Culture

Introducing the newly designed 'meta-grid' of nanoparticles into the epoxy casing of light-emitting diodes (LEDs) offers a substantial improvement of their light output, besides increasing lifetime, according to the scientists who invented it. A 'meta-grid' is a specially designed, optimized two-dimensional array of metallic nanoparticles, which needs to be placed at a specific location within the epoxy casing of the LEDs.

LEDs are overwhelmingly employed in the modern world. From traffic lights to backlighting for electronic displays, smartphones, large outdoor screens, and general decorative lightings and to sensing, water purification, and decontamination of infected surfaces -- LEDs are all around us! Increasing LED light output would reduce energy needs, contributing to curbing global warming and climate change.

Over the years, the task of producing greater light output for the given input, was central for LEDs. The mainstream of research in this direction was in exploring new materials for LED chip encapsulation, mainly by using either higher refractive index glasses or nanoparticle-loaded-epoxy or epoxy materials incorporated with filler powders or engineered epoxy resins, to name a few. However, with these techniques either the LED chips become bulkier or their fabrication becomes more difficult and less economical for mass production.

In a new paper published in Light Science & Application, a team of scientists -- Dr. Debabrata Sikdar, from Indian Institute of Technology Guwahati, Department of Electronics and Electrical Engineering, along with Prof. Sir John B. Pendry and Prof. Alexei Kornyshev from Imperial College London -- reported an alternative route for improving light extraction from LEDs. It proposes increasing transmission of the light generated inside the LED chip across the LED-chip/encapsulant interface by reducing the Fresnel reflection loss at the chip/encapsulant interface within a fixed photon escape cone, while prescribing minimal changes to the manufacturing process.

The enhancement in light transmission is based on destructive interference between light reflected from the chip/epoxy interface and light reflected by the 'meta-grid'. Reducing reflection from the chip/epoxy interface can also increase the lifetime of the LED chip by eliminating heating of the chip from unwanted reflections within the chip.

These scientists summarize the operational principle and merits of their 'meta-grid' scheme for LED light enhancement below:

"A significant enhancement in light extraction from LEDs can be achieved by boosting the transmission across LED-chip/encapsulant interface, by introducing a monolayer of plasmonic nanoparticles (much smaller than the wavelength of the emitted light) on top of the LED chip which can reduce the Fresnel reflection loss at the chip/encapsulant interface, through enhanced transmission originating from the Fabry-Perot effect. A similar effect is also applicable for enhancing the trapping of light in solar cells", they said.
"Our scheme can be deployed by itself or in combination with other schemes available for increasing the LED efficiency by reducing critical angle losses. The entire original theoretical framework needed for the invention has been developed in-house and is rigorously tested against standard commercial simulation tools. We plan to fabricate a prototype device within one year and corroborate our theoretical predictions with experiments."
"Our theoretical model allows determination of the optimal conditions for the structure and properties of the nanoparticle 'meta-grid' layer: viz. the material and composition of nanoparticles, their sizes and average interparticle spacing, and the distance from the surface of the LED chip -- that could provide the maximum enhancement in light extraction from the LED chip into the encapsulating casing, over any emission spectral range of LEDs", they added.

Debabrata Sikdar further commented: "with continuous advancement in nanofabrication technology, it is becoming less difficult to fabricate the nanoparticles which are mostly monodisperse and have a very narrow spread. Still, there could always be some randomness in particle size and/or position, flatness of grid, and variation in refractive index due to fabrication error or material defects, which are unavoidable. Effects from most of these inaccuracies can be roughly estimated from our tolerance study and it has shown the robustness of the mechanism of enhanced light extraction".
"There could be different engineering solutions for the meta-grids in the LED-chips. One of them would be to use drying-mediated self-assembly of nanoparticles, e.g. made of silver or alternative less-lossy plasmonic materials capped with appropriate ligands, to form free-standing the Sikdar-Premaratne-Cheng 'plasmene' sheets. Those nanoparticle monolayer sheets could be made stretchable for precise tuning of the interparticle separation and could be stamped on the LED chip before the encapsulating casing is fabricated. The distance of the 'meta-grid' from the LED chip surface can be controlled via the thickness of the plasmene's substrate", Alexei Kornyshev further added.

The authors claimed: "In this invention, we have demonstrated the effect of the 'meta-grid' for the standard commercial LEDs, based on group III-V materials. But the proposed concept of enhancing light transmission from an emissive layer to its encapsulant casing can be extended to other types of light emitting devices containing emissive-layer/encapsulant interface. Generally, our idea of using the nanoparticle 'meta-grid' for enhanced light extraction could potentially cater to a wider range of optical gadgets, not just semiconductor LEDs".

"The simplicity of the proposed scheme and the clear physics underpinning it should make it robust and, hopefully, easily adaptable to the existing LED manufacturing process. It is obvious that with larger light extraction efficiency, LEDs will provide greater energy savings as well as longer lifetimes of the devices. This will definitely have a global impact on the versatile LED based applications and their multi-billion-dollar market worldwide", Sir John B. Pendry forecasted.

Women compose half of the entering classes of medical students, yet they are underrepresented in many of the largest surgical specialties. While some efforts are underway to recruit more women into surgical specialties, little information has been available on the rate at which the gender gap is closing. A new study led by investigators from Brigham and Women's Hospital analyzed national data available through the National Graduate Medical Education Census to determine how rates of women in surgical specialties have changed over the last 11 years and use that to project how they might change in the future. In JAMA Surgery, the team reports that, among the largest resident specialties in the U.S., little progress has been made, with most of the largest residencies demonstrating a less than 1 percent increase in women trainees per year. For many specialties, including neurosurgery and orthopaedic surgery, it will take decades to reach equal female representation if progress continues at the current pace.

"This paper shows that not all fields are created equal," said co-senior author Erika Rangel, MD, MS, a surgeon and researcher in the Division of Trauma, Burn and Surgical Critical Care. "Some fields are reaching parity or have surpassed it, but many are lagging behind."

The research team analyzed publicly available, deidentified, aggregate data from 2007 to 2018 and looked across 20 specialties with the most residents. Of the 20 programs, women were underrepresented in 13. Specialties with the lowest representation included otolaryngology, plastic surgery, urology, orthopaedic surgery and neurosurgery. The researchers then estimated how long it would take to reach gender parity at the current rate of change. They found that for orthopaedic surgery, for instance, it would require more than 100 years for female residents to be equitably represented in the specialty.

