Culture

WASHINGTON (Aug. 6, 2020) -- George Washington University (GW) researchers found five biomarkers, medical indicators found in the blood, associated with higher odds of clinical deterioration and death in COVID-19 patients. Published in Future Medicine, these findings will help physicians better predict outcomes for COVID-19 patients in the U.S.

"When we first started treating COVID-19 patients, we watched them get better or get worse, but we didn't know why," said Juan Reyes, MD, co-author of the study and assistant professor of medicine at the GW School of Medicine and Health Sciences. "Some initial studies had come out of China showing certain biomarkers were associated with bad outcomes. There was a desire to see if that was true for our patients here in the U.S."

The research team evaluated 299 patients diagnosed with COVID-19 admitted to GW Hospital between March 12 and May 9, 2020. Of these patients, 200 had all five biomarkers being evaluated - IL-6, D-dimer, CRP, LDH and ferritin. Elevated levels of these biomarkers were associated with inflammation and bleeding disorder, showing an independent increased risk for ICU admission, invasive ventilatory support, and death. The highest odds of death occurred when the LDH level was greater than 1200 units/l and a D-dimer level was greater than 3 μg/ml.

"We hope these biomarkers help physicians determine how aggressively they need to treat patients, whether a patient should be discharged, and how to monitor patients who are going home, among other clinical decisions," said Shant Ayanian, MD, first author of the study and assistant professor of medicine at the GW School of Medicine and Health Sciences.

Currently, physicians determine risk for COVID-19 deterioration and death based on age and certain underlying medical conditions, like having an immunocompromised state, obesity, and heart disease. Performing a simple blood test for patients admitted to the emergency department, then also making decisions based on biomarkers present, may further aid point-of-care clinical decision making. Reyes, Ayanian, and the GW research team will continue to analyze this data to help physicians make more informed decisions for patients, as well as help hospitals that may need to stratify resources.

"The association between biomarkers and clinical outcomes in novel coronavirus pneumonia in a US cohort" was published in Future Medicine and is available at https://www.futuremedicine.com/doi/10.2217/bmm-2020-0309.

Bacteria are always with us: These tiny organisms are found within and on our body as is the case with all animals and plants. As part of a healthy microbiome they ensure our wellbeing. But if the microbial community gets dysbalanced, infections can follow. Even in soil and water they are a crucial component of the respective environments and their functioning.

Still, we are just beginning to understand these essential unicellular organisms. The Jena microbiologist Prof. Kai Papenfort and his team were able to shed more light on this subject with their latest publication in the journal eLife. They discovered a new mechanism of autoregulation during gene expression that relies on small regulatory ribonucleic acids (sRNAs) and the major endoribonuclease RNase E.

"This autoregulation controls gene expression - that means, the proteins are synthesized based on genetic information. Bacteria use this process to adapt to their environment for example," explains Papenfort, Chair of General Microbiology at the Friedrich Schiller University Jena. The sRNAs play a decisive role in gene regulation. Through their interaction with the messenger RNA they influence the structure or metabolism of the bacterium, among other things.

"Based on the collected data, we were able to show that sRNAs from a specific section of the messenger RNA serve as autoregulatory elements. That allows negative feedback control at the post-transcriptional level," says Papenfort. Negative feedback regulation is very common in biology. It often has a stabilising effect. For example, in humans both the regulation of body temperature and blood pressure are due to negative feedback regulation. Normally, the feedback controls are triggered by the corresponding proteins during transcription. "It is notable, that the autoregulatory small RNAs we have discovered are independent of auxiliary transcription factors. Therefore, they provide a more rapid response," continues Papenfort.

With the findings from this study, Papenfort's team contributes to the research of the Cluster of Excellence "Balance of the Microverse" at the Friedrich Schiller University Jena. Its goal is to generate a holistic understanding of microorganisms, their interaction and communication with each other and with their environment.

Bacteria are survival artists: When they get nutrition, they multiply rapidly, albeit they can also survive periods of hunger. But, when they grow too quickly, their ability to survive is hampered, as studies by a research team at the Technical University of Munich (TUM) on E. coli bacteria show. The results could help increase the effectiveness of antibiotics.

"The fitness of bacteria is more complex than expected," explains Ulrich Gerland, professor for the theory of complex biosystems at the Technical University of Munich. The physicist has been studying the survival strategies of E. coli bacteria for several years.

The unicellular organisms, which go by the Latin name Escherichia coli and support digestion in the large intestine of mammals, are a popular model organism. They facilitate investigations into the way living beings can adapt to changing environmental conditions.

Surviving hard times

"We have known for some time that biological fitness depends on two things: the growth rate when food is available and the ability to survive periods of nutrient deficiency," explains the scientist. "What was not clear is how these two factors are related."

For the first time, Gerland and his team have now systematically investigated the extent to which fast or slow growth influences the survivability of E. coli bacteria: "It turns out that changes in growth conditions have a direct impact on death rates. These follow a simple law: The best-nourished and fastest-growing bacteria are the first to die when deprived of food."

Fat bacteria - poor fitness

So, a good diet is bad for the fitness of bacteria. But why? To find an answer to this question, the TUM researchers carried out a number of experiments: First, cultures of E. coli bacteria were provided nutrient solutions with different compositions.

In the second step, the unicellular organisms were put on a zero diet. Throughout the entire period, the scientists examined whether and how quickly the cells multiplied, and how long they survived.

The fight for survival

The research showed that regardless of how well or poorly they were previously fed, bacteria stopped reproducing when they were deprived of food. In this "maintenance phase," organisms struggle for bare survival. All available energy sources - for example, the cellular remains of dead bacteria - are used to sustain the metabolism.

In this extreme situation, many cells die of starvation within a few days. However, the death rate is particularly high among rapidly growing E. coli bacteria. "They are primed for rapid growth and waste energy resources. This leads to their demise during the hunger phase," explains Gerland.

