Culture

Disagreements help team perception, study finds

image: This is one of the sample images used during the study.

Image: 
US Army photo

ABERDEEN PROVING GROUND, Md. (April 7, 2020) - Team disagreements might be the key to helping Soldiers identify objects in battle, researchers say.

While studies on combat identification typically focus on how technology can help identify enemy forces, researchers sought to understand how teams work together to identify armored vehicles--using only their training and each other.

"We wanted to know what factors would contribute the most to their success," said Dr. Anthony Baker, a scientist at the U.S. Army Combat Capabilities Development Command's Army Research Laboratory, who executed the study while a doctoral student at Embry-Riddle Aeronautical University. "While previous lab studies of combat identification have looked at the performance of an individual, this is the first lab study to our knowledge that considers team combat identification, especially without any technological aids like an automated combat identification system. This was key for helping us understand the aspects of the team, and its members, that contribute the most to their ability to understand and identify what they are seeing."

The Human Factors journal published the research, "Team Combat Identification: Effects of Gender, Spatial Visualization, and Disagreement," in its February issue.

Spatial visualization skills are particularly important for noticing the finer details that distinguish combat vehicles, which are more difficult to identify from the front than other angles, Baker said.

"Combat vehicles can be broadly similar in their shape and components," Baker said. "For example, many tanks have a similar general shape involving a large, blocky body with a rotating turret. Because of this, few viewing angles may highlight easily-identifiable cues, making it difficult to tell exactly what it is you're looking at."

In this study, researchers prepared pictures and videos of 10 armored vehicles from different angles and views, and presented them to 39 two-person teams. The researchers identified every point when the participants disagreed about which vehicle they saw.

Researchers found that teams that disagreed more performed better at combat identification, regardless of whether their disagreements actually resulted in more correct answers. The data suggested that disagreeing with a team member's first guess caused the team to verify why they identified a vehicle a certain way.

"In other words, when the team disagreed, they had to justify an answer by recounting the details of what they had seen," Baker said. "This process of recalling and discussing details caused teams to think more deeply about their original responses, compared to teams with fewer disagreements that may have simply trusted what the other teammate believed."

Previous studies show that spatial skills are very important when an individual performs combat identification, with men having a slight advantage over women in spatial visualization scores, Baker said; however, the data from this study suggest that while men typically have a slim advantage over women in spatial ability measures, team gender composition was not an important indicator of overall performance.

"The team members' individual spatial abilities--and the team's ability to communicate--are more important than gender," Baker said. "You can have a team of men with lower spatial skills that would likely perform worse at this task than a team of women with better spatial skills, or any other combination."

This research reinforces that to understand how a team does its job, one must consider both individual differences such as spatial skills, and team processes such as communication, Baker said.

Credit: 
U.S. Army Research Laboratory

Personalized microrobots swim through biological barriers, deliver drugs to cells

image: Illustration (top) and scanning electron microscopy image (bottom) of biohybrid bacterial microswimmers, which were fabricated by combining genetically engineered E. coli MG1655 and nanoerythrosomes made from red blood cells. A biotin-streptavidin interaction was used to attach nanoerythrosomes to the bacterial membrane.

Image: 
Image courtesy of the authors

WASHINGTON, April 7, 2020 -- Tiny biohybrid robots on the micrometer scale can swim through the body and deliver drugs to tumors or provide other cargo-carrying functions. The natural environmental sensing tendencies of bacteria mean they can navigate toward certain chemicals or be remotely controlled using magnetic or sound signals.

To be successful, these tiny biological robots must consist of materials that can pass clearance through the body's immune response. They also have to be able to swim quickly through viscous environments and penetrate tissue cells to deliver cargo.

In a paper published this week in APL Bioengineering, from AIP Publishing, researchers fabricated biohybrid bacterial microswimmers by combining a genetically engineered E. coli MG1655 substrain and nanoerythrosomes, small structures made from red blood cells.

Nanoerythrosomes are nanovesicles derived from red blood cells by emptying the cells, keeping the membranes and filtering them down to nanoscale size. These tiny red blood cell carriers attach to the bacterial membrane using the powerful noncovalent biological bond between biotin and streptavidin. This process preserves two important red blood cell membrane proteins: TER119 needed to attach the nanoerythrosomes, and CD47 to prevent macrophage uptake.

The E. coli MG 1655 serves as a bioactuator performing the mechanical work of propelling through the body as a molecular engine using flagellar rotation. The swimming capabilities of the bacteria were assessed using a custom-built 2D object-tracking algorithm and 20 videos taken as raw data to document their performance.

Biohybrid microswimmers with bacteria carrying red blood cell nanoerythrosomes performed at speeds 40% faster than other E. coli-powered microparticles-based biohybrid microswimmers, and the work demonstrated a reduced immune response due to the nanoscale size of the nanoerythrosomes and adjustments to the density of coverage of nanoerythrosomes on the bacterial membrane.

These biohybrid swimmers could deliver drugs faster, due to their swimming speed, and encounter less immune response, due to their composition. The researchers plan to continue their work to further tune the immune clearance of the microrobots and investigate how they might penetrate cells and release their cargo in the tumor microenvironment.

