Culture

A new, highly sensitive chemical sensor uses protein nanowires

image: Protein nanowires (light green) harvested from Geobacter (background) are sandwiched between electrodes (gold) to form bioelectronic sensor for detection of biomolecules (red). 

Image: 
UMass Amherst/Yao lab

AMHERST, Mass. - Writing in the journal NanoResearch, a team at the University of Massachusetts Amherst reports this week that they have developed bioelectronic ammonia gas sensors that are among the most sensitive ever made.

The sensor uses electric-charge-conducting protein nanowires derived from the bacterium Geobacter to provide biomaterials for electrical devices. More than 30 years ago, senior author and microbiologist Derek Lovley discovered Geobacter in river mud. The microbes grow hair-like protein filaments that work as nanoscale "wires" to transfer charges for their nourishment and to communicate with other bacteria.

First author and biomedical engineering doctoral student Alexander Smith, with his advisor Jun Yao and Lovley, say they designed this first sensor to measure ammonia because that gas is important to agriculture, the environment and biomedicine. For example, in humans, ammonia on the breath may signal disease, while in poultry farming, the gas must be closely monitored and controlled for bird health and comfort and to avoid feed imbalances and production losses.

Yao says, "This sensor allows you to do high-precision sensing; it's much better than previous electronic sensors." Smith adds, "Every time I do a new experiment, I'm pleasantly surprised. We didn't expect them to work as well as they have. I really think they could have a real positive impact on the world."

Smith says existing electronic sensors often have either limited or low sensitivity, and they are prone to interference from other gases. In addition to superior function and low cost, he adds, "our sensors are biodegradable so they do not produce electronic waste, and they are produced sustainably by bacteria using renewable feedstocks without the need for toxic chemicals."

Smith conducted the experiments over the past 18 months as part of his Ph.D. work. It was known from Lovley's earlier studies that the protein nanowires' conductivity changed in response to pH - the acid or base level- of solution around the protein nanowires. This moved the researchers to test the idea that they could be highly responsive to molecule binding for biosensing. "If you expose them to a chemical, the properties change and you can measure the response," Smith notes.

When he exposed the nanowires to ammonia, "the response was really noticeable and significant," Smith says. "Early on, we found we could tune the sensors in a way that shows this significant response. They are really sensitive to ammonia and much less to other compounds, so the sensors can be very specific."

Lovley adds, that the "very stable" nanowires last a long time, the sensor functions consistently and robustly after months of use, and work so well "it is remarkable."

Yao says, "These protein nanowires are always amazing me. This new use is in a completely different area than we had worked in before." Previously, the team has reported using protein nanowires to harvest energy from humidity and applying them as memristors for biological computing.

Smith, who calls himself "entrepreneurial," won first place in UMass Amherst's 2018 Innovation Challenge for the startup business plan for the company he formed with Yao and Lovley, e-Biologics. The researchers have followed up with a patent application, fundraising, business development and research and development plans.

Lovley says, "This work is the first proof-of-concept for the nanowire sensor. Once we get back in the lab, we'll develop sensors for other compounds. We are working on tuning them for an array of other compounds."

Support for the work came as a CAREER grant and Graduate Research Fellowship from the National Science Foundation, UMass Amherst's Office of Technology Commercialization and Ventures and the campus's Center for Hierarchical Manufacturing, an NSF-funded Nanoscale Science and Engineering Center.

Credit: 
University of Massachusetts Amherst

T. rex was a champion walker, super-efficient at lower speeds

image: Daspletosaurus (a cousin of T. rex) chasing a Spinops (a centrosaurine ceratopsian, in the same family as Triceratops).

Image: 
Julius Csotonyi, 2020

While smaller dinosaurs needed speed, huge predators like T. rex were optimized for energy-efficient walking, according to a study published May 13, 2020 in the open-access journal PLOS ONE by Alexander Dececchi of Mount Marty College, South Dakota and colleagues.

Theropod dinosaurs included the dominant bipedal predators of the Mesozoic Era, and plenty of research has explored the relationship between their locomotion and lifestyle. Much of this work has focused on running speeds, but in this study, Dececchi and colleagues argue that speed might not be the most important factor, especially for the biggest theropods.

The authors gathered data on limb proportions, body mass, and gaits of more than 70 species of theropod dinosaurs. They then applied a variety of methods to estimate each dinosaur's top speed as well as how much energy they expended while moving around at more relaxed walking speeds. Among smaller to medium-sized species, longer legs appear to be an adaptation for faster running, in line with previous results. But for the real titans weighing over 1000kg, top running speed is limited by body size, so longer legs instead correlated with low-energy walking.

Running is important for hunters, but they generally spend much more time roaming around in search of food. The authors suggest that while speed was a major advantage for dinosaurs who needed to hunt prey and also escape predators, the biggest theropods relied more on efficiency while foraging. Among giant theropods, the champions were tyrannosaurs like T. rex, whose long legs were apparently well-adapted for reduced energy expenditure while prowling for prey.

The authors add: "Size matters. Smaller theropods were both hunter and the hunted, so their lives were lived at high speed. For giants like T. rex, a top predator with no natural enemies, life was a marathon not a sprint."

Credit: 
PLOS

T. rex's long legs were made for marathon walking

image: In this artist's depiction of wildlife from Alberta, Canada, 77 million years ago, the tyrannosaur Daspletosaurus hunts a young horned Spinops, while an adult Spinops tries to interfere and a Coronosaurus watches from a distance.

Image: 
Illustration by Julius Csotonyi.

Long legs may make good runners, but they're great for walking, too. Scientists have generally assumed that long-limbed dinosaurs evolved their leggy proportions for speed to catch prey and avoid predators.

But a new study by the University of Maryland's Thomas Holtz and his colleagues suggests that long legs evolved among the biggest dinosaurs to help them conserve energy and go the distance as they ambled along searching for prey. The study was published in the journal PLOS ONE on May 13, 2020.

"The assumption tends to be that animals with adaptations for running, such as long legs, are adapted for a higher maximum speed, but this paper shows that there's more to running than top speed," said Thomas Holtz, principal lecturer in the UMD Department of Geology. "When you're a bigger animal, those adaptations may also be for endurance and efficiency. It may be about being a marathoner rather than a sprinter."

