Culture

A negative experience with food usually leaves us unable to stomach the thought of eating that particular dish again. Using sugar-loving snails as models, researchers at the University of Sussex believe these bad experiences could be causing a switch in our brains, which impacts our future eating habits.

Like many other animals, snails like sugar and usually start feeding on it as soon as it is presented to them. But through aversive training which involved tapping the snails gently on the head when sugar appeared, the snails' behaviour was altered and they refused to feed on the sugar, even when hungry.

When the team of Sussex Neuroscience researchers led by Dr Ildiko Kemenes looked a little closer, they discovered a neuronal mechanism that effectively reversed the snails' usual response to sugar after the conditioning training had taken place.

Dr Ildiko Kemenes, Reader in Neuroscience in the University of Sussex's School of Life Sciences, explained: "There's a neuron in the snail's brain which normally suppresses the feeding circuit. This is important, as the network is prone to becoming spontaneously activated, even in the absence of any food. By suppressing the feeding circuit, it ensures that the snail doesn't just eat everything and anything. But when sugar or other food stimulus is present, this neuron becomes inhibited so that feeding can commence.

"After the aversive training, we found that this neuron reverses its electrical response to sugar and becomes excited instead of inhibited by it. Effectively, a switch has been flipped in the brain which means the snail no longer eats the sugar when presented with it, because sugar now suppresses rather than activates feeding."

When researchers presented the trained snails with a piece of cucumber instead, they found that the animal was still happy to eat the healthy option - showing that the taps were associated with only the particular type of food they were trained to reject.

George Kemenes, Professor of Neuroscience at the University of Sussex and a senior member of the investigator team, added: "Snails provide us with a similar yet exceptionally basic model of how human brains work.

"The effect of the inhibitory neuron which suppresses the feeding circuit in the snail is quite similar to how, in the human brain, cortical networks are under inhibitory control to avoid 'runaway' activation which may lead to overeating resulting in obesity.

"In our research, the negative experience the snail had with the sugar could be likened to eating a bad takeaway curry which then puts us off that particular dish in future.

"We believe that in a human brain, a similar switch could be happening where particular groups of neurons reverse their activity in line with the negative association of a particular food. "

The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and published in Current Biology, also revealed that when the neuron was removed entirely from trained snails, they returned to eating sugar again.

Dr Ildiko Kemenes said: "This suggests that the neuron is necessary for the expression of the learned behaviour and for altering the response to sugar.

"However, we cannot rule out that the sugar-activated sensory pathway also undergoes some changes, so we don't make the assumption that this is all that's happening in the brain."

Low-income middle-aged African-American women with high blood pressure very commonly suffer from depression and should be better screened for this serious mental health condition, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

The researchers found that in a sample of over 300 low-income, African-American women, aged 40-75, with uncontrolled hypertension, nearly 60 percent screened positively for a diagnosis of depression based on a standard clinical questionnaire about depressive symptoms.

The results appeared February 10 in JAMA Psychiatry.

"Our findings suggest that low-income, middle-aged African-American women with hypertension really should be screened for depression symptoms," says study senior author Darrell Gaskin, PhD, William C. and Nancy F. Richardson Professor in Health Policy and director of the Johns Hopkins Center for Health Disparities Solutions in the Bloomberg School's Department of Health Policy and Management.

Recent research suggests that hypertension and depression often occur concurrently. Gaskin and colleagues note that the connection has not been well studied in African Americans, but should be, given they have relatively high rates of hypertension. Moreover, women in general have much higher rates of depression compared to men and depression is often under diagnosed and untreated.

The sample of women in the study were participants in an ongoing clinical trial of the Prime Time Sister Circles intervention--a health education-, lifestyle-change- and support-group-based intervention in Washington, DC, aimed at helping African American women better managed their blood pressure, weight, other chronic conditions and stress levels. The women were in the 40- to 75-age range, and had hypertension (?140 mmHg systolic or ?90 mmHg diastolic) that had been diagnosed at a federally qualified health center. At the outset of the study, the women filled out a standard questionnaire called the CES-D-10 which asks about depression symptoms in the past week. The analysis from the Bloomberg School team covered the 316 women age 40 to 75 who completed the questionnaires.

The researchers found that 180 of the 316, or about 57 percent, scored 10 or greater on the CES-10-D questionnaire--generally considered evidence of significant depressive symptoms. The women in this group were significantly more likely to have a high school education or less, and to be smokers. More than 34 percent of these women reported that at least once in the previous six months they had stayed in bed for more than half the day owing to depression, compared to only 9 percent of the women with CES-D-10 scores below 10.

The nearly 60 percent prevalence of apparent depression among these hypertensive, low-income middle-aged African American women suggests that these women should be routinely screened for, and, if need be, treated for depression, Gaskin and colleagues emphasize.

They note, however, that 85 percent of the women with depression-level CES-D-10 scores reported receiving some treatment for depression within the prior six months--implying that much of the depression among these low-income middle-aged, hypertensive African-American women is already treated, albeit inadequately.

The Prime Time Sister Circles intervention encourages African American women to prioritize and better manage their health. The clinical trial of that intervention, which is focused mainly on its ability to reduce hypertension but secondarily on its impact on depression, is still ongoing.

"We are hopeful that those women who are in that trial will do better not just in regard to depression but also with regard to other underlying factors that may contribute to high blood pressure," Gaskin says.

New research shows that biodiversity is important not just at the traditional scale of short-term plot experiments--in which ecologists monitor the health of a single meadow, forest grove, or pond after manipulating its species counts--but when measured over decades and across regional landscapes as well. The findings can help guide conservation planning and enhance efforts to make human communities more sustainable.

Published in a recent issue of Frontiers in Ecology and the Environment, the multi-institutional study was led by Dr. Christopher Patrick of William & Mary's Virginia Institute of Marine Science, along with Kevin McCluney of Bowling Green State University, Albert Ruhi of University of California-Berkeley, Andrew Gregory of the University of North Texas, John Sabo of Arizona State University, and James Thorp of the University of Kansas.

