The study, led by investigators at St. Michael’s Hospital, a site of Unity Health Toronto, and the University of Vermont Larner College of Medicine, is available as a preprint on MedRxiv.

Heparin — a blood thinner given regularly at low dose to hospitalized patients — stops clots from forming and reduces inflammation. “This study was designed to detect a difference in the primary outcome that included ICU transfer, mechanical ventilation or death,” says Mary Cushman, M.D., M.Sc., study co-principal investigator and a professor of medicine at the University of Vermont’s Larner College of Medicine.

The open-label randomized international multi-center RAPID Trial (also known as the RAPID COVID COAG — RAPID Trial) examined the benefits of administering a therapeutic full dose of heparin versus a prophylactic low dose to moderately ill patients admitted to hospital wards with COVID-19.

The primary outcome was a composite of ICU admission, mechanical ventilation, or death up to 28 days. Safety outcomes included major bleeding. Primary outcome occurred in 37 of 228 patients (16.2%) with therapeutic full dose heparin, and 52 of 237 (21.9%) with low dose heparin (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.43-1.10; p=0.12). Four patients (1.8%) with therapeutic heparin died vs. 18 (7.6%) with prophylactic heparin (OR, 0.22; 95% CI, 0.07-0.65).

“While we found that therapeutic heparin didn’t statistically significantly lower incidence of the primary composite of death, mechanical ventilation or ICU admission compared with low dose heparin, the odds of all-cause death were significantly reduced by 78 percent with therapeutic heparin,” says first author and co-principal investigator Michelle Sholzberg, M.D.C.M., M.Sc., Head of Division of Hematology-Oncology, medical director of the Coagulation Laboratory at St. Michael’s Hospital of Unity Health Toronto, and assistant professor at the University of Toronto.

Peter Jüni, M.D., co-principal investigator, director of the Applied Health Research Centre (AHRC) at St. Michael’s, and professor of medicine at the University of Toronto, says that the researchers also presented a meta-analysis of randomized evidence (including data from a large multiplatform trial of ATTACC, ACTIV-4a and REMAP-CAP), which clearly indicated that therapeutic heparin is beneficial in moderately ill hospitalized COVID-19 patients. He adds that an additional meta-analysis presented in the preprint showed that therapeutic heparin is beneficial in moderately ill hospitalized patients but not in severely ill ICU patients.

Another unique aspect of the RAPID Trial was its funding mechanism — a sort of grassroots effort in which support was gathered via Defence Research Development Canada, St. Michael’s Hospital Foundation, St. Joseph’s Healthcare Foundation, participating institutional grants, and even a GoFundMe campaign, among other sources.

“We called this trial ‘The Little Engine that Could,’ because of the sheer will of investigators around the world to conduct it,” says Cushman.

Sholzberg says, “We believe that the findings of our trial and the multiplatform trial taken together should result in a change in clinical practice for moderately ill ward patients with COVID-19.”

The study, published in Biological Conservation, evaluates potential tradeoffs between climate benefits and energy costs, especially any negative impacts on biodiversity. While the environmental consequences of some renewable energy sources, like hydropower, have been widely studied, the large-scale impacts of other renewables, like solar, aren’t well known.

“The study points to a need for the global community to understand the opposing endpoints of sustainability, which are scale-dependent,” McManamay said. “At one endpoint, efforts to mitigate climate change at global scales via large-scale energy transitions may be completely incognizant of the consequences on local biodiversity. Likewise, local conservationists may not appreciate the magnitude of energy transitions required to shift global carbon emissions. Finally, I think there is a broad misconception among much of the community that if renewable energies are good for climate, they must also be good for the local ecosystem. Energies like solar have the potential to be deployed haphazardly with that mindset.”