Holtz and his colleagues analyzed a variety of metrics like limb proportions, size ratio, body mass and gaits to estimate the top speeds of more than 70 species from a group of dinosaurs called theropods. Theropods ranged in size from less than a half-pound to more than nine tons. They included Tyrannosaurus rex and the many other two-legged predators that dominated the age of dinosaurs for 180 million years. Bipedalism and running speed have often been cited as major contributors to their success.

The study revealed a more nuanced story. According to the new analysis, longer legs were associated with higher top speeds in small and medium-sized dinosaurs, but that didn't hold true for dinosaurs weighing over 2,200 pounds. Scientists have known that larger body size can limit speed, and the study showed that large dinosaur species with longer legs were no faster than their stubby-limbed brethren. But they moved more efficiently.

By calculating how much energy each dinosaur expended while moving at walking speeds, the researchers found that among the largest dinosaurs, those with longer legs needed less energy to cruise around.

"That's actually a very beneficial savings, because predators tend to spend a great deal of their time foraging, searching for prey," Holtz said. "If you are burning less fuel during the foraging part of the day, that's an energy savings that dinosaurs with shorter leg forms didn't get."

These results highlight the often-overlooked impact of body proportions on running ability and the limiting effect of large body size on running speed. Clearly, there are different kinds of runners. This work should broaden the discussion about what it means to be adapted for running.

Credit: 
University of Maryland

Older, larger companies benefit from not investing in worker safety, study finds

CORVALLIS, Ore. -- Companies best equipped to provide safe workplaces are the least likely to do so, because they benefit financially from forgoing the cost of enacting workplace safety practices, a recent study found. In some cases, companies with worker injury claims were more than 50% more likely to survive than their safer counterparts.

When it's cheaper to pay nominal fines for violating workplace regulations than to provide safe workplaces, that indicates current safety regulations are not enough to protect workers, researchers say.

Oregon State University Public Health and Human Sciences associate professor Anthony Veltri was one of several authors on the study, an international collaboration between Mark Pagell, Mary Parkinson, Michalis Louis and Brian Fynes of University College Dublin in Ireland; John Gray of the Ohio State University in Columbus, Ohio; and Frank Wiengarten of Universitat Ramon Llull in Spain.

"Organizations that do not provide a safe workplace gain an economic advantage over those that do," said Veltri, who studies occupational safety and health. "The goal of improving the longevity of a business conflicts with the goal of protecting the workforce."

The study, published last week in the journal Management Science, looked at both short- and long-term survival of more than 100,000 Oregon-based organizations over a 25-year period. In this study, "survival" was defined as ongoing operations, even in the face of an ownership change.

Researchers determined whether a company provided a safe workplace by examining the company's history of disabling claims, using data provided by the Oregon Department of Consumer Affairs. Disabling claims include those where a worker suffers a temporary disability that forces them to take at least three days off work, or where there is the expectation of a permanent disability. More costly claims stem from more severe incidents, and higher costs indicate more frequent or more severe claims.

Results from the study indicated that providing a safe workplace generally hindered organizational survival, as organizations with worker injury claims survived up to 56% longer than organizations with no claims. The effect was strongest among larger, older companies -- those most likely to have the resources to invest in safety practices.

High claims costs were more likely to harm the survival of younger or smaller companies, or companies that are growing quickly. Thus they have a greater incentive to protect their workforce, but likely fewer resources to do so, the researchers said.

Companies with more than 100 employees and claims filed against them were more likely to survive compared with similar-sized companies without claims. That outcome holds until quarterly claims reach just over $9 million, a level that is unlikely to ever be reached.

Conversely, companies with fewer than 30 employees get no or minimal benefit from having claims relative to similar-sized companies without claims.

Despite the presence of regulatory bodies like the Occupational Safety and Health Administration (OSHA), "Our results imply that the regulations of a developed economy are not enough to incent the elimination of poor safety," the study says.

The researchers suggest that future regulations need to be written and enforced to reward innovation that both improves worker safety and improves the business's likelihood of survival.

While the dataset did not allow researchers to explain why having claims makes a business more likely to survive, it allowed them to refute the idea that improving worker safety improves profits.

Although there are businesses that provide safe workplaces and also improve their competitiveness, such businesses are not the norm, the study says. And while organizations seeking to maximize their survival are unlikely to harm workers on purpose, they are correct in calculating that the costs of preventing all harm to workers is higher than the cost of not doing so.

Credit: 
Oregon State University

Dynamics of gut bacteria follow ecological laws

The seemingly chaotic bacterial soup of the gut microbiome is more organized than it first appears and follows some of the same ecological laws that apply to birds, fish, tropical rainforests, and even complex economic and financial markets, according to a new paper in Nature Microbiology by researchers at Columbia University Irving Medical Center.

One of the main challenges facing researchers who study the gut microbiome is its sheer size and amazing organizational complexity. Many trillions of bacteria, representing thousands of different species, live in the human intestinal tract, interacting with each other and the environment in countless and constantly changing ways.

The study's discovery of multiple principles of gut bacterial dynamics should help researchers to understand what makes a gut microbiome healthy, how it may become perturbed in disease and unhealthy diets, and also suggest ways we could alter microbiomes to improve health.

Gut microbiome dynamics remain poorly understood

Although current DNA sequencing technologies make it possible to identify and track bacteria in the gut over time, "the biological processes governing the short- and long-term changes in the gut's microbiome remain very poorly understood," says the study's senior author, Dennis Vitkup, PhD, associate professor of systems biology and of biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons.

As a first step in identifying the factors that describe microbial communities in the gut, Vitkup and his co-authors, graduate students Brian W. Ji and Ravi U. Sheth and research scientists Purushottam Dixit and Konstantine Tchourine, looked for mathematical relationships describing dynamical changes of the gut microbiome of four healthy people followed for a year. They also analyzed microbiome data obtained for mice fed either high fiber or high fat diets every day for several weeks.

With this data, the researchers explored statistical connections between various aspects of microbiome dynamics, such as fluctuations and abundances of various bacteria over time, or the average times different microbes continuously reside in the human gut. "Up to now, it has been an open question whether there are any natural laws describing dynamics of these complex bacterial communities," Vitkup says.

Chaotic fluctuations follow statistical laws

As expected, they discovered large fluctuations in the composition and daily changes of the human and mouse gut microbiomes. But strikingly, these apparently chaotic fluctuations followed several elegant ecological laws.