"Having low biodiversity is like putting all your eggs in one basket and puts us at greater risk of something catastrophic happening," says Patrick. "We've known this for a long time, but never before have we shown this to be true for entire regions and landscapes." The team reached their findings by compiling, analyzing, and modeling data collected over decades and across both aquatic and terrestrial ecosystems. The analysis focused on abundance and diversity trends within 50 families of terrestrial beetles from the Sonoran Desert, 25 species of submerged aquatic vegetation or SAV within the Chesapeake Bay, and 56 species of fish from small streams in Maryland.

The threats posed by low biodiversity are exemplified by a recent drop in coverage of SAV within the Chesapeake, as recorded by VIMS' long-term monitoring program. "For the past few years, our gains in seagrass coverage were mostly due to the expansion of one species, widgeon grass," says Patrick. "That made us vulnerable. When widgeon grass had a bad year in 2019, we saw the single biggest drop in Chesapeake Bay SAV in the history of the VIMS monitoring program." Program scientists began recording SAV acreage in the bay in 1978.

Patrick says "The lesson here is that promoting biodiversity will increase ecosystem resilience." This is particularly important given increased variability in temperature and precipitation, population sizes, and ecosystem functions--often the result of human influence--which can increase the risk for local extinctions, promote outbreaks of pests or disease vectors, and curtail yields from human fisheries and agriculture.

Patrick notes that he and others at VIMS are already starting to put the findings from the recent study into practice. Researchers from Patrick's lab are collaborating with colleagues at the Chesapeake Bay National Estuarine Research Reserve on a multi-species restoration of SAV in Broad Bay near the Chesapeake Bay mouth in Virginia Beach. "In the past we've only planted one species, eelgrass," he says, "so trying to plant both eelgrass and widgeon grass together is a big change and one that will hopefully enhance the long-term success of the restoration of SAV to Broad Bay."

The team anticipates their findings will benefit conservation efforts within other ecosystems as well. "Understanding the interplay between regional and local controls of ecosystem variability may aid in the design of more effective conservation actions, management practices, and monitoring networks worldwide," says Patrick.

"Our results," he adds, "bolster the argument for conserving biodiversity by showing that it is needed at both local and regional scales to maintain stable delivery of ecosystem services across entire landscapes. We should not only avoid putting all our eggs in one basket, but ensure that we have lots of different kinds of eggs in lots of different kinds of baskets."

With the help of the international Gemini Observatory, a Program of NSF's NOIRLab, and other ground-based telescopes, astronomers have confirmed that a faint object discovered in 2018 and nicknamed "Farfarout" is indeed the most distant object yet found in our Solar System. The object has just received its designation from the International Astronomical Union.

Farfarout was first spotted in January 2018 by the Subaru Telescope, located on Maunakea in Hawai'i. Its discoverers could tell it was very far away, but they weren't sure exactly how far. They needed more observations.

"At that time we did not know the object's orbit as we only had the Subaru discovery observations over 24 hours, but it takes years of observations to get an object's orbit around the Sun," explained co-discoverer Scott Sheppard of the Carnegie Institution for Science. "All we knew was that the object appeared to be very distant at the time of discovery."

Sheppard and his colleagues, David Tholen of the University of Hawai'i and Chad Trujillo of Northern Arizona University, spent the next few years tracking the object with the Gemini North telescope (also on Maunakea in Hawai'i) and the Carnegie Institution for Science's Magellan Telescopes in Chile to determine its orbit. [1] They have now confirmed that Farfarout currently lies 132 astronomical units (au) from the Sun, which is 132 times farther from the Sun than Earth is. (For comparison, Pluto is 39 au from the Sun, on average.)

Farfarout is even more remote than the previous Solar System distance record-holder, which was discovered by the same team and nicknamed "Farout." Provisionally designated 2018 VG18, Farout is 124 au from the Sun.

However, the orbit of Farfarout is quite elongated, taking it 175 au from the Sun at its farthest point and around 27 au at its closest, which is inside the orbit of Neptune. Because its orbit crosses Neptune's, Farfarout could provide insights into the history of the outer Solar System.

"Farfarout was likely thrown into the outer Solar System by getting too close to Neptune in the distant past," said Trujillo. "Farfarout will likely interact with Neptune again in the future since their orbits still intersect."

Farfarout is very faint. Based on its brightness and distance from the Sun, the team estimates it to be about 400 kilometers (250 miles) across, putting it at the low end of possibly being designated a dwarf planet by the International Astronomical Union (IAU).

The IAU's Minor Planet Center in Massachusetts announced today that it has given Farfarout the provisional designation 2018 AG37. The Solar System's most distant known member will receive an official name after more observations are gathered and its orbit becomes even more refined in the coming years.

"Farfarout takes a millennium to go around the Sun once," said Tholen. "Because of this, it moves very slowly across the sky, requiring several years of observations to precisely determine its trajectory."

Farfarout's discoverers are confident that even more distant objects remain to be discovered on the outskirts of the Solar System, and that its distance record might not stand for long.

"The discovery of Farfarout shows our increasing ability to map the outer Solar System and observe farther and farther towards the fringes of our Solar System," said Sheppard. "Only with the advancements in the last few years of large digital cameras on very large telescopes has it been possible to efficiently discover very distant objects like Farfarout. Even though some of these distant objects are quite large -- the size of dwarf planets -- they are very faint because of their extreme distances from the Sun. Farfarout is just the tip of the iceberg of objects in the very distant Solar System."

ITHACA, N.Y. - As more male-dominated industries look for ways to hire women, new Cornell University research offers employers a simple solution - make your initial job candidate short list longer.

Many professional advancement opportunities - jobs, promotions, trainings and mentorships - are filled through informal recruitment practices. But these practices pose an unintended barrier to gender diversity in male-dominant workplaces because when hiring managers consult their "mental Rolodex," they are more likely to associate certain jobs with specific genders.

