The neurons in our brains are connected with each other, forming small functional units called neural circuits. A neuron that is connected to another one via a synapsis can transmit information to the second neuron by sending a signal. This, in turn, might prompt the second neuron to transmit a signal to other neurons in the neural circuit. If that happens, the first neuron is likely an excitatory neuron: one that prompts other neurons to fire. But neurons with the exact opposite task are equally important to the functionality of our brain: inhibitory neurons, which make it less likely that the neurons they are connected to send a signal to others.

The interplay of excitation and inhibition is crucial for normal functionality of neural networks. Its dysregulation has been linked to many neurological and psychiatric disorders, including epilepsy, Alzheimer’s disease, and autism spectrum disorders.

From cell cultures in the lab…

Interestingly, the share of inhibitory neurons among all neurons in various brain structures (like the neocortex or the hippocampus) remains fixed throughout the lifetime of an individual at 15 to 30 percent. “This prompted our curiosity: how important is this particular proportion?,” recalls Anna Levina, a researcher at Tübingen University and the Max Planck Institute for Biological Cybernetics. “Can neural circuits with a different proportion of excitatory and inhibitory neurons still function normally?” Her collaborators from the Weizmann Institute of Science in Rehovot (Israel) designed a novel experiment that would allow to answer these questions. They grew cultures that contained different, even extreme ratios of excitatory and inhibitory neurons.

The scientists then measured the activity of these artificially designed brain tissues. “We were surprised that networks with various ratios of excitatory and inhibitory neurons remained active, even when these ratios were very far from natural conditions,” explains Levina’s PhD student Oleg Vinogradov. “Their activity does not change dramatically, as long as the share of inhibitory neurons stays somewhere in the range of 10 to 90 percent.” It seems that the neural structures have a way of compensating for their unusual composition to remain stable and functional.

…to a theoretical understanding

So naturally the researchers asked next: what mechanism allow the brain tissue to adjust to these different conditions? The researchers theorized that the networks adapt by adjusting the number of connections: If there few inhibitory neurons, they have to take on a bigger role by building more synapses with the other neurons. Conversely, if the share of inhibitory neurons is large, the excitatory neurons have to make up for this by establishing more connections.

The theoretical model of the Tübingen scientists can explain the experimental findings of their colleagues in Rehovot and uncover the mechanisms helping to maintain stable dynamics in the brain. The results provide a clearer picture of how excitation/inhibition balance is preserved and where it fails in living neural networks. In the longer term, they might be useful for the emergent field of precision medicine: induced pluripotent stem cell derived neural cultures could be used to find mechanisms of neuropsychiatric disorders and novel medications.

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With the recent rush of small investors into so-called meme stocks and reemerging interest in cryptocurrencies talk of market instability, rising volatility, and bursting bubbles is surging. However, “traditional economic theories cannot foresee events like the US subprime mortgage collapse of 2007” according to study author Areejit Samal. He and his colleagues from more than ten mathematics, physics, economics, and complex systems focused institutions around the globe have made a great stride in characterizing stock market instability.

Their paper abstracts the complexity of the financial market into a network of stocks and employs geometry-inspired network measures to gauge market fragility and financial dynamics. They analyzed and contrasted the stock market networks for the USA S&P500 and the Japanese Nikkei-225 indices for a 32-year period (1985-2016) and for the first time were able to show that several discrete Ricci curvatures are excellent indicators of market instabilities. The work was recently published in the Royal Society Open Science journal and allows analysts to distinguish between ‘business-as-usual’ periods and times of fragility like bubbles or market crashes.

The network created by connecting stocks with highly correlated prices and trading volumes forms the structural basis of their work. The researchers then employ four discrete curvatures, developed by the director of Max Planck Institute for Mathematics in the Sciences Jürgen Jost and his coworkers, to study the changes in the structure of stock market networks over time. Their comparisons to other market stability metrics have shown that their four notions of curvature serve as generic indicators of market instability.

