Culture

A University of Massachusetts Amherst environmental health scientist has used an unprecedented objective approach to identify which molecular mechanisms in mammals are the most sensitive to chemical exposures.

The study, published in the journal Chemosphere, advances the understanding of the interaction of chemicals, both pollutants and pharmaceuticals, on gene expression and the impact on human health.

"When we identified all the sensitive genes, we were very much surprised that almost every well-known molecular pathway is sensitive to chemicals to a certain degree," says lead author Alexander Suvorov, associate professor in the School of Public Health and Health Sciences.

The study identified genes and molecular pathways most sensitive to chemical exposures, including mechanisms involving aging, lipid metabolism and autoimmune disease. "These findings for the first time prove that current epidemics in metabolic and autoimmune disorders may be partly due to a very broad range of chemical exposures," Suvorov says.

To carry out their analysis, Suvorov and five students - undergraduates Victoria Salemme, Joseph McGaunn and Menna Teffera, and graduate students Anthony Poluyanoff and Saira Amir - extracted data on chemical-gene interactions from the Comparative Toxicogenomics Database, which includes human, rat and mouse genes.

The UMass Amherst team created a database of 591,084 chemical-gene interactions reported in 2,169 studies that used high-throughput gene expression analysis, which means they looked at multiple genes. Low-throughout analysis focuses only on a single gene.

"In the recent past, everything that we knew about molecular mechanisms affected by chemicals was coming from low-throughput experiments," Suvorov says, which led toxicology researchers to focus on those already identified genes, rather than looking for chemical sensitivity among a fuller range of genes.

"I wanted to find some approach that would tell us in a completely unbiased way which mechanisms are sensitive and which are not. I wondered if we were missing a significant toxic response just because no one ever looked for it," Suvorov says. "By overlaying many high-throughput studies, we can see changes in the expression of all genes all at once. And that is unbiased because we are not cherry-picking any particular molecular mechanisms."

The interactions analyzed encompassed 17,338 unique genes and 1,239 unique chemicals. The researchers split their database of chemicals into two parts - pharmaceutical chemicals, which are designed to target known molecular cascades; and other chemicals such as industrial, agricultural, cosmetics and pollutants. When the sensitivity of genes to pharmaceutical chemicals was compared to the sensitivity of genes to the other chemicals, the results were the same. "That proves that when analysis is done on really big numbers of chemicals, their composition does not matter," Suvorov says.

The study confirmed the molecular mechanisms that were previously recognized as being sensitive to chemical exposure, such as oxidative stress. The study's new findings that the pathways involving aging, lipid metabolism and autoimmune disease are also highly sensitive suggest that chemical exposures may have a role in such conditions as diabetes, fatty liver disease, lupus and rheumatoid arthritis, among others.

"This study represents a significant step forward in the use of genomic data for the improvement of public health policies and decisions," Suvorov says, "and the public health field will benefit from a future focus of toxicological research on these identified sensitive mechanisms."

The coronavirus doesn't spread uniformly through a community.

But in the world of disease modeling, many projections take a high-level approach to a geographic area, like a county or state, and forecast based on a general idea that a virus will take root and spread at an equal rate until it reaches its peak of infection.

A research team led by UC Irvine and the University of Washington has created a new model of coronavirus diffusion through a community. This approach, published Sept. 10 in the Proceedings of the National Academy of Sciences, factors in network exposure -- whom one interacts with -- and demographics to simulate at a more detailed level both where and how quickly the coronavirus could spread through Seattle and 18 other major cities.

The team used U.S. Census Bureau tract demographics, simulation techniques and COVID-19 case data from spring 2020 to estimate a range of days for the virus to spread within a given city.

The result: Some neighborhoods peak sooner than others. And in every city, the virus sticks around far longer than some might expect.

"The most basic takeaway from this research is risk. People are at risk longer than they think, the virus will last longer than expected, and the point at which you think you don't need to be vigilant means that it just hasn't happened to you yet," said co-author Zack Almquist, an assistant professor of sociology at the UW.

Almquist and the team took on their study with two basic premises: Account for the social and geographic connections within a tract that could affect the course of the virus; and assume no vaccine or other major intervention alters its path. Then, based on actual COVID-19 and demographic data, project a likely scenario for spread over time.

Take Seattle. The study's map of the city outlines each census tract and provides a color-coded range of days each tract could take to reach peak infection before the virus goes into a low remission. The overall range is vast, from neighborhoods with the fastest peak -- 83 days -- to those that take more than 1,000. That's more than three years, assuming there is no significant intervention to stem the spread.

Denser neighborhoods in Seattle, such as Capitol Hill or the University District, reach peak infection rate earlier. But simulations predict that even nearby neighborhoods won't reach peak infection until weeks or even years later. These models predict more "burst-like" behavior of the virus' spread than standard models -- with short, sudden episodes of infection across the city, Almquist said.

In the study's model of Washington, D.C., census tracts also appear to reach peak infection rates at different times. Again, denser areas tend to peak sooner. But the network connections can cause "bursty" peak infection days, with some areas seeing early peak infections and others seeing it much later based on the neighborhoods' relative connections with each other, Almquist said.

Projecting the path of the virus can help estimate the impact on local hospitals. Researchers predicted this in several ways, such as modeling the number of cases per hospital over time and the number of days a hospital is at peak capacity.

The model of projected hospital cases shows how the geographic variations in the timing in peak COVID-19 infections could affect hospitals in different areas. Without outside intervention, some hospitals would remain at capacity for years, especially those farthest from major population centers.

These types of models are important because they provide a more detailed and nuanced prediction of an unknown like the novel coronavirus, said Almquist. Gauging how the virus might spread throughout a city and strain its hospitals can help local officials and health care providers plan for many scenarios. And while this study assumes no major interventions will rein in the virus, it's reasonable to believe the virus will linger to some degree, even with solutions such as a vaccine, according to Almquist.