"Our research investigates informal short lists," said Brian Lucas, assistant professor in the ILR School and co-author of "A Longer Shortlist Increases the Consideration of Female Candidates in Male-Dominant Domains," recently published by Nature Human Behaviour.

"These are the initial shortlists that hiring managers generate on their own and bring with them into the formal recruitment process," Lucas said. "For positions with no formal process, the informal list is the final list."

Lucas and his co-authors conducted 10 studies asking individuals to generate an informal short list of candidates for a male-dominant role and then to extend the list.

"We consistently found more female candidates in the extended lists," Lucas said. "This longer short list intervention is a low-cost and simple way to support gender equity efforts."

The study also integrates insights from Lucas' previous research on the creative cliff illusion, which finds that as people generate more ideas, their ideas increasingly deviate from the status quo.

"It is important to elucidate the barriers to gender equity at all stages of the professional advancement pathway," said Lucas. "Our research shines a light on the gender biases that can operate at the informal shortlist generation stage and offers a simple and low-cost way to attenuate the gender bias."

Skoltech scientists have proposed a Mass Spectrometry Imaging (MSI) method leveraging the unique features of human vision. The research was published in the journal Analytical Chemistry.

High-resolution mass spectrometry is an analytical technique that accurately measures the mass-to-charge ratio (m/z) of ions, produced from molecules by an ionization process, and the ion signal intensity (the relative number of ions). These measurements allow determining molecules' weights and structure, (by fragmenting them), thereby identifying various compounds, such as proteins, lipids, metabolites, peptides, drug components, and the like. MSI provides information about the spatial distribution of molecules in tissues by performing mass spectrometry analysis of ions using local laser ionization of molecules at each point of the sample (for example, a tumor section).

Interpreting MSI data is quite a challenge. One can start by imaging the distribution of molecules over the tissue section surface and creating a full color image where each color represents a points with similar ion composition. So thousands of ions with corresponding intensities at each point should be represented by just three numerical values that reflect the MSI data to the utmost extent and are correlated with a 3D color space to enable further analysis by a researcher.

"It is essential to glean as much information from the image as possible, taking into account the genuine features of human vision, such as non-linearity and essentially different sensitivity to changes in brightness and color. Although the theory of color perception has been studied since the first half of the 20th century, experts still lack commonly accepted mathematical models accurately explaining all the known properties of human vision," Anastasia Sarycheva, the lead author and a Skoltech PhD student, explains.

Researchers from the Skoltech Center for Computational and Data-Intensive Science and Engineering (CDISE) and A.A. Kharkevich Institute for Information Transmission Problems of RAS have proposed a new MSI approach leveraging the theory of human color perception and comparable to the existing techniques in the level of detail. The new method preserves borders and gradients when superposing regions of similar ion composition. Thus, the resulting image is more interpretable than in other MSI visualization techniques. The method has been tested on both simulated and experimental data obtained by researchers from the Skoltech Mass Spectrometry Laboratory jointly with biologists from the Skoltech Center for Neurobiology and Brain Restoration (CNBR).

Getting around without the need to concentrate on every step is something most of us can take for granted because our inner ears drive reflexes that make maintaining balance automatic. However, for about 1.8 million adults worldwide with bilateral vestibular hypofunction (BVH) -- loss of the inner ears' sense of balance -- walking requires constant attention to avoid a fall. Now, Johns Hopkins Medicine researchers have shown that they can facilitate walking, relieve dizziness and improve quality of life in patients with BVH by surgically implanting a stimulator that electrically bypasses malfunctioning areas of the inner ear and partially restores the sensation of balance.

Results from their study of eight patients using the device are published today in the New England Journal of Medicine.

To maintain balance while moving through the world around us, our brains receive and process data from multiple sensory systems, including vision, proprioception (muscles and joints) and vestibular sensation from the inner ears. People with BVH have difficulty keeping their eyes, head and body steady. Head movements make their vision jump and blur, and walking requires conscious effort. Forced to deal with this mental distraction, individuals with BVH suffer a more than thirtyfold increase in fall risk and the social stigma of appearing to walk like someone who's intoxicated.

Current therapy for BVH is limited to vestibular rehabilitation exercises. Doctors advise their patients with BVH to avoid medications that damage the inner ear (ototoxic drugs) or suppress brain function (sedatives), and caution them to steer clear of activities that might endanger them or others, such as driving, swimming and walking in poorly lit areas.

"Although about 20 individuals had been implanted elsewhere with devices used to stimulate the vestibular nerve in a laboratory setting, participants in this trial are true pioneers -- the first to use a vestibular implant as a long-term, 24-hour-per-day sensory restoration treatment," says senior study author Charley Della Santina, M.D., Ph.D., professor of otolaryngology-head and neck surgery and biomedical engineering at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Vestibular NeuroEngineering Laboratory, which conducted the study.

To achieve this milestone, Della Santina and his colleagues used basic research and engineering technology to modify a cochlear implant -- a device that improves hearing loss by electrically stimulating the inner ear's cochlear nerve -- to instead activate the nearby vestibular nerve in response to signals from a motion sensor on the patient's head. Electrical pulse strength and timing convey information about the speed and direction of the patient's head motion which, in turn, drives head and eye reflexes that help maintain clearer vision during head movement and reduce the need to exert conscious effort to avoid falls.

In their study, the Johns Hopkins Medicine researchers evaluated eight patients with BVH who received the vestibular implant, assessing changes in postural stability, walking, hearing and patient-reported outcomes, including dizziness and quality of life. Assessments were conducted before implantation surgery (the baseline measure) and at six months and one year afterward. Median scores improved for the group on four of the five posture and gait metrics, and on three of the four patient-reported outcomes.

All eight patients experienced some hearing loss in the implanted ear. Five maintained hearing in the implanted ear sufficient to use a telephone without a hearing aid, and three experienced greater hearing loss.