As it turns out, the abundantly fed bacteria have an increased need for energy, as further experiments prove. Surviving times of scarcity is more difficult for organisms with a high energy consumption. "We now understand why evolution doesn't favor the fastest possible reproduction," says Gerland. "The biological fitness that is crucial for the survival of a species builds on a balance between growth and survivability."

Antibiotic therapy with a carrot and a stick

The research results may find application in the future, for example, to improve the effect of antibiotics: "Applying a carrot and stick principle, intestinal bacteria growth could be stimulated by consuming a sweet dish. This would weaken the bacteria if an antibiotic against an intestinal infection is then administered," explains Gerland. However, it is still too early for concrete recommendations. More research will be necessary.

Taking advantage of a total lunar eclipse, astronomers using NASA's Hubble Space Telescope have detected Earth's own brand of sunscreen - ozone - in our atmosphere. This method simulates how astronomers and astrobiology researchers will search for evidence of life beyond Earth by observing potential "biosignatures" on exoplanets (planets around other stars).

Hubble did not look at Earth directly. Instead, the astronomers used the Moon as a mirror to reflect sunlight, which had passed through Earth's atmosphere, and then reflected back towards Hubble. Using a space telescope for eclipse observations reproduces the conditions under which future telescopes would measure atmospheres of transiting exoplanets. These atmospheres may contain chemicals of interest to astrobiology, the study of and search for life.

Though numerous ground-based observations of this kind have been done previously, this is the first time a total lunar eclipse was captured at ultraviolet wavelengths and from a space telescope. Hubble detected the strong spectral fingerprint of ozone, which absorbs some of the sunlight. Ozone is important to life because it is the source of the protective shield in Earth's atmosphere.

On Earth, photosynthesis over billions of years is responsible for our planet's high oxygen levels and thick ozone layer. That's one reason why scientists think ozone or oxygen could be a sign of life on another planet, and refer to them as biosignatures.

"Finding ozone is significant because it is a photochemical byproduct of molecular oxygen, which is itself a byproduct of life," explained Allison Youngblood of the Laboratory for Atmospheric and Space Physics in Boulder, Colorado, lead researcher of Hubble's observations.

Although ozone in Earth's atmosphere had been detected in previous ground-based observations during lunar eclipses, Hubble's study represents the strongest detection of the molecule to date because ozone - as measured from space with no interference from other chemicals in the Earth's atmosphere - absorbs ultraviolet light so strongly.

Hubble recorded ozone absorbing some of the Sun's ultraviolet radiation that passed through the edge of Earth's atmosphere during a lunar eclipse that occurred on January 20 to 21, 2019. Several other ground-based telescopes also made spectroscopic observations at other wavelengths during the eclipse, searching for more of Earth's atmospheric ingredients, such as oxygen and methane.

"One of NASA's major goals is to identify planets that could support life," Youngblood said. "But how would we know a habitable or an uninhabited planet if we saw one? What would they look like with the techniques that astronomers have at their disposal for characterizing the atmospheres of exoplanets? That's why it's important to develop models of Earth's spectrum as a template for categorizing atmospheres on extrasolar planets."

Her paper is available online in The Astronomical Journal.

Sniffing Out Planetary Atmospheres

The atmospheres of some extrasolar planets can be probed if the alien world passes across the face of its parent star, an event called a transit. During a transit, starlight filters through the backlit exoplanet's atmosphere. (If viewed close up, the planet's silhouette would look like it had a thin, glowing "halo" around it caused by the illuminated atmosphere, just as Earth does when seen from space.)

Chemicals in the atmosphere leave their telltale signature by filtering out certain colors of starlight. Astronomers using Hubble pioneered this technique for probing exoplanets. This is particularly remarkable because extrasolar planets had not yet been discovered when Hubble was launched in 1990 and the space observatory was not initially designed for such experiments.

So far, astronomers have used Hubble to observe the atmospheres of gas giant planets and super-Earths (planets several times Earth's mass) that transit their stars. But terrestrial planets about the size of Earth are much smaller objects and their atmospheres are thinner, like the skin on an apple. Therefore, teasing out these signatures from Earth-sized exoplanets will be much harder.

That's why researchers will need space telescopes much larger than Hubble to collect the feeble starlight passing through these small planets' atmospheres during a transit. These telescopes will need to observe planets for a longer period, many dozens of hours, to build up a strong signal.

To prepare for these bigger telescopes, astronomers decided to conduct experiments on a much closer and only known inhabited terrestrial planet: Earth. Our planet's perfect alignment with the Sun and Moon during a total lunar eclipse mimics the geometry of a terrestrial planet transiting its star.

But the observations were also challenging because the Moon is very bright, and its surface is not a perfect reflector because it is mottled with bright and dark areas. The Moon is also so close to Earth that Hubble had to try and keep a steady eye on one select region, despite the Moon's motion relative to the space observatory. So, Youngblood's team had to account for the Moon's drift in their analysis.

Where There's Ozone, There's Life?

Finding ozone in the skies of a terrestrial extrasolar planet does not guarantee that life exists on the surface. "You would need other spectral signatures in addition to ozone to conclude that there was life on the planet, and these signatures cannot necessarily be seen in ultraviolet light," Youngblood said.

On Earth, ozone is formed naturally when oxygen in the Earth's atmosphere is exposed to strong concentrations of ultraviolet light. Ozone forms a blanket around Earth, protecting it from harsh ultraviolet rays.

"Photosynthesis might be the most productive metabolism that can evolve on any planet, because it is fueled by energy from starlight and uses cosmically abundant elements like water and carbon dioxide," said Giada Arney of NASA's Goddard Space Flight Center in Greenbelt, Maryland, a co-author of the science paper. "These necessary ingredients should be common on habitable planets."

Seasonal variability in the ozone signature also could indicate seasonal biological production of oxygen, just as it does with the growth seasons of plants on Earth.

But ozone can also be produced without the presence of life when nitrogen and oxygen are exposed to sunlight. To increase confidence that a given biosignature is truly produced by life, astronomers must search for combinations of biosignatures. A multiwavelength campaign is needed because each of the many biosignatures are more easily detected at wavelengths specific to those signatures.

