Culture

ABERDEEN PROVING GROUND, Md. -- Imagine a silent helicopter stealthily moving troops and supplies around a future battlefield. U.S. Army researchers look to helicopter noise reduction technology as a top priority in aircraft design.

At the U.S. Army Combat Capabilities Development Command, now known as DEVCOM, Army Research Laboratory, researchers collaborated with Uber and the University of Texas at Austin to investigate the acoustic properties of electric vertical takeoff and landing aircraft, which use distributed electric propulsion to power flight.

These eVTOL vehicles may aid the Army with important tasks such as aerial surveillance and cargo transport; however, they feature smaller rotors than traditional helicopters. As a result, eVTOL rotors may emit a different sound signature that researchers will have to take into consideration.

"The noise you hear from these smaller rotors is generated through fundamentally different physical mechanisms," said Dr. George Jacobellis, Army research engineer at the laboratory's Vehicle Technology Directorate. "Traditional modeling techniques need to be improved to account for all of the noise generated so that vehicle designers can be aware of what will actually be heard."

Standard helicopter noise simulations focus primarily on predicting thickness noise and loading noise, because they constitute the dominant noise sources for large helicopters.

Thickness noise stems from the displacement of the air by the rotor blades, while loading noise occurs when lift and drag forces act on the air that flows around the rotary wings. Together, they make up what experts refer to as tonal noise.

In contrast, Army researchers suspected that eVTOL rotors generate more broadband noise, which refers to sounds caused by turbulence, than tonal noise.

"We didn't know whether broadband noise was important or not, but we knew that the tonal and broadband noise scaled differently," Jacobellis said. "We thought that as rotors became smaller there would be some point at which broadband noise would be the dominant source."

The team confirmed their hypothesis in their research study, which not only measured the acoustic characteristics of various eVTOL rotor configurations but also assessed the modeling capabilities of helicopter noise simulations for eVTOL rotors.

During the field experiment, the researchers set up a test stand with two electrically-powered rotors and recorded the noise generated above and below the rotor plane with nine microphones placed in a circular array surrounding the rotor hub.

For the simulations, the team utilized the Rotorcraft Comprehensive Analysis System coupled with a separate program called PSU-WOPWOP, a routine noise prediction code named after an onomatopoeia for the sound that helicopter blades make.

"RCAS computes the aerodynamic loads, or forces, on the blades as well as the bending and twisting of the blades," Jacobellis said. "This information is necessary to use as inputs to PSU-WOPWOP, which computes the noise generated by the rotor. Connecting the two programs required a significant amount of work, which was done by our group as well."

The researchers modeled the broadband noise in PSU-WOPWOP with Pegg's method, one of the two settings present in the simulation program with the other called Brooks' method.

While Pegg's method makes broadband noise predictions based off of experimental data of the entire rotor, Brooks' method accounts for the unique distribution of lift along the blade.

"[These technologies] are promising in their ability to predict the noise of eVTOL rotors, but we need to do more work to obtain acceptable accuracy," Jacobellis said. "The next steps are to implement the Brooks method for higher accuracy acoustic predictions and to compare the unsteady loads between the simulation and experiment to check the accuracy of the simulations in predicting the unsteady loads. The Brooks method should be better at capturing unique configurations and loading distributions."

Researchers also found that co-axial co-rotating rotors, or stacked rotors, may potentially offer better performance and lower noise than a conventional rotor. Unlike conventional rotors which employ blades arranged in a single plane, stacked rotors place blades in multiple planes.

According to the results of their study, stacked rotors with equally spaced rotor blades produced the lowest noise level, around the same level as that of a traditional rotor.

By investigating different values of axial spacing, Army researchers believe that they may uncover a stacked rotor configuration that produces lower noise than the conventional rotor.

"I do think that a stacked rotor can be beneficial for eVTOL applications," Jacobellis said. "The added degree of freedom for the design will allow for gains in efficiency and control over the acoustic signature, which has been shown in the results. More investigation is needed, however, to quantify the noise reduction with axial spacing."

ASM Journal editors and staff seek to improve gender equity after analysis shows that women are not only underrepresented but receive more negative outcomes

Highlights:

Researchers analyzed nearly 80,000 manuscript submissions to ASM journals to gather baseline data on gender bias in the publication process.

They found that women are underrepresented in ASM journals.

Studies with women listed as corresponding authors were more likely to be rejected during the first two rounds of editorial review.

Men hold more editorial positions at ASM journals than women.

The analysis will guide new mechanisms to promote gender equity in the publishing process.

Washington, DC - December 1, 2020 - Over the past 6 months, leading scientific societies and journals have been taking a close look at their own publication data to identify biases against women scientists and guide new solutions. This week in mBio, researchers report on the first such study to focus on inclusivity in microbiology.

Patrick Schloss, Ph.D, a microbiologist at the University of Michigan in Ann Arbor, and Ada Hagan, Ph.D, a former postdoctoral researcher in his lab, led a group of scientists who analyzed 6 years' worth of manuscripts submitted to journals published by the American Society for Microbiology.

They found that ASM journals have a significant representation problem.

The study revealed that the percentage of papers in ASM journals that listed women as senior authors was significantly lower than global and society-level estimates of the percentage of women in the field. In addition, manuscripts that listed women as corresponding authors were rejected after the initial review by an editor or after the first round of peer review by as much as 12 percentage points more often than those authored by men.