"This work is an important stepping stone in our overarching goal of developing and deploying biohybrid microrobots for therapeutic cargo delivery," author Metin Sitti said. "If you decrease the size of red blood cells to nanoscale and functionalize the body of the bacteria, you could obtain additional superior properties that will be crucial in the translation of the medical microrobotics to clinics."

Credit: 
American Institute of Physics

Wild tomato resistance to bacterial canker has implications for commercial tomato industry

image: F. Christopher Peritore-Galve, lead author of paper, and fellow graduate student Martha Sudermann.

Image: 
F. Christopher Peritore-Galve

Bacterial canker of tomato is a disease that leads to wilt, cankers, and eventually death. The disease was first discovered in Grand Rapids, Michigan, in 1909, but annual outbreaks now affect tomato production areas worldwide. For some farmers, bacterial canker can be devastating and spoil an entire season's planting.

Bacterial canker is caused by the pathogen Clavibacter michiganensis, which infects commercially bred tomatoes by colonizing the xylem, a series of tubes that transports water and minerals throughout the plant. There are no commercially available tomatoes resistant to bacterial canker and management options are limited. However, breeders have known that wild tomato species are less susceptible to bacterial canker, but this knowledge is limited.

Scientists at the School of Integrative Plant Science at Cornell University were interested in understanding how C. michiganensis colonized the xylem in wild tomato and comparing to colonization of cultivated tomatoes. They found a significant difference, according to the paper published in Phytopathology.

F. Christopher Peritore-Galve, lead author of this paper, explains: "Interestingly, the pathogen colonizes to high densities close to the inoculation site in wild tomatoes, but it is found in much lower densities 5 and 10 centimeters above that site, meaning that the bacteria are unable to spread through the xylem as well as in cultivated tomato xylem."

Additional research showed that the pathogen was restricted to the protoxylem vessels in vascular bundles of wild tomato.

"Protoxylem are early formed xylem vessels that are smaller in diameter that enable water transport during early, rapid plant growth," said Peritore-Galve. "We currently do not know why C. michiganensis preferentially colonizes these vessels, but that will be an avenue of future research."

Understanding what makes wild tomatoes able to tolerate this pathogen may help with future breeding efforts. For more information about this study, read "Characterizing Colonization Patterns of Clavibacter michiganensis During Infection of Tolerant Wild Solanum Species."

Credit: 
American Phytopathological Society

RSNA publishes Fleischner Society statement on chest imaging and COVID-19

OAK BROOK, Ill. (April 7, 2020) - A multinational consensus statement from the Fleischner Society on the role of chest imaging in the management of patients with COVID-19 was jointly published today in the journals Radiology and Chest.

"We need to understand that conditions across the globe vary greatly. Our goal in developing this statement was to offer guidance that is sensitive to these differences and applicable broadly," said Geoffrey D. Rubin, M.D., George B. Geller Professor of Cardiovascular Research, professor of radiology and bioengineering at Duke University School of Medicine in Durham, North Carolina.

The statement represents the collective opinions and perspectives of thoracic radiology, pulmonology, intensive care, emergency medicine, laboratory medicine and infection control experts practicing in 10 countries, representative of the highest burden of COVID-19 worldwide.

"The willingness of experts from around the world to pause from their care of patients to contribute their knowledge and experience toward this international consensus was inspiring," Dr. Rubin said.

Chest CT and X-ray are key tools in the diagnosis and management of numerous respiratory ailments, but their role in the management of COVID-19 has not been considered within the context of many variables, including the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints.

"The Fleischner statement was uniquely comprised of a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments," said Radiology Editor David A. Bluemke, M.D.

The panel evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions and resource constraints.

Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest X-ray and CT in the management of COVID-19.

The results suggested that imaging is not routinely indicated in asymptomatic individuals or patients with suspected COVID-19 and mild clinical symptoms. Use of chest imaging is indicated in patients with COVID-19 who have worsening respiratory status. Imaging is also indicated for patients with moderate to severe features of COVID-19 regardless of COVID-19 test results.

In a resource-constrained environment (lack of personal protection equipment or availability of COVID-19 testing), imaging is indicated for medical triage of patients with suspected COVID-19 who present with moderate to severe clinical features and a high pre-test probability of disease.

The panel also found that CT is appropriate in patients with functional impairment and/or hypoxemia (low level of oxygen in the blood) after recovery from COVID-19. When there is known community transmission, evidence of COVID-19 has been incidentally found on CT scans. In these cases, patients should have COVID-19 testing using a reverse-transcription polymerase chain reaction (RT-PCR) viral assay.

The authors note that this consensus statement represents opinion at a moment in time within a highly dynamic environment where the status of regional epidemics and the availability of critical resources to combat those epidemics vary daily. Recommendations may undergo refinement as the situation evolves.

"Currently, no therapy has been confirmed to alter the course of COVID-19, there is no known cure, and there is no vaccine for prevention," Dr. Rubin said. "As effective treatments are developed, thoracic imaging may find new roles by establishing treatment response or characterizing patients as likely responders to novel therapies."

RSNA is committed to connecting radiologists and the radiology community to the most timely and useful COVID-19 information and resources. RSNA's COVID-19 Resources page houses the latest guidance, original research, image collection and more. The page will be updated on an ongoing basis.

An associated special edition podcast from Dr. Bluemke is available.

