Culture

A Korean research team has developed a technology to fabricate an ultrathin material for electromagnetic interference(EMI) shielding. The research team, led by Koo Chong-Min, the head of the Materials Architecturing Research Center at the Korea Institute of Science and Technology (KIST, Acting President Yoon Seok-jin), announced that it had developed an ultrathin nanometer-thick film, using MXene, a new two-dimensional nanomaterial for EMI shielding. The research was jointly conducted with a team led by Professor Kim Sang-ouk of the Department of Materials Science and Engineering at Korea Advanced Institute of Science and Technology (KAIST, President: Shin Sung-chul) and a research team led by Professor Yury Gogotsi from Drexel University, USA.

Micrometer thick MXene films with high electrical conductivity, reported by Koo Chong-min in 2016, presented outstanding electromagnetic interference shielding. However, there were no technologies that could be used to directly apply MXene to highly integrated electronic devices, such as h5G communications and mobile devices.

*MXene: A 2D nano material with the same level of electrical conductivity (10,000 S/cm) as metals. Reported by a research team led by Koo Chong-Min, head of the Materials Architecturing Research Center, KIST, the higher a material's electrical conductivity, the higher its electromagnetic interference shielding performance (?Science 353, Issue 6304, pp. 1137-1140).

The KIST-KAIST-Drexel joint research team used self-assembly technique to fabricate an ultrathin MXene film with uniform atomic-scale thickness. MXene film is reported to have exceptional absolute electromagnetic shielding performance (shielding effectiveness relative to thickness and density) that is far greater than that of any other material reported to date.

By adding a volatile solution onto the surface of a diluted MXene solution, the research team was able to induce floating MXene flakes. Vertical convection, resulting from differences in surface tension, caused the self-assembly of the micron-sized MXene flakes, thereby creating a large-size ultrathin MXene film with uniform atomic-scale thickness. The research team found that MXene films layered to reach 55 nm in thickness provide 99% electromagnetic shielding efficiency. Ultrathin MXene films fabricated using the team's new technology can easily be transferred onto any substrate and layered multiple times for customized thickness, transmittance, and surface resistance.

"We used a self-assembly technique to fabricate an ultrathin Ti3C2Tx MXene film with uniform atomic-scale thickness. This technology helped to examine the electromagnetic shielding mechanism of nanometer-thick 2D nano materials and to develop an ultrathin electromagnetic shielding application technology for flexible electronics," said Koo Chong-Min, the head of the Materials Architecturing Research Center at KIST. "We believe that the ultrathin coated MXene technology can be applied to various electronic devices and be used for mass production, thereby facilitating research on the application of next-generation lightweight electromagnetic shielding and flexible and printable electronics."

Some new crop varieties are bred to be more nutritious. Others are more resilient, bred to tolerate harsher environmental conditions.

In a new study, researchers report a variety of wheat that combines enhanced nutrition with increased resilience. The researchers also tested a breeding method that could reduce costs and save time compared to traditional methods.

The newly developed wheat variety contains higher levels of a naturally occurring carbohydrate, called fructans.

"Wheat with increased fructan levels can be more climate-resilient in certain situations," says Lynn Veenstra, a researcher at Cornell University. "These situations include high salinity or cold temperatures".

Fructans are long chains of the sugar fructose. Unlike the fructose present in foods, such as high-fructose corn syrup, fructans cannot be digested by humans. This makes fructans a good source of soluble fiber.

Previous research has shown that consuming foods with higher fructan levels could also promote healthy gut bacteria.

In the US, a large portion of daily fructan intake comes from wheat products, such as bread. That makes developing high-fructan wheat important.

There's yet another advantage to using high-fructan wheat. "We wouldn't have to supplement wheat products with fructans or fiber from other sources," says Veenstra. "This wheat would already contain higher levels of fructans."

But breeding high-fructan wheat can be time-consuming and expensive. "The development of nutritionally improved wheat varieties often requires extensive resources," says Veenstra.

Typically, a process called phenotyping takes the most time. Phenotyping is the measurement of crop characteristics - like fructan levels or yield.

Phenotyping allows plant breeders to compare new and existing varieties of crops. For example, they can test if newer varieties have higher or lower fructan levels than existing crops. At the same time, they need to make sure other crop features - like yield or disease resistance - haven't been reduced.

A relatively new breeding method can expedite the development of new crop varieties. Veenstra and colleagues tested variations of this method, called genomic selection.

Genomic selection uses a relatively small 'training' set of individual plants. Researchers combine phenotyping and genetic data from this training set of plants. Then they use these data to train a statistical model.

Once trained, the statistical model can predict plant characteristics - like fructan levels - based solely on genetics.

"This allows crop breeding without needing to collect data on observed characteristics," says Veenstra.

Genomic selection saves time and resources in two ways. First, the training set of plants is relatively small. That allows phenotyping to be concluded quickly. Second, genetic testing can often be much quicker than measuring crop characteristics.

Ultimately, genomic selection can allow breeders to save both cost and time during the breeding process.

There are some caveats to using genomic selection, though. Inbreeding can happen, for instance, which can reduce crop diversity. Reduced diversity can make crops susceptible to diseases.

So Veenstra and her colleagues tested two different modes of genomic selection. They found that one method led to wheat with higher fructans while maintaining genomic diversity.

"I think this is the most important finding of this study," says Veenstra. "Genomic selection can be used for nutritional breeding."

Researchers still need to know more about the fructans in the new wheat variety. "We also want to determine how stable these fructans are during food processing," says Veenstra.

For example, yeast degrades different fructans at different rates. That would impact how much fructan ends up in a loaf of bread.