"Similar to many animal ecologies and complex financial markets, a healthy gut microbiome is never truly at equilibrium," Vitkup says. "For example, the number of a particular bacterial species on day one is never the same on day two, and so on. It constantly fluctuates, like stocks in a financial market or number of animals in a valley, but these fluctuations are not arbitrary. In fact, they follow predictable patterns described by Taylor's power law, a well-established principle in animal ecology that describe how fluctuations are related to the relative number of bacteria for different species."

Other discovered laws of the gut microbiome also followed principles frequently observed in animal ecologies and economic systems, including the tendency of gut bacteria abundances to slowly but predictably drift over time and the tendency of species to appear and disappear from the gut microbiome at predictable times.

"It is amazing that microscopic biological communities--which are about six orders of magnitude smaller than macroscopic ecosystems analyzed previously--appear to be governed by a similar set of mathematical and statistical principles," says Vitkup.

Laws allow identification of abnormal bacterial behavior

These universal principles should help researchers to better understand what processes govern the microbial dynamics in the gut. Using the statistical laws, the Columbia researchers were able to identify particular bacterial species with abnormal fluctuations. These wildly fluctuating bacteria were associated with documented periods of gut distress or travel to foreign countries in humans providing data for the study. Thus, this approach may immediately allow researchers to understand and identify which specific bacteria are out of line and behave in a potentially harmful fashion.

Using mice data, the researchers also observed that microbiomes associated with unhealthy high fat diets drift in time significantly faster compared with microbiomes feeding on healthier high fiber diets. This demonstrates that ecological laws can be applied to understand how various dietary changes may affect and perhaps alleviate persistent microbiome instabilities.

Gut microbiome as miniature ecological laboratory

The study by Columbia researchers also opens an exciting opportunity to use the gut microbial communities as a model system for exploring general ecological relationships. "Ecologists have debated for years why and how these natural ecological laws arise, without any clear answers," says Vitkup. "Previous ecological research has been mostly limited to observational studies, which can take decades to perform for animals and plants. And some key experiments, such as additions or removal of particular species simply cannot be performed."

The gut microbiome, in contrast, provides an ideal miniature laboratory, where researchers could easily manipulate different variables, such as the number and composition of microorganisms, and then explore various aspects of environmental influences. "One of our next goals is to understand the origin of these general ecological laws using gut microbiota," Vitkup says.

Credit: 
Columbia University Irving Medical Center

Infecting the mind: Burnout in health care workers during COVID-19

image: Health care workers are fighting two pandemics: COVID-19 and burnout.

Image: 
Texas A&M University College of Engineering

Doctors and nurses across the country are experiencing occupational burnout and fatigue from the increased stress caused by the COVID-19 pandemic. A team of researchers and medical professionals at Texas A&M University and Houston Methodist Hospital are working together to fight two afflictions: COVID-19 and the mental strain experienced by medical professionals.

In an article recently published in the journal Anesthesia & Analgesia, Dr. Farzan Sasangohar, assistant professor in the Department of Industrial and Systems Engineering and colleagues at Houston Methodist Hospital, outline the effects of fatigue and burnout on intensive care unit (ICU) workers, and the steps that can be taken to mitigate these symptoms.

"The COVID-19 pandemic exacerbated an already existing problem within our health care systems and is exposing the pernicious implications of provider burnout," Sasangohar said.

Health care workers are experiencing added stress from multiple areas. Many of them are working longer shifts and experiencing more loss of life. The lack of personal protective equipment (PPE) and training on how to use new equipment causes many professionals to question if they have been exposed. This leads to fear that they could infect their family and loved ones. In addition to those fears, there is anxiety surrounding job security. To reduce the spread of infection, many states have stopped elective procedures and consequently, many health care professionals have been laid off or had their hours reduced.

Sasangohar and the research team documented four major areas of stress with the goal of identifying mitigation strategies to reduce burnout among these life-saving workers. The four areas identified by the researchers include occupational hazards, national versus locally scaled responses, process inefficiencies and financial instability.

The symptoms

Health care workers need effective PPE readily accessible and available to ensure their safety and that of their patients. Getting the necessary equipment has been challenging due to the low numbers of PPE and ventilators in the U.S. Strategic National Stockpile and delays getting equipment into local areas. This slow response, which has caused some providers to reuse PPE past the point of safety and warranty protections, can contribute to anxiety in providers.

"Minimizing occupational hazard is the most important criteria to assure that our health care workforce is fully equipped and assured to be safe in order to face the battle against this virus," said Dr. Bita Kash, professor of health policy and management in the Texas A&M School of Public Health and director of the Joint Center for Outcomes Research at Houston Methodist Hospital.

The process to secure assistance from federal authorities has been cumbersome and slow for providers. Many requests for additional ventilators and PPE are not being met. These uncertainties about when assistance will arrive has resulted in widespread anxiety among providers.

Process inefficiencies have also contributed to fatigue and burnout due to misinformation or conflicting information given between different specialties. While one subspecialty's professional organization recommends a certain guideline, another specialty could recommend something else, which leads to confusion.

Anxiety and worry about future career prospects and the overall economy can also lead to provider burnout. Elective surgeries have been canceled or delayed, causing financial stress on some physicians. Others not directly affected by financial hardship may be worried about loved ones or their own family and how they will weather a coming economic recession.

Prescription for the future

While this is the first world-wide pandemic in many years, there will be more. Working together, local researchers, health care professionals and government officials can prepare for future pandemics and subsequent waves of the COVID-19 pandemic. Houston Methodist Hospital has already begun learning from this pandemic and making changes to be more resilient in response to the current crisis and prepared for similar crises in the future.

In response to the pandemic, Houston Methodist Hospital adapted their policies and focused on constant and responsive communication from leadership to their employees. Proactive and positive responses have allowed the hospital to adapt quickly during the pandemic and reduce employee stress overall. This success has led to recommendations for future preparations.

