NeuroD1 preferentially in the glial cells that form these scars, turning them directly into neuronal cells. Such direct glia-to-neuron conversion technology not only increased neuronal density in the stroke areas, but also significantly reduced brain tissue loss caused by the stroke.

Interestingly, the newly converted neurons showed similar neuronal properties to the neurons that were lost after stroke. This suggests a potential impact of the local glial lineage on the converted neuronal identity.

"The most exciting finding of this study is to see the newly converted neurons being fully functional in firing repetitive action potentials and forming synaptic networks with other preexisting neurons," said Gong Chen. "They also send out long-range axonal projections to the right targets and facilitate motor functional recovery."

A separate collaborative work led by Gregory Quirk, professor at the University of Puerto Rico, further tested the NeuroD1-based gene therapy in a rat stroke model. Quirk and colleagues also found that this direct glia-to-neuron conversion technology can rescue cognitive functional deficits induced by stroke.

"Because glial cells are everywhere in the brain and can divide to regenerate themselves, our study provides the proof-of-concept that glial cells in the brain can be tapped as a fountain of youth to regenerate functional new neurons for brain repair not only for stroke but also for many other neurological disorders that result in neuronal loss," said Yuchen Chen. "Our next step is to further test this technology and ultimately to translate it into clinically effective therapies to benefit millions of patients worldwide."

Credit: 
Penn State

It takes a 'consortium': Researchers develop metabolic engineering technique

For years, scientists have explored ways to alter the cells of microorganisms in efforts to improve how a wide range of products are made - including medicines, fuels, and even beer. By tapping into the world of metabolic engineering, researchers have also developed techniques to create "smart" bacteria capable of carrying out a multitude of functions that impact processes involved in drug delivery, digestion, and even water decontamination.

But, altering the genetic and regulatory processes that take place within cells presents challenges.

To start, cells are already programmed to carry out their normal, everyday processes with maximum efficiency; any alterations that engineers make to increase a cell's production of a certain substance can, in turn, upset these processes and overburden the cell.

To address this problem, William E. Bentley, a University of Maryland bioengineering professor and director of the university's Robert E. Fischell Institute for Biomedical Devices, is working with a team of researchers to focus on engineering microbial consortia, wherein cell subpopulations are engineered to work together to carry out a desired function. This strategy - which others in the field have also explored - allows engineers to design specialized cells and divvy up the target workload among a group of cells. The tradeoff is that driving a consortium to carry out a specific set of tasks requires engineers to somehow regulate how many of each cell subpopulation are present.

Despite this challenge, few scientific studies have focused on the development of devices or systems that could regulate the compositions of cellular subpopulations within a consortium. Most often, such studies require engineers to rely on manual or user-controlled techniques to strike a balance among cell subpopulations.

As such, Bentley and his team realized that a more powerful approach would be to reengineer the cells themselves to coordinate their subpopulation densities autonomously. Their technique was highlighted in a Nature Communications paper published today.

Like others in the field, Bentley and members of his Biomolecular and Metabolic Engineering Lab previously investigated quorum sensing (QS) - a bacterial form of cell-to-cell communication - to engineer communication circuits amongst and between bacterial strains in order to coordinate their behaviors. QS involves the synthesis of small signaling molecules, called autoinducers (AI), which are secreted by individual bacteria but serve to coordinate their responses. Once the AI level reaches a threshold - signaling a "quorum" of cells - the AI signals are transported intracellularly, where they activate gene expression and enable coordinated responses.

But, Bentley and his team took the research a step further. The group developed the first known platform for autonomous and targeted regulation of consortia composition based on the presence of an environmental cue known as autoinducer-2 (AI-2). AI-2 is considered a universal QS signal, which means it is both recognized and produced by many species of bacteria. It broadly indicates cell population density, and is considered to be an important signal in naturally occurring consortia and microbiomes.

To create an autonomous system, Bentley and his team rewired the bacterial QS systems at play in two strains of E. coli so that the growth rate of communicating cell subpopulations within the consortia would be dictated by signaling between the cells. Their system works like a feedback loop. The first strain senses AI-2 and, in response, yields an output of autoinducer-1 (AI-1). The second E. coli strain, considered the"controller" strain, is engineered to carry out a signal-driven, tunable growth rate of the consortia cells, regulated by none other than the AI-1 produced by the first strain. In this way, the team's system employs its own process of checks and balances between AI-1 and AI-2 that, in turn, regulates the makeup of synthetic consortia.

