Culture

HOUSTON - (June 28, 2021) - Rice University computer scientists are sending RAMBO to rescue genomic researchers who sometimes wait days or weeks for search results from enormous DNA databases.

DNA sequencing is so popular, genomic datasets are doubling in size every two years, and the tools to search the data haven't kept pace. Researchers who compare DNA across genomes or study the evolution of organisms like the virus that causes COVID-19 often wait weeks for software to index large, "metagenomic" databases, which get bigger every month and are now measured in petabytes.

RAMBO, which is short for "repeated and merged bloom filter," is a new method that can cut indexing times for such databases from weeks to hours and search times from hours to seconds. Rice University computer scientists presented RAMBO last week at the Association for Computing Machinery data science conference SIGMOD 2021.

"Querying millions of DNA sequences against a large database with traditional approaches can take several hours on a large compute cluster and can take several weeks on a single server," said RAMBO co-creator Todd Treangen, a Rice computer scientist whose lab specializes in metagenomics. "Reducing database indexing times, in addition to query times, is crucially important as the size of genomic databases are continuing to grow at an incredible pace."

To solve the problem, Treangen teamed with Rice computer scientist Anshumali Shrivastava, who specializes in creating algorithms that make big data and machine learning faster and more scalable, and graduate students Gaurav Gupta and Minghao Yan, co-lead authors of the peer-reviewed conference paper on RAMBO.

RAMBO uses a data structure that has a significantly faster query time than state-of-the-art genome indexing methods as well as other advantages like ease of parallelization, a zero false-negative rate and a low false-positive rate.

"The search time of RAMBO is up to 35 times faster than existing methods," said Gupta, a doctoral student in electrical and computer engineering. In experiments using a 170-terabyte dataset of microbial genomes, Gupta said RAMBO reduced indexing times from "six weeks on a sophisticated, dedicated cluster to nine hours on a shared commodity cluster."

Yan, a master's student in computer science, said, "On this huge archive, RAMBO can search for a gene sequence in a couple of milliseconds, even sub-milliseconds using a standard server of 100 machines."

RAMBO improves on the performance of Bloom filters, a half-century-old search technique that has been applied to genomic sequence search in a number of previous studies. RAMBO improves on earlier Bloom filter methods for genomic search by employing a probabilistic data structure known as a count-min sketch that "leads to a better query time and memory trade-off" than earlier methods, and "beats the current baselines by achieving a very robust, low-memory and ultrafast indexing data structure," the authors wrote in the study.

Gupta and Yan said RAMBO has the potential to democratize genomic search by making it possible for almost any lab to quickly and inexpensively search huge genomic archives with off-the-shelf computers.

"RAMBO could decrease the wait time for tons of investigations in bioinformatics, such as searching for the presence of SARS-CoV-2 in wastewater metagenomes across the globe," Yan said. "RAMBO could become instrumental in the study of cancer genomics and bacterial genome evolution, for example."

A connective tissue protein known to support the framework of organs also encourages immune responses that fight bacterial infections, while restraining responses that can be deadly in the condition called sepsis, a new study finds.

Led by researchers from NYU Grossman School of Medicine, the work revolves around the extracellular matrix (ECM) of connective tissues, once thought of as an inert framework that shapes bodily compartments, but increasingly recognized as a signaling partner with nearby cells in normal function, and a contributor to disease when signals go awry. Among the key players in the ECM are fibroblasts, the cells that make tough structural matrix proteins like collagen.

Published online June 28 in the Proceedings of the National Academy of Sciences, the new analysis found that lumican, a protein-sugar combination (proteoglycan) secreted by fibroblasts, and known to partner with collagen in connective tissues, also promotes immune system responses in immune cells called macrophages that fight bacterial infections. At the same time, the study found that lumican protects tissues by restraining a different type of immune response that reacts to DNA, whether from an invading virus, or from human cells that spill their DNA as they die (a signal that tissues are under stress).

Such inflammatory responses represent as a transition into healing, but grow too big in sepsis, damaging the body's own tissues to the point of organ failure. Sepsis affects 48.9 million people worldwide, the authors say, but the role of the ECM in the condition is largely unknown.

"Lumican may have a dual protective role in ECM tissues, promoting defense against bacteria on the one hand, and on the other, limiting immune overreactions to DNA that cause self-attack, or autoimmunity," says corresponding study author Shukti Chakravarti, PhD, professor in the departments of Ophthalmology and Pathology at NYU Langone Health.

The findings suggest that connective tissue, and extracellular matrix proteins like lumican, operate outside of cells normally, but as disease or damage break down ECM, get sucked into and regulate immune cells homing in on the damage.

Maintaining the Balance

Lumican happens to interact with two proteins on surfaces of immune cells that control the activity of proteins called toll-like receptors known to recognize structural patterns common to molecules made by invading microbes, say the study authors. Because they are less specific than other parts of the immune system, toll-like receptors can also cause attacks by immune cells on the body's own tissues if over-activated.

The current study authors found that lumican promotes the ability of toll-like receptor (TLR)-4 on the surfaces of immune cells to recognize bacterial cell-wall toxins called lipopolysaccharides (LPS). Specifically, the study found that lumican, by attaching to two proteins, CD14 and Caveolin1, likely using regions normally covered by collagen, stabilizes their interactions with TLR4 to increase its ability to react to LPS. This in turn leads to production of TNF alpha, a signaling protein that amplifies immune responses.

Along with describing the effect of lumican on the surfaces of immune cells, the new study finds that lumican is taken up from outside cells into membrane-bound pouches called endosomes, and pulled into cells. Such compartments deliver ingested bacteria to other endosomes that destroy them, or heighten inflammation or protective interferon responses. Once pulled inside, the researchers found, lumican bolstered TLR4 activity by slowing down its passage into lysosomes, pockets where such proteins are broken down and recycled.

While it encouraged TLR4 activity on cell surfaces, lumican, once inside immune cells, had the opposite effect on toll-like receptor 9 (TLR9), which is known react to DNA instead of bacterial LPS. Experiments showed that lumican's binding of DNA in endosomes keeps it away from, and prevents it from activating, TLR9.

Experiments confirmed that mice engineered to lack the gene for lumican have trouble both fighting off bacterial infections (less cytokine response, slower clearance, greater weight loss), and trouble restraining the immune overreaction to bacteria (sepsis). The study authors also found elevated lumican levels in human sepsis patients' blood plasma, and that human immune cells (blood monocytes) treated with lumican had elevated TLR4 activity, but suppressed TLR9 responses.