"Improvement in performance on standardized clinical tests of balance and walking has been remarkable," says Margaret Chow, study lead author and biomedical engineering doctoral candidate at The Johns Hopkins University. "Even more gratifying is that our patients have been able to return to activities that enrich their daily lives, such as exercising, riding a bike, gardening or dancing at a daughter's wedding."

Overall, the improvement in quality of life and relief from the misery of BVH has been life altering, says A'ndrea Messer, Ph.D., one of the patients chronicled in the Johns Hopkins Medicine study and a senior science and research information officer at Penn State University.

"The multichannel vestibular implant is incredible," says Messer. "Before receiving it, I couldn't walk in the dark, on uneven ground or without a cane. Now, I can do all of those things and am living a fairly normal life."

For some 15,000 years, dogs have been our hunting partners, workmates, helpers and companions. Could they also be our next allies in the fight against COVID-19?

According to UC Santa Barbara professor emeritus Tommy Dickey(link is external) and his collaborator, BioScent researcher Heather Junqueira, they can. And with a review paper(link is external) published in the Journal of Osteopathic Medicine they have added to a small but growing consensus that trained medical scent dogs can effectively be used for screening individuals who may be infected with the COVID-19 virus.

This follows a comprehensive survey of research devoted to the use of trained scent dogs for detecting COVID. "The most striking result is that studies have already demonstrated that dogs can identify people who are COVID-19 positive," Dickey said of their findings. "Not only that," he added, "they can do it non-intrusively, more rapidly and with comparable or possibly better accuracy than our conventional detection tests."

Not surprisingly, the magic lies in canine sense of smell, which gives dogs the ability to detect molecules in tiny concentrations -- "one part in a quadrillion compared with one part in one billion for humans," according to the paper. Add to that other optimizations for smell, such as a large nasal area and the structure of their noses, which allows inflow through the nostrils and outflow through nasal folds. Further, with 125-300 million olfactory cells and a third of their brains devoted to interpreting odors, dogs are well equipped with the ability to sniff out the volatile organic compounds that indicate the presence of COVID.

"The dogs are basically smelling the sweat of the person," Dickey said of a series of experiments by French and Lebanese researchers(link is external) testing canines' capacity to sense COVID infection. Although the virus itself has no odor, metabolic products excreted by COVID-positive individuals through their sweat glands were detected by the 18 dogs selected for the study (16 Belgian malinois, one German shepherd and one Jack Russell terrier) with an accuracy rate of 83-100% after only four days of training. True failures, according to the study, could be attributed to "distractive external smells or movements by a TV filming crew."

"One dog twice indicated positive results that could not be confirmed," Dickey said. "Two weeks later they found that both people who gave those samples had to be hospitalized with COVID."

Meanwhile, a German research group employed eight scent detection dogs(link is external) in a randomized, double-blind controlled pilot study. The group trained the dogs for a week and then set them to sniffing 1,012 samples of saliva or tracheobronchial secretions. They returned an average detection rate of 94% with a sensitivity (ability to detect a true positive) of 67.9% to 95.2% and a specificity (ability to detect a true negative) of 92.4% to 98.9%. This pilot study used positive samples from severely affected individuals and negative samples from people with no symptoms. Future studies, according to that paper, could focus more on identifying different phases of infection or perhaps the detection of different disease phenotypes.

Using dogs to detect disease is not new. In fact, co-author Junqueira has previously published results showing that her scent dogs (beagles, bassett hounds and mixes of the two) can effectively detect non-small cell lung cancer.

"Canines are capable of detecting other types of cancer as well as malaria, Parkinson's disease and diabetes," Junqueira said, adding that "medical scent dog research has really only gained traction in recent years and that it will take many more peer-reviewed papers before the idea of using dogs for disease detection hits the mainstream."

Dickey's own interest in the subject was sparked over the course of his work as a therapy dog handler of three Great Pyrenees (over 3,000 therapy dog visits), a longtime avocation he leaned on after cancer forced him to retire from UC Santa Barbara's Department of Geography in 2013. "I loved UCSB," he said. "I loved teaching and I brought my therapy dogs to class all the time. I just had the life, what can I say?"

In fact, he couldn't stay away -- he and his dogs have been on hand to see the UCSB community through hard times, offering their shaggy coats, wet noses and calm demeanors through tragedy and stress. In retirement, Dickey has published three therapy dog books for children, some of which recount stories of their UCSB therapy dog adventures. In addition, he and his canines have presented educational demonstrations at the California Science Center and the Los Angeles Public Library, work that sparked his interest in the power of a dog's sense of smell for medical detection.

So when the new disease called COVID-19 hit, Dickey was primed to ask: Can dogs detect the novel coronavirus? Naturally, there was little in the way of refereed research on the topic, so he teamed up with Junqueira, who was already conducting her own COVID detection research(link is external) with her scent dogs in Florida. "One of our big motivations was to write a peer-reviewed paper that basically gave a progress report," he said. "Where are we? Is this stuff really possible?"

Dickey and Junqueira found that researchers used a variety of dogs. "There were a lot of Belgian malinois that were used, and dogs who have been trained on explosives and on colon cancer. So they were pro sniffers," Junqueira said. "Other groups, such as the one behind a Colombian study(link is external), were motivated by the need to find a quick, accurate and cost-effective form of COVID early detection." The Colombian group utilized a variety of dogs -- four Belgian malinois, one Alaskan malamute-Siberian mix and an American pit bull terrier.

"The pit bull had been previously mistreated," Dickey said, "but they rehabilitated him, and he was perfectly capable and doing a great job at sniffing." After almost two months of training and thousands of samples later, this Colombian canine cohort performed with a remarkable 95.5% sensitivity and 99.6% specificity.

During the various blind, controlled experiments, the total time for detection was a matter of minutes or less. Such speed is a huge asset in real world scenarios. In particular, a U.K.-based research group(link is external) has outlined their plans to train and ultimately deploy dogs at United Kingdom airports and ports of entry as part of the COVID-19 screening process.

