Author: Futurity (National Geo)

A new diagnostic test is 1,000 times more sensitive than conventional tests, researchers report.

When Srikanth Singamaneni and Guy Genin, both professors of mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, established a new collaboration with researchers from the School of Medicine in late 2019, they didn’t know the landscape of infectious disease research was about to shift dramatically. The team had one goal in mind: tackle the biggest infectious disease problem facing the world right then.

“Srikanth and I had a vision of a simple, quantitative diagnostic tool, so we connected with infectious disease physicians here at WashU and asked them, ‘What are the most important questions that could be answered if you could get really detailed information cheaply at the point of care?’” says Genin, professor of mechanical engineering.

“Greg Storch told us that one of the most important challenges facing the field of infectious disease is finding a way to figure out quickly if a patient has a bacterial infection and should get antibiotics or has a viral infection, for which antibiotics will not be effective.”

Storch, professor of pediatrics at the School of Medicine, was interested in diseases that affect most people regularly—colds, strep throat, or the flu—but that weren’t getting as much research attention as rarer diseases.

“Even with great advances that have been made in infectious disease diagnostics, there is still a niche for tests that are simple, rapid, and sensitive,” Storch says. “It would be especially powerful if they could provide quantitative information. Tests with these characteristics could be employed in sophisticated laboratories or in the field.”

Drawing on his years of experience in developing nanomaterials for applications in biology and medicine, Singamaneni sought to overcome these limitations in point-of-care diagnostic tests. Singamaneni and his lab developed ultrabright fluorescent nanolabels called plasmonic-fluors, which could be quickly integrated into a common testing platform, the lateral flow assay (LFA).

Plasmon-enhanced LFAs (p-LFAs) improve inexpensive, readily available rapid tests to levels of sensitivity required by physicians for confidence in test results without the need for lab-based confirmation.

According to new findings, the team’s p-LFAs are 1,000 times more sensitive than conventional LFAs, which show results via a visual color and fluorescence signal on the strip.

When analyzed using a fluorescence scanner, p-LFAs are also substantially faster than gold-standard lab tests, returning results in only 20 minutes instead of several hours, with comparable or improved sensitivity.

The p-LFAs can detect and quantify concentrations of proteins, enabling them to detect bacterial and viral infections as well as markers of inflammation that point to other diseases.

“Plasmonic-fluors are composed of metal nanoparticles that serve as antennae to pull in the light and enhance the fluorescence emission of molecular fluorophores, thus making it an ultrabright nanoparticle,” Singamaneni explains.

“Our p-LFAs can pick up even very small concentrations of antibodies and antigens, typical markers of infection, and give clinicians clear, quick results without the need for specialized equipment. For quantitative testing beyond the initial screening, the same LFA strip can be scanned with a fluorescence reader, enabling rapid and ultrasensitive colorimetric and fluorometric detection of disease markers with only one test.”

“It’s like turning up the volume on standard color-changing test strips. Instead of getting a faint line indicating only a positive or negative result, the new p-LFAs give clearer results with fewer particles, enabling one to move from simply ‘yes or no?’ to exactly ‘how much?’ with the aid of an inexpensive, portable scanner,” says Jeremiah Morrissey, a research professor in anesthesiology in the Division of Clinical and Translational Research at the School of Medicine. Morrissey is a coauthor of the new study and a long-term collaborator with the Singamaneni lab.

This improved testing capability has obvious benefits for a population now all too familiar with the need for quick and reliable test results and the risk of false negatives.

“When we took on this problem in 2019, we thought our biggest challenge would be getting an adequate number of samples from sick people,” Genin recalls. “Where on Earth could we find a massive set of samples from patients whose symptoms were carefully documented and whose diagnosis was verified by slow and expensive PCR tests?”

In a matter of months, COVID-19 would erase that obstacle while introducing a whole host of new challenges and opportunities.

“The pandemic was a big shift for us, like it was for everyone,” says first author Rohit Gupta, who worked on the p-LFA study as a graduate student in Singamaneni’s lab and is now a senior scientist at Pfizer.

“We had to move away from our original focus on distinguishing viruses from bacteria, but it turned out to be an opportunity to do practical science with real stakes. We were working with epidemiologists to get samples for testing, with diagnosticians to compare our test to what was available, and with clinicians to gain insights into the real needs for patient care.”

Input from the entire collaboration helped Gupta and Singamaneni refine the design of the p-LFAs, which ultimately achieved 95% clinical sensitivity and 100% specificity for SARS-CoV-2 antibodies and antigens. Genin describes the results as stunning.