"As an influencer of both processes, lumican-based peptides could be used as a lever, to tweak inflammation related to TNF-alpha, or endosomal interferon responses, to better resolve inflammation and infections," says George Maiti, PhD, a post-doctoral fellow in Chakravarti's lab. "Our results argue for a new role for ECM proteins at sites of injury. Taken up by incoming immune cells it shapes immune responses beyond the cell surface by regulating the movement and interaction of endosomal receptors and signaling partners," says

India and Pakistan have fought four wars in the past few decades, but when India faced an oxygen shortage in its hospitals during its recent COVID-19 surge, Pakistan offered to help.

On Twitter, hashtags like #IndiaNeedsOxygen and #PakistanStandsWithIndia trended. Finding these positive tweets, however, was not as easy as simply browsing the supportive hashtags or looking at the most popular posts. Negative tweets often hijack the supportive hashtags for trolling or fighting with other users. And Twitter's algorithm isn't tuned to surface the most positive tweets during a crisis.

Ashique KhudaBukhsh of Carnegie Mellon University's Language Technologies Institute led a team of researchers who used machine learning to identify supportive tweets from Pakistan during India's COVID crisis. In the throes of a public health crisis, words of hope can be welcome medicine.

"When a country is experiencing a national health crisis, the more supportive messages you see, the better," KhudaBukhsh said. "If you're just randomly searching, you'll find positive tweets about 44% of the time. Our method gives a person positive tweets 83% of the time. That person will have to do a lot less work to find the supportive tweets."

By combining existing language classifiers -- algorithms trained by machine learning that determine, for example, whether speech is positive or negative, hopeful or distressing -- the team developed a system that identified supportive or positive Pakistani tweets about India 83% of the time, far better than existing methods. The team used their method to conclude that more than 85% of the tweets posted about the COVID crisis in India from Pakistan were supportive.

"We have boundaries but not in our hearts," one tweet detected by the team began.

The team included KhudaBukhsh, Clay H. Yoo and Rupak Sarkar from the LTI and Shriphani Palakodety, an engineer the blockchain and AI company Onai who earned his master's from the LTI. They published their results in a paper titled, "Empathy and Hope: Resource Transfer To Model Inter-country Social Media Dynamics," which was accepted into the ACL Association for Computational Linguists Workshop on Natural Language Processing for Positive Impact. The work was performed in real-time with the crisis and as members of the team worried about the health of loved ones in India.

The research is significant on several fronts. First, the team showed that existing language classifiers could be useful in broad contexts. This is important because to deploy a classifier that will be useful in the middle of the crisis, it must be built quickly. It cannot be built from scratch, and the team wanted to see if existing research into language classifiers could help.

To detect supportive tweets during India's COVID crisis, the team used a hope-speech classifier that KhudaBukhsh and Palakodety built with the late Jaime Carbonell, a distinguished professor in the School of Computer Science who founded the LTI, to identify positive YouTube comments on videos posted about the 2019 escalation of conflict between India and Pakistan over Kashmir. The team then combined the hope-speech classifier with a known empathy-distress classifier.

Despite these two language classifiers being built for different reasons and trained on different data, they effectively detected positive tweets during India's COVID surge.

"We showed that there is some sort of universality in how we express emotions," KhudaBukhsh said. "And we showed that we can use existing solutions, combine them and attack future crises quickly.

The research was also potentially significant to the crisis in India. KhudaBukhsh and Carbonell envisioned the hope-speech classifier as an alternative way to combat hate speech. Instead of detecting and deleting, downplaying or blocking hate speech -- which exists in droves on the internet -- the pair sought to use their hope-speech classifier to identify and amplify supportive messages. People are influenced by what they see and read, and if hopeful messages are put in front of them rather than hateful ones, it could affect how they think and act.

The team identified tweets that offered prayers to India, spoke to the common humanity of two countries, and sent love.

"Heartbreaking to see this situation in our neighbourhood. Send love and prayers from Pakistan. May Almighty Allah help humanity through this pandemic. Stay strong. Stay safe," a tweet found by the team read.

Emphasizing the support between India and Pakistan could make a difference, KhudaBukhsh said. And since so many fights now happen over the internet, maybe that's the place to start.

"These two countries have such an acrimonious past," KhudaBukhsh said. "Any positive behavior from either side can help promote world peace."

Public opinion surveys could be used more widely to understand regional variation in vaccine hesitancy, experts have recommended.

The research shows vaccine uptake rates for childhood vaccines are significantly lower in regions where hesitancy observed in mass public opinion surveys is more pronounced.

This data is often not widely available, which makes it challenging for experts to analyse the links between attitudes and real-world behaviour. The study says this data should be used by public health officials to understand where vaccines are more likely to be rejected, and who should be the target of information campaigns.

The research published in the journal Vaccine, was carried out by Dr Florian Stoeckel and Professor Jason Reifler from the University of Exeter, Professor Ben Lyons from the University of Utah and Charlie Carter from the London School of Economics.

They analysed regional level data for the EU from 2019 for the uptake of various childhood vaccines in 177 regions of 20 European countries - DTP3 (diphtheria, tetanus toxoids, and pertussis), MCV1 (the first dose of the measles-containing vaccine), and MCV2 (second dose of the measles vaccine) for 2019. Data on vaccine hesitancy was taken from the Eurobarometer survey of Spring 2019, which included about 1,000 respondents from each EU country except for Luxembourg, Cyprus, and Malta, where about 500 individuals were interviewed.

Dr Stoeckel said: "Our analysis shows public opinion surveys can play a valuable role in public health as a tool to understand immunization behaviour. It is currently high time for more opinion surveys on citizens' attitudes towards vaccines. Assessing the link between survey responses and actual uptake is important, because public opinion survey data on vaccine hesitancy is only useful if it is in fact related to behaviour."

"We found statistically significantly lower regional vaccine immunization rates in regions where vaccine hesitancy is more pronounced. Surveys can be used to observe where vaccine uptake is likely to be low (when vaccine uptake data is incomplete) and to learn from regions with high uptake (despite high vaccine hesitancy) so that best practices could be applied elsewhere."

