Saturday, January 30, 2021

COVID face mask painted on giant English chalk figure

LONDON (Reuters) - British police are searching for the vandal or vandals who painted a COVID-19 face mask on the figure of a mysterious giant carved into a hillside in southern England.
© Reuters/JEREMY CHRISTEY Long Man of Wilmington with "mask" added in South Downs

The Long Man of Wilmington, a 235-foot high chalk outline holding a white stick in each hand, is protected by law as an ancient monument. Its exact origins are disputed but many archaeologists date it to the Anglo-Saxon or medieval periods.

"Whilst this damage may have been perpetrated for humour or some other reason, the actions that have been taken are unacceptable," said Tom Carter, a sergeant with Sussex Police.

"The Long Man of Wilmington is protected by law as a Scheduled Ancient Monument for its historical significance."

A Reuters photographer who visited the site on Saturday afternoon said the mask had been removed.

(Reporting by Andrew MacAskill; Editing by David Holmes)
Spartan Bioscience says Health Canada approves rapid COVID-19 test

© Supplied by Spartan Bioscience The Ottawa-based company says Health Canada 
has approved the sale of the Spartan COVID-19 System, a rapid, on-site molecular diagnostic test.

Ottawa-based Spartan Bioscience has received Health Canada approval for its made-in-Canada rapid COVID-19 test, authorizing the sale of the device.

"The Spartan COVID-19 System offers the speed and ease of use of a rapid test, while using the technology of lab-based COVID-19 testing solutions," a news release from the company states.

The test offers hope because it is one of only a handful of approved quick-result tests that uses the polymerase chain reaction (PCR) testing method — widely considered the gold standard for accurate COVID-19 diagnostics — at the point-of-care, without the need to send anything to a lab.

The Spartan test isn't the first point-of-care PCR test to be approved in Canada, but it is the first to be made by a Canadian company with plans to sell solely to the Canadian market.

Health Canada originally provided regulatory approval for the company's device in April 2020 — with the federal government ordering 40,000 tests monthly. At the time, the portable test was being called a "game changer" by health officials because it could deliver on-location results within 60 minutes.

The federal agency restricted the device to research use in May, however, after finding problems with the test that made it unreliable. Approval was granted on Friday after the company conducted clinical trials based on a new device design, Health Canada spokesperson Natalie Mohamed told CBC News in an email.

"The Spartan Bioscience test is a point-of-care molecular test," Mohamed wrote. "This new device meets Health Canada's requirements for safety and effectiveness."
New swab, upgrades to chemistry kit

Dr. James Spiegelman, a co-founder of the company who also practises internal medicine at Humber River Regional Hospital in Toronto, said the problems stemmed from the efficacy of the swabs used to collect tissue samples, not the machine itself.

Spartan originally used a proprietary cheek swab that it developed for other DNA diagnostics, he said, but it became clear that the swab wasn't collecting enough genetic material to produce consistent, reliable results.

The company now uses standard nasopharyngeal swabs to collect tissue from the nose.

"We found that that provides the best sample for increased sensitivity of the test," Spiegelman said.

Spiegelman said the company also made improvements to the sample processing kit so that it no longer needs to be shipped and stored at frozen temperatures but can be stored at room temperature.

With the Spartan test, a trained health-care professional swabs the nose of the person being tested, places the swab into a processing kit that generates a chain reaction and then puts that kit into the cube-shaped device, which takes about 50 minutes to analyze and produce results.

Spiegelman said the test could be used to provide quick and accurate COVID-19 diagnostics everywhere from hospitals and workplaces to pharmacies and remote communities.

"I think [Spartan's rapid test] will really help alleviate and give us a tool in our toolbox to reduce the spread of COVID-19," he said.

Rapid tests already in use across Canada

Rapid diagnostic tests are already in use in many settings across Canada to test for COVID-19, including in homeless shelters, long-term care homes and remote communities. Prime Minister Justin Trudeau said last Tuesday that the federal government had distributed more than 14 million to the provinces and territories.

"Hopefully we see these integrated into work environments, especially work environments where we know they're at greater risk for outbreaks," said infectious disease specialist Dr. Isaac Bogoch, who is also a member of the Ontario COVID-19 vaccine task force.

"I think you could think about certainly integrating them into certain schools or certain school settings, rural, remote, underserviced locations. There's a lot of places where rapid tests would be extremely helpful."

Spartan Bioscience CEO Roger Eacock said the company currently has the manufacturing capacity to produce 60,000 tests per week, but it plans to ramp that up to 200,000 per week in the future.

Eacock said the company already has deals with the federal government and several provinces, as well as some airlines and resource companies, and that shipments are expected to begin in the coming week.

"Everything that we produce here today, we are going to be shipping internally within Canada to all of our Canadian accounts," he said. "So we're a dedicated supply chain to the Canadian market."