"Increasingly, consortia of microbes will be tasked with converting raw materials into valuable products," Bentley said. "The raw materials may be wastes or byproducts of industrial processes. The synthetic capabilities of consortia may far surpass those of pure monocultures, so methodologies that help to align consortia will be needed. This could prove especially valuable in situations where processing equipment isn't available, such as in the gastrointestinal (GI) tract."

Credit: 
University of Maryland

Half-a-billion-year-old tiny predator unveils the rise of scorpions and spiders

image: Reconstruction of Mollisonia plenovenatrix, by Joanna Liang. Mollisonia was only about 2.5 cm long.

Image: 
Illustration by Joanna Liang © Royal Ontario Museum

Two palaeontologists working on the world-renowned Burgess Shale have revealed a new species, called Mollisonia plenovenatrix, which is presented as the oldest chelicerate. This discovery places the origin of this vast group of animals--of over 115,000 species, including horseshoe crabs, scorpions and spiders--to a time more than 500 million years ago. The findings are published in the prestigious journal Nature on September 11, 2019.

Mollisonia plenovenatrix would have been a fierce predator--for its size. As big as a thumb, the creature boasted a pair of large egg-shaped eyes and a "multi-tool head" with long walking legs, as well as numerous pairs of limbs that could all-together sense, grasp, crush and chew. But, most importantly, the new species also had a pair of tiny "pincers" in front of its mouth, called chelicerae. These typical appendages give the name to the group of scorpions and spiders, the chelicerates, which use them to kill, hold, and sometimes cut, their prey.

"Before this discovery, we couldn't pinpoint the chelicerae in other Cambrian fossils, although some of them clearly have chelicerate-like characteristics," says lead author Cédric Aria, a member of the Royal Ontario Museum's Burgess Shale expeditions since 2012, and is presently a post-doctoral fellow at the Nanjing Institute of Geology and Palaeontology (China). "This key feature, this coat of arms of the chelicerates, was still missing."

Other features of this fossil, including back limbs likened to gills, further suggest that Mollisonia was not some "primitive" version of a chelicerate, but that it was in fact already close morphologically to modern species.

"Chelicerates have what we call either book gills or book lungs," explains Aria. "They are respiratory organs are made of many collated thin sheets, like a book. This greatly increases surface area and therefore gas exchange efficiency. Mollisonia had appendages made up with the equivalent of only three of these sheets, which probably evolved from simpler limbs."

The authors believe that Mollisonia preferentially hunted close to the sea floor, thanks to its well-developed walking legs, a type of ecology called benthic predation. Because Mollisonia is so modern-looking, chelicerates seem therefore to have prospered quickly, filling in an ecological niche that was otherwise left poorly attended to by other arthropods at that time. The authors conclude that the origin of the chelicerates must lie even deeper within the Cambrian, when the heart of the "explosion" really took place.

"Evidence is converging towards picturing the Cambrian explosion as even swifter than what we thought," says Aria. "Finding a fossil site like the Burgess Shale at the very beginning of the Cambrian would be like looking into the eye of the cyclone."

The importance of the Burgess Shale and similar deposits, such as the Chengjiang biota in China, lies in their exceptional preservation of the earliest marine animal communities at a time of uniquely rapid diversification of body forms called the "Cambrian explosion." Fossil animals from these sites are notable for preserving an extensive array of morphological features, such as limbs and eyes, but also guts and, much more rarely, nervous system tissues.

Mollisonia was first described more than a century ago by the discoverer of the Burgess Shale, Charles Doolittle Walcott. However, so far, only rare exoskeletons of this animal were known. "It is the first time that evidence of the limbs and other soft-tissues of this type of animal are described, which were key to revealing its affinity," says co-author Jean-Bernard Caron, Richard M. Ivey Curator of Invertebrate Palaeontology at the Royal Ontario Museum (Canada). The exceptionally well-preserved fossils come from a new Burgess Shale sites near Marble Canyon, in Kootenay National Park, British Columbia.