Credit: 
Radiological Society of North America

Evaluating embryo quality with ultrasensitive protein detection

image: Diagram of hCGβ detection by microfluidic droplet and multicolor fluorescence detection

Image: 
Zeng Yong

WASHINGTON, April 7, 2020 -- Infertility is estimated to affect 9% of reproductive-aged couples globally, and many couples consequently turn to assisted reproductive technology (ART). Selecting embryos with maximum development potential plays a pivotal role in obtaining the highest rate of success in ART treatment, which ultimately determines whether a couple gets pregnant.

The conventional way to select embryos is based mainly on a morphological score, a score based on the form of the embryo. This method, however, is subjective, and there is inherent variability in how embryologists score embryos' morphology.

In comparison, researchers have found it more objective to evaluate the quality of an embryo by detecting the content of proteins secreted by the embryo. In a paper for Biomicrofluidics, from AIP Publishing, a method to detect trace proteins secreted by embryos using microfluidic droplets and multicolor fluorescence holds promise to select embryos for ART. The researchers analyzed spent embryo culture media from 30 patients in Shenzhen, China, collected between May to July 2019.

Extensive research in ART in secretomics, the analysis of the secretome, or the secreted proteins of a cell, tissue or organism, allows for the detection of these trace proteins. However, researchers are faced with a challenge because of the very small quantities of these proteins and the limits of detection tools.

"The proposed method aims to predict the developmental potential of the embryo based on the secretomics. We only need a small drop of medium to achieve this," said Yong Zeng, chief scientist of the Fertility Center at Shenzhen Zhongshan Urology Hospital in Shenzhen, China.

The team used microfluidic chips, which are tiny devices that enable a small amount of liquid to be processed or visualized. Zeng and his team were able to ensure the accuracy of their results by using a multi fluorescence detector (MFD).

Fluorescent magnetic beads and beta-glucanase enzyme-induced fluorescence products have different excitation and emission wavelengths and can be detected by MFD. The team was consequently able to eliminate the false positive signals generated by free beta-glucanase.

Using this ultrasensitive detection method, the researchers found that human corionic gonadotropin secreted by top-quality blastocysts was significantly higher than that of non-top-quality blastocysts and the embryos which did not develop into blastocysts. Human corionic gonadotropin is a protein secreted by the placenta and also secreted by embryo cultured in vitro.

"In the future, we will test other different kinds of proteins secreted by the embryo and analyze the relationship between those proteins and embryo quality," said Zeng.

Since various embryo-secreted proteins often appear in very small amounts, they will also work to develop increasingly sensitive and multifactor protein detection systems.

Credit: 
American Institute of Physics

The evolution of color: Team shows how butterfly wings can shift in hue

video: A selective mating experiment by a curious butterfly breeder has led scientists to a deeper understanding of how butterfly wing color is created and evolves.
Rachel Thayer, Frances Allen and Nipam Patel (2020) eLife, doi: 10.7554/eLife.52187

Image: 
Emily Greenhalgh, MBL

WOODS HOLE, Mass. - A selective mating experiment by a curious butterfly breeder has led scientists to a deeper understanding of how butterfly wing color is created and evolves. The study, led by scientists at University of California, Berkeley, and the Marine Biological Laboratory, Woods Hole, is published today in eLife.

When the biologists happened upon the breeder's buckeye butterflies--which normally are brown--sporting brilliant blue wings through selective mating, they jumped on the chance to explore what caused the change in color of the tiny, overlapping scales that produce the wing's color mosaic and pattern. They found that buckeyes and other Junonia species can create a rainbow of structural colors simply by tuning the thickness of the wing scale's bottom layer (the lamina), which creates iridescent colors in the same way a soap bubble does.

Structural color, often used in butterflies and other animals to create blue and green, is created by microscopic structures interacting with light to intensify some colors and diminish others. In contrast, pigmentary coloration is created by the absorption of specific colors (wavelengths) of light and is commonly employed to create colors such as yellow, orange, and brown.

"It was a surprise to find that the lamina, a thin sheet that looks very simple and plain, is the most important source of structural color in so many butterfly wing scales," says first author Rachel Thayer. Previous studies of structural coloration had largely focused on some extreme examples and mostly involved analyzing complex, 3D shapes on the top of the scales.

First, the team showed that blueness in the selectively bred buckeye wings was, in fact, structural color and was generated largely by the lamina. They then compared these blue scales with wild-type brown scales, and found the same general architecture except the lamina was about 75 percent thicker in the blue scales. Finally, they measured lamina thickness in nine species of Junonia and a tenth species, Precis octavia, and found a consistent relationship with scale color.

"In each Junonia species, structural color came from the lamina. And they are producing a big range of lamina thicknesses that create a rainbow of different colors, everything from gold to magenta to blue to green," says Thayer. "This helps us understand how structural color has evolved over millions of years." The color shifts as lamina thickness increases according to Newton's series, a characteristic color sequence for thin films, the team found.

"The color comes down to a relatively simple change in the scale: the thickness of the lamina," says senior author Nipam Patel, director of the Marine Biological Laboratory. "We believe that this will be a genetically tractable system that can allow us to identify the genes and developmental mechanisms that can control structural coloration." They identified one gene, optix, that can regulate lamina structural colors, and are currently searching for other candidates.