"Astronomers will also have to take the developmental stage of the planet into account when looking at younger stars with young planets. If you wanted to detect oxygen or ozone from a planet similar to the early Earth, when there was less oxygen in our atmosphere, the spectral features in optical and infrared light aren't strong enough," Arney explained. "We think Earth had low concentrations of ozone before the mid-Proterozoic geological period (between roughly 2.0 billion to 0.7 billion years ago) when photosynthesis contributed to the build up of oxygen and ozone in the atmosphere to the levels we see today. But because the ultraviolet-light signature of ozone features is very strong, you would have a hope of detecting small amounts of ozone. The ultraviolet may therefore be the best wavelength for detecting photosynthetic life on low-oxygen exoplanets."

NASA has a forthcoming observatory called the James Webb Space Telescope that could make similar kinds of measurements in infrared light, with the potential to detect methane and oxygen in exoplanet atmospheres. Webb is currently scheduled to launch in 2021.

PROVIDENCE, R.I. [Brown University] -- Two federal environmental standards regulating lead hazards in homes and child care facilities have different maximum thresholds, a discrepancy putting more than 35,000 kids in the United States at increased risk of lead poisoning.

That's according to a new study led by a Brown University researcher as the U.S. Environmental Protection Agency (EPA) moves to revise protective standards for dust lead levels on floors and windowsills in buildings constructed before 1978. 

"Lead exposure presents a major risk to hundreds of thousands of children across the nation, and it's imperative that federal EPA regulations offer a clear and consistent standard to reduce that risk," said Joseph Braun, an associate professor of epidemiology at Brown. "Currently, these standards are counterproductive to public health."

In 2019, the EPA tightened the standard for the amount of residential dust lead considered hazardous to children from 40 micrograms per square foot (μg/ft2) to 10 on floors, and from 250 μg/ft2 to 100 on windowsills. The change came after a federal appeals court ordered the agency to reduce dust lead hazard standards after a 2016 lawsuit filed by environmental groups.

Traditionally, the residential standard had been the same as the clearance standard for dust lead levels after completing lead abatement work -- yet despite the more aggressive standard imposed after the court's order, the EPA left the post-abatement clearance standard where it has stood since 2001. Both standards fall under the Toxic Substances Control Act, which authorizes EPA to impose restrictions related to chemical substances.

Conceivably, a risk assessment could identify a dust lead hazard above 10 μg/ft2 but below 40 μg/ft2 on the floor of a home where there is a child with lead poisoning. Braun, an expert on children's environmental health, said an abatement contractor could theoretically do nothing, but given the discrepancy in standards, the unit would pass the clearance. 

"When I read this, initially, I thought this is absolutely crazy," Braun said. 

So Braun and his coauthors wanted to find out how many extra cases of lead poisoning would result from the post-abatement clearance standard being higher than the dust lead hazard standard. 

Their study, published on July 28 in Pediatric Research, found that children in homes with floor dust lead loadings between 10 and 40 μg/ft2 had nearly four times the risk of lead poisoning compared to children from homes with floor dust lead loadings at or under 10 μg/ft2. They estimated that 36,700 cases of childhood lead poisoning - nearly 7% of U.S. children between the ages of 1 and 5 with lead poisoning -- were attributable to this regulatory discrepancy. 

Dust from lead-based paint is a common cause of lead poisoning in young children, Braun said, and so the implications of the double standard are significant. Their greater hand-to-mouth behavior makes them vulnerable to lead exposure.

"I have a two-and-a half year old who puts everything in his mouth," Braun said. "That's how they explore their environment at this age."

Lead poisoning can cause learning disabilities and behavioral problems that last a lifetime and affect kids from all social and economic levels, though those living at or below the poverty line in older housing are at greatest risk. Earlier work by Braun and his colleagues found higher blood lead levels and risk of lead poisoning among Black children compared to white.

For the new study, the researchers looked at 250 children from Cincinnati living in homes built before 1978 -- the year lead-based paints were banned for residential use -- whose mothers participated in a longitudinal pregnancy and birth cohort study between 2003 and 2006. 

Researchers took samples of floor and interior windowsill dust lead loadings with wipes over a 1-square foot area when participants joined the study, when their children turned 1 year old and again when they turned 2. Blood samples were also collected from the children at these same times.

The study adds to a vast body of scientific research guiding housing and environmental policymakers. But Braun points out that the bulk of these studies were completed 20 and 30 years ago when lead exposure was much higher.

"The fact that we're still seeing these relationships at contemporary levels of lead exposure indicates that this is still a significant problem, so that's the real contribution here," Braun said.

The EPA has issued a proposed rule to align the post-abatement clearance standard with the tighter standard revised in 2019. Its two-month public comment period ends on Aug. 24. An EPA spokeswoman said Braun's study will be considered when developing a final rule along with all other feedback received.

Braun said the proposed change still won't go far enough to protect children. In 2012, the U.S. Centers for Disease Control and Prevention acknowledged there is no known safe blood lead level.

The study found children were at 45% higher risk of having blood poisoning at the newly revised floor dust lead hazards of 10 μg/ft2 compared to a more stringent standard of 5 μg/ft2.

"Reducing sources of lead exposure in children is imperative to optimize children's health," Braun said. 

The Barotse Floodplain in Zambia is one of Africa's largest wetlands, representing varied ecotypes and high biodiversity conservation value. However, the Lozi People who live in the region face an intense "hungry season" from November to January when accessibility to food is very limited. This means that year-round nutrition and food security are consistently top priorities.

Conventional intensive agriculture is not well-suited for the Barotse landscape. Over-expansion of agriculture would have cascading negative effects on local people, wildlife, downstream ecosystems, and economic sectors such as hydropower.

To help improve livelihoods through sustainable agricultural development and environmental protection, researchers from the Alliance of Bioversity International and CIAT worked with Lozi communities to identify locally relevant strategies. They published some of their findings in a recent study in the International Journal of Agricultural Sustainability.