With all the sniffing going on in the presence of an airborne disease, it's natural to be concerned over whether dogs can catch and transmit COVID-19. It's still the topic of ongoing research, but evidence points to a low likelihood of transmission, according to the paper, though precautionary measures should be taken to protect everyone involved.

"Current research supports the use of scent detection dogs for pilot COVID-19 screening studies involving humans in venues such as airports and sporting events," Dickey said. "In addition, the JOM paper points out that another line of research can utilize medical scent detection dogs involving the development of medical electronic noses."

In principle, you wouldn't even need a dog to sniff out COVID if you could mimic the way it smells and processes scents, according to the researchers. Through sensors and artificial intelligence, they said, it might be possible to someday match a dog's performance using wearable electronic noses, similar to wristband sensors for reporting heart beat rate and patterns, blood pressure and oxygen, that could monitor a person's sweat for metabolites and biomarkers that could indicate diseases such as COVID-19.

DURHAM, N.C. - People who have a gene variant associated with an increased risk of developing Alzheimer's disease also tend to have changes in the fluid around their brain and spinal cord that are detectable years before symptoms arise, according to new research from Duke Health.

The work found that in people who carry the APOE4 gene variant, which is found in roughly 25 percent of the population, the cerebrospinal fluid contains lower levels of certain inflammatory molecules. This raises the possibility that these inflammatory molecules may be collecting in the brain where they may be damaging synapses, rather than floating freely in the cerebrospinal fluid.

The findings, which were published online last month in the Journal of Alzheimer's Disease, provide a potential means to identify the earliest mechanisms occurring among APOE4 carriers that might contribute to Alzheimer's disease before people develop memory problems or other symptoms of dementia.

"Our work suggests a potential role for a long-studied molecule called C-reactive protein (CRP), which is typically elevated when there's inflammation, as a factor in the increased Alzheimer's disease risk seen in APOE4 carriers," said lead author Miles Berger, M.D., Ph.D., associate professor in Duke's Department of Anesthesiology.

Berger and colleagues analyzed data from targeted cerebrospinal fluid of Alzheimer's Disease Neuroimaging Institute research participants. Controlling for Alzheimer's disease clinical status, they identified protein level variations in the cerebrospinal fluid from people with an increasing number of APOE4 gene variant copies. They found that people with more APOE4 copies had lower CRP levels circulating in their cerebrospinal fluid.

Berger said this is consistent with the current risk profile associated with APOE4 carriers. People with a single APOE4 variant have about a three- to four-fold increased risk of developing Alzheimer's disease, while those who carry two APOE4 variants have a greater than 10-fold risk.

"We found that spinal fluid CRP levels are lower in people with the APOE4 allele, before they ever develop dementia or even mild cognitive impairment," Berger said. "This suggests that CRP might be actively involved in damaging synapses. We think CRP is doing this together with a cascade of inflammatory proteins called complement, which sequentially activate each other like a row of dominos falling.

"Altered complement activity has also been found at autopsy in the brains of patients who suffered from Alzheimer's disease, and the complement pathway can both damage synapses and target them for destruction," Berger said. "Our results raise the possibility that processes like these operating over many years and even decades in APOE4 carriers could eventually result in Alzheimer's disease pathology and cognitive decline."

Berger said there are other inflammatory diseases for which CRP can be decreased rather than elevated, notably lupus. He said therapies used to control CRP for conditions such as rheumatoid arthritis and vasculitis might warrant investigation for Alzheimer's disease, but additional studies are needed to further illuminate the Duke team's findings.

"Maybe those with more APOE4 variants have excessive deletion of synapses throughout life, until it gets to point where brain can't process information anymore," Berger said. "It would be like taking a book and randomly deleting every 1000th letter. For a while, you could do that and the book would still make sense. But after time, too many letters would be gone and you would lose the information in the book. We think that might be what's happening in the brain."

New research from the Indiana University Kelley School of Business shows first evidence that watching and learning from others can help reduce bias and improve decision-making.

The research, published in the journal Organizational Behavior and Human Decision Processes, used a computer game designed to decrease bias to see if people who watched others play the game could in turn reduce their own bias. Through three experiments, researchers found that watching others solve bias-related problems helped the observers learn about decision biases and improve on their own. Their study showed this observational learning reduced decision biases such as anchoring - or, relying too much on an original bit of information -- and also improved how the observers take advice.

"Everyone has biases when it comes to making decisions," said study co-author Haewon Yoon, assistant professor of marketing at the Indiana University Kelley School of Business on the IUPUI campus. "We've found these biases can be mitigated by watching others and observing how they make decisions. For example, as people observe others playing these interactive games, they're able to see inside the game player's decision process and learn from their mistakes. Likewise, in a business setting, a training module or video showing employees how managers or co-workers demonstrate decision biases -- or avoid such biases -- could reduce that employee's own decision biases. This is a more cost-effective way to teach employees than through extensive training with individualized feedback."

"From childhood on, we learn by watching others like our parents, siblings, and friends: 'What is safe to eat? How do I do that? How should we behave in social contexts?'" said Carey Morewedge, professor of marketing at Boston University Questrom School of Business and co-author of the study. "This kind of observational learning teaches us important lessons about the world around us. Unfortunately, it also leads us to absorb many of the biases we observe and exhibit those biased behaviors ourselves. This new research shows that we can learn to improve our decision-making and unlearn some of our biases by watching others. We glean unique insights from seeing others solve problems that help us make better and less biased decisions."

The researchers explain there is value in reducing decision bias in both personal and professional domains - Take, for example, buying a house. Research has shown that whatever price the seller puts it up for sale at - No matter how much - buyers tend to adjust based on that price. These researchers argue that if you watch someone else committing or correcting the bias, you could take away insights that help you better make those decisions. For hiring managers, this could be used while onboarding employees - or interviewing employees. Asking others to watch and learn helps reduce bias.