The researchers' recommendations to reduce provider burnout and fatigue:

Pandemic plans should include guidance for relevant industries to quickly transition into producing needed medical supplies

National and regional disaster mitigation plans to help shorten the time needed to provide necessary equipment and testing

Provision of adequate numbers of test kits and PPE

Training on disaster management and response for medical professionals

Relaxing licensing restrictions for individuals licensed outside their state of residence

Creating a medical reserve corps of these licensed individuals

Using wearable sensors to monitor health care workers' mental health and provide simple ways to mitigate anxiety and stress

"There is much to learn from the response to COVID-19," said Sasangohar. "In our approach, we used a multi-disciplinary systems approach to learn not just from failures and shortcomings, but also from successful adaptations and improvised interventions at the individual, team and system levels to improve our resilience."

While ICU workers in Houston have weathered many storms, including Hurricanes Ike and Harvey, the COVID-19 pandemic has brought new challenges to already challenging work. The areas identified by the researchers can help make this work safer, more effective and reduce burnout in these critical roles.

Credit: 
Texas A&M University

Gut ecology

For something that has evolved with us over millions of years, and remains part of our physiology over our entire lives, our gut microbiome, oddly, remains somewhat of a mystery. Comprised of trillions of microbes of at least a thousand different species, this community of bacteria, viruses, protozoa and fungi in our gastrointestinal tracts is unique to each individual and has been found to be intimately connected to various fundamental aspects of our fitness, from our immunity to our metabolism and mental health.

For UC Santa Barbara researchers Eric Jones, Zipeng Wang and Joshua Mueller, the gut microbiome is a remarkable machine, full of interactions and competitions that directly impact our wellness. Tuning this machine in a favorable direction, they say, could improve our resistance to disease.

"Can medical therapies improve host health by modifying the microbiome composition? We still don't really know, so it's a huge field of research," Jones said. "This question is a great motivator."

In our daily lives, many of us hope to improve our gut microbiome by taking probiotics and eating fermented foods. In clinical situations, fecal transplants have been shown to successfully treat recurring infections of the gut bacteria Clostridium difficile, which often recur after antibiotics used to treat infections wipe out "helpful" gut bacteria as well.

But outside of sweeping and heroic measures to add populations of good bacteria to the GI tract, there isn't a whole lot known about how to subtly point the system in a healthy direction.

"It's about more than just putting in the right microbes," Jones said. "You need to understand the environment that the microbes are in and you need to understand what facilitates a stable gut microbiome composition."

To tackle this problem, the researchers, under the guidance of UC Santa Barbara physics professor Jean Carlson, propose a technique for driving a mathematical gut microbiome model toward a target microbiome composition by manipulating certain parameters of the model. Called SPARC (SSR-guided parameter change), this approach reduces the complexity of the system without sacrificing it. And, according to a study published in the journal Physical Review E, it also "offers a systematic understanding of how environmental factors and species-species interactions can be manipulated to control ecological outcomes."

Old equation, new use

"So basically, the goal is to find a parameter change that corresponds to a change in the microbiome environment," said lead author Zipeng Wang. It helps to envision the gut microbiome as a ball perched on the top of a hill, poised to roll down in one direction or another. In this idealization, the gut environment dictates the shape of the hill. A healthy microbiome composition lies at the base of one side of the hill, and a disease-associated composition on the other. While fecal transplants directly push the ball to the healthy side of the hill, SPARC, according to the researchers, controls the shape of the hill, effectively rolling the ball down on one side or the other.

To describe this gut ecosystem (data was collected from mouse model experiments at Memorial Sloan-Kettering Center in New York), the researchers used the generalized Lotka-Volterra (gLV) equations. Known also as predator-prey equations, the gLV equations stem from a century-old method used in traditional ecology to describe the interactions between species on Earth, such as competition and predation, as well as effects from indirect interactions.

"But, one of the difficulties is that the gut microbiome has all these different bacterial species," Wang said, "So the Lotka-Volterra equations become very high-dimensional, which means that there are a lot of parameters, and a lot of different ways for bacteria to interact with one another. It would be very hard for us to find the right parameters to achieve the desired microbiome composition."

To avoid the trial-and-error of manipulating an unwieldy number of different parameters, the team opted instead to examine a compressed but reliable 2D representation of the ecological model generated by the dimensionality reduction technique called "steady state reduction" (SSR). According to the researchers, this allowed them to zoom out and identify the key parameters that control the shape of the hill.

"What we like about our model is that it gives us a systematic strategy to identify these low-dimensional features that are really sensitive, that are the most important," Jones explained. "I was really surprised and pleased that we could, for example, find a single parameter and change it by 10% of its value and that would change the shape of the hill."

What is that parameter? Well, given the diversity of gut microbiomes, diets, co-occurring conditions and environmental influences, there is not necessarily one universal parameter change -- say, acidity, or fiber content -- that fits all. The SPARC method, the researchers say, guides thinking on how to identify the significant parameters based on data.

In addition, SPARC currently is primarily a mathematical exercise, though the researchers are eager to try it out in an experimental setting.

"There are people working on what they call gut-on-a-chip systems, which are kind of like miniature Petri dishes that replicate some of the conditions of the human gut microbiome," said Joshua Mueller. "It would be really exciting to validate SPARC in these tightly controlled experimental circumstances."

In the rather more distant future, Jones said, this method could also help pave the way for personalized microbiome management, in which real-time readouts of the state of our microbiomes -- say, from a smart toilet -- could tell us to change our dietary habits to avoid illness and improve our general well-being.

"In order to get to that point, we need mechanistic models of the microbiome," he said. "We need to understand how to control it. We need to understand how environmental feedbacks play into microbial dynamics."

Credit: 
University of California - Santa Barbara

US maternal health spending varies by state, driven by cost of childbirth

Washington, DC - The average cost of childbirth varies widely from state to state, according to new national analysis from the Health Care Cost Institute, which also found that spending on postpartum care extended across the full year after delivery. The research drew on HCCI's database of medical claims from approximately 40 million U.S. individuals with employer-sponsored insurance.

"The care that parents receive before, during and after childbirth represents a substantial proportion of national health care spending and utilization," said Niall Brennan, president and CEO of HCCI. "Better information about how and when new parents use care can help drive improvements in quality and value."

The average cost of childbirth in the US was nearly $14,000 nationally and varied widely across the country - from $8,361 in Arkansas to $19,771 in New York - according to HCCI's analysis of claims data from more than 350,000 deliveries. About 1 in 3 of those deliveries happened by Caesarean section, which is the most common operating room procedure during an inpatient hospital stay for privately-insured Americans. The cost of childbirth and the rate of C-section varied widely across states, but in almost every state, the average price level accounted for the majority of the difference in spending per childbirth relative to the national average.