Why identify ecosystem services?

Ecosystem services encompass a plethora of benefits to humans that come from natural and managed lands. However, researcher and co-author Natalia Estrada-Carmona says, only a small fraction of these tend to be considered, valued, and measured (e.g., CO2 or crop yields) in economic and agriculture development agendas.

The research team used a gender-sensitive ecosystem services approach to work with three local communities. Focus group participants (separated into men and women) used 1,992 coded cards in English and the local language Silozi to assess 17 ecosystem services, from fishing to erosion control.

Questions such as "Where do you go to get water for consumption?" and "What eco-types are important for controlling floods?" identified services according to provisioning, regulating, and cultural uses and benefits.

"The activities carried out with the local communities helped to visualize all the benefits from the different eco-types present in the floodplain. It was very interesting to see that many of the most important ecosystem services for both women and men come from native vegetation eco-types," explains Estrada-Carmona. "Additionally, this exercise facilitated discussing and visualizing the trade-offs associated with converting natural vegetation to cultivated eco-types. Those trade-offs are often invisible in agriculture development agendas and programs. This research confirms that assuming that agricultural expansion can occur everywhere without consequences is a pretty biased perception."

Implications from applying a gender lens

The study suggests several differences between how men and women access their ecosystems: for example, women go to shallower river areas for smaller fish and cultivate diverse crops, including neglected and underutilized species (NUS), that complement household nutrition security.

The dynamic nature of the floodplain also translates into seasonal changes in human migration, and labor shortages. Estrada-Carmona elaborates: "Communities in the uplands are settling more as access to schools, roads, and electricity increases. Women tend to stay caring for kids, elders, and land during the dry season while men migrate to the plains in the hunt for fish and cash. Therefore, agricultural practices or activities that ignore women's reality in the uplands during the dry season would either add a burden or exclude them from implementing those practices or activities."

Agroecological intensification - multifunctional agricultural land

Although the study revealed that forests in the uplands and grasslands in the plains provide the bulk of ecosystem services, these fertile lands are often converted to agricultural land. The authors point out that rather than monocultures focused on cash crops, such as hybrid maize and rice, local food security and livelihoods would benefit most from agroecological intensification. Approaches such as multiple cropping, conservation agriculture, and agroforestry could restore and maintain the identified ecosystem services in cultivated lands while reducing the pressure on natural lands.

Local people and the Zambian government already recognize the value of crop diversity in mitigating environmental, food security, and market risks, with researchers finding that at least 17 NUS are currently being planted. However, maize is the most common crop, and there is a lack of support for experimentation and innovation that can identify the cultivation system best suited to ensure year-round, long-term production and other benefits.

"Agricultural land is seen as a source of yields or calories only," says Estrada-Carmona. "In reality, it is the most malleable land that can contribute to maintaining soil fertility, erosion or flood control, water quality, wildlife connectivity/habitat, etc. Hence, identifying the cropping systems and crop diversification strategies at the farm and landscape level that generate those multiple benefits is vital for sustainable and holistic development."

The study concludes: "The intertwined drivers of change and the complex trade-offs between ecosystem services demand looking beyond 'agriculture' and 'conservation' as two separate challenges... All stakeholders' agendas could be better articulated by integrating the traditional place-based knowledge for jointly planning a sustainable future of the Barotse Floodplain for livelihoods, well-being, and conservation."

(WASHINGTON, August 6, 2020) -- Today, ASH published new guidelines to help older adults with acute myeloid leukemia (AML) and their health care providers make critical care decisions, including if and how to proceed with cancer treatment and the need for blood transfusions for those in hospice care.

Each year, nearly 20,000 people receive a diagnosis of AML. The disease generally develops in older people; the median age of diagnosis is 68. As the "baby boomer" generation ages and the average demographic age in the United States increases, evidence-based recommendations for the optimal treatment of older adults with AML take on greater urgency and importance.

The American Society of Hematology 2020 Guidelines for Treating Newly Diagnosed Acute Myeloid Leukemia in Older Adults, developed in partnership with the McMaster GRADE Centre, offer treatment recommendations for this vulnerable population based on rigorous, systematic reviews of all available evidence. The recommendations are guided by the principle that throughout a patient's disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment. If appropriate based on an individual patient's treatment plan, the guidelines recommend chemotherapy or other treatments over supportive care, and more-intensive therapy over less-intensive when deemed tolerable, among other common critical questions patients and clinicians discuss upon diagnosis. Notably, they also outline the clinical benefit of palliative red blood cell transfusions for those who are no longer receiving antileukemic therapy, including those in end-of-life or hospice care. The guidelines are published in Blood Advances.

"These guidelines take providers through the conversations they have with newly diagnosed patients, almost in real-time," said Mikkael Sekeres, MD, chair of the ASH AML guideline panel and director of the Leukemia Program at Cleveland Clinic Taussig Cancer Institute. "A discussion between patient and physician is instrumental to creating a personalized treatment plan, and these guidelines are unique in that they keep a patient's goals and wishes front and center in that conversation."

AML prognosis in older adults is poor. In fact, on average, a 75-year-old diagnosed with AML usually has a life expectancy measured in just months. The prognosis for those up to 10 years younger is only slightly better, with most dying in the year or two following their diagnosis. There is no single curative therapy, and while progress has been made in treating the disease, this population often has a high prevalence of comorbidities and age-related decline in organ function that can lead to a greater likelihood of treatment toxicities.

In addition to the paucity of curative treatment options and high prevalence of comorbidities complicating treatment in this patient population, some providers may be reluctant to recommend intensive therapies, or any therapy at all, because they fear toxicities in older patients. And some patients may not wish to spend their valuable remaining time in the hospital.

"We recognize the serious issues that patients face, including the side effects and risks of chemotherapy and time in the hospital. Weighing these issues against possible benefits, including remission and extended life, patients can decide what treatment is consistent with their goals," said Dr. Sekeres.