"Using the rate of change that we saw in those specialties, we did further analyses to create projections to see how long it would take the specialties with the least representation to reach levels of female representation seen among all residents overall and then that of the U.S. population," said corresponding author Christopher L. Bennett, MD, MA, a former resident in the Brigham and Women's/Massachusetts General Hospital Harvard Affiliated Emergency Medicine Residency.

The authors describe several strategies that could help to improve female student recruitment to specialties. These include recognizing and rewarding mentorship; early outreach to medical students; and implicit bias training.

"At the current pace, gender parity among many surgical specialties is still decades away," the authors write. "These data call for concerted efforts to increase the pipeline for female surgical residents."

The possibility of achieving room temperature superconductivity took a tiny step forward with a recent discovery by a team of Penn State physicists and materials scientists.

The surprising discovery involved layering a two-dimensional material called molybdenum sulfide with another material called molybdenum carbide. Molybdenum carbide is a known superconductor -- electrons can flow through the material without any resistance. Even the best of metals, such as silver or copper, lose energy through heat. This loss makes long-distance transmission of electricity more costly.

"Superconductivity occurs at very low temperatures, close to absolute zero or 0 Kelvin," said Mauricio Terrones, corresponding author on a paper in Proceedings of the National Academy of Sciences published this week. "The alpha phase of Moly carbide is superconducting at 4 Kelvin."

When layering metastable phases of molybdenum carbide with molybdenum sulfide, superconductivity occurs at 6 Kelvin, a 50% increase. Although this is not remarkable in itself -- other materials have been shown to be superconductive at temperatures as high as 150 Kelvin -- it was still an unexpected phenomenon that portends a new method to increase superconductivity at higher temperatures in other superconducting materials.

The team used modeling techniques to understand how the effect occurred experimentally.

"Calculations using quantum mechanics as implemented within density functional theory assisted in the interpretation of experimental measurements to determine the structure of the buried molybdenum carbide/molybdenum sulfide interfaces," said Susan Sinnott, professor of materials science and engineering and head of the department. "This work is a nice example of the way in which materials synthesis, characterization and modeling can come together to advance the discovery of new material systems with unique properties."

According to Terrones, "It's a fundamental discovery, but not one anyone believed would work. We are observing a phenomenon that to the best of our knowledge has never been observed before."

The team will continue experimenting with superconductive materials with the goal of someday finding materials combinations that can carry energy through the grid with zero resistance.

Air conditioning and other space cooling methods account for about 10% of all electricity consumption in the U.S., according to the U.S. Energy Information Administration. Now, researchers reporting in ACS Applied Materials & Interfaces have developed a material that cools the wearer without using any electricity. The fabric transfers heat, allows moisture to evaporate from the skin and repels water. Watch a video about the new fabric here.

Cooling off a person's body is much more efficient than cooling an entire room or building. Various clothing and textiles have been designed to do just that, but most have disadvantages, such as poor cooling capacity; large electricity consumption; complex, time-consuming manufacturing; and/or high cost. Yang Si, Bin Ding and colleagues wanted to develop a personal cooling fabric that could efficiently transfer heat away from the body, while also being breathable, water repellent and easy to make.

The researchers made the new material by electrospinning a polymer (polyurethane), a water-repelling version of the polymer (fluorinated polyurethane) and a thermally conductive filler (boron nitride nanosheets) into nanofibrous membranes. These membranes repelled water from the outside, but they had large enough pores to allow sweat to evaporate from the skin and air to circulate. The boron nitride nanosheets coated the polymer nanofibers, forming a network that conducted heat from an inside source to the outside air. In tests, the thermal conductivity was higher than that of many other conventional or high-tech fabrics. The membrane could be useful not only for personal cooling, but also for solar energy collection, seawater desalination and thermal management of electronic devices, the researchers say.

In a pilot study of people living with HIV or high levels of cholesterol, Johns Hopkins Medicine researchers found that a six-week course of a cholesterol-lowering medication improved the function of the coronary arteries that provide oxygen to the heart.

The drug used in the study, a PCSK9 inhibitor, lowers the activity of PCSK9, a protein involved in cholesterol metabolism. These levels are higher in people with HIV and in those with high cholesterol.

In a pilot study of people living with HIV or high levels of cholesterol, Johns Hopkins Medicine researchers found that a six-week course of a cholesterol-lowering medication improved the function of the coronary arteries that provide oxygen to the heart.

The drug used in the study, a PCSK9 inhibitor, lowers the activity of PCSK9, a protein involved in cholesterol metabolism. These levels are higher in people with HIV and in those with high cholesterol. Currently, people with HIV receive antiretroviral medications and rarely die from the virus itself. However, the same people have an increased risk of cardiovascular disease as a result of chronic inflammation due to the virus, and they are significantly more likely to die from cardiovascular disease than the general population.

In a study published July 17 in the Journal of the American Heart Association, the Johns Hopkins researchers suggest there may be a way to limit cardiovascular disease risk in those living with HIV and other cardiovascular risk factors, such as high cholesterol, by improving the function of blood vessels.

"We hypothesized that PCSK9 mediates an inflammatory response that impairs vascular function in addition to its effects on cholesterol metabolism, and we tested this idea with the protein's inhibitor to learn whether it could help people who have impaired blood vessel function," says lead author of the study, Thorsten M. Leucker, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine. "We were surprised that this worked so well, but also heartened that there may be a way we can improve blood vessel function in those with increased inflammation."

For the study, 19 people with HIV and 11 people with high blood lipids but no HIV were given the drug evolocumab, a PCSK9 inhibitor, for six weeks. At the start of the study and following the course of treatment, the team used cardiac magnetic resonance imaging (MRI) to measure the area of, and blood flow in, the right coronary artery at rest and during a hand exercise, which normally results in relaxation of the blood vessels. When healthy people perform the test, the coronary artery responds to the exercise and its area increases, enabling more blood to flow through. In people with impaired blood vessel function, such as those with HIV or high cholesterol, the artery doesn't get larger or may even constrict. Therefore, blood flow remains the same or decreases in those with impaired blood vessel function.

After the six-week treatment with the PCSK9 inhibitor, the participants living with HIV had an average 7.9% increase in coronary artery area and a 10.1% increase in blood flow during the hand grip exercise when compared to the resting value. These changes were significantly greater than the changes from rest to hand grip exercise during the baseline pre-treatment visit. Participants with high blood lipids also had improvements in coronary artery area and an increase in blood flow after six weeks of treatment.

