Culture

UVA researchers have discovered that concussions and traumatic brain injuries, even when mild, cause swelling that blocks the brain's ability to clean itself of harmful toxins and debris.

In addition to an immediate impact on memory and brain inflammation, this may seed the brain for Alzheimer's, dementia and other neurodegenerative diseases.

The discovery helps explain why repeated brain injuries are so harmful and suggests they increase the risk of long-term problems.

It also suggests a reason why blows to the head affect different people differently.

The findings point to a new approach to treating brain injury and could lead to a better way to determine when it is safe for athletes and military personnel to resume their duties.

Even mild concussions cause severe and long-lasting impairments in the brain's ability to clean itself of toxins, and this may seed it for Alzheimer's disease, dementia and other neurodegenerative problems, new research from the University of Virginia School of Medicine reveals.

The discovery offers important insights into traumatic brain injury (TBI), a poorly understood condition that has become a major public concern, particularly in sports and for the military. The findings help explain why TBI is so harmful and why it can have such long-term effects. The research also suggests that certain patients are at greater risk of a decline in brain function later in life, and it paves the way for new and better treatments.

"This provides some of the best evidence yet that if you haven't recovered from a brain injury and you get hit in the head again, you're going to have even more severe consequences," said John Lukens, PhD, of UVA's Department of Neuroscience and the Center for Brain Immunology and Glia (BIG). "This reinforces the idea that you have to give people an opportunity to heal. And if you don't, you're putting yourself at a much higher risk for long-term consequences that you might not see in a year but could see in a couple of decades."

New Understanding of TBI

Lukens' research identifies a previously unknown consequence of TBI that can have long-lasting effects. When the brain swells, it presses against the skull; trapped in-between are tiny lymphatic vessels that clean the brain. This pressure on the vessels, the UVA researchers found, causes serious and long-lasting impairment of the brain's ability to purge itself of toxins. Working with lab mice, one of the best models of TBI available, the scientists found the impairment could last at least two weeks - a long time for mice - and possibly much longer.

These lymphatic vessels were identified by Jonathan Kipnis, PhD, and his collaborators at UVA in 2015. Until then, medical textbooks insisted the vessels did not exist and that the brain was "immune privileged," meaning that it did not interact with the immune system. Kipnis' discovery changed all that, and he has since determined the vessels play important roles in both Alzheimer's and the cognitive decline that comes with age.

Now they emerge as an important player in TBI. "We know that traumatic brain injury carries an increased risk for a bunch of long-term issues like dementia, Alzheimer's disease and CTE [chronic traumatic encephalopathy], and this has really been made extra public because of the NFL," said researcher Ashley C. Bolte, an MD/PhD student. "Then there's also anxiety, depression, suicide. The reasons why TBI results in increased risk for this isn't totally known, and we think that our findings might provide a mechanism as to why."

People Most at Risk

The research suggests that people who have pre-existing problems with their brain drainage, either from prior concussions or naturally, are likely to suffer much more severe consequences from TBI. In mice, this led to more brain inflammation and worse outcomes, including memory impairment. "If you have a pre-existing kink in the pipes and you get hit in the head, then everything is taken to a higher level - the impacts on memory, the neuroinflammation," Lukens said. "There are a lot of implications to it."

Emerging imaging technology may eventually make it possible for doctors to identify people who will suffer the greatest consequences of TBI. More good news: Lukens also believes that doctors may one day be able to rejuvenate the impaired lymphatic vessels with drugs to improve patients' outcomes and possibly stave off long-term consequences. (This also may prove useful in the battle against the cognitive decline that naturally occurs with age.)

In addition, Lukens said, it eventually may be possible for doctors to evaluate brain drainage after injury to determine when it is safest for patients to return to action.

"Right now, we really don't know what to tell these kids who want to get back out on the field, or even members of the military," Lukens said. "It would be important to have empirical tests to say you can continue or never to do those things ever again."

Researchers at Tel Aviv University (TAU) have analyzed 18 ancient texts dating back to around 600 BCE from the Tel Arad military post using state-of-the-art image processing, machine learning technologies, and the expertise of a senior handwriting examiner. They have concluded that the texts were written by no fewer than 12 authors, suggesting that many of the inhabitants of the kingdom of Judah during that period were able to read and write, with literacy not reserved as an exclusive domain in the hands of a few royal scribes.

The special interdisciplinary study was conducted by TAU's Dr. Arie Shaus, Ms. Shira Faigenbaum-Golovin, and Dr. Barak Sober of the Department of Applied Mathematics; Prof. Eli Piasetzky of the Raymond and Beverly Sackler School of Physics and Astronomy; and Prof. Israel Finkelstein of the Jacob M. Alkow Department of Archeology and Ancient Near Eastern Civilizations. The forensic handwriting specialist, Ms. Yana Gerber, is a senior expert who served for 27 years in the Questioned Documents Laboratory of the Israel Police Division of Identification and Forensic Science and its International Crime Investigations Unit.

The results were published in PLOS ONE on September 9, 2020.

"There is a lively debate among experts as to whether the books of Deuteronomy, Joshua, Judges, Samuel, and Kings were compiled in the last days of the kingdom of Judah or after the destruction of the First Temple by the Babylonians," Dr. Shaus explains. "One way to try to get to the bottom of this question is to ask when there was the potential for the writing of such complex historical works.

"For the period following the destruction of the First Temple in 586 BC, there is very scant archaeological evidence of Hebrew writing in Jerusalem and its surroundings, but an abundance of written documents has been found for the period preceding the destruction of the Temple. But who wrote these documents? Was this a society with widespread literacy, or was there just a handful of literate people?"

To answer this question, the researchers examined the ostraca (fragments of pottery vessels containing ink inscriptions) writings discovered at the Tel Arad site in the 1960s. Tel Arad was a small military post on the southern border of the kingdom of Judah; its built-up area was about 20,000 square feet and it housed between 20 and 30 soldiers.

"We examined the question of literacy empirically, from different directions of image processing and machine learning," says Ms. Faigenbaum-Golovin. "Among other things, these areas help us today with the identification, recognition, and analysis of handwriting, signatures, and so on. The big challenge was to adapt modern technologies to 2,600-year-old ostraca. With a lot of effort, we were able to produce two algorithms that could compare letters and answer the question of whether two given ostraca were written by two different people."

In 2016, the researchers theorized that 18 of the Tel Arad inscriptions were written by at least four different authors. Combined with additional textual evidence, the researchers concluded that there were in fact at least six different writers. The study aroused great interest around the world.

The TAU researchers then decided to compare the algorithmic methods, which have since been refined, to the forensic approach. To this end, Ms. Gerber joined the team. After an in-depth examination of the ancient inscriptions, she found that the 18 texts were written by at least 12 distinct writers with varying degrees of certainty. She examined the original Tel Arad ostraca at the Israel Museum, the Eretz Israel Museum, the Sonia and Marco Nedler Institute of Archaeology of Tel Aviv University, and the Israel Antiquities Authority's warehouses at Beit Shemesh.