It was fortunate that the butterfly farmer, Edith Smith, had chosen buckeyes (Junonia coenia) for her mating experiment. For a variety of reasons, it is an ideal species for scientists to work with. "The buckeye genome is sequenced and other labs are working with it and have developed a number of experimental tools and protocols," Patel says. "And it grows reasonably well in the lab, which is a big plus because many butterflies can be hard to raise."

Smith's bred buckeyes, which displayed "rapid evolution" from brown scales to blue, helped them to understand that the same, simple mechanism of tuning lamina thickness can facilitate evolutionary change that can span just several generations or millions of years.

Credit: 
Marine Biological Laboratory

Study demonstrates the need for immediate ICU care for severe COVID-19 pneumonia

April 07, 2020-- Researchers have identified the most common clinical characteristics of 109 patients with COVID-19 related pneumonia who died in Wuhan, China in the early stages of the coronavirus pandemic, according to a new study published online in the Annals of the American Thoracic Society.

In "Hospitalization and Critical Care of 109 Decedents With COVID-19 Pneumonia in Wuhan, China," Huan-Zong Shi, MD, PhD, and co-authors report on the age, comorbidities (other diseases), treatments and other commonalities among patients who died from this viral infection in three Wuhan hospitals between Dec. 25, 2019 and Feb. 24, 2020. The study was conducted to describe the hospitalization and critical care of patients who died from COVID-19 pneumonia.

"Mortality due to COVID-19 pneumonia was concentrated in patients above 65 years of age, especially those with major comorbidities," stated Dr. Shi, professor and director of the Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University. "We also found that patients who were admitted to the ICU lived longer than those who didn't. Our findings should aid in the recognition and clinical management of such infections, especially in ICU resource allocation."

The researchers looked back at the medical records of 109 deceased patients (out of 1,017) with confirmed COVID-19 pneumonia admitted to three Wuhan hospitals: Wuhan Pulmonary Hospital, which is designated as a "COVID-19 hospital," Tianyou Hospital affiliated with Wuhan University of Science and Technology, and Central Hospital of Wuhan. They recorded information on patients' demographics, clinical symptoms, laboratory results on admission and during hospitalization, treatment and date of death. The team created a database containing this information, and then cross-checked it. They then performed statistical analyses.

The average age of these patients was 70.7 years. Eighty-five suffered from comorbidities. The most common conditions were hypertension (high blood pressure), cardiovascular or cerebrovascular diseases and diabetes. All 109 patients were critically ill at hospital admission, and their most common condition was progressive shortness of breath (dyspnea). Prof. Shi observed, "Dyspnea was the most remarkable symptom that rapidly worsened."

Although all of these patients needed ICU care, only 46.8 percent were admitted to the ICU because of a bed shortage. Although all of the patients studied died, patients who were in the ICU group in comparison to the non-ICU group, lived an average of 15.9 days vs. 12.5 days following hospitalization.

"It is not surprising that there were approximately twice as many men as women among non-survivors with COVID-19 pneumonia," stated Prof. Shi. "In most infectious diseases and related conditions such as sepsis and septic shock men always represent a larger proportion of cases and have higher mortality rates."

All patients received antibiotics to treat secondary infections and nearly all received antivirals, while all ICU patients also received antifungal drugs. Other medicines, including glucocorticoids and intravenous immune globulin, were given to some patients. Oxygen therapy of various types was given to all patients.

Based on their observations and analyses, the authors concluded: "Since multiple organ failure, especially respiratory failure and heart failure, occurred rapidly after hospital admission, an organ protection strategy and ICU care should be provided as soon as possible to patients with severe COVID-19 pneumonia in order to prolong their survival. A social distancing policy should also be proposed to slow the rate of cases and prevent health care systems from being overwhelmed by patients for whom they cannot provide ICU care."

Credit: 
American Thoracic Society

Seeking COVID cures: Scientists find promising first step in antiviral treatment

ITHACA, N.Y. - Researchers from Cornell University have identified a possible target for antiviral treatment for COVID-19.

The researchers initially set out to analyze the structure and characteristics of SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus), with a focus on the spike protein - specifically the fusion peptide - that allows these viruses to infect cells by transferring their genome.

As the current pandemic escalated, the researchers compared the biological sequences of the fusion peptides of SARS-CoV to SARS-CoV-2, the virus that causes COVID-19, and found them to be a 93% match.

Susan Daniel's lab specializes in the biophysics of the cell membrane envelope; Gary Whittaker's team studies the entry of influenza and coronaviruses into host cells. Their combined group is drilling down into the intricate procedure of membrane fusion - a critical part of the mechanism by which coronaviruses spread.

Membrane fusion is a multistep process that begins with the virus recognizing that it's found the right type of cell to infect. To do this, the virus receives feedback from the chemical environment, including cues like the receptor that the host cell presents. The virus then attaches to the host cell receptor by way of the spike protein.

Next, a piece of the spike protein, called the fusion peptide, interacts directly with the host cell membrane and facilitates merging to form a fusion pore, or opening. The virus then transfers its genome into the host cell through this pore. These genomic instructions essentially commandeer the host's machinery to produce more viruses.