“We didn’t know it was going to work so well,” he says. “We knew it would be good, but we didn’t know this $1 test with a $300 readout device would be so much better—10 times better—than state of the art that we all used during the COVID pandemic.”

Now that they’ve proven p-LFAs can outperform standard lab tests in sensitivity, speed, convenience and cost for one disease, the team is looking to develop new applications for the technology, including returning to their original goal of identifying bacterial versus viral infections and getting their diagnostic tool into the hands of physicians around the world.

The p-LFA technology has been licensed to Auragent Bioscience LLC by Washington University’s Office of Technology Management. Singamaneni and Morrissey are among the cofounders of Auragent.

“We expect to have p-LFAs commercially available in the next one to two years,” Singamaneni says. “Right now, we’re working on improving our portable scanner technology, which adds a more sensitive, fluorescent reading capability to the test strips in addition to the color change that can be seen with the naked eye. We think we can get that cost down to a point where it’s accessible to rural clinics in the US and abroad, which was one of our original goals.”

“We’re also excited about the potential to detect many more diseases than COVID, possibly using a skin patch that can take a painless sample,” Singamaneni adds.

“This technology has the potential to detect any number of diseases, ranging from STIs to respiratory infections and more, as well as cytokines indicative of inflammation seen in conditions such as rheumatoid arthritis and sepsis.”

The research appears in Nature Biomedical Engineering.

Support for the research came from the National Science Foundation, the National Cancer Institute-Innovative Molecular Analysis Technologies, and the Washington University Institute of Clinical and Translational Sciences from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH).

Source: Washington University in St. Louis

New research in cells finds that the PFAS chemical GenX suppresses the neutrophil respiratory burst—the method white blood cells known as neutrophils use to kill invading pathogens.

The study is an important first step in understanding how both legacy and emerging PFAS chemicals might affect the body’s innate immune system.

PFAS are a class of per- and polyfluoroalkyl chemicals used to make consumer and industrial products more resistant to water, stains, and grease. According to the US Environmental Protection Agency, there are more than 12,000 known PFAS, which also include fluoroethers such as GenX.

“It’s pretty well-established that PFAS are toxic to the adaptive immune system, but there hasn’t been as much research done on their effects on the innate immune system,” says Drake Phelps, a former PhD student at North Carolina State University and first author of the study.

The human immune system has two branches: adaptive and innate. The adaptive branch contains T cells and B cells that “remember” pathogens the body has encountered, but it is slow to mount a defense, acting days—sometimes weeks—after it detects a pathogen.

The innate immune system serves as the body’s first responders, and contains white blood cells that can be dispatched to the site of an invasion within hours. These white blood cells include neutrophils, which can dump reactive oxygen species—think tiny amounts of bleach or hydrogen peroxide that neutrophils manufacture inside their cells—directly onto pathogens, killing them. That process is called the respiratory burst.

Drake and the research team looked at the effect of nine environmentally relevant legacy and emerging PFAS on neutrophils from zebrafish embryos, neutrophil-like cells (cells that can be chemically treated to behave like neutrophils), and human neutrophil cells cultured from donor blood.

Emerging PFAS are chemicals, like GenX, developed to replace older, legacy PFAS that had proven toxic. All of the PFAS included in this study were detected in both the Cape Fear River in North Carolina and the blood serum of residents whose drinking water came from the Cape Fear River.

The embryos and cells were exposed to 80 micromolar solutions of each chemical:
perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na).

Of the nine PFAS tested, only GenX suppressed the neutrophil respiratory burst in embryonic zebrafish, neutrophil-like cells, and human neutrophils. PFHxA also suppressed the respiratory burst, but only in embryonic zebrafish and neutrophil-like cells.

The researchers caution that while the results of this preliminary study are interesting, they raise more questions than they answer.

“The longest chemical exposure in our study was four days, so obviously we can’t compare that to real human exposure of four decades,” says Jeff Yoder, professor of comparative immunology and corresponding author of the work. “We looked at a high dose of single PFAS over a short period, whereas people in the Cape Fear River basin were exposed to a mixture of PFAS—a low dose over a long period.

“So while we can say that we see a toxic effect from a high dose in the cell lines, we can’t yet say what effects long-term exposure may ultimately have on the immune system. This paper isn’t the end of the road—it’s the first step. Hopefully our work may help prioritize further study of these two chemicals.”