Ms. Gerber explained:

"This study was very exciting, perhaps the most exciting in my professional career. These are ancient Hebrew inscriptions written in ink on shards of pottery, utilizing an alphabet that was previously unfamiliar to me. I studied the characteristics of the writing in order to analyze and compare the inscriptions, while benefiting from the skills and knowledge I acquired during my bachelor's degree studies in classical archaeology and ancient Greek at Tel Aviv University. I delved into the microscopic details of these inscriptions written by people from the First Temple period, from routine issues such as orders concerning the movement of soldiers and the supply of wine, oil, and flour, through correspondence with neighboring fortresses, to orders that reached the Tel Arad fortress from the high ranks of the Judahite military system. I had the feeling that time had stood still and there was no gap of 2,600 years between the writers of the ostraca and ourselves.

"Handwriting is made up of unconscious habit patterns. The handwriting identification is based on the principle that these writing patterns are unique to each person and no two people write exactly alike. It is also assumed that repetitions of the same text or characters by the same writer are not exactly identical and one can define a range of natural handwriting variations specific to each one. Thus, forensic handwriting analysis aims at tracking features corresponding to specific individuals, and concluding whether a single or rather different authors wrote the given documents.

"The examination process is divided into three steps: analysis, comparison, and evaluation. The analysis includes a detailed examination of every single inscription, according to various features, such as the spacing between letters, their proportions, slant, etc. The comparison is based upon the aforementioned features across various handwritings. In addition, consistent patterns,such the same combinations of letters, words, and punctuation, are identified. Finally, an evaluation of identicalness or distinctiveness of the writers is made. It should be noted that, according to an Israel Supreme Court ruling, a person can be convicted of a crime based on the opinion of a forensic handwriting expert."

Dr. Shaus further elaborated:

"We were in for a big surprise: Yana identified more authors than our algorithms did. It must be understood that our current algorithms are of a "cautious" nature -- they know how to identify cases in which the texts were written by people with significantly different writing; in other cases they refrain from definite conclusions. In contrast, an expert in handwriting analysis knows not only how to spot the differences between writers more accurately, but in some cases may also arrive at the conclusion that several texts were actually written by a single person. Naturally, in terms of consequences, it is very interesting to see who the authors are. Thanks to the findings, we were able to construct an entire flowchart of the correspondence concerning the military fortress -- who wrote to whom and regarding what matter. This reflects the chain of command within the Judahite army.

"For example, in the area of Arad, close to the border between the kingdoms of Judah and Edom, there was a military force whose soldiers are referred to as "Kittiyim" in the inscriptions, most likely Greek mercenaries. Someone, probably their Judahite commander or liaison officer, requested provisions for the Kittiyim unit. He writes to the quartermaster of the fortress in Arad "give the Kittiyim flour, bread, wine" and so on. Now, thanks to the identification of the handwriting, we can say with high probability that there was not only one Judahite commander writing, but at least four different commanders. It is conceivable that each time another officer was sent to join the patrol, they took turns."

According to the researchers, the findings shed new light on Judahite society on the eve of the destruction of the First Temple -- and on the setting of the compilation of biblical texts. Dr. Sober explains:

"It should be remembered that this was a small outpost, one of a series of outposts on the southern border of the kingdom of Judah. Since we found at least 12 different authors out of 18 texts in total, we can conclude that there was a high level of literacy throughout the entire kingdom. The commanding ranks and liaison officers at the outpost, and even the quartermaster Eliashib and his deputy, Nahum, were literate. Someone had to teach them how to read and write, so we must assume the existence of an appropriate educational system in Judah at the end of the First Temple period. This, of course, does not mean that there was almost universal literacy as there is today, but it seems that significant portions of the residents of the kingdom of Judah were literate. This is important to the discussion on the composition of biblical texts. If there were only two or three people in the whole kingdom who could read and write, then it is unlikely that complex texts would have been composed."

Prof. Finkelstein concludes:

"Whoever wrote the biblical works did not do so for us, so that we could read them after 2,600 years. They did so in order to promote the ideological messages of the time. There are different opinions regarding the date of the composition of biblical texts. Some scholars suggest that many of the historical texts in the Bible, from Joshua to II Kings, were written at the end of the 7th century BC, very close to the period of the Arad ostraca. It is important to ask who these texts were written for. According to one view, there were events in which the few people who could read and write stood before the illiterate public and read texts out to them. A high literacy rate in Judah puts things into a different light.

"Until now, the discussion of literacy in the kingdom of Judah has been based on circular arguments, on what is written within the Bible itself, for example on scribes in the kingdom. We have shifted the discussion to an empirical perspective. If in a remote place like Tel Arad there was, over a short period of time, a minimum of 12 authors of 18 inscriptions, out of the population of Judah which is estimated to have been no more than 120,000 people, it means that literacy was not the exclusive domain of a handful of royal scribes in Jerusalem. The quartermaster from the Tel Arad outpost also had the ability to read and appreciate them."

Face masks have become an important tool in fighting against the COVID-19 pandemic. However, improper use or disposal of masks may lead to "secondary transmission". A research team from City University of Hong Kong (CityU) has successfully produced graphene masks with an anti-bacterial efficiency of 80%, which can be enhanced to almost 100% with exposure to sunlight for around 10 minutes. Initial tests also showed very promising results in the deactivation of two species of coronaviruses. The graphene masks are easily produced at low cost, and can help to resolve the problems of sourcing raw materials and disposing of non-biodegradable masks.

The research is conducted by Dr Ye Ruquan, Assistant Professor from CityU's Department of Chemistry, in collaboration with other researchers. The findings were published in the scientific journal ACS Nano, titled "Self-Reporting and Photothermally Enhanced Rapid Bacterial Killing on a Laser-Induced Graphene Mask".

Commonly used surgical masks are not anti-bacterial. This may lead to the risk of secondary transmission of bacterial infection when people touch the contaminated surfaces of the used masks or discard them improperly. Moreover, the melt-blown fabrics used as a bacterial filter poses an impact on the environment as they are difficult to decompose. Therefore, scientists have been looking for alternative materials to make masks.

Converting other materials into graphene by laser

Dr Ye has been studying the use of laser-induced graphene in developing sustainable energy. When he was studying PhD degree at Rice University several years ago, the research team he participated in and led by his supervisor discovered an easy way to produce graphene. They found that direct writing on carbon-containing polyimide films (a polymeric plastic material with high thermal stability) using a commercial CO2 infrared laser system can generate 3D porous graphene. The laser changes the structure of the raw material and hence generates graphene. That's why it is named laser-induced graphene.

Graphene is known for its anti-bacterial properties, so as early as last September, before the outbreak of COVID-19, producing outperforming masks with laser-induced graphene already came across Dr Ye's mind. He then kick-started the study in collaboration with researchers from the Hong Kong University of Science and Technology (HKUST), Nankai University, and other organisations.

Excellent anti-bacterial efficiency

The research team tested their laser-induced graphene with E. coli, and it achieved high anti-bacterial efficiency of about 82%. In comparison, the anti-bacterial efficiency of activated carbon fibre and melt-blown fabrics, both commonly-used materials in masks, were only 2% and 9% respectively. Experiment results also showed that over 90% of the E. coli deposited on them remained alive even after 8 hours, while most of the E. coli deposited on the graphene surface were dead after 8 hours. Moreover, the laser-induced graphene showed a superior anti-bacterial capacity for aerosolised bacteria.