"If you project these models for what it means over the country, we might expect to see some areas, such as rural populations, not see infection for months or even years before their peak infection occurs," Almquist said. "These projections, as well as others, are beginning to suggest that it could take years for the spread of COVID-19 to reach saturation in the population, and even if it does so it is likely to become endemic without a vaccine."

Researchers based in Brazil and the United States have completed the first-ever mapping exercise to profile the toxins produced by tube-dwelling anemones, or cerianthids, a family of marine animals belonging to the same phylum (Cnidaria) as sea anemones, jellyfish and corals. The analysis revealed that the toxins that can act on the nervous system, cardiovascular system, and cell walls, among other functions, paving the way to the discovery of novel medications.

“Tube anemones and sea anemones were assigned to the same family for a long time, but since 2014 our group has shown that aside from external anatomy they’re very different. They display distinct forms of behavior, lifecycle, and other traits. We assumed the toxins they produce must also be different,” said Sérgio Stampar, a professor in São Paulo State University’s School of Sciences and Letters (FCL-UNESP) at Assis, Brazil, and principal investigator for the study, which is published in the journal Marine Drugs.

The research was supported by FAPESP via funding for three projects (15/24408-4, 19/03552-0 and 17/50028-0), and was conducted in collaboration with scientists affiliated with the University of Kansas, the University of North Carolina at Charlotte and Florida Southern College.

The researchers took samples of the animals’ tentacles and extracted the RNA, which they then sequenced. They used bioinformatics software to classify most of what was transcribed, which they grouped into families of toxins. The analysis showed that 525 genes were associated with these substances.

The toxins belong to families also found in jellyfish, whose venoms burn humans and can even kill them. In addition, because anemones’ tentacles are part of their digestive system, the researchers expected to find similar compounds in both groups.

More than substances used in digestion, however, tube anemones produce neurotoxins and other substances that affect the bloodstream and destroy cell walls, as is typical of toxins used to kill prey and defend against predators.

“Curiously enough, there are no reports of accidents involving these animals,” Stampar said. “I’ve handled them without gloves a few times and never been stung. We don’t yet know why humans aren’t affected by their toxic arsenal.”

Toxin diversity

Isarachnanthus nocturnus, a species found in Brazil, was found to secrete toxins similar to those of the Australian box jellyfish (Chironex fleckeri), whose venom can be lethal to humans and forms pores in cell walls. Stampar’s group recently sequenced the mitochondrial genome of I. nocturnus, the largest of any animal sequenced to date (read more at: agencia.fapesp.br/30727).

One of the possible explanations for the diversity of toxins in the species is that its larval stage, which lasts about four months, is much longer than those of other tube anemones, which drift for two or three days in the water column before settling on the seabed. Like corals, tube anemones and sea anemones spend most of their lives attached to the ocean floor. I. nocturnus may have developed more effective defenses than other species because it interacts a great deal with predators.

I. nocturnus and Ceriantheomorphe brasiliensis were the only Brazilian species included in the study, which also analyzed Pachycerianthus borealis, the Atlantic tube anemone, found in North America, and Pachycerianthus maua, the Banded tube anemone, found in the Red Sea, Gulf of Aden, and Tanzania.

Hemostatic and hemorrhagic toxins were the most diverse in all four species. One of the toxins found belongs to the same family as the toxins produced by venomous reptiles and resembles the venom of the Komodo dragon (Varanus komodoensis), which uses it to kill mammals larger than itself.

Toxins that alter circulation offer potential for use in drugs to treat cardiovascular problems. Captopril, widely used to treat high blood pressure, is derived from the venom of the jararaca pit viper (Bothrops jararaca), for example.

The researchers also found innate immunity toxins and protease inhibitors, which belong to the family used in antiretroviral drugs against HIV, for example.

“It’s important to bear in mind that marine organisms have been around far longer than humans and have a much more elaborate chemical arsenal,” Stampar said. “As they evolved, they refined their defenses against viruses, bacteria, and even tumors. Isolating these substances could be well worth our while.”

One of the toxins the researchers identified is being tested on breast cancer cells by Karina Alves de Toledo, another professor at FCL-UNESP. Preliminary results have been promising and suggest the compound can kill cancer cells without damaging healthy cells.

Prospecting marine biodiversity for molecules is now one of the most promising branches of biotechnology. The global market for such products is projected to be worth USD 6.4 billion in 2025. Redemsivir, an antiviral drug used against Ebola and recently approved to treat COVID-19 patients in the United States, for example, is made from a substance found in sea sponges; a complete course of treatment can cost between USD 2,000 and USD 3,000 in the US.

Four new species described

In another study, reported in an article published in Records of the Australian Museum, Stampar and collaborators based in Australia and New Zealand described three new species of tube anemones found in the region and a fourth found in Antarctica. The latter, Pachycerianthus antarcticus, is the southernmost species known to science. This distinction previously pertained to a tube anemone that is native to Argentina and has also been described by Stampar’s group.

The Australian species Ceriantheopsis microbotanica is one of the smallest described to date. It is about 5 cm long, compared with 30-40 cm for the rest. It is native to the shallow waters of Botany Bay in Sydney.

“The material resulted from a dredging operation to extend the airport and had been stored in the museum for several years,” Stampar said. “I thought the first specimens I analyzed must be juveniles but realized they were adults when I examined their sexual structures. This may be an adaptation to the uninvitingly dark water.”