Many hospice organizations will not allow patients to receive blood product transfusions, often for economic reasons. For AML patients in end-of-life and hospice care, the guidelines recommend that blood transfusions should be considered standard supportive care, as they can address palliative needs related to breathlessness, bleeding, and profound fatigue, as well as improve overall quality of life. This guidance supports an ASH policy statement in support of ensuring Medicare hospice beneficiaries can access palliative transfusions.

The guidelines were developed by a panel of experts in leukemia, geriatric oncology, quality of life, end-of-life, and frailty. "We brought together this incredible spectrum of specialists to address every aspect of care so that people with AML can be empowered and informed as they decide," said Dr. Sekeres.

The AML guidelines are the most recent product of a larger guideline development initiative for ASH, which includes a commitment to the timely update of existing guidelines and the development of new ones on a range of hematologic conditions. In the coming months, resources to aid in the implementation of the guidelines will be added to the ASH website.

Consider it Earth's ultimate mirror selfie.

In a new study, a team led by astrophysicist Allison Youngblood at the University of Colorado Boulder set out to achieve something new in planetary photography: The group used the Hubble Space Telescope to try to view Earth as if it were an exoplanet--or a world orbiting a star many light years from our own.

It wasn't easy: To capture Earth as an alien world, the researchers had to use the moon as a giant mirror, recording sunlight that had passed through our planet's atmosphere, bounced off the lunar surface and come back.

"It's like what an astronaut might see standing on the surface of the moon," said Youngblood, a research scientist at the Laboratory for Atmospheric and Space Physics (LASP).

Previous studies have taken a similar look at Earth as an exoplanet. But the new research, which appears August 6 in The Astronomical Journal, is the first to succeed in taking such a selfie using a combination of a space instrument and the moon. Youngblood said that the group's findings could one day help scientists to hone how they search distant planets for the possible fingerprints of life--in this case, ozone in the atmosphere.

"Ozone is what we call a biosignature," said Youngblood, who worked on the project as a postdoctoral fellow at NASA's Goddard Space Flight Center. "It's a byproduct of molecular oxygen, which can be a byproduct of life."

The search for life

Over the last several decades, scientists have confirmed the existence of more than 4,000 planets beyond Earth's solar system. Many of them were spotted using what researchers call the "transit" method--a planet passes in front of its host star, causing the light from that star to dim ever so slightly.

This approach has an added benefit, too, Youngblood said. Train a powerful enough telescope, such as Hubble, on an alien planet, and you can see how starlight filters through its atmosphere. Scientists, in turn, can analyze that starlight to identify the gases that are present in the atmosphere.

In the coming decades, one of the big targets that planet hunters will be looking for is ozone. It's created when ultraviolet light from the sun reacts with oxygen gas in the atmosphere--meaning that, at least on Earth, ozone is often connected to the activity of photosynthesizing organisms.

In the hunt for life, "one biosignature alone isn't enough," Youngblood said. "But if you, for example, saw ozone and methane together, that might indicate that there is life."

The problem is that ozone is also tricky to spot from the ground on Earth. To get around that limitation, Youngblood and her colleagues had to go to space.

Total eclipse

They got their chance in the wee hours of January 21, 2019. On that day, Earth's orbit brought the planet directly between the sun and the moon, leading to the first total lunar eclipse of the year. (The event also turned the moon an eerie blood-orange color, which gave it the nickname "super blood wolf eclipse.")

"During a total eclipse, all of the light you see reflected off the moon has already passed through Earth's atmosphere," Youngblood said.

To capture that reflection, and particularly the ultraviolet light shining off of the moon, the team pointed Hubble at the lunar surface--not something the telescope was designed for.

"I talked to colleagues and they said, 'Pointing Hubble at the moon is really challenging,'" Youngblood said. "The moon is too close."

Put differently, getting a stable image of the moon using Hubble is a bit like hitting the bullseye on a dart board while standing on a swaying cruise ship in the middle of a storm. But with a bit of luck and mathematical savvy, the team prevailed. Youngblood and her colleagues were able to detect the distinct ultraviolet signals of ozone in Earth's atmosphere.

The team's results aren't a perfect representation of what ozone might look like on a real-life exoplanet. For starters, Youngblood and her colleagues were able to peer much deeper into Earth's atmosphere than would be possible in a world many lightyears away.

But, she said, the study is a good proof-of-concept that it can be done. And that means that scientists may one day be able to locate the hints of living organisms on a planet far, far away.

Movie studios estimate that they lose billions of dollars to digital movie piracy. But a new marketing study from the University of Georgia finds that piracy can actually boost ticket sales in certain situations.

The reason: pirates talk.

Pirated movies circulated online after their theatrical release saw about 3% higher box office receipts because of the increase in word-of-mouth advertising, according to Neil Bendle, an associate professor of marketing at the Terry College of Business.

Bendle is quick to point out that prerelease piracy is still financially damaging for movie studios. But post-theatrical release piracy was connected to more word-of-mouth and higher ticket sales.

"We don't want to give the impression that piracy is a good thing, but there is something to the argument that piracy can increase markets," Bendle said. "We wanted to find out when that might be the case."

Bendle and his co-authors -- Shane Wang of the University of Western Ontario and Shije Lu of the University of Houston -- published their findings in a recent issue of Management Science.

They analyzed movie ticket sales, piracy rates and crowdsourced movie reviews between July 2015 and June 2017, using data from Russia, where authorities have blocked the popular Pirate Bay torrent since 2015.

Pirate Bay was one of the most significant digital piracy sites on the internet for several years between 2010 and 2020 but is now banned in many countries. The research team used activity on the site as a benchmark for piracy rates. They analyzed movie revenues before and during 2015, after a late 2014 law enforcement raid shut down the Pirate Bay website for about a year.

During Pirate Bay's hiatus, word-of-mouth and movie revenues both dipped.

"When the Pirate Bay was taken down by the Swedish police, we see a drop in word-of-mouth because people can't watch these movies on the Pirate Bay," Bendle said. "And then, we see a contemporaneous decline in ticket sales. When we see that associated fall in word-of-mouth, and then a decline in movie sales, it was a nice bit of evidence that we were moving in the right direction."