"The gender of the author was one of the biggest predictors of whether a manuscript would be editorially rejected," Hagan said.

The study also revealed gender disparities within the editorial ranks of the journals. Between 2012 and 2018, the period of the study, women represented only 17.6% of the Editors-in-Chief of the journals. Additionally, only 28.8% of the group of all editors were women. For comparison, women account for at least half of Ph.D.s in biology, though they represent less than 30% of tenure-track positions in the field.

With more than 40,000 members and 16 peer-reviewed journals, the American Society for Microbiology is one of the largest societies in the life sciences. Schloss is the Chair of the ASM Journals Committee, and Hagan's position was funded by ASM.

Schloss said ASM is committed to promoting and increasing diversity in the field, and scientists have a responsibility to look at all levels of the research process to identify and address biases. The goal of the new study, he said, was to gather baseline data about representation in the publishing process that could be used to inform solutions.

"We cannot improve things unless we know where we are," he said. "It might make people uncomfortable, but it's very important as a community that we figure this out."

The researchers identified nearly 80,000 unique manuscripts submitted to ASM journals between 2012 and 2018. They tracked the papers through the stages of publication and used an algorithm that categorized the gender of authors by first names. (If the algorithm reported a low degree of confidence, then the researcher's gender was classified as "unknown.")

"There won't be any easy fixes to these problems," Schloss said.

However, he said the new analysis can help guide society-level changes that engender a more equitable publishing process. For example: The study authors recommended that journals commit to inclusion and diversity in their mission statement--and support that statement by supporting women and implementing protocols for reporting discrimination. The ASM Journals committee is also taking several steps to improve the representation of Black microbiologists in ASM's journals.

Schloss said scientific societies should also aim for gender parity at leadership levels. Right now, the editorial boards at ASM journals are generally dominated by men. "Ideally, we'd like to have 50% of the masthead be women, and that they handle 50% of the papers," he said. "There's no reason why that can't be a 50-50 population."

Hagan and Schloss point out gender disparities in STEM fields extend beyond the publication process, but that by addressing the new findings, the ASM can build a more welcoming environment.

"We're talking about it a lot more than we used to," Schloss said, "but we still need to do better."

Historically credited as being the first bacterium ever characterized as a plant pathogen, fire blight is a bacterial disease that leads to significant losses of pear and apple. The role of insects in the spread of this disease has been long studied. In a new study, plant pathologists based at Cornell University and Cornell AgriTech take a hypothesis that has been more or less ignored for 100 years and provided support for its validity.

According to first author Matthew Boucher, the study describes a long hypothesized but never experimentally supported transmission mechanism for fire blight. Boucher and colleagues show that flies in an apple orchard can acquire the bacterial agent (Erwinia amylovora) of fire blight from sugary droplets exuding from diseased apple trees and subsequently transmit the bacterium to uninfected shoots so long as those shoots are damaged in some way.

"This transmission mechanism is mechanical, the bacterium does not appear to have a close evolutionary relationship with any given insect and may seem inefficient to an unsuspecting observer," explained Boucher. "However, we show that the massive populations of E. amylovora in the sugary droplets exuding from trees allow flies to acquire enough bacteria for the population to persist in and on flies for as long as seven days in some cases."

Flies can continually shed bacteria over the course of those seven days, resulting in multiple opportunities for a single insect to initiate an infection.

"Demonstrating that bacterial populations can survive within the insect is important because previous research largely discounted E. amylovora survivability within an insect." More research is needed, especially under field conditions, but this is an exciting step toward understanding the diversity of interactions between plants, insects, and phytopathogens.

"We also show that insects do not need to have intimated, co-evolved relationships with plant pathogens to be important agents in the disease cycle. There are only one or two similar pathogens in documented research, but there are likely more out there that need to be studied to advance our knowledge of this end of the disease-vector spectrum," Boucher said when asked what makes his work groundbreaking. "As a collective work, we show the importance of integrating historical literature into modern research and revisiting topics and hypothesis that may not have been technologically feasible to investigate when they were first proposed."

If there is a silver lining in cancer's chaotic biology, it's that the same traits that give cancer cells a growth advantage often present opportunities for sabotaging them.

That's the central idea behind a new research paper published November 23 in Proceedings of the National Academy of Sciences (PNAS) by Xuejun Jiang, a cell biologist in the Sloan Kettering Institute, and Craig Thompson, President and CEO of Memorial Sloan Kettering. They found that cancer cells often exhibit metabolic changes that make them vulnerable to a particular type of cell death called ferroptosis.

Ferroptosis -- literally, death by iron -- is often triggered by oxidative stress, the buildup in cells of free radicals and other corrosive chemicals that are byproducts of using oxygen to burn fuel for energy. But many cancer cells, which need abundant amounts of energy to grow and divide, have found a way around this problem.

"Genetic mutations that allow cancer cells to cope with oxidative stress make them more resistant to ferroptosis," Dr. Jiang says. "Another way to say this is that without the benefit of those mutations, cancer cells might be very, very sensitive to ferroptosis."

He and his colleagues, including postdoctoral fellows Junmei Yi and Jiajun Zhu, tested this idea by giving mice a combination of drugs -- one that promotes ferroptosis and one that blocks the effect of the mutations. The results of this one-two punch were dramatic.