The challenges of climate mitigation in relation to different climate policy scenarios are projected in five Shared Socio-economic Pathways (SSPs) — qualitative descriptions of plausible alternative socio-economic development in the next century. The SSPs include alternative projections in deployment of electricity generations by technology. Considering scenarios under the SSPs, ecological footprinting was used to evaluate the potential land and biodiversity tradeoffs of 10 different energy sources: solar photovoltaic, concentrated solar power, wind, hydropower, coal, conventional oil, conventional gas, unconventional oil, unconventional gas, and biomass.

“Ecological footprinting took into account land-use efficiencies of each technology as well as estimates of the degree of habitat alteration arising from technology deployment,” McManamay said. “This provides a standardized way to compare the biodiversity consequences of large-scale deployment of alternative energy technologies.”

Researchers estimated a biodiversity footprint for each of the 10 energy sources by overlaying energy densities and habitat alteration probabilities with biodiversity patterns. They then used spatial modeling to examine regional variations in future energy deployment and potential biodiversity impacts at a high-resolution. Different biodiversity footprints were scored based on their impact and a cumulative biodiversity score was determined for each of the 10 energy sources.

The cumulative impact scores among the SSPs showed significant and consistent differences — the fossil-fueled development pathway (SSP 5) had the highest impacts while the regional rivalry scenario (SSP3) had the lowest. The sustainability-focused scenario (SSP1) represented a moderate impact score by comparison. Unexpectedly, the variation among SSPs didn’t show a clear tradeoff between global climate mitigation and cumulative biodiversity impact.

“It was surprising to see the lack of a clear tradeoffs among sustainability endpoints,” McManamay said. “This elicited us to take a deeper look into differences among the SSPs. Although SSP5 is termed ‘fossil-fueled’ development, the pathway includes significant technological advances in both advanced fossil and renewable technologies to meet highly consumptive, energy-luxurious lifestyles. In other words, the biodiversity impacts are more related to total energy deployment than fossil versus renewable technologies. Although SSP1 is also characterized by significant renewable energy deployment, overall energy demand decreases due to increases in energy efficiencies. So, our work suggests that climate mitigation may not necessarily have to be at odds with biodiversity conservation.”

Additionally, land constraints accounted for the most variation in biodiversity impact, particularly with regard to protected land use. Downscaled electricity generation scenarios were constrained by alternative land conservation and energy development policies.

The results offer an approximation of land and biodiversity impacts of future energy strategies outlined in the SSPs. While there were differences in the SSPs, the impact scores suggest that land protection measures and energy diversification could have greater implications for biodiversity challenges than the national-level global energy pathways outlined in the SSPs. Future planning and objectives for climate mitigation will require both broad and local consideration of biodiversity challenges.

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Significantly, the results from the research with human-derived neurons validated previous and new experiments that found the same major decrease in neurotransmitter release and synaptic signaling in genetically engineered human neurons with the same genetic variant — the deletion of neurexin 1 (NRXN1). NRXN1 is a protein-coding gene at the synapse, a cellular junction that connects two nerve cells to communicate efficiently.

Both the research with human-derived and engineered human neurons also found an increase in the levels of CASK, an NRXN1-binding protein, which were associated with changes in gene expression.

“Losing one copy of this neurexin 1 gene somehow contributes to the etiology or the disease mechanism in these schizophrenia patients,” says molecular neuroscientist ChangHui Pak, assistant professor of biochemistry and molecular biology at the University of Massachusetts Amherst and lead author of the research published in the Proceedings of the National Academy of Sciences. “It causes a deficit in neural communication.”

Pak is quick to add that although this single-gene mutation puts people at risk for schizophrenia, autism, Tourette syndrome and other neuropsychiatric disorders, “at the end of the day, we don’t know what causes schizophrenia. This variant gives us insight into what cellular pathways would be perturbed among people with schizophrenia and a lead to study this biology.”

When she conducted most of the research, Pak was working in the Stanford University lab of Thomas Südhof, a neuroscientist who shared the 2013 Nobel Prize in Physiology or Medicine for helping to lay the molecular basis for brain chemistry, including neurotransmitter release.