One curvature candidate, the Forman-Ricci curvature (FRE), has a particularly high correlation with traditional financial indicators and can accurately capture market fear (volatility) and fragility (risk). Their study confirms that in normal trading periods the market is very fragmented, whereas in times of bubbles and impending market crashes correlations between stocks become more uniform and highly interconnected. The FRE is sensitive to both sector-driven and global market fluctuations and whereas common indicators like the returns remain inconspicuous, network curvatures expose these dynamics and reach extreme values during a bubble. Thus, the FRE can capture the interdependencies within and between sectors that facilitate the spreading of perturbations and increase the danger of market crashes.

Max Planck Institute for Mathematics in the Sciences director Jürgen Jost summarizes the struggle of analyzing market fragility: “there are no easy definitions of a market crash or bubble and merely monitoring established market indices or log-returns does not suffice, but our methodology offers a powerful tool for continuously scanning market risk and thus the health of the financial system.” The insights gained by this study can help decision-makers to better understand systemic risk and identify tipping points, which can potentially forecast coming financial crises or possibly even avoid them altogether.

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Healthy forests play a vital role in providing a clean, stable water supply, says eco-hydrologist Dr. Adam Wei.

Acting as natural reservoirs, forests in watersheds release and purify water by slowing erosion and delaying its release into streams. But forests are changing — in part because of human activity — and that’s having an impact on forests’ interaction with hydrological processes.

Dr. Wei, Forest Renewal BC’s chair of watershed research and management, is a professor of earth, environmental and geographic sciences in the Irving K. Barber Faculty of Science, and study co-author.

He says activities like logging, deforestation, creating new forests on previously bare land, agriculture and urbanization are changing the landscape of forests worldwide.

“The notion that humans have left enormous, often negative, footprints on the natural world isn’t new,” he says. “It’s why the term Anthropocene was created, to describe these phenomena. But now we need to acknowledge where we’re at and figure out a way to fix what’s broken.”

While humans bear much of the blame, they aren’t the only culprits.

Natural disturbances like insect infestations and wildfires are also contributing to the swift transformation of forests, leading Dr. Wei to examine current forest-water research and management practices. His goal is to identify the gaps and propose a new approach that reflects numerous variables and their interactions that may be at play at any given watershed.

He points to an example in the study to illustrate the need for a new perspective.

“We were looking at the impacts of deforestation on annual streamflow — and though we were able to draw the conclusion that deforestation increased it, the variations between studies were large, with increases between less than one per cent to nearly 600 per cent,” he explains.

Dr. Wei saw similar variations when he researched the ‘why.’

“We concluded this was due to when water in the soil and on plants evaporates due to a loss of forest cover,” explains Wei. “But the amount lost ranged from less than two per cent to 100 per cent — that’s a huge difference that can be attributed to scale, type and severity of forest disturbance, as well as climate and location of watershed properties. There are so many variables that need to be taken into account, and not doing so can result in contradictory research conclusions.”

To limit disparities, Dr. Wei says future research and watershed management approaches need to be systematic, include key contributing factors and a broad spectrum of response variables related to hydrological services.

He also suggests new tools like machine learning and climatic eco-hydrological modelling should be utilized.

“Implementing a systematic approach to all forest-water research will reduce the likelihood of procuring misleading assessment, which in turn will give us a better chance to solve some of the problems we’ve created,” says Dr. Wei.

This study, published in Science, was conducted by Dr. Wei, and his then-graduate student Dr. Mingfang Zhang, with support from the China National Science Foundation.

The study is part of a larger, ongoing collaboration involving the Centers for Disease Control and Prevention (CDC), Washington University School of Medicine in St. Louis, the Missouri Department of Health and Senior Services, the Missouri Department of Elementary and Secondary Education, Saint Louis University, the Springfield-Greene and St. Louis County health departments, and school districts in the St. Louis and Springfield, Mo., areas.