A professor from RUDN University developed new liquid crystals

RUDN UNIVERSITY

Research News

IMAGE

IMAGE: A PROFESSOR FROM RUDN UNIVERSITY TOGETHER WITH HIS INDIAN COLLEAGUES SYNTHESIZED AND STUDIED NEW DIBENZOPHENAZINE-BASED LIQUID CRYSTALS THAT COULD POTENTIALLY BE USED IN OPTOELECTRONICS AND SOLAR PANELS. view more 

CREDIT: RUDN UNIVERSITY

A professor from RUDN University together with his Indian colleagues synthesized and studied new dibenzophenazine-based liquid crystals that could potentially be used in optoelectronics and solar panels. The results of the study were published in the Journal of Molecular Liquids.

Liquid crystals are an intermediate phase between a liquid and a solid body. They are ordered like regular chrystals but at the same time have a flow like liquids. It is this duality that allows them to be used in organic LEDs and LCDs. Unlike other liquid crystals, discotic ones (DLC) are capable of self-assembly into ordered structures. This makes them a promising material for industrial electronics, namely, for the production of displays. A professor from RUDN University together with his Indian colleagues synthesized and described new dibenzophenazine-based DLCs.

"Discotic liquid crystals are interesting because of their ability to form self-assembled ordered columnar structures. In such structures, an electric charge can move along the column, which makes them useful for optoelectronic devices such as organic LEDs, organic field-effect transistors (OFET), photoelectric solar elements, and sensors," said Prof. Viktor Belyaev, a Ph.D. in Technical Sciences from the Department of Mechanics and Mechatronics at RUDN University.

DLCs consist of disc-shaped molecules aligned in columns. In the center of each disc, there is an aromatic ring (a cyclical organic fragment) surrounded by chains of other organic fragments. Due to this aromatic center, a DLC can transfer a charge along the axis of a column. Prof. Belyaev developed discotic liquid crystals with an aromatic compound called dibenzophenazine in the center. As for the chains that surrounded it, the team tried three different types of fragments. The molecular structure of the new DLCs was studied using spectral, X-ray diffraction, and elementary analysis. Then, the team tested the three groups of DLCs in a set of experiments.

The experiments showed that alkoxy thiol chains increased the polarity of the molecules in liquid crystals thus improving the internal structure of the columns and making them more even. All new DLCs were able to withstand temperatures up to 330?. However, the crystals that consisted of smaller molecules (i.e. the ones with their aromatic center surrounded by alkyl thiols) lost their intermediary status and transitioned from the liquid crystal to the liquid form at lower temperatures (55.1 ?) that the crystals from the other two groups. This is due to the size of the molecules in the columns: the bigger they are, the more stable is the liquid crystal state.

"The new discotic liquid crystals could play an important role in organic optoelectronic devices and solar panels," added Prof. Viktor Belyaev from RUDN University.

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Experts call for more pragmatic approach to higher education teaching

Millions of students around the world could benefit if their educators adopted a more flexible and practical approach, say Swansea University experts

SWANSEA UNIVERSITY

Research News

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IMAGE: A UNIVERSITY LECTURE BUT COULD THE STANDARD OF TEACHING BE IMPROVED IF A DIFFERENT APPROACH WAS TAKEN BY EDUCATORS? view more 

CREDIT: SWANSEA UNIVERSITY

Millions of students around the world could benefit if their educators adopted a more flexible and practical approach, say Swansea University experts.

After analysing the techniques current being used in higher education, the researchers are calling for a pragmatic and evidence-based approach instead.

Professor Phil Newton, director of learning and teaching at of Swansea University Medical School, said: "Higher education is how we train those who carry out important professional roles in our society. There are now more than 200 million students in HE worldwide and this number is likely to double again over the next decade.

"Given the size, impact, importance and cost of HE, it would be reasonable to assume that policies and practices employed are the best available, based upon rigorous evidence. However, this does not appear to be the case."

In a new paper, Professor Newton, Dr Ana Da Silva and Sam Berry argue that the findings of higher education research are not being used to develop and benefit educational practice.

They say belief in ineffective methods such as Learning Styles persist, teaching quality and teacher performance are measured using subjective and potentially biased feedback while university educators have limited access to professional development.

Instead, the academics are proposing a pragmatic model of evidence-based higher education which they say could deliver results that are more obviously useful, focusing on practical teaching skills.

Prof Newton added: "The model is intended for educators and policymakers, to help them make the best use of existing education research evidence when making contextual decisions about local practice.

"It can also be used by learners to make decisions about how, when, why and what to study, and for the teaching of study skills to learners."

The model and how it can be applied in education settings is detailed in their research which has been published in the journal Frontiers in Education.

However, they say any decisions made using the model would need to be reviewed regularly, as the evidence base updates and the context shifts.

The need for this flexibility - and the benefits of adopting a pragmatic approach - have been highlighted by the pandemic which has led the global HE sectors to embrace online learning.

Prof Newton said: "There is an abundant evidence-base regarding learning online and at a distance, but much of this was developed to optimize learning under planned circumstances where students could choose to learn online, or in a structured blended way, very different to the situation we find ourselves in now.

"A pragmatic application of the existing evidence to the new context can help us with this rapid change and help us plan for what might become a 'new normal'."

