Culture

New Rochelle, NY, June 24, 2020--Bacteriophage can reduce bacterial growth in the lungs, limiting fluid build-up. This could decrease the mortality of patients affected by COVID-19, according to the peer-reviewed journal PHAGE: Therapy, Applications, and Research. Click here to read the article.

"The bacterial growth rate could potentially be reduced by the aerosol application of natural bacteriophages. These prey on the main species of bacteria known to cause respiratory failure," says Marcin Wojewodzic, PhD, University of Birmingham (U.K.).

Decreasing bacterial growth would also give the body more time to produce protective antibodies against the disease-causing coronavirus.

"Used correctly, phages have an advantage here of being able to very specifically target the bacteria that cause secondary infections," said Martha Clokie, PhD, Editor-in-Chief of PHAGE and Professor of Microbiology, University of Leicester (U.K.). "They would remove the problematic bacterium but leave an otherwise fragile microbiome intact."

Levitation has long been a staple of magic tricks and movies. But in the lab, it's no trick. Scientists can levitate droplets of liquid, though mixing them and observing the reactions has been challenging. The pay-off, however, could be big as it would allow researchers to conduct contact-free experiments without containers or handling that might affect the outcome. Now, a team reporting in ACS' Analytical Chemistry has developed a method to do just that. 

Scientists have made devices to levitate small objects, but most methods require the object to have certain physical properties, such as electric charge or magnetism. In contrast, acoustic levitation, which uses sound waves to suspend an object in a gas, doesn't rely on such properties. Yet existing devices for acoustic levitation and mixing of single particles or droplets are complex, and it is difficult to obtain measurements from them as a chemical reaction is happening. Stephen Brotton and Ralf Kaiser wanted to develop a versatile technique for the contactless control of two chemically distinct droplets, with a set of probes to follow the reaction as the droplets merge.

The team made an acoustic levitator and suspended two droplets in it, one above the other. Then, they made the upper droplet oscillate by varying the amplitude of the sound wave. The oscillating upper droplet merged with the lower droplet, and the resulting chemical reaction was monitored with infrared, Raman and ultraviolet-visible spectroscopies. The researchers tested the technique by combining different droplets. In one experiment, for example, they merged an ionic liquid with nitric acid, causing a tiny explosion. The new levitation method could help scientists study many different types of chemical reactions in areas such as material sciences, medicinal chemistry and planetary science, the researchers say.

Bristol innovation challenges regular touchscreens with new spray-on technique

A team at Bristol has challenged the idea that touchscreens are limited to 2D and rectangular shapes by developing an interactive display that can be sprayed in any shape.

Inspired by the way an artist creates graffiti on a wall and using a novel combination of sprayable electronics and 3D printing, the technique, called ProtoSpray, allows the creation of displays on surfaces that go beyond the usual rectangular and 2D shapes.

"We have liberated displays from their 2D rectangular casings by developing a process so people can build interactive objects of any shape. The process is very accessible: it allows end-users to create objects with conductive plastic and electroluminescent paint even if they don't have expertise in these materials," said Ollie Hanton, PhD student and lead author of the research.

Mr Hanton's paper on the innovation was presented and received an honourable mention at the ACM Conference on Human Factors in Computing Systems (CHI) - generally considered the most prestigious academic conference in the field of human-computer interaction.

The aim of the EPSRC-funded research was to broaden the scope of how people can interact with digital technologies.

The ProtoSpray process, developed in collaboration with the MIT media lab, opens up potential for makers, hobbyists and researchers to develop interactive objects of different (arbitrary) shapes.

"3D printers have enabled personal fabrication of objects but our work takes this even further to where we print not only plastic but also other materials that are essential for creating displays. Using 3D printing of plastics and spraying of materials that light up when electricity is applied, we can support makers to produce objects of all shapes that can display information and detect touch.

"Our vision is to make screen/display a fundamental expressive medium in the same way people currently use ink, paint, or clay," said Mr Hanton.

Dr Anne Roudaut, Associate Professor in Human-Computer Interaction at the University of Bristol, who supervised the research, said the next step would be to create a machine that can both 3D print and spray automatically onto the 3D printed objects.

A summer internship in Bilbao, Spain, has led to a paper in the journal Physical Review Letters for Jack Mayo, a Master's student at the University of Groningen, the Netherlands. He has helped to create a universal model that can predict the number distribution of topological defects in non-equilibrium systems. The results can be applied to quantum computing and to studies into the origin of structure in the early Universe.

Mayo, student of the Top Master Programme in Nanoscience at the Zernike Institute for Advanced Materials at the University of Groningen, spent his 2019 summer holidays on the Basque coast immersed in theoretical physics. The project in which he participated took place in the research group led by Professor Adolfo del Campo at the Donostia International Physics Center (DIPC), and was aimed at solving a problem in quantum computing - but it has much wider implications, from nanoscale magnets to the cosmos. In all these systems, the onset of order (for example, order induced by cooling) is almost always accompanied by the development of defects. 'Take a system in which particles have a magnetic moment that can flip between up and down,' Mayo explains. 'If you increase their attractive interaction, they will start to align with each other.'

Ice crystals

This alignment will begin at certain uncorrelated points in a medium and then grow - like ice crystals in water. The alignment of each domain (up or down in the example of the magnetic moments) is a matter of chance. 'Local alignments will grow outwards and at a certain stage, domains will begin to meet and interact,' says Mayo. For example, if an up-domain meets a down-domain, the result will be a domain wall at their interface - a symmetry-breaking defect in the ordered structure, leaving behind an artifact of the material in its higher-symmetry phase.