Dr Ye said that more research on the exact mechanism of graphene's bacteria-killing property is needed. But he believed it might be related to the damage of bacterial cell membranes by graphene's sharp edge. And the bacteria may be killed by dehydration induced by the hydrophobic (water-repelling) property of graphene.

Previous studies suggested that COVID-19 would lose its infectivity at high temperatures. So the team carried out experiments to test if the graphene's photothermal effect (producing heat after absorbing light) can enhance the anti-bacterial effect. The results showed that the anti-bacterial efficiency of the graphene material could be improved to 99.998% within 10 minutes under sunlight, while activated carbon fibre and melt-blown fabrics only showed an efficiency of 67% and 85% respectively.

The team is currently working with laboratories in mainland China to test the graphene material with two species of human coronaviruses. Initial tests showed that it inactivated over 90% of the virus in five minutes and almost 100% in 10 minutes under sunlight. The team plans to conduct testings with the COVID-19 virus later.

Their next step is to further enhance the anti-virus efficiency and develop a reusable strategy for the mask. They hope to release it to the market shortly after designing an optimal structure for the mask and obtaining the certifications.

Dr Ye described the production of laser-induced graphene as a "green technique". All carbon-containing materials, such as cellulose or paper, can be converted into graphene using this technique. And the conversion can be carried out under ambient conditions without using chemicals other than the raw materials, nor causing pollution. And the energy consumption is low.

"Laser-induced graphene masks are reusable. If biomaterials are used for producing graphene, it can help to resolve the problem of sourcing raw material for masks. And it can lessen the environmental impact caused by the non-biodegradable disposable masks," he added.

Dr Ye pointed out that producing laser-induced graphene is easy. Within just one and a half minutes, an area of 100 cm² can be converted into graphene as the outer or inner layer of the mask. Depending on the raw materials for producing the graphene, the price of the laser-induced graphene mask is expected to be between that of surgical mask and N95 mask. He added that by adjusting laser power, the size of the pores of the graphene material can be modified so that the breathability would be similar to surgical masks.

A new way to check the condition of the mask

To facilitate users to check whether graphene masks are still in good condition after being used for a period of time, the team fabricated a hygroelectric generator. It is powered by electricity generated from the moisture in human breath. By measuring the change in the moisture-induced voltage when the user breathes through a graphene mask, it provides an indicator of the condition of the mask. Experiment results showed that the more the bacteria and atmospheric particles accumulated on the surface of the mask, the lower the voltage resulted. "The standard of how frequently a mask should be changed is better to be decided by the professionals. Yet, this method we used may serve as a reference," suggested Dr Ye.

Using public transportation, visiting a place of worship, or otherwise traveling from the home is associated with a significantly higher likelihood of testing positive with the coronavirus SARS-CoV-2, while practicing strict social distancing is associated with a markedly lower likelihood, suggests a study from researchers at the Johns Hopkins Bloomberg School of Public Health.

For their analysis, the researchers surveyed a random sample of more than 1,000 people in the state of Maryland in late June, asking about their social distancing practices, use of public transportation, SARS-CoV-2 infection history, and other COVID-19-relevant behaviors. They found, for example, that those reporting frequent public transport use were more than four times as likely to report a history of testing positive for SARS-CoV-2 infection, while those who reported practicing strict outdoor social distancing were just a tenth as likely to report ever being SARS-CoV-2 positive.

The study is believed to be among the first large-scale evaluations of COVID-19-relevant behaviors that is based on individual-level survey data, as opposed to aggregated data from sources such as cellphone apps.

The results were published online on September 2 in Clinical Infectious Diseases.

"Our findings support the idea that if you're going out, you should practice social distancing to the extent possible because it does seem strongly associated with a lower chance of getting infected," says study senior author Sunil Solomon, MBBS, PhD, MPH, an associate professor in the Bloomberg School's Department of Epidemiology and an associate professor of medicine at Johns Hopkins School Medicine. "Studies like this are also relatively easy to do, so we think they have the potential to be useful tools for identification of places or population subgroups with higher vulnerability."

The novel coronavirus SARS-CoV-2 has infected nearly 27 million people around the world, of whom some 900,000 have died, according to the World Health Organization. In the absence of a vaccine, public health authorities have emphasized practices such as staying at home, and wearing masks and maintaining social distancing while in public. Yet there hasn't been a good way to monitor whether--and among which groups--such practices are being followed.

Solomon and colleagues, including first author Steven Clipman, a PhD candidate in the Bloomberg School's Department of International Health, quickly accessed willing survey participants via a company that maintains a large nationwide pool of potential participants as a commercial service for market research. The 1,030 people included in the study were all living in Maryland, which has logged more than 113,000 SARS-CoV-2 confirmed cases and nearly 3,700 confirmed deaths, according to the Maryland Department of Health.

The researchers asked the survey participants questions about recent travel outside the home, their use of masks, social distancing and related practices, and any confirmed infection with SARS-CoV-2 either recently or at all.

The results indicated that 55 (5.3 percent) of the 1,030 participants had tested positive for SARS-CoV-2 infection at any time, while 18 (1.7 percent) reported testing positive in the two weeks before they were surveyed.

The researchers found that when considering all the variables they could evaluate, spending more time in public places was strongly associated with having a history of SARS-CoV-2 infection. For example, an infection history was about 4.3 times more common among participants who stated that they had used public transportation more than three times in the prior two weeks, compared to participants who stated they had never used public transportation in the two-week period.

An infection history also was 16 times more common among those who reported having visited a place of worship three or more times in the prior two weeks, compared to those who reported visiting no place of worship during the period. The survey did not distinguish between visiting a place of worship for a religious service or other purposes, such as a meeting, summer camp or meal.

Conversely, those who reported practicing social distancing outdoors "always" were only 10 percent as likely to have a SARS-CoV-2 history, compared to those who reported "never" practicing social distancing.

An initial, relatively simple analysis linked many other variables to SARS-CoV-2 infection history, including being Black or Hispanic. But a more sophisticated, "multivariable" analysis suggested that many of these apparent links were largely due to differences in movement and social distancing.

"When we adjusted for other variables such as social distancing practices, a lot of those simple associations went away, which provides evidence that social distancing is an effective measure for reducing SARS-CoV-2 transmission," Clipman says.

The data indicated a greater adoption of social distancing practices among some groups who are especially vulnerable to serious COVID-19 illness, suggesting that they were relatively aware of their vulnerability. For example, 81 percent of over-65 participants reported always practicing social distancing at outdoor activities, while only 58 percent of 18-24 year olds did so.

The results are consistent with the general public health message that mask-wearing, social distancing, and limiting travel whenever possible reduce SARS-CoV-2 transmission. The researchers suggest, though, that studies such as these, employing similarly rapid surveys of targeted groups, could also become useful tools for predicting where and among which groups infectious diseases will spread most quickly.