Among the paper's recommendations, the researchers are calling for:

  • Faculty development programmes and credentials for HE educators to be practical and skills based;
  • Establishing pragmatic practical evidence summaries for use across international HE, allowing adjustment for context;
  • More syntheses of existing primary research that answer useful questions such as what works, for whom, in what circumstances, and why? How much does it cost, what is it compared to, how practical is it to implement?
  • Increased funding for research into the effectiveness of learning and teaching approaches in HE.

Prof Newton added "There is an abundance of academic literature on higher education, stretching back decades. We owe it to all involved in education to ensure that this can best inform innovation and improvement, in a way that allows for professional judgement and a consideration of context.

"This could be achieved by adopting principles of pragmatic, evidence-based higher education."

CAPTION

A decision-making model for the application of research evidence to improving educational practice. The most useful research evidence is combined with practitioner judgement about how and why to apply it in a specific context, with specific questions for each aspect. At the intersection of these three factors is Pragmatic Evidence-Based Education (EBE).

CREDIT

Prof Phil Newton


Food export restrictions by a few countries could skyrocket global food crop prices

Global shocks such as COVID-19 call for improved political decisions and accountability to secure food for everyone

AALTO UNIVERSITY

Research News

Recent events such as the Covid-19 pandemic, locust infestations, drought and labour shortages have disrupted food supply chains, endangering food security in the process. A recent study published in Nature Food shows that trade restrictions and stockpiling of supplies by a few key countries could create global food price spikes and severe local food shortages during times of threat.

'We quantified the potential effects of these co-occurring global and local shocks globally with their impacts on food security,' explains Aalto University Associate Professor Matti Kummu. The results of this research have critical implications on how we should prepare for future events like Covid-19, he says.

The researchers modelled future scenarios to investigate the impact of export restrictions and local production shocks of rice, wheat, and maize would have on their supply and price. These three crops form the backbone of global trade in staple crops and are essential for food security across the globe.

The results show that restriction by only three key exporters of each crop would increase the price of wheat by 70%, while maize and rice would rise by 40% and 60%. When combining this with potential local shocks that occurred last year, the prices would nearly double.

Kummu explains: 'This is the result of an increasingly interconnected world, in which the majority of countries are dependent on imported food and, so, vulnerable to this kind of shock.'

'We saw that trade restrictions by only a few key actors can create large short-term price spikes in the world market export price of grains, which can lead to food insecurity in import-dependent countries,' explains Postdoctoral Researcher Theresa Falkendal, Potsdam Institute for Climate Impact Research.

By suddenly losing more than one-third of their annual grain supply, many low-income and lower-middle-income countries in Africa and Asia would not be able to cover this grain supply deficit with their domestic reserves, and would need alternative grain sources to survive.

'It's important to realise that food security depends on both local and remote conditions, and imprudent policy decisions in the rich part of the world can plunge people into real hardship in poorer parts of the world,' states Falkendal.

But shock scenarios such as those modelled by the researchers and the risks they bring may become commonplace thanks in part to global warming.

The Covid-19 pandemic's effect on global agricultural supply chains, as well as locusts destroying crops and livelihoods in the Horn of Africa and South Asia, have had a devastating effect on food security.

'To help prevent such devastation in the future, we need proactive strategies, like reducing food waste, changing the diet towards more plant-based protein sources, and increasing the yields sustainably particularly in the most vulnerable countries,' says Kummu.

'While sustainable design of agricultural systems is important, it must go hand-in-hand with efforts to improve political decisions and accountability,' says Michael J. Puma, research scientist and fellow at Center for Climate Systems Research, Earth Institute, Columbia University.

These solutions would ease a lot of pressure on resources that are needed for food production and help improve the self-sufficiency of low-income and middle-income countries.

Thus, timely and coordinated international responses are needed to minimise threats to food security especially to low-income and middle-income countries which lack the resources and purchasing power of larger nations, to ensure affordable staple grains for the world's poorest citizens, and to avert a humanitarian crisis.

'It's essential that humanitarian institutions strengthen their efforts to support democratic accountability around the world, which will ultimately help us to avoid severe food insecurity and famine,' concludes Puma.

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High schoolers discover four exoplanets through Harvard and Smithsonian mentorship program

The high schoolers turned scientists published their findings this week, thanks to a research mentorship program at the Center for Astrophysics; Harvard and Smithsonian

HARVARD-SMITHSONIAN CENTER FOR ASTROPHYSICS

Research News

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IMAGE: A FIVE-PLANET SYSTEM AROUND TOI-1233 INCLUDES A SUPER-EARTH (FOREGROUND) THAT COULD HELP SOLVE MYSTERIES OF PLANET FORMATION. THE FOUR INNERMOST PLANETS WERE DISCOVERED BY HIGH SCHOOLERS KARTIK PINGLÉ AND JASMINE... view more 

CREDIT: NASA/JPL-CALTECH

Cambridge, Massachusetts - They may be the youngest astronomers to make a discovery yet.

This week, 16-year-old Kartik Pinglé and 18-year-old Jasmine Wright have co-authored a peer-reviewed paper in The Astronomical Journal describing the discovery of four new exoplanets about 200-light-years away from Earth.