A Commonly Mutated Pathway

The particular mutations Dr. Jiang and colleagues studied affect a signal-sending pathway called PI3K-AKT-mTOR, which controls metabolism. Mutations in this pathway are among the most common found in cancer. That likely reflects the fact that cancer cells have increased metabolic demands owing to how quickly they reproduce. Cancers with mutations in the PI3K-AKT-mTOR pathway are some of the most difficult to treat.

The team found that tumor cells with these mutations demonstrated a hardy resistance to an experimental ferroptosis-inducing drug that was administered to cells growing in a dish. When the scientists added drugs that block the action of this metabolic pathway to the ferroptosis-inducing drug, the cancer cells died.

Next, they tested whether this same effect would be seen in mouse models of breast and prostate cancers containing these mutations. Indeed, the drug combination resulted in near-complete tumor destruction in the mice.

"These were some of the most significant tumor regressions I've ever seen coming from experiments in my lab," Dr. Jiang says.

He and his collaborators further showed that the way the mutated PI3K-AKT-mTOR pathway protects cancer cells is by increasing the activity of a protein that is involved in making lipids for the cell's outer membrane. These extra lipids help to protect the cells against oxidative stress, and therefore ferroptosis. Blocking PI3K-AKT-mTOR prevents this lipid synthesis and re-sensitizes the cells to ferroptosis.

The new findings complement previous work from the Jiang lab, published in 2019 in the journal Nature. In that paper, Dr. Jiang found the some cancers have mutations that make them more sensitive to ferroptosis, even without administering metabolism-altering drugs. In a sense, the new results represent the flipside of the equation.

"The key point is that many cancers have genetic alterations that can be exploited to trigger ferroptosis and kill the cells. It's an exciting way to think about developing new cancer treatments."

The team has applied for a patent related to this work. Their next step is to test the drug combination in tumor samples obtained from patients being treated at MSK.

CHICAGO --- After recovering from COVID-19, some patients are left with chronic, debilitating pain, numbness or weakness in their hands, feet, arms and legs due to unexplained nerve damage. A new Northwestern Medicine study shows how advanced imaging technology can pinpoint what may have caused patients' nerve damage and help determine the best course of treatment.

"Let's say you have numbness in your fingers. That might actually be due to problems in your neck, elbow or wrist, and the best way to figure it out is with an MRI or ultrasound," said lead author Dr. Swati Deshmukh, assistant professor of radiology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine radiologist. "We offer advanced imaging that shows even really, really small nerves, which helps us localize where the problem is, assess the severity and suggest what might be causing it."

This is the first known publication to summarize how these advanced imaging techniques can help physicians identify and treat nerve damage in COVID-19 patients. The study will be published December 1 in the journal Radiology.

TWO NEW CAUSES OF NERVE DAMAGE

Previous research from Northwestern and Shirley Ryan AbilityLab found COVID-19 patients can experience nerve damage after being flipped onto their stomachs (prone positioning) in the ICU as a life-saving measure to help them breathe. This new paper demonstrates how advanced imaging aids this cohort of patients as well as two additional patient cohorts with COVID-19-related nerve damage:

Secondary to an inflammatory immune response that attacked the nerves or

From a hematoma (when blood collects outside of the blood vessels).

"Similar to how the body's immune response attacks the lungs in severe COVID cases, some patients have an immune response that affects their nerves," Deshmukh said. "Another group of patients developed hematomas as a complication from the blood thinners they were treated with when they had COVID."

Deshmukh said she hopes the findings will raise awareness of this imaging technology.

"I have to wonder if there are physicians out there who are seeing these otherwise young, healthy patients, and they don't know exactly what's wrong and they're thinking, 'What am I supposed to do for patients with post-COVID pain and weakness?'" Deshmukh said. "I want physicians and patients to be aware of the diagnostic options available due to recent innovations in technology, and inquire if advanced imaging might be right for them."

HOW THE TECHNOLOGY WORKS

The imaging described in the paper includes ultra-high-resolution ultrasound and MR neurography (MRI of peripheral nerves, which impact the arms and legs). They can help localize where a patient's problem is, show the severity of nerve damage, how many nerves are affected and if the nerve damage also has impacted the muscles.

The advanced ultrasound technology is new, portable, less expensive and can sometimes be even better at detecting nerve damage than MRI, Deshmukh said. Ultrasound also can be performed on patients who are unable to tolerate MR imaging.

GUIDING TREATMENT DECISIONS

If imaging technology discovers nerve damage caused by stretch injury because of prone positioning, Deshmukh said, that patient may be referred to a physician who specializes in rehabilitation or peripheral nerve surgery. If imaging finds nerve damage due to an inflammatory response, the patient may be better served by seeing a neurologist. If imaging reveals nerve damage from a hematoma, blood thinner medications would have to be adjusted immediately and the patient may even have to see a surgeon.

For COVID-19 patients and survivors with neuromuscular complications or "long-hauler" symptoms, imaging can help reveal the problem and guide further treatment.

All patients in the study had tested positive for COVID-19.

When healthcare professionals treat patients suffering from advanced cancers, they usually need to use a combination of different therapies. In addition to cancer surgery, the patients are often treated with radiation therapy, medication, or both.