"We did this study in Maryland in June, and it showed among other things that younger people in the state were less likely to reduce their infection risk with social distancing--and a month later a large proportion of the SARS-CoV-2 infections detected in Maryland was among younger people," says Solomon. "So, it points to the possibility of using these quick, inexpensive surveys to predict where outbreaks are going to happen based on behaviors, and then mobilizing public health resources accordingly."

Solomon and his team are now conducting similar surveys in other states and are studying the surveys' potential as predictive epidemiological tools.

Interferon (IFN) responses are one of the first defenses the body mounts against viral infections, and research has shown that it plays a role controlling viral replication. But when researchers at Baylor College of Medicine investigated whether IFN restricted human norovirus (HuNoV) infection in human intestinal enteroids (HIEs), a cultivation system that recapitulates many of the characteristics of the human infection, they unexpectedly discovered that endogenous IFN responses by HIEs restricted growth of HuNoV strain GII.3, but not of GII.4, the most common strain worldwide.

The findings, published in the Proceedings of the National Academy of Sciences USA, highlight the importance of considering strain differences when studying HuNoV biology and designing therapies.

"HuNoVs cause the majority of the cases of viral gastroenteritis in the world and bring about significant mortality in all age groups; yet, there are still no vaccines or other approved therapeutic strategies available," said first author Shih-Ching Lin, a graduate student in the laboratory of Dr. Mary Estes at Baylor. "In-depth studies of how virus and host interact have been possible only recently thanks to the development of several laboratory cultivation systems. In this study, we worked with HIEs to investigate their response to HuNoV infection and how it affects viral replication."

Novel insights into the interplay between HuNoV and HIEs

The researchers infected HIEs with HuNoV strain GII.3 or pandemic strain GII.4 and determined which HIE genes were activated as a result.

"We discovered that both strains preferentially triggered a type III IFN response, including activation of a number of IFN-stimulated genes, as well as increases in a subset of long non-coding RNAs. Changes in long non-coding RNAs, which are known to regulate gene expression, had never been reported before for gastrointestinal virus infections," Lin said.

Next, Lin, Estes and their colleagues studied the effect of IFN on the replication of HuNoV. Adding IFN to the cultures reduced replication of both strains, suggesting that IFN may have value as therapeutics for HuNoV infections. This could be important for chronically infected immunocompromised patients who can suffer with diarrhea for years.

To obtain insights into the genes of the IFN pathway that contribute to the antiviral response to HuNoV, the researchers knocked out several of these genes in HIE cultures, infected them with strain GII.3 or GII.4 and measured the rate of viral proliferation.

"We expected that the absence of IFN responses by HIEs would promote viral replication in both strains. It was surprising and very exciting to find significant strain differences," Lin said.

"We saw that only strain GII.3 was able to spread and multiply more when HIEs could not activate IFN responses. Replication of GII.4, on the other hand, was not enhanced," said Estes, Cullen Foundation Endowed Chair and Distinguished Service Professor of molecular virology and microbiology at Baylor. Estes also is a member of the Dan L Duncan Comprehensive Cancer Center. "It was exciting to see the GII.3 strain proliferate and spread in the cultures as we had never seen it before."

"The strain-specific sensitivities of innate IFN responses to HuNoV replication we observed provide a potential explanation for why GII.4 infections are more widespread and become pandemic," Lin said. "Our findings also show the importance of keeping potential strain differences in mind when studying the biology of HuNoV and developing therapies. Our new genetically modified HIE cultures also will be useful tools for studying innate immune responses to other viral or microbial pathogens."

Philadelphia, September 10, 2020 - Investigators have determined that treating patients with an advanced form of age-related macular degeneration (AMD) with levodopa, a safe and readily available drug commonly used to treat Parkinson's disease, stabilized and improved their vision. It reduced the number of treatments necessary to maintain vision, and as such, will potentially reduce the burden of treating the disease, financially and otherwise. Their findings appear in the American Journal of Medicine, published by Elsevier.

More than 15 percent of the US population over the age of 70 has AMD, a common cause of blindness in developed nations. Neovascular AMD (nAMD) is characterized by the abnormal growth of new blood vessels, triggered by vascular endothelial growth factor (VEGF), which can cause fluid and blood to leak in the subretinal space of the eye. While nAMD represents only 10-15 percent of all AMD cases, it is responsible for 90 percent of the vision loss attributed to the disease. The standard treatment requires frequent injections of agents to block VEGF. While effective, the injections are expensive and painful.

Earlier research found that patients being treated with levodopa for movement disorders such as Parkinson's disease were significantly less likely to develop any type of AMD. Lead investigator Robert W. Snyder, MD, PhD, Department of Biomedical Engineering, The University of Arizona, Tucson, and Snyder Biomedical Corporation, Tucson, AZ, USA, explained, "Levodopa has a receptor (GPR143) selectively expressed on pigmented cells. This receptor can be supportive of retinal health and survival, which led to the development of our hypothesis that it may prevent or treat AMD."

The investigators developed two proof-of-concept studies to test whether levodopa improves visual acuity and the anatomical changes caused by nAMD. They also evaluated the safety and tolerability of the drug in treating nAMD and whether treatment reduced or delayed the need for anti-VEGF therapy.

In the first study, 20 patients newly diagnosed with nAMD who had never had VEGF treatment were given a small daily dose of levodopa for one month and were evaluated weekly by their referring retina specialist, who determined whether anti-VEGF treatment was needed. In the second part of the study, the patients who completed the first study and a second group of 14 patients who had received anti-VEGF treatment for at least three months before the study received escalating doses of levodopa to test the tolerance and efficacy of the drug. The patients continued to be evaluated monthly by their referring retina specialist.

This trial demonstrated for the first time that levodopa is safe, well-tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29 percent. After six months the decrease in retinal fluid was sustained and mean visual acuity improved enabling patients in the first and second group to read an additional line on the eye chart. This is the equivalent of improvement from 20/40 to 20/32. Side effects were limited.

The investigators noted that levodopa may be unlikely as a standalone treatment in patients with newly diagnosed nAMD since 11 of the patients did require anti-VEGF injections. However, they required fewer than the standard monthly treatments, and in the second group, monthly injections of anti-VEGF decreased by 52 percent.

According to Dr. Snyder, although this limited proof-of-concept study included a small sample size and limited patient diversity, its findings suggest efficacy and support the targeting of the GPR13 receptor with levodopa for the treatment of nAMD in future studies.

The concept had its genesis 20 years ago when Dr. Snyder began working with co-investigator Brian S. McKay, who had developed techniques to culture and examine retinal endothelial pigment cells. "We had a strong desire to make an impact in AMD, and I had a strong hunch that Dr. McKay could make a significant contribution," Dr. Snyder said. "Although this is nowhere near completed, I am happy to say, 20 years later, we have all persevered, and I believe the GPR143/levodopa story will make a significant impact on our treatment and prevention of AMD."

Sun-seeking behaviour is linked to genes involved in addiction, behavioural and personality traits and brain function, according to a study of more than 260,000 people led by King's College London researchers.

This means that people's behaviour towards seeking sun is complicated by a genetic predisposition, and this needs to be taken into account when designing skin cancer awareness campaigns.