"I believe both wheat growers and consumers stand to benefit from high-fructan wheat," says Veenstra. "For wheat growers, high-fructan varieties have the potential to withstand climatic stress. For consumers, high-fructan wheat products may have positive impacts on gut-health."

As human activity shapes Earth's climate, animals must increasingly adapt to new environmental conditions. The thermoneutral zone -- the ambient temperature range in which mammals can maintain their body temperature without expending extra energy -- is a key factor in estimating a species' ability to survive in a warming world.

Reptiles and other ectotherms that rely on the environment to regulate their body temperature are believed to be more vulnerable to global warming in the tropics than in temperate climates. However, less is known about small tropical mammals, especially those active during the day.

To better understand if small tropical mammals also have increased vulnerability as their environments heat up, Danielle Levesque, University of Maine assistant professor of mammology and mammal health, and collaborators from the Universiti Malaysia Sarawak studied Bornean treeshrews. They measured the oxygen consumption of the wild-caught lesser treeshrews (Tupaia minor) over a range of temperatures, calculating the animals' resting metabolic rate and thermoneutral zone.

The team found that, like other treeshrew species, the animals exhibited more flexibility in body temperature regulation than other small mammals. This contradicts current assumptions that the upper limit of the thermoneutral zone between mammal species has little variation. The findings highlight the importance of further research on the energetics of mammals in the equatorial tropics.

Emotional, social and psychiatric problems in children and adolescents have been linked to higher levels of genetic vulnerability for adult depression.

University of Queensland scientists made the finding while analysing the genetic data of more than 42,000 children and adolescents from seven cohorts across Finland, the Netherlands, Norway, Sweden and UK.

Professor Christel Middeldorp said researchers have also found a link with a higher genetic vulnerability for insomnia, neuroticism and body mass index.

"By contrast, study participants with higher genetic scores for educational attainment and emotional wellbeing were found to have reduced childhood problems," Professor Middeldorp said.

"We calculated a person's level of genetic vulnerability by adding up the number of risk genes they had for a specific disorder or trait, and then made adjustments based on the level of importance of each gene.

"We found the relationship was mostly similar across ages."

The results indicate there are shared genetic factors that affect a range of psychiatric and related traits across a person's lifespan.

Professor Christel Middeldorp said around 50 per cent of children and adolescents with psychiatric problems, such as attention deficit hyper-activity disorder (ADHD), continue to experience mental disorders as adults, and are at risk of disengaging with their school community among other social and emotional problems.

"Our findings are important as they suggest this continuity between childhood and adult traits is partly explained by genetic risk," Professor Christel Middeldorp said.

"Individuals at risk of being affected should be the focus of attention and targeted treatment..

"Although genetic vulnerability is not accurate enough at this stage to make individual predictions about how a person's symptoms will develop over time, it may become so in the future, in combination with other risk factors.

"And, this may support precision medicine by providing targeted treatments to children at the highest risk of persistent emotional and social problems."

24 experts publish a research roadmap to help keep us mentally healthy through the pandemic

A new poll shows the public are already substantially concerned about their mental health in response to COVID-19

Experts call for real time monitoring of mental health to be rolled out urgently in UK and globally

Front line medical staff and vulnerable groups must be a priority for mental health support

Digital apps and remotely delivered programmes must be designed to protect our mental health

A new paper, to be published today in The Lancet Psychiatry (at 23.30hrs UK time on Wednesday 15 April), highlights an urgent need to tackle the harmful impacts of the COVID-19 pandemic on mental health and potentially the brain and calls for research on these areas to be central to the global response to the pandemic.

The paper warns that the COVID-19 pandemic could have a 'profound' and 'pervasive impact' on global mental health now and in the future, yet a separate recent analysis shows that so far, only a tiny proportion of new scientific publications on COVID-19 have been on mental health impacts.

The paper calls for more widespread mental health monitoring and better ways to protect against, and treat, mental ill health - both of which will require new funding and better coordination.

The general public already have substantial concerns about mental health in relation to the pandemic - according to an Ipsos MORI poll of 1099 members of the UK public, and a survey of 2198 people by the UK mental health research charity, MQ, that included many people with experience of mental health conditions.*

Both surveys were carried out in late March, the week lockdown measures were announced, to inform the Lancet Psychiatry paper. They showed the public had specific concerns related to COVID-19 including increased anxiety, fear of becoming mentally unwell, access to mental health services and the impact on mental wellbeing.

Paper author Professor Emily Holmes from the Department of Psychology, Uppsala University in Sweden, commented:

"We are all dealing with unprecedented uncertainty and major changes to the way we live our lives as a result of the coronavirus pandemic. Our surveys show these changes are already having a considerable impact on our mental health.

"Governments must find evidence-based ways to boost the resilience of our societies and find ways to treat those with mental ill health remotely to come out of this pandemic in good mental health.

"Front line medical staff and vulnerable groups such as the elderly and those with serious mental health conditions must be prioritised for rapid mental health support."

The paper calls for 'moment to moment' monitoring of anxiety, depression, self-harm, suicide, as well as other mental health issues in the UK and global population. It also calls for the rapid roll out of evidence-based programmes and treatments, which can be accessed by computer, mobile phone or other remote ways, to treat mental health conditions and increase resilience to keep people mentally healthy.

24 leading experts on mental health, including neuroscientists, psychiatrists, psychologists, public health experts and those with lived experience of a mental health condition, came together to create the roadmap that is published today. The expert group was established and supported by the Academy of Medical Sciences and the mental health research charity, MQ.

Professor Matthew Hotopf CBE FMedSci, Vice Dean Research at King's College London's Institute of Psychiatry Psychology & Neuroscience and Director NIHR Maudsley Biomedical Research Centre and one of the paper authors, said:

"This paper gives us a research roadmap to help protect our mental health at this incredibly difficult time and in the future.