The study appears in the Journal of Immunotoxicology and had support from the National Institute of Environmental Health Sciences (NIEHS), the North Carolina State University Center for Environmental and Health Effects of PFAS, and the North Carolina State University Center for Human Health and the Environment (CHHE). Jamie DeWitt, professor of pharmacology and toxicology at East Carolina University, is coauthor.

Source: NC State

Researchers have developed an inhalable powder that could protect lungs and airways from viral invasion.

The powder, called Spherical Hydrogel Inhalation for Enhanced Lung Defense, or SHIELD, reduced infection in both mouse and non-human primate models over a 24-hour period, and can be taken repeatedly without affecting normal lung function.

“The idea behind this work is simple—viruses have to penetrate the mucus in order to reach and infect the cells, so we’ve created an inhalable bioadhesive that combines with your own mucus to prevent viruses from getting to your lung cells,” says Ke Cheng, corresponding author of the paper describing the work. “Mucus is the body’s natural hydrogel barrier; we are just enhancing that barrier.”

Cheng is a professor in regenerative medicine at North Carolina State University’s College of Veterinary Medicine and a professor in the NC State/UNC-Chapel Hill joint department of biomedical engineering.

“SHIELD… works like an ‘invisible mask’ for people in situations where masking is difficult…”

The inhalable powder microparticles are composed of gelatin and poly(acrylic acid) grafted with a non-toxic ester. When introduced to a moist environment—such as the respiratory tract and lungs—the microparticles swell and adhere to the mucosal layer, increasing the “stickiness” of the mucus.

The effects are most potent during the first eight hours after inhalation. SHIELD biodegrades over a 48-hour period, and is completely cleared from the body.

In a mouse model, SHIELD blocked SARS-CoV-2 pseudovirus particles with 75% efficiency four hours after inhalation, which fell to 18% after 24 hours. The researchers found similar results when testing against pneumonia and H1N1 viruses.

In a non-human primate model of both the original and Delta SARS-CoV-2 variants, SHIELD-treated subjects had reduced viral loads—from 50 to 300-fold less than control subjects—and none of the symptoms commonly associated with infection in primates, such as lung inflammation or fibrosis. Since primates do not exhibit the same symptoms of infection as humans, viral load is the standard marker used to determine exposure.

The researchers also looked at potential toxicity both in vitro and in vivo: 95% of cell cultures exposed to a high concentration (10 mg ml-1) of SHIELD remained healthy, and mice who were given daily doses for two weeks retained normal lung and respiratory function.

“SHIELD is easier and safer to use than other physical barriers or anti-virus chemicals,” Cheng says. “It works like an ‘invisible mask’ for people in situations where masking is difficult, for example during heavy exercise, while eating or drinking, or in close social interactions. People can also use SHIELD on top of physical masking to have better protection.

“But the beauty of SHIELD is that it isn’t necessarily limited to protecting against COVID-19 or flu. We’re looking at whether it could also be used to protect against things like allergens or even air pollution—anything that could potentially harm the lungs.”

The study appears in Nature Materials. Funding comes from the National Institutes of Health, the American Heart Association, and special funding from the NC State Provost’s Office. The researchers have filed a patent and are working on FDA approval for human use.

Source: NC State

If ChatGPT sounds like a human, does that mean it learns like one, too? And just how similar is the computer brain to a human brain?

ChatGPT, a new technology developed by OpenAI, is so uncannily adept at mimicking human communication that it will soon take over the world—and all the jobs in it. Or at least that’s what the headlines would lead the world to believe.

In a February 8 conversation organized by Brown University’s Carney Institute for Brain Science, two Brown scholars from different fields of study discussed the parallels between artificial intelligence and human intelligence. The discussion on the neuroscience of ChatGPT offered attendees a peek under the hood of the machine learning model-of-the-moment.

Ellie Pavlick is an assistant professor of computer science and a research scientist at Google AI who studies how language works and how to get computers to understand language the way that humans do.

Thomas Serre is a professor of cognitive, linguistic, and psychological sciences and of computer science who studies the neural computations supporting visual perception, focusing on the intersection of biological and artificial vision. Joining them as moderators were Carney Institute director and associate director Diane Lipscombe and Christopher Moore, respectively.

Pavlick and Serre offered complementary explanations of how ChatGPT functions relative to human brains, and what that reveals about what the technology can and can’t do. For all the chatter around the new technology, the model isn’t that complicated and it isn’t even new, Pavlick said. At its most basic level, she explained, ChatGPT is a machine learning model designed to predict the next word in a sentence, and the next word, and so on.