"Social learning interventions like observational learning are not only promising in their effectiveness; they are relatively inexpensive to implement and scalable," said Irene Scopelliti, professor at the Business School (formerly Cass) and co-author of the study. "The findings could benefit all kinds of cases where people have to make decisions under uncertainty (i.e., without all the facts), from which gift to buy a friend to major business, law and policy decisions. We hope this strategy for debiasing decision making is added to the many training interventions used by teachers, government officials and industry leaders to help people make better decisions."

Irvine, CA - February 11, 2021 - Subconsciously, our bodies keep time for us through an ancient means - the circadian clock. A new University of California, Irvine-led article reviews how the clock controls various aspects of homeostasis, and how organs coordinate their function over the course of a day.

"What is fascinating is that nearly every cell that makes up our organs has its own clock, and thus timing is a crucial aspect of biology," said Kevin B. Koronowski, PhD, lead author and a postdoctoral fellow in Biological Chemistry at the UCI School of Medicine. "Understanding how daily timing is integrated with function across organs has implications for human health, as disruption of the clock and circadian rhythms can be both a cause and effect of diseases from diabetes to cancer."

The circadian clock generates a ~24 hour rhythm that controls behavior, hormones, the immune system and metabolism. Using human cells and mice, researchers from the Paolo Sassone-Corsi Laboratory at UCI's Center for Epigenetics and Metabolism aim to uncover the physiological circuits, for example between the brain and liver, whereby biological clocks achieve coherence. Their work, titled, "Communicating clocks shape circadian homeostasis," was published today in Science.

Circadian clocks align internal processes with external time, which enables diverse lifeforms to anticipate daily environmental changes such as the light-dark cycle. In complex organisms, clock function starts with the genetically encoded molecular clock or oscillator within each cell and builds upward anatomically into an organism-wide system. Circadian misalignment, often imposed in modern society, can disrupt this system and induce adverse effects on health if prolonged.

"Strategies to tune our clocks and boost rhythms have been promising in pre-clinical studies, which illustrates the importance of unraveling this aspect of our biology and unlocking the potential it holds for treatments and medicines of the future," said Koronowski.

Without electrical light, high-speed travel, constant food availability and around the clock work-life schedules, our ancestors' clocks were in constant harmony with the environment. However, due to these pressures of modern society, aligning our internal time with geophysical time has become a challenge in today's world. Chronic misalignment - when eating and sleeping patterns conflict with the natural light-dark cycle - is associated with an increased risk of metabolic syndrome, cardiovascular disease, neurological conditions, and cancer. A large portion of the global workforce has atypical hours and may be particularly vulnerable.

"It has become urgent that we uncover the molecular underpinnings of the relationship between the circadian clock and disease," explained Koronowski. "Deciphering the means by which clocks communicate across metabolic organs has the potential to transform our understanding of metabolism, and it may hold therapeutic promise for innovative, noninvasive strategies to promote health."

The needs of millions of overlooked, 'left behind' adolescent women must become a more significant priority within international efforts to end poverty by 2030, a UK Government-commissioned report is urging.

The University of Cambridge report, which was commissioned by the Foreign, Commonwealth and Development Office, argues that there is an urgent need to do more to support marginalised, adolescent women in low and middle-income countries; many of whom leave education early and then face an ongoing struggle to build secure livelihoods.

Amid extensive evidence which highlights the difficulties these women face, it estimates that almost a third of adolescent women in many such countries are not in education, training, or work.

'Adolescents' (technically people aged 10 to 19) comprise about one sixth of the world's population. Women in this age group are some of the most vulnerable people in the world. The report argues that unless more is done to support them, it is unlikely that the UN's 2030 Sustainable Development Goals - which include ending poverty, ensuring inclusive education, and empowering women and girls - will be met.

In particular, the document highlights the need for more concerted efforts to be made to prevent gender discrimination in labour markets, strengthen social safety nets for women, and provide both formal education and continued training for the huge numbers of adolescent women who, it says, 'have missed out on acquiring relevant skills to enhance their livelihood opportunities.'

Professor Pauline Rose, Director of the Research for Equitable Access and Learning (REAL) Centre at the Faculty of Education, University of Cambridge, said: "Marginalised adolescent girls are those who experience extreme poverty, live in rural areas, have disabilities, are affected by conflict, or belong to disadvantaged groups. We need to prioritise these young women both in education and as they transition into work. Millions are being left behind by a range of interlocking problems, and strong, sustained political leadership is needed to turn that around."

The Government has identified girls' education as a key focus of the UK's presidency of the G7 group of industrial countries this year, and gender equality will be mainstreamed across the different ministerial tracks. The new report raises gender inequality - both in education and employment - as major areas of concern for the international community.

The report further stresses that adolescence is a make-or-break time for many girls in low- and lower-middle-income countries and should therefore be a focal point of international efforts. During this period, many young women leave education early, either to work, or because they are expected to marry and start a family. Often, they do so without having acquired basic literacy or numeracy. In addition, very few have the transferable skills or training that they need to succeed in the world of work.

The document draws on more than 150 sources to evidence both the scale of the problem and the nature of the barriers that marginalised adolescent girls face. For many, a quality education remains a far-off dream. In sub-Saharan Africa, for example, fewer than one in 10 girls from poor households in rural areas complete lower secondary education.

Many also struggle to find secure employment. Data from 30 low- and middle-income countries suggests that 31% of young women are not in education, employment or training, compared with 16% of boys. Those who do find jobs frequently work for low wages, in unsafe settings and without any sort of social safety net.

One of the main reasons for this, the report says, is a lack of access to appropriate skills development and training. For example, one in three unemployed adolescent girls in the Asia-Pacific region, and one in five in sub-Saharan Africa, report that the entry requirements for their preferred career path exceed their education and training.