The high schoolers participated in the research through the Student Research Mentoring Program (SRMP) at the Center for Astrophysics | Harvard & Smithsonian. Directed by astrochemist Clara Sousa-Silva, the SRMP connects local high schoolers who are interested in research with real-world scientists at Harvard and MIT. The students then work with their mentors on a year-long research project.

"It's a steep learning curve," says Sousa-Silva, but it's worth it. "By the end of the program, the students can say they've done active, state-of-the-art research in astrophysics."

Pinglé and Wright's particular achievement is rare. High schoolers seldom publish research, Sousa-Silva says. "Although that is one of the goals of the SRMP, it is highly unusual for high-schoolers to be co-authors on journal papers."

With guidance from mentor Tansu Daylan, a postdoc at the MIT Kavli Institute for Astrophysics and Space Research, the students studied and analyzed data from the Transiting Exoplanet Survey Satellite (TESS). TESS is a space-based satellite that orbits around Earth and surveys nearby bright stars with the ultimate goal of discovering new planets.

The team focused on TESS Object of Interest (TOI) 1233, a nearby, bright Sun-like star. To perceive if planets were orbiting around the star, they narrowed in on TOI-1233's light.

"We were looking to see changes in light over time," Pinglé explains. "The idea being that if the planet transits the star, or passes in front of it, it would [periodically] cover up the star and decrease its brightness."

To the team's surprise, they discovered not one but four planets orbiting around TOI-1233.

"I was very excited and very shocked," Wright says. "We knew this was the goal of Daylan's research, but to actually find a multiplanetary system, and be part of the discovering team, was really cool."

Three of the planets are considered "sub-Neptunes," gaseous planets that are smaller than, but similar to our own solar system's Neptune. It takes between 6 and 19.5 days for each of them to orbit around TOI-1233. The fourth planet is labeled a "super-Earth" for its large size and rockiness; it orbits around the star in just under four days.

Daylan hopes to study the planets even closer in the coming year.

"Our species has long been contemplating planets beyond our solar system and with multi-planetary systems, you're kind of hitting the jackpot," he says. "The planets originated from the same disk of matter around the same star, but they ended up being different planets with different atmospheres and different climates due to their different orbits. So, we would like to understand the fundamental processes of planet formation and evolution using this planetary system."

Daylan adds that it was a "win-win" to work with Pinglé and Wright on the study.

"As a researcher, I really enjoy interacting with young brains that are open to experimentation and learning and have minimal bias," he says. "I also think it is very beneficial to high school students, since they get exposure to cutting-edge research and this prepares them quickly for a research career."

The SRMP was established in 2016 by Or Graur, a former postdoctoral fellow at the Center for Astrophysics |Harvard & Smithsonian. The program accepts about a dozen students per year with priority given to underrepresented minorities.

Thanks to a partnership with the City of Cambridge, the students are paid four hours per week for the research they complete.

"They are salaried scientists," Sousa-Silva says. "We want to encourage them that pursuing an academic career is enjoyable and rewarding--no matter what they end up pursuing in life."

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Pinglé, a junior in high school, is considering studying applied mathematics or astrophysics after graduation. Wright has just been accepted into a five-year Master of Astrophysics program at the University of Edinburgh in Scotland.

About the Center for Astrophysics | Harvard & Smithsonian

The Center for Astrophysics | Harvard & Smithsonian is a collaboration between Harvard and the Smithsonian designed to ask--and ultimately answer--humanity's greatest unresolved questions about the nature of the universe. The Center for Astrophysics is headquartered in Cambridge, MA, with research facilities across the U.S. and around the world.

Massey researchers review geographic factors that affect HPV vaccinatio

VIRGINIA COMMONWEALTH UNIVERSITY

Research News

Human papillomavirus (HPV) is the most common sexually transmitted infection, with an estimated 79 million Americans currently infected with the virus, according to the Centers for Disease Control and Prevention. If a high-risk HPV infection does not go away, it can lead to the development of a variety of cancers, including 91% of all cervical cancers, 70% of oropharyngeal cancers and cancers of the vulva, vagina, penis and anus.

HPV vaccination can significantly reduce the number of new cancer diagnoses linked to the virus, in addition to preventing a number of other health complications.

"Given the effect that HPV vaccination has had on cancer prevention, it is important to identify factors influencing HPV vaccination coverage," said Bernard Fuemmeler Ph.D., associate director for population science, the Gordon D. Ginder, M.D., Chair in Cancer Research and co-leader of the Cancer Prevention and Control research program at VCU Massey Cancer Center.

Fuemmeler and his team conducted the first-ever systematic review of area-level data reported in the United States between 2006 and 2020 to determine how geography, neighborhoods and sociodemographic factors impact HPV vaccination rates among adolescents and young adults. The study was published in Cancer Epidemiology, Biomarkers and Prevention.

The CDC recommends two doses of the HPV vaccine six to 12 months apart beginning at age 11 or 12 and for everyone through age 26 if not already vaccinated. Despite this federal recommendation from health experts, Fuemmeler's team found that, across these studies, vaccination uptake is not uniform within the population and existing studies suggest that vaccination coverage varies markedly across the U.S and within local regions of the U.S.