Vaccine uptake for the childhood vaccines that we examined differs both between countries and within countries. Most national uptake rates of the childhood vaccines examined are above 90 percent. For instance, average national level uptake of the MCV1 vaccine varies between 85.94 percent in Cyprus and 99.87 percent in Hungary. However, there is a considerable amount of variation within countries. Uptake of MCV1 in Croatia ranges from 73.24 percent to 98.38 percent.

The analysis shows average country level vaccine hesitancy is lowest in Denmark and highest in Latvia. The least vaccine hesitant sub-national region in Latvia is more vaccinate hesitant than the most vaccine-hesitant region in Denmark.

An incredibly rare hybrid warbler with mismatched color patterns has allowed researchers to disentangle the genetic drivers of two traits that usually come as a package deal--the black face mask and the black throat patch in blue-winged and golden-winged warblers. A new study describing the peculiar bird and pinpointing the location in the genome that controls the face mask and throat patch appears online in the journal Ecology.

"Golden-winged warblers have both a black face mask and a black throat patch, while blue-winged warblers have neither," said Marcella Baiz, postdoctoral researcher at Penn State and first author of the study. "When individuals of each species mate with each other, almost all of their hybrid offspring have matched traits, so both black plumage traits are present or both are absent. But we captured this very weird bird that looks almost entirely like a golden-winged warbler but is missing the black throat patch."

The researchers believe this unique combination occurs in less than 0.5% of the hybrid warblers. To their knowledge, this type of hybrid had been previously documented only once in a bird that was collected in 1934 and described in 1951 from a museum collection.

"We originally found this bird thanks to a tip from a local birder who works at Shaver's Creek Environmental Center," said David Toews, professor of biology at Penn State and an author of the study. "He suggested that a nearby area seemed like good warbler habitat and also uploaded observations of warblers onto the app eBird, which scientists can use in their research. We went to scout the location when we spotted this unique and exciting bird. We carefully captured the bird so we could document its plumage, took a blood sample so we could sequence its genome, and then released it."

In a previous study, the researchers sequenced the genomes of blue- and golden-winged warblers and their hybrids and identified a small region that drives the black coloration in these birds upstream of the Agouti-signaling protein (ASIP) gene. But because the two traits are almost always inherited together, it was unclear if ASIP regulated the traits together or separately.

"Because we already had genome sequencing data from the parent species and hybrids with the matched face and throat color, sequencing the genome of the mismatched bird allowed us to separate out the genetic regions underlying the face mask versus the throat patch," said Baiz.

The team confirmed that the previously identified region is connected to the black throat patch, and also identified a new location--nearby, but further upstream in the genome--that they believe is connected to the black face mask. For black pigment to occur in these birds, the two copies (one on each chromosome) must have originally come from the golden-winged warbler, suggesting that these are "recessive" traits. Having one or both copies from the blue-winged warbler in these spots results in no face mask or throat patch.

"More than a hundred years ago, a biologist named John Treadwell Nichols hypothesized that the black throat coloration was a recessive trait," said Toews. "Later, when Kenneth Parkes described the rare hybrid in 1951, he suggested that if throat and mask color were controlled separately, they would need to be linked in some way or located very close together on the genome. Parkes described his theory as a 'genetic problem for future study,' and we were able to confirm both theories using modern genetic tools."

The researchers suggest that the locations they identified might be located within two separate promoter regions for the ASIP gene, which turn the gene on or off in different contexts. Because they are located so close to each other on the chromosome, the promoters would usually be inherited together--even if genetic material is shuffled between chromosomes during reproduction--which would explain why most hybrids carry both or neither of these black plumage traits. The mismatched bird, however, was likely a result of an extremely rare instance where this was not the case, followed by several generations of backcrossing with golden-winged warblers.

"If coloration genes in warblers have a similar genetic architecture, with multiple promoters controlling where pigment is deposited, it's easy to see how just a few mutations could produce a variety of different color patterns among these songbird species," said Baiz. "This may help explain why there are so many different species of warblers with such a diversity of colors."

Because a warbler's coloration is an important cue for behaviors like mating, it is possible there are implications of the mismatched hybrid bearing only one of the traits. For example, it may be attractive to females of both species because it has qualities of both, or to neither. The researchers hope to observe this bird in the future and determine if it has a mate, and future research linking plumage traits to reproductive success would clarify these implications.

"We have now observed this bird two years in a row, so it has survived at least two migration events," said Toews. "This study and the story of how we found this bird is an excellent example of how birders and citizen scientists can make a real difference in research."

WASHINGTON, D.C.--A new study in Annals of Emergency Medicine highlights the importance of protecting physician residents--early-career doctors still in training--and emergency care teams from incidents of physical or verbal abuse.

The survey of 123 physicians, residents, and staff in one emergency department found that 78 percent of all health care workers experienced a violent assault in the prior 12 months, including more than one in five (22 percent) emergency physician residents. Eighty-nine percent of residents experienced verbal assault by a patient in the prior 12 months, compared to 80 percent of other health care workers.

"Violent or threatening incidents in the emergency department pose risks to everyone's safety but can also impact health workers' mental health and may increase the likelihood of burnout," said Lauren Querin, MD, MS, lead author and emergency physician with the University of North Carolina (UNC) Chapel Hill Department of Emergency Medicine. "These encounters happen frequently and often go unreported."

Of the total respondents who experienced physical assault or violence, 19 percent did not discuss the incident with anyone. About half (53 percent) only discussed the incident with colleagues while only 20 percent filed a formal incident report with the hospital or police. Among residents, 96 percent discussed incidents with only a colleague or no one at all. None of the residents filed formal reports.

Residents' experience with assault became more common with time in the program, the analysis shows. Sixty-two percent of first year residents and 100 percent of second- and third-year residents experienced verbal assault. While no first-year residents reported a physical assault, 25 percent of second-year residents and 36 percent of third-year residents indicated that they have been physically assaulted.

"More can be done to make sure that every member of the emergency care team can prioritize patient care rather than worrying about their own safety at work," said RJ Sontag, MD, president of the Emergency Medicine Residents' Association (EMRA). "This study looks at one emergency department but stories like these are common nationwide. We must empower residents and others to report these incidents and take the necessary steps to protect health care workers and patients."

Only 24 percent of the residents believe that workplace violence protocols in place at their facility are adequate while 30 percent do not think the protections are sufficient and 38 percent were unsure. Eight percent were not certain what the protocols were.

Anonymous firsthand accounts of violence, sexual assault, or personal threats are detailed in the analysis:

One resident reported that a patient being discharged threatened to "come find me and shoot me in the kneecaps."