"We are calling for real time monitoring of mental health of the population to develop effective treatments. This needs to be on a bigger scale than we have ever seen previously, and must be coordinated, targeted and comprehensive to give us an evidence based picture of what is really going on in societies around the world.

"Knowing what is happening in real time will allow us to respond by designing more user friendly and effective ways to promote good mental health while people are in their homes. Above all, however, we want to stress that all new interventions must be informed by top notch research to make sure they work."

The paper stresses there will be no 'one size fits all' approach to keeping us mentally healthy - and any new approaches will need to be tailored to particular groups of people, such as front line medical and social care staff.

It also calls for research to understand what makes people resilient in the face of this crisis, and actions to build resilience in society - whether supporting people to sleep well, be physically active or do activities that improve their mental health. The surveys* showed many people had already started activities to boost their mental health, such as prioritising family time, staying connected, connecting to nature and doing exercise.

Study author Kate King MBE, Adviser on lived experience to The Mental Health Act Review 2018, has personal experience of severe depression and said:

"It is not surprising that concerns reported in our surveys related to anxiety and isolation, or that social communication is seen by many as important in supporting good mental health. This highlights the vulnerability of those who have little contact with family or friends, and particularly those for whom relationships are abusive.

"The digital age, for all its problems, has bestowed a real gift: social media, the internet, video and phone meetings mean that social communication and research can continue in a way that would have been impossible even twenty years ago. We are all in this together so at this time it's essential that researchers continue to listen and work with people with lived, and living, experience to help those living with mental health challenges."

The paper notes that 'almost nothing is yet known with certainty about the impact of COVID-19 on the human nervous system'. As other coronaviruses have been shown to pass into the central nervous system, the paper recommends research to monitor and understand whether COVID-19 also has effects on the brain and nervous system. It calls for a new database to be set up to monitor any psychological or brain effects of COVID-19 and for research to look at the way the virus could enter the nervous system.

Study author Professor Ed Bullmore FMedSci, Head of Department of Psychiatry, University of Cambridge, said:

"We need an unprecedented research response if we are to limit the negative consequences of this pandemic on the mental health of our society now and in the future.

"To make a real difference we will need to harness the tools of our digital age - finding smart new ways to measure the mental health of individuals remotely, finding creative ways to boost resilience and finding ways to treat people in their homes. This effort must be considered central to our global response to the pandemic."

Previous outbreaks of infectious disease have been known to have an impact on mental health of the population, for example, the SARS epidemic was associated with a 30% increase in suicide in over 65s and 29% of healthcare workers experienced probable emotional distress.** Authors stressed that an increase in suicides as a result of the COVID-19 pandemic was not inevitable, but that monitoring and research is needed urgently.

The paper urges UK research funding agencies to work with researchers and people with experience of the mental health impacts of the pandemic to create a 'high-level co-ordination group' to ensure these mental health science research priorities are tackled as a matter of urgency.

Professor Rory O'Connor, Professor of Health Psychology, University of Glasgow, and one of the paper authors said:

"Increased social isolation, loneliness, health anxiety, stress and an economic downturn are a perfect storm to harm people's mental health and wellbeing.

"If we do nothing we risk seeing an increase in mental health conditions such as anxiety and depression, and a rise in problem behaviours such as alcohol and drug addiction, gambling, cyberbullying or social consequences such as homelessness and relationship breakdown. The scale of this problem is too serious to ignore, both in terms of every human life that may be affected, and in terms of the wider impact on society.

"Despite this situation making some of us feel trapped, it shouldn't make us feel powerless - we can make a difference if we act now. We are calling on funding bodies, research institutes and policy to act now to limit the impact the pandemic has on all our lives."

MINNEAPOLIS - Most people's blood pressure goes down during the night, which doctors call "dipping." But for some people, especially those with high blood pressure, their nighttime pressure stays the same or even goes up, called "reverse dipping." A new study shows that people with high blood pressure and reverse dipping may be more likely to have small areas in the brain that appear damaged from vascular disease and associated memory problems. The study is published in the April 15, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"These results add to the mounting evidence that shows the importance of vascular risk factors in contributing to memory problems," said study author Adam M. Brickman, Ph.D., of Columbia University in New York, N.Y. "They also point to the potential impact of preventing high blood pressure through efforts such as maintaining a healthy weight, being physically active and having a healthy diet."

The study involved 435 people with an average age of 59 who were enrolled in a study of aging in Venezuela. Their blood pressure was monitored for 24 hours at home with a device that took their pressure every 15 minutes during the day and every 30 minutes at night. They had brain scans to look for the small areas in the brain that appear damaged from vascular disease, called white matter hyperintensities. They also took tests of their memory and other thinking skills.

A majority of the people, 59%, had high blood pressure, which was defined as a 24-hour average of more than 130/80 mmHg, or were taking medication for high blood pressure. In half the people, the blood pressure dipped at night, in 40% it stayed the same, and in 10% it went up.

The researchers found that after adjusting for age, the people with high blood pressure and reverse dipping had over twice the amount of white matter hyperintensities as the other participants. They had an average of over six cubic centimeters of these white matter changes in the periventricular area of the brain, while the other participants had an average of 2.5 cubic centimeters or less.

Those with high blood pressure and the reverse dipping were also more likely to havehad lower scores on a memory test than the other participants. They had average scores of about 33 while the other participants had average scores of about 40. These differences in memory across groups were explained partially by the differences in blood pressure and dipping status.

"It appears that reverse dipping may amplify the effects of high blood pressure on people's cerebrovascular health and associated cognitive abilities," Brickman said.