The group found that calcium ions interacting with the fusion peptide can change the peptide's structure, and how it interacts with membranes in ways that promote infection in MERS and SARS. Now, the researchers are turning their attention to SARS-CoV-2 because the fusion peptides are consistent in all three viruses.

The team is hopeful the research can illuminate some of the chemistry-related questions surrounding COVID-19, such as how it was able to move into humans, what chemical cues facilitated that process, and why the virus is able to replicate so easily in the respiratory tract. The team's findings have led to supplemental funding from the National Institutes of Health (NIH), through its Research Project Grant program, to develop an antibody that could block the virus's entry by interacting with the fusion peptide.

Credit: 
Cornell University

Applying CRISPR beyond Arabidopsis thaliana

Few technologies have made as big a splash in recent years as CRISPR/Cas9, and rightfully so. CRISPR/Cas9, or clustered regularly interspaced palindromic repeats (CRISPR) and associated genes, is a bacterial gene editing toolbox that allows researchers to edit genomic sequences much more precisely and efficiently than previously possible, opening up doors to new ways of doing research. As with many new biotechnologies, the application of CRISPR in biology began with genetic model organisms such as Arabidopsis thaliana. In research presented in a recent issue of Applications in Plant Sciences, Shengchen Shan and colleagues review the prospects for expanding the use of CRISPR for research beyond genetic model plant species.

"Developing CRISPR/Cas9 in nongenetic models holds enormous potential in plant biology," says Shan, a PhD candidate at the University of Florida, Gainesville. "Almost all CRISPR applications have focused on genetic models, like Arabidopsis and major crops. However, many nongenetic models are economically important and/or biologically significant."

Indeed, while our in-depth knowledge of the biology of genetic model species makes them enormously valuable for research, these species represent only a tiny sample of plant diversity. Much could be gained from expanding genetic studies of non-model species, including through the use of new tools like CRISPR.

Polyploidy, or whole genome duplication, is one example Shan and colleagues highlight of a research area that CRISPR could revolutionize. "We are very excited about future CRISPR/Cas9 applications in studies of evolutionary biology, especially the role of polyploidy in plant evolution. Polyploidy is a major evolutionary force in land plants, but the genotype-phenotype relationships following genome doubling are largely unknown," explains Shan. "CRISPR/Cas9 could be used to disrupt the observed genetic patterns in polyploids, and therefore, by comparing phenotypes of the mutant and wild-type plants, researchers will be able to reveal the biological underpinnings of many intriguing genetic consequences, such as nonrandom gene losses following polyploidy."

Researchers looking to study non-genetic model species using CRISPR will face some technical obstacles, including difficulties in genetic transformation, the process of introducing and expressing foreign genes in a plant species. However, looking to transformation systems established in closely related species can help. According to Shan, "The biggest barrier is developing the transformation system. Although we have summarized a few commonly used transformation strategies, plant transformation is a very species-specific process." He goes on to note, "As we reviewed, both transformation and CRISPR systems from a phylogenetically closely related genetic model species can be adapted for an initial attempt of establishing CRISPR in a newly studied plant species." In this way, the development of transformation and CRISPR systems in genetic models has helped pave the way for expanding CRISPR beyond these species.

The research done using CRISPR in genetic model species thus far has lowered the bar for entry in other ways too, as researchers have optimized techniques, hammered out details, and built up expertise in the use of this exciting new technology. "For people studying ecology or evolutionary biology, using a state-of-the-art technique in molecular biology research, like CRISPR/Cas9, might seem intimidating," says Shan. "However, based on our own experience, with the help from collaborators from a molecular biology lab, it is not that hard!"

Credit: 
Botanical Society of America

Pilot study suggests promise of new approach to treat adults with autism and depression

image: Medical University of South Carolina researcher Dr. Mark George, a pioneer in transcranial magnetic stimulation, demonstrates the technology.

Image: 
Brennan Wesley, Medical University of South Carolina

In a pilot study in adults with autism and depression, transcranial magnetic stimulation, or TMS, was effective in reducing depressive symptoms and had some effects on autistic symptoms, report researchers at the Medical University of South Carolina in Autism Research. This study suggests that TMS warrants further study as a potential treatment for adults with both depression and autism.

TMS has been used as a therapy for treatment-resistant depression and is a candidate treatment for depressed adults with autism. It uses a magnet placed on the scalp to generate electromagnetic pulses that activate neurons in the brain near the magnet.

The study was performed by a team of MUSC researchers led by M. Frampton Gwynette, M.D., director of the General Psychiatry Clinic, Project Rex and the Autism News Network, and Mark George, M.D., a pioneer in TMS, is the Layton McCurdy Endowed Chair in Psychiatry and director of the Brain Stimulation Lab.

People with autism have challenges with social interactions and communication. For example, they might not make eye contact, or they might hold one-way conversations. They can also have restricted interests, fixating on a singular interest, such as trains, for instance, and everything about them, as well as exhibiting repetitive behaviors, such as rocking or hand flapping when excited.

Such communication challenges can make autism very isolating, according to Gwynette, and render people with autism more prone to depression.

"You'll see very high rates of major depressive disorder in adults with autism, up to 26-50%," explained Gwynette. "When they have depression, it tends to be more severe than in typically developing individuals. They're also more likely to have suicidal ideation and more likely to attempt suicide. In addition, their depression is more likely to be refractory to treatment."