Medication can be combined, with different drugs acting on different cancer cells. Combinatorial drug therapies often improve the effectiveness of the treatment and can reduce the harmful side-effects if the dosage of individual drugs can be reduced. However, experimental screening of drug combinations is very slow and expensive, and therefore, often fails to discover the full benefits of combination therapy. With the help of a new machine learning method, one could identify best combinations to selectively kill cancer cells with specific genetic or functional makeup.

Researchers at Aalto University, University of Helsinki and the University of Turku in Finland developed a machine learning model that accurately predicts how combinations of different cancer drugs kill various types of cancer cells. The new AI model was trained with a large set of data obtained from previous studies, which had investigated the association between drugs and cancer cells. 'The model learned by the machine is actually a polynomial function familiar from school mathematics, but a very complex one,' says Professor Juho Rousu from Aalto University.

The research results were published in the prestigious journal Nature Communications, demonstrating that the model found associations between drugs and cancer cells that were not observed previously. 'The model gives very accurate results. For example, the values ??of the so-called correlation coefficient were more than 0.9 in our experiments, which points to excellent reliability,' says Professor Rousu. In experimental measurements, a correlation coefficient of 0.8-0.9 is considered reliable.

The model accurately predicts how a drug combination selectively inhibits particular cancer cells when the effect of the drug combination on that type of cancer has not been previously tested. 'This will help cancer researchers to prioritize which drug combinations to choose from thousands of options for further research,' says researcher Tero Aittokallio from the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki.

The same machine learning approach could be used for non-cancerous diseases. In this case, the model would have to be re-taught with data related to that disease. For example, the model could be used to study how different combinations of antibiotics affect bacterial infections or how effectively different combinations of drugs kill cells that have been infected by the SARS-Cov-2 coronavirus.

UNIVERSITY PARK, Pa. -- An inexpensive, FDA-approved drug -- cholestyramine -- taken in conjunction with an antibiotic prevents the antibiotic from driving antimicrobial resistance, according to new research by scientists at Penn State and the University of Michigan. The team's findings appear today (Dec. 1) in the journal eLife.

"Antimicrobial resistance is a serious problem that has led to people dying from common bacterial infections," said Andrew Read, Evan Pugh Professor of Biology and Entomology and director of the Huck Institutes of the Life Sciences, Penn State. "Many of our most important antibiotics are failing, and we are beginning to run out of options. We have created a therapy that may help in the fight against antimicrobial resistance, an 'anti-antibiotic' that allows antibiotic treatment without driving the evolution and onward transmission of resistance."

According to Valerie Morley, postdoctoral scholar in the Huck Institutes of the Life Sciences, Penn State, an important cause of antibiotic-resistant infections in healthcare settings is vancomycin-resistant [VR] Enterococcus faecium.

"E. faecium is an opportunistic pathogen that colonizes the human gastrointestinal tract and spreads via fecal-oral transmission," she said. "The bacterium is asymptomatic in the gut but can cause serious infections, such as sepsis and endocarditis, when introduced to sites like the bloodstream or the spinal cord."

Morley noted that daptomycin is one of the few remaining antibiotics to treat VR E. faecium infection, yet VR E. faecium is quickly becoming resistant to daptomycin as well. Daptomycin is administered intravenously to treat infections caused by VR E. faecium. The antibiotic is mostly eliminated by the kidneys, but 5-10% of the dose enters the intestines, where it can drive the evolution of resistance.

To investigate whether systemic daptomycin treatment does, indeed, drive an increase in daptomycin-resistant VR E. faecium, the team inoculated mice orally with different strains of daptomycin-susceptible VR E. faecium. Beginning one day after inoculation, the researchers gave the mice daily doses of either subcutaneous daptomycin, oral daptomycin or a control mock injection for five days. The team used a range of doses and routes of administration, including those that would be similar to clinical human doses, to maximize the likelihood of observing resistance emergence. Next, they collected fecal samples from the mice to measure the extent of VR E. faecium shedding into the environment and to determine daptomycin susceptibility of the E. faecium bacteria that were present in the feces.

The researchers found that only the highest doses of daptomycin consistently reduced fecal VR E. faecium below the level of detection, whereas lower doses resulted in VR E. faecium shedding. From the bacteria that were shed, the team found that one strain acquired a mutation in a gene that had previously been described in association with daptomycin resistance, while another acquired several mutations that had not previously been associated with daptomycin resistance.

"Our experiments show that daptomycin resistance can emerge in E. faecium that has colonized the GI tract, and that this resistance can arise through a variety of genetic mutations," said Morley.

The team also observed that daptomycin-resistant bacteria were shed even when the daptomycin was administered subcutaneously.

Finally, the team investigated whether the orally administered adjuvant cholestyramine -- an FDA-approved bile-acid sequestrant -- could reduce daptomycin activity in the GI tract and prevent the emergence of daptomycin-resistant E. faecium in the gut. They found that cholestyramine reduced fecal shedding of daptomycin-resistant VR E. faecium in daptomycin-treated mice by up to 80-fold.

"We have shown that cholestyramine binds the antibiotic daptomycin and can function as an 'anti-antibiotic' to prevent systemically administered daptomycin from reaching the gut," said Read.

Amit Pai, professor and chair of the Department of Clinical Pharmacy, University of Michigan, noted that no new strategies have been developed to reduce antimicrobial resistance beyond the use of combination therapy, the development of vaccines for upper and lower respiratory tract infections and simply reducing the unnecessary use of antibiotics.