The study looked at people at one point in time. It does not show that nighttime blood pressure increases cause the white matter changes and memory problems. It only shows the association.

"Longer studies that follow people over time will be needed to determine whether these factors do indeed lead to white matter changes and memory problems, although our initial findings are indeed consistent with this hypothesis," Brickman said.

He noted that the study included only middle-aged and older adults, so the results may not apply to people of other ages.

Interventional cardiologists should prioritize the conservation of medical resources, minimization of potential COVID-19 exposure and reallocation of resources, according to a paper published on April 9 in the Journal of Invasive Cardiology.

In the article, Le Bonheur Children's Hospital and the University of Tennessee Health Science Center Interventional Cardiologist Shyam Sathanandam, MD, suggests that catheterization laboratories should develop strategies for patient care by preserving and repurposing resources.

Sathanandam published the work after issuing a web-based survey to 56 unique U.S. centers, with the objective of describing current practice patterns and recommending potential resource allocation for congenital cardiac catheterization during the COVID-19 pandemic.

"We are faced with a fundamental question," said Sathanandam, who serves as the medical director of Le Bonheur Children's Interventional Cardiac Imaging and Interventional Catheterization Laboratory. "How can we, as pediatric and congenital interventional cardiologists, continue to care for patients who require intervention, while also being good stewards of limited medical resources and maintain an appropriate level of preparedness when we are uncertain about how this pandemic will affect our discipline?"

Medical Resource Utilization and Case Selection

The majority of survey respondents felt they had sufficient PPE to care for COVID-19 positive patients or PUIs. However, limited access to PPE and ventilators necessitates postponing elective catheterization cases to assist with the preservation of medical resources. The paper recommends using a multi-disciplinary clinical leadership team to triage case priority and timing - at present, only one-half of the reporting U.S. programs employed this strategy to review case selection.

While responding centers have canceled elective procedures with relative uniformity, centers in counties with 2,000 or more COVID-19 cases were more likely to delay certain cases including PDA closures in premature infants, pre-Glenn catheterization and coarctation stenting.

Minimizing Exposure

The responses suggest that many programs may not be adequately prepared for a surge of COVID-19 positive patients. Centers located in areas with higher number of COVID-19 cases have been more involved in a simulation of donning and doffing PPE equipment than low-prevalence centers (46.7% vs. 10.3%). Only 10.8% had converted a Cath lab to a negative pressure room for potential COVID-19 positive patient or PUI. The majority (65%) were only testing for COVID-19 prior to cardiac catheterization if the patient was symptomatic. Only 15% tested all patients prior to aerosol-generating procedures in the Cath lab.

However, responding centers were employing various strategies to reduce staff exposure to COVID-19.

31% did not allow fellow participation in cardiac catheterization cases.

76% minimized staff exposure through changes to the work and call schedule.

10.8% reassigned staff to provide clinical services outside the typical scope of practice.

41.7% had discussed or planned reassignment.

In addition, many facilities are minimizing staff presence in the Cath lab before and after airway manipulation in order to reduce potential exposure.

Resource Reallocation and Potential Repurposing

The primary way responding centers are conserving resources is by decreasing elective cases. "For subspecialists like pediatric interventional cardiologists, this raises the question of how best to utilize our clinical skills if the typical volume of patients with congenital heart is reduced," said Sathanandam.

This decision will vary by pediatric institution and may depend on geographic proximity to and relationship with adult centers. Pediatric interventional cardiologists will likely be deployed for services outside of the Cath lab depending on where resources are strained whether inpatient services, ICUs, emergency departments or vascular access teams.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summaries below are 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.

Clinician Education and Adoption of Preventive Measures for COVID-19: A Survey of a Convenience Sample of General Practitioners in Lombardy, Italy

Researchers from Humanitas Clinical and Research Center and Humanitas University; Milan, Italy surveyed 450 general practitioners (GPs) affiliated with their hospital to assess the challenges faced by GPs in the prevention and management of COVID-19 in a region with one of the largest populations affected by the COVID-19 outbreak. Read the full text: http://annals.org/aim/article/doi/10.7326/M20-1447.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Silvio Danese, MD, PhD, can be reached at sdanese@hotmail.com.

The Cochrane Review, "Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff," has been updated as a rapid review in response to the COVID-19 pandemic. The full review is now published in the Cochrane Library and freely available here.

Plain language summary - Protective clothes and equipment for healthcare workers to prevent them catching coronavirus and other highly infectious diseases

Background

Healthcare workers treating patients with infections such as coronavirus (COVID-19) are at risk of infection themselves. Healthcare workers use personal protective equipment (PPE) to shield themselves from droplets from coughs, sneezes or other body fluids from infected patients and contaminated surfaces that might infect them. PPE may include aprons, gowns or coveralls (a one-piece suit), gloves, masks and breathing equipment (respirators), and goggles. PPE must be put on correctly; it may be uncomfortable to wear, and healthcare workers may contaminate themselves when they remove it. Some PPE has been adapted, for example, by adding tabs to grab to make it easier to remove. Guidance on the correct procedure for putting on and removing PPE is available from organisations such as the Centers for Disease Control and Prevention (CDC) in the USA.

This is the 2020 update of a review first published in 2016 and previously updated in 2019.

What did we want to find out?

We wanted to know:

what type of PPE or combination of PPE gives healthcare workers the best protection;

whether modifying PPE for easier removal is effective;

whether following guidance on removing PPE reduced contamination;

whether training reduced contamination.

What did we find?