The researchers say future studies will need to include more patients and study them over a longer time.

Paleontologists have described in the Journal of Vertebrate Paleontology a large owl that killed medium-sized mammals with its feet and claws some 55 million years ago. "Today, owls kill with their beak," says paleontologist Thierry Smith (RBINS), who participated to the study of the well-preserved skeleton from Wyoming, USA. Primoptynx poliotaurus is a new species and a new genus.

The skeleton excavated by American paleontologists at Bighorn Basin in Wyoming thirty years ago, is one of the most complete fossilized owls of the Paleogene, the geological period after the extinction of the non-avian dinosaurs 66 million years ago. The fossil, of which all major postcranial bones have been preserved, is 54.5 to 55 million years old (early Eocene).

Different Toes

Primoptynx poliotaurus was about 50 centimeters in size - comparable to Hedwig, the snowy owl of Harry Potter - and belongs to a group of owls closely related to extinct family Protostrigidae. "Its feet are different from those of today's owls", says paleontologist Thierry Smith of the Royal Belgian Institute of Natural Sciences (RBINS), co-author of the study with Gerald Mayr of the Senckenberg Research Institute in Frankfurt and Philip Gingerich of the University of Michigan. "Owls today have four toes with claws of equal size to catch relatively small preys and kill them with the beak. Primoptynx has a longer first and second toe, as seen in hawks and other members of the family Accipitridae. Those more developed toes are used to pin down prey, which are punctured by the talons. So it was an owl that hunted like a hawk on medium-sized mammals."

This fossil shows - together with other finds - that during the early Eocene there were already many species of owls, of different sizes, which occupied different ecological niches. The success of the owls runs parallel to that of the mammals, which became very diverse after the fifth mass extinction, that wiped out the dinosaurs. The later extinction of Primoptynx poliotaurus and other proto-owls may have been due to the emergence of daytime birds of prey in the Late Eocene.

Discoveries from the early stages of owl evolution are exceedingly rare. An approximately 60-million-year-old leg bone is the oldest fossil that can be assigned to an owl. "Other owls from this time period are also only known on the basis of individual bones and fragments. Therefore, I was especially pleased when I received a largely complete owl skeleton from the North American Willwood Formation for study, which my colleague and the study's co-author, Philip Gingerich, had discovered 30 years ago," explains Dr. Gerald Mayr of the Senckenberg Research Institute and Natural History Museum in Frankfurt, Germany.

The newly described animal belongs to a previously unknown, very large species of fossil owl. Except for the skull, all major bones of the 55-million-year-old bird are preserved. "The fossil owl was about the size of a modern Snowy Owl. However, it is clearly distinguished from all extant species by the different size of its talons. While in present-day owls the talons on all toes are approximately the same size, the newly described species Primoptynx poliotauros has noticeably enlarged talons on its hind toe and second toe," explains Mayr.

These toe proportions are known from modern diurnal raptors, e.g., eagles and goshawks. These birds, which are not closely related to owls, pierce their prey with their sharp talons. Mayr and his colleagues therefore assume that the extinct owl also used its feet to kill its prey. "By contrast, present-day owls use their beak to kill prey items--thus, it appears that the lifestyle of this extinct owl clearly differed from that of its modern relatives," adds the ornithologist from Frankfurt.

Moreover, the new discovery reveals a high level of diversity among the owls of the early Eocene in North America--from the small species Eostrix gulottai, measuring a mere 12 centimeters, to the newly discovered, roughly 60-centimeter-tall bird.

"It is not clear why owls changed their hunting technique in the course of their evolution. However, we assume that it may be related to the spread of diurnal birds of prey in the late Eocene and early Oligocene, approximately 34 million years ago. Competition for prey with diurnal birds of prey may have triggered feeding specializations in owls, possibly also leading to these charismatic birds' nocturnal habits," says Mayr.

When we get a wound on our skin, the cells in our bodies quickly mobilize to repair it. While it has been known how cells heal wounds and how scars form, a team led by researchers from Washington University in St. Louis has determined for the first time how the process begins, which may provide new insight into wound healing, fibrosis and cancer metastasis.

The team, led by Delaram Shakiba, a postdoctoral fellow from the NSF Science and Technology Center for Engineering Mechanobiology (CEMB) at the McKelvey School of Engineering, discovered the way fibroblasts, or common cells in connective tissue, interact with the extracellular matrix, which provides structural support as well as biochemical and biomechanical cues to cells. The team uncovered a recursive process that goes on between the cells and their environment as well as structures in the cells that were previously unknown.

Results of the research were published in ACS Nano on July 28. Senior authors on the paper are Guy Genin, the Harold and Kathleen Faught Professor of Mechanical Engineering at the McKelvey School of Engineering, and Elliot Elson, professor emeritus of biochemistry and molecular biophysics at the School of Medicine.

"Clinical efforts to prevent the progression of fibrocontractile diseases, such as scarring and fibrosis, have been largely unsuccessful, in part because the mechanisms that cells use to interact with the protein fibers around them are unclear," Shakiba said. "We found that fibroblasts use completely different mechanisms in the early -- and I think the most treatable -- stages of these interactions, and that their responses to drugs can therefore be the opposite of what they would be in the later stages."

Genin, who is the co-director of the CEMB, said the process has stymied mechanobiology researchers for some time.

"Researchers in the field of mechanobiology thought that cells pulled in collagen from the extracellular matrix by reaching out with long protrusions, grabbing it and pulling it back," Genin said. "We discovered that this wasn't the case. A cell has to push its way out through collagen first, then instead of grabbing on, it essentially shoots tiny hairs, or filopodia, out of the sides of its arms, pulls in collagen that way, then retracts."

Now that they understand this process, Genin said, they can control the shape that a cell takes.

"With our colleagues at CEMB at the University of Pennsylvania, we were able to validate some mathematical models to go through the engineering process, and we now have the basic rules that cells follow," he said. "We can now begin to design specific stimuli to direct a cell to behave in a certain way in building a tissue-engineered structure."

The researchers learned they could control the cell shape in two ways: First, by controlling the boundaries around it, and second, by inhibiting or upregulating particular proteins involved in the remodeling of the collagen.

Fibroblasts pull the edges of a wound together, causing it to contract or close up. Collagen in the cells then remodels the extracellular matrix to fully close the wound. This is where mechanobiology comes into play.