"Childbirth is the most frequent reason for an inpatient admission in the United States," said HCCI Senior Fellow Katie Martin. "We found that the price per delivery drove wide variations in the cost of childbirth from state to state."

To understand drivers of postpartum spending, HCCI analyzed claims from 160,000 new parents in the year after birth. For these parents, spending spanned the full year following childbirth. Nearly 20% of overall postpartum spending happened in the first 60 days (which is the period of Medicaid eligibility for new mothers in many states), and nearly 30% in the first 90 days. But approximately 70% of postpartum spending occurred over the rest of the year. Birthing parents between the ages of 25 and 34, the largest group in the sample, tended to have the lowest per-person spending average of the age groups examined. Per-person spending rose 16% higher for age group 35-44; 26% higher for age group 18-24; and 59% higher for age group 45-54.

Overall postpartum spending was driven by infrequent emergent services. Surgery represented 26% of overall postpartum spending, followed by emergency room and ambulance services, which represented 17% of overall postpartum spending.

HCCI also analyzed data on prenatal care in the United States, finding that utilization increased with age and the presence of risk factors.

Credit: 
Health Care Cost Institute

Study confirms cats can become infected with and may transmit COVID-19 to other cats

MADISON, Wis. -- In a study published today (May 13, 2020) in the New England Journal of Medicine, scientists in the U.S. and Japan report that in the laboratory, cats can readily become infected with SARS-CoV-2, the virus that causes COVID-19, and may be able to pass the virus to other cats.

Professor of Pathobiological Sciences at the University of Wisconsin School of Veterinary Medicine Yoshihiro Kawaoka led the study, in which researchers administered to three cats SARS-CoV-2 isolated from a human patient. The following day, the researchers swabbed the nasal passages of the cats and were able to detect the virus in two of the animals. Within three days, they detected the virus in all of the cats.

The day after the researchers administered virus to the first three cats, they placed another cat in each of their cages. Researchers did not administer SARS-CoV-2 virus to these cats.

Each day, the researchers took nasal and rectal swabs from all six cats to assess them for the presence of the virus. Within two days, one of the previously uninfected cats was shedding virus, detected in the nasal swab, and within six days, all of the cats were shedding virus. None of the rectal swabs contained virus.

Each cat shed SARS-CoV-2 from their nasal passages for up to six days. The virus was not lethal and none of the cats showed signs of illness. All of the cats ultimately cleared the virus.

"That was a major finding for us -- the cats did not have symptoms," says Kawaoka, who also holds a faculty appointment at the University of Tokyo. Kawaoka is also helping lead an effort to create a human COVID-19 vaccine called CoroFlu.

The findings suggest cats may be capable of becoming infected with the virus when exposed to people or other cats positive for SARS-CoV-2. It follows a study published in Science by scientists at the Chinese Academy of Agricultural Sciences that also showed cats (and ferrets) could become infected with and potentially transmit the virus. The virus is known to be transmitted in humans through contact with respiratory droplets and saliva.

"It's something for people to keep in mind," says Peter Halfmann, a research professor at UW-Madison who helped lead the study. "If they are quarantined in their house and are worried about passing COVID-19 to children and spouses, they should also worry about giving it to their animals."

Both researchers advise that people with symptoms of COVID-19 avoid contact with cats. They also advise cat owners to keep their pets indoors, in order to limit the contact their cats have with other people and animals.

Kawaoka is concerned about the welfare of animals. The World Organization for Animal Health and the Centers for Disease Control and Prevention say there is "no justification in taking measures against companion animals that may compromise their welfare."

Humans remain the biggest risk to other humans in transmission of the virus. There is no evidence cats readily transmit the virus to humans, nor are there documented cases in which humans have become ill with COVID-19 because of contact with cats.

There are, however, confirmed instances of cats becoming infected because of close contact with humans infected with the virus, and several large cats at the Bronx Zoo have also tested positive for the virus.

For instance, according to an April 22 announcement from the U.S. Department of Agriculture, two cats in two private homes in New York state tested positive for COVID-19. One had been in a home with a person with a confirmed case of the viral disease. The cats showed mild signs of respiratory illness and were expected to make a full recovery.

Additional cats have also tested positive for COVID-19 after close contact with their human companions, says Sandra Newbury, director of the UW-Madison Shelter Medicine Program. Newbury is leading a research study in several states in the U.S. to test animal-shelter cats that might have previously been exposed to human COVID-19 cases.

"Animal welfare organizations are working very hard in this crisis to maintain the human-animal bond and keep pets with their people," says Newbury. "It's a stressful time for everyone, and now, more than ever, people need the comfort and support that pets provide."

Newbury has worked with the CDC and the American Veterinary Medical Association to develop recommendations for shelters housing potentially exposed pets, which they may do while owners are hospitalized or otherwise unable to provide care because of their illness. The UW-Madison study helps confirm experimentally that cats can become infected, though the risk of natural infection from exposure to SARS-CoV-2 seems to be quite low, Newbury says. Of the 22 animals the program has tested, none have had positive polymerase chain reaction tests for the virus, she adds.

"Cats are still much more likely to get COVID-19 from you, rather than you get it from a cat," says Keith Poulsen, director of the Wisconsin Veterinary Diagnostic Laboratory, who recommends that pet owners first talk to their veterinarians about whether to have their animals tested. Testing should be targeted to populations of cats and other species shown to be susceptible to the virus and virus transmission.

With respect to pets, "we're targeting companion animals in communal residences with at-risk populations, such as nursing homes and assisted living facilities," Poulsen says. "There is a delicate balance of needing more information through testing and the limited resources and clinical implications of positive tests."

So, what should pet owners do?

Ruthanne Chun, associate dean for clinical affairs at UW Veterinary Care, offers the following advice:

If your pet lives indoors with you and is not in contact with any COVID-19 positive individual, it is safe to pet, cuddle and interact with your pet.

If you are COVID-19 positive, you should limit interactions with your pets to protect them from exposure to the virus.

Additional guidance on managing pets in homes where people are sick with COVID-19 is available from the American Veterinary Medical Association and CDC, including in this FAQ from AVMA.