We found 24 relevant studies with 2278 participants that evaluated types of PPE, modified PPE, procedures for putting on and removing PPE, and types of training. Eighteen of the studies did not assess healthcare workers who were treating infected patients but simulated the effect of exposure to infection using fluorescent markers or harmless viruses or bacteria. Most of the studies were small, and only one or two studies addressed each of our questions.

Types of PPE

Covering more of the body leads to better protection. However, as this is usually associated with increased difficulty in putting on and removing PPE, and the PPE is less comfortable, it may lead to more contamination. Coveralls are the most difficult PPE to remove but may offer the best protection, followed by long gowns, gowns and aprons. Respirators worn with coveralls may protect better than a mask worn with a gown, but are more difficult to put on. More breathable types of PPE may lead to similar levels of contamination but be more comfortable. Contamination was common in half the studies despite improved PPE.

Modified PPE

Gowns that have gloves attached at the cuff, so that gloves and gown are removed together and cover the wrist area, and gowns that are modified to fit tightly at the neck may reduce contamination. Also, adding tabs to gloves and face masks may lead to less contamination. However, one study did not find fewer errors in putting on or removing modified gowns.

Guidance on PPE use

Following CDC guidance for apron or gown removal, or any instructions for removing PPE compared to an individual's own preferences may reduce self-contamination. Removing gown and gloves in one step, using two pairs of gloves, and cleaning gloves with bleach or disinfectant (but not alcohol) may also reduce contamination.

User training

Face-to-face training, computer simulation and video training led to fewer errors in PPE removal than training delivered as written material only or a traditional lecture.

Certainty of the evidence

Our certainty (confidence) in the evidence is limited because the studies simulated infection (i.e. it was not real), and they had a small number of participants.

What do we still need to find out?

There were no studies that investigated goggles or face shields. We are unclear about the best way to remove PPE after use and the best type of training in the long term.

Hospitals need to organise more studies, and researchers need to agree on the best way to simulate exposure to a virus.

In future, simulation studies need to have at least 60 participants each, and use exposure to a harmless virus to assess which type and combination of PPE is most protective.

It would be helpful if hospitals could register and record the type of PPE used by their workers to provide urgently needed, real-life information.

Search date

This review includes evidence published up to 20 March 2020.

Imagine a Fitbit that measures much more than steps, heart rate, and calories burned. It continually tracks all of the indicators of physiological health that currently require expensive and time-consuming analyses of blood plasma. The device is inexpensive, reliable, and powered by the same proteins that our bodies produce all day, every day. Although it sounds like a far-fetched concept by today's standards, James Galagan, a Boston University biomedical engineer, says research conducted in his lab could speed that device along from the drawing board to our daily lives.

A team of researchers from Galagan's BU lab and the University of Bordeaux was inspired by the one commercially successful biometric device that monitors a physiological function around the clock: the continuous glucose monitor, whose central task is performed by a protein obtained from a microbe that senses glucose.

"There are potentially millions of similar proteins," says team leader Galagan, a BU College of Engineering associate professor of biomedical engineering. "They can sense just about anything that affects our health. A primary reason we don't have more sensors like the glucose sensor is that the proteins needed to make those sensors haven't been identified."

So, Galagan's team, which includes BU College of Engineering faculty members Mark Grinstaff, Allison Dennis, and Catherine Klapperich, set out to find a few. Their findings, described in a paper published in Nature Communications, used a novel screening approach to identify the first known bacteria-derived sensor for detecting progesterone, a female hormone that plays a critical role in reproduction. The team then developed technology that translated the sensor's detection capabilities into an optical output, creating the first real-time, optical--and reversible--progesterone sensor.

The sensor's reversibility, says Galagan, allows it to generate continuous measurements as the hormone's level rises and falls in the body, similar to the glucose sensor. It also sets the sensor apart from existing antibody-based methods for measuring progesterone, which provide only a measurement from a single point in time.

In a test using artificial urine, the researchers found that the sensor, which can be equipped with an inexpensive and portable electronic reader for point-of-care applications, could detect progesterone with a specificity sufficient for clinical use. All of which suggests that it could be suitable for home use, replacing many laboratory-based tests for progesterone measurements that are required during the process of in vitro fertilization.

The study's big takeaway, says Galagan, is that it's a "first proof of principle that we could take an organism, identify a new sensing protein, isolate this protein from the bacterium, and engineer it into a sensor device that is applicable to point-of-care use. As far as we know, this has never been done before." He emphasizes that the newly developed approach does not use the bacteria as a sensor. Rather, it mines the bacteria for protein parts, isolates those parts, and then turns them into sensors that can be used for device engineering.

"Up to now, wearable technologies have focused primarily on macro [indicators] of health, such as heart rate, blood pressure, etc.," says Kenneth Lutchen, dean of BU's College of Engineering. "But we desperately need methods to predict disease emergence well before they create dangerous changes in such measures. Dr. Galagan and colleagues have shown proof of principle to provide real-time monitoring of microbial indicators of health status in a way that may radically transform our capacity to engage in predictive, at-home telemedicine. In principle, they can provide specific and sensitive early insight into disease emergence leading to early intervention, so that quality of life is improved while dramatically reducing healthcare cost."

The paper, whose technology was recently showcased at the kickoff symposium of the new BU Precision Diagnostics Center, provides a foundation for developing many more sensor devices, based on the same class of proteins. The researchers are currently building on that foundation--developing technology to immobilize and deploy such sensors, and working on ways to convert its detection capabilities into a direct electronic signal.

"Co-opting biology for technological purposes typically requires translating biological signals into a flow of photons or electrons," says Galagan. "We are working on that now."

"The great thing about this is the interdisciplinary nature of the research," says Klapperich, director of BU's Precision Diagnostics Center. "We have people doing computational work, molecular work, and people from materials science who are building the sensors. To work with so many people from different parts of the University is exciting."