"These are blunt instruments for antimicrobial resistance reduction at the population level but do not readily translate to an intervention that can be used in individuals," said Pai. "Reducing selective antibiotic pressure on bacteria that reside in the colon is a potential individual-level strategy that deserves greater attention."

Lockdowns, job losses and social isolation have been the hallmarks of 2020 as COVID-19 tightens its grip on the world, not only infecting millions and leaving a mounting death toll, but also denying humans the most basic sense - touch.

In the absence of human-to-human contact, in millions of households worldwide, animals have stepped into the breach for many people, providing much-needed comfort via cuddles, pats and a constant physical presence.

A new study published by University of South Australia researchers points to the lifesaving role that pets have played in 2020 and why governments need to sit up and take notice.

The Journal of Behavioural Economics for Policy (JBEP) paper outlines how pets have a crucial role to play in an era where human-human contact can be life endangering.

Lead author Dr Janette Young says physical touch is a sense that has been taken for granted - even overlooked - until COVID-19 visited our door earlier this year.

"In a year when human contact has been so limited and people have been deprived of touch, the health impacts on our quality of life have been enormous," Dr Young says.

"To fill the void of loneliness and provide a buffer against stress, there has been a global upsurge in people adopting dogs and cats from animal shelters during lockdowns. Breeders have also been inundated, with demands for puppies quadrupling some waiting lists."

Spending on pets was already hitting record levels, topping $13 billion in Australia and in the region of US$260 billion globally in 2020, but this is bound to be surpassed.

It is estimated that more than half the global population share their lives with one or more pets. The health benefits have been widely reported, but little data exists regarding the specific benefits that pets bring to humans in terms of touch.

"Pets seem to be particularly important when people are socially isolated or excluded, providing comfort, companionship and a sense of self-worth," Dr Young says.

"Touch is an understudied sense, but existing evidence indicates it is crucial for growth, development and health, as well as reducing the levels of the stress hormone cortisol in the body. It is also thought that touch may be particularly important for older people as other senses decline."

In interviews with 32 people, more than 90 per cent said touching their pets both comforted and relaxed them - and the pets seemed to need it as well.

Examples of dogs and cats touching their owners when the latter were distressed, sad, or traumatised were cited.

Many people referenced pets' innate ability to just "know" when their human counterparts weren't feeling well and to want to get physically close to them.

"The feedback we received was that pets themselves seem to get just as much pleasure from the tactile interaction as humans," Dr Young says.

Not just dogs and cats either. Interviewees mentioned birds, sheep, horses and even reptiles who reciprocate touch.

"Animals, like people, are living, breathing others, with individual interests, styles and preferences. While culturally, animals are not seen as 'human', they are still seen as individuals with likes and dislikes.

"In the era of COVID-19, social distancing, sudden lockdowns and societal upheaval, our pets may be the only living beings that many people are able to touch and draw comfort from.

"Humans have an innate need to connect with others but in the absence of human touch, pets are helping to fill this void. They need to be considered from a policy angle, therefore, to help mitigate some of the mental and physical stressors that people are experiencing during this time."

Dr Young says hospitals, hospices and aged care facilities should be encouraging pet connections with residents.

"Residential aged care is yet to recognise the value of human-animal relationships. Had more pets being living with their owners in aged care when COVID-19 restrictions were applied, it could have helped people immeasurably," she says.

New Rochelle, NY, November 30, 2020--A standardized "Artificial Pancreas (AP) Dashboard" should provide easy to use single-page hybrid closed-loop system (HCL) reporting for insulin requiring patients with diabetes. The AP Dashboard will help standardize HCL reporting similar to standardized CGM reporting and an electrocardiogram (EKG) and will be likely to help improve glycemic control and reduce hypoglycemia. It is described in the peer-reviewed journal Diabetes Technology & Therapeutics (DTT). Click here to read the article now.

The developers of the AP Dashboard concept propose a single-page report comprised of seven main components. These provide detailed information and visualization of glucose, insulin, and HCL-specific metrics. They include glucose metrics, hypoglycemia, insulin, user experience, hyperglycemia, glucose modal-day profile, and insight. Each main component may be divided into subcomponents. For example, glucose metrics include four variables: mean glucose; standard deviation; glucose management indicator; and a visual graph displaying the recommended continuous glucose monitor metrics, such as time-in-range, time-above-range, and time-below-range. The recommendations also include the optimal sampling duration for HCL data download and color coding for visualization ease.

"Successful use of an HCL system requires interpretation of the glucose and insulin metrics and optimization of HCL settings," state coauthors Viral Shah, MD and Satish Garg, MD, University of Colorado Anschutz Medical Campus. "We believe it is time to standardize the terminology and reporting of different HCL systems. We recommend various HCL metrics and visualizations for a standardized HCL reporting similar to an EKG. We realize that this is only a starting point and fully understand that this can and will be improved with others' input."

Anecdotal reports claim that the incidence of cancer in sharks is very low, but there is not enough data to confirm this estimate categorically. A study published in the journal Genomics, however, presents strong evidence of anti-tumor activity in the genome of the Shortfin mako shark, Isurus oxyrinchus.

This large pelagic species, which can be as long as 4 meters, inhabits temperate and tropical seas worldwide. It is classified as endangered by IUCN, owing mainly to non-selective longline fishing with hundreds of hooks by factory ships that capture many animals in a single pass. They spend up to two months at sea, bringing back hundreds or even thousands of tons of fish.