This annealing of a medium is described by the Kibble-Zurek mechanism, originally designed to explain how a phase transition resulted in ordered structures in the early Universe. It was subsequently discovered that it could be used to describe the transition of liquid helium from a fluid to a superfluid phase. 'The mechanism is universal and is also used in quantum computing based on quantum annealing,' explains Mayo. This technology is already on the market and is capable of solving complex puzzles such as the travelling salesman problem. However, a problem with this type of work is that defects that occur during the annealing process will distort the results.

Phase transitions

The number of defects that show up in quantum annealing depends on the time taken to pass the phase transition. 'If you have millions of years to slowly change the interactions between units, you do not get defects, but that is not very practical,' Mayo remarks. The trick is in designing finite-time - and therefore more practical - schedules to obtain an acceptable number of defects with high probability. The research project in which he participated was aimed at creating a model that could estimate the number of defects and guide the optimum design of these systems.

Statistical model

To do this, the physicists used theoretical tools to describe phase transitions and numerical simulations to estimate the defect distribution during cooling. As each domain can have one of two values (up or down in the example of the magnetic moments), they could estimate the chances of two opposite domains meeting and creating a defect. This led to a statistical model based on binomial distribution, which could be used to predict how a system should be cooled to create the smallest number of defects. The model was verified against independent numerical simulations and appeared to work well. This new model was described in a paper that was published on 17 June in Physical Review Letters and was accompanied by a 'Viewpoint' published in Physics, a comment on the results by the independent physicist Professor Smitha Vishveshwara from the University of Illinois at Urbana-Champaign.

A new study of childhood epilepsy has identified the world's first environmental risk factor for the disease - maternal smoking in pregnancy, and discovered a new genetic association with the condition, pointing to potential new treatments for the disease.

The research was led by an international team of clinicians and scientists including Professor Matt Brown, Professor of Medicine at King's College London and Director of the National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas'.

The study focussed on one of the most common forms of childhood epilepsy, Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS). Around 1% of children globally suffer with epilepsy with around 15% of those affected by BECTS. Driven by tendency for BECTS to run in families, previous research efforts focussed on identifying potential rare genetic mutations associated with the disease, but offered no robust evidence for the genetic association for the condition.

Unlike previous studies, the study team used genome wide complex trait analysis to examine and explain the most common type of genetic variations in people with BECTS.

This enabled the team to demonstrate that BECTS does indeed have a significant common genetic component, for the first time demonstrating that the reason that BECTS runs in families is because of genetic variants carried by patients. The study identified an association with a gene called CHRNA5 being involved in BECTS risk.

It is commonly known that genetic variations within the CHRNA5 and related genes are associated with nicotine dependence and smoking associated lung disease. This along with suggestive evidence that smoking increases the risk of epilepsy overall led the team to perform analysis between risk factors and disease using summary-level data from independent genome-wide association studies from the UK Biobank. The analysis demonstrated that maternal smoking during pregnancy quadrupled the risk of BECTS. This is the first ever environmental risk factor identified for the disease.

Commenting on the findings Professor Matt Brown from King's College London said: "The new evidence in our study showing that common genetic variants play an important role in BECTS susceptibility opens up immense research possibilities to better understand how epilepsy is caused.

Maternal smoking in pregnancy being identified as the first ever environmental risk factor described in the development of BECTS offers a very clear message to clinicians and mothers about what can and should be done to limit the risk of children developing this common form of epilepsy."

He added: "With the association of the CHRNA5 gene which encodes a cholinergic receptor expressed in the brain involved in BECTS risk, our research also suggests that a class of drugs called 'anticholinergics' may be effective in the treatment of BECTS, however, further research into this is needed."

Invasive fire ants common in the Gulf Coast and Texas likely are limiting a tick-acquired meat allergy in these areas, scientists report.
The ants are moving northward and could reduce the prevalence of the red meat allergy in some Southern states. However, fire ant bites are also a cause of severe allergic reactions.
The new UVA research maps the extent of the red meat allergy in the United States.
The findings further implicate the lone star tick as the cause of the meat allergy and hint that the tick may be increasing in some Northern states.

Invasive fire ants with a nasty bite are limiting the spread of a dangerous meat allergy, new research suggests. But it’s not all good news, as the ants themselves can also cause severe allergic reactions.

School of Medicine researchers and their collaborators made the discovery while seeking to understand the scope of the “alpha-gal” meat allergy in the United States. Spread by the bite of the lone star tick, the allergy causes people to develop potentially severe allergic reactions to mammalian meat, including beef and pork.

The allergy is commonly seen throughout the Southeast, the Mid-Atlantic and the Midwest, but rarely in the Gulf Coast and Texas. That is likely caused by the steady expansion of fire ants accidentally imported from South America in the 1930s, the researchers conclude.

But the ants are no heroes, as their bites can be very painful and cause severe allergic reactions. In some cases, the bites can cause life-threatening anaphylaxis. That’s in addition to the dangers the ants pose to animals and crops. And the strong-jawed insects are marching relentlessly northward.

“We did not set out to study fire ants, but when the number of alpha-gal cases in the Gulf Coast was consistently lower than we expected, the fire ant emerged as an interesting explanation,” said UVA researcher Behnam Keshavarz, PhD, a co-first author of a new scientific paper outlining the discovery.

Mapping the Meat Allergy

The meat allergy was first identified more than a decade ago by UVA’s Thomas Platts-Mills, MD, PhD, an internationally renowned allergist. Since then, he and his colleagues have shed light on how and why the tick’s bite causes people to develop allergic reactions to a particular sugar, alpha-gal, present in meat and other mammalian products. The symptoms can include itchy rashes, nausea and difficulty breathing. Severe reactions can progress to anaphylaxis if untreated.

Until now, there has been little examination of the geographic scope of the allergy in the United States. The UVA researchers set out to change that. They surveyed allergists across the country to map out cases of the meat allergy. They also tested blood samples from two different geographic areas where it was particularly prevalent. The latter was important to show that the allergy is “immunologically similar” across the country.