This type of predictive-learning model has been around for decades, said Pavlick, who specializes in natural language processing. Computer scientists have long tried to build models that exhibit this behavior and can talk with humans in natural language. To do so, a model needs access to a database of traditional computing components that allow it to “reason” overly complex ideas.

What is new is the way ChatGPT is trained, or developed. It has access to unfathomably large amounts of data—as Pavlick said, “all the sentences on the internet.”

“ChatGPT, itself, is not the inflection point,” Pavlick said. “The inflection point has been that sometime over the past five years, there’s been this increase in building models that are fundamentally the same, but they’ve been getting bigger. And what’s happening is that as they get bigger and bigger, they perform better.”

What’s also new is the way that the ChatGPT and its competitors are available for free public use. To interact with a system like ChatGPT even a year ago, Pavlick said, a person would need access to a system like Brown’s Compute Grid, a specialized tool available to students, faculty, and staff only with certain permissions, and would also require a fair amount of technological savvy. But now anyone, of any technological ability, can play around with the sleek, streamlined interface of ChatGPT.

Does ChatGPT really think like a human?

Pavlick said that the result of training a computer system with such a massive data set is that it seems to pick up general patterns and gives the appearance of being able to generate very realistic-sounding articles, stories, poems, dialogues, plays, and more. It can generate fake news reports, fake scientific findings, and produce all sorts of surprisingly effective results—or “outputs.”

The effectiveness of their results have prompted many people to believe that machine learning models have the ability to think like humans. But do they?

ChatGPT is a type of artificial neural network, explained Serre, whose background is in neuroscience, computer science, and engineering. That means that the hardware and the programming are based on an interconnected group of nodes inspired by a simplification of neurons in a brain.

Serre said that there are indeed a number of fascinating similarities in the way that the computer brain and the human brain learn new information and use it to perform tasks.

“There is work starting to suggest that at least superficially, there might be some connections between the kinds of word and sentence representations that algorithms like ChatGPT use and leverage to process language information, vs. what the brain seems to be doing,” Serre said.

For example, he said, the backbone of ChatGPT is a state-of-the-art kind of artificial neural network called a transformer network. These networks, which came out of the study of natural language processing, have recently come to dominate the entire field of artificial intelligence. Transformer networks have a particular mechanism that computer scientists call “self-attention,” which is related to the attentional mechanisms that are known to take place in the human brain.

Another similarity to the human brain is a key aspect of what has enabled the technology to become so advanced, Serre said. In the past, he explained, training a computer’s artificial neural networks to learn and use language or perform image recognition would require scientists to perform tedious, time-consuming manual tasks like building databases and labeling categories of objects.

Modern large language models, such as the ones used in ChatGPT, are trained without the need for this explicit human supervision. And that seems to be related to what Serre referred to as an influential brain theory known as the predictive coding theory. This is the assumption that when a human hears someone speak, the brain is constantly making predictions and developing expectations about what will be said next.

While the theory was postulated decades ago, Serre said that it has not been fully tested in neuroscience. However, it is driving a lot of experimental work at the moment.

“I would say, at least at those two levels, the level of attention mechanisms at the core engine of this networks that are consistently making predictions about what is going to be said, that seems to be, at a very coarse level, consistent with ideas related to neuroscience,” Serre said during the event.

There has been recent research that relates the strategies used by large language models to actual brain processes, he noted: “There is still a lot that we need to understand, but there is a growing body of research in neuroscience suggesting that what these large language models and vision models do [in computers] is not entirely disconnected with the kinds of things that our brains do when we process natural language.”

On a darker note, in the same way that the human learning process is susceptible to bias or corruption, so are artificial intelligence models. These systems learn by statistical association, Serre said. Whatever is dominant in the data set will take over and push out other information.

“This is an area of great concern for AI, and it’s not specific to languages,” Serre said. He cited how the overrepresentation of Caucasian men on the internet has biased some facial recognition systems to the point where they have failed to recognize faces that don’t appear to be white or male.

“The systems are only as good as the training data we feed them with, and we know that the training data isn’t that great in the first place,” Serre said. The data also isn’t limitless, he added, especially considering the size of these systems and the voraciousness of their appetite.

The latest iteration of ChatCPT, Pavlick said, includes reinforcement learning layers that function as guardrails and help prevent the production of harmful or hateful content. But these are still a work in progress.