Another resident commented, "I was not only scared for myself and other staff...but also scared regarding the injuries the patient would sustain and I would need to treat."

This qualitative analysis echoes findings from a 2018 poll of more than 3,500 emergency physicians across the nation from the American College of Emergency Physicians (ACEP). ACEP is leading efforts with physicians, hospitals, care teams, regulators, and policymakers to address violence in the emergency department, including extensive work to support the introduction of the "Workplace Violence Prevention for Health Care and Social Service Workers Act of 2021," by Rep. Joe Courtney (D-CT) and a bipartisan coalition in the House of Representatives.

For its members, ACEP offers education, training, and advocacy opportunities aimed at curbing violence in the emergency department. The association also launched "No Silence on ED Violence," a campaign with the Emergency Nurses Association (ENA) that gives those impacted a chance to share stories and increase awareness of workplace violence while providing resources and a peer network that supports emergency nurses and physicians.

Philadelphia, June 28, 2021--Researchers at Children's Hospital of Philadelphia (CHOP) have discovered that a specific type of lung cell exhibits unconventional immune properties and may contribute to the outcome of respiratory viral infections. The researchers focused on type II alveolar (AT2) cells, which are non-immune cells of the lung that are critical for basic lung health and tissue repair after lung injury. They found that AT2 cells express high levels of major histocompatibility complex II (MHC-II), an important immune system trigger, and that AT2 MHC-II expression appears to confer an appreciable advantage in the outcome of respiratory viral infection. The findings were published today in Nature Communications.

"This study shows that MHC-II expression is regulated in a unique way in AT2 cells, which has important implications for the health of lungs when faced with infection," said senior author Laurence Eisenlohr, VMD, PhD, investigator and Professor of Pathology and Laboratory Medicine at CHOP. "Future research should explore whether alterations in AT2 MHC-II expression or function contribute to the wide variation in outcome of lung diseases in humans, particularly SARS-CoV-2 infection, as AT2s are a major cell type infected with this virus in the human lung."

MHC-II triggers an immune cascade that activates helper T cells, which in turn drive B cells, cytotoxic T cells and other important immune cells required to fight an infection. The sequence begins when a peptide from the infectious pathogen connects with MHC-II protein, and that complex is presented on the surface of the cell, a process known as "antigen presentation." Historically, only certain types of specialized immune cells, termed "professional antigen presenting cells," have been shown to express MHC-II at steady state, including B cells, dendritic cells, and macrophages; other cells outside of the immune system are thought to express MHC-II only when inflammation is present, such as during an infection. However, recent research has shown that some of these other "non-immune" cell types, including AT2s, can also express MHC-II under normal conditions as well, and this is thought to be driven by small amounts of inflammation that are still present even at homeostasis.

AT2 cells are epithelial cells in the lung parenchyma that produce surfactant and promote cell renewal. Previous studies of AT2 MHC-II expression and function have varied widely, and as a result, researchers have not fully understood how well AT2 cells express MHC-II, what triggers AT2 MHC-II expression, and how AT2 MHC-II functions in lung immunity both at baseline and during lung infection.

To better understand the role of AT2 MHC-II, the researchers analyzed mouse and human AT2 cells and found that despite being non-immune cells, AT2s express MHC-II uniformly and to high levels under normal conditions, at levels similar to the "professional antigen presenting cells." They also found that in AT2 cells, MHC-II expression is activated independently of the inflammation cascade that is thought to set the complex into action in essentially all other non-immune cells, suggesting it is triggered in AT2s by unique mechanisms.

Given the role of MHC-II in initiating an immune response, the researchers examined the role of AT2 MHC-II in protecting the lungs from respiratory disease. To test this, the researchers generated mice with an AT2-specific deletion of MHC-II. Under normal conditions, the health of the mice did not seem to be affected by the deletion of MHC-II; they did not develop spontaneous respiratory disease and the lung tissue was comparably healthy to mice with functional AT2 MHC-II, leading researchers to conclude that MHC-II does not seem to be required for effective surfactant production or lung regeneration, or lung immunity at homeostasis. However, when the mice were exposed to influenza A virus and Sendai virus, the mice with MHC-II deletions had higher morbidity and mortality than those with intact MHC-II, implying that it does contribute to improved outcomes during lung infection.

Although loss of AT2 MHC-II worsened respiratory virus disease, the effect was smaller than the researchers had anticipated based on the abundance of AT2 cells in the lung and the magnitude of AT2 MHC-II expression. Surmising this might be a result of a limitation in the actual function of MHC-II on AT2 cells, the researchers examined the ability of AT2 cells to present infectious and non-infectious antigens via MHC-II to stimulate other immune cells. They found that AT2 cells are capable of presenting antigen via MHC-II and that this is enhanced in the setting of inflammation, but compared to the specialized "professional antigen presenting cells," AT2 cells exhibit very limited antigen presentation capacity.

"Although future studies will need to explore the reasons why this combination of high MHC-II expression but limited antigen presentation occurs in AT2 cells, we propose that this is actually part of a carefully balanced system in the lung, where excessive T cell activation would be especially damaging," Eisenlohr said. "We propose that high MHC-II expression by AT2s allows them to participate in immune responses, but restrained MHC-II antigen presentation establishes a higher threshold that must be overcome in order to for them to activate the immune system, allowing for AT2s to contribute in a more tempered manner. This way, MHC-II presentation by AT2s would only trigger T cell activation in the setting of high antigen burden, such as a severe lung infection, but would prevent AT2-induced amplification of T cells in response to low levels of inhaled innocuous environmental antigens."

The use of transparent masks during communication increases comprehension of speech by about 10% for people with hearing loss and people with normal hearing, according to a study published in the journal Ear and Hearing.

The study was conducted at the University of Texas in Dallas (USA), with the participation of Regina Tangerino, a professor at the University of São Paulo's Bauru Dental School (FOB-USP) in Brazil, and with support from São Paulo Research Foundation - FAPESP.

"Our findings show that wearing a transparent mask can facilitate communication for everyone, minimizing stress and improving interaction. Protection obviously has to be the primary concern, and no clear models with proven effectiveness are sold in Brazil right now," Tangerino told.

In the US, she explained, two models of mask with a see-through portion in the mouth area have been approved by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC). "One of our aims is calling attention to the importance of the topic," she said.