The researchers found the meat allergy was common in significant portions of at least 14 states. Eleven states had at least one allergist report more than 100 case in their practice: Alabama, Arkansas, Georgia, Kentucky, Maryland, Missouri, New York, North Carolina, Oklahoma, Tennessee and Virginia.

In contrast, six of 10 allergy practices in Eastern Texas – the domain of the invasive fire ant – reported no cases of the meat allergy at all.

Weirdness in Minnesota

Oddly, there were an unexpectedly high number of cases in an area of Minnesota where the lone star tick is not thought common. Three separate providers in the northern portion of the state reported at least five cases of the meat allergy, with one reporting more than 40.

That, the UVA researchers note, may suggest there are more lone star ticks in the area than thought – or perhaps that another tick or even other parasite is spreading the meat allergy. Other species of ticks are known to cause the allergy outside North America.

“The best evidence is that lone stars are the dominant cause of the alpha-gal meat allergy in North America,” said co-first author Jeffrey Wilson, MD, PhD. “That said, we wouldn’t be surprised if other ticks, chiggers or even other kinds of parasitic organisms can occasionally contribute to allergic sensitization to alpha-gal.”

Fire Ants Marching

After collecting reports of the meat allergy from 44 states the researchers were surprised to see few cases in the Gulf Coast or Texas. This was unexpected because the lone star tick is usually reported on CDC maps in the area. After considering potential explanations, the researchers again surveyed many of the same allergists about allergic reactions caused by the fire ant. They overlaid their results, and the results showed a striking, inverse relationship: Areas with the most fire ant cases had the lowest presence of the meat allergy.

That suggests that the fire ants are either preying on or somehow competing with the ticks, limiting the spread of the meat allergy, the researchers say. They also identified an increasing number of allergy cases caused by the fire ants. This likely will continue as the fire ants spread north, they report.

The spread should help control the number of meat allergy cases in the Southeast and Mid-Atlantic, they predict. But it also likely will lead to an increase in allergic reactions caused by the fire ant.

“These are two arthropod-related allergic diseases that are connected with each other,” Platts-Mills concludes. “The situation is unique because we think we can predict how both will change over time.”

Read a patient’s experiences with the meat allergy.

Meat Allergy Findings

The researchers have published their findings in the Journal of Allergy and Clinical Immunology. The research team consisted of Wilson, Keshavarz, Maya Retterer, Lisa J. Workman, Alexander J. Schuyler, Emily C. McGowan, Charles Lane, Alaaddin Kandeel, Jane Purser, Eva Ronmark, Joseph LaRussa, Scott P. Commins, Tina Merritt and Platts-Mills. Platts-Mills and Merritt have a patent on a test for the meat allergy, while Wilson has received funding from Thermo Fisher/Phadia. A full list of disclosures is included in the paper.

The research was supported by the National Institutes of Health, grant R37 AI-20565.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Journal

Journal of Allergy and Clinical Immunology

DOI

10.1016/j.jaci.2020.05.034

As technology shrinks, the need to characterize the properties of very small materials?measured in nanometers (1 nanometer = 1 billionth of a meter)?has become increasingly important. Nanomaterials that measure from 1 and 20 nanometers show promise for use in next-generation electronic devices, solar cells, laser technology, and chemical and biosensors, to name a few. For scale, the width of a human hair is 75,000 nanometers.

To understand the surface potential of nanomaterials, the most commonly used nanoscience tool is the Kelvin Probe Force Microscopy (KPFM), which is an atomic force microscopy (AFM) based technique that measures work function and surface potential. Unfortunately, KPFM has its limitations due to its use of AC voltage to charge the AFM probe.

"Every KPFM technique operates on the same measurement paradigm: AC voltage is used to completely charge an AFM probe, thus producing a detectable electrostatic force for image acquisition," explains Xiaoji Xu, assistant professor in Lehigh University's Department of Chemistry. "Overloading the probe with charges forces a limit on the spatial resolution, since the charges are not limited to the apex of the AFM probe. Instead, excess charges occupy the entire cantilever and contribute to the signal."

Now, Xu and his graduate student Devon S. Jakob have introduced an entirely new measurement paradigm based on the alignment on Fermi levels. While traditional KPFM methods produce images with a spatial resolution of 30 to 100 nanometers, the new Xu Research Group method, called Pulsed Force Kelvin Probe Force Microscopy (PF-KPFM), allows for less than 10 nanometer measurements of work function and surface potential in a single-pass AFM scan. Their findings have been published in an article in ACS Nano: "Pulsed Force Kelvin Probe Force Microscopy." (Authors: Xiaoji Xu and graduate students Devon S. Jakob and Haomin Wang)

"In Pulsed Force Kelvin Probe Force Microscopy, we removed the need for the AC voltage by implementing a custom circuit of a field effect transistor between the tip and the sample which acts as a binary switch," says Xu. "When the switch is on, the circuit acts as a simple wire, allowing charges to pass between tip and sample. A small amount of charges spontaneously migrates between tip and sample based on the relative difference in their intrinsic Fermi levels. When the switch is off, the circuit does not allow for charges to pass, and acts as a capacitor to re-absorb the charges from the tip and sample region."

The PF-KPFM also exclusively operates in the pulsed force mode, according to Xu. By using the pulsed force mode, he says, PF-KPFM measurements can be accurately obtained at very small tip-sample distances, where the electrical force is large, allowing for small sample heterogeneities to be revealed.