"There's a balance between tension and compression inside a cell that is newly exposed to fibrous proteins," Genin said. "There is tension in actin cables, and by playing with that balance, we can make these protrusions grow extremely long," Genin said. "We can stop the remodeling from occurring or we can increase it."

The team used a 3D-mapping technique -- the first time it has been applied to collagen -- along with a computational model to calculate the 3D strain and stress fields created by the protrusions from the cells. As cells accumulated collagen, tension-driven remodeling and alignment of collagen fibers led to the formation of collagen tracts. This requires cooperative interactions among cells, through which cells can interact mechanically.

"New methods of microscopy, tissue engineering and biomechanical modeling greatly enhance our understanding of the mechanisms by which cells modify and repair the tissues they populate," Elson said. "Fibrous cellular structures generate and guide forces that compress and reorient their extracellular fibrous environment. This raises new questions about the molecular mechanisms of these functions and how cells regulate the forces they exert and how they govern the extent of matrix deformation."

"Wound healing is a great example of how these processes are important in a physiologic way," Genin said. "We'll be able to come up with insight in how to train cells not to excessively compact the collagen around them."

Aaron Lojewski, who leads aurora sightseeing tours in Alaska, was lucky enough to photograph a "eruption" of brilliant pink light in the night skies one night in February.

The same perturbations of the Earth's magnetic field that lit up the sky for Lojewski's camera were also captured by seismometers on the ground, a team of researchers reports in the journal Seismological Research Letters.

By comparing data collected by all-sky cameras, magnetometers, and seismometers during three aurora events in 2019, University of Alaska Fairbanks seismologist Carl Tape and colleagues show that it's possible to match the striking display of lights with seismic signals, to observe the same phenomenon in different ways.

Researchers have known for a while that seismometers are sensitive to magnetic fluctuations--and have worked hard to find ways to shield their instruments against magnetic influence or to remove these unwanted signals from their seismic data. But the aurora study offers an example of how seismometers could be paired with other instruments to study these fluctuations.

"It can be hard to be definitive that these seismometer recordings are originating from the same influence as what's going on 120 kilometers up in the sky," Tape said. "It helps to have a simultaneous view of the sky, to given you more confidence about what you're seeing from the signals at ground level."

The aurora borealis, or northern lights, occurs when solar winds--plasma ejected from the Sun's surface--meet the protective magnetic field that surrounds the Earth. The collision of particles produces colorful lights in the sky and creates fluctuations in the magnetic field that are sometimes called solar or space "storms." Magnetometers deployed on the Earth's surface are the primary instrument used to detect these fluctuations, which can significantly impact electrical grids, GPS systems and other crucial infrastructure. The aurora is commonly visible in wintertime in high-latitude regions such as Alaska.

The seismometers in the study are part of the USArray Transportable Array, a network of temporary seismometers placed across North America as part of the EarthScope project. The array in Alaska and western Canada was completed in the fall of 2017. The aurora paper is one of several included in an upcoming SRL focus section about EarthScope in Alaska and Canada.

These temporary seismic stations are not shielded from magnetic fields, unlike more permanent stations that are often cloaked in mu-metal, a nickel-iron alloy that directs magnetic fields around the instrument's sensors. As a result, "I was blown away by how well you can record magnetic storms across the array," said U.S. Geological Survey seismologist Adam Ringler, a co-author on the SRL paper.

Last month, Ringler and his colleagues published a paper demonstrating how the array's 200-plus seismometers in Alaska can be used to record space weather, potentially augmenting the 13 magnetometers in operation in the state.

Along with the all-sky camera data, seismic array data can help make sense of the strong variations in the magnetic field that occur in a magnetic east-west direction, adding a second dimension to typical north-south directional studies of the aurora and other magnetic storms, Tape and colleagues suggest.

The researchers noted in their paper that the link between the aurora borealis and magnetic perturbations was first discovered in Sweden in 1741, and that a seismometer in Germany detected an atmosphere-generated magnetic event for the first time during a strong solar storm in 1994.

"People have been making these connections for 250 years," Tape said. "This shows that we can still make discoveries, in this case with seismometers, to understand the aurora."

A new University of Maryland-led study shows that subsidies can help people continually purchase insurance products, but only if they have the financial literacy to understand the benefits of the policy and have the experience of seeing the benefits in action. In a new paper published in American Economic Review, researchers conducted the first ever experimental study to look at the impact of subsidy policies on insurance policy adoption. In the US, most insurance products are highly subsidized by the government, but recent studies on health insurance show that people seem to put very low value on health and agricultural insurance products alike, leading to low adoption. This paper provides insight into this dilemma known as the "insurance puzzle", with implications for insurance subsidy policies and educational programs.

"We know that there is an insurance demand puzzle in both developed and developing countries, in that people put a very low value on insurance so there is low adoption of agricultural and health insurance," says Jing Cai, assistant professor in Agricultural & Resource Economics at UMD. "And in poor countries, agricultural cultivation is their main source of income and they often face a lot of weather challenges where insurance could help recuperate their losses, but even then, insurance adoption is very low. It is puzzling."

Cai wanted to take a closer look at this puzzle. "Governments frequently provide subsidies with new products and technologies so that more people will buy it, try it, and see the benefit of the product with the long term goal that when the subsidy is removed, people will still see the benefit and be willing to purchase the product for the unsubsidized cost. This is why subsidies are a widely used government policy," explains Cai.

The paper is the first to use an experimental design to look at the impact of subsidy policy on insurance demand and purchasing behavior, but also combines subsidy policy with financial education, another commonly used tactic to increase insurance adoption. This combination of tactics is also unique to this paper, examining how these two common practices interact. "The idea behind financial education interventions is to improve trust and provide understanding of the benefits of the product, but these interventions still don't highly improve insurance uptake rates either, just like subsidy programs," says Cai.

In this study, a new insurance product was introduced to rice-producing farmers in rural China. Some of the 130 villages (representing 3500 households) selected randomly received the insurance for free, and others had to pay a subsidized amount. The households were then randomized, with some receiving financial education on the insurance concepts, contracts, and concrete examples of simulated payout scenarios for continually purchasing insurance to show the long term financial benefit.

Similarly to previous studies, the researchers found that subsidies and financial education have small effects on their own. However, when financial education and subsidy policy is combined with an actual payout, there was a significant interaction effect that led to long term insurance purchasing, monitored up to five years after the initial financial education and introduction of the insurance product.