"As always, animal owners should include pets and other animals in their emergency preparedness planning, including keeping on hand a two-week supply of food and medications," she says. "Preparations should also be made for the care of animals should you need to be quarantined or hospitalized due to illness."

Credit: 
University of Wisconsin-Madison

Trial E3311 validates a less intense treatment for HPV+ throat cancer

image: A lump in the neck and a sore throat are the most common signs of oropharynx cancer, a disease in which cancer cells form in the tissues of the oropharynx--the middle part of the throat (pharynx), at the base of the tongue and tonsils. About 60% of oropharynx cancers are associated with HPV infection. 

Image: 
© 2016 Terese Winslow LLC, U.S. Govt. has certain rights

The final results of the randomized phase two trial E3311 will be presented at the American Society of Clinical Oncology (ASCO) annual meeting, to occur virtually from May 29-31. The trial, conducted in patients undergoing transoral robotic surgery (TORS), tested reduced postoperative radiation therapy in patients with human papillomavirus-associated oropharynx squamous cell carcinoma at intermediate risk for recurrence. ASCO is highlighting the importance of the positive results by making it the first presentation in its Head and Neck Oral Abstract Session (Abstract 6500). The ECOG-ACRIN Cancer Research Group designed and conducted the trial with funding from the National Cancer Institute, part of the National Institutes of Health.

"Transoral resection followed by low-dose radiation is safe in patients with intermediate-risk locally advanced oropharynx cancer, with very good oncologic outcome," said lead investigator Robert L. Ferris, MD, PhD, director, UPMC Hillman Cancer Center in Pittsburgh and a surgical oncologist specializing in head and neck cancer (pictured). "These results present a promising deintensification approach."

Most pharynx cancers caused by HPV have a very good outcome, and the cancer does not return or spread to other parts of the body after treatment. Dr. Ferris and colleagues sought to prove the benefits of using tumor pathologic features, obtained in specimens collected at surgery, to determine patients' risk of recurrence-low, intermediate or high. In particular, they sought to more clearly define the prognostic and predictive role of traditional pathologic biomarkers such as extensive nodal or extranodal disease, to give the right amount of postoperative treatment for each risk group.

Patients at low risk were observed. Patients at intermediate risk were randomized to two arms of radiation alone, both at doses lower (50Gy or 60Gy) than usual (60-66Gy). At the time the trial opened in 2013, the optimal dose of radiation therapy was not defined. Patients at high risk were assigned to usual radiation therapy plus chemotherapy.

"Study E3311 met its primary endpoint," said Dr. Ferris. "For intermediate risk patients-those with uninvolved surgical margins, less than five involved nodes, and less than 1mm extranodal extension-reduced-dose postoperative radiation therapy without chemotherapy appears sufficient. In our study, this group had better outcomes than the group on usual high-dose radiation plus chemotherapy, showing that our patient stratification identified low and intermediate risk patients well, preserving patients' throat function and sparing them unnecessary short- and long-term toxicities."

For patients with low-risk disease, two-year progression-free survival (PFS) was favorable without postoperative therapy (observation alone). All arms had two-year survival rates above 90% and there was no excess of local recurrences with reduction in radiation or chemotherapy (Arms B and C). Risk stratification appeared to appropriately select patients for observation (Arm A).

The overall intent of E3311 was to gather essential data for the design of a future, randomized phase three trial. The primary endpoint was to determine the feasibility and oncologic efficacy of a prospective multi-institutional study of TORS for HPV+ oropharynx cancer followed by risk-adjusted adjuvant therapy. The primary endpoint was two-year progression-free survival in patients determined to be at intermediate risk after surgical excision.

"The tissue samples and imaging studies collected in the course of this trial are a rich resource for studying the biology of intermediate- and high-risk disease, in work that is ongoing," said ECOG-ACRIN Head and Neck Committee Chair, Barbara A. Burtness, MD, Professor of Medicine, and Co-Leader, Developmental Therapeutics Program, Yale Cancer Center and Yale School of Medicine (pictured). "ECOG-ACRIN plans to pursue the current data with a randomized phase three trial of TORS-based treatment deintensification compared with conventional chemoradiation."

A lump in the neck and a sore throat are the most common signs of oropharynx cancer, a disease in which cancer cells form in the tissues of the oropharynx-the middle part of the throat (pharynx), at the base of the tongue and tonsils. About 60% of oropharynx cancers are associated with HPV infection. The incidence has been increasing in recent years, especially in individuals under the age of 45. This change is attributed to the increasing prevalence of HPV infection in developed countries, the practice of oral sex, and the rising number of sexual partners.

While surgeons and patients widely favor the organ-preservation approach of transoral robotic surgery, there remain serious concerns about both short- and long-term toxicities associated with chemotherapy. Besides, given the potential long-term consequences of radiation therapy for a younger population, re-evaluation of adjuvant treatment intensity is needed.

Credit: 
ECOG-ACRIN Cancer Research Group

What's Mars made of?

image: The red planet

Image: 
CC-0

Earth-based experiments on iron-sulfur alloys thought to comprise the core of Mars reveal details about the planet's seismic properties for the first time. This information will be compared to observations made by Martian space probes in the near future. Whether the results between experiment and observation coincide or not will either confirm existing theories about Mars' composition or call into question the story of its origin.

Mars is one of our closest terrestrial neighbors, yet it's still very far away -- between about 55 million and 400 million kilometers depending on where Earth and Mars are relative to the sun. At the time of writing, Mars is around 200 million kilometers away, and in any case, it is extremely difficult, expensive and dangerous to get to. For these reasons, it is sometimes more sensible to investigate the red planet through simulations here on Earth than it is to send an expensive space probe or, perhaps one day, people.

Keisuke Nishida, an Assistant Professor from the University of Tokyo's Department of Earth and Planetary Science at the time of the study, and his team are keen to investigate the inner workings of Mars. They look at seismic data and composition which tell researchers not just about the present state of the planet, but also about its past, including its origins.

"The exploration of the deep interiors of Earth, Mars and other planets is one of the great frontiers of science," said Nishida. "It's fascinating partly because of the daunting scales involved, but also because of how we investigate them safely from the surface of the Earth."