"The next logical step was to combine PF-KPFM with Peak Force Infrared (PFIR) microscopy, an infrared imaging technique invented in our lab, since both techniques use the pulsed force mode," says Xu. "The resulting technique, named PFIR-KPFM, provides topographical, mechanical, chemical, and electrical information at

So, in addition to achieving significant improvements in measuring electrical potential in nanomaterials in a single-pass AFM scan, PF-KPFM can be combined with (PFIR) microscopy for high-throughput correlative measurements, according to the researchers. This follow-up study is described in an article, "Peak Force Infrared ? Kelvin Probe Force Microscopy," forthcoming in Angewandte Chemie International Edition. (Authors: Xiaoji Xu, Devon S. Jakob and Haomin Wang from Lehigh University; Yong Yan, San Diego State University; Guanghong Zeng, Danmarks Nationale Metrologiinstitut, A/S, DENMARK; and Daniel E. Otzen, Aarhus Universitet, iNANO, Denmark.

"Pulsed force KPFM is the first KPFM technique to truly implement the pulsed force mode of AFM for nanoscale surface potential characterization, and the first KPFM technique to be combined with simultaneous infrared detection in the same scan," says Xu.

The importance of accurately measuring the nanoelectrical properties of materials is far-reaching in both academia and industry, according to the researchers. Due to the increasingly smaller size of semiconductor devices, PF-KPFM may be especially helpful for technology companies, as the high spatial resolution of PF-KPFM reveals features that are too small for other KPFM techniques. Similarly, they say, PFIR-KPFM will be beneficial in revealing the correlations between chemical heterogeneity, structure, and electrical properties of lab-made solar cell components.

"Ultimately," says Xu, "we hope that our invention will open the door for characterization of new materials, and help pave the way for more efficient energy-related devices."

Xu's research group develops new methods and instruments for chemical measurement and imaging at the nanoscale with

Xu was named a 2020 Sloan Research Fellow. This prestigious award, funded by the Alfred P. Sloan Foundation, places Xu among "the most promising scientific researchers working today." Additionally, was named a Beckman Young Investigator, earning a prestigious grant awarded by the Arnold and Mabel Beckman Foundation for "the most promising young faculty members in the early stages of their academic careers in the chemical and life sciences."

PULLMAN, Wash. - As the SARS-CoV-2 puts new focus on zoonotic pathogens, a Washington State University researcher has developed a method to use environmental DNA (eDNA) to detect disease in the vast international trade of aquatic animals.

The problem with monitoring the pet trade is one of magnitude. In the Unites States alone, more than 225 million live animals are imported every year, the majority destined for the aquatic or pet industries. Creating a "clean trade" by detecting infections in these populations requires huge sample sizes, a labor-intensive and costly process.

In a paper published in Scientific Reports on June 24, Associate Professor of Disease Ecology Jesse Brunner outlines two potential ways to test captive animals for pathogen DNA: batching test samples from individuals and sampling eDNA from the water in the animals' tanks. The eDNA method proved to be much more efficient, Brunner said.

"The best way to prevent the emergence of these pathogens, and the diseases that come from them, is to keep them from getting here in the first place," said Brunner. "It's an important goal but a really hard one because of the scale of the problem. With the eDNA method you are theoretically sampling an entire population at once, so you are more likely to detect whatever is there, and you can do that much more efficiently than with traditional approaches."

Environmental DNA is already used to look for the presence of invasive species in places like the Great Lakes. Brunner saw that it might also be useful to sample water from the tanks of captive species being transported in the pet trade since infected animals will shed pathogens into their water.

As an example, Brunner used Bsal (Batrachochochytrium salamandrivorans) a chytrid fungus which threatens salamander populations. Bsal is a cousin of the devastating Bd (Batrachocytrium dendrobatidis) that was responsible for the decline of more than 500 amphibian species around the world, including 90 that likely went extinct.

Now Bsal has jumped into wild salamander populations in Europe from imported pets from Southeastern Asia. While it has not yet been found in North America, the threat of Bsal prompted the U.S. Fish and Wildlife Service to enact a ban in 2016 on the import of 201 species of salamanders into the United States, which is home to tremendous salamander diversity.

Brunner's paper outlines the statistical formulas needed to conduct surveillance of imported salamanders for Bsal using eDNA. It shows the volume of samples needed to be taken and tested to produce a good degree of confidence in a negative or positive result. If proven out, the method could reduce the amount of sampling and work required to effectively monitor for the pathogen. This paper provides the framework for the method, and Brunner and colleagues are currently testing it with real samples.

As part of a Bsal Task Force, Brunner and his colleagues are in conversation with the pet industry which is naturally interested in creating a clean trade for salamanders, but finding better solutions to test for pathogens in salamanders also has broader implications.

"The problem that we're having with amphibians is also the same problem that we're having with all sorts of wildlife and with human disease," said Brunner. "I think if we can solve this problem, we'll be in much better shape to solve others."

Scientists at Sanford Burnham Prebys Medical Discovery Institute and Radboud University Medical Center in the Netherlands have identified mutations in a gene called CNOT1 that affect brain development and impair memory and learning. The study is the first to link neurodevelopmental delays with CNOT1, suggesting that drugs that help restore the gene's function may have therapeutic benefit. The research, published in The American Journal of Human Genetics, also revealed that CNOT1 interacts with several known autism spectrum disorder (ASD) genes, opening new research avenues for the condition.

"Prior to this work, the CNOT1 gene was not on the radar of autism researchers," says Rolf Bodmer, Ph.D., director and professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys and the study's co-corresponding and co-senior author. "This discovery could help us better understand the genetic mechanisms underlying ASD. Our work is also a first step toward exploring drugs that could augment the function of CNOT1 and might be able to help children with neurodevelopmental delays who have these specific mutations."

The cause of developmental disabilities, including ASD, is poorly understood. Research indicates that there may be a genetic component to these conditions, but the precise impact of the genetic variations that have been uncovered to date is unclear. Identifying the underlying cause of developmental disabilities would allow scientists to create diagnostic tests that would provide early diagnoses and potential treatments.