Since their breakthrough was reported in Nature Communications, the researchers have already developed a second-generation approach that allows them to screen for parts from complex microbial samples, rather than from a single cultured bacterium. That "meta-genomic" screening can search such things as soil, or our own microbiome, essentially granting access to the full diversity of microbes for researchers looking for sensing parts. And because the approach identifies a specific gene as well as a sensing protein, it enables researchers to modify the transcription factor in ways that could make it more powerful or gain the ability to sense other chemical compounds, such as cortisol or estrogen.

"Right now, we are working with hormones," says Klapperich. "But this can work with all kinds of things. I can't wait until we get this ramped up."

The grand challenge ahead, Galagan says, is the deployment of such sensors to monitor our health and environment. His team hopes to use technology being built in labs around the world to develop a wide range of applications: from sensing coral health to monitoring physiological variables from sweat and interstitial fluid with a noninvasive or minimally invasive wearable device.

"This is really just the tip of the iceberg," says Galagan. "We are now positioned to mine the full diversity of microbes to engineer sensors for a wide array of health, biotechnological, and consumer applications. We hope that one day these sensors will be available on the shelves next to the continuous glucose monitor."

DALLAS - April 15, 2020 - Millions of Americans are being impacted by the psychological fallout from the COVID-19 pandemic and its economic aftermath, and large numbers may experience emotional distress and be at increased risk of developing psychiatric disorders such as depression and anxiety, according to a new article published this week in the New England Journal of Medicine.

The Perspective article, co-authored by Carol North, M.D., a UT Southwestern crisis psychiatrist who has studied survivors of disasters including the 9/11 terrorist attacks and Hurricane Katrina, calls on already stretched health care providers to monitor the psychosocial needs of their patients as well as themselves and fellow health care workers during this time.

"Almost everyone may experience some distress - some more than others," says North, a member of UT Southwestern's Peter O'Donnell Jr. Brain Institute who wrote the article with first author Betty Pfefferbaum, M.D., a psychiatrist at the University of Oklahoma College of Medicine. While conditions arising from a naturally occurring pandemic do not meet the criteria for trauma required to diagnose post-traumatic stress disorder (PTSD), depression and anxiety may result from this pandemic, according to the article, and some people may even become suicidal.?

Shortages of resources needed to treat patients, uncertain prognoses, and public health measures such as shelter-in-place orders - along with the resulting financial upheaval - are among the "major stressors that undoubtedly will contribute to widespread emotional distress and increased risk for psychiatric illness associated with COVID-19," the article says.

Certain groups will be more highly affected, according to the paper. That includes people who contract the disease, those at heightened risk including the elderly and people living with underlying health conditions, and those with preexisting psychiatric or substance abuse problems.

Health care providers are also especially vulnerable to emotional distress during the pandemic, the paper continues, given their risk of exposure amid shortages of personal protective equipment, long work hours, and involvement in the "emotionally and ethically fraught" need to allocate scarce resources when treating patients.

A recent review of the effects on quarantined people and health care providers in earlier disease outbreaks found stress, depression, insomnia, fear, anger, and boredom, among other problems, the article says.

While not directly comparable, many who went through other catastrophic events such as 9/11 or 1995's Oklahoma City bombings developed depression as well as PTSD, says North. After 9/11, 26 percent of the attack's survivors developed a new episode of major depression, according to an earlier study she co-authored. But COVID-19 is new territory, she emphasizes. "We haven't studied depression in pandemics."

The pandemic is creating a multilayered disaster, North says.

"There is the fear of being exposed and getting sick and dying, as well as loss of the lives of friends and relatives. Then there are secondary effects - lost paychecks and the economic woes. Rates of suicide go up in populations when economic times get bad. People get stressed more in general when times are bad," she says.

First responders and health care professionals should be trained to evaluate the psychosocial issues surrounding COVID-19, the report says, and health care systems need to pay attention to the stress level of their workers and alter assignments and schedules if needed.

Health care workers should ask patients about COVID-19-related stress factors, such as an infected family member and any depression or anxiety, and also check for vulnerabilities like a preexisting psychological condition. While some patients will need a referral for mental health care, others may benefit simply from support to improve their ability to cope.

Providers can offer suggestions for stress management. Because parents often underestimate their children's distress, they should be encouraged to have open discussions to address their children's reactions and concerns, the report adds.

People in quarantine or sheltering at home should try to reach out to loved ones electronically, North says. "People are now communicating more with loved ones and friends than they did before this crisis. For example, I did a Zoom meeting with my siblings recently for the first time. It was very nice."

Maintaining a schedule helps as well, she says: "Get up. Have breakfast. Get dressed."

And avoid following the COVID-19 news if that adds to stress, North says.

"Most people are resilient. Most people don't develop psychiatric illness after even horrible things, and most people who develop psychiatric illness can recover," she says. "After 9/11, only a third of the people directly exposed developed PTSD (35 percent in her study)."

Temple University Hospital has treated the first patient in the United States in the BREATHE clinical trial evaluating the impact of intravenous treatment with gimsilumab on mortality for patients with COVID-19 and acute respiratory distress syndrome (ARDS).

Gerard J. Criner, MD, FACP, FACCP, Chair and Professor of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine at Temple University and Director of the Temple Lung Center, is the principal investigator at Temple University Hospital for the adaptive, randomized, double-blind, placebo-controlled pivotal trial, which includes a planned interim analysis.