Fishery observers with the Portuguese Institute for Sea and Atmosphere (IPMA) collected tissue samples of various organs from four mako sharks on one of these ships. Brazilian researchers genetically sequenced eye and liver tissue samples, finding that nine out of the ten most overexpressed genes in the animal's liver relate to tumor suppression in humans.

"Because these fishing cruises stay out at sea for such a long time, few of the tissue samples had well-conserved RNA. We managed to retrieve genetic material only from four livers and three eyes, but even so they produced surprising results," said Rodrigo Domingues, first author of the paper. The study was conducted while Domingues was on a postdoctoral internship at the Federal University of São Paulo (UNIFESP) in its Department of Marine Sciences in Santos, Brazil, under the supervision of Fernando Mendonça.

Domingues performed part of the analysis while he was an intern at the Interdisciplinary Center of Marine and Environmental Research (CIIMAR) in Portugal, also with a scholarship from FAPESP (São Paulo Research Foundation). The research is part of a project involving Brazil-Portugal collaboration, funded by FAPESP and Portugal's Foundation for Science and Technology (FCT).

The analysis revealed 3,774 differentially expressed genes in the two organs - 1,612 in the eye and 2,162 in the liver. Most of the genes that were overexpressed in the eye related to the structure of the organ and visual signaling to the brain. Few genes relating to light reception were found, suggesting that the mako probably has monochrome vision and can see only shades of the same color, like all other sharks known to science.

The recently completed genome sequencing of the Great white shark (Carcharodon carcharias), the largest sequencing of any shark species, revealed two positively selected genes with anti-tumor activity. Hence the Brazilian researchers' surprise on finding that out of the top ten overexpressed genes in the mako's genome, no fewer than nine are cancer-related.

From colon cancer to glioma

Among the genes with above-normal activity in the liver, HABP2 is known to reduce colony formation and cellular migration in thyroid tumors, while PON3 encodes an enzyme that can act as a cellular antioxidant, protecting cells from oxidative stress, which is a significant factor in cancer.

NIT2, RMC1 and FGFRK1 are expressed in various tissues and are potential tumor suppressants. The first two relate to suppression of colon cancer cells, while the third has a negative effect on cell proliferation in the initiation and progression of prostate cancer.

ITIH3 is involved in inflammatory diseases, schizophrenia, depression, heart attack, and stomach cancer. CBS and A1CF are involved in the progression of colon, ovarian, and breast cancer, although CBS has tumor-suppressant effects in glioma, a common type of brain cancer. SERPIND1 plays a role in rapid wound healing in sharks, and in inflammation, blood clotting, and cancer metastasis in humans.

"To find out if any compounds from shark livers could act on human cells, we would need to make an extract from the organ and test it on tumor cells. If such bioactive compounds were found to produce a significant benefit, other groups could synthesize them and possibly use them to produce a new drug for therapeutic use," Domingues said.

The authors note that the mako is already being overfished by commercial fleets, which sell its fins to Asian markets and its meat in Brazil. "We, therefore, discourage increased fishing of the species and a further population decline for this additional purpose. On the other hand, it might be possible to combine research activities in order to optimize the sampling of this endangered shark species, especially when scientific observers are on commercial vessels and can continue to take samples from specimens that are already dead when captured," they write.

To contribute to the conservation of the species, the researchers are now looking for single nucleotide polymorphisms (SNPs), which can act as biological markers to locate mutations and help explain whether there are several population groups in this or that ocean, for example. If differences are found in certain regions of the genome in 200 samples from the Atlantic and Indian Oceans, it may be possible to use them to identify oceanographic factors (water temperature and salinity, chlorophyll levels etc.) that contribute to this separation into groups. If so, the information can be used to formulate fishery policy, including a ban on shark fishing in certain areas.

Defensive behaviours are common responses when people feel personally attacked but can undermine our ability to identify problems and find solutions.

Addressing why defensiveness manifests will help relationships, conflict management and decision making to reduce defensiveness meet people's psychological need for belonging, according to a study.

Research published in the British Journal of Social Psychology has shown that defensiveness in response to wrongdoing is exacerbated by making the wrong doer feel like they're an outcast.

Psychological defensiveness includes the many ways that we let ourselves off the hook when we do wrong: misrepresenting or misremembering what occurred, not paying attention to information that is critical deflecting blame to others, minimising any harm caused, denying responsibility or disengaging entirely from the situation.

The research conducted at Flinders University by Professor Michael Wenzel, Associate Professor Lydia Woodyatt, and Dr Ben McLean, from the College of Education, Psychology and Social Work, is focused on understanding and reducing defensive responses.

"This research shows that defensiveness is strengthened by negative social responses, but is reduced when people feel secure in their group identity, respected and valued," says Associate Professor Woodyatt.

"Based on our research over the past several years, our recommendations for reducing defensiveness when dealing with someone who may have done something wrong is to emphasise respect and value for the person, even if you disagree with their views or actions. Also provide opportunity for the person to express their values prior to talking about the specific problem."

The researchers outline why defensive responses to transgressions undermine our ability to identify a problem correctly and act to solve it, negatively impacting on decision-making within government and organizations, in relationships, and even in relation to our own individual wellbeing.