The researchers studied detailed health information of 2,500 twins from TwinsUK, including their sun-seeking behaviour and genetics. Identical twins in a pair were more likely to have a similar sun-seeking behaviour than non-identical twins, indicating that genetics play a key role.

The team then identified five key genes involved in sun-seeking behaviour from a further analysis of 260,000 participants from other cohorts. Some of these genes have been linked to behavioural traits associated with risk-taking and addiction, including smoking, cannabis and alcohol consumption and number of sexual partners.

Senior author Dr Mario Falchi from King's College London said: "Our results suggest that tackling excessive sun exposure or use of tanning beds might be more challenging than expected, as it is influenced by genetic factors. It is important for the public to be aware of this predisposition, as it could make people more mindful of their behaviour and the potential harms of excessive sun exposure."

Dr Veronique Bataille, Consultant Dermatologist involved in the research from King's College London added: "It is clear that we see individuals who have very unhealthy sun behaviour and are fully aware of it. They will continue to expose themselves excessively even if they have clear skin cancer risk factors. Our research shows that genes regulating addiction and other risky behaviour are important and may explain some of the reticence in changing behaviours in the sun."

Scientists have long debated the respiratory workings of sea scorpions, but a new discovery by a West Virginia University geologist concludes that these largely aquatic extinct arthropods breathed air on land.

James Lamsdell dug into the curious case of a 340 million-year-old sea scorpion, or eurypterid, originally from France that had been preserved at a Glasgow, Scotland museum for the last 30 years.

An assistant professor of geology in the Eberly College of Arts and Sciences, Lamsdell had read about the “strange specimen” 25 years ago while conducting his doctoral studies. Existing research suggested it would occasionally go on land.

Yet nothing was known on whether it could breathe air. The closest living relative to the eurypterid is the horseshoe crab, which lays eggs on land but is unable to breathe above water.

These details puzzled Lamsdell through the years until he reached out to a colleague, Victoria McCoy at the University of Wisconsin-Milwaukee, and asked, “Do you have access to a CT scanner?”

“We wondered if we could apply new technology to look further into what was preserved of this specimen,” said Lamsdell, who heads a paleobiology lab at WVU. “I like the science and detective work that goes into research. And this was a cold case where we knew there was potential evidence.”

Through computed tomography (CT) imaging, Lamsdell and his team found that evidence, which is published in Current Biology.

Researchers managed to study the respiratory organs of the three-dimensional eurypterid, leading to two findings that stood out to Lamsdell. First, he noticed that each gill on the sea scorpion was composed of a series of plates. But the back contained fewer plates than the front, prompting researchers to question how it could even breathe.

Then they zeroed in on pillars connecting the different plates of the gill, which are seen in modern scorpions and spiders, Lamsdell said. These pillars, or small beams of tissue, are called trabeculae.

“That props the gills apart so they don’t collapse when out of water,” Lamsdell explained. “It’s something that modern arachnids still have. Finding that was the final indication.

“The reason we think they were coming onto land was to move between pools of water. They could also lay eggs in more sheltered, safer environments and migrate back into the open water.”

The discovery of air-breathing structures in the eurypterids indicate that terrestrial characteristics occurred in the arachnid stem lineage, the researchers wrote, suggesting that the ancestor of arachnids were semi-terrestrial.

In addition to Lamsdell and McCoy, co-authors include Opal Perron-Feller of Oberlin College and Melanie Hopkins of the American Museum of Natural History.

Now that Lamsdell has cracked the case living in the back of his head for 20-plus years, he believes there’s more to unearth from the fossil. He noted that the sea scorpion’s back legs expand into a paddle shape, which he suspects would have been used to swim. The bases of their legs also had spikes that ground up food for them that they maneuvered into their mouths, Lamsdell added.

“One of the things that would be really cool to do is to flesh out this model and try to reconstruct exactly how the legs could move and how they were positioned,” Lamsdell said, “like reconstructing the fossil as a living animal.”

Citation: ‘Air Breathing in an Exceptionally Preserved 340-Million-Year-Old Sea Scorpion’

Journal

Current Biology

Leesburg, VA, September 10, 2020--According to ARRS' American Journal of Roentgenology (AJR), artificial intelligence (AI) predictive analytics performed moderately well in solving complex multifactorial operational problems--outpatient MRI appointment no-shows, especially--using a modest amount of data and basic feature engineering.

"Such data may be readily retrievable from frontline information technology systems commonly used in most hospital radiology departments, and they can be readily incorporated into routine workflow practice to improve the efficiency and quality of health care delivery," wrote lead author Le Roy Chong of Singapore's Changi General Hospital.

To train and validate their model, Chong and colleagues extracted records of 32,957 outpatient MRI appointments scheduled between January 2016 and December 2018 from their institution's radiology information system, while acquiring a further holdout test set of 1,080 records from January 2019. Overall, the no-show rate was 17.4%.

After evaluating various machine learning predictive models developed with widely used open-source software tools, Chong and team deployed a decision tree-based ensemble algorithm that uses a gradient boosting framework: XGBoost, version 0.80 [Tianqi Chen].

As Chong et al. explained, "the simple intervention measure of using telephone call reminders for patients with the top 25% highest risk of an appointment no-show as predicted by the model was implemented over 6 months."

Six months after deployment, the no-show rate of the predictive model was 15.9%, compared with 19.3% in the preceding 12-month preintervention period--corresponding to a 17.2% improvement from the baseline no-show rate (p

"We believe that the main strength of the present study lies in its empirical approach, given the lack of published literature quantifying the impact of actual workflow implementation, with previous studies postulating the potential benefits of applying machine learning techniques to this problem," the authors of this AJR article concluded. "The aim of our study was not to produce a highly complex model but, rather, to produce one that could be developed relatively quickly, would require minimal data processing, and would be readily deployable in workflow practice for quality improvement."

The ocean plays an invaluable role in capturing carbon dioxide (CO2) from the atmosphere, taking in somewhere between five to 12 gigatons (billion tons) annually. Due to limited research, scientists aren't sure exactly how much carbon is captured and stored--or sequestered--by the ocean each year or how increasing CO2 emissions will affect this process in the future.

A new paper published in the journal Science of the Total Environment from the Woods Hole Oceanographic Institution (WHOI) puts an economic value on the benefit of research to improve knowledge of the biological carbon pump and reduce the uncertainty of ocean carbon sequestration estimates.

Using a climate economy model that factors in the social costs of carbon and reflects future damages expected as a consequence of a changing climate, lead author Di Jin of WHOI's Marine Policy Center places the value of studying ocean carbon sequestration at $500 billion.

"The paper lays out the connections between the benefit of scientific research and decision making," says Jin. "By investing in science, you can narrow the range of uncertainty and improve a social cost-benefit assessment."

Better understanding of the ocean's carbon sequestration capacity will lead to more accurate climate models, providing policymakers with the information they need to establish emissions targets and make plans for a changing climate, Jin adds.

With co-authors Porter Hoagland and Ken Buesseler, Jin builds a case for a 20-year scientific research program to measure and model the ocean's biological carbon pump, the process by which atmospheric carbon dioxide is transported to the deep ocean through the marine food web.