In Gwynette's experience, depressive symptoms can in turn make autism symptoms more challenging.

"We're really swimming upstream trying to treat this group," said Gwynette. "We also know that our standard antidepressant medications are not as effective or as well-tolerated in adults with autism because they're prone to irritability. Sometimes, the antidepressants can make their autism symptoms worse, so it's a really difficult thing to treat."

No treatments for core autism symptoms have been approved by the Food and Drug Administration, so new therapies to treat patients with both autism and depression are urgently needed.

In the study, the researchers recruited 13 adults ages 18-65 with depression and autism to participate in 25 daily TMS treatments. The treatments targeted the left dorsolateral prefrontal cortex, a brain region associated with depression.

After treatment, 70% of participants had a decrease in depressive symptoms, and 40% experienced remission. No changes were seen in self-reported autism symptoms. However, people who knew the participants detected decreases in repetitive behaviors, hyperactivity and irritability.

Overall, the repetitive TMS treatments were well-tolerated, with two participants withdrawing due to anxiety or irritability. Side effects included fatigue, headache and scalp discomfort.

Limitations of the study included its small number of participants and the fact that all participants received the treatment and knew about the treatment. Further conclusions will need to be derived from larger studies that randomize patients to either TMS or a sham intervention and "blind" them as to which treatment group they are assigned.

This study provides early evidence that TMS is safe for treating adults with autism and depression and shows promise in treating depression. These findings will need to be confirmed in future studies. More studies are also needed to elucidate the role of TMS in treating autism symptoms.

George and Gwynette are both optimistic about the future role of TMS in patients with autism and depression and eager to see the results of the next round of studies.

"Daily left prefrontal TMS, as we used in this study, appears to treat not just pure depression but also depression arising in the setting of autism and other disorders like Alzheimer's," said George. "These are promising results. I'm particularly intrigued by the improvements not just in depressive symptoms but also in other symptoms in the autism spectrum. That was unexpected. The true answer will come with a double-blind trial."

"I'm optimistic, as an autism specialist, that TMS will have a role in treating mental and comorbid conditions that come along with autism but also autism itself," said Gwynette.

Credit: 
Medical University of South Carolina

Housing prescriptions improve health outcomes in children, anxiety and depression in adults

BOSTON - Results of a study show that enrollment in a program that supports housing and health needs of medically complex families was associated with improved child health and parent mental health within six months. The program, Housing Prescription as Health Care (HPHC), helps families experiencing homelessness and housing instability in Boston and uses a multi-dimensional approach to address families' specific needs. Led by Children's HealthWatch at Boston Medical Center, the intervention reduced the share of children with fair or poor health by 32 percentage points in the first six months of the study.

Published in Health Affairs, the HPHC pilot program enrolled 78 families between 2016 and 2019 to determine whether the coordination of services that address housing, financial, legal, social, and health needs may improve health outcomes, when compared with current approaches.

"Our study aimed to explore how a multi-faceted intervention designed for families experiencing housing instability and homelessness might improve the health of children and their families," said Allison Bovell-Ammon, M.Div, director of policy strategy at Children's HealthWatch and the study's corresponding author. "Secure housing allows families to direct focus toward their health, while living in an environment that allows them to thrive."

At the beginning of the randomized controlled trial, 71 percent of families in the intervention group and 64 percent of those in the control group identified as homeless, while 58 percent and 55 percent report that they were behind on rent. At the six-month mark, 67 families completed the follow-up, and an analysis showed improvement in the share of children identified as having fair or poor health, and in the average anxiety and depression among parents in the intervention group. Average scores for anxiety and depression among adult family members declined by 1.38 and 1.04 points, using the Patient Health Questionnaire-2 for depression and the Generalized Anxiety Disorder two-item scale for anxiety.

Within the intervention group, there were also significant changes in child health status, and children who were housed at six months had a lower prevalence of developmental risk than those who were not. They also showed a decrease in being behind on rent, and both groups demonstrated significant reductions in their use of health care.

"Without significant new investment from the federal government, it will be difficult for health systems to adequately respond to housing needs," said Megan Sandel, MD, MPH, a pediatrician at Boston Medical Center, and coauthor on this study. "Our goal is to set families on a positive trajectory toward stability, but we can't do this alone."

Future analysis is necessary to assess the long-term impacts of this model, and to define the cost benefits associated with the direct benefits of improving child physical health and parent mental health services. This is important for understanding the ways in which tailored housing and health interventions may be able to produce a positive return on investment within pediatric populations.

Credit: 
Boston Medical Center

Researchers reveal new understandings of synthetic gene circuits

Recent discoveries by two research teams in the Ira A. Fulton Schools of Engineering at Arizona State University are advancing the field of synthetic biology.

Assistant Professor Xiaojun Tian and Associate Professor Xiao Wang conducted a year-long collaboration with their laboratory groups in the School of Biological and Health Systems Engineering, one of the six Fulton Schools. Results from their novel research into ways that engineered gene circuits interact with biological host cells have been published this week in the scientific journal Nature Chemical Biology.

Synthetic biology applies engineering methods to design new biological networks or redesign aspects of existing biological systems. It is a rapidly emerging field of study, and many significant advances have been made during the past 20 years.