For a long time it has been theorized that the core of Mars probably consists of an iron-sulfur alloy. But given how inaccessible the Earth's core is to us, direct observations of Mars' core will likely have to wait some time. This is why seismic details are so important, as seismic waves, akin to enormously powerful sound waves, can travel through a planet and offer a glimpse inside, albeit with some caveats.

"NASA's Insight probe is already on Mars collecting seismic readings," said Nishida. "However, even with the seismic data there was an important missing piece of information without which the data could not be interpreted. We needed to know the seismic properties of the iron-sulfur alloy thought to make up the core of Mars."

Nishida and team have now measured the velocity for what is known as P-waves (one of two types of seismic wave, the other being S-waves) in molten iron-sulfur alloys.

"Due to technical hurdles, it took more than three years before we could collect the ultrasonic data we needed, so I am very pleased we now have it," said Nishida. "The sample is extremely small, which might surprise some people given the huge scale of the planet we are effectively simulating. But microscale high-pressure experiments help exploration of macroscale structures and long time-scale evolutionary histories of planets."

A molten iron-sulfur alloy just above its melting point of 1,500 degrees Celsius and subject to 13 gigapascals of pressure has a P-Wave velocity of 4,680 meters per second; this is over 13 times faster than the speed of sound in air, which is 343 meters per second. The researchers used a device called a Kawai-type multianvil press to compress the sample to such pressures. They used X-ray beams from two synchrotron facilities, KEK-PF and SPring-8, to help them image the samples in order to then calculate the P-wave values.

"Taking our results, researchers reading Martian seismic data will now be able to tell whether the core is primarily iron-sulfur alloy or not," said Nishida. "If it isn't, that will tell us something of Mars' origins. For example, if Mars' core includes silicon and oxygen, it suggests that, like the Earth, Mars suffered a huge impact event as it formed. So, what is Mars made of and how was it formed? I think we are about to find out."

Credit: 
University of Tokyo

Randomly selecting leaders could prove to be a remedy for hubris

Amsterdam, May 13, 2020- While history shows us that power tends to corrupt, a team of Swiss and German researchers have recently examined historical examples of large-scale business fraud and misconduct at the highest-levels of government in order to highlight how leaders sometimes lose all sense of morality. Inflicting serious harm on their company or society in the process.

This new study in The Leadership Quarterly, published by Elsevier, suggests a change in the selection process may mitigate the one key factor to blame: hubris.

Leaders often attribute their success to their superior ability and bask in their own brilliance. Drunk from power and overconfidence, they embark on endeavors that often begin to bring about detrimental outcomes. In recent times, we have witnessed accounting fraud at Enron, software fraud at Volkswagen, and corruption at FIFA - the list of misconduct by successful top managers is long.

"In classical Athens and medieval Venice, political positions were filled using a mixed procedure of targeted selection and drawing by lots," explained author Professor Katja Rost, University of Zurich, Switzerland. "We wanted to see how appointing leaders partly by random selection affected their performance."

Candidates were pre-selected according to conventional performance criteria. After conducting a large laboratory experiment and reviewing the existing literature, Dr. Berger, Assistant Professor, University of Bern, Switzerland and his research team including, Profs. Margit Osterloh, University Basel, Switzerland, Rost, and Thomas Ehrmann, University Münster, Germany confirm that partly random selection avoids hubris in leaders.

Their analysis found that overconfident leaders selected partly randomly are less prone to misusing their power and making decisions that are more beneficial to other members of the group, compared to overconfident leaders selected through the usual competitive selection process.

A competitive selection process typically triggers leadership hubris of overconfident people due to two factors. First, positions of power are often occupied by persons with overconfidence; and second, competitive selection methods confirm overconfident leaders' feeling that they are exceptional and perform far "above the average" of other candidates and feel entitled to enrich themselves.

In contrast, partly random selected leaders are more "humbled" than those selected by competitive methods without performing any less effectively.

"This study is intriguing and points to the problem of a current leaders selection methods. Yet, a potential better solution was discovered by city states and institutions of the past, who used, in part, random selection from a pool of candidates to appoint leaders," said Dr. John Antonakis, Editor-in-Chief of The Leadership Quarterly. "Dr. Berger and his colleagues now provide experimental evidence to support such a practice; this article should stimulate more research but more importantly, further reflection too by institutional legislators and selectors of leaders."

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Elsevier

Mucus breakthrough could help patients breathe easy

image: The study was led by Associate Professor Ethan Goddard-Borger from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.

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The Walter and Eliza Hall Institute

At a glance

Researchers have discovered the reason why the excessive amounts of mucus produced by patients with respiratory illnesses is thicker than usual.

Mucus viscosity is driven by proteins called 'trefoil factors' that bind to 'mucin glycoproteins' which are very long protein strands coated with unique sugar molecules.

Understanding these mechanisms could help to significantly improve airway-clearing treatments for patients with chronic respiratory diseases.

Worldwide, hundreds of millions of people are impacted by chronic respiratory disease. COPD alone affects more than 250 million people, causing 3 million deaths each year. People with chronic respiratory diseases typically produce an excessive amount of thick mucus in the lungs which obstructs their airways, making it difficult to breathe.

Significant leap in mucus biology

Mucus is mostly comprised of water and mucin glycoproteins which are very long protein strands coated with glycans - a type of sugar molecule. Associate Professor Goddard-Borger said the study's findings revealed that proteins called 'trefoil factors' interact with mucins by recognising and binding to the unique glycan signatures on their surface.

"Trefoil factors have long been known to make mucus more viscous (thicker), and it has been postulated that this thickening occurs in respiratory diseases. However, until now we did not completely understand how the trefoil factor proteins achieved this," he said.

Associate Professor Goddard-Borger said the research showed trefoil factors had two glycan-binding sites and could cross-link mucins strands to make the mucus gel more rigid. "Within mucus, trefoil factors essentially 'staple' the mucin strands into a mesh: the more staples, the denser the mesh and the thicker the mucus becomes."

Understanding what trefoil factors bind to and how they do this represents a significant leap forward in understanding mucus and how it functions in the respiratory, gastrointestinal and reproductive tracts.

Improving therapies for blocked airways

Associate Professor Goddard-Borger said that going forward the aim was to inhibit the bonds created between trefoil factors and mucin strands, and that the development of such a technology could lead to new therapeutics for the treatment of respiratory diseases.