Compounding these problems, gender discrimination in both labour markets and wider society is an accepted norm in many countries. Among many other examples, this manifests itself in inheritance laws which transfer land and property to sons but not daughters; the tendency to force girls who struggle to find work into early marriage and childbearing; and widespread gender-related violence. One study in Nigeria, cited in the report, found that two-thirds of young female apprentices had experienced physical violence - and 39% said that their employer was the most recent perpetrator.

While the research also identifies many successful individual programmes around the world that address some of these issues, it stresses the need for policy-makers internationally to prioritise adolescent girls in larger-scale, systemic reforms.

It makes numerous recommendations about how that can be done, including:

Implementing measures and laws that challenge gender discrimination in education, labour markets and wider society.

Curriculum reforms to develop women's transferrable skills in school, supported by skills development programmes outside the education system.

Catch-up programmes for those who have missed out on a basic education.

Strengthening social safety nets, which have been shown to benefit women in particular.

Providing sexual and reproductive health services and information for all adolescent girls.

Providing counselling and rehabilitation services that offer practical support to adolescent girls who have been forced into unsafe work settings.

The report highlights the particular role that female political leaders and parliamentarians can play in driving forward a more integrated agenda for marginalised young women, and in challenging patriarchal norms that hold back gender equality.

It also warns that many of the trends documented are currently at risk of becoming worse as a result of COVID-19. "The best way that Governments can signal their commitment to this problem is by putting women and girls at the forefront of COVID-19 recovery efforts and ambitions to build back better," Rose said. "It is vital that this includes a strong focus on adolescent girls."

Oncotarget published "Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer" which reported that HNSCC is frequently associated with either amplification or mutational changes in the PI3K pathway, making PI3K an attractive target, particularly in cetuximab-resistant tumors.

Here, the authors explored the antitumor activity of the selective, pan-class I PI3K inhibitor copanlisib with predominant activity towards PI3Kα and δ in monotherapy and in combination with cetuximab using a mouse clinical trial set-up with 33 patient-derived xenograft models with known HPV and PI3K mutational status and available data on cetuximab sensitivity.

Combination treatment with copanlisib and cetuximab was superior to either of the monotherapies alone in the majority of the models, and the effect was particularly pronounced in cetuximab-resistant tumors.

While no correlation was observed between PI3K mutation status and response to either cetuximab or copanlisib, increased PI3K signaling activity evaluated through gene expression profiling showed a positive correlation with response to copanlisib.

Together, these data support further investigation of PI3K inhibition in HNSCC and suggests gene expression patterns associated with PI3K signaling as a potential biomarker for predicting treatment responses.

Dr. Konrad Klinghammer from The Charité - Universitätsmedizin Berlin said, "Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common type of cancer with 0.65 million new cases and 0.33 million deaths annually worldwide."

Upregulated PI3K/AKT/mTOR signaling has also been shown to increase resistance to radiotherapy and cytostatic drugs, and PI3K has been defined as an alternate signaling pathway in cetuximab-resistant HNSCC.

Accordingly, based on the cancer genome atlas data, up to 56% of HNSCC display either amplification or mutational changes in the PI3K pathway, and according to the head and neck cancer tissue array data, the PI3K/AKT/mTOR pathway is upregulated in over 90% in both HPV-positive and negative HNSCCs.

Upregulated PI3K/AKT/mTOR signaling, the occurrence of mutational changes in the PI3K pathway, and emerging clinical data from trials with PI3K inhibitors make PI3K an attractive target for cancer therapy, particularly in patients with recurrent/metastatic HNSCC.

Copanlisib is a highly selective, pan-class I PI3K inhibitor with preferential activity against the p110α and p110Δ isoforms that lead to the downregulation of PI3K signaling.

To this end, a panel of altogether 33 HPV-positive or negative HNSCC PDX models were selected based on PI3KCA mutation status and cetuximab sensitivity to evaluate the efficacy of copanlisib given as monotherapy and in combination with cetuximab, and furthermore, the capacity of copanlisib to overcome resistance to cetuximab.

The Klinghammer Research Team concluded in their Oncotarget Research Paper "we demonstrated an improved tumor control by combining copanlisib with cetuximab using 33 patient-derived xenograft models and thereby establishing a preclinical rationale for the evaluation of this combination therapy in a clinical setting. A phase Ib/II study of copanlisib in combination with cetuximab in HNSCC patients harboring a PI3KCA mutation/amplification and/or a PTEN loss is currently ongoing."

Scientists and public health experts have long known that certain individuals, termed "super-spreaders," can transmit COVID-19 with incredible efficiency and devastating consequences.

Now, researchers at Tulane University, Harvard University, MIT and Massachusetts General Hospital have learned that obesity, age and COVID-19 infection correlate with a propensity to breathe out more respiratory droplets -- key spreaders of SARS-CoV-2, the virus that causes COVID-19. Their findings were published in Proceedings of the National Academy of Sciences.

Using data from an observational study of 194 healthy people and an experimental study of nonhuman primates with COVID-19, researchers found that exhaled aerosol particles vary greatly between subjects. Those who were older with higher body mass indexes (BMI) and an increasing degree of COVID-19 infection had three times the number of exhaled respiratory droplets as others in the study groups.

Researchers found that 18% of the human subjects accounted for 80% of the exhaled particles of the group, reflecting a distribution of exhaled aerosol particles that follows the 20/80 rule seen in other infectious disease epidemics - meaning 20% of infected individuals are responsible for 80% of transmissions.

Aerosol droplets in nonhuman primates increased as infection with COVID-19 progressed, reaching peak levels a week after infection before falling to normal after two weeks. Notably, as infection with COVID-19 progressed, viral particles got smaller, reaching the size of a single micron at the peak of infection. Tiny particles are more likely to be expelled as people breathe, talk or cough. They can also stay afloat much longer, travel farther in the air and penetrate deeper into the lungs when inhaled.

The increase in exhaled aerosols occurred even among those with asymptomatic cases of COVID-19, said Chad Roy, PhD, corresponding author and director of infectious disease aerobiology at the Tulane National Primate Research Center.