The findings are published March 19 in the CDC’s journal, Morbidity and Mortality Weekly Report. The Missouri school findings mirror those of schools in other states, demonstrating that COVID-19 prevention efforts can significantly curb the spread of SARS-CoV-2 among students, teachers and staff.

“This work is imperative because keeping kids in school provides not only educational enrichment but also social, psychological and emotional health benefits, particularly for students who rely on school-based services for nutritional, physical and mental health support,” said senior author Johanna S. Salzer, DVM, PhD, a veterinary medical officer with the CDC’s National Center for Emerging and Zoonotic Infectious Diseases.

The pilot study involved 57 schools in the Pattonville School District in St. Louis County and the Springfield Public School District in Greene County in southwest Missouri, as well as two private schools in St. Louis County. All schools in the pilot study required students, teachers, staff and visitors to wear masks while on campus or buses.

Other safety measures included a focus on hand hygiene, deep cleaning of facilities, physical distancing in classrooms, daily symptom screenings for COVID-19, installing physical barriers between teachers and students, offering virtual learning options, and increasing ventilation.

For two weeks in December, the schools involved in the pilot project notified the research team of students, teachers and staff who were either infected with COVID-19 or quarantined due to being considered a close contact of someone who had tested positive. In St. Louis, close contacts of students or teachers who had tested positive were placed in quarantine, meaning they were not to leave their homes for 14 days from when last exposed to a positive case. In Springfield, however, some of the close contacts of those who had tested positive were placed in modified quarantine — meaning they could stay in school if they and the infected person were wearing masks when in close contact; in this scenario, the infected person still isolated at home.

Participants in the pilot study included 193 persons across 22 of the 57 schools — 37 who tested positive for COVID-19 and 156 of their close contacts. Among participants who were COVID-19 positive, 24 (65%) were students, and 13 (35%) were teachers or staff members. Of the close contacts, 137 (88%) were students, and 19 (12%) were teachers or staff members.

Among the 102 close contacts who agreed to testing for COVID-19 using saliva tests, only two people received positive test results indicating probable school-based SARS-CoV-2 secondary transmission. Further, no outbreaks were identified in participating schools despite the high rates of community spread in December, even among the Springfield schools that followed modified quarantine protocols allowing some close contacts of positive individuals to remain in school.

“Schools can operate safely during a pandemic when prevention strategies are followed,” said one of the study’s leading researchers, Jason Newland, MD, a Washington University professor of pediatrics, who treats patients at St. Louis Children’s Hospital. Newland led the pilot program with the CDC and has advised multiple school districts in Missouri on plans for reopening schools. “The pilot study demonstrates low transmission in schools and no student-to-teacher transmission — and this was during the height of the pandemic in December, with high rates of community spread.”

Added Randall Williams, MD, director of the Missouri Department of Health and Senior Services: “Schools with proper prevention strategies remain a safe environment for students and teachers during the pandemic.”

Since mid-January, the CDC, Washington University and Saint Louis University researchers, and the St. Louis County and Springfield-Greene County health departments, along with three school districts from St. Louis County, and three school districts in Greene County have been participating in a larger study to further examine the COVID-19 prevention strategies and quarantine policies. The St. Louis County school districts involved are Rockwood, Pattonville and University City; the Greene County school districts involved are Springfield, Republic and Logan-Rogersville.

In addition, the researchers are going into classrooms to measure the distances between desks to evaluate whether the 6-foot social distancing rule can be relaxed in school settings. They’re also sending surveys to parents, teachers and staff to assess the stress and mental health challenges surrounding quarantine. In Springfield, the researchers are continuing to study modified quarantine policies.

“We are pleased to continue to work on this joint project with the CDC, Washington University, and the Springfield-Greene County Health Department,” said Jean Grabeel, director of health services for Springfield Public Schools. “The initial results helped verify that our mitigation strategies have been successful in the school setting. This continued work will help to further guide the full-time return of students to in-person learning, five days a week, in a safe manner. We deeply appreciate this unique opportunity to collaborate on such a meaningful, impactful project.”