The biological carbon pump is fueled by tiny plant-like organisms floating on the ocean surface called phytoplankton, which consume carbon dioxide in the process of photosynthesis. When the phytoplankton die or are eaten by larger organisms, the carbon-rich fragments and fecal matter sink deeper into the ocean, where they are eaten by other creatures or buried in seafloor sediments, which helps decrease atmospheric carbon dioxide and thus reduces global climate change.

Rising carbon dioxide levels in the atmosphere, a result of human activity such as burning fossil fuels, warms the planet by trapping heat from the sun and also dissolves into seawater, lowering the pH of the ocean, a phenomenon known as ocean acidification. A warmer, more acidic ocean could weaken the carbon pump, causing atmospheric temperatures to rise--or it could get stronger, with the opposite effect.

"When we try to predict what the world is going to look like, there's great uncertainty," says Buesseler, a WHOI marine chemist. "Not only do we not know how big this pump is, we don't know whether it will remove more or less carbon dioxide in the future. We need to make progress to better understand where we're headed, because the climate affects all of humanity."

Buesseler added that efforts like WHOI's Ocean Twilight Zone initiative and NASA's EXport Processes in the global Ocean from RemoTe Sensing (EXPORTS) program are making important strides in understanding the ocean's role in the global carbon cycle, but this research needs to be vastly scaled up in order to develop predictive models such as those used by the Intergovernmental Panel on Climate Change (IPCC). Current IPCC models do not account for change in the ocean's ability to take up carbon, which Buesseler said affects their accuracy.

Though the paper's assessment doesn't account for the cost of a global research program, Buesseler said that investment would be a small fraction of the $500 billion expected benefit. The authors warn that this savings could also be viewed as a cost to society if the research does not lead to policy decisions that mitigate the effects of climate change.

"Just like a weather forecast that helps you decide whether or not to bring an umbrella, you use your knowledge and experience to make a decision based on science," Jin says. "If you hear it's going to rain and you don't listen, you will get wet."

It is established that matter can transition between different phases when certain parameters, such as temperature, are changed. Although phase transitions are common (like water turning into ice in a freezer), the dynamics that govern these processes are highly complex and constitute a prominent problem in the field of nonequilibrium physics.

When a system undergoes a phase transition, matter in the new phase has many possible energetically equal "configurations" to adopt. In these cases, different parts of the system adopt different configurations over regions called "domains." The interfaces between these domains are known as topological defects and reducing the number of these defects formed can be immensely valuable in many applications.

One common strategy to reduce defects is easing the system through the phase transition slowly. In fact, according to the "Kibble-Zurek" mechanism (KZM), it is predicted that the average number of defects and the driving time of the phase transition follow a universal power law. However, experimentally testing the KZM in a quantum system has remained a coveted goal.

In a recent study published in Physical Review Research, a team of scientists led by Professor Emeritus Hidetoshi Nishimori from Tokyo Institute of Technology, Japan, probed the validity of the KZM in two commercially available quantum annealers, a type of quantum computer designed for solving complex optimization problems. These devices, known as D-Wave annealers, can recreate controllable quantum systems and control their evolution over time, providing a suitable experimental testbed for the KZM.

First, the scientists checked whether the "power law" between the average number of defects and the annealing time (driving time of the phase transition) predicted by the KZM held for a quantum magnetic system called the "one-dimensional transverse-field Ising model." This model represents the orientations (spins) of a long chain of "magnetic dipoles," where homogenous regions are separated by defects seen as neighboring spins pointing in incorrect directions.

While the original prediction of the KZM regarding the average number of defects was valid in this system, the scientists took it a step further: although this extension of the KZM was originally intended for a completely "isolated" quantum system unaffected by external parameters, they found good agreement between its predictions and their experimental results even in the D-Wave annealers, which are "open" quantum systems.

Excited by these results, Prof Nishimori remarks: "Our work provides the first experimental test of universal critical dynamics in a many-body open quantum system. It also constitutes the first test of certain physics beyond the original KZM, providing strong experimental evidence that the generalized theory holds beyond the regime of validity theoretically established."

This study showcases the potential of quantum annealers to perform simulations of quantum systems and also helps gain insight on other areas of physics. In this regard, Prof Nishimori states: "Our results leverage quantum annealing devices as platforms to test and explore the frontiers of nonequilibrium physics. We hope our work will motivate further research combining quantum annealing and other universal principles in nonequilibrium physics." Hopefully, this study will also promote the use of quantum annealers in experimental physics. After all, who doesn't love finding a new use for a tool?

MIT researchers have developed a wireless, private way to monitor a person's sleep postures -- whether snoozing on their back, stomach, or sides -- using reflected radio signals from a small device mounted on a bedroom wall.

The device, called BodyCompass, is the first home-ready, radio-frequency-based system to provide accurate sleep data without cameras or sensors attached to the body, according to Shichao Yue, who will introduce the system in a presentation at the UbiComp 2020 conference on Sept. 15. The PhD student has used wireless sensing to study sleep stages and insomnia for several years.

"We thought sleep posture could be another impactful application of our system" for medical monitoring, says Yue, who worked on the project under the supervision of Professor Dina Katabi in the MIT Computer Science and Artificial Intelligence Laboratory. Studies show that stomach sleeping increases the risk of sudden death in people with epilepsy, he notes, and sleep posture could also be used to measure the progression of Parkinson's disease as the condition robs a person of the ability to turn over in bed.

In the future, people might also use BodyCompass to keep track of their own sleep habits or to monitor infant sleeping, Yue says: "It can be either a medical device or a consumer product, depending on needs."

Other authors on the conference paper, published in the Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies, include graduate students Yuzhe Yang and Hao Wang, and Katabi Lab affiliate Hariharan Rahul. Katabi is the Andrew and Erna Viterbi Professor of Electrical Engineering and Computer Science at MIT.

Restful reflections

BodyCompass works by analyzing the reflection of radio signals as they bounce off objects in a room, including the human body. Similar to a Wi-Fi router attached to the bedroom wall, the device sends and collects these signals as they return through multiple paths. The researchers then map the paths of these signals, working backward from the reflections to determine the body's posture.

For this to work, however, the scientists needed a way to figure out which of the signals were bouncing off the sleeper's body, and not bouncing off the mattress or a nightstand or an overhead fan. Yue and his colleagues realized that their past work in deciphering breathing patterns from radio signals could solve the problem.

Signals that bounce off a person's chest and belly are uniquely modulated by breathing, they concluded. Once that breathing signal was identified as a way to "tag" reflections coming from the body, the researchers could analyze those reflections compared to the position of the device to determine how the person was lying in bed. (If a person was lying on her back, for instance, strong radio waves bouncing off her chest would be directed at the ceiling and then to the device on the wall.) "Identifying breathing as coding helped us to separate signals from the body from environmental reflections, allowing us to track where informative reflections are," Yue says.

Reflections from the body are then analyzed by a customized neural network to infer how the body is angled in sleep. Because the neural network defines sleep postures according to angles, the device can distinguish between a sleeper lying on the right side from one who has merely tilted slightly to the right. This kind of fine-grained analysis would be especially important for epilepsy patients for whom sleeping in a prone position is correlated with sudden unexpected death, Yue says.