The study began early in the pandemic, in 2020, when the group posted on the internet a set of videos lasting 40 minutes, with Tangerino voicing several utterances against background noise without a mask, wearing a mask with a clear mouth panel, and wearing an opaque fabric mask.

The study used 154 volunteers recruited via social media or by email. They were divided into three groups based on whether they had normal hearing, or confirmed or suspected hearing loss (with or without cochlear implants or hearing aids). They were invited to watch the videos in a quiet place and to type what they understood after each sentence. They also had to rate their level of confidence in responding and how intensely they had to concentrate to understand what was said. Each volunteer's score was computed at the end.

On average, the volunteers in all three groups correctly understood 83.8% of the sentences spoken without a mask, 68.9% of utterances with a see-through mask, and 58.9% with an opaque mask.

"The difference of 10 percentage points [between the latter two averages] is statistically significant. This benefit applies to more than just comprehension: the participants also felt more self-confident and were able to follow what was said with less effort when the see-through mask was used," Tangerino said. "In another study, conducted in the UK with 460 participants, the researchers noted that opaque masks influenced fatigue, anxiety and emotions in both listeners and speakers."

Visual cues

To find out if the difference in comprehension between transparent and opaque masks was due to visual cues such as lip reading, acoustic differences between the recordings, or the tendency for some masks to muffle sound, a follow-up study using audio only was conducted with 29 volunteers, who were not told which sentences were recorded with or without a mask.

"In this case, the average performance was actually worse for sentences spoken with a clear mask than with an opaque mask, confirming the significance of visual cues in the first study. They helped listeners surmount the problem of muffled sound when a mask is worn," Tangerino said.

Production of transparent masks certified by ANVISA, the national health surveillance agency, should be stimulated in Brazil, she added. Currently, the only see-through type available is a vinyl mask, considered insufficiently effective to block transmission of the novel coronavirus.

Scientists isolated a molecule, extracted from the leaves of the European chestnut tree, with the power to neutralize dangerous, drug-resistant staph bacteria. Frontiers in Pharmacology published the finding, led by scientists at Emory University.

The researchers dubbed the molecule Castaneroxy A, after the genus of the European chestnut, Castanea. The use of chestnut leaves in traditional folk remedies in rural Italy inspired the research.

"We were able to isolate this molecule, new to science, that occurs only in very tiny quantities in the chestnut leaves," says Cassandra Quave, senior author of the paper and associate professor in Emory's Center for the Study of Human Health and the School of Medicine's Department of Dermatology. "We also showed how it disarms Methicillin-resistant Staphylococcus aureus by knocking out the bacteria's ability to produce toxins."

Methicillin-resistant Staphylococcus aureus (MRSA) causes infections that are difficult to treat due to its resistance to antibiotics. It is one of the most serious infectious disease concerns worldwide, labeled as a "serious threat" by the Centers for the Disease Control and Prevention. In the United States alone, nearly 3 million antibiotic-resistant infections occur in the U.S. each year, killing more than 35,000 people.

Antibiotics work by killing staph bacteria, which can lead to greater resistance among those few bacteria that survive, spawning "super bugs." The Quave lab has identified compounds from the Brazilian peppertree, in addition to the European chestnut tree, that simply neutralize the harmful effects of MRSA, allowing cells and tissue to naturally heal from an infection without boosting resistance.

"We're trying to fill the pipeline for antimicrobial drug discovery with compounds that work differently from traditional antibiotics," Quave says. "We urgently need these new strategies." She notes that antimicrobial infections kill an estimated 700,000 globally each year, and that number is expected to grow exponentially if new methods of treatment are not found.

First author of the Frontiers in Pharmacology paper is Akram Salam, who did the research as a PhD student in the Quave lab through Emory's Molecular Systems and Pharmacology Graduate Program.

Quave is a medical ethnobotanist, researching traditional plant remedies to find promising leads for new drugs. Although many major drugs are plant-based, from aspirin (the bark of the willow tree) to Taxol (the bark of the Pacific yew tree), Quave is one of the few ethnobotanists with a focus on antibiotic resistance.

The story behind the current paper began more than a decade ago, when Quave and her colleagues researched written reports and conducted hundreds of field interviews among people in rural southern Italy. That pointed them to the European, or sweet, chestnut tree, native to Southern Europe and Asia Minor. "In Italian traditional medicine, a compress of the boiled leaves is applied to the skin to treat burns, rashes and infected wounds," Quave says.

Quave took specimens back to her lab for analysis. By 2015, her lab published the finding that an extract from the leaves disarms even the hyper-virulent MRSA strains capable of causing serious infections in healthy athletes. Experiments also showed the extract did not disturb normal, healthy bacteria on skin cells.

Finally, the researchers demonstrated how the extract works, by inhibiting the ability of MRSA bacteria to communicate with one another, a process known as quorum sensing. MRSA uses this sensing signaling system to make toxins and ramp up its virulence.

For the current paper, the researchers wanted to isolate these active ingredients from the plant extract. The process is painstaking when done manually, because plant extracts typically contain hundreds of different chemicals. Each chemical must be separated out and then tested for efficacy. Large scale fraction collectors, coupled to high-performance liquid chromatographic systems, automate this separation process, but they can cost tens of thousands of dollars and did not have all the features the Quave lab needed.

Marco Caputo, a research specialist in the lab, solved the problem. Using a software device from a child's toy, the LEGO MINDSTORMS robot creator, a few LEGO bricks, and some components from a hardware store, Caputo built an automated liquid separator customized to the lab's needs for $500. The lab members dubbed the invention the LEGO MINDSTORMS Fraction Collector. They published instructions for how to build it in a journal so that other researchers can tap the simple, but effective, technology.

The Quave lab first separated out a group of molecules from the plant extract, cycloartane triterpenoids, and showed for the first time that this group actively blocks the virulence of MRSA. The researchers then dove deeper, separating out the single, most active molecule from this group, now known as Castaneroxy A.

"Our homemade piece of equipment really helped accelerate the pace of our discovery," Quave says. "We were able to isolate this molecule and derive pure crystals of it, even though it only makes up a mere .0019 percent of the chestnut leaves."

Tests on mouse skin infected with MRSA, conducted in the lab of co-author Alexander Horswill at the University of Colorado, confirmed the molecule's efficacy at shutting down MRSA's virulence, enabling the skin to heal more rapidly.

Co-author John Bacsa, director of Emory Department of Chemistry's X-ray Crystallography Center, characterized the crystal shape of Castaneroxy A. Understanding the three-dimensional configuration of the crystal is important for future studies to refine and optimize the molecule as a potential therapeutic.