"Understanding how HPV vaccination coverage varies by geography can help to identify areas of need for prevention and control efforts," said Fuemmeler, a professor in the Department of Health Behavior and Policy at the VCU School of Medicine.

Many intervention strategies have been implemented to address several of the factors that contribute to low vaccination rates, including education level, health insurance coverage, income and vaccine awareness, but those efforts are often untargeted or limited to certain areas, creating widespread geographical disparities throughout the country. For example, Fuemmeler's research shows that HPV vaccination completion rates vary from nearly 80% in Rhode Island to less than 29% in Mississippi.

Upon completion of their review, Fuemmeler's team proposed five recommendations and future considerations to overcome the current barriers to effectively address and improve national HPV vaccination coverage: 1) foster interdisciplinary collaborations and research to support more detailed analyses of geographic disparities in HPV vaccination coverage; 2) standardize procedures for immunization reporting systems to make information consistent across states; 3) standardize variable definitions in research on HPV vaccination coverage; 4) incorporate spatial regression modeling approaches to identify where HPV-related burdens are elevated and prevention and intervention efforts are needed; and 5) obtain data on HPV prevalence in smaller geographic areas for a more detailed understanding of HPV vaccination coverage nationwide.

"Our findings demonstrate the need to adopt geospatial, standardized and collaborative approaches in future studies that allow for the effective mapping, detection and reporting of geographic areas with low HPV vaccination coverage," Fuemmeler said.

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Fuemmeler's collaborators on this study include Askar Chukmaitov, M.D., Ph.D., M.P.A., and David Wheeler, M.P.H., Ph.D., members of the Cancer Prevention and Control research program at Massey; Carrie Miller, Ph.D., M.P.H., of the VCU School of Medicine; Elizabeth Do, Ph.D., M.P.H., of Truth Initiative and formerly of the VCU School of Medicine; Brianna Rossi, M.P.H., and Albert Ksinan, Ph.D., postdoctoral fellows at VCU; John Cyrus of VCU Libraries.

Additionally, Massey received $200,000 from the National Cancer Institute in 2020 for a one-year HPV supplement to its Cancer Center Support Grant. Led by Shillpa Naavaal, B.D.S., M.S., M.P.H., member of the Cancer Prevention and Control research program at Massey and assistant professor in the Department of Dental Public Health and Policy at the VCU School of Dentistry, this supplemental funding will investigate vaccine hesitancy in rural counties of Virginia and the resulting findings will inform and support the growth of infrastructure to increase HPV vaccination uptake within Massey's catchment area. This P30HPV supplement will serve three primary objectives: 1) determine reasons for vaccine hesitancy among parents of middle school-aged children in rural counties; 2) understand HPV vaccination practices and perceived barriers among health care providers and key community stakeholders; and 3) disseminate survey and interview findings and encourage conversation on how to improve HPV vaccination.

Co-investigators on this supplement include Fuemmeler, Chukmaitov and Wheeler; Tegwyn Brickhouse, DDS, Ph.D., of the VCU School of Dentistry; and Janaye Oliver, M.P.H., of the Virginia Department of Health.

No more needles for diagnostic tests?

Nearly pain-free microneedle patch can test for antibodies and more in the fluid between cells

WASHINGTON UNIVERSITY IN ST. LOUIS

Research News

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IMAGE: ENGINEERS AT THE MCKELVEY SCHOOL OF ENGINEERING AT WASHINGTON UNIVERSITY IN ST. LOUIS HAVE DEVELOPED A MICRONEEDLE PATCH THAT CAN BE APPLIED TO THE SKIN, CAPTURE A BIOMARKER OF INTEREST... view more 

CREDIT: IMAGE: SISI CAO

Blood draws are no fun.

They hurt. Veins can burst, or even roll -- like they're trying to avoid the needle, too.

Oftentimes, doctors use blood samples to check for biomarkers of disease: antibodies that signal a viral or bacterial infection, such as SARS-CoV-2, the virus responsible for COVID-19; or cytokines indicative of inflammation seen in conditions such as rheumatoid arthritis and sepsis.

These biomarkers aren't just in blood, though. They can also be found in the dense liquid medium that surrounds our cells, but in a low abundance that makes it difficult to be detected.

Until now.

Engineers at the McKelvey School of Engineering at Washington University in St. Louis have developed a microneedle patch that can be applied to the skin, capture a biomarker of interest and, thanks to its unprecedented sensitivity, allow clinicians to detect its presence.

The technology is low cost, easy for a clinician or patients themselves to use, and could eliminate the need for a trip to the hospital just for a blood draw.

The research, from the lab of Srikanth Singamaneni, the Lilyan & E. Lisle Hughes Professor in the Department of Mechanical Engineering & Material Sciences, was published online Jan. 22 in the journal Nature Biomedical Engineering.

In addition to the low cost and ease of use, these microneedle patches have another advantage over blood draws, perhaps the most important feature for some: "They are entirely pain-free," Singamaneni said.

Finding a biomarker using these microneedle patches is similar to blood testing. But instead of using a solution to find and quantify the biomarker in blood, the microneedles directly capture it from the liquid that surrounds our cells in skin, which is called dermal interstitial fluid (ISF). Once the biomarkers have been captured, they're detected in the same way -- using fluorescence to indicate their presence and quantity.