BodyCompass has some advantages over other ways of monitoring sleep posture, such as installing cameras in a person's bedroom or attaching sensors directly to the person or their bed. Sensors can be uncomfortable to sleep with, and cameras reduce a person's privacy, Yue notes. "Since we will only record essential information for detecting sleep posture, such as a person's breathing signal during sleep," he says, "it is nearly impossible for someone to infer other activities of the user from this data."

An accurate compass

The research team tested BodyCompass' accuracy over 200 hours of sleep data from 26 healthy people sleeping in their own bedrooms. At the start of the study, the subjects wore two accelerometers (sensors that detect movement) taped to their chest and stomach, to train the device's neural network with "ground truth" data on their sleeping postures.

BodyCompass was most accurate -- predicting the correct body posture 94 percent of the time -- when the device was trained on a week's worth of data. One night's worth of training data yielded accurate results 87 percent of the time. BodyCompass could achieve 84 percent accuracy with just 16 minutes' worth of data collected, when sleepers were asked to hold a few usual sleeping postures in front of the wireless sensor.

Along with epilepsy and Parkinson's disease, BodyCompass could prove useful in treating patients vulnerable to bedsores and sleep apnea, since both conditions can be alleviated by changes in sleeping posture. Yue has his own interest as well: He suffers from migraines that seem to be affected by how he sleeps. "I sleep on my right side to avoid headache the next day," he says, "but I'm not sure if there really is any correlation between sleep posture and migraines. Maybe this can help me find out if there is any relationship."

For now, BodyCompass is a monitoring tool, but it may be paired someday with an alert that can prod sleepers to change their posture. "Researchers are working on mattresses that can slowly turn a patient to avoid dangerous sleep positions," Yue says. "Future work may combine our sleep posture detector with such mattresses to move an epilepsy patient to a safer position if needed."

Astronomers have discovered that there may be a missing ingredient in our cosmic recipe of how dark matter behaves.

They have uncovered a discrepancy between the theoretical models of how dark matter should be distributed in galaxy clusters, and observations of dark matter's grip on clusters.

Dark matter does not emit, absorb, or reflect light. Its presence is only known through its gravitational pull on visible matter in space. Therefore, dark matter remains as elusive as Alice in Wonderland's Cheshire Cat - where you only see its grin (in the form of gravity) but not the animal itself.

One way astronomers can detect dark matter is by measuring how its gravity distorts space, an effect called gravitational lensing.

Researchers found that small-scale concentrations of dark matter in clusters produce gravitational lensing effects that are 10 times stronger than expected. This evidence is based on unprecedentedly detailed observations of several massive galaxy clusters by NASA's Hubble Space Telescope and the European Southern Observatory's Very Large Telescope (VLT) in Chile.

Galaxy clusters, the most massive structures in the universe composed of individual member galaxies, are the largest repositories of dark matter. Not only are they held together largely by dark matter's gravity, the individual cluster galaxies are themselves replete with dark matter. Dark matter in clusters is therefore distributed on both large and small scales.

"Galaxy clusters are ideal laboratories to understand if computer simulations of the universe reliably reproduce what we can infer about dark matter and its interplay with luminous matter," said Massimo Meneghetti of the INAF (National Institute for Astrophysics)-Observatory of Astrophysics and Space Science of Bologna in Italy, the study's lead author.

"We have done a lot of careful testing in comparing the simulations and data in this study, and our finding of the mismatch persists," Meneghetti continued. "One possible origin for this discrepancy is that we may be missing some key physics in the simulations."

Priyamvada Natarajan of Yale University in New Haven, Connecticut, one of the senior theorists on the team, added, "There's a feature of the real universe that we are simply not capturing in our current theoretical models. This could signal a gap in our current understanding of the nature of dark matter and its properties, as these exquisite data have permitted us to probe the detailed distribution of dark matter on the smallest scales."

The team's paper will appear in the Sept. 11 issue of the journal Science.

The distribution of dark matter in clusters is mapped via the bending of light, or the gravitational lensing effect, they produce. The gravity of dark matter magnifies and warps light from distant background objects, much like a funhouse mirror, producing distortions and sometimes multiple images of the same distant galaxy. The higher the concentration of dark matter in a cluster, the more dramatic its light bending.

Hubble's crisp images, coupled with spectra from the VLT, helped the team produce an accurate, high-fidelity dark-matter map. They identified dozens of multiply imaged, lensed, background galaxies. By measuring the lensing distortions, astronomers could trace out the amount and distribution of dark matter.

The three key galaxy clusters used in the analysis, MACS J1206.2-0847, MACS J0416.1-2403, and Abell S1063, were part of two Hubble surveys: The Frontier Fields and the Cluster Lensing And Supernova survey with Hubble (CLASH) programs.

To the team's surprise, the Hubble images also revealed smaller-scale arcs and distorted images nested within the larger-scale lens distortions in each cluster's core, where the most massive galaxies reside.

The researchers believe that the embedded lenses are produced by the gravity of dense concentrations of dark matter associated with individual cluster galaxies. Dark matter's distribution in the inner regions of individual galaxies is known to enhance the cluster's overall lensing effect.

Follow-up spectroscopic observations added to the study by measuring the velocity of the stars orbiting inside several of the cluster galaxies. "Based on our spectroscopic study, we were able to associate the galaxies with each cluster and estimate their distances," said team member Piero Rosati of the University of Ferrara in Italy.

"The stars' speed gave us an estimate of each individual galaxy's mass, including the amount of dark matter," added team member Pietro Bergamini of the INAF-Observatory of Astrophysics and Space Science in Bologna, Italy.

The team compared the dark-matter maps with samples of simulated galaxy clusters with similar masses, located at roughly the same distances as the observed clusters. The clusters in the computer simulations did not show the same level of dark-matter concentration on the smallest scales - the scales associated with individual cluster galaxies as seen in the universe.

The team looks forward to continuing their stress-testing of the standard dark-matter model to pin down its intriguing nature.

COLUMBUS, Ohio -- Almost seven in 10 Americans would be interested in receiving a COVID-19 vaccine when one becomes available, according to a new study. But researchers say there are concerning gaps in interest, particularly among Black Americans, who suffer disproportionately from the virus.

Researchers from The Ohio State University surveyed more than 2,000 Americans in May, asking them about their willingness to be vaccinated and 11 factors that could influence that decision. They found that 1,374 out of 2006 people in the survey, 69%, said they would "definitely" or "probably" get a vaccine. The survey found that 17% were "not sure" and 14% were "probably or "definitely" not willing.

The study, one of the first estimates of COVID-19 vaccine acceptance in the U.S., appears online in the journal Vaccine.

Lead researcher Paul Reiter, an associate professor of health behavior and health promotion, said he suspected there would be higher-than-normal interest in this vaccine, considering the nature of the pandemic and the severity of illness many people have experienced.

"The interest here is higher than what we typically see for flu vaccine and other vaccines where there is a strong public health need for widespread protection," he said.

The strongest predictors of whether someone said they'd accept a vaccine were how well the vaccine works and whether their health care provider would recommend it. Individuals' perceived personal health threat from COVID-19 also played strongly into their willingness to be vaccinated, the researchers found.