A common genetic thread

In the current study, scientists at Radboud University Medical Center identified a commonality between 39 people with a neurological disorder: variations in the CNOT1 gene. These individuals, whose ages ranged from newborn to 22 years old, had symptoms that spanned from severe intellectual disability to nearly normal IQ and everyday functioning. The researchers hoped to determine if the variations in the CNOT1 gene were benign or the cause of the neurological symptoms--the first step to finding potential treatments.

To answer this question, the researchers at Radboud University turned to Bodmer, a world-renowned genetics expert who studies how genes contribute to disease using a fruit fly model. Sreehari Kalvakuri, Ph.D., a postdoctoral researcher in the Bodmer lab, created fruit flies that contained the same CNOT1 variations seen in the patients, including DNA sequences that were "misspelled" (missense), cut short (truncated) or otherwise altered.

This work identified nine CNOT1 variants that impaired learning and memory, which was measured by several independent approaches--including a courtship assay that tested the ability of male fruit flies to remember if their female partners had paired with other males. All of these variants appeared spontaneously (de novo) in the patients, meaning they were not inherited. The scientists also discovered that these CNOT1 mutations interact with known ASD genes--revealing a genetic link to ASD that can be further explored.

"Fruit flies are a great biological model because we can complete genetic studies very quickly. This work only took a few months instead of the potential decade using a mouse model," says Kalvakuri, the study's co-first author. "Additionally, the CNOT1 gene is highly conserved between fruit flies and humans, meaning it does not change much, so we are optimistic these findings can be extrapolated to people."

Next, the scientists plan to identify which molecular components interact with CNOT1, which functions as a scaffold that builds up a larger protein complex. This work might uncover additional potential drug targets for intellectual, learning or memory disorders, including ASD.

"The first step toward helping children with neurodevelopmental delays is to determine the cause of the condition," says Bodmer. "Our ultimate hope is to find a treatment that could be given as early as possible to help these children stay on track developmentally."

Surprisingly, the findings also have implications for heart disease, the primary focus of Bodmer's lab.

"A significant fraction of these patients also have cardiac defects," says Bodmer. "Conversely, children who are born with heart defects are at a higher risk of developing ASD, too. This study on CNOT1 also provides a previously unknown genetic link between heart function and ASD."

Developmental disabilities are a group of conditions characterized by impairments in physical, learning, language or behavioral areas. About one in six children in the U.S. have one or more developmental disabilities or other developmental delays, according to the Centers for Disease Control and Prevention.

A new study, investigating factors associated with verbal fluency among a large sample of anglophone Canadians aged 45-85, found that individuals who consumed more vegetables and fruits and more nuts and pulses (such as lentils and beans) scored higher on tests of verbal fluency.

"These findings are consistent with other research that has found a Mediterranean diet high in fruits, vegetables, nuts, and legumes is protective against cognitive decline," reported co-author Dr. Karen Davison, a nutrition informatics research program director at Kwantlen Polytechnic University, in British Columbia and a North American Primary Care Research Fellow. "Every increase in average daily fruit and vegetable intake was linked to higher verbal fluency scores, but the best outcomes were found among those who consumed at least 6 servings a day."

Verbal fluency is an important measure of cognitive function. To test it, subjects are asked to list as many words from a given category as they can in one minute. This measures language and executive function and can be used to detect cognitive impairment.

Adults who have insufficient appetite, face challenges in preparing food or consume low-quality diets, may be at risk of malnourishment, and grip strength can be used to assess under-nutrition. Those in the study who had poor grip strength and/or high nutritional risk scores also had lower verbal fluency.

"Previous research has also indicated that measures of under-nutrition are associated with cognitive decline," said co-author Zahraa Saab, a recent Masters of Public Health graduate of the University of Toronto.

The researchers investigated the relationship between other factors and cognitive health, as well, including immigrant status, age, blood pressure, obesity, and body fat.

Immigration status

Anglophone immigrants who had lived in Canada at least 20 years had higher verbal fluency scores than their Canadian-born peers. The researchers suspect that this protective effect may be partially due to better cognitive reserve among immigrants.

"Our earlier research on a big British cohort of individuals born in 1946 found that those who emigrated from United Kingdom had, on average, 5 points higher IQ than their peers who remained in the UK," says senior author, Esme Fuller-Thomson, professor at University of Toronto's Factor-Inwentash Faculty of Social Work (FIFSW) and director of the Institute for Life Course & Aging. "We purposively restricted the current study to those whose mother tongue was English, so we could investigate the association between immigrant status and verbal fluency, independent of bilingualism."

Previous research suggests that those who are bilingual have a lower incidence and delayed onset of dementia. Most of the studies finding a 'bilingualism advantage' have, unfortunately, neglected to account for immigration status.

"Our findings suggest that this is an important omission, because even immigrants whose mother tongue is English had significantly higher verbal fluency scores than anglophones born in Canada. Thus, the 'bilingualism advantage' may be at least partially attributable to the "healthy immigrant effect," said Fuller-Thomson, who is also cross-appointed to U of T's Department of Family and Community Medicine and the Faculty of Nursing.

Age & Education

"Consistent with other studies, those younger in age had better cognitive functioning scores when compared to older participants." says co-author Hongmei Tong, assistant professor of Social Work at MacEwan University in Edmonton.

The association between cognitive impairment and advanced age may be mediated or moderated by cognitive reserve factors such as high educational levels, which are protective against cognitive decline.

"Respondents who were aged 75-85 with a high school degree had verbal fluency scores comparable to individuals a decade younger who had not completed high school," says co-author Vanessa Taler, associate professor of psychology, University of Ottawa.

Blood Pressure, Obesity & Body Fat

Adults with stage 2 hypertension had lower verbal fluency scores.

"Our findings underline the importance of managing blood pressure for brain health in mid-life and beyond," says co-author Shen (Lamson) Lin, a doctoral student at the FIFSW.

Both obesity and higher percent body fat were associated with worse verbal fluency scores.