"A healthy amount of mucus is very important for capturing and clearing potential threats to the lung, such as dust particles, dead cells and bacteria, so we're not looking to remove mucus altogether. We are seeking to develop innovative approaches for reducing the viscosity of the mucus to aid in clearing excess mucus from the lungs of patients with chronic respiratory disease.

"The next step is to work with commercial collaborators to progress our vision to develop new mucolytic drugs that can more effectively clear mucus from the airways. Achieving this could make a significant impact on the quality of life and life expectancy of people struggling with debilitating respiratory conditions," Associate Professor Goddard-Borger said.

Credit: 
Walter and Eliza Hall Institute

Chemical composition of bedrock limits vegetation growth in karst regions, research shows

image: Rocky desertification exposing bedrock in the Chenqi catchment in the Karst Critical Zone Observatory Guizhou Province, China

Image: 
University of Exeter

Scientists have revealed the critical role that the chemical composition of bedrock plays in limiting vegetation growth in some of the world's most barren and rocky terrains.

A team of international scientists, including Professor Tim Quine from the University of Exeter, has conducted pioneering new research into vegetation productivity in a karst region of Southwest China.

Covering around 15 per cent of the Earth's land surface, karst terrains are usually characterised as being barren, rocky ground - usually with caves and sinkholes - and an absence of surface lakes and streams.

Crucially, the areas have well-jointed, dense limestone found near the surface, and a moderate to heavy rainfall - with the water being able to percolate away through the rock, dissolving and removing the limestone as it goes.

While this topography is known to hinder vegetation productivity, the role that geochemistry of the bedrock - that is its chemical composition - plays in reducing plant growth has not been extensively studied.

In the new study, the research team used a 'critical zone approach' - studying an area that extends from the base of the weathered bedrock to the top of the vegetation canopy - across a typical karst region of southwest china.

They found significant variations in the chemical composition of the bedrock across the region, which influenced both the amount and the distribution of soil. They discovered that this, in turn, also played a pivotal role in controlling plant growth.

The researchers showed not only that plant productivity is controlled not by both the soil and the bedrock's ability to retain water, but also this in turn is controlled by bedrock's geochemistry.

The research team believe this is especially important when water is in short supply - the hottest driest months of the year - and during droughts.

They also believe that the findings offer a pivotal tool in helping authorities to optimise land use, as well as assessing ecosystem resilience and sensitivity to climate change climate.

The study is published in Nature Communications on Wednesday, May 13th 2020.

Professor Quine said: "Our international team and interdisciplinary critical zone approach have given us invaluable insight into bedrock controls on vegetation growth in the iconic landscapes of China's Karst zone. We have been able to show that bedrock chemistry provides us with a valuable quantitative measure of the capacity of ecosystems to retain the water that is essential to sustain plant growth through dry seasons and droughts."

Professor Hongyan Liu of Peking University, and principle investigator, said: "Our research also shows the global significance of the bedrock influence on vegetation productivity. We selected 12 of the main karst regions in the world, 10 of which show significant differences in vegetation productivity due to bedrock geochemistry".

Professor Meersmans of the University of Liege said: "This study highlights the importance of interdisciplinary research across the boundaries of soil-, plant- and geosciences in order to unravel the impact and interplay of various key factors determining primary production in karst regions. Moreover, the present study offers a basis for future research assessing the resilience of these fragile ecosystems when facing climate change and other environmental threats."

The research was carried out as part of the UK-China (NERC-NSFC) SPECTRA project, called Soil Processes and Ecological Services in the Karst Critical Zone of Southwest China, which aims to enhance the sustainable development of one of the poorest regions of China, Guizhou.

The Guizhou karst region, with a population of 35 million, is one of the poorest regions in China with a GDP less than 50% of the national average. In response to the environmental deterioration and changing social conditions in the Guizhou karst region, the Chinese government has intervened to promote the abandonment of the most degraded cultivated land and its succession to grassland, shrub and forest.

The SPECTRA project is designed to identify the biological controls on nutrient availability, soil formation and loss, and their response to perturbation, providing the rich evidence base needed to inform land management decision-making in the Guizhou province.

Credit: 
University of Exeter

Coordination polymer glass provides solid support for hydrogen fuel cells

image: The molecular structure of the new polymer glass facilitated the movement of protons (H+) across it under dry conditions at 120°C.

Image: 
Mindy Takamiya/Kyoto University iCeMS

Scientists at Japan's Institute for Integrated Cell-Material Sciences (iCeMS) are leading efforts to synthesize stronger and efficient materials for hydrogen fuel cell membranes. Most fuel cells currently on the market employ liquid membranes. A new coordination polymer glass membrane, reported in the journal Chemical Science, works just as well as its liquid counterparts with added strength and flexibility.

Hydrogen fuel cells are fed hydrogen and oxygen to produce electricity, with water as their only by-product. These fuel cells contain 'proton conducting membranes' that facilitate the separation of hydrogen's positive and negative particles, protons and electrons, a process that ultimately leads to the production of electricity.

Protons need to easily move across these membranes for the process to be efficient. Current proton conducting membranes are made from liquids and cannot operate effectively under dry conditions, making their fabrication complicated and expensive. Scientists are looking for ways to fabricate solid membranes made from water-free electrolytes that provide better mechanical and thermal stability than their liquid counterparts, but are also cost-effective and still conduct protons well.

"Our coordination polymer glass performed better than recently reported ionic liquids and crystalline coordination polymers," says Satoshi Horike, a materials scientist at Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) who led the research.

Horike, Tomohiro Ogawa and colleagues in Japan fabricated their coordination polymer glass membrane by mixing a 'protic ionic liquid' with zinc ions. Protic ionic liquids are liquid salts made by mixing an acid and a base. The team used a protic ionic liquid called diethylmethylammonium dihydrogen phosphate. Adding zinc to this liquid led to the formation of a solid, elastic polymer glass.

The molecular structure of the coordination polymer glass facilitated the movement of protons across it under dry conditions at 120°C. When tested in a hydrogen fuel cell, it produced high voltage (0.96 volts), well within the range of typical polymer electrolyte membranes. Its power output was also similar to commonly used Nafion membranes.

Ogawa believes their findings offer an interesting approach for using glass polymers in fuel cell applications. The team plans to continue their work with the aim of achieving fuel cell membranes with higher performance and long-term stability.

Credit: 
Kyoto University