ISF is a rich source of biomolecules, densely packed with everything from neurotransmitters to cellular waste. However, to analyze biomarkers in ISF, conventional method generally requires extraction of ISF from skin. This method is difficult and usually the amount of ISF that can be obtained is not sufficient for analysis. That has been a major hurdle for developing microneedle-based biosensing technology.

Another method involves direct capture of the biomarker in ISF without having to extract ISF. Like showing up to a packed concert and trying to make your way up front, the biomarker has to maneuver through a crowded, dynamic soup of ISF before reaching the microneedle in the skin tissue. Under such conditions, being able to capture enough of the biomarker to see using the traditional assay isn't easy.

But the team has a secret weapon of sorts: "plasmonic-fluors," an ultrabright fluorescence nanolabel. Compared with traditional fluorescent labels, when an assay was done on microneedle patch using plasmonic-fluor, the signal of target protein biomarkers shined about 1,400 times as bright and become detectable even when they are present at low concentrations.

"Previously, concentrations of a biomarker had to be on the order of a few micrograms per milliliter of fluid," Zheyu (Ryan) Wang, a graduate student in the Singamaneni lab and one of the lead authors of the paper, said. That's far beyond the real-world physiological range. But using plasmonic-fluor, the research team was able to detect biomarkers on the order of picograms per milliliter.

"That's orders of magnitude more sensitive," Ryan said.

These patches have a host of qualities that can make a real impact on medicine, patient care and research.

They would allow providers to monitor biomarkers over time, particularly important when it comes to understanding how immunity plays out in new diseases.

For example, researchers working on COVID-19 vaccines need to know if people are producing the right antibodies and for how long. "Let's put a patch on," Singamaneni said, "and let's see whether the person has antibodies against COVID-19 and at what level."

Or, in an emergency, "When someone complains of chest pain and they are being taken to the hospital in an ambulance, we're hoping right then and there, the patch can be applied," Jingyi Luan, a student who recently graduated from the Singamaneni lab and one of the lead authors of the paper, said. Instead of having to get to the hospital and have blood drawn, EMTs could use a microneedle patch to test for troponin, the biomarker that indicates myocardial infarction.

For people with chronic conditions that require regular monitoring, microneedle patches could eliminate unnecessary trips to the hospital, saving money, time and discomfort -- a lot of discomfort.

The patches are almost pain-free. "They go about 400 microns deep into the dermal tissue," Singamaneni said. "They don't even touch sensory nerves."

In the lab, using this technology could limit the number of animals needed for research. Sometimes research necessitates a lot of measurements in succession to capture the ebb and flow of biomarkers -- for example, to monitor the progression of sepsis. Sometimes, that means lot of small animals.

"We could significantly lower the number of animals required for such studies," Singamaneni said.

The implications are vast -- and Singamaneni's lab wants to make sure they are all explored.

There is a lot of work to do, he said: "We'll have to determine clinical cutoffs," that is, the range of biomarker in ISF that corresponds to a normal vs. abnormal level. "We'll have to determine what levels of biomarker are normal, what levels are pathological." And his research group is working on delivery methods for long distances and harsh conditions, providing options for improving rural healthcare.

"But we don't have to do all of this ourselves," Singamaneni said. Instead, the technology will be available to experts in different areas of medicine.

"We have created a platform technology that anyone can use," he said. "And they can use it to find their own biomarker of interest."

We don't have to do all of this ourselves

Singamaneni and Erica L. Scheller, assistant professor of Medicine in the Division of Bone and Mineral Disease at the School of Medicine, worked together to investigate the concentration of biomarkers in local tissues.

Current approaches for such evaluation require the isolation of local tissues and do not allow successive and continuous inspection. Singamaneni and Scheller are developing a better platform to achieve long term monitoring of local biomarker concentration.

Working together

Srikanth Singamaneni, the Lilyan E. Lisle Hughes Professor in the Department of Mechanical Engineering & Materials Science, and Jai S. Rudra, assistant professor in the Department of Biomedical Engineering, worked together to look at cocaine vaccines, which work by blocking cocaine's ability to enter the brain.

Current candidates for such a vaccine don't confer long-lasting results; they require frequent boosting. Singamaneni and Rudra wanted a better way to determine when the effects of the vaccine had waned. "We've shown that we can use the patches to understand whether a person is still producing the necessary antibodies," Singamaneni said. "No blood draw necessary."

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UTMB team proves potential for reducing pre-term birth by treating fetus as patient

Scientists successfully tested innovative drug delivery system developed by ILIAS Biologics, Inc.

UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON

Research News

GALVESTON, Texas - The results of a study by researchers at the University of Texas Medical Branch may pave the way for a new medicine delivery system that could reduce the incidence of pre-term labor and premature birth by allowing physicians to treat the 'fetus as the patient'. The study has been published in Science Advances.

It has long been suspected that pre-term labor is triggered by inflammation caused by a sick fetus. A new study by scientists at UTMB has proved the hypothesis by studying several important assumptions about the relationship between the health of a mother and her unborn child.