"Of course these responses do not always feel natural or easy - especially when faced with someone who we think has done wrong to us. Our instinct is also self-protective. As a result when people are caught doing something wrong in our society we often stigmatise, reject or punish them, but this is likely only strengthening those defensive responses over time, not just of that person but of other people in similar situations."

Psychological defensiveness is an evolved self-protective response, and in some mild forms may have some benefits such as helping us to bounce back after failures and helping us to maintain optimism and self-esteem- but defensiveness also has costs.

"Defensiveness creates blind spots in decision-making. When individual and groups respond defensively problems go unrecognised, victims go unacknowledged, and relationships deteriorate."

The researchers examined defensiveness in response to interpersonal transgressions and perceived ethical violations. In these contexts, defensiveness (denying responsibility, deflecting blame, minimising harm, and moral justifications) increased when people felt stigmatised or rejected.

"Humans have a primary psychological need to be valued and included by others, to feel that they are good and appropriate group members or relationship partners," says Associate Professor Woodyatt.

"When people do something wrong this primary psychological need is threatened, driving a defensive response. But addressing that psychological need to belong can reduce their defensiveness."

Alternatively, people were less defensive when they were secure in their own group identity- achieved through reinforcing their own values prior to discussing the underlying event.

"While it is beyond this research, we suggest that Restorative practices and Acceptance Commitment Therapy are both readily available frameworks that can help an individual or group when working through wrongdoing and will likely reduce defensiveness because both approaches provide strategies in line with these recommendations."

A repurposed mouse model can develop symptoms of both severe COVID-19 (lung damage, blood clots, abnormal blood vessels, and death) and also of milder disease, including loss of the sense of smell, according to a recent University of Iowa study published in Nature.

The study also showed that convalescent plasma from a patient who had recovered from COVID-19 protected the mice against lethal disease. The findings suggest the K18-hACE2 mouse model is useful for understanding a spectrum of COVID-19 disease symptoms, and for developing and testing new treatments.

When COVID-19 started spreading across the world earlier this year, UI researchers Stanley Perlman, MD, PhD, and Paul McCray, MD, realized that a mouse model they had created a decade earlier to study SARS might be an invaluable tool for understanding the concerning new disease and for testing potential treatments.

In the new study, Perlman, McCray, and colleagues present a detailed characterization of the effects of SARS-CoV-2 infection in these K18-hACE2 mice, which are now readily available from Jackson Laboratories.

Infection with a high dose of the virus produced many of the signs of illness seen in people with severe COVID-19, including severe lung damage, abnormalities in blood vessels known as vasculitis, blood clots, and death.

"The mouse develops pretty robust lung disease that is on the severe end of the spectrum. That gives us an opportunity to investigate what's going on with lung disease with COVID," says McCray, UI professor of pediatrics-pulmonology, and of microbiology and immunology, and the Roy J. Carver Chair in Pulmonary Research. "Also, people who die from this disease often have vasculitis, which is unusual for coronavirus infections, and we found that the mice may develop signs of vasculitis in the liver, lung, and brain."

One particularly interesting finding was that the infected mice lost their sense of smell. This effect, also known as anosmia, is seen in a large proportion of people who get COVID-19, but is not well understood.

The study showed that K18-hACE2 mice treated with convalescent plasma and then infected with SARS-CoV-2 infection did not succumb to the infection but, like many infected patients with mild disease, had loss of smell as a major symptom.

Further investigation of the cells in the nasal passage suggested that the anosmia results from initial infection and damage to a type of cell that helps to support the function of neighboring sensory neurons that detect smell.

"The loss of sense of smell or taste occurs in a large proportion of patients who have COVID-19, whether they're really sick or if that's the only sign of illness they have. Most people recover their sense of smell pretty quickly, but some don't," says Perlman, UI professor of pediatrics, and of microbiology and immunology, and the Mark Stinski Chair in Virology. "This mouse model opens up the possibility of learning more about how that happens, and if we could understand the mechanisms of why people lose their sense of smell, this will help us treat people."

Nanoengineers at the University of California San Diego have developed new and improved probes, known as positive controls, that could make it easier to validate rapid, point-of-care diagnostic tests for COVID-19 across the globe.

The positive controls, made from virus-like particles, are stable and easy to manufacture. Researchers say the controls have the potential to improve the accuracy of new COVID-19 tests that are simpler, faster and cheaper, making it possible to expand testing outside the lab.

"Our goal is to make an impact not necessarily in the hospital, where you have state-of-the-art facilities, but in low-resource, underserved areas that may not have the sophisticated infrastructure or trained personnel," said Nicole Steinmetz, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering.

Positive controls are a staple in the lab--they are used to verify that a test or experiment indeed works. The positive controls that are primarily used to validate today's COVID-19 tests are naked synthetic RNAs, plasmids or RNA samples from infected patients. But the issue is RNA and plasmids are not stable like viral particles. They can degrade easily and require refrigeration, making them inconvenient and costly to ship around the world or store for long periods of time.

In a paper published Nov. 25 in ACS Nano, UC San Diego researchers led by Steinmetz report that by packaging segments of RNA from the SARS-CoV-2 virus into virus-like particles, they can create positive controls for COVID-19 tests that are stable--they can be stored for a week at temperatures up to 40 C (104 F), and retain 70% of their activity even after one month of storage--and can pass detection as the novel coronavirus without being infectious.