"There is a financial education effect itself, but it is not as great as with the payout effect. People can understand why it is important and beneficial to buy insurance, but they still might not buy it without the subsidy or without the chance to experience the product," says Cai.

Cai continues, "If you purchase insurance and no event happens, you aren't learning the importance of that insurance necessarily, you aren't seeing that benefit. It is only when you purchase insurance and an event happens, then you see how insurance will pay for your loss driven by risks and can compare the income after and before insurance. This is where farmers can really learn something."

Based on the findings, Cai explains that it isn't enough for people to be able to afford the product through a subsidy, or even to see it in action by personally receiving a payout or knowing someone who has, but they need to be able to understand why and how it is beneficial to purchase insurance every single year with financial literacy education. The combination of these three things is what ultimately leads to long term insurance uptake.

"This explains why often subsidy policies do not work in promoting products with technology adoption or insurance that requires complicated learning," says Cai. "In this case, if you provide subsidies without improving people's financial literacy, they aren't going to be able to process the information that they should acquire from the payout experience because they don't have the initial insurance context to make sense of their experience and realize the value of insurance long term."

This finding has clear implications for insurance policies, not just in rural areas, but across all settings where insurance adoption is a problem. "In order to improve insurance uptake, policy makers should think about combining subsidy policies with education programs to improve the chance that people will actually learn from their experiences, which is the original hope of the policy maker."

WORCESTER, MA - UMass Medical School researchers Zhiping Weng, PhD, and Jill Moore, PhD, and MD/PhD students Michael Purcaro and Henry Pratt are lead authors on the latest publication of data from the ambitious ENCODE project. Collaborating with other members of the ENCODE consortium, the UMMS team used computational biology to identify functional elements in the human genome.

These elements act as switches, controlling when and where genes are turned on and how they are tuned. Results from their data analysis, published in the latest issue of Nature, identified 926,535 human candidate cis-regulatory elements (cCREs), which are regions of noncoding DNA that control neighboring genes. The full data set is now available to scientists in visual form at screen.encodeproject.org, a web tool also developed by the team.

"There are 3 billion base pairs in our genome and not every one of them has a known function," said Dr. Weng, the Li Weibo Chair in Biomedical Research, professor of biochemistry & molecular pharmacology and director of the Program in Bioinformatics & Integrative Biology. "Identifying and annotating the specific regions of DNA that help control our genes is key to understanding the complexity of the genome and how it works."

Only about 20,000 genes make up the protein coding portion of the human genome. Genes can be thought of as the primary workhorses of the genome, carrying instructions for making proteins, the large, complex molecules that do most of the work in cells and that are required for the body's tissues and organs to do their respective jobs. Genes have been methodically studied down to the specific genetic code with which they encode their instructions. However, this leaves large swaths of DNA outside of these protein coding areas, many of which are known to affect health and promote disease.

"If our genome is like a car, then the protein coding part of the car is the engine," said Weng. "It propels us forward. How we control and make use of that engine--accelerating, turning, braking--is controlled by other mechanisms. In the genome, one family of these mechanisms is the cis-regulatory elements that promote and enhance, turn on or off, and fine-tune our genes."

Established in 2003, the ENCODE project--short for Encyclopedia of DNA Elements--is a global effort to understand how the human genome works. The goal is to develop an annotated encyclopedia of the functional elements--regions of DNA that code for molecular products or biochemical activities with roles in gene regulation--contained in the human genome. While much is known about protein coding genes, this only represents 2 percent of the entire genome. Far less is known about the other 98 percent of the genome, some of which helps control these genes. Working as an integral part of the ENCODE consortium during Phase III of the project, the UMMS team established a registry of a million candidate DNA "switches" from the human genome. This represents 7.8 percent of the genome that could potentially play an important role in how genes work.

The human body is made up of thousands of different cell types--liver cells, skin cells, neurons. Although all of these cells carry identical sets of DNA, these diverse cells carry out very different functions by using the information encoded in the genome differently. The DNA regions that turn genes on or off and tune the exact levels of activity are responsible for this diversity. They drive the formation of different cell types and control how they function in the body.

To find the different switches that lead to such a diverse array of cell types, the 500 plus scientists that make up ENCODE studied sets of biochemical features that are associated with the genetic switches that control genes. In total, researchers performed more than 6,000 biochemical experiments (4,834 involving human samples and 1,158 with mouse samples). They analyzed chromatin accessibility, histone modifications, DNA methylation, chromatin looping and a host of other assays, to pinpoint regions of the genome where chemical reactions associated with regulatory activity were occurring. Performed in more than 500 different cell types, these experiments yielded millions of locations in the human genome where these regulatory switches could potentially reside, from which the UMMS team established the Registry of cCREs.

The hope is that scientists will use these candidate areas to help establish potential links between regulatory switches and disease. For example, the ENCODE data could be employed to provide new insights into genome-wide association studies that connect areas outside of protein-coding genes that are associated with genetic diseases, explained Dr. Moore, a bioinformatician in the Weng Lab and project manager of the ENCODE Data Analysis Center.

Of the almost 1 million human cCREs identified, Weng and ENCODE collaborators tested 150 using functional assays to see if genetic changes in these areas might impact health. One area of interest, which resides near the neural gene AGAP1 and has been associated with schizophrenia, was shown to have regulatory activity in the brains of embryonic mice. Further functional testing can be performed on these elements to explore how and why they impact disease. Scientists can also use the candidate areas to compare against their genetic studies for health and disease. The Weng lab leads such effort in the PsychENCODE Consortium, a large-scale collaborative project like ENCODE that focuses on the role of regulatory elements in human brain development and psychiatric disorders.

To make use of all this data, Purcaro and Pratt developed online resources to share this information with members of the scientific community. SCREEN, short for Search Candidate cis-Regulatory Elements by ENCODE, allows scientists to visualize and interactively search the 926,535 human cCREs derived from the ENCODE data, along with ENCODE data and other rich annotations in more than one thousand biological samples.

"Over the last 10 years, genome-wide association studies into disease have identified many areas of potential interest outside of the protein coding genes," said Weng. "This tool gives scientists a new and powerful way to explore if some of those disease-causing areas of the genome are in regulatory regions."

The full ENCODE III findings are included in a collection of 14 papers in Nature, Nature Methods and Nature Communications, as well as a corresponding perspective piece in Nature by Weng and colleagues.