According to Dr. Ramkumar Menon, a Professor in UTMB's Department of Obstetrics and Gynecology and Cell Biology, his team worked with ILIAS Biologics, Inc., a South Korean biotechnology company, to test their bioengineered exosomes as a delivery system for anti-inflammatory medicine directly to the fetus.

"Exosomes are natural nanoparticles or vesicles in our bodies, and we have trillions of them circulating through us at all times. By packaging the medicine inside a bioengineered exosome and injecting it into the mother intravenously, the exosomes travel through the blood system, cross the placental barrier and arrive in the fetus, where they deliver the medicine," explains Dr. Menon.

In laboratory tests with mice, there were several steps prior to testing the drug delivery. First, Menon said it was important to prove that fetal cells, specifically immune cells, actually migrated through the mother's body to her uterine tissues as well as to her, which can cause inflammation, the leading cause of pre-term labor.

To prove migration of cells, female mice were mated with male mice who had been genetically engineered with a red fluorescent dye called tdtomato. The dye causes cells in the male to turn red, so once mating has occurred, cells in the developing fetus also turn red and can easily be tracked as they migrate through the mother. This model was developed by Dr Sheller-Miller, a post-doctoral fellow in the Menon lab who is also the first author of this report. Development of this model that determined fetal immune cells reaching maternal tissues was also a turning point in this research.

Once scientists had proof of cell migration, they next used the mouse model to determine if bioengineered exosomes could deliver a special anti-inflammatory medicine, an inhibitor of NF-kB, called super repressor (SR) IkB from the mother's bloodstream to the fetus.

The exosomes were created using an innovative approach developed by ILIAS Biologics, Inc. called EXPLOR®, or Exosomes engineering for Protein Loading via Optically Reversible protein to protein interaction. The study proved that the exosomes effectively delivered medicine to the fetus, slowed the migration of fetal immune cells, and delayed pre-term labor.

In addition, the study found that: * Sustained effects/delays in labor required repeated dosing * Prolongation of gestation improved pup viability * Mouse models provided valuable information to help understand the mechanisms often seen in humans * Future studies, including human clinical trials are needed to confirm laboratory results

"Pre-term birth rates have not reduced in the past few decades, and this technology (the bioengineered exosomes) could lead the way to other treatments for the delivery of drugs to treat the underlying cause of inflammation in a fetus," said Dr. Menon. This technology can also be used to package other drugs in exosomes to treat other adverse pregnancy complications.

This study result is the second proof of concept that suggests significant anti-inflammatory effects of the same exosomes from ILIAS Biologics. In April 2020, the researchers at Korea Advanced Institute of Science and Technology (KAIST) and the ILIAS team published the same exosomes' substantial efficacy in the septic mouse model in Science Advances. (Link: https://advances.sciencemag.org/content/6/15/eaaz6980)

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Additional research team members include Samantha Sheller-Miller (first author), Enkhtuya Radnaa and Lauren Richardson of UTMB, Jae-Kwang Yoo, Eunsoo Kim, Kyungson Choi, Youngeun Kim, Una Kim of ILIAS Biologics, Inc., and Chulhee Choi of ILIAS Biologics, Inc and the Korea Advanced Institute of Science and Technology.

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ABOUT THE UNIVERSITY OF TEXAS MEDICAL BRANCH: Texas' first academic health center opened its doors in 1891 and today has fourcampuses, four health sciences schools, fourinstitutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, a Level 1 Trauma Center and a health system offering a full range of primary and specialized medical services throughout the Texas Gulf Coast region. UTMB is an institution in the University of Texas System and a member of the Texas Medical Center.

ABOUT ILIAS Biologics, Inc.: ILIAS Biologics Inc. was established in 2015 in South Korea to develop exosome-based therapeutics. Its platform technology, EXPLOR™, makes it possible to load large therapeutic molecules into exosomes. ILIAS Biologics Inc. is actively developing various therapeutic exosomes, Exo-Targets®, as potential treatments for sepsis, pre-term birth, and various hard-to-treat diseases in inflammatory, metabolic areas and oncology. To learn more about ILIAS Biologics Inc., visit the website at http://www.iliasbio.com.

ABOUT EXPLOR® technology: EXPLOR® technology is a novel protein-loading method that enables active loading of large therapeutic cargo proteins into the lumen of exosomes--nanosized extracellular vesicles--through cellular biogenesis processes. This process involves controllable and reversible detachment of cargo proteins from the membrane of exosomes once they load into exosomes, which increases the ef?ciency of delivery of payload proteins into the cytoplasm or nucleus of target cells. While exosomes have been actively studied as novel therapeutic vehicles for intracellular drug delivery, the controllable loading of therapeutic cargo proteins as free forms in the exosomal lumen has remained a technical hurdle. ILIAS's technology provides a unique solution to overcome this challenge.

Lack of sleep, stress can lead to symptoms resembling concussion

Study suggests baseline symptoms may help interpret recovery scores

OHIO STATE UNIVERSITY

Research News

COLUMBUS, Ohio - A new study suggests that a lot of people might be going through life with symptoms that resemble concussion - a finding supporting researchers' argument that athletes recovering from a brain injury should be assessed and treated on a highly individualized basis.