The research team obtained cell specimens from schizophrenia patients with an NRXN1 deletion who donated samples to a national biorepository for genetic studies of psychiatric disorders. Pak and colleagues converted the participants’ specimens into stem cells and then turned them into functional neurons to study. “We’re rewinding these cells back, almost like a time machine — what did these patients’ brains look like early on,” Pak explains.

Labs at Stanford, Rutgers University and FUJIFILM Cellular Dynamics were independently involved in the generation and analysis of neurons. For comparison with the human-derived neurons, Pak and team also created human neurons from embryonic stem cells, engineering them to have one less copy of the NRXN1 gene. With engineered human neurons, they had previously noted the neurotransmitter impairment and were interested in whether they would have the same findings with patient-derived neurons.

“It was good to see the consistent biological finding that indeed the neurexin 1 deletion in these patients actually does mess up their neuronal synaptic communication, and secondly that this is reproducible across different sites whoever does the experiment,” Pak says.

Notably, the researchers did not see the same decrease in neurotransmitter release and other effects in engineered mouse neurons with analogous NRXN1 deletion. “What this suggests is there is a human-specific component to this phenotype. The human neurons are particularly vulnerable to this genetic insult, compared to other organisms, adding to the value of studying human mutations in human cellular systems,” Pak says.

Being able to reproduce the results is key to the development of drugs that can better treat schizophrenia. “Everything was done blindly and at different sites. We wanted to not only learn about the biology but also be at the top of our game to ensure rigor and reproducibility of these findings,” Pak says. “We showed the field how this can be done.”

Pak and her team are now continuing the research in the Pak Lab, supported by a five-year, $2.25 million grant from the National Institute of Mental Health. The scientists are using the latest stem cell and neuroscience methodologies to explore the molecular basis of synaptic dysfunction in schizophrenia and other neuropsychiatric disorders.

Many aquatic organisms, including jellies and fish, are transparent. But transparent butterfly and moth wings are so arresting that merely catching a glimpse of one typically causes a human to lunge for a camera or at least point it out to their friends. These enigmatic, transparent butterfly wings have not been studied comprehensively.

Doris Gomez and Marianne Elias (French National Center for Scientific Research) set out to change that. Last week, along with a multidisciplinary team of ecologists, biologists and physicists, they published a massive survey on the optics and ecological implications of moths and butterflies with transparent wings in the Ecological Society of America’s journal Ecological Monographs. They discovered that transparency has evolved in Lepidoptera more than once, and that there are many ways to be transparent.

Gomez, an ecologist who has studied the physics and ecological aspects of iridescence in hummingbird wings and other bird coloration, was intrigued by these so-called “glasswing” butterflies and moths when she met Elias, an evolutionary biologist who worked on the ecology and evolution of the tropical butterflies Ithomiini, which have transparent wings. Gomez was startled to find that almost nothing had been written about transparency in Lepidoptera, nor in any other terrestrial animal.

“This paper is a breakthrough because everything that’s been known so far on transparency was about aquatic organisms,” Gomez said. “Transparency is so rare in terrestrial organisms that people never bothered to study it comprehensively.”

She and her team analyzed 123 species of Lepidoptera from samples in the French Museum of Natural History’s collection. They found transparency, or “clearwing” species, in 31 out of 124 families. But not all species accomplish transparency in the same way. They examined the extent to which transparency affects thermoregulation and provides protection against ultraviolet radiation.

Many insects, including wasps, flies and dragonflies, have clear wings. Their wings consist of a transparent membrane made of chitin. Butterfly and moth wings are made of the same kind of transparent membrane, but in most cases moths and butterflies have opaque scales obscuring the membrane. The scales are what are responsible for their mesmerizing patterns and coloration.