"Marble Canyon is the biggest spotlight of my career so far. This area keeps giving us wonderful treasures year after year," says Caron, who has been leading the Royal Ontario Museum's Burgess Shale expeditions for the past 10 years. "I would not have imagined that we could, in a way, rediscover the Burgess Shale like this, a hundred years later, with all the new species we are finding."

The specimens of Mollisonia plenovenatrix described in this new research are better preserved than the ones found at the original Walcott quarry that is located about 40 kilometers northwest of the Marble Canyon quarry. Many other fossils found at Marble Canyon and surrounding areas have already played a critical role in our understanding of the early evolution of many animal groups. These notably include the vertebrates, our own lineage, thanks to numerous and exceptionally well-preserved specimens of the primitive fish Metaspriggina walcotti. Many new species await to be described; the latest one, a "flying saucer-like" new predatory arthropod with huge rake-like claws called Cambroraster falcatus, was just recently published on July 31, 2019.

The Burgess Shale fossil sites are located within Yoho and Kootenay national parks and are managed by Parks Canada. Parks Canada is proud to work with leading scientific researchers to expand knowledge and understanding of this key period of earth history and to share these sites with the world through award-winning guided hikes. The Burgess Shale was designated a UNESCO World Heritage Site in 1980 due to its outstanding universal value and is now part of the larger Canadian Rocky Mountain Parks World Heritage Site.

Mollisonia will be among the many exceptional fossils from the Burgess Shale planned to be on display in the ROM's future new gallery, The Willner Madge Gallery, Dawn of Life, scheduled to open in 2021.

Credit: 
Royal Ontario Museum

Towering balloon-like features discovered near centre of the Milky Way

Published in Nature today, scientists have shown how this hourglass-like feature, which dwarfs all other radio structures in the Galactic Centre, is likely the result of a phenomenally energetic burst that erupted near the Milky Way's supermassive black hole a few million years ago.

Using the South African Radio Astronomy Observatory (SARAO) MeerKAT telescope, Ian Heywood of the University of Oxford's Department of Physics and his colleagues mapped out broad regions in the centre of the galaxy, conducting observations at wavelengths near 23 centimetres. Radio emission of this kind is generated in a process known as synchrotron radiation, in which free-floating electrons are accelerated as they interact with powerful magnetic fields. This produces a characteristic radio signal that can be used to trace energetic regions in space. The radio light seen by MeerKAT penetrates the dense clouds of dust that block visible light from the centre of the galaxy.

Lead author Dr. Heywood, who processed the large amount of observational data which led to this result, said: 'The centre of our galaxy is relatively calm when compared to other galaxies with very active central black holes. Even so, the Milky Way's central black hole can become uncharacteristically active, flaring up as it periodically devours massive clumps of dust and gas. It's possible that one such feeding frenzy triggered powerful outbursts that inflated this previously unseen feature.'

By examining the nearly identical extent and morphology of the twin bubbles, the scientists believe they have found convincing evidence that these features were formed from a violent eruption that over a short period of time punched through the interstellar medium in opposite directions.

MeerKAT has unprecedented sensitivity and imaging capabilities which, coupled with its geographic vantage point for observing the Galactic centre, has resulted in the clearest ever image of the radio waves emanating from the centre of the Milky Way, a part of the sky that is notoriously difficult to image at such wavelengths.

These new observational capabilities are unlocking a "fossil record" which allows scientists to piece together the history of the Galactic centre and the supermassive black hole that lurks there. Although the structure is likely to be a few million years old it is still possible to observe it, and from there scientists can infer from where it came.

Head of Astrophysics at the University of Oxford, Professor Steve Balbus, said: 'It is extremely exciting to be able to peer at the centre of the Galaxy with such high definition and precision. This is the nearest supermassive black hole to us in the Universe, and MeerKAT has provided us with front row centre seats. We are going to learn an enormous amount about how black holes feed themselves and how they influence their environments. In the relatively brief time that MeerKAT has been up and running, the science that the team at Oxford has already produced has been transformational. Oxford can be rightly proud of their leadership involvement with the MeerKAT Project, and I personally can't wait to see what more there is to come - this is only the beginning of a new era in radio astronomy.'