Stampar conducted the study while working as a visiting researcher at the Australian Museum on a project funded by FAPESP. Later a New Zealander contacted him to request help with descriptions of two local species. One, Pachycerianthus fiordlandensis, is common enough to be photographed frequently by divers yet had not been described by scientists. The other, Ceriantheopsis zealandiaensis, was described on the basis of two specimens collected in New Zealander region of Fiordland. There are currently 57 species of tube anemone.

An international team of researchers that includes a Texas A&M University professor has studied the lineage of dogs and found that there were at least five different types of dogs as far back as 11,000 years ago.

Anna Linderholm, director of the BiG (bioarchaeology and genomics) Laboratory and an archaeologist at Texas A&M, and a team of worldwide researchers have had their work published in the current issue of Science magazine.

The team studied dog DNA dating as far back as 11,000 years ago, immediately following the last Ice Age. By sequencing the DNA of 27 dogs found in Europe, the Near East and Siberia, team members discovered five different types of dogs with distinct genetic ancestries dating from before any other animal had been domesticated.

Linderholm was part of the genomics team that extracted DNA from skeletal material to see how dogs evolved from thousands of years ago when all humans were still hunters and gatherers.

"We examined dogs from across the old world, and they represent a period that stretches almost 11,000 years back in time," she said.

"The dog samples have been gathered from museums, and other collections from across the world and by several members of this team. Since we don't know when and where dogs were domesticated, we have collected most of the known dogs from the old world, going back as far in time as possible and using dog DNA that has been best preserved."

Linderhom said that samples were taken from collected dog remains, such as a tooth or a piece of bone. From the samples, the DNA was sequenced, enabling the team to read the genetic code that explains the origins of each dog and how it might have been related to modern-day dogs.

"By looking at a dog's genome, we can look at that dog's history, look at his parents and their parents and so on," she said. "It is much like today when people do an ancestry test for humans, trying to find out where they come from."

Linderholm added that dogs look similar genetically, meaning they share a more recent common ancestor.

"The five linages from over 11,000 years ago is more diversity than we have been able to identify before," she said. "Having said this, all dogs seem to have originated from one ancient wolf population, a wolf population that has since disappeared. We have no connection with our modern-day wolf populations with our first domesticated dogs."

She added that the human-dog bond can now be seen a bit more clearly. When humans moved, they almost always took their dogs with them.

"We see this happening when farming was introduced into Europe and other areas such as the Steppes in Asia," she said. "We note a clear link between the movement of people and the introduction of a new type of dogs. This is new, and we also don't see this pattern repeating itself when we have another large population movement. So humans were not always consistent in their actions at this time, but we do see a much greater connection between humans and their dogs, more so than any other animal."

Oct. 29, 2020-- A new study published online in the Annals of the American Thoracic Society examines whether the amount of RNA, or genomic load, of SARS-CoV-2 detected in swab tests of patients being admitted to the hospital with viral pneumonia is associated with more severe COVID-19. SARS-CoV-2 is the virus that causes COVID-19. Previous studies on this question have had conflicting results.

In "Association of SARS-CoV-2 Genomic Load With COVID-19 Patient Outcomes," Ioannis M. Zacharioudakis, MD, infectious disease specialist in the Department of Medicine at the New York University Grossman School of Medicine, and co-authors looked at the medical records of 314 patients who came to the NYU Langone Health emergency room between March 31 and April 10, 2020, diagnosed with COVID-19 on a molecular diagnostic (RT-PCR) test who also had viral pneumonia serious enough to require hospitalization. This research was conducted as a retrospective cohort study--one that follows former patients who had common characteristics.

"We demonstrated that for patients admitted to the hospital with COVID-19 pneumonia, SARS-CoV-2 load, as reflected by the cycle threshold (Ct) value of the PCR, should be looked at as a predictor of adverse outcomes," said Dr. Zacharioudakis. "High viral load was shown to be a predictor of poor outcomes above and beyond age, other medical problems and severity of illness on presentation, indicating that it can be used to risk-stratify, or triage, patients."

Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 are the most accurate class of COVID tests available today, and they can sample and analyze the greatest amount of genetic material, even at presymptomatic stages of the disease. In this study, respiratory samples that were analyzed by RT-PCR technology were gathered from patients using nasopharyngeal swabs, the long swabs that are widely used in health care settings as well as at public testing sites.

A cycle threshold value is one of the results that the PCR technique gives and can be used as a surrogate of the amount of virus that is detected on nasopharyngeal swabs. Since Ct value is obtained on most commercial RT-PCR testing platforms, it can prove a readily available tool to the provider to help risk-stratify and triage patients admitted to the hospital with COVID-19 pneumonia.

The researchers determined that study endpoints would include whether a patient required mechanical ventilation or extracorporeal membrane oxygenation (ECMO), and whether the patient died while in the hospital or was discharged to hospice. Statistical calculations were done to determine how frequently the endpoints were reached by patients who had high versus low viral load after adjusting for the patients' co-occurring conditions (comorbidities) using the Charlson Comorbidity Index and how severe the pneumonia was at the time of presentation, as shown in the Pneumonia Severity Index.

"We know that the virus multiplies rapidly in the asymptomatic and early symptomatic phases of COVID-19," Dr. Zacharioudakis stated. "Our study is in keeping with this conclusion, as indicated by our finding of higher viral load in patients who presented earlier in the disease."

He added: "The study also found that patients who had multiple comorbid conditions, such as heart disease, diabetes and cancer--or who were immunocompromised due to solid organ transplant--were more likely to have a higher SARS-CoV-2 load at hospital admission and as a result an increased risk for poor outcomes."

An important characteristic of this study was that it focused on patients who required admission to the hospital for COVID-19 pneumonia, a group who are at high risk for serious illness or death. The fact that the association of the high viral load with poor patient outcomes remained after taking into account the patients' underlying conditions, how long they were sick before coming to the hospital and how sick they were at the time they presented adds valuable evidence that demonstrates the ability of SARS-CoV-2 viral load to predict COVID outcomes.