Researchers at University of California San Diego School of Medicine are among the contributors to a package of 10 studies, published July 29, 2020 in the journal Nature, describing the latest results from the ongoing Encyclopedia of DNA Elements (ENCODE) project, a worldwide effort led by the National Institutes of Health (NIH) to understand how the human genome functions.

This third series of published papers includes descriptions of millions of candidate DNA "switches" from the human and mouse genomes that appear to regulate when and where genes are turned on, a new registry that assigns a portion of these DNA switches to useful biological categories and new visualization tools to assist in the use of ENCODE's large datasets.

To assess the potential functions of different DNA regions, ENCODE researchers studied biochemical processes that are typically associated with the switches that regulate genes. This biochemical approach is an efficient way to explore the entire genome rapidly and comprehensively. This method helps to locate regions in the DNA that are "candidate functional elements"-- DNA regions that researchers predict are functional elements based on these biochemical properties. They can then test candidates in further experiments to identify and characterize their functional roles in gene regulation.

"A key challenge in ENCODE is that different genes and functional regions are active in different cell types," said Elise Feingold, PhD, scientific advisor for strategic implementation in the Division of Genome Sciences at the National Human Genome Research Institute, part of the NIH, and a lead on ENCODE for the institute. "This means that we need to test a large and diverse number of biological samples to work towards a catalog of candidate functional elements in the genome."

Research teams headed by Bing Ren, PhD, professor of cellular and molecular medicine, director of the Center for Epigenomics at UC San Diego School of Medicine and a member of the San Diego branch of the Ludwig Institute for Cancer Research, and Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine, each published a study in the latest issue of Nature.

Chromatin atlas

The laboratory mouse is widely used in biomedical research to model human biology and disease. One key advantage of the mouse is that researchers have access to stages of fetal development that are difficult or impossible to study in humans. In the study by Ren, with first author David Gorkin, PhD, and colleagues, scientists profiled the chromatin structure in 12 different tissues over multiple stages of development in the mouse, revealing information about the activity of underlying genes during an organism's development. They then used the maps to define more than 500,000 candidate transcriptional regulatory elements in the mouse genome, which serve to control when and where the more than 20,000 genes in the mouse genome are activated during fetal development.

Their results have two major implications for human disease research, said Ren.

"First, we found that genetic risk variants for a variety of human diseases are located in regions of the human genome that share evolutionary origins with the mapped mouse gene regulatory sequences, suggesting that these regions of the human genome may be functional in humans, and that some of the disease risk variants in them may be affecting fetal development.

"Second, our results provide important tools for researchers using mice to model human disease, helping them focus on specific tissues, developmental stages and regions of the genome that may be most relevant to their targeted disease."

RNA-binding proteins

In Yeo's study, with first author Eric L. Van Nostrand, PhD, and colleagues, researchers introduce a new set of regulatory elements embedded in human DNA that are recognized by RNA-binding proteins that interact with these elements only when they are transcribed into RNA. The study authors write that these RNA-binding proteins act as computers that read these RNA elements and act on their instructions to "process" RNA, such as trimming excess pieces (splicing) or adding "tails" to stabilize messages.

The work represents the most comprehensive dataset yet of RNA-binding protein-interactomes.

Yeo said the findings are significant because they reveal novel functions for many RNA-binding proteins and identify genetic elements that will serve as the foundation to decipher which human mutations cause misregulated or failed RNA "processing." The Yeo team has already leveraged the information to create principles of regulation by these proteins, highlighting the importance of RNA research that will aid new therapeutic arenas.

"I am astounded by the complexity of regulation by these RNA-binding proteins and I believe our new datasets will open the doors to every field of disease, genetics and molecular biology," Yeo said.

Of note: More than two dozen UC San Diego faculty or researchers with UC San Diego affiliations are listed among the co-authors of the 10 published papers in the latest ENCODE issue of Nature. Full contents of the journal can be found here.

Significant progress has been made in characterizing protein-coding genes, which comprise less than 2 percent of the human genome. Researchers know much less about the remaining 98 percent of the genome, including how much and which parts of it perform other functions. ENCODE was created to help fill in this knowledge gap.

The human body is composed of trillions of cells, with thousands of types of cells. While all these cells share a common set of DNA instructions, the diverse cell types, such as heart, lung and brain, carry out distinct functions by using the information encoded in DNA differently. The DNA regions that act as switches to turn genes on or off, or to tune the exact levels of gene activity, help drive the formation of distinct cell types in the body and govern their functioning in health and disease.

As a new feature, ENCODE 3 researchers created a resource detailing different kinds of DNA regions and their corresponding candidate functions. A web-based tool called SCREEN allows users to visualize the data supporting these interpretations.

The ENCODE Project began in 2003 and is an extensive collaborative research effort involving groups across the United States and around the world, comprising more than 500 scientists with diverse expertise. It has benefited from and built upon decades of research on gene regulation performed by independent researchers around the world.

ENCODE researchers have created a community resource, ensuring that the project's data is accessible to any researcher for their studies. These efforts in open science have resulted in more than 2,000 publications from non-ENCODE researchers who used data generated by the ENCODE Project.

"This demonstrates that the encyclopedia is widely used, which is what we had always aimed for," said Feingold. "Many of these publications are related to human disease, attesting to the resource's value for relating basic biological knowledge to health research."

Shade from urban trees has long been understood to offer respite from the urban heat island effect, a phenomenon that can result in city centers that are 1-3 degrees Centigrade warmer than surrounding areas. Less frequently discussed, however, are the effects of tree transpiration in combination with the heterogeneous landscapes that constitute the built environment.
Writing in BioScience, Joy Winbourne and her colleagues present an overview of the current understanding of tree transpiration and its implications, as well as areas for future research. Their work, derived from tree sap flow data, reveals the complexity and feedbacks inherent in trees' and urban zones' responses to extreme heating events.
Dr. Winbourne joins us on this episode of BioScience Talks to discuss the newly published article, as well as directions for future research and the prospects for using trees to better mitigate urban heat in the face of a changing climate.

The classic dinosaur family tree has two subdivisions of early dinosaurs at its base: the Ornithischians, or bird-hipped dinosaurs, which include the later Triceratops and Stegosaurus; and the Saurischians, or lizard-hipped dinosaurs, such as Brontosaurus and Tyrannosaurus.

In 2017, however, this classical view of dinosaur evolution was thrown into question with evidence that perhaps the lizard-hipped dinosaurs evolved first -- a finding that dramatically rearranged the first major branches of the dinosaur family tree.