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients experience an overactive immune response that leads to lung injury, ARDS, and ultimately death.1 ARDS is a life-threatening inflammatory lung injury characterized by a lack of oxygen to the tissue and stiff lungs. It necessitates hospitalization and mechanical ventilation, and, when implementing standard of care, including mechanical ventilation, it has an overall mortality rate of 41%.6

Gimsilumab is a fully human monoclonal antibody targeting granulocyte macrophage-colony stimulating factor (GM-CSF), which is believed to be a key driver of lung hyper-inflammation. Previous evidence from SARS-CoV-1 animal models and emerging data from COVID-19 patients suggests that GM-CSF contributes to the immunopathology caused by SARS-CoV-2 infection in patients with or at risk of developing ARDS.2-5 GM-CSF has been found to be up-regulated in the serum of COVID-19 patients according to recent data from patients in China.2

“Emerging evidence suggests that GM-CSF may contribute to clinical worsening in COVID-19,” Dr. Criner said. “We are proud to participate in this clinical trial testing gimsilumab in this vulnerable patient population.”

Gimsilumab has been tested in numerous non-clinical studies and two prior clinical studies, including a four-week Phase 1 study in healthy volunteers which completed dosing in February. It has demonstrated a favorable safety and tolerability profile based on data collected to date.

The multi-site clinical trial will enroll up to 270 patients with a confirmed diagnosis of COVID-19 and clinical evidence of acute lung injury or ARDS. Subjects will be randomized 1:1 to receive either gimsilumab or placebo. The primary endpoint of the study is incidence of mortality by Day 43. Key secondary endpoints include the incidence and duration of mechanical ventilation use during the study, number of days in the intensive care unit, and number of days of inpatient hospitalization. The trial is sponsored by Roivant Sciences.

Pterosaurs were the largest animals ever to fly. They soared the skies for 160 million years--much longer than any species of modern bird. Despite their aeronautic excellence, these ancient flyers have largely been overlooked in the pursuit of bioinspired flight technologies. In a review published April 15 in the journal Trends in Ecology and Evolution researchers outline why and how the physiology of fossil flyers could provide ancient solutions to modern flight problems, such as aerial stability and the ability of drones to self-launch.

"There's a lot of really cool stuff in the fossil record that goes unexplored because engineers generally don't look to paleontology when thinking about inspiration for flight," says first author Liz Martin-Silverstone (@gimpasaura), a post-doctoral researcher and paleontologist at the University of Bristol. "If we're only looking at modern animals for inspiration, we're really missing a large degree of the morphology out there and ignoring a lot of options that I think could be useful."

Previously, engineers have largely focused on the physiology of modern birds and insects when designing aeronautic technology like drones and planes; they might not think to examine fossils that--by their nature--are often incomplete. However, Martin-Silverstone says there are a select few pterosaur fossils that provide extraordinarily deep insight into the anatomy of their wings, which is essential for understanding their flight capabilities.

"There are two or three absolutely amazingly preserved pterosaur fossils that let you see the different layers within the wing membrane, giving us insight into its fibrous components. Also, some fossils are preserved enough to show the wing attachments beneath the hip," she says. "While you don't know exactly the shape of the wing, by knowing the membrane attachments you can model the effectiveness of different wing shapes and determine which would have performed best in natural conditions." Analyzing the morphology and predicted flight mechanics of these ancient creatures has revealed novel tactics that don't exist in modern flyers.

Becoming airborne is one example. Launching into the air through a leap or jump, also known as ballistic launch, is standard throughout the animal kingdom. However, larger birds require a running start to gain enough momentum for lift-off. Pterosaurs, on the other hand, may have developed a method to launch from a stationary position despite some specimens weighing nearly 300 kilograms. One hypothesis, proposed by review co-author Mike Habib (@aeroevo) of the Dinosaur Institute at the Natural History Museum of Los Angeles County, suggests that the wing membrane and the robust muscle attachments in the wings allowed pterosaurs to generate a high-powered leap off of their elbows and wrists, giving them enough height to become airborne.

"Today, something like a drone requires a flat surface to launch and is quite restricted on how it actually gets into the air. The unique launch physiology of pterosaurs might be able to help solve some of these problems," Martin-Silverstone says.

Pterosaurs can also provide insights on how to prevent flight instability once in the air. Contrary to how sails can become unstable in a strong wind, pterosaurs evolved strategies to resist flutter of their broad wings. "So far we've struggled to design things like flight suits that can resist the pressures of flight. If we can understand how pterosaurs did it, for instance by understanding how their wing membrane was actually structured, then that's something we can use to answer modern engineering questions," she says.

These unique physiological elements aren't limited to pterosaurs, either. Other ancient flyers, like Microraptor, had feathered wings on both their arms and legs, while newly discovered dinosaur, Yi qi, had wings that combine feathers with a bat-like membrane--a body plan that has never been repeated since their extinction. As such, the authors say many flight strategies remain to be properly explored.

Martin-Silverstone suggests that if we combine our knowledge from flyers both living and extinct, we will have a much better chance of overcoming the hurdles still hindering man-made flight. She says: "We want biologists and engineers alike to reach out to paleontologists when they are looking to solving flight problems, as there might be something extinct that could help. If we limit ourselves to looking at the modern animals, then we're missing out on a lot of diversity that might be useful."

Most quantum computers being developed around the world will only work at fractions of a degree above absolute zero. That requires multi-million-dollar refrigeration and as soon as you plug them into conventional electronic circuits they'll instantly overheat.

But now researchers led by Professor Andrew Dzurak at UNSW Sydney have addressed this problem.

"Our new results open a path from experimental devices to affordable quantum computers for real world business and government applications," says Professor Dzurak.

The researchers' proof-of-concept quantum processor unit cell, on a silicon chip, works at 1.5 Kelvin - 15 times warmer than the main competing chip-based technology being developed by Google, IBM, and others, which uses superconducting qubits.