"We're laying the groundwork for new strategies to fight bacterial infections at the clinical level," Quave says. "Instead of being overly concerned about treating the pathogen, we're focusing on ways to better treat the patient. Our goal is not to kill the microbes but to find ways to weaken them so that the immune system or antibiotics are better able to clear out an infection."

Photobombs - when something or someone unexpectedly enters a camera's field of sight during the taking of a photograph - happen every day. Sometimes it is a friend, other times a stranger or perhaps a bird. Rarely, however, is it a whole planet. Yet, this is exactly what happened while CHEOPS, the Swiss-led space telescope, was taking pictures of a planetary system 50 light-years away.

A planet like no other

The planetary system is located in the constellation Lupus (latin for Wolf), around a star called Nu2 Lupi, visible to the naked eye (but not from Switzerland). In 2019, Swiss astronomers announced the detection of three exoplanets around this bright, Sun-like star. The three exoplanets have masses between those of Earth and Neptune (17 times the Earth) and take 12, 28 and 107 days to circle their parent star. "What makes these exoplanets really outstanding is that we can see them passing just in front of their star; they're said to 'transit'", says Yann Alibert, professor of astrophysics at the University of Bern and co-author of the study which has been published in Nature Astronomy. "We knew that already for the two inner planets, which led us to point CHEOPS to the system in the first place. However, the third planet is quite far away from the star, no one was expected to see its transit!", Alibert adds. In fact, the farther away the planet is from its star, the less likely it is to transit.

This proved a game changer, as it is the first time an exoplanet with a revolution period of over 100 days - which corresponds to a distance from the star somewhere between that of Mercury and Venus from the Sun - has been spotted transiting a star that is bright enough to be visible to the naked eye.

"Due to its relatively long period, the amount of stellar radiation reaching the planet is mild in comparison to many other discovered exoplanets. The less radiation a planet receives, the less it changes over time. Therefore, a planet with a long period could have retained more information about its origin", says David Ehrenreich, professor at the University of Geneva and mission scientist of CHEOPS, who co-signed the study. But so far, the few such exoplanets astronomers had found orbited faint stars. In other words: little of their light reaches Earth and therefore makes them difficult to study. Not this time: "Since its bright host star is quite close to us, it is easier to study. This makes it a golden target for future study with no known equivalent", Ehrenreich adds.

Further insights from other telescopes

The high-precision measurements of CHEOPS reveal the third planet, called nu2 Lupi d, to be about 2.5 times the size of Earth and almost 9 times its mass. By combining these measurements with archival data from other observatories and numerical models developed by the University of Bern, Laetitia Delrez, a visiting researcher at the University of Geneva and lead-author of the study, was able to accurately characterize the density and composition the planet and its neighbors. "The innermost planet is mainly rocky, while the outer two appear to be enshrouded in envelopes of hydrogen and helium gases beneath which they hold large amounts of water", Delrez explains. Far more water, in fact, than the Earth has: a quarter of each planet's mass is made up of water, compared to less than 0.1% for Earth. This water, however, is not liquid, instead taking the form of high-pressure ice or high-temperature steam, making the planets uninhabitable. But these insights could only be the beginning.

"Now that we discovered that all three planets transit and have precisely measured their properties, the next step is to study them with bigger and more powerful instruments than CHEOPS, like the Hubble Space Telescope or its successor, the James Webb Space Telescope. They could reveal further details, such as the composition of the atmosphere" says Ehrenreich. Given its overall properties and orbit, planet d is going to become the poster-child of exoplanets with a mild-temperature atmosphere around a star similar to the Sun.

Annapolis, MD; June 28, 2021—Drones keep getting smaller and smaller, while their potential applications keep getting bigger and bigger. And now unmanned aircraft systems are taking on some of the world’s biggest small problems: insect pests.

From crop-munching caterpillars to disease-transmitting mosquitoes, insects that threaten crops, ecosystems, and public health are increasingly being targeted with new pest-management strategies that deploy unmanned aircraft systems (UAS, or drones) for detection and control. And a variety of these applications are featured in a new special collection published this week in the Journal of Economic Entomology.

“Ten years ago, there was not much happening in the space in terms of entomologists deploying UAS for pest management,” says Nathan Moses-Gonzales, CEO of M3 Agriculture Technologies, who compiled the research collection alongside Michael Brewer, Ph.D., professor of field crops entomology with AgriLife Research at Texas A&M University. But, in the time since, technological advances have opened the doors for creative collaborations between entomologists and drone developers, Moses-Gonzales says. “The evolution of UAS technology in entomology has been fascinating to watch.”

The collection in the Journal of Economic Entomology, featuring both newly released and recently published research, gathers examples illustrating both the progress and potential of drone technology in insect pest management settings. Case studies include:

Locating and sampling standing water for mosquito larvae and improving accuracy of insecticide applications targeting mosquito larvae and adults.
Applying precise amounts of pheromones via drone over cranberry beds to disrupt the mating of cranberry fruitworms (Acrobasis vaccinii) and blackheaded fireworms (Rhopobota naevana).

Photographing tree canopies from above via drone in winter to survey for presence of cocoons of the moth Monema flavescens and prevent defoliation in the subsequent summer.
Delivering and releasing predator and parasitoid insects via drone to target the European corn borer (Ostrinia nubilalis) and the eastern spruce budworm (Choristoneura fumiferana).
Using drones to release sterile Mexican fruit flies (Anastrepha ludens) and codling moths (Cydia pomonella) to suppress wild populations of the pests—a modern improvement on the classic sterile insect technique.

Several articles in the collection also explore potential future applications for drone technology in insect pest management, including aerial spectral imagery of crops and plants to assess signs of pest damage, enhanced deployment of traps and monitoring systems to detect insects in hard-to-reach locations, and more.

“Our special collection speaks to the uniqueness of these partnerships and demonstrates the vital role entomologists play in bringing concepts to reality through methods development and field testing,” Moses-Gonzales says.

Of course, continued research, development, and experimentation will refine drone technology in the pest management context, and research in related fields such as automation and artificial intelligence will be critical, as well. Moses-Gonzales and Brewer say they see a bright future for this multidisciplinary field.

“Here, we hope that the Journal of Economic Entomology will serve as a venue that not only supports rigorous research but also details the development of new and novel tools for use in pest management,” Moses-Gonzales says.