Early work included creating synthetic gene circuits and placing them within natural host cells.

"But the concept of a circuit here is an abstract one," Wang says. "Imagine a sequence of genetic segments in which the first one encodes or produces a particular protein. That protein, in turn, can either activate or inhibit the expression or protein production from another segment in the genetic sequence. If you keep expanding this idea, you can imagine it's like a network."

It is this chain of influence or inducement that is functioning as a circuit, rather than the physical connections within the genetic sequence. However, previous research has focused on just the behaviors of engineered genetic circuits themselves, with little attention to the background or context represented by host cells.

"It is hard to predict how these interactions affect the functions of the engineered genetic circuits," Tian says, "not to mention how to control them and make the circuits operate as desired within complicated, real-life environments."

Indeed, these synthetic gene circuits generally work only in a laboratory environment, not in more lifelike conditions. And this limitation greatly inhibits the application of engineered gene circuits in clinical settings.

Seeking to advance the field in that practical direction, the new research by Tian and Wang explored the relationship between the synthetic gene circuits and their host cells. Specifically, they examined the impact of "memory" circuits implanted within host cells, and the influence of gene circuit "topologies," or the architecture of interconnections among circuit components, in relation to host cell growth.

In the context of this work, the idea of memory relates to the continuation of influence or inducement within an engineered gene circuit even with the absence of a stimulus.

"Think about a light switch in your house," Wang says. "The light stays on even when you remove your finger from the switch. We refer to that persistent state as memory."

Tian and Wang's new research revealed that memory circuit topologies are significantly influenced by host cell behavior.

"We verified that influences are exchanged between the gene circuit and the host cell," Tian says. "That is, the circuit impacts the host cell, which in return has an impact on the circuit. It's like a loop.

"But we also demonstrated that the impact on a circuit's functionality is dependent on its topology," he says. "So, one circuit topology shows better performance than others within a dynamic host environment."

Their discovery relating circuit topology to a host cell's impact on circuit function is a first in the field of synthetic biology, and it expands meaningful scientific understanding of these complex interactions.

"It paves the way for building robust, engineered gene circuits," Tian says. "These could one day enhance interventions against the metastasis of cancer, for example, by slowing the ability of cancer cells to translate their development."

Progressing from the research that Tian and Wang have published includes examining the impact of adding additional synthetic gene circuits or modules into host cells, which substantially elevates the level of complexity as modules compete for resources within the cellular system.

Wang says that the School of Biological and Health Systems Engineering within the Fulton Schools is particularly well-placed for discoveries in synthetic biology.

"We have a critical mass of dedicated people who are strategically invested in advancing this area of research for the long term," he says. "So, we are seeking to be a leader in this field."

Credit: 
Arizona State University

Ride-hailing linked to more crashes for motorists and pedestrians

Ride-hailing trips increase the number of crashes for motorists and pedestrians at pick-up and drop-off locations, reports a new study from researchers at the Columbia University Mailman School of Public Health. The research is the first to use data for individual ride-hailing trips, rather than comparing cities where ride-hailing is available to those where it is not available. The findings are published in the journal Injury Prevention.

Motor vehicle crashes are one of the main causes of death globally, and each year around 1.3 million people die on the roads. In the U.S., 33,654 were killed in 2018, and a further 2.3 million people were injured.

Ride-hailing services, such as Uber and Lyft, have facilitated over 11 billion trips in the U.S. since operations began in 2010. Several studies have identified that alcohol-involved motor vehicle crashes decrease when ride-hailing services become available in a city, but these studies also find no change in the overall number of crashes.

The team from Columbia Mailman School, along with collaborators from Oxford University in the United Kingdom, used data for 372 million ride-hail trips in New York City for 2017 and 2018. They identified areas of the city where a motor vehicle crash occurred, and then calculated the number of ride-hailing trips that originated nearby at the time of the crash and compared this to the number of ride-hailing trips that originated in the same location one week before the crash and one week afterwards. They performed this same procedure for taxis, and separated crashes according to the people who were injured--motorists, pedestrians, and cyclists.

The results demonstrated that increases in ride-hailing were linked to the rise in crashes in which motorists and pedestrians were injured. They did not find any link for cyclists crashes or for taxi trips.

"Ridesharing is changing the way we move around cities," said Christopher Morrison, PhD, assistant professor of epidemiology at Columbia Mailman School, and first author on the research. "It is becoming clear that the technology reduces alcohol-related crashes, but these benefits do not seem to extend to the overall number of crashes. These findings help explain why that might be--because the reductions in alcohol-related crashes are off-set by increases in other types of crashes."

The authors suggest that cities and ride-hailing companies can use this information to help prevent injuries. "There are so many rideshare trips every day in our cities, even tiny changes in risks can have a big impact on the total number of injuries," said Morrison. "In congested areas with large numbers of rideshare pick-ups and drop-offs, cities could consider installing taxi-rank style infrastructure to protect pedestrians and prevent crashes."