Now an MIT geochronologist, along with paleontologists from Argentina and Brazil, has found evidence to support the classical view of dinosaur evolution. The team's findings are published today in the journal Scientific Reports.

The team reanalyzed fossils of Pisanosaurus, a small bipedal dinosaur that is thought to be the earliest preserved Ornithiscian in the fossil record. The researchers determined that the bird-hipped herbivore dates back to 229 million years ago, which is also around the time that the earliest lizard-hipped Saurischians are thought to have appeared.

The new timing suggests that Ornithiscians and Saurischians first appeared and diverged from a common ancestor at roughly the same time, giving support to the classical view of dinosaur evolution.

The researchers also dated rocks from the Ischigualasto Formation, a layered sedimentary rock unit in Argentina that is known for having preserved an abundance of fossils of the very earliest dinosaurs. Based on these fossils and others across South America, scientists believe that dinosaurs first appeared in the southern continent, which at the time was fused together with the supercontinent of Pangaea. The early dinosaurs are then thought to have diverged and fanned out across the world.

However, in the new study, the researchers determined that the period over which the Ischigualasto Formation was deposited overlaps with the timing of another important geological deposit in North America, known as the Chinle Formation.

The middle layers of the Chinle Formation in the southwestern U.S. contain fossils of various fauna, including dinosaurs that appear to be more evolved than the earliest dinosaurs. The bottom layers of this formation, however, lack animal fossil evidence of any kind, let alone early dinosaurs. This suggests that conditions within this geological window prevented the preservation of any form of life, including early dinosaurs, if they walked this particular region of the world.

"If the Chinle and Ischigualasto formations overlap in time, then early dinosaurs may not have first evolved in South America, but may have also been roaming North America around the same time," says Jahandar Ramezani, a research scientist in MIT's Department of Earth, Atmospheric, and Planetary Sciences, who co-authored the study. "Those northern cousins just may not have been preserved."

The other researchers on the study are first author Julia Desojo from the National University of La Plata Museum, and a team of paleontologists from institutions across Argentina and Brazil.

"Following footsteps"

The earliest dinosaur fossils found in the Ischigualasto Formation are concentrated within what is now a protected provincial park known as "Valley of the Moon" in the San Juan Province. The geological formation also extends beyond the park, albeit with fewer fossils of early dinosaurs. Ramezani and his colleagues instead looked to study one of the accessible outcrops of the same rocks, outside of the park.

They focused on Hoyada del Cerro Las Lajas, a less-studied outcrop of the Ischigualasto Formation, in La Rioja Province, which another team of paleontologists explored in the 1960s.

"Our group got our hands on some of the field notes and excavated fossils from those early paleontologists, and thought we should follow their footsteps to see what we could learn," Desojo says.

Over four expeditions between 2013 to 2019, the team collected fossils and rocks from various layers of the Las Lajas outcrop, including more than 100 new fossil specimens, though none of these fossils were of dinosaurs. Nevertheless, they analyzed the fossils and found they were comparable, in both species and relative age, to nondinosaur fossils found in the park region of the same Ischigualasto Formation. They also found out that the Ischigualasto Formation in Las Lajas was significantly thicker and much more complete than the outcrops in the park. This gave them confidence that the geological layers in both locations were deposited during the same critical time interval.

Ramezani then analyzed samples of volcanic ash collected from several layers of the Las Lajas outcrops. Volcanic ash contains zircon, a mineral that he separated from the rest of the sediment, and measured for isotopes of uranium and lead, the ratios of which yield the mineral's age.

With this high-precision technique, Ramezani dated samples from the top and bottom of the outcrop, and found that the sedimentary layers, and any fossils preserved within them, were deposited between 230 million and 221 million years ago. Since the team determined that the layered rocks in Las Lajas and the park match in both species and relative timing, they could also now determine the exact age of the park's more fossil-rich outcrops.

Moreover, this window overlaps significantly with the time interval over which sediments were deposited, thousands of kilometers northward, in the Chinle Formation.

"For many years, people thought Chinle and Ischigualasto formations didn't overlap, and based on that assumption, they developed a model of diachronous evolution, meaning the earliest dinosaurs appeared in South America first, then spread out to other parts of the world including North America," Ramezani says. "We've now studied both formations extensively, and shown that diachronous evolution isn't really based on sound geology."

A family tree, preserved

Decades before Ramezani and his colleagues set out for Las Lajas, other paleontologists had explored the region and unearthed numerous fossils, including remains of Pisanosaurus mertii, a small, light-framed, ground-dwelling herbivore. The fossils are now preserved in an Argentinian museum, and scientists have gone back and forth on whether it is a true dinosaur belonging to the Ornithiscian group, or a " basal dinosauromorph" -- a kind of pre-dinosaur, with features that are almost, but not quite fully, dinosaurian.

"The dinosaurs we see in the Jurassic and Cretaceous are highly evolved, and ones we can nicely identify, but in the late Triassic, they all looked very much alike, so it's very hard to distinguish them from each other, and from basal dinosauromorphs," Ramezani explains.

His collaborator Max Langer from the University of São Paulo in Brazil painstakingly reanalyzed the museum-preserved fossil of Pisanosaurus, and concluded, based on certain key anatomical features, that it is indeed a dinosaur -- and what's more, that it is the earliest preserved Ornithiscian specimen. Based on Ramezani's dating of the outcrop and the interpretation of Pisanosaurus, the researchers concluded that the earliest bird-hipped dinosaurs appeared around 229 million years ago -- around the same time as their lizard-hipped counterparts.

"We can now say the earliest Ornithiscians first showed up in the fossil record roughly around the same time as the Saurischians, so we shouldn't throw away the conventional family tree," Ramezani says. "There are all these debates about where dinosaurs appeared, how they diversified, what the family tree looked like. A lot of those questions are tied to geochronology, so we need really good, robust age constraints to help answer these questions."

A consensus statement published today in JAMA Dermatology by an international group of melanoma researchers evaluates the use of prognostic genetic expression profile (GEP) testing to guide clinical management of patients with melanoma. The group cautioned against routine use of currently available GEP tests for patients with cutaneous melanoma.