The authors note that, among patients with a severe clinical presentation, those with a high SARS-CoV-2 viral load were almost twice as likely to get intubated or die.

Dr. Zacharioudakis added, "Our study provides a justification for using patients' SARS-CoV-2 load at the time of hospital admission to assess their risk of adverse outcomes. In an era when the availability of antiviral medications proven effective against COVID might be limited and the capacity for intensive monitoring is finite, it is of utmost importance to be able to prioritize the patients who will benefit the most from early treatment or a higher level of care. Further studies are needed to evaluate whether a decrease in viral load of patients hospitalized with COVID-19, who may or may not be treated with antiviral medications such as Remdesivir, correlate with an improvement in clinical status."

The plant pathogenic nematode Heterodera schachtii infects more than 200 different plants, including sugar beets, and causes significant economic losses. Over the past 50 years, the primary management tool in California has been crop rotation. When the number of H. schachtii in a soil exceeds a threshold, growers are contractually required by the local sugar factory to plant crops that do not support the nematode's reproduction. This practice reduces the nematode population so that the next sugar beet crop can flourish.

In a recent study from plant pathologists at the University of California, Riverside, the authors examined a soil fungus that parasitizes the nematode's females and eggs. This fungus, Hyalorbilia aff. multiguttulata (formerly Dactylella oviparasitica), was originally shown to cause a long-term suppression of cyst nematode populations in a field at the University of California Riverside's Agricultural Operations. Other scientists have detected closely related fungal species in Arkansas and California that were able to parasitize and destroy different important nematodes, including the soybean cyst and root-knot nematodes.

In the current study, the authors showed that similar fungi inhabited sugar beet fields in California, suggesting that a group of naturally occurring fungi, given the right conditions, might be able to dramatically reduce nematode populations in one season. Borneman, Becker, and colleagues detected identical or closely related Hyalorbilia species in 21 of 25 field soils. More importantly, baiting with young female H. schachtii and its host Swiss chard led to an approximately 10,000-fold increase in the population densities of these fungi over one nematode generation. "This research could lead to more frequent planting of sugar beets," explained James Borneman. "When the population densities of both the nematode and the fungus are above their threshold values, our research suggests that planting sugar beets would lead to the development of an H. schachtii-suppressive soil by the time the sugar beets are harvested."

"Relatively little is known about the Hyalorbilia spp., yet they appear to occur worldwide as effective parasites of cyst nematodes," said Borneman. "Nematode-suppressive soils are fascinating examples of natural pathogen control. In this example, the key to defeating the enemy is fungus' ability to destroy the mothership (the female nematode) before it can release hundreds of eggs into the soil."

BOSTON - Nearly one-third of cancer patients who decide to undergo surgery for their condition may have second thoughts, and this decision conflict may lead to less favorable treatment outcomes in both the near- and long-term, according to a team of investigators at Massachusetts General Hospital (MGH) and Ariadne Labs, a joint center for health systems innovation at the Harvard T.H. Chan School of Public Health and Brigham and Women's Hospital (BWH).

In a pilot study to see whether a survey and sensor data collected from a smartphone app could help identify clinically significant decision conflict in patients scheduled to undergo cancer surgery, Nikhil Panda, MD, MPH, from MGH and colleagues found that 27 percent reported having a conflict about their decision.

"When we followed that group out to 90 days after surgery, and even after accounting for potential differences between the group that reported conflict before surgery and the group that didn't, the people who said they had conflict were less active overall," Panda said. "In surgery, we know that if people are more active, it's an independent predictor of having better functional outcomes over the long term."

The findings are reported in the journal Annals of Surgery.

Patients with cancers that can be treated by surgery often wrestle with issues such as their treatment goals (for example, the potential for cure or symptom relief) and their health-related quality of life following treatment.

Cancer specialists try their best to engage patients in decision making regarding their care, but as Panda and colleagues write, "the lack of scalable, generalizable, and patient-centered outcome measurement tools means that many patients face cancer treatment, including surgery, without an understanding of how the intervention will affect outcomes that matter the most to them."

That lack of understanding can lead to clinically significant decision conflict, which has been shown in previous studies to be associated with problems such as patients not following treatment plans, strained patient-provider relationships and poorer emotional and psychological health.

To get a better understanding of the effects of decision conflict on postoperative health, the investigators recruited patients who were scheduled for surgery within a week or so to treat cancers of the breast, skin, soft tissues, abdomen or thyroid/parathyroid, and who owned a smartphone running on the Apple iOS or Android operating systems.

The patients were asked to download a data-gathering application that delivered to their phones the Decision Conflict Scale, a certified tool for measuring clinically significant decision conflict. The app also used the phone's motion-sensing accelerometer to gather continual data about activity following surgery.

Of 85 patients who downloaded the app and completed the Decision Conflict Scale, 27 percent reported clinically significant decision conflict, and although this group did not differ in pre-operative physical activity from the patients who did not report decision conflict, Panda and colleagues found that at 30, 60, and 90 days after surgery the patients with decision conflict had significantly lower levels of physical activity.

"If we can find something that's easily modifiable to improve that outcome, that would be a good thing. Factors such as obesity and smoking are very difficult to modify in the short term, but we may be able to reduce conflict by better informed consent, using decision aids, or improving communication between patients and their surgeons. These are all low-hanging fruit," Panda said.