Though it sounds counterintuitive, Bendle's team connected the dips to a decline in movie fans talking about the titles online. With the reduction in online buzz, fewer people were interested in seeing the movies in theaters or streaming them legally.

"With post-theatrical release piracy, people who are super keen on it or would have gone anyhow have already gone," Bendle said. "People who are not going on the opening weekend can be drawn to it by people who have watched the movie and blogged about it. Bloggers don't have to produce their ticket before they write about it. Pirates can still give a useful, valid opinion for consumers."

Movies only benefitted from the boost in word-of-mouth advertising if the title was pirated and circulated after its theatrical release. Films that were pirated before their release dates saw an 11% decline in their overall revenue, despite increased word-of-mouth.

"There's a key distinction between pre- and post-release piracy," Bendle said. "We substantiate that prerelease piracy is very bad. It can undermine a film before it comes out."

The takeaway for movie studios is that they should target their anti-piracy efforts to prevent pirated copies of their movies from leaking onto the internet before their theatrical release, Bendle said.

"They've got limited resources to try to track down movie pirates," he said. "We're saying that the best use of those resources should be put toward controlling digital copies of the movie prerelease and not at who's pirating it after the theatrical release."

FAIRFAX, Va. -- Researchers demonstrated the success of a fully implantable wireless medical device called a stentrode brain-computer interface designed to improve functional independence in patients with severe paralysis. The abstract was presented today at the Society of NeuroInterventional Surgery's (SNIS) 17th Annual Meeting.

The study, Motor Neuroprosthesis Implanted using Cerebral Venography Improves Activities of Daily Living in Severe Paralysis, is the first-in-human examination of the stentrode, an implantable brain- computer interface, conducted at The Royal Melbourne Hospital. The first patient to receive the device was a 75-year-old man with severe paralysis due to amyotrophic lateral sclerosis (ALS), who was totally dependent on his wife for care.

"The implantation procedure combined functional MRI coregistration with angiography to precisely place the stentrode over the motor cortex," said Professor Peter Mitchell, principal investigator and leader of the operative team.

Following implantation of the device, the patient increased independence and could perform essential activities, such as text messaging, online shopping and managing his finances.

"The results in this first human trial show promise that this device may restore voluntary motor function of personal computers and devices for patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction," said Dr. Thomas Oxley, lead author of the study and Associate Professor in the Vascular Bionics Laboratory at the University of Melbourne. "We need to conduct additional research to confirm our preliminary results and prove the validity of this ground-breaking technology."

The stentrode brain-computer interface translates brain activity associated with attempted movements and digitally converts thoughts into command functions of external devices. The data shows successful control of devices that improve instrumental activities of daily living, which can include texting, emailing, online shopping and banking.

EAST LANSING, Mich. - How much of a treatment is mind over matter? It is well documented that people often feel better after taking a treatment without active ingredients simply because they believe it's real -- known as the placebo effect.

A team of researchers from Michigan State University, University of Michigan and Dartmouth College is the first to demonstrate that placebos reduce brain markers of emotional distress even when people know they are taking one.

Now, evidence shows that even if people are aware that their treatment is not "real" -- known as nondeceptive placebos -- believing that it can heal can lead to changes in how the brain reacts to emotional information.

"Just think: What if someone took a side-effect free sugar pill twice a day after going through a short convincing video on the power of placebos and experienced reduced stress as a result?", said Darwin Guevarra, MSU postdoctoral fellow and the study's lead author. "These results raise that possibility."

The new findings, published in the most recent edition of the journal Nature Communications, tested how effective nondeceptive placebos -- or, when a person knows they are receiving a placebo -- are for reducing emotional brain activity.

"Placebos are all about 'mind over matter," said Jason Moser, co-author of the study and professor of psychology at MSU. "Nondeceptive placebos were born so that you could possibly use them in routine practice. So rather than prescribing a host of medications to help a patient, you could give them a placebo, tell them it can help them and chances are -- if they believe it can, then it will."

To test nondeceptive placebos, the researchers showed two separate groups of people a series of emotional images across two experiments. The nondeceptive placebo group members read about placebo effects and were asked to inhale a saline solution nasal spray. They were told that the nasal spray was a placebo that contained no active ingredients but would help reduce their negative feelings if they believed it would. The comparison control group members also inhaled the same saline solution spray, but were told that the spray improved the clarity of the physiological readings the researchers were recording.

The first experiment found that the nondeceptive placebos reduced participants' self-reported emotional distress. Importantly, the second study showed that nondeceptive placebos reduced electrical brain activity reflecting how much distress someone feels to emotional events, and the reduction in emotional brain activity occurred within just a couple of seconds.

"These findings provide initial support that nondeceptive placebos are not merely a product of response bias - telling the experimenter what they want to hear -- but represent genuine psychobiological effects," said Ethan Kross, co-author of the study and a professor of psychology and management at the University of Michigan.

FAIRFAX, Va. -- Two new studies indicate that racial disparities related to outcomes exist among stroke patients, including one study that specifically examines stroke patients with COVID-19. The abstracts were presented today at the Society of NeuroInterventional Surgery's (SNIS) 17th Annual Meeting.

The first study, Ischemic Stroke Associated with Covid-19 and Racial Outcome Disparity in North America,
finds mortality rates in African American stroke patients with COVID-19 are significantly greater than all other races combined in North America. Additionally, the study, which emanates from the North American Neurovascular COVID-19 (NAN-C) Consortium, shows that the mortality rate of COVID-19-positive stroke patients is greater than previously reported in patients who just have COVID-19 or stroke alone. The research analyzed 69 cases of acute stroke in patients positive for SARS-CoV-2, including 27 African Americans and 42 of other racial backgrounds.

"Clearly it is important to better understand the reasons for increased mortality in African Americans with COVID-19-associated stroke," said Dr. Adam A. Dmytriw, lead author of the study and Fellow at Harvard Medical School and Brigham and Women's Hospital. "It is our hope that further research will help us reduce racial disparities and prevent negative outcomes."