“Part of the challenge is that… you can’t, give the model a rule—you can’t just say, ‘never generate such-and-such,’” Pavlick said. “It learns by example, so you give it lots of examples of things and say, ‘Don’t do stuff like this. Do do things like this.’ And so it’s always going to be possible to find some little trick to get it to do the bad thing.”

Nope, ChatGPT doesn’t dream

One area in which human brains and neural networks diverge is in sleep—specifically, while dreaming. Despite AI-generated text or images that seem surreal, abstract, or nonsensical, Pavlick said there’s no evidence to support the notion of functional parallels between the biological dreaming process and the computational process of generative AI. She said that it’s important to understand that applications like ChatGPT are steady-state systems—in other words, they aren’t evolving and changing online, in real-time, even though they may be constantly refined offline.

“It’s not like [ChatGPT is] replaying and thinking and trying to combine things in new ways in order to cement what it knows or whatever kinds of things happen in the brain,” Pavlick said. “It’s more like: it’s done. This is the system. We call it a forward pass through the network—there’s no feedback from that. It’s not reflecting on what it just did and updating its ways.”

Pavlick said that when AI is asked to produce, for example, a rap song about the Krebs cycle, or a trippy image of someone’s dog, the output may seem impressively creative, but it’s actually just a mash-up of tasks the system has already been trained to do. Unlike a human language user, each output is not automatically changing each subsequent output, or reinforcing function, or working in the way that dreams are believed to work.

The caveats to any discussion of human intelligence or artificial intelligence, Serre and Pavlick emphasized, are that scientists still have a lot to learn about both systems. As for the hype about ChatGPT, specifically, and the success of neural networks in creating chatbots that are almost more human than human, Pavlick said it has been well-deserved, especially from a technological and engineering perspective.

“It’s very exciting!” she said. “We’ve wanted systems like this for a long time.”

Source: Brown University

Baby kangaroo feces might help provide an unlikely solution to the environmental problem of cow-produced methane, according to a new study.

A microbial culture developed from the kangaroo feces inhibited methane production in a cow stomach simulator.

After researchers added the baby kangaroo culture and a known methane inhibitor to the simulated stomach, it produced acetic acid instead of methane. Unlike methane, which cattle discard as flatulence, acetic acid has benefits for cows as it aids muscle growth.

“Methane emissions from cows are a major contributor to greenhouse gases, and at the same time, people like to eat red meat,” says Birgitte Ahring, professor in with the bioproducts, sciences, and engineering laboratory at Washington State University and corresponding author of the study in the journal Biocatalysis and Agricultural Biotechnology. “We have to find a way to mitigate this problem.”

Reducing the burps and farts of methane emissions from cattle is no laughing matter. Methane is the second largest greenhouse gas contributor and is about 30 times more potent at heating up the atmosphere than carbon dioxide. More than half of the methane released to the atmosphere is thought to come from the agricultural sector, and ruminant animals, such as cattle and goats, are the most significant contributors. Furthermore, the process of producing methane requires as much as 10% of the animal’s energy.

Researchers have tried changing cows’ diets as well as giving them chemical inhibitors to stop methane production, but the methane-producing bacteria soon become resistant to the chemicals. They also have tried to develop vaccines, but a cow’s microbiome depends on where it’s eating, and there are far too many varieties of the methane-producing bacteria worldwide. The interventions can also negatively affect the animals’ biological processes.

Ahring and colleagues study fermentation and anaerobic processes and had previously designed an artificial rumen, the largest stomach compartment found in ruminant animals, to simulate cow digestion.

With many enzymes that are able to break down natural materials, rumens have “amazing abilities,” says Ahring, who is also a professor in the School of Chemical Engineering and Bioengineering and in Biological System Engineering.

Looking to investigate how to outcompete the methane-producing bacteria in their reactor, Ahring learned that kangaroos have acetic acid-producing, instead of methane-producing, bacteria in their foregut. Her students tracked down some kangaroos, took samples, and learned that the specialized acetic acid-producing process only occurred in baby kangaroos—not in adults. Unable to separate out specific bacteria that might be producing the acetic acid, the researchers used a stable mixed culture developed from the feces of the baby kangaroo.

After initially reducing the methane-producing bacteria in their reactor with a specialized chemical, the acetic acid bacteria were able to replace the methane-producing microbes for several months with a similar growth rate as the methane-producing microbes.

While the researchers have tested their system in the simulated rumen, they hope to try it on real cows sometime in the future.