Until now, scientists believed the male fin whale sings just one song pattern, which is unique to the males in his particular group -- but new research has blown this theory out of the water. The study, published in Frontiers in Marine Science, suggests that these endangered deep-sea giants actually sing multiple different songs, which may spread to different parts of the ocean through migrating individuals. Understanding the complexity of fin whale song provides new insights into how their populations move and change over time, helping efforts to better protect and manage the world's second largest mammal.

"There is still a lot of uncertainty around the fin whale population size and structure in the North Pacific, and so learning about the song could help us understand population dynamics in this region much better", says Dr Tyler Helble of the Naval Information Warfare Center Pacific, United States. "Male fin whales in the Pacific sing just two very low notes, which are produced in different rhythms to create song. Previously, some marine mammal scientists thought that fin whales each sang a single pattern of notes, which was found only within their specific group and region. Our research indicates that fin whale song is more complex than this".

Using hydrophones (underwater microphones), the team of researchers recorded the songs and locations of 115 whale encounters near Kauai, Hawaii over six years. Dr Regina Guazzo, also of the Naval Information Warfare Center Pacific, explains, "The sound is recorded on multiple hydrophones, allowing us to triangulate on the signal and formulate a position for the animal. By showing that different song patterns were coming from the same location, we demonstrated that these were likely made by the same individual".

Five main song patterns were recorded. Some were unique to this area, but some were similar to song patterns recorded several years before in populations off the north-west coast of the US. "When a new whale song is recorded in a region, researchers often read it as a signal that a new group or individual has arrived from a different part of the world", reveals Guazzo. "However, this study suggests that these new song patterns may have been picked up by a local whale on his migratory travels, in a process of cultural transmission between groups from different regions".

To confirm whether these whales recorded in Hawaiian waters are from a single population or multiple converging populations, scientists should use additional methods of monitoring the whales. "Visual identification, genetic analyses, or long-duration tags could be used to determine where these whales go when they are not singing off Kauai", Helble recommends.

Our Galaxy may be teeming with rogue planets, gravitationally unbound to any star. An international team of scientists, led by Polish astronomers, has announced the discovery of the smallest Earth-sized free-floating planet found to date.

Over four thousand extrasolar planets have been discovered to date. Although many of the known exoplanets do not resemble those in our solar system, they have one thing in common - they all orbit a star. However, theories of planet formation and evolution predict the existence of free-floating (rogue) planets, gravitationally unattached to any star. Indeed, a few years ago Polish astronomers from the OGLE team from the Astronomical Observatory of the University of Warsaw provided the first evidence for the existence of such planets in the Milky Way. Writing in Astrophysical Journal Letters, OGLE astronomers announced the discovery of the smallest rogue planet found to date.

Exoplanets can be only rarely directly observed. Usually, astronomers find planets using observations of the light from the planet's host star. For example, if a planet crosses in front of its parent star's disk, then the observed brightness of the star periodically drops by a small amount causing so called transits. Astronomers can also measure the motion of the star caused by the planet.

Free-floating planets emit virtually no radiation and - by definition - they do not orbit any host star, so they cannot be discovered using traditional methods of astrophysical detection. Nevertheless, rogue planets can be spotted using an astronomical phenomenon called gravitational microlensing. Microlensing results from Einstein's theory of general relativity - a massive object (the lens) may bend the light of a bright background object (the source). The lens' gravity acts as a huge magnifying glass which bends and magnifies the light of distant stars.

'If a massive object (a star or a planet) passes between an Earth-based observer and a distant source star, its gravity may deflect and focus light from the source. The observer will measure a short brightening of the source star' - explains dr Przemek Mroz, a postdoctoral scholar at the California Institute of Technology and a lead author of the study. 'Chances of observing microlensing are extremely slim because three objects - source, lens, and observer - must be nearly perfectly aligned. If we observed only one source star, we would have to wait almost a million year to see the source being microlensed' - he adds.

This is why modern surveys hunting for gravitational microlensing events are monitoring hundreds of millions of stars in the Milky Way center, where the chances of microlensing are highest. The OGLE survey - led by Warsaw University astronomers - carries out one of such experiments. OGLE is one of the largest and longest sky surveys, it started operations over 28 years ago. Currently, OGLE astronomers are using a 1.3-meter Warsaw Telescope located at Las Campanas Observatory, Chile. Each clear night, they point their telescope to the central regions of the Galaxy and observe hundreds of millions of stars, searching for those which change their brightness.

Gravitational microlensing does not depend on the lens' brightness, so it enables the study of faint or dark objects such as planets. Duration of microlensing events depends on the mass of the lensing object - the less massive the lens, the shorter the microlensing event. Most of the observed events, which typically last several days, are caused by stars. Microlensing events attributed to free-floating planets have timescales of barely a few hours. By measuring the duration of a microlensing event (and shape of its light curve) we can estimate the mass of the lensing object.

The scientists announced the discovery of the shortest-timescale microlensing event ever found, called OGLE-2016-BLG-1928, which has the timescale of just 42 minutes. 'When we first spotted this event, it was clear that it must have been caused by an extremely tiny object' - says dr Radoslaw Poleski from the Astronomical Observatory of the University of Warsaw, a co-author of the study. Indeed, models of the event indicate that the lens must have been less massive than Earth, it was probably a Mars-mass object. Moreover, the lens is likely a rogue planet. 'If the lens were orbiting a star, we would detect its presence in the light curve of the event' - adds dr Poleski. 'We can rule out the planet having a star within about 8 astronomical units (the astronomical unit is the distance between the Earth and the Sun)'.

OGLE astronomers provided the first evidence for a large population of rogue planets in the Milky Way a few years ago. However, the newly-detected planet is the smallest rogue world ever found. 'Our discovery demonstrates that low-mass free-floating planets can be detected and characterized using ground-based telescopes' - says Prof. Andrzej Udalski, the PI of the OGLE project.