"We've seen a similar increase in droplets during the acute infection stage with other infectious diseases like tuberculosis," Roy said. "It seems likely that viral and bacterial infections of the airway can weaken airway mucus, which promotes the movement of infectious particles into this environment."

The generation of respiratory drops in the airways varies between people depending on their body composition, said lead author David Edwards, PhD, professor of the practice of biomedical engineering at Harvard University.

"While our results show that the young and healthy tend to generate far fewer droplets than the older and less healthy, they also show that any of us, when infected by COVID-19, may be at risk of producing a large number of respiratory droplets," Edwards said.

Human language can be inefficient. Some words are vital. Others, expendable.

Reread the first sentence of this story. Just two words, "language" and "inefficient," convey almost the entire meaning of the sentence. The importance of key words underlies a popular new tool for natural language processing (NLP) by computers: the attention mechanism. When coded into a broader NLP algorithm, the attention mechanism homes in on key words rather than treating every word with equal importance. That yields better results in NLP tasks like detecting positive or negative sentiment or predicting which words should come next in a sentence.

The attention mechanism's accuracy often comes at the expense of speed and computing power, however. It runs slowly on general-purpose processors like you might find in consumer-grade computers. So, MIT researchers have designed a combined software-hardware system, dubbed SpAtten, specialized to run the attention mechanism. SpAtten enables more streamlined NLP with less computing power.

"Our system is similar to how the human brain processes language," says Hanrui Wang. "We read very fast and just focus on key words. That's the idea with SpAtten."

The research will be presented this month at the IEEE International Symposium on High-Performance Computer Architecture. Wang is the paper's lead author and a PhD student in the Department of Electrical Engineering and Computer Science. Co-authors include Zhekai Zhang and their advisor, Assistant Professor Song Han.

Since its introduction in 2015, the attention mechanism has been a boon for NLP. It's built into state-of-the-art NLP models like Google's BERT and OpenAI's GPT-3. The attention mechanism's key innovation is selectivity -- it can infer which words or phrases in a sentence are most important, based on comparisons with word patterns the algorithm has previously encountered in a training phase. Despite the attention mechanism's rapid adoption into NLP models, it's not without cost.

NLP models require a hefty load of computer power, thanks in part to the high memory demands of the attention mechanism. "This part is actually the bottleneck for NLP models," says Wang. One challenge he points to is the lack of specialized hardware to run NLP models with the attention mechanism. General-purpose processors, like CPUs and GPUs, have trouble with the attention mechanism's complicated sequence of data movement and arithmetic. And the problem will get worse as NLP models grow more complex, especially for long sentences. "We need algorithmic optimizations and dedicated hardware to process the ever-increasing computational demand," says Wang.

The researchers developed a system called SpAtten to run the attention mechanism more efficiently. Their design encompasses both specialized software and hardware. One key software advance is SpAtten's use of "cascade pruning," or eliminating unnecessary data from the calculations. Once the attention mechanism helps pick a sentence's key words (called tokens), SpAtten prunes away unimportant tokens and eliminates the corresponding computations and data movements. The attention mechanism also includes multiple computation branches (called heads). Similar to tokens, the unimportant heads are identified and pruned away. Once dispatched, the extraneous tokens and heads don't factor into the algorithm's downstream calculations, reducing both computational load and memory access.

To further trim memory use, the researchers also developed a technique called "progressive quantization." The method allows the algorithm to wield data in smaller bitwidth chunks and fetch as few as possible from memory. Lower data precision, corresponding to smaller bitwidth, is used for simple sentences, and higher precision is used for complicated ones. Intuitively it's like fetching the phrase "cmptr progm" as the low-precision version of "computer program."

Alongside these software advances, the researchers also developed a hardware architecture specialized to run SpAtten and the attention mechanism while minimizing memory access. Their architecture design employs a high degree of "parallelism," meaning multiple operations are processed simultaneously on multiple processing elements, which is useful because the attention mechanism analyzes every word of a sentence at once. The design enables SpAtten to rank the importance of tokens and heads (for potential pruning) in a small number of computer clock cycles. Overall, the software and hardware components of SpAtten combine to eliminate unnecessary or inefficient data manipulation, focusing only on the tasks needed to complete the user's goal.

The philosophy behind the system is captured in its name. SpAtten is a portmanteau of "sparse attention," and the researchers note in the paper that SpAtten is "homophonic with 'spartan,' meaning simple and frugal." Wang says, "that's just like our technique here: making the sentence more concise." That concision was borne out in testing.

The researchers coded a simulation of SpAtten's hardware design -- they haven't fabricated a physical chip yet -- and tested it against competing general-purposes processors. SpAtten ran more than 100 times faster than the next best competitor (a TITAN Xp GPU). Further, SpAtten was more than 1,000 times more energy efficient than competitors, indicating that SpAtten could help trim NLP's substantial electricity demands.

The researchers also integrated SpAtten into their previous work, to help validate their philosophy that hardware and software are best designed in tandem. They built a specialized NLP model architecture for SpAtten, using their Hardware-Aware Transformer (HAT) framework, and achieved a roughly two times speedup over a more general model.

The researchers think SpAtten could be useful to companies that employ NLP models for the majority of their artificial intelligence workloads. "Our vision for the future is that new algorithms and hardware that remove the redundancy in languages will reduce cost and save on the power budget for data center NLP workloads" says Wang.

On the opposite end of the spectrum, SpAtten could bring NLP to smaller, personal devices. "We can improve the battery life for mobile phone or IoT devices," says Wang, referring to internet-connected "things" -- televisions, smart speakers, and the like. "That's especially important because in the future, numerous IoT devices will interact with humans by voice and natural language, so NLP will be the first application we want to employ."

Han says SpAtten's focus on efficiency and redundancy removal is the way forward in NLP research. "Human brains are sparsely activated [by key words]. NLP models that are sparsely activated will be promising in the future," he says. "Not all words are equal -- pay attention only to the important ones."