“It is a very good culture. I have no doubt it is promising,” Ahring says. “It could be really interesting to see if that culture could run for an extended period of time, so we would only have to inhibit the methane production from time to time. Then, it could actually be a practice.”

Washington State’s College of Agricultural, Human, and Natural Resource Sciences’ Appendix A program supported the work.

Source: Washington State University

A quick clinical test can predict which people with neck pain are more likely to benefit from epidural steroid injections, researchers report.

These injections deliver drugs directly around the spinal nerves to stop nerve inflammation and reduce pain.

The uncomfortable injections are a common treatment for neck pain, but can cost hundreds of dollars each, carry risks, and help only a minority of patients, studies show.

A new variation on physical exam, as described in the journal Mayo Clinic Proceedings among 78 people with neck pain, could help guide best use of the treatment.

“Until now, it was really a 50/50 coin flip whether an epidural steroid injection would help any given neck pain patient,” says Steven P. Cohen, professor of anesthesiology and critical care medicine at Johns Hopkins University School of Medicine.

“We looked at many different variables and believe we’ve figured out a quick and reliable way to provide patients with much more accurate, personalized information on their chances of getting better, and actually improve their odds of treatment success.”

According to the American Medical Association, neck and back pain are among the ailments that incur the highest amounts of total health care spending in the United States. Each year, doctors administer more than 10 million epidural steroid injections for back and neck pain.

Injected steroids can reduce the swelling and pressure on nerves that contribute to pain. However, the underlying causes of back and neck pain are diverse, and not all patients experience pain relief from the injections. As a result, the procedure is facing increased scrutiny by hospital systems and insurers, fueling a search for ways to better identify patients most likely to benefit.

In the new study, Cohen and collaborators adapted Waddell signs—a group of eight physical signs, named for the physician who developed them, more than 50 years ago, as a tool to identify patients whose back pain may not be due to physical abnormalities that can be treated surgically—for neck pain patients.

The signs, which can be assessed in a few minutes by a clinician, include checking for tenderness, overreaction to light stimulation, weakness not clearly explained by any physical injury or abnormality, pain that disappears when the patient is distracted, and pain that extends beyond expected areas of the body. “These physical exam maneuvers are incredibly simple to perform and easy to identify,” says Cohen.

For back pain, Waddell signs are used primarily to determine whether back pain is non-organic (not associated with a direct anatomic cause). Previously, many clinicians interpreted these signs as indicative of malingering or psychological factors. More recently, however, researchers have shown that such non-organic signs may also point to complex underlying causes of pain. In general, studies have shown that back pain patients with more Waddell signs are less likely to benefit from treatment.

To conduct the new study, clinicians examined 78 neck pain patients for the eight non-organic physical signs before treating them with epidural steroid injections. Overall, 29% (23) of the patients showed no non-organic signs; 21% (16) had one non-organic sign; and 50% (39) of patients had two or more signs before injections.

One month later, patients whose pain was still decreased by the epidural steroid injection had, on average, just 1.3 non-organic signs, while those whose pain was not decreased at the one-month mark had, on average, 3.4 non-organic signs.

Some of the individual Waddell signs were highly correlated with a lack of response to the injections. For example, 55% of injection non-responders showed apparent overreactions to light touch, while only 11% of those helped by the injections showed this sign. The researchers also found that people with more non-organic signs associated with their neck pain were more likely to report chronic pain in other areas of the body, as well as fibromyalgia and psychiatric conditions.

Cohen says it appears that the presence of multiple non-organic signs are identifying patients who might benefit from other treatment approaches, before trying epidural steroid injections. “But further research must be done to determine the best options.”

For now, Cohen says the findings can immediately help guide conversations between patients with neck pain and their doctors, when weighing the potential risks and benefits of an epidural steroid injection.

Additional coauthors are from Walter Reed National Military Medical Center, the District of Columbia Veterans Affairs Medical Center, Seoul National University in Korea, and Johns Hopkins.

The research was supported in part by the US Department of Defense.

Source: Johns Hopkins University

Contrary to popular belief, snakes can hear and react to airborne sound, according to a new study.

The researchers played three different sound frequencies to captive-bred snakes one at a time in a soundproof room and observed their reactions.

“Because snakes don’t have external ears, people typically think they’re deaf and can only feel vibrations through the ground and into their bodies,” says Christina Zdenek from University of Queensland’s School of Biological Sciences.

“But our research—the first of its kind using non-anesthetized, freely moving snakes—found they do react to soundwaves traveling through the air, and possibly human voices.”