Co-author, William Cotton, from the National Radio Astronomy Observatory in Charlottesville, Virginia, said: 'The shape and symmetry of what we have observed strongly suggests that a staggeringly powerful event happened a few million years ago very near our galaxy's central black hole. This eruption was possibly triggered by vast amounts of interstellar gas falling in on the black hole, or a massive burst of star formation which sent shockwaves careening through the galactic centre. In effect, this inflated energetic bubbles in the hot, ionized gas near the galactic centre, energizing it and generating radio waves which we could eventually detect here on Earth.'

The event, reported today in Nature, could also be the origin of the population of electrons that are required to power the radio emission from mysterious magnetised filaments. These thread-like structures have been seen nowhere but in the Galactic centre, and there has been no definitive explanation for their origin since they were first discovered 35 years ago. "Almost all of the more than one hundred filaments are confined by the radio bubbles," said co-author Prof. Farhad Yusef-Zadeh of Northwestern University in Evanston, Illinois.

Co-author Fernando Camilo of SARAO in Cape Town, said: 'These enormous bubbles have until now been hidden by the glare of extremely bright radio emission from the centre of the galaxy. Teasing out the bubbles from the background 'noise' was a technical tour de force, only made possible by MeerKAT's unique characteristics and propitious location in the Southern hemisphere. With this unexpected discovery we're witnessing in the Milky Way a novel manifestation of galaxy-scale outflows of matter and energy, ultimately governed by the central black hole.'

Today's result cements the great "discovery machine" potential of the new generation of radio telescopes as we move towards the construction of the Square Kilometre Array.

Credit: 
University of Oxford

What is risk of new long-term opioid use among patients with Hidradenitis suppurtiva?

What The Study Did: Hidradenitis suppurativa is a painful skin condition where lumps form under the skin. This observational study examined the risk of new long-term opioid use among patients with the condition who hadn't previously used opioids.

Authors: Amit Garg, M.D., of the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in New Hyde Park, New York, is the corresponding author.

(doi:10.1001/jamadermatol.2019.2610)

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

Credit: 
JAMA Network

'Flying fish' robot can propel itself out of water and glide through the air

video: Video of the robot in action and how it works

Image: 
Aerial Robotics Lab/Imperial College London

A bio-inspired bot uses water from the environment to create a gas and launch itself from the water's surface.

The robot, which can travel 26 metres through the air after take-off, could be used to collect water samples in hazardous and cluttered environments, such as during flooding or when monitoring ocean pollution.

Robots that can transition from water to air are desirable in these situations, but the launch requires a lot of power, which has been difficult to achieve in small robots.

Now, researchers at Imperial College London have invented a system that requires just 0.2 grams of calcium carbide powder in a combustion chamber. The only moving part is a small pump that brings in water from the environment the robot is sat in, such as a lake or ocean.

The water and the calcium-carbide powder then combine in a reaction chamber, producing a burnable acetylene gas. As the gas ignites and expands, it pushes the water out as a jet, which propels the robot clear of the water and into a glide of up to 26 metres.

The details of the robot are published today in Science Robotics.

Lead researcher Dr Mirko Kovac, Director of the Aerial Robotics Laboratory at Imperial, said: "Water-to-air transition is a power-intensive process, which is difficult to achieve on a small-scale flying vehicle that needs to be lightweight for flight.

"We have used water-reactive chemicals to reduce the materials that the robot needs to carry. Since the chamber fills passively and the environmental water acts as a piston, we can create a full combustion cycle with only one moving part, which is the pump that mixes the water with the fuel."

The team tested the robot in a lab, in a lake, and in a wave tank, showing that it can escape from the water's surface even under relatively rough conditions. While similar robots often require calm conditions to leap from the water, the team's invention generates a force 25 times the robot's weight, giving it a greater chance of overcoming the waves.

The robot, which weighs just 160 grams, can 'jump' multiple times after refilling its water tank. This could allow it to float on water and take samples at multiple points without additional power, saving energy over longer distances compared to an electrically powered robot.

The team are now working with the Swiss Federal Laboratories for Materials Science and Technology (Empa) to build new vehicles using advanced materials and begin field trials of the robot in a range of environments, including monitoring the oceans around coral reefs and offshore energy platforms.

Raphael Zufferey, first author on the paper said: "These kinds of low-power, tether-free robots could be really useful in environments that are normally time- and resource-intensive to monitor, including after disasters such as floods or nuclear accidents."

Credit: 
Imperial College London