In the national study, between 11% and 27% of healthy college athletes with no history of a recent concussion reported combinations of symptoms that met criteria for post-concussion syndrome (PCS) as defined by an international classification system. Among the nearly 31,000 student-athletes surveyed, three factors stood out as the most likely to predict PCS-like symptoms: lack of sleep, pre-existing mental health problems and stress.

The participants were cadets from four U.S. military service academies - who undergo rigorous training and are required to participate in athletics - and students who competed in NCAA sports at 26 U.S. higher education institutions.

Beyond the substantial numbers of students who reported clusters of PCS-like symptoms, between one-half and three-quarters of all of the athletes surveyed reported one or more symptoms commonly experienced by people who've had a concussion, the most common being fatigue or low energy and drowsiness.

"The numbers were high, and were consistent with previous research in this area, but it is quite shocking," said study lead author Jaclyn Caccese, assistant professor in The Ohio State University School of Health and Rehabilitation Sciences. "These are elite athletes who are physically fit, and they are experiencing that many symptoms commonly reported following concussion. So looking across the general population, they'd probably have even more."

It's important to understand that there are multiple sources of these symptoms, researchers say, so that student-athletes' post-concussion care zeroes in on symptoms caused by the injury. In addition, knowing athletes' medical history and baseline symptom status may help clinicians predict which pre-existing factors could contribute to a slower recovery from a concussion.

"When a patient comes into a clinic and they are a month or more out from their most recent concussion, we need to know what symptoms they were experiencing before their concussion to know if their symptoms are attributable to their concussion or something else. Then we can start treating the concussion-related symptoms to hopefully help people recover more quickly," Caccese said.

This study, published last week in the journal Sports Medicine, was conducted by the Concussion Assessment, Research and Education (CARE) Consortium established by the NCAA and U.S. Department of Defense. Caccese completed the research while she was a PhD student and postdoctoral researcher at the University of Delaware, a consortium member institution.

The initiative is designed to fill gaps in knowledge about concussion effects and recovery among student-athletes at colleges, universities and military service academies by collecting and analyzing data on men and women who compete in a range of sports and undergo military training.

Participants in this study included 12,039 military service academy cadets and 18,548 NCAA student-athletes who completed the Sport Concussion Assessment Tool symptom evaluation as part of the consortium's baseline testing. The consortium also collected demographic data and personal and family medical histories from participants.

Statistical analyses showed which factors in athletes' medical histories were most closely associated with reports of symptoms that aligned with PCS criteria. Among cadets, 17.8% of men and 27.6% of women reported a cluster of symptoms that met PCS criteria. Among NCAA athletes, 11.4% of men and 20% of women reported combined symptoms that mimicked the PCS criteria. (Caccese said the varied timing of data collection at military service academies compared to NCAA preseason testing likely contributed to the symptoms reported by a higher percentage of cadets.)

For both groups, sleep problems - and particularly insufficient sleep the night before the test - and pre-existing psychiatric disorders were the most predictive conditions, and a history of migraines also contributed to symptoms that met PCS criteria. In cadets, academic problems and being a first-year student increased odds of having symptoms that met PCS criteria, and in NCAA athletes, a history of ADHD or depression contributed to meeting PCS criteria.

The International Classification of Diseases, Tenth Revision uses the term post-concussion syndrome for persistent symptoms following concussion, although the cause or causes of these symptoms can be difficult to determine. Symptoms range from persistent headaches, dizziness and fatigue to anxiety, insomnia and loss of concentration and memory.

A complicating factor with high symptom reporting is that recognizing concussion and determining return to play is based on reported symptoms. And while some symptoms may be more closely connected to concussion than others - such as dizziness, pressure in the head, or sensitivity to light or noise - others, like fatigue, drowsiness and even headaches, can be linked to a variety of causes.

"Perhaps we can create a battery of symptoms more specific to concussion," Caccese said. "That is another project in this series - trying to see if there are groups of symptoms or specific symptoms that may be more able to identify individuals with concussion."

The CARE Consortium also aims to identify factors that will help predict outcomes in student-athletes and cadets who suffer concussions.

"This hopefully not only shows clinicians that we need to consider how people would have presented before injury, but also provides some normative data so they can interpret other patients' data," Caccese said. "We really don't know a lot about why people have persistent symptoms, and it seems to be very variable. So we're trying to understand this better to help predict who will have a prolonged recovery, and who will not."

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Co-authors of the study were investigators from multiple CARE Consortium member institutions.

Contact:
Jaclyn Caccese,
Caccese.1@osu.edu

Written by Emily Caldwell,
Caldwell.151@osu.edu

This publication was made possible, in part, with support from the Grand Alliance Concussion Assessment, Research, and Education (CARE) Consortium, funded, in part, by the National Collegiate Athletic Association (NCAA) and the Department of Defense (DOD). The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014, is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Combat Casualty Care Research Program, endorsed by the Department of Defense, through the Joint Program Committee 6/ Combat Casualty Care Research Program - Psychological Health and Traumatic Brain Injury Program under Award No. W81XWH1420151. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.