Added Mark T. Miles, PhD, superintendent of the Rockwood School District, the largest school system in St. Louis County and one of the largest in the state, with 22,268 students: “I am grateful for Rockwood’s opportunity to participate in this collaboration. We all share the same priority: keeping schools safe for students, teachers and staff as well as the community at large.”

Dawson P, Worrell MC, Orscheln RC, Williams RW, Newland JG, Salzer JS et al and the COVID-19 Surge Laboratory Group. Pilot investigation of SARS-CoV-2 secondary transmission in Kindergarten through Grade 12 schools implementing mitigation strategies — St. Louis County and City of Springfield, Missouri, December 2020. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. March 19, 2021.

For this analysis, researchers accessed the American Heart Association’s COVID-19 Cardiovascular Disease Registry to investigate stroke risk among patients hospitalized for COVID-19, their demographic characteristics, medical histories and in-hospital survival. The COVID-19 Registry data pulled for this study included more than 20,000 patients hospitalized with COVID-19 across the U.S. between January and November 2020.

“These findings suggest that COVID-19 may increase the risk for stroke, though the exact mechanism for this is still unknown,” said lead study author Saate S. Shakil, M.D., a cardiology fellow at the University of Washington in Seattle. “As the pandemic continues, we are finding that coronavirus is not just a respiratory illness, but a vascular disease that can affect many organ systems.”

Two hundred eighty-one people (1.4%) in the COVID-19 CVD Registry had a stroke confirmed by diagnostic imaging during hospitalization. Of these, 148 patients (52.7%) experienced ischemic stroke; 7 patients (2.5%) had transient ischemic attack (TIA); and 127 patients (45.2%) experienced a bleeding stroke or unspecified type of stroke.

The analysis of COVID-19 patients also found:

• Those with any type of stroke were more likely to be male (64%) and older (average age 65) than patients without stroke (average age 61);
• 44% of patients who had an ischemic stroke also had Type 2 diabetes vs. about one-third of patients without stroke, and most of the ischemic stroke patients had high blood pressure (80%) compared to patients without stroke (58%);
• 18% of ischemic stroke patients had atrial fibrillation, while 9% of those without stroke also had atrial fibrillation;
• Patients who had a stroke spent an average of 22 days in the hospital, compared to 10 days of hospitalization for patients without stroke; and
• In-hospital deaths were more than twice as high among stroke patients (37%) compared to patients without stroke (16%).

In addition, stroke risk varied by race. Black patients accounted for 27% of the patients in the COVID-19 CVD Registry pool for this analysis; however, 31% of ischemic stroke cases were among Black patients.

“We know the COVID-19 pandemic has disproportionately affected communities of color, but our research suggests Black Americans may have higher risk of ischemic stroke after contracting the virus, as well,” Shakil said. “Stroke on its own can have devastating consequences and recovering from COVID-19 is often a difficult path for those who survive. Together, they can exact a significant toll on patients who have had both conditions.”

Shakil added, “It is more important than ever that we curb the spread of COVID-19 via public health interventions and widespread vaccine distribution.”

In April 2020, the American Heart Association created the COVID-19 CVD Registry within weeks of the declaration of the global pandemic to rapidly collect and provide insights into patients hospitalized with the novel coronavirus. The Association’s robust Get With the Guidelines registry infrastructure has allowed for rapid data collection, including over 37,000 patient records and more than 135,000 lab reports, with more than 160 registry sites enrolled (data as of 2/23/21).

Co-authors are Sophia Emmons-Bell, B.A.; Christine Rutan, B.A.; Jason Walchok, B.A., N.R.P.; James A. de Lemos, M.D.; Babak Navi, M.D., M.S.; Alexander E. Merkler, M.D., M.S.; Gregory A. Roth, M.D., M.P.H.; and Mitchell S.V. Elkind, M.D., M.S., FAHA, FAAN. Disclosures are available in the abstract.

This study was funded by the American Heart Association.

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Materials provided by American Heart Association. Note: Content may be edited for style and length.