Astronomers suspect that free-floating planets actually formed in protoplanetary disks around stars (as "ordinary" planets) and they have been ejected from their parent planetary systems after gravitational interactions with other bodies, for example, with other planets in the system. Theories of planet formation predict that the ejected planets should be typically smaller than Earth. Thus studying free-floating planets enables us to understand the turbulent past of young planetary systems, such as our solar system.

The search for free-floating planets is one of the science drivers of the Nancy Grace Roman Space Telescope, which is currently being constructed by NASA. The observatory is scheduled to start operations in the mid-2020s.

Because of the brevity of the event, additional observations collected by the Korea Microlensing Telescope Network (KMTNet) were needed to characterize the event. KMTNet operates a network of three telescopes - in Chile, Australia, and South Africa.

Embargoed until 4 a.m. CT/5 a.m. ET Thursday, Oct. 29, 2020

DALLAS, Oct. 29, 2020 -- Computed tomography angiogram (CTA) scans may offer fast and early detection of COVID-19 in acute ischemic stroke (AIS) patients, according to new research published today in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

The study, titled "The Utility of Apical Lung Assessment on CTA as a COVID-19 Screen in Acute Stroke," found that in addition to patient-reported COVID-19 symptoms, routine or standard care CTA scans were an accurate screening method for faster detection of COVID-19 since they include imaging of the upper portion of the lungs.

Researchers conducted a retrospective analysis of patients treated for AIS at three hospitals in the Bronx from March 1 to April 30, 2020, the height of the COVID-19 surge in New York City. A total of 57 patients who received a CTA scan within 24 hours of hospitalization for AIS were included in the study. Researchers used CTA scans to evaluate the lung apices (the upper area of the lungs) for signs of COVID-19 pneumonia. They then analyzed the accuracy of using CTA scans for COVID-19 diagnosis alone as well as in combination with patient-reported symptoms, such as cough and/or shortness of breath.

"Every second counts when treating a person experiencing a stroke," said Charles Esenwa, M.D., M.S., lead author of the study, an assistant professor and a stroke neurologist at the Albert Einstein College of Medicine in the Bronx, New York City. "Conducting a CTA is already part of the stroke management process, and these scans provide an opportunity to assess the lungs for signs suggestive of COVID-19. Our team sought to determine if this already necessary scan could have a secondary use of identifying potential COVID-19 patients more quickly than a standard nasal swab COVID-19 test."

The study defined confirmed COVID-19 positive cases from nasal swab PCR-test results, which are the standard required by the U.S. Food and Drug Administration (FDA) for COVID-19 testing, and it can take several days for results. Of the 57 study participants, three were diagnosed with COVID-19 prior to the date when a nasal swab COVID-19 test was administered.

Researchers found that:

CTA scans in combination with patient feedback to COVID-19 symptom questions were able to diagnose COVID-19 with 83% accuracy before results were received from traditional nasal swab tests in AIS patients.

30 of the 57 patients included in the study were COVID-19 positive.

20 of the COVID-19 positive patients and 2 of the COVID-19 negative patients had findings highly suspicious for COVID-19 pneumonia on their CTA lung scans.

"In combination with symptoms, CTA scan analysis is relatively accurate in diagnosing COVID-19, even compared to the nasal swab test. Since this analysis is much faster and at no extra cost, we hope it could be incorporated as a rapid diagnosis tool for patients with acute stroke," Esenwa said. "In addition, accurately diagnosing COVID-19 within hours, rather than the sometimes days wait-time to receive the results from nasal swab tests could help protect both patients and medical professionals."

While these findings are promising, the study had some limitations. As there is no universally defined standard for diagnosing COVID-19, the study confirmed infection positivity through the nasal swab COVID-19 test (RT-PCR). Patients who did not have the RT-PCR test performed were excluded from the study. Additionally, diagnostic accuracy may have been higher because the study participants were in an area with higher geographic incidence of COVID-19, which may not be the case in an area with a lower rate of COVID-19 infections.

"Screening questionnaires alone are often inaccurate because of the absence of symptoms or the patient is unable to speak because they are suffering from an acute stroke," Esenwa said. "Early diagnosis via CT scans has helped our center protect other patients and staff through early isolation, and it has also allowed us to start early supportive care for those suspected of having stroke who are COVID-19 positive," Esenwa added.

Embargoed until 4 a.m. CT / 5 a.m. ET Thursday, Oct. 29, 2020

DALLAS, Oct. 29, 2020 -- Patients in cardiac intensive care units (CICUs) could benefit from the CICU health care team using a daily checklist to prevent infections and other common complications, according to a new American Heart Association Scientific Statement, "Prevention of Complications in the Cardiac Intensive Care Unit," published today in the Association's flagship journal Circulation. This Statement reviews evidence from general medical and surgical ICUs to identify opportunities to apply them to the care of critically ill heart patients and improve CICU outcomes.

"Patients admitted to cardiac intensive care often have serious, non-cardiovascular conditions, such as lung, kidney or liver disease, increasing their risk for complications," said Christopher B. Fordyce, M.D., M.H.S., M.Sc., chair of the writing group for the Scientific Statement, an assistant professor in the division of cardiology at the University of British Columbia and director of the cardiac intensive care unit at Vancouver General Hospital in Vancouver, Canada. "Cardiac patients require increasingly complex care, and it is important for cardiovascular health care professionals to be experts in treating both cardiovascular and non-cardiovascular conditions, and to understand ways to prevent complications in the CICU."

Coordinated care for CICU patients includes a multi-disciplinary team of health care professionals across various specialties. The use of a daily, bedside checklist during patient rounds is encouraged to provide standardized approaches to preventative care.