The year 2020 was a period of economic hardship and significant change in a wide range of sectors for most countries. A team of authors from HSE University has explored how Russia will recover from this crisis and which industries will be affected by the economic recovery. Their study was published in the journal Voprosy ekonomiki.

Last year, the global economy experienced a crisis due to the coronavirus pandemic, with output falling by 3.5% compared to 2019. Russia's decline from the coronavirus measures was more moderate than in many developed countries (industrial production fell by 3.1% in 2020) and much less severe than in past crises (7.8% in 2009 and 5.3% in 1998). Recovery following those crises took different trajectories -- in the early 2000s the Russian economy showed very high growth rates, while the 2008-2009 crisis was followed by stagnation. Experts are now attempting to predict which scenario the recovery will mimic in the coming years and how sustainable growth will be.

The authors of the paper analysed the sources that shaped economic growth in Russia from 1995 to 2016. To do so, they compared the contribution of various production factors to economic growth in different industries, labour productivity and resource efficiency. Separately, the authors sought to distinguish between intensive growth (due to lower specific labour and capital costs) and extensive growth (due to the new resources).

Economists have used the term Total Factor Productivity (TFP), which characterizes the efficiency of production and use of resources (other than capital and labour) and determines the growth generated by lower factor inputs per unit of output. For example, in 2002-2007, almost all productivity growth was achieved through an increase in TFP (5.5 p.p. out of 6 per cent), while in 2011-2016 productivity rose (through capital inputs) but TFP declined, indicating less sustainable economic growth after the 2008-2009 crisis.

In Russia, this approach tends to be applied to the economy as a whole rather than to individual industries. In this case, differences in productivity across industries and labour reallocation between industries are not taken into account; this can affect conclusions about the degree of intensity and sustainability of growth. To avoid this problem, researchers have used the KLEMS indicator system, which allows individual industries' contribution to economic growth to be assessed and compared, as well as productivity growth and resource efficiency to be measured.

There are two sources of productivity growth: intra-industry (technology development, improvements in labour quality, capital inflows) and that which is due to structural shifts (reallocation of workers between sectors). Total labour productivity growth between 1995 and 2016 was 2.9%, three-quarters of which came from intra-industry sources. During the period of rapid TFP growth (2002-2007), the largest contributors were construction, trade and telecommunications, the expanded mining complex (EMC - mining, including oil and gas, fuel production and wholesale trade), finance, and business services. In 2011-2016, only finance and agriculture remained on the plus side, while the EMC saw the biggest drop, which also had a significant effect on overall economic growth.

The remaining quarter of the productivity increase comes from the reallocation of labour. The main direction is from goods to services: from agriculture and manufacturing to construction, trade, telecommunications and finance. At the same time, agricultural productivity remains very low (it is highest in EMC and finance), so reallocation of workers increases average productivity in the economy.

In making their forecast, the researchers have assumed that main pre-COVID proximate sources of growth remain the same. In this scenario, the calculations show that the largest contribution to economic growth is to be expected from the contribution of capital formation to the EMC. In terms of possible growth stimulating policy the most promising issue seems to be some efforts to make EMC more efficient. Additional growth under these conditions can be provided primarily through measures to improve production efficiency and exports of natural resources; these measures should be based on further analysis of the reasons for the decline in EMC efficiency, which started well before the pandemic. Such causes can be both objective (e.g., worsening production conditions), as well as subjective and able to be corrected (e.g., imperfect transportation tariffs for petroleum products). Reducing the Russian economy's dependence on the state of the EMC requires economic diversification and reducing the share of the EMC. Despite the fact that the need to reduce the share of the EMC has been discussed for decades, the share of the EMC in value added has remained unchanged since 1995, holding steady at 20-25%.

'For now, I assume the situation will be similar to the early 2010s -- a boom period in China, a build-up of commodity exports in resource-exporting countries, including Russia, increased investment in the Russian mining complex and associated infrastructure. As a consequence, we will see a tangible contribution to growth through capital intensity in natural resource extraction and export activities. We should see this in the dynamics of investment in oil and gas extraction, infrastructure, mining and processing of metal ores, and corresponding export positions,' said Ilya Voskoboynikov https://www.hse.ru/en/org/persons/503434, Assistant Professor in the Faculty of Economic Sciences and director of the Centre for Productivity Studies at HSE and one of the authors of the study, in sharing his forecast. 'A noticeable recovery in other areas will indicate the possible emergence of other sources of growth.'

LAWRENCE -- Despite facing cultural and political pushback, the evidence remains clear: Face masks made a difference in Kansas.

"These had a huge effect in counties that had a mask mandate," said Donna Ginther, the Roy A. Roberts Distinguished Professor of Economics and director of the Institute for Policy & Social Research at the University of Kansas. "Our research found that masks reduced cases, hospitalizations and deaths in counties that adopted them by around 60% across the board."

Ginther's article "Association of Mask Mandates and COVID-19 Case Rates, Hospitalizations and Deaths in Kansas" examines the effect of masks on the state's 105 counties. It appears in JAMA Network Open, a journal published by the American Medical Association.

Kansas boasts the fifth-highest total of counties among all the states. Executive Order No. 20-52 that took effect in July of 2020 was initially adopted by only 15 counties, with 68 others not adopting the order through October. A second mandate in November was embraced by an additional 40 counties.

"We thought masks would matter for certain cases, but the effect size for hospitalizations and deaths being the same rate was pretty astonishing," Ginther said.

Co-written with Carlos Zambrana, an associate researcher at the Institute for Policy & Social Research, Ginther estimated masks saved about 500 lives in adoptive counties. And, yet, other counties often refused to adopt the mandate, citing personal freedoms and lack of scientific evidence as reasons.

"There's no way to run a clinical trial on masks because you'd have to observe people using them all the time, and we can't observe everyone's behavior. This type of observational study is the best we can do," Ginther said.

"But in terms of personal freedom, I would say that wearing a mask is a public good. There's a negative externality to not wearing one, and you could get infected or infect others. In a pandemic, where close to 600,000 people have died, this is a low-cost preventative measure that preserves life."

Data for her study was corralled from several sources. She used the daily total number of cases per county from The New York Times COVID-19 data in the U.S. GitHub repository. The state information came from the list of county official actions compiled by the Kansas Health Institute. Linear regression difference-in-difference models were then employed, with cases regressed on an indicator variable that started 21 days after the mandate to allow for changes in mask-wearing behavior, an indicator for no coronavirus cases and the number of days since the first recorded case.