Credit: 
Columbia University's Mailman School of Public Health

Neither surgical nor cotton masks effectively filter SARS COV-2

Below please find a summary of new coronavirus-related content published today in Annals of Internal Medicine. The summary is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Neither surgical nor cotton masks effectively filter SARS COV-2

Free content: http://annals.org/aim/article/doi/10.7326/M20-1342

Both surgical and cotton masks were found to be ineffective for preventing the dissemination of SARS-CoV-2 from the coughs of patients with COVID-19. A study conducted at two hospitals in Seoul, South Korea, found that when COVID-19 patients coughed into either type of mask, droplets of virus were released to the environment and external mask surface. A brief research report is published in Annals of Internal Medicine.

During respiratory viral infection, face masks are thought to prevent transmission, leading health care experts to recommend their use during the COVID-19 pandemic. With a shortage of both N95 and surgical masks, which have been shown to prevent the spread of influenza virus, cotton masks have gained interest as a substitute. However, it is not known if surgical or cotton masks worn by patients with COVID-19 prevent contamination of the environment.

Researchers from Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea instructed 4 patients with COVID-19 to cough 5 times each onto a petri dish while wearing the following sequence of masks: no mask, surgical mask, cotton mask, and again with no mask. Mask surfaces were swabbed with aseptic Dacron swabs in the following sequence: outer surface of surgical mask, inner surface of surgical mask, outer surface of cotton mask, and inner surface of cotton mask. The researchers found SARS COV-2 on all surfaces. These findings suggest that recommendations to wear face masks to prevent the spread of COVID-19 may not be effective.

Media contacts : The lead author, Sung-Han Kim, M.D, can be reached at kimsunghanmd@hotmail.com or +82-2-3010-3305.

2. Nonmedical health care personnel are at highest risk for psychological distress during the COVID-19 outbreak

Free content: http://annals.org/aim/article/doi/10.7326/M20-1083

A survey of health care workers from two major tertiary institutions in Singapore who were caring for patients with COVID-19 suggests that nonmedical healthcare personnel are at highest risk for psychological distress related to the pandemic. A brief research report is published in Annals of Internal Medicine.

Researchers from National University Health System and Yong Loo Lin School of Medicine, National University of Singapore used a self-administered questionnaire to examine the psychological distress, depression, anxiety, and stress experienced by health care workers in Singapore in the midst of the COVID-19 outbreak and compared these outcomes between medically and non-medically trained hospital personnel. They found that the medically trained workers scored significantly lower on measures of depression and anxiety and impact of the event. Nonmedical health care workers had higher prevalence of anxiety even after adjustment for possible confounders. These findings are consistent with those of a recent COVID-19 study demonstrating that frontline nurses had significantly lower vicarious traumatization scores than non-frontline nurses and the general public. Reasons for this may include reduced accessibility to formal psychological support, less first-hand medical information on the outbreak, less intensive training on personal protective equipment and infection control measures.

Media contacts: Vijay K. Sharma, MD can be reached through Binny Tay at binny_tay@nuhs.edu.sg and Winnie Lim at Lim_winnie@nuhs.edu.sg

Also published today:

COVID-19: Peer Support and Crisis Communication Strategies to Promote Institutional Resilience

Albert W. Wu, MD, MPH1; Cheryl Connors, BSN, DNP2; George S. Everly, Jr, PhD1
Brief Research Report

Free content: http://annals.org/aim/article/doi/10.7326/M20-1236

Media Contact: Lead author, Albert W. Wu, MD, MPH, an be reached directly at awu@jhu.edu.

Credit: 
American College of Physicians

Researchers help expand search for new state of matter

A recent discovery by University of Arkansas physicists could help researchers establish the existence of quantum spin liquids, a new state of matter. They've been a mystery since they were first proposed in the 1970s. If proven to exist, quantum spin liquids would be a step toward much faster, next-generation quantum computing.

Scientists have focused attention and research on the so-called Kitaev-type of spin liquid, named in honor of the Russian scientist, Alexei Kitaev, who first proposed it. In particular, they have looked extensively at two materials - RuCl3 and Na2IrO - as candidates for this type. Both have small quantum spin numbers.

"Traditional candidates are pretty limited to only these two," said Changsong Xu, a researcher in the Department of Physics and first author of a paper published in the journal Physical Review Letters.

In their recent work, U of A physicists have greatly expanded the number of materials that might be candidates as Kitaev quantum spin liquids by looking at materials with higher quantum spin numbers, and by putting materials under physical strain to tune their magnetic states.

"Suddenly, we realize there are dozens of candidates we can propose," said Xu.

Quantum spin liquids are defined by their unusual magnetic arrangement. Magnets have a north and south pole, which combined are called dipoles. These are typically produced by the quantum spin of electrons. Inside a magnetic material, dipoles tend to all be parallel to each other (ferromagnetism) or periodically alternate their up and down direction (antiferromagnetism).

In the case of hypothetical quantum spin liquids, dipoles aren't as well ordered. Instead, they exhibit unusual ordering within a small distance of each other. Different ordering creates different types of spin liquids.

Xu, along with Distinguished Professor of Physics Laurent Bellaiche and colleagues in China and Japan, used computational models to predict a Kitaev quantum spin liquid state in materials such as chromium iodide and chromium germanium telluride. The work, which was supported by grants from the Arkansas Research Alliance and the Department of Energy, will give researchers many more materials to study in a search to prove the existence of quantum spin liquids, said Xu.

Credit: 
University of Arkansas