The checklist includes strategies to optimize care and prevent complications related to:

infections;

pain management;

ventilator complications;
l
ack of mobilization (early mobilization is recommended for the majority of patients);

gastrointestinal complications and proper nutrition;

medication use and errors;

device use; and

inclusion of the appropriate specialists for multidisciplinary care.

Hand hygiene is a mainstay of infection prevention, and CICUs should monitor for the presence of pathogens. Other preventative strategies include proper cleaning and stringent disinfection of equipment and the environment.

Monitoring and support devices used in the CICU are also a source of potential infection. These include catheters, mechanical circulatory support and ventilators. The longer that these devices are used, the higher the risk of infection for these patients. Invasive devices should be used for as short a time as possible to reduce the risk of associated infections. Special attention to intravenous access sites, catheter placement, and monitoring for infection can reduce device-related infections and complications.

In the case of mechanical ventilation, required by more than 25% of CICU patients, noninvasive, positive pressure ventilation (e.g. ventilation through a nasal mask, face mask or nasal plugs) should be considered when appropriate. Daily, spontaneous breathing trials are important to test the patient's ability to breathe with minimal or no ventilator support. This allows early identification of patients who are ready to be taken off the ventilator.

Fordyce added, "A central tenet to preventing CICU complications is to anticipate the need for invasive procedures and devices to avoid emergency procedures when possible. Rates of infections and other complications are higher in urgent procedures."

As many as one-third of critically ill cardiac patients experience ICU-acquired muscle weakness, which can be reduced with early, progressive mobilization. Mobilization protocols can help improve physical functioning, decrease time on a ventilator and shorten a hospital stay.

Routine adherence to the checklist can also help minimize gastrointestinal complications, feeding complications, medication errors and adverse drug events that are prevalent in ICU settings. Malnutrition, hyperglycemia and stress ulcers - common in the CICU - are associated with adverse outcomes, including increased length of hospital stay, readmission, infection and in-hospital mortality. In addition, using the lowest effective dose of medicines minimizes the potential adverse effects of the high-risk cardiovascular medications that are frequently prescribed in the CICU.

"Cardiac critical care is a growing field, and there is an urgent need to implement strategies to optimize care among patients admitted to the CICU," said Fordyce. "These strategies can help CICU professionals anticipate and prevent complications in this unique patient population, and we encourage critical care teams to reflect upon their current practices and consider implementing these strategies where any gaps exist."

People with dementia are more likely to go missing in areas where road networks are dense, complicated and disordered - according to new research from the University of East Anglia.

Researchers studied hundreds of 'missing person' police reports for people with dementia and compared each case to the surrounding road network.

They hope their findings could help inform future safeguarding guidelines.

Prof Michael Hornberger, from UEA's Norwich Medical School, said: "People with dementia getting lost or going missing is a problem worldwide. Around 70 percent of people with dementia may go missing at least once, with some at risk of going missing multiple times.

"Around 40,000 people with dementia go missing for the first time every year in the UK - and this figure is likely to grow with the projected increase in the dementia population.

"Unfortunately, the first event when people with dementia go missing comes completely out of the blue, when doing such routine activities as going for a walk with the dog or getting the newspaper from the local shop.

"When a person with dementia goes missing, it can have life-threatening consequences. But very little is known about what actually causes people with dementia to go missing."

The research team set out to find out whether the design of road networks could be linked to people going missing.

They looked at 210 police records of people with dementia going missing in Norfolk over three years - and compared each case to the nearby road network.

PhD student Vaisakh Puthusseryppady, also from UEA's Norwich Medical School, said: "We know that people with dementia have difficulty navigating so we wanted to see whether there was a relationship between people going missing and the outdoor environment they went missing from.

"We were particularly interested in road layouts as they determine significantly our navigation, in particular the complexity of the road network, the complexity of road intersections, and how ordered the overall layout of the road network is.

"We found that the higher the density of road intersections, the more complicated the road intersections are, and the less ordered or less grid-like the overall road network layout, the greater the risk for people with dementia to get lost.

"We think this is because each road intersection represents a point at which a person needs to make a critical navigation decision. The more intersections there are, the more complex these intersections are, and the more disorganised the overall road network is - the bigger the problem for people with dementia.

"This is because these factors can make it more likely for people with dementia to make an error and make a wrong turn, causing them to get lost and go missing.

"We hope that by identifying these environmental risk factors, our findings can potentially help identify or predict areas where people with dementia may be at higher risk of going missing from - and contribute to the development of safeguarding guidelines to prevent them from going missing in future.

"It will also inform future recommendations for dementia-friendly urban design," he added.

BOSTON - Some patients with COVID-19 have persistent skin-related symptoms long after their initial infection has cleared, according to a new analysis. The findings, presented at the 29th Congress of the European Academy of Dermatology and Venereology by investigators at Massachusetts General Hospital (MGH), point to another burden experienced by so-called "long haulers" who get better but don't seem to fully recover from COVID-19.

For the analysis, researchers established an international registry for COVID-19 skin manifestations in April 2020, in collaboration with the International League of Dermatological Societies and the American Academy of Dermatology. Clinicians were contacted in June and August to update COVID-19 laboratory test results and the duration of patients' COVID-19 skin symptoms. The team defined long haulers as anyone with skin symptoms of COVID-19 that persisted for at least 60 days.