"We are required to wear seatbelts in the state to save lives. We get driver's licenses to save lives. We have vaccine mandates for children going to school to prevent the spread of infectious disease. These are all public health measures that we follow. At some point, the government steps in and says, 'These are the right things to do to save lives,'" she said.

Aside from the health implications of ignoring a mask mandate, there are also economic ones.

"COVID-19 costs money," she said. "It slows down economic activity. It drains money for hospitalizations. We show that if you prevent COVID, you save the health care system money."

Now in her 18th year at KU, Ginther believes "Association of Mask Mandates" demonstrates the importance of nonmedical interventions for preventing the spread of respiratory diseases.

She said, "Given everything that's happening around the world, this may not be the last pandemic in our lifetime. Just think about places like India that don't have access to the vaccine. If you're wanting to slow the spread, knowing that a mask works and is a cost-effective approach to public health is really important."

In the context of recent debate over the FDA's approval of aducanumab, it's refreshing to learn about a model of Alzheimer's neurodegeneration that doesn't start with the pathogenic proteins amyloid or Tau.

A new paper in Alzheimer's & Dementia from Emory neuroscientist Shan Ping Yu and colleagues focuses on an unusual member of the family of NMDA receptors, signaling molecules that are critical for learning and memory. Their findings contain leads for additional research on Alzheimer's, including drugs that are already FDA-approved that could be used preventively, and genes to look at for risk factors.

"It's not just another rodent model of Alzheimer's," Yu says. "We are emphasizing a different set of mechanisms leading to neurodegeneration."

Those mechanisms include alterations in calcium and neuronal hyperactivity, which occur first in this mouse model, rather than standard models that have clumps of amyloid or Tau as the primary drivers.

For the last several years, Yu and his laboratory have been studying the NMDA receptor subunit GluN3A in the context of stroke and also brain development. According to their research, GluN3A acts like a control rod in a nuclear reactor, cooling down signaling in the brain so that things don't overheat. It's an inhibitory part of a receptor assembly that is usually stimulatory.

Yu says GluN3A's role in the adult brain is understudied, because it is generally thought to fade away after early development. Mice that are missing the gene for GluN3A get a benefit earlier in life, in that they have enhanced memory and spatial learning. But later on, the missing gene's function catches up, and the mice develop several features of Alzheimer's, including olfactory deficits, cognitive decline, neurodegeneration and neuroinflammation, and eventually amyloid/tau pathology.

"We show that virtually all clinical symptoms and pathophysiology spontaneously developed in the GluN3A knockout mouse in an age-dependent manner," Yu says.

Yu says he was originally motivated to examine GluN3A's role in neurodegeneration because the GluN3A-knockout mice develop the early symptom of olfactory dysfunction, which is commonly seen in Alzheimer's and Parkinson's patients. In the current paper, Yu and colleagues show that loss of GluN3A leads to elevated calcium levels, normally tightly regulated, and what they call "degenerative excitotoxicity".

This is distinct from the excitotoxicity that is harmful in traumatic brain injury or stroke - milder and more chronic. They connect the hyperactivity and inflammation to the "calcium hypothesis" for Alzheimer's - a well-established idea that dysregulated calcium drives neurodegeneration. Yu says that their discovery of the role of GluN3A relates more to the early stages of the disease, before amyloid plaque formation.

Looking forward, the findings on GluN3A have implications for additional investigation. First, the NMDA receptor inhibitor memantine is FDA-approved for Alzheimer's, but it is generally thought only to have an effect on symptoms. Yu's lab showed that they could prevent some (but not all) deficits by treating GluN3A-mutant mice with memantine. Maybe memantine or a similar drug could play a preventive role if given to people with mild cognitive impairment or early Alzheimer's? Second, genetic variations in GluN3A has barely been studied in Alzheimer's, and studies on other neuropsychiatric conditions suggest that a significant percentage of people carry mutations or deletions affecting GluN3A gene function.

Middle ear infections, also known as otitis media, affect more than 80% of the children in the U.S. In a new study, researchers have designed a miniaturized 3D-printed device to inactivate Pseudomonas aeruginosa, a common bacterium that causes the infection.

The device--a microplasma jet array--generates plasma, which is composed of charged particles and reactive molecules that have been previously shown to inactivate various pathogens. "This is the first time anyone has tried treating middle ear infections using plasma technology," said Jungeun Won, a graduate student in the Boppart lab. "Usually, the treatment involves using antibiotics or surgical intervention."

The problem with using antibiotics is two-fold. First, antibiotics are ineffective in more than 30% of the patients with acute infections. Second, their use can lead to increased antibiotic resistance because the bacteria form biofilms--aggregates that attach to the surface of the ear.

"Biofilms are very dense, making it difficult for the antibiotics to penetrate," said Helen Nguyen (IGOH), an Ivan Racheff Professor in Civil and Environmental Engineering. "Our idea was that if we could disrupt the structure of the biofilm, we could increase the penetration of the antibiotics."

The researchers tested the microplasma jet array by building a model of the middle ear. They used an excised rat eardrum and tested the antimicrobial effects of the microplasma on the bacteria that were located behind the eardrum.

"We used different duration times for the treatment and found that 15 minutes and longer was effective in inactivating the bacteria," Won said. "We also monitored the tissue to see if we had created any holes or ruptures, but we didn't find any obvious physical damage."

"We think that the microplasma disrupts the biofilm by disturbing the bacterial cell membrane," Nguyen said. "So far, we only have indirect measurements supporting our idea, but we will look into it in the future."

Although the thickness of the rat eardrum is 30% lower than that of a human, which is about the width of a hair strand, the results suggest that the microplasma treatment could be used to treat middle ear infections in humans.

"Middle ear infections and the over-prescription of antibiotics to treat these are major clinical challenges that are in need of new treatment technologies and solutions," said Stephen Boppart, Grainger Distinguished Chair in Engineering, who is also a medical doctor.

The researchers are now designing a smaller, earbud-shaped jet array for treatments that will allow longer exposure times. They will also test the devices on animal models using biofilms of the other bacteria that cause middle ear infections, including, but not limited to, Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, to test whether the treatment is also effective with these bacteria. Additionally, the researchers will closely monitor the tissues of the middle ear to ensure that there is no structural and functional tissue damage from the plasma technology.