"Obesity has been linked in other research to inflammation and to greater insulin resistance, both of which have been associated to cognitive decline," says co-author Karen Kobayashi, professor in the Department of Sociology and a research fellow at the Institute on Aging & Lifelong Health at the University of Victoria.

The study team analyzed data from the baseline Canadian Longitudinal Study on Aging, which included 8,574 anglophone participants aged 45-85, of whom 1,126 were immigrants who had arrived in Canada 20 or more years earlier. All participants were living in the community and were free from dementia. Two verbal fluency tests were examined: the Controlled Oral Word Association Test (COWAT) and the Animal Fluency (AF) task. The article was published this month in the Journal of Nutrition Health and Aging.

"The team's findings suggest that it may be beneficial to design policies and health care practices to reduce nutrition risk, improve diet quality, and address obesity and hypertension among midlife and older citizens in order to improve these potentially modifiable risk factors for lower verbal fluency scores," adds Dr. Fuller-Thomson. "The good news is that the higher levels of education obtained by baby boomers and subsequent birth cohorts may mitigate some of the cognitive decline often observed in previous generations of older adults."

Scientists at St. Jude Children's Research Hospital alongside global partners are studying a common TP53-R337H variant found among people of Brazilian descent. The researchers found that a variant in the tumor suppressor gene XAF1 increases cancer risk when combined with the inherited TP53-R337H mutation. The work appears as an advance online publication today in Science Advances.

"We expect these results to have a significant impact on public health," said corresponding author Emilia Pinto, Ph.D., of St. Jude Pathology. "Once clinicians know what variants to look for, they will know how to better manage those patients with higher cancer risk."

A finding 20 years in the making

More than 20 years ago, St. Jude researchers led by Raul Ribeiro, M.D., identified the TP53-R337H inherited variant among Brazilians. Pinto and her colleagues later identified TP53-R337H as a founder mutation, one introduced to Brazil during its colonization. While rare in the general population, TP53-R337H is common in Brazil. It is found in 1 out of every 300 Brazilians.

"The TP53-R337H mutation does not explain the entirety of cancer risk," said senior author Gerard Zambetti, Ph.D., of St. Jude Pathology. "Variation among individuals with TP53-R337H can lead some to develop several forms of cancer, some to develop a single cancer and others to never develop cancer at all."

From their whole genome sequencing study, the researchers identified a variant in the tumor suppressor gene XAF1 in a subset of TP53-R337H mutation carriers. Individuals who have inherited both the XAF1 variant and the TP53-R337H mutation are at a greater risk of cancer than those who have only the TP53-R337H mutation.

TP53 mutations are prevalent in individuals with rare pediatric adrenocortical carcinoma. However, TP53 mutations are a prominent factor in many other types of cancer. The knowledge that XAF1 modifies TP53 may fuel further research into whether this target can become the basis of novel treatment strategies.

Finding helps fine-tune public health approach

St. Jude researchers studied the causes of this variation through whole genome sequencing of individuals of Brazilian ancestry. The partnerships forged through St. Jude Global were key to obtaining the samples necessary to do this work.

Led by the Department of Global Pediatric Medicine, St. Jude Global has formed the St. Jude Global Alliance, which includes programs in the Asia-Pacific, Central and South America, China, the East and Mediterranean, Eurasia, Mexico and Sub-Saharan Africa.

"This study would not have been possible without the collaboration of our partners around the world," said author Carlos Rodriguez-Galindo, M.D., St. Jude Department of Global Pediatric Medicine chair. "These results will have an impact on public health in Brazil but are also important for the pediatric cancer community at large."

In 2013, researchers at Boston Children's Hospital and Brigham and Women's Hospital launched a multi-center study comparing a work schedule that included traditional, extended work shifts for resident physicians (24 hours or more) with a schedule that eliminated extended shifts and cycled resident physicians through day and night shifts (maximum, 16 hours). They expected the new schedule with shorter shifts would reduce serious medical errors by allowing residents to get more sleep. But as they report today in The New England Journal of Medicine, they found something different: patient safety worsened at some of the sites. On further analysis, a key factor that appeared to drive medical errors was how many patients each resident cared for.

"Our first finding was that the new scheduling didn't work -- it actually appeared to make outcomes worse overall," says Christopher Landrigan, MD, MPH, chief of General Pediatrics at Boston Children's Hospital and the study's first author. "When we tried to understand why, it became clear that workload was a major component of medical errors. We didn't set out to look at workload, so this was an unexpected finding."

Comparing work schedules

The randomized study, called ROSTERS, was conducted in six pediatric intensive care units in different parts of the U.S. In a "crossover" design, the hospitals followed each work schedule for eight months, in random order. Total work hours for the traditional schedule and the new schedule were the same. The researchers collected data on adverse events, work rosters, work hours, sleep hours, residents' reports of sleepiness, and residents' performance on vigilance tasks.

To the researchers' surprise, serious medical errors increased by about 50 percent overall when ICUs followed the new schedule. But there were differences among the hospitals: One logged many fewer serious medical errors, three reported more errors, and two saw no change.

"The Data Safety Monitoring Board charged us with investigating why one center had a 75 percent reduction in serious errors, while another had a tripled error rate," says senior author Charles Czeisler, MD, PhD, Chief of the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital. "We spent a year going through the data trying to understand what was happening. We thought there was a problem with the intervention."

The additional analyses showed that residents got more sleep with the new schedule, and did better on performance tests, as expected. Though the number of patient "handoffs" between shifts increased by about 25 percent, this was consistent across sites, and didn't appear to account for why some sites did better and others did worse. So the team began looking at workload.