Prognostic gene expression profiling is a technique that measures the expression of a particular group of genes that may help predict patient outcomes. For melanoma, GEP tests are designed to predict whether a patient's tumor is likely to be aggressive and metastasize. Although routine GEP testing is not endorsed by national melanoma care guidelines, its use is increasing among clinicians who care for patients with melanoma to guide decisions on treatment and surveillance imaging. GEP testing may have limitations, however, particularly in early-stage tumors where a "low risk" result could give patients a false sense of security or a "high risk" result could subject them to more aggressive treatments or monitoring that may be unnecessary. Further, there are no national standards for which type of test should be used, when it should be used, or how accurate these tests need to be.

An international group of melanoma experts, the Melanoma Prevention Working Group, sought to advance conversations around how and when gene expression profiling should be used by clinicians caring for patients with melanoma. Through a series of meetings, surveys, and literature reviews, they authored this statement to review the current data and make recommendations on use of GEP testing in melanoma. Their goal is to assist clinicians in determining when and how gene expression profiling should be adopted in clinical practice and to outline the criteria by which tests should be evaluated and incorporated into clinical care guidelines.

The group included approximately 200 dermatologists, medical oncologists, surgical oncologists, and laboratory researchers who specialize in melanoma. "We are optimistic about the future use of gene expression profiling in melanoma patients and are hopeful that this consensus statement can be a resource to clinicians in understanding the limitations of GEP testing and guiding the evaluation and use of new tests as they become available," said Doug Grossman, MD, PhD, Melanoma Center leader at Huntsman Cancer Institute (HCI) and professor of dermatology at the University of Utah. Grossman convened the working group and is lead author of this consensus statement.

The researchers hope the statement will provide a road map to help understand how GEP testing should be used when caring for patients with melanoma and what further evaluation is needed for its adoption in this field.

Of the first confirmed COVID-19 case in each affected country outside mainland China, almost two thirds had travel links to Italy, China, or Iran.

Study suggests 1 in 4 of these first cases originated in Italy, and 1 in 5 in China.

Many small clusters of household transmission were reported among early cases, but clusters in occupational and community settings tended to be larger--supporting the role of physical distancing to slow the spread of COVID-19.

Web-based surveillance of the global spread of SARS-CoV-2 (the virus that causes COVID-19) during the first 11 weeks of the outbreak (Dec 31, 2019, to March 10, 2020), reveals that three-quarters (75/99) of affected countries outside mainland China reported their first COVID-19 case in people who had recently travelled to an affected country--with almost two-thirds of these first cases linked to travel to Italy (27%), China (22%), or Iran (11%), according to new research published in The Lancet Infectious Diseases journal.

"Our findings suggest that travel from just a few countries with substantial SARS-CoV-2 transmission may have seeded additional outbreaks around the world before the characterisation of COVID-19 as a pandemic on March 11, 2020", says Dr Fatimah Dawood from the Centers for Disease Control and Prevention (CDC), USA, who co-led the research.

The study is the first of its kind to use publicly available global case data to describe travel exposure and case cluster characteristics among early COVID-19 cases in different countries. However, the authors caution that given almost all cases in the analysis were reported in middle-income and high-income countries from Asia and Europe (due to late detection in other regions), they were unable to draw a complete picture of COVID-19's early global epidemiology.

In this study, researchers examined publicly available online reports from national ministries of health and other government agency websites, social media feeds, and press releases on a daily basis to identify newly confirmed cases of COVID-19 reported between Dec 31, 2019, and March 10, 2020 (ie, during the prepandemic period, corresponding to weeks 1-11 of the outbreak). Countries with at least one case were classified as affected. Early cases were defined as the first 100 cases reported in each country, and later cases as those after the first 100 cases. The researchers analysed travel history for the first case reported in each country outside mainland China, case characteristics (eg, age, sex, exposure), and cluster frequencies and sizes.

During the first 11 weeks of the COVID-19 outbreak, 32,459 COVID-19 cases were identified from 99 countries and locations outside mainland China (figure 1).

The analysis found that travel history of the first reported case in each affected country varied by world region (figure 3 and infographic). Travel to Italy was linked with half (3/6 cases) of the first-reported cases in Africa, and over a third (36%, 16/45) in Europe and the Americas (38%, 5/13). Travel to mainland China accounted for 83% (10/12) of the first-reported cases in the Western Pacific and over half (57%, 4/7) in Southeast Asia. Seven (44%) first-reported cases in the Eastern Mediterranean region had a history of travel to Iran.

Among 1,200 cases from 68 countries with age or sex information available [2], 874 (73%) were early cases, with an average age of 51 years. Just 3% of cases (25/762 with age information available) occurred in children younger than 18 years. In total, 2% (21/1,200) of early cases occurred in health-care workers.

During the prepandemic period, 101 clusters involving 386 cases were identified in 29 countries (table 3). Household transmission was reported in three-quarters (76/101) of clusters, with an average of 2.6 cases in each cluster. By contrast, the 11 clusters related to community gatherings (ie, tour groups, faith-based groups, and dinner parties; average 14.2 cases per cluster), and the 14 clusters reported in non-health-care occupational settings (average 4.3 cases per cluster), tended to be larger--supporting a possible role for physical distancing in slowing the spread of COVID-19, researchers say.

"Four large clusters in our analysis, and large outbreaks reported elsewhere, have been linked with transmission in faith-based settings, highlighting the need to partner with faith-based organisations when designing and implementing community mitigation efforts", says co-author Dr Philip Ricks from the US CDC. "Six healthcare-associated clusters were also identified, underscoring the need for strict infection prevention and control practices and monitoring health-care workers for signs of illness." [1]

The analysis also highlights the relatively late detection of COVID-19 in Africa, with only 6 out of 46 (13%) countries studied in the region reporting cases by the time WHO characterised the outbreak a pandemic on March 11, 2020. This compares with a third (13/35) of countries in the Americas and the majority of countries in Europe (45/54, 83%), Eastern Mediterranean (16/23, 70%), and Southeast Asia (7/11, 64%).

"The epidemiology of COVID-19 in low-income countries and in Africa could differ, as reported in previous influenza pandemics, and accurate data from these settings will be needed to assess the full global effect of the COVID-19 pandemic", says Dawood. [1]

The authors note some important limitations of their study, including that the analysis of case characteristics was limited to only 4% (1,200/32,459) of global confirmed cases that had sufficient information about a case's age or sex; and publicly available data varied in completeness, which could have resulted in some case characteristics going undetected. They also note that the first confirmed case in each country might not have been the first true case of infection in some countries, since early case detection efforts varied substantially.