"That aligns with what we see in public health in a variety of areas -- if someone perceives themselves to be at a higher risk of a health issue, that's going to make them more likely to engage in the health behavior, in this case vaccination," Reiter said.

One of the more unexpected findings in this study - and something that isn't typical of public health research - is the correlation between political affiliation and willingness to adopt a public health intervention, Reiter said. Respondents who identified as liberal or moderate were significantly more likely to accept a vaccine.

"COVID-19 has turned into a political issue in many cases, and I think that some people just pick their side based on that, without much research," he said. "We've seen that with mask wearing. It's a promising public health intervention, but it's turned into a political powder keg."

The most worrisome finding was among Black survey respondents, as only 55% said they were willing to get a vaccine.

"Given the disproportionate burden of COVID-19 infection and death among Black Americans, it's concerning to see that Black survey participants had less interest in a vaccine," Reiter said.

"I think there are likely several factors at play, including access to care and trust in health care and potential socioeconomic barriers."

Reducing such barriers is important since only 35% of participants in the study would pay $50 or more out-of-pocket for a COVID-19 vaccine, Reiter said.

As of the first week of September, 10 states had indicated plans to offer free vaccines when they become available, according to KFF (formerly known as the Kaiser Family Foundation.)

Reiter said public health leaders and policymakers can look to this study as they shape efforts to communicate the benefits (and any risks) of a COVID-19 vaccine, once one is approved for general use.

"You hear a lot of talk of vaccination and the benefits of herd immunity, the idea that when enough people have resistance to a virus it reduces the threat to the entire population. At 70%, we may or may not get there," Reiter said.

That makes it especially important to work toward educational efforts, the elimination of obstacles and other strategies to increase the chances of vaccination among those who face increased risks of severe illness or death. If the vaccine against COVID-19 requires more than one dose, it will present even more challenges, he said -- a reality that has been made clear in recent years with efforts to fully vaccinate young people against HPV to help prevent cancer. The HPV vaccine requires at least two doses, and three when given later in the teen years.

Though the survey was conducted four months ago, Reiter said he doesn't expect much has changed in terms of public perception.

"As we get closer to a vaccine becoming available, factors that could further affect the public's interest will include cost and the number of doses required," he said.

Observations by the NASA/ESA Hubble Space Telescope and the European Southern Observatory's Very Large Telescope (VLT) in Chile have found that something may be missing from the theories of how dark matter behaves. This missing ingredient may explain why researchers have uncovered an unexpected discrepancy between observations of the dark matter concentrations in a sample of massive galaxy clusters and theoretical computer simulations of how dark matter should be distributed in clusters. The new findings indicate that some small-scale concentrations of dark matter produce lensing effects that are 10 times stronger than expected.

Dark matter is the invisible glue that keeps stars, dust, and gas together in a galaxy. This mysterious substance makes up the bulk of a galaxy's mass and forms the foundation of our Universe's large-scale structure. Because dark matter does not emit, absorb, or reflect light, its presence is only known through its gravitational pull on visible matter in space. Astronomers and physicists are still trying to pin down what it is.

Galaxy clusters, the most massive and recently assembled structures in the Universe, are also the largest repositories of dark matter. Clusters are composed of individual member galaxies that are held together largely by the gravity of dark matter.

"Galaxy clusters are ideal laboratories in which to study whether the numerical simulations of the Universe that are currently available reproduce well what we can infer from gravitational lensing," said Massimo Meneghetti of the INAF-Observatory of Astrophysics and Space Science of Bologna in Italy, the study's lead author [1].

"We have done a lot of testing of the data in this study, and we are sure that this mismatch indicates that some physical ingredient is missing either from the simulations or from our understanding of the nature of dark matter," added Meneghetti.

"There's a feature of the real Universe that we are simply not capturing in our current theoretical models," added Priyamvada Natarajan of Yale University in Connecticut, USA, one of the senior theorists on the team. "This could signal a gap in our current understanding of the nature of dark matter and its properties, as these exquisite data have permitted us to probe the detailed distribution of dark matter on the smallest scales."

The distribution of dark matter in clusters is mapped by measuring the bending of light -- the gravitational lensing effect -- that they produce. The gravity of dark matter concentrated in clusters magnifies and warps light from distant background objects. This effect produces distortions in the shapes of background galaxies which appear in images of the clusters. Gravitational lensing can often also produce multiple images of the same distant galaxy.

The higher the concentration of dark matter in a cluster, the more dramatic its light-bending effect. The presence of smaller-scale clumps of dark matter associated with individual cluster galaxies enhances the level of distortions. In some sense, the galaxy cluster acts as a large-scale lens that has many smaller lenses embedded within it.

Hubble's crisp images were taken by the telescope's Wide Field Camera 3 and Advanced Camera for Surveys. Coupled with spectra from the European Southern Observatory's Very Large Telescope (VLT), the team produced an accurate, high-fidelity, dark-matter map. By measuring the lensing distortions astronomers could trace out the amount and distribution of dark matter. The three key galaxy clusters, MACS J1206.2-0847, MACS J0416.1-2403, and Abell S1063, were part of two Hubble surveys: The Frontier Fields and the Cluster Lensing And Supernova survey with Hubble (CLASH) programs.

To the team's surprise, in addition to the dramatic arcs and elongated features of distant galaxies produced by each cluster's gravitational lensing, the Hubble images also revealed an unexpected number of smaller-scale arcs and distorted images nested near each cluster's core, where the most massive galaxies reside. The researchers believe the nested lenses are produced by the gravity of dense concentrations of matter inside the individual cluster galaxies. Follow-up spectroscopic observations measured the velocity of the stars orbiting inside several of the cluster galaxies to therby pin down their masses.

"The data from Hubble and the VLT provided excellent synergy," shared team member Piero Rosati of the Università degli Studi di Ferrara in Italy, who led the spectroscopic campaign. "We were able to associate the galaxies with each cluster and estimate their distances."

"The speed of the stars gave us an estimate of each individual galaxy's mass, including the amount of dark matter," added team member Pietro Bergamini of the INAF-Observatory of Astrophysics and Space Science in Bologna, Italy.

By combining Hubble imaging and VLT spectroscopy, the astronomers were able to identify dozens of multiply imaged, lensed, background galaxies. This allowed them to assemble a well-calibrated, high-resolution map of the mass distribution of dark matter in each cluster.

The team compared the dark-matter maps with samples of simulated galaxy clusters with similar masses, located at roughly the same distances. The clusters in the computer model did not show any of the same level of dark-matter concentration on the smallest scales -- the scales associated with individual cluster galaxies.

"The results of these analyses further demonstrate how observations and numerical simulations go hand in hand", said team member Elena Rasia of the INAF-Astronomical Observatory of Trieste, Italy.

"With high-resolution simulations, we can match the quality of observations analysed in our paper, permitting detailed comparisons like never before," added Stefano Borgani of the Università degli Studi di Trieste, Italy.

Astronomers, including those of this team, look forward to continuing to probe dark matter and its mysteries in order to finally pin down its nature.