The study involved 19 snakes, representing five genetic families of reptile.

“We played one sound which produced ground vibrations, while the other two were airborne only,” Zdenek says. “It meant we were able to test both types of ‘hearing’—tactile hearing through the snakes’ belly scales and airborne through their internal ear.”

The reactions strongly depended on the genus of the snakes.

“Only the woma python tended to move toward sound, while taipans, brown snakes, and especially death adders were all more likely to move away from it,” Zdenek says.

“The types of behavioral reactions also differed, with taipans in particular more likely to exhibit defensive and cautious responses to sound.

“For example, woma pythons are large nocturnal snakes with fewer predators than smaller species and probably don’t need to be as cautious, so they tended to approach sound,” Zdenek says.

“But taipans may have to worry about raptor predators and they also actively pursue their prey, so their senses seem to be much more sensitive.”

The findings challenge the assumption that snakes can’t hear sound, such as humans talking or yelling, and could reshape the view on how they react to sound.

“We know very little about how most snake species navigate situations and landscapes around the world. But our study shows that sound may be an important part of their sensory repertoire.

“Snakes are very vulnerable, timid creatures that hide most of the time, and we still have so much to learn about them.”

The research appears in PLOS ONE. Damian Candusso, a professor at Queensland University of Technology is a coauthor.

Source: University of Queensland

The ability of fish in temperate and polar ecosystems to transition back and forth from shallow to deep water triggers species diversification, a new study finds.

Fish, the most biodiverse vertebrates in the animal kingdom, present evolutionary biologists a conundrum: The greatest species richness is found in the world’s tropical waters, yet the fish groups that generate new species most rapidly inhabit colder climates at higher latitudes.

The findings of the new study, published in Nature Communications, help to explain the paradox and suggest that as climate change warms the oceans at higher latitudes, it will impede the evolution of fish species.

“The fish clades contributing the most fish diversity in today’s oceans are leveraging the water column and the ocean depths, in particular, to diversify,” says lead author Sarah T. Friedman, who conducted the research while a postdoctoral associate at Yale University.

“Fishes that make these forays into the deep ocean are almost exclusively located in high latitudes, where it’s easier to move along the water column. These regions are experiencing the most drastic warming due to climate change, which threatens to disrupt speciation by making it more difficult for fish to change depths.”

Friedman, now a research fish biologist at the National Oceanic and Atmospheric Administration, coauthored the study with Martha Muñoz, an assistant professor of ecology and evolutionary biology at Yale and an assistant curator of vertebrate zoology at the Yale Peabody Museum.

For the study, the researchers analyzed existing data on the global species occurrence of 4,067 fish species that included information on species geographic range and speciation rate. In part, their analysis modeled how often fish lineages might be expected to transition across ocean depths.

By laying out a distribution of anticipated shifts in depth, the researchers could compare the number of observed transitions in specific lineages. They found that species-rich, high-latitude lineages—eelpouts, rockfishes, flatfishes, icefishes, and snailfishes—transitioned up and down the water column more often than expected. Meanwhile, hyper-diverse tropical lineages, such as gobies and wrasses, changed depth less frequently than predicted.

Fish clades, evolutionary lineages that share a common ancestor, that can freely disperse along the depth gradient may be more likely to capitalize on novel resources or niches at specific depths and become isolated from other members of their group, the researchers say. This can lead to repeated local adaptation and the evolution of new species.

Many variables can affect a fish’s ability to move between depths, including water temperature, pressure, and light penetration. Friedman and Muñoz suggest that temperature plays an important role in the ability of high-latitude fish clades to transition along the water column.

Fish clades that inhabit colder water have an easier time traveling into ocean depths, where water temperature plummets dramatically. By contrast, tropical fish, which spend their lives in warm, shallow waters, face steep thermal barrier to transitioning to the deep ocean, the researchers say.

The existing high biodiversity in tropical waters could be a remnant of the deep past when warmer regions were hotbeds of species generation, but over time, most diversification began occurring closer to the Earth’s poles, the researchers explain.

But this biodiversity engine at higher latitudes is vulnerable to climate change. Since the water profile is so much more uniform at higher latitudes than in the tropics, the fish that inhabit them are physiologically fine-tuned to those environments, Muñoz explains.

For them, a one-degree shift in temperature will be physiologically more challenging than for an organism that is more of a thermal generalist.

“As the oceans warm, organisms might face steeper barriers to dispersal across the depth column,” Muñoz says. “Over time, I think we’ll see a slowdown of this engine of biodiversification.”