Gomez and her team discovered that clearwing species have a number of ways to make their wings transparent. Some transparent moths and butterflies have no scales on their wings at all, leaving the chitin membrane to show through. Many other species do have scales, which can be transparent, upright, narrow or hair-like, allowing light through the wing.

Physicists have studied instances of transparency in individual species or genera, in the hopes of understanding the physics of how to adapt biological concepts to make people, vehicles and even structures invisible or transparent. But before now, no one had appreciated the wealth of approaches lepidopterans can take to achieve transparency, or the fact that it has evolved multiple times in different groups.

“This is the first comparative analysis of transparent butterfly wings,” said Elias. “What is notable is that transparency has evolved several times independently. But the way the wings become transparent can be dramatically different, from highly packed transparent scales to the mere absence of scales, through scale reduction in size and density. There are many ways of being transparent. We don’t know why this diversity exists.”

In some cases, different strategies lead to the same level of transparency, leaving researchers pondering why such diversity exists at all. They theorize that transparency may be beneficial in different ways for different species, including as camouflage or to mimic wasp and bees. Transparency also seems to help moths and butterflies regulate their body temperature, but does not protect them from UV radiation.

Gomez, who has a passion for working with scientists from across other disciplines, included physicists in the study to explore the optical properties of the wings including discerning what birds, their would-be predators, see when they look at a transparent butterfly. They found that the more light that can pass through a wing — i.e., the more transparent it is — the less visible the butterfly is to predators. Transparency acts like the ultimate camouflage.

Like the butterflies themselves, the results are compelling. However, the scientists emphasize that the study has raised more questions and avenues of exploration to continue to uncover the evolutionary role and ecological implications of transparency.

“Butterflies are such iconic organisms,” said Gomez. “They’re so wonderful to study. I like to study complex concepts, like iridescence and transparency because there is so much to explore — and it’s so easy to get everyone excited about them.”

Researchers at Texas A&M University have conducted a computational study that validates using a shape-memory alloy to reduce the unpleasant plane noise produced during landing. They noted that these materials could be inserted as passive, seamless fillers within airplane wings that automatically deploy themselves into the perfect position during descent.

“When landing, aircraft engines are throttled way back, and so they are very quiet. Any other source of noise, like that from the wings, becomes quite noticeable to the people on the ground,” said Dr. Darren Hartl, assistant professor in the Department of Aerospace Engineering. “We want to create structures that will not change anything about the flight characteristics of the plane and yet dramatically reduce the noise problem.”

The researchers have described their findings in the Journal of Aircraft.

Aircraft noise has been an ongoing public health issue. Airplanes can generate up to 75-80 decibels during landing, which can be damaging to hearing over the long term. For example, studies have shown that people exposed to sustained aircraft noise can experience disturbed sleep and an increased risk of stroke and heart disease compared to those who do not live near airports.

The source of aircraft noise is different during ascent and descent. During takeoff, the engines are the primary source of noise. On the other hand, when airplanes slow down to land, the engines do not need to generate power and are mostly idling. At this time, the wings begin to reconfigure themselves to slow down the airplane and prepare for touchdown. Similar to the opening of Venetian blinds, the front edge of the wing separates from the main body. This change causes air to rush into the space created, circle around quite violently and produce noise.

“The idea is similar to how a sound is generated in a flute,” said Hartl. “When a flute is played, air blown over a hole begins to swirl around the hole, and the size, the length and how I cover the holes, produces a resonant sound of a certain frequency. Similarly, the circulating air in the cove created between the front edge of the wing and the main wing resonates and creates a sharp, unpleasant noise.”

Earlier work from Hartl’s collaborators at NASA showed that fillers used as a membrane in the shape of an elongated “S” within this cove could circumvent the noise-causing air circulation and thereby lessen the jarring sound. However, a systematic analysis of candidate materials that can assume the desired S-shaped geometry during descent and then recess back into the front edge of the wing after landing was lacking.