The team developed two different controls: one made from plant virus nanoparticles, the other from bacteriophage nanoparticles. Using them is simple. The controls are run and analyzed right alongside a patient sample, providing a reliable benchmark for what a positive test result should look like.

To make the plant virus-based controls, the researchers use the cowpea chlorotic mottle virus, which infects black-eyed pea plants. They essentially open the virus, remove its RNA contents, replace them with a synthesized RNA template containing specific sequences from the SARS-CoV-2 virus, then close everything back up.

The process to make the bacteriophage-based controls starts with plasmids, which are rings of DNA. Inserted into these plasmids are the gene sequences of interest from the SARS-CoV-2 virus, as well as genes coding for surface proteins of the bacteriophage Qbeta. These plasmids are then taken up by bacteria. This process reprograms the bacteria to produce virus-like particles with SARS-CoV-2 RNA sequences on the inside and Qbeta bacteriophage proteins on the outside.

Both controls were validated with clinical samples. A big advantage, the researchers point out, is that unlike the positive controls used today, these can be used in all steps of a COVID-19 test.

"We can use these as full process controls--we can run the analysis in parallel with the patient sample starting all the way from RNA extraction," said first author Soo Khim Chan, a postdoctoral researcher in Steinmetz's lab. "Other controls are usually added at a later step. So if something went wrong in the first steps, you won't be able to know."

So far, the researchers have adapted their controls for use in the CDC-authorized RT-PCR test. While this is currently the gold standard for COVID-19 testing, it is expensive, complex, and can take days to return results due to the logistics of sending samples off to a lab with PCR capability.

Steinmetz, Chan and colleagues are now working on adapting the controls for use in less complex diagnostic tests like the RT-LAMP test that can be done on the spot, out of the lab and provide results right away.

"It's a relatively simple nanotechnology approach to make low-tech assays more accurate," Steinmetz said. "This could help break down some of the barriers to mass testing of underserved populations in the U.S. and across the world."

It is conventional to believe that the police role in society centers on violence. A forthcoming article in the December issue of Current Anthropology explores that belief and shows how the weakness of police power can be treated as an index for the strength of democratic values institutionalized in the wider political environment.

In "Weak Police, Strong Democracy: Civic Ritual and Performative Peace in Contemporary Taiwan," Jeffrey Martin argues that, in a democratic society, the police role should be defined by their capacity to resolve problems without violence. As an example of what this actually looks like, the author presents an ethnographic study of policing in Taiwan, centering on the relationship between neighborhood police and a locally powerful union. His focal question is: How do police who lack the capacity to impose order by force effectively keep the peace? The author proposes a normative ideal of "weak policing" as the democratic midpoint between the excesses of violent control and the deficiency of uncontrolled violence.

BINGHAMTON, NY -- In the lizard world, flashy colors attract the interest of females looking for mates. But they can make colorful males desirable to other eyes, too -- as lunch.

Assistant Research Professor of Biological Sciences Lindsey Swierk is the first author of an article in the journal Evolutionary Ecology on the topic. Called "Intrasexual variability of a conspicuous social signal influences attach rate of lizard models in an experimental test," the article details an experiment involving clay models of water anoles (Anolis aquaticus), a species of lizard only found in Costa Rica and a small slice of Panama. The researchers conducted the experiment at the Las Cruces Biological Station in Costa Rica, which is one of the Organization for Tropical Studies' field stations.

To attract females' notice, male anoles have dewlaps: colorful extendable flaps of skin under their chins. In most species of anole, dewlaps evolved to be as noticeable as possible within the environment, given an environment's predominant colors and lighting conditions.

"Even so, we see a lot of variation within a species in just how bright dewlaps are," Swierk said.

While some water anoles have dramatic red-orange flaps, others have more muted colors, more of a dull brownish-red. Researchers wanted to determine the effect these color variations had on their risk of predation.

While it's widely assumed that flashier males will attract more attention from predators, few studies actually test this assumption. Logistics may be a factor: Researchers have to separate the effects of sexual colors from other aspects of a creature's body and behavior, a difficult task when using real animals. As a result, many studies show correlation but not causation.

To prove that flashier males face greater risks of being attacked, the researchers created clay models with colored dewlaps -- some bright, some more muted. Many visual predators use a stereotyped "search image" to identify prey, so the models only had to approximate anoles' general size, color and shape. The dewlap color, however, required special attention.

"Because different animals have different visual sensitivities than we do as humans, getting the colors right was an important consideration in our model design," Swierk explained. "We ran some pilot trials before this experiment to make sure our models were convincing as 'lizards' -- and they certainly seemed to be, as many birds and other lizards took bites out of them!"

Researchers were able to identity predators from bite marks in the clay models. They included many species of bird, including the strikingly beautiful motmot with its serrated beak. Basilisks and whiptail lizards were also among the likely attackers. The results proved that flashier lizards really do end up as lunch more often.

If bright colors have deadly consequences, why do female anoles prefer them? One answer is that brighter males have either high-quality genetic material or resources that allow them to handle the risk of getting eaten, Swierk explained.

"Because every individual's evolutionary 'mission' in life is to pass on as many copies of its genes as it can, conspicuous traits like these can evolve if they give an individual a high level of reproductive success -- even if the flashy trait ends up killing them in the end," Swierk said.