Funding came from the G. Evelyn Hutchinson Environmental Postdoctoral Fellowship, which aims to enable creative research collaborations in the environmental sciences at Yale by developing diverse academic excellence at the postdoctoral level.

Source: Yale University

The brown basilisk, a nonnative lizard, is gaining ground across South Florida, and University of Florida scientists need more data to determine its status and potential impacts.

Wildlife specialists with the UF Institute of Food and Agricultural Sciences (UF/IFAS) depend on geographic information to determine this lizard’s potential impacts on the environment, wildlife, and human health. They need more information to stay ahead.

“We receive anecdotal reports of brown basilisks in areas where the reported sightings are thin and sporadic, but we know they are thriving in South and Central Florida. There are reports of brown basilisks from the Florida Keys to Gainesville,” says Ken Gioeli, a natural resources and environment agent at University of Florida Institute of Food and Agricultural Sciences (UF/IFAS) Extension St. Lucie County. “Residents and visitors can enhance the data by taking photos of brown basilisks and uploading them to EddMapS or the IveGot1 app.”

This call to action goes out as National Invasive Species Awareness Week begins on February 20.

The lizard has prominent markings and characteristics that distinguish it from other reptilian species. Most notable is the head crest. They also appear to run across water. There remains a mystery to scientists about how far and wide they have spread and what they are eating and disturbing.

To help residents and visitors identify the brown basilisk, a peer-reviewed Extension document is available in English and Spanish. UF/IFAS faculty hope the information will galvanize more people to report the species.

“Providing information in multiple languages is vital to extending the reach in search of scientific data,” says Lourdes Perez Cordero, an agriculture and natural resources agent at UF/IFAS Extension Highlands County. “Hispanics living throughout Florida can provide valuable insight to the presence of brown basilisks in places where they haven’t been reported previously. Their feedback also enriches our general knowledge of these lizards and helps us develop more educational materials for Spanish speakers in the future that can reach local communities in both languages.”

Currently, numbers indicate that the reptiles are in South and Central Florida.

“It is important for us to determine where the invasion front currently is, where it might be heading, and the numbers likely to be found,” says Gioeli, a coauthor of the document. “Right now, we can work with the limited reported sightings on EddMaps, but scientists need more accurate numbers.”

Of particular interest is the space between Orlando and Palm Beach County, says Gioeli. “We know the brown basilisks are on the Treasure Coast, and we can see there is a likely move northward and west.”

Florida’s west coast has also seen sporadic reports. More residents reporting their locations provides credible research-based information to scientists and keeps residents informed among local communities.

The additional geographic points can give researchers a jump ahead of the invasion front and start letting people know what to watch out for. This will help scientists record how far and wide the brown basilisk continues to spread while studying their behaviors, impacts, and potential as an invasive species.

“There is still a lot we don’t know about the impacts of brown basilisks in south and central Florida,” Gioeli says.

While not all nonnative species evolve to become invasive, those that become established can affect waterways, wildlife, agriculture and urban areas—a concern for scientists, wildlife organizations, and communities.

Key things to know about the brown basilisk:

• The brown basilisk is in the family Corytophanidae, also known as iguanian lizards. They go by several names, such as helmeted or casque-headed lizards due to their head crests and as “Jesus lizards” because they can sprint across the surface of waters when fleeing predators.
• Brown basilisks are brown or dark olive. They have a distinct yellow or cream-colored stripe on each side of their body that runs from the eye down their back. A second stripe is often visible on the face extending to the shoulder. They have long, thin tails and long rear toes. Adults can range in size from 11 to 27 inches.
• A study published in the journal Frontiers in 2022 finds that Culex mosquitoes prefer to feed on nonnative lizards. The brown basilisks are among five identified nonnative lizards that could potentially serve as significant hosts for West Nile virus and St. Louis encephalitis virus vectors in Florida.
• As of February 2023, more than 160 specimens have been collected and recorded at the Florida Museum of Natural History Herpetology Collection database. The range of specimens in the database are from primarily coastal counties stretching from Brevard to Monroe, with additional samples from Manatee, Lee, Pinellas, and Collier counties. The southern shore of Lake Okeechobee also has established populations.
• While they are typically found near fresh water, including canals, shorelines of lakes, retention ponds, and ditches, they prefer areas with thick vegetation and are often seen basking and searching for insects on sidewalks, roads, and parking lots.

Source: University of Florida