Another study released on the same day, Racial Disparities in Acute Stroke Thrombectomy Management and Outcomes in the United States: Evidence from the NVQI-QOD Registry, by lead author Vineeth Thirunavu found several racial disparities after stroke thrombectomy with respect to post-procedure management and outcomes. Specifically, minorities exhibited worse immediate post-procedural outcomes and a greater length of in-hospital and ICU stays. Although African Americans suffer less in-hospital mortality compared to Caucasians, the odds of increased favorable clinical outcome did not increase.

For the second study, researchers analyzed data from the NVQI-QOD registry and compared racial differences with respect to technical and functional outcomes of stroke thrombectomy in 3,281 African American, Caucasian, Hispanic, and Asian patients from 23 U.S. stroke centers across 17 states between January 2015 and March 2020.

"The study suggests disparities in how African American and Hispanic patients fare with regard to post-stroke recovery and hospital course after thrombectomy," said Dr. Sameer Ansari, senior author of the second study, Medical Director of the SNIS Patient Safety Organization, and an Associate Professor in the Departments of Radiology, Neurology, and Neurological Surgery, Northwestern University Feinberg School of Medicine. "We are just initiating our investigations and the research potential of the NVQI-QOD registry for uncovering racial disparities in stroke patients, and with this increased knowledge we can strive to ensure better outcomes for all patients, irrespective of their racial and genetic profile."

To receive a copy of either abstracts or to speak with the authors, please contact Maria Enie at menie@vancomm.com or 202-248-5454.

About the Society of NeuroInterventional Surgery

The Society of NeuroInterventional Surgery (SNIS) is a scientific and educational association dedicated to advancing the specialty of neurointerventional surgery through research, standard-setting, and education and advocacy to provide the highest quality of patient care in diagnosing and treating diseases of the brain, spine, head, and neck. Visit http://www.snisonline.org and follow us on Twitter (@SNISinfo) and Facebook (@SNISOnline).

JUPITER, FL--Scripps Research chemists Hans Renata, PhD, and Alexander Adibekian, PhD, have discovered a way to efficiently create a synthetic version of a valuable natural compound called cepafungin I, which has shown promise as an anti-cancer agent.

Through this, they were able to understand how the bacterial secretion is able to block a piece of molecular machinery known as a proteasome--a strategy that many existing cancer medications use to destroy tumor cells. They found that cepafungin I bound to not one but two places on the proteasome, enacting a powerful result. Their report appears in the journal Cell Chemical Biology.

"Because cepafungin I is able to engage the proteasome in two ways, it allows for amplification of its effect," Renata says. "We showed that this compound elicits many similar downstream biological responses as the FDA-approved chemotherapy bortezomib, while also having certain qualities that may translate into fewer unwanted side effects for patients."

Recreating nature

Cepafungin I first intrigued researchers because of its usefulness as an antifungal substance, and later as a promising anti-cancer agent. It kills cells by acting on the proteasome, which is responsible for clearing away the "garbage" produced by cells. When the proteasome's function is blocked, cells are overcome with their waste and die.

But making enough of the compound to be able to study its activity or enable its eventual use a medication has proven challenging, due largely to its complex molecular structure. In the field of chemistry, scientists seek to create the desired structure in as few steps as possible, which leads to cost and time savings. But with complex compounds, that isn't an easy task.

The Scripps Research team was able to overcome these challenges and synthesize the compound in just nine steps. For comparison, a related compound known as glidobactin A was synthesized in 21 steps in 1992--and that was considered a landmark at the time.

The team was able to speed up the process by using certain enzymes that enabled construction of one of the compound's key building blocks, an amino acid. Then they developed other creative chemistry methods to simplify construction of other parts of the molecule, including a branched lipid portion that was subsequently found to contribute to the compound's potent activity.

"Our approach saved us many steps in synthesizing the final compound compared with using classical chemical approaches," says Alexander Amatuni, a graduate student at Scripps Research.

A good sign for safety

After creating the compound, the chemists discovered that in addition to being exceptionally selective at targeting two sites on the proteasome, it didn't show any undesired cross-reaction with other proteins in cells, a feature that could make it a better drug candidate.

Three proteasome inhibitors--bortezomib, carfilzomib and ixazomib--have already been approved by the U.S. Food and Drug Administration for the treatment of multiple myeloma. "But those medications have some potentially serious side effects, and cancer cells may develop resistance to them over time," says co-author Adibekian, associate professor of chemistry at Scripps Research. "There is a need for alternative, more specific proteasome inhibitors."

Graduate student Anton Shuster noted that the team's discoveries were made possible by a close collaboration of labs with different expertise

"By combining the two complementary technological platforms--chemoenzymatic synthesis from the Renata lab and chemoproteomics from the Adibekian lab--we were able to succeed," Shuster says. "Having the opportunity to work with scientists with divergent research background is what makes working at Scripps Research particularly exciting."

Going forward, the scientists plan to continue structure-guided design of similar molecules with alternative structural features in search of useful compounds with superior anti-cancer activity.

The methods they developed will enable them to change various parts of the structure with relative ease, Amatuni says, allowing for further investigation of biological activity. "The emphasis on translational research at Scripps Research enables this discovery," Adibekian says. "We're excited about developing the molecule further."

PITTSBURGH, Aug. 6, 2020 - New research by neuroscientists at the University of Pittsburgh and University of California San Francisco (UCSF) revealed that a simple, earbud-like device developed at UCSF that imperceptibly stimulates a key nerve leading to the brain could significantly improve the wearer's ability to learn the sounds of a new language. This device may have wide-ranging applications for boosting other kinds of learning as well.

Mandarin Chinese is considered one of the hardest languages for native English speakers to learn, in part because the language -- like many others around the world -- uses distinctive changes in pitch, called "tones," to change the meaning of words that otherwise sound the same. In the new study, published today in npj Science of Learning (a Nature partner journal), researchers significantly improved the ability of native English speakers to distinguish between Mandarin tones by using precisely timed, non-invasive stimulation of the vagus nerve -- the longest of the 12 cranial nerves that connect the brain to the rest of the body. What's more, vagus nerve stimulation allowed research participants to pick up some Mandarin tones twice as quickly.