Variable workloads

Looking at staffing ratios, they found that resident physicians' workload increased by about 25 percent across the six sites when the new schedule was implemented--from an average of 6.7 to 8.8 ICU patients per resident. ICUs with the highest resident workloads before the study fared worst with the new schedule, the investigators found.¬¬¬

"There was remarkable variability between the sites in the baseline number of ICU patients each resident cared for every day," says Czeisler. "At one site, there were four to five ICU patients per resident physician; at another, there were 10 ICU patients per resident even before the intervention. If you increase that by 25 percent, it suddenly it gets to a breaking point, and you see a lot of medical errors."

The results contrast with a study Czeisler and Landrigan conducted more than a decade ago, which found that residents made 36 percent fewer medical errors when following a new schedule that eliminated 24-hour shifts. However, that study held resident workload constant and involved just one center, Brigham and Women's Hospital.

The new study spanned a broad range of children's hospitals with varying resources and unit organizational structures, and each hospital was allowed to develop its own staffing plan to accommodate the new schedule.

"Once we adjusted for workload, the intervention was associated with a 50 percent reduction in medical errors," says Czeisler. "That tells us we need good standards as to what staffing is safe. Moreover, we recently found that work hour limits are better for physician safety and health."

A call for more attention to resident staffing

The study is one of the first to document a connection between resident physician caseloads and medical errors. More attention has been focused on nursing; for example, Massachusetts passed a law requiring a 1:1 or 1:2 nurse to patient ratio in the ICU.

In the U.S., as many as 250,000 patients per year die as a result of medical errors, many of which occur in settings where resident physicians care for them.

"There is a lot of literature on nursing workload and patient safety, but the literature is surprisingly sparse when it comes to physicians' workloads," says Landrigan. "Future research should directly address this issue. Our findings suggest that we need to fundamentally redesign our care systems to ensure patient safety and invest funds and personnel to keep workload from rising. The status quo just isn't working."

For more than a decade, astronomers have searched for planets orbiting AU Microscopii, a nearby star still surrounded by a disk of debris left over from its formation. Now scientists using data from NASA's Transiting Exoplanet Survey Satellite (TESS) and retired Spitzer Space Telescope report the discovery of a planet about as large as Neptune that circles the young star in just over a week.

The system, known as AU Mic for short, provides a one-of-kind laboratory for studying how planets and their atmospheres form, evolve and interact with their stars.

"AU Mic is a young, nearby M dwarf star. It's surrounded by a vast debris disk in which moving clumps of dust have been tracked, and now, thanks to TESS and Spitzer, it has a planet with a direct size measurement," said Bryson Cale, a doctoral student at George Mason University in Fairfax, Virginia. "There is no other known system that checks all of these important boxes."

The new planet, AU Mic b, is described in a paper co-authored by Cale and led by his advisor Peter Plavchan, an assistant professor of physics and astronomy at George Mason. Their report was published on Wednesday, June 24, in the journal Nature.

AU Mic b is featured in a new NASA poster available in English and Spanish, part of a Galaxy of Horrors series. The fun but informative series resulted from a collaboration of scientists and artists and was produced by NASA's Exoplanet Exploration Program Office.

AU Mic is a cool red dwarf star with an age estimated at 20 million to 30 million years, making it a stellar infant compared to our Sun, which is at least 150 times older. The star is so young that it primarily shines from the heat generated as its own gravity pulls it inward and compresses it. Less than 10% of the star's energy comes from the fusion of hydrogen into helium in its core, the process that powers stars like our Sun.

The system is located 31.9 light-years away in the southern constellation Microscopium. It's part of a nearby collection of stars called the Beta Pictoris Moving Group, which takes its name from a bigger, hotter A-type star that harbors two planets and is likewise surrounded by a debris disk.

Although the systems have the same age, their planets are markedly different. The planet AU Mic b almost hugs its star, completing an orbit every 8.5 days. It weighs less than 58 times Earth's mass, placing it in the category of Neptune-like worlds. Beta Pictoris b and c, however, are both at least 50 times more massive than AU Mic b and take 21 and 3.3 years, respectively, to orbit their star.

"We think AU Mic b formed far from the star and migrated inward to its current orbit, something that can happen as planets interact gravitationally with a gas disk or with other planets," said co-author Thomas Barclay, an associate research scientist at the University of Maryland, Baltimore County and an associate project scientist for TESS at NASA's Goddard Space Flight Center in Greenbelt, Maryland. "By contrast, Beta Pictoris b's orbit doesn't appear to have migrated much at all. The differences between these similarly aged systems can tell us a lot about how planets form and migrate."

Detecting planets around stars like AU Mic poses a particular challenge. These stormy stars possess strong magnetic fields and can be covered with starspots -- cooler, darker and highly magnetic regions akin to sunspots -- that frequently erupt powerful stellar flares. Both the spots and their flares contribute to the star's brightness changes.

In July and August 2018, when TESS was observing AU Mic, the star produced numerous flares, some of which were more powerful than the strongest flares ever recorded on the Sun. The team performed a detailed analysis to remove these effects from the TESS data.

When a planet crosses in front of its star from our perspective, an event called a transit, its passage causes a distinct dip in the star's brightness. TESS monitors large swaths of the sky, called sectors, for 27 days at a time. During this long stare, the mission's cameras regularly capture snapshots that allow scientists to track changes in stellar brightness.

Regular dips in a star's brightness signal the possibility of a transiting planet. Usually, it takes at least two observed transits to recognize a planet's presence.

"As luck would have it, the second of three TESS transits occurred when the spacecraft was near its closest point to Earth. At such times, TESS is not observing because it is busy downlinking all of the stored data," said co-author Diana Dragomir, a research assistant professor at the University of New Mexico in Albuquerque. "To fill the gap, our team was granted observing time on Spitzer, which caught two additional transits in 2019 and enabled us to confirm the orbital period of AU Mic b."

Spitzer was a multipurpose infrared observatory operating from 2003 until its decommissioning on Jan. 30, 2020. The mission proved especially adept at detecting and studying exoplanets around cool stars. Spitzer returned the AU Mic observations during its final year.