The team evaluated almost 1,000 cases of patients with skin manifestations of COVID-19. Among 224 total suspected cases and 90 laboratory-confirmed cases of COVID-19 from 39 countries with information on symptom duration, the median duration of symptoms was 12 days. Rash-like morbilliform and urticarial eruptions lasted a median of seven days and four days, respectively, for patients with lab-confirmed COVID-19, with a maximum duration of 28 days. Papulosquamous eruptions, which are scaly papules and plaques, lasted a median of 20 days in lab-confirmed cases, with one confirmed long hauler eruption lasting 70 days. Pernio/chilblains, or redness and swelling of the feet and hands, commonly known as "COVID toes," lasted a median of 15 days in patients with suspected COVID-19 and 10 days in lab-confirmed cases. Notably, six patients with pernio/chilblains were long haulers with toe symptoms lasting at least 60 days, with two lab-confirmed patients with COVID toes lasting longer than 130 days.

"Our findings reveal a previously unreported subset of patients with long-standing skin symptoms from COVID-19, in particular those with COVID toes. This data adds to our knowledge about the long-term effects of COVID-19 in different organ systems. The skin is potentially a visible window into inflammation that could be going on in the body," said senior author Esther E. Freeman, MD, PhD, director of Global Health Dermatology at MGH. "We encourage clinicians taking care of patients with COVID-19 to ask about and evaluate any skin symptoms. Health care providers can enter information into our registry to further our understanding of the dermatologic effects of COVID-19."

LUGANO, 29 October, 2020 - Some COVID-19 patients experience long-lasting skin symptoms that vary according to type of COVID-19 skin rash, a late-breaking abstract will reveal today at the 29th EADV Congress, EADV Virtual.

Analysis of the largest registry of COVID-19 patients with dermatological symptoms has revealed a subset of patients, called 'long-haulers' or 'long COVID', who experience prolonged symptoms (lasting >60 days) on their skin (1).

Data from 990 cases from 39 countries input into the registry, a collaboration between the International League of Dermatological Societies and the American Academy of Dermatology, show an average duration of 12 days for all dermatological symptoms, with some lasting as long as >150 days (1).

Patients presented with a broad spectrum of dermatologic manifestations lasting for different lengths of time, including hives (urticaria), lasting for median 5 days, and pernio/chilblains (''COVID toes''), lasting 15 days but sometimes as long as 130-150 days, and papulosquamous eruptions, which are scaly papules and plaques, persisting for 20 days (1).

The identification of this unique subset of "COVID toes" patients with symptoms lasting long after the acute phase of COVID-19 may have implications for understanding the prolonged inflammatory response in some patients after infection.

Skin symptoms vary by COVID-19 severity. Some symptoms, such as retiform purpura, are associated with severe COVID-19, since 100% of these patients were hospitalised, while COVID toes travel with relatively mild disease, with only 16% hospitalised. Furthermore, although COVID toes often appear 1-4 weeks after initial infection, 15% were found to still be PCR positive for COVID-19.

Dr Esther Freeman, Principal Investigator of the International COVID-19 Dermatology Registry and Director, Global Health Dermatology, Massachusetts General Hospital says: "Our registry identified a previously unreported subset of patients with longstanding skin symptoms from COVID-19. We highlight patients with pernio/chilblains, also known as COVID toes, who have had symptoms for as long as 150 days. This data adds to our knowledge about how COVID-19 can affect multiple different organ systems, even after patients have recovered from their acute infection. The skin can provide a visual window into inflammation that may be going on elsewhere in the body."

At EADV 2020, COVID-19 is a key talking point and something that the world is learning more about every day. Dermatological symptoms of COVID-19 and the impact of COVID-19 on dermatology practitioners and patients is just beginning to be understood and is being explored at the Congress.

An EADV survey of 490 dermatologists has revealed that 35% saw patients presenting skin-signs of COVID-19 and that 4% of the dermatologists themselves tested positive for COVID-19 (2). These findings highlight the need for further research into the dermatological symptoms of COVID-19 and the interaction between COVID and underlying skin conditions. These data also stress the importance of using protection means such as facemasks during dermatological consultations.

Finally, Dr Asja Prohic, Medical Faculty University of Sarajevo, is presenting growing research investigating the possible association between male pattern baldness (androgenetic alopecia) and men hospitalised with COVID-19 (3).

A new analysis of federal surveys on health insurance coverage concludes that the number of uninsured Americans increased by about 2.3 million between 2016 and 2019. The analysis by researchers at Harvard Medical School and the City University of New York's Hunter College, published today in Health Affairs blog, concludes that the contraction of coverage under President Trump caused at least 3,399, and perhaps as many as 25,180, excess deaths even before the onset of the COVID-19 pandemic. 

The researchers examined results of three benchmark federal surveys that collect data on health insurance coverage -- the American Community Survey (ACS), the Current Population Survey, and the National Health Interview Survey.  All three surveys indicate that uninsurance has risen under President Trump, but the researchers cite the ACS results as the most reliable. (Changes in methodology and data collection processes since 2016 hinder interpretation of year-to-year changes in the other two federal surveys). Using the ACS-based data indicating that the number of uninsured Americans has risen by 2.3 million, the researchers calculated the number of resulting excess deaths by applying estimates of the mortal consequences of being uninsured from previous rigorous, peer-reviewed studies.

"I see that my uninsured patients often can't get the care they need, and research proves that many who lack coverage die as a result," noted study author Dr. Steffie Woolhandler, a Distinguished Professor of Urban Public Health at Hunter College and Lecturer at Harvard Medical School. "President Trump has tried at every turn to undermine the ACA and chip away at coverage. That's costing thousands of lives," she added.

"Our analysis warns that much worse is ahead if the Supreme Court overturns the ACA, as Trump's Justice Department is advocating," stated lead author Dr. Adam Gaffney, a pulmonary and critical care physician at Harvard Medical School and the Cambridge Health Alliance. "Gutting the ACA  would throw another 19.9 million Americans off of insurance, and cause up to 68,345 extra deaths each year. We need to expand insurance, not shrink it. With 30 million uninsured today, we could save thousands of lives by achieving universal coverage," he added.