"Showing that non-invasive peripheral nerve stimulation can make language learning easier potentially opens the door to improving cognitive performance across a wide range of domains," said lead author Fernando Llanos, Ph.D., a postdoctoral researcher in Pitt's Sound Brain Lab.

"This is one of the first demonstrations that non-invasive vagus nerve stimulation can enhance a complex cognitive skill like language learning in healthy people," said Matthew Leonard, Ph.D., an assistant professor, Department of Neurological Surgery, UCSF Weill Institute for Neurosciences, whose team developed the nerve stimulation device. Leonard is a senior author of the new study, alongside Bharath Chandrasekaran, Ph.D., professor and vice chair of research, Department of Communication Science and Disorders, Pitt School of Health and Rehabilitation Sciences, and director of the Sound Brain Lab.

Researchers used a non-invasive technique called transcutaneous vagus nerve stimulation (tVNS), in which a small stimulator is placed in the outer ear and can activate the vagus nerve using unnoticeable electrical pulses to stimulate one of the nerve's nearby branches.

For their study, the researchers recruited 36 native English-speaking adults and trained them to identify the four tones of Mandarin Chinese in examples of natural speech, using a set of tasks developed in the Sound Brain Lab to study the neurobiology of language learning.

Participants who received imperceptible tVNS paired with two Mandarin tones that are typically easier for English speakers to tell apart showed quick improvements in learning to distinguish these tones. By the end of the training, those participants were 13% better on average at classifying tones and reached peak performance twice as quickly as control participants who wore the tVNS device but never received stimulation.

"There's a general feeling that people can't learn the sound patterns of a new language in adulthood, but our work historically has shown that's not true for everyone," Chandrasekaran said. "In this study, we are seeing that tVNS reduces those individual differences more than any other intervention I've seen."

"This approach may be leveling the playing field of natural variability in language learning ability," added Leonard. "In general, people tend to get discouraged by how hard language learning can be, but if you could give someone 13% to 15% better results after their first session, maybe they'd be more likely to want to continue."

The researchers now are testing whether longer training sessions with tVNS can impact participants' ability to learn to discriminate two tones that are harder for English speakers to differentiate, which was not significantly improved in the current study.

Stimulation of the vagus nerve has been used to treat epilepsy for decades and has recently been linked to benefits for a wide range of issues ranging from depression to inflammatory disease, though exactly how these benefits are conferred remains unclear. But most of these findings have used invasive forms of stimulation involving an impulse generator implanted in the chest. By contrast, the ability to evoke significant boosts to learning using simple, non-invasive vagus nerve stimulation could lead to significantly cheaper and safer clinical and commercial applications.

The researchers suspect tVNS boosts learning by broadly enhancing neurotransmitter signaling across wide swaths of the brain to temporarily boost attention to the auditory stimulus being presented and promote long-term learning, though more research is needed to verify this mechanism.

"We're showing robust learning effects in a completely non-invasive and safe way, which potentially makes the technology scalable to a broader array of consumer and medical applications, such as rehabilitation after stroke," Chandrasekaran said. "Our next step is to understand the underlying neural mechanism and establish the ideal set of stimulation parameters that could maximize brain plasticity. We view tVNS as a potent tool that could enhance rehabilitation in individuals with brain damage."

Scientists from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago discovered that a set of genes with decreased expression in individuals with Down syndrome may lead to clinical abnormalities in this population, such as poor muscle development and heart valve problems. Impairment in these same genes may also protect people with Down syndrome from developing solid tumors. Their findings were published in Scientific Reports.

"Our promising preliminary data carries strong potential for ultimately developing gene-targeted therapies to inhibit solid tumor growth in the general population," says co-lead author Yekaterina Galat, BS, Research Associate at the Manne Research Institute at Lurie Children's. "Our findings may also provide gene targets for therapies aimed at alleviating the clinical abnormalities in people with Down syndrome."

Down syndrome is a congenital genetic disorder that is associated with cognitive impairment, reduced muscle tone, heart defects, and other clinical anomalies. At the same time, individuals with Down syndrome have lower prevalence of solid tumor formation.

The study used skin samples from two patients with Down syndrome to create induced pluripotent stem cells that were then differentiated into endothelial cells, which build blood vessels and the vascular system, and mesodermal cells, which are responsible for connective tissues and muscle development. During the process of differentiation, in the progenitor phase, Manne Research Institute scientists discovered down-regulated genes that appear to be involved in the abnormal muscle development and heart problems that are common in people with Down syndrome.

By studying the role of these genes in biochemical pathways relevant to solid tumor development, they found that the decreased expression of such genes interferes with the processes needed for solid tumor formation and growth. These genes produced impeded cell movement, slower proliferation and reduced inflammatory response - creating a microenvironment that is not conducive to solid tumors. Genome-wide analyses was then performed to confirm these findings, using publicly available data from 11,000 patients.

"When we performed genomic analyses comparing mesodermal and endothelial cell lines, we were surprised to find that trisomy 21 impacted gene expression across the entire genome. Furthermore, the decreased expression of the genes we studied was consistent, and the large extent of their down-regulation was notable as well," says co-lead author Mariana Perepitchka, BA, Research Associate at the Manne Research Institute at Lurie Children's. "This significant down-regulation potentially creates conditions that are opposite of what solid tumors would need to take hold. So in a way, Down syndrome provides us with a non-traditional lens to study cancer development."

"We still need to validate our findings in an animal model," says senior author Vasil Galat, PhD, Director of Human iPS and Stem Cell Core at Manne Research Institute at Lurie Children's and Research Assistant Professor of Pathology at Northwestern University Feinberg School of Medicine. "The potential for gene-targeted therapies is very exciting, especially since it could help individuals born with Down syndrome and the general population battling cancer."