Because the amount of light blocked by a transit depends on the planet's size and orbital distance, the TESS and Spitzer transits provide a direct measure of AU Mic b's size. Analysis of these measurements show that the planet is about 8% larger than Neptune.

Observations from instruments on ground-based telescopes provide upper limits for the planet's mass. As a planet orbits, its gravity tugs on its host star, which moves slightly in response. Sensitive instruments on large telescopes can detect the star's radial velocity, its motion to-and-fro along our line of sight. Combining observations from the W. M. Keck Observatory and NASA's InfraRed Telescope Facility in Hawaii and the European Southern Observatory in Chile, the team concluded that AU Mic b has a mass smaller than 58 Earths.

This discovery shows the power of TESS to provide new insights into well-studied stars like AU Mic, where more planets may be waiting to be found.

"There is an additional candidate transit event seen in the TESS data, and TESS will hopefully revisit AU Mic later this year in its extended mission," Plavchan said. "We are continuing to monitor the star with precise radial velocity measurements, so stay tuned."

For decades, AU Mic has intrigued astronomers as a possible home for planets thanks to its proximity, youth and bright debris disk. Now that TESS and Spitzer have found one there, the story comes full circle. AU Mic is a touchstone system, a nearby laboratory for understanding the formation and evolution of stars and planets that will be studied for decades to come.

TESS is a NASA Astrophysics Explorer mission led and operated by MIT in Cambridge, Massachusetts, and managed by NASA's Goddard Space Flight Center. Additional partners include Northrop Grumman, based in Falls Church, Virginia; NASA's Ames Research Center in California's Silicon Valley; the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts; MIT's Lincoln Laboratory; and the Space Telescope Science Institute in Baltimore. More than a dozen universities, research institutes and observatories worldwide are participants in the mission.

NASA's Jet Propulsion Laboratory (JPL) in Southern California managed the Spitzer mission for the agency's Science Mission Directorate in Washington. Spitzer science data continue to be analyzed by the science community via the Spitzer data archive located at the Infrared Science Archive housed at IPAC at Caltech in Pasadena. Science operations were conducted at the Spitzer Science Center at Caltech. Spacecraft operations were based at Lockheed Martin Space in Littleton, Colorado. Caltech manages JPL for NASA.

En español: http://ciencia.nasa.gov/las-misiones-tess-y-spitzer-de-la-nasa-descubren-un-planeta-orbitando-una-joven-e-inusual-estrella

"Squeezing" is used in physics, among other things, to improve the resolution of measuring instruments. It allows disturbing noise to be suppressed in a way that smaller signals can be detected more sensitively.

The research team led by physicist Professor Eva Weig at the University of Konstanz has now been able to show how such a squeezed state can be measured in a much simpler way than with the existing methods. Moreover, the new method allows examining squeezed states in systems where such measurements were not possible before.

The results are published in the current issue of the journal Physical Review X.

An international research team led by Dr. Tali Ilovitsh of the Biomedical Engineering Department at Tel Aviv University developed a noninvasive technology platform for gene delivery into breast cancer cells. The technique combines ultrasound with tumor-targeted microbubbles. Once the ultrasound is activated, the microbubbles explode like smart and targeted warheads, creating holes in cancer cells' membranes, enabling gene delivery. Conducted over two years, the research was published on June 9 in the journal Proceedings of the National Academy of Sciences (PNAS).

Dr. Ilovitsh developed this breakthrough technology during her post-doctorate research at the lab of Prof. Katherine Ferrara at Stanford University. The technique utilizes low frequency ultrasound (250 kHz) to detonate microscopic tumor-targeted bubbles. In vivo, cell destruction reached 80% of tumor cells.

"Microbubbles are microscopic bubbles filled with gas, with a diameter as small as one tenth of a blood vessel," Dr. Ilovitsh explains. "At certain frequencies and pressures, sound waves cause the microbubbles to act like balloons: they expand and contract periodically. This process increases the transfer of substances from the blood vessels into the surrounding tissue. We discovered that using lower frequencies than those applied previously, microbubbles can significantly expand, until they explode violently. We realized that this discovery could be used as a platform for cancer treatment and started to inject microbubbles into tumors directly."

Dr. Ilovitsh and the rest of the team used tumor-targeted microbubbles that were attached to tumor cells' membranes at the moment of the explosion, and injected them directly into tumors in a mouse model. "About 80% of tumor cells were destroyed in the explosion, which was positive on its own," says Dr. Ilovitsh. "The targeted treatment, which is safe and cost-effective, was able to destroy most of the tumor. However, it is not enough. In order to prevent the remaining cancer cells to spread, we needed to destroy all of the tumor cells. That is why we injected an immunotherapy gene alongside the microbubbles, which acts as a Trojan horse, and signaled the immune system to attack the cancer cell."

On its own, the gene cannot enter into the cancer cells. However, this gene aimed to enhance the immune system was co-injected together with the microbubbles. Membrane pores were formed in the remaining 20% of the cancer cells that survived the initial explosion, allowing the entry of the gene into the cells. This triggered an immune response that destroyed the cancer cell.

"The majority of cancer cells were destroyed by the explosion, and the remaining cells consumed the immunotherapy gene through the holes that were created in their membranes," Dr. Ilovitsh explains. "The gene caused the cells to produce a substance that triggered the immune system to attack the cancer cell. In fact, our mice had tumors on both sides of their bodies. Despite the fact that we conducted the treatment only on one side, the immune system attacked the distant side as well."

Dr. Ilovitsh says that in the future she intends to attempt using this technology as a noninvasive treatment for brain-related diseases such as brain tumors and other neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. "The blood-brain barrier does not allow for medications to penetrate through, but microbubbles can temporary open the barrier, enabling the arrival of the treatment to the target area without the need for an invasive surgical intervention."