To address this gap, the researchers performed comprehensive simulations to investigate if a membrane made of a shape-memory alloy could go back and forth, changing shape for every landing. Their analysis considered the geometry, the elastic properties of the shape-memory alloy and the aerodynamic flow of air around the material during descent. As a comparison, the researchers also modeled the motion of a membrane made of a carbon-fiber-reinforced polymer composite under the same airflow conditions.

Hartl said these types of simulations are computationally expensive since the flow of air around the conformal material has to be modeled while analyzing the air-induced motion of the material.

“Every time the air applies some pressure to the material, the material moves. And every time the material moves, the air moves differently around it,” he said. “So, the behavior of the airflow changes the structure, and the motion of the structural changes the airflow.”

Consequently, the team had to perform calculations hundreds to thousands of times before the motion of the materials was correctly simulated. When they analyzed the outcomes of their simulations, they found that both the shape-memory alloy and the composite could change their shape to reduce air circulation and thereby reduce noise. However, the researchers also found that the composite had a very narrow window of designs that would enable noise canceling.

As a next step, Hartl and his team plan to validate the results of their simulations with experiments. In these tests, the researchers will place scaled-down models of aircraft wings with the shape-memory alloy fillers into wind tunnels. The goal is to check if the fillers can deploy into the correct shape and reduce noise in near real-world situations.

“We would also like to do better,” said Hartl. “We might be able to create smaller structures that can reduce noise and do not require the S-shape, which are actually quite large and potentially heavy.”

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Materials provided by Texas A&M University. Original written by Vandana Suresh. Note: Content may be edited for style and length.

Optical singularities typically occur when the phase of light with a specific wavelength, or color, is undefined. These regions appear completely dark. Today, some optical singularities, including optical vortices, are being explored for use in optical communications and particle manipulation but scientists are just beginning to understand the potential of these systems. The question remains — can we harness darkness like we harnessed light to build powerful, new technologies?

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a new way to control and shape optical singularities. The technique can be used to engineer singularities of many shapes, far beyond simple curved or straight lines. To demonstrate their technique, the researchers created a singularity sheet in the shape of a heart.

“Conventional holography techniques are good at shaping light, but struggle to shape the darkness,” said Federico Capasso, the Robert L. Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering at SEAS and senior author of the paper. “We have demonstrated on-demand singularity engineering, which opens up a vast set of possibilities in wide-ranging fields, from super-resolution microscopy techniques to new atomic and particle traps.”

The research is published in Nature Communications.

Capasso and his team used flat metasurfaces with precisely-shaped nanopillars to shape the singularities.

“The metasurface tilts the wavefront of light in a very precise manner over a surface so that the interference pattern of the transmitted light produces extended regions of darkness,” said Daniel Lim, a graduate student at SEAS and first author of the paper. “This approach allows us to precisely engineer dark regions with remarkably high contrast.”

Engineered singularities could be used to trap atoms in dark regions. These singularities could also improve super high-resolution imaging. While light can only be focused to regions about half a wavelength (the diffraction limit) in size, darkness has no diffraction limit, meaning it can be localized to any size. This allows darkness to interact with particles over length scales much smaller than the wavelengths of light. This could be used to provide information on not only the size and the shape of the particles but their orientation as well.

Engineered singularities could extend beyond waves of light to other types of waves.

“You can also engineer dead zones in radio waves or silent zones in acoustic waves,” said Lim. “This research points to the possibility of designing complex topologies in wave physics beyond optics, from electron beams to acoustics,” said Lim.

The Harvard Office of Technology Development has protected the intellectual property relating to this project and is exploring commercialization opportunities.

The research was co-authored by Joon-Suh Park, Maryna L. Meretska, and Ahmed H. Dorrah. It was supported in part by the Air Force Office of Scientific Research under award number FA9550- 19-1-0135 and ?by the Office of Naval Research (ONR) under award number N00014-20-1-2450.