"This is still very cold, but is a temperature that can be achieved using just a few thousand dollars' worth of refrigeration, rather than the millions of dollars needed to cool chips to 0.1 Kelvin," explains Dzurak.

"While difficult to appreciate using our everyday concepts of temperature, this increase is extreme in the quantum world."

Quantum computers are expected to outperform conventional ones for a range of important problems, from precision drug-making to search algorithms. Designing one that can be manufactured and operated in a real-world setting, however, represents a major technical challenge.

The UNSW researchers believe that they have overcome one of the hardest obstacles standing in the way of quantum computers becoming a reality.

In a paper published in the journal Nature today, Dzurak's team, together with collaborators in Canada, Finland and Japan, report a proof-of-concept quantum processor unit cell that, unlike most designs being explored worldwide, doesn't need to operate at temperatures below one-tenth of one Kelvin.

Dzurak's team first announced their experimental results via the academic pre-print archive in February last year. Then, in October 2019, a group in the Netherlands led by a former post-doctoral researcher in Dzurak's group, Menno Veldhorst, announced a similar result using the same silicon technology developed at UNSW in 2014. The confirmation of this 'hot qubit' behaviour by two groups on opposite sides of the world has led to the two papers being published 'back-to-back' in the same issue of Nature today.

Qubit pairs are the fundamental units of quantum computing. Like its classical computing analogue - the bit - each qubit characterises two states, a 0 or a 1, to create a binary code. Unlike a bit, however, it can manifest both states simultaneously, in what is known as a "superposition".

The unit cell developed by Dzurak's team comprises two qubits confined in a pair of quantum dots embedded in silicon. The result, scaled up, can be manufactured using existing silicon chip factories, and would operate without the need for multi-million-dollar cooling. It would also be easier to integrate with conventional silicon chips, which will be needed to control the quantum processor.

A quantum computer that is able to perform the complex calculations needed to design new medicines, for example, will require millions of qubit pairs, and is generally accepted to be at least a decade away. This need for millions of qubits presents a big challenge for designers.

"Every qubit pair added to the system increases the total heat generated," explains Dzurak, "and added heat leads to errors. That's primarily why current designs need to be kept so close to absolute zero."

The prospect of maintaining quantum computers with enough qubits to be useful at temperatures much colder than deep space is daunting, expensive and pushes refrigeration technology to the limit.

The UNSW team, however, have created an elegant solution to the problem, by initialising and "reading" the qubit pairs using electrons tunnelling between the two quantum dots.

The proof-of-principle experiments were performed by Dr Henry Yang from the UNSW team, who Dzurak describes as a "brilliant experimentalist".

A little extra sugar can make us crave just about anything, from cookies to condiments to coffee smothered in whipped cream. But its sweetness doesn't fully explain our desire. Instead, new research shows this magic molecule has a back channel to the brain.

Like other sweet-tasting things, sugar triggers specialized taste buds on the tongue. But it also switches on an entirely separate neurological pathway - one that begins in the gut, Howard Hughes Medical Institute Investigator Charles Zuker and colleagues report on April 15, 2020 in the journal Nature.

In the intestines, signals heralding sugar's arrival travel to the brain, where they nurture an appetite for more, the team's experiments with mice showed. This gut-to-brain pathway appears picky, responding only to sugar molecules - not artificial sweeteners.

Scientists already knew sugar exerted unique control over the brain. A 2008 study, for example, showed that mice without the ability to taste sweetness can still prefer sugar. Zuker's team's discovery of a sugar-sensing pathway helps explain why sugar is special - and points to ways we might quell our insatiable appetite for it.

"We need to separate the concepts of sweet and sugar," says Zuker, a neuroscientist at Columbia University. "Sweet is liking, sugar is wanting. This new work reveals the neural basis for sugar preference."

Sweet stuff

The term sugar is a catchall, encompassing a number of substances our bodies use as fuel. Eating sugar activates the brain's reward system, making humans and mice alike feel good. However, in a world where refined sugar is plentiful, this deeply ingrained appetite can run amok. The average American's annual sugar intake has skyrocketed from less than 10 pounds in the late 1800s to more than 100 pounds today. That increase has come at a cost: Studies have linked excess sugar consumption to numerous health problems, including obesity and type 2 diabetes.

Previously, Zuker's work showed that sugar and artificial sweeteners switch on the same taste-sensing system. Once in the mouth, these molecules activate the sweet-taste receptors on taste buds, initiating signals that travel to the part of the brain that processes sweetness.

But sugar affects behavior in a way that artificial sweetener doesn't. Zuker's team ran a test pitting sugar against the sweetener Acesulfame K, which is used in diet soda, sweetening packets, and other products. Offered water with the sweetener or with sugar, mice at first drank both, but within two days switched almost exclusively to sugar water. "We reasoned this unquenchable motivation that the animal has for consuming sugar, rather than sweetness, might have a neural basis," Zuker says.

Sugar circuit

By visualizing brain activity when the rodents consumed sugar versus artificial sweetener or water, the researchers for the first time identified the brain region that responds solely to sugar: the caudal nucleus of the solitary tract (cNST). Found in the brain stem, separate from where mice process taste, the cNST is a hub for information about the state of the body.

The path to the cNST, the team determined, begins in the lining of the intestine. There, sensor molecules spark a signal that travels via the vagus nerve, which provides a direct line of information from the intestines to the brain.

This gut-to-brain circuit favors one form of sugar: glucose and similar molecules. It ignores artificial sweeteners -- perhaps explaining why these additives can't seem to fully replicate sugar's appeal. It also overlooks some other types of sugar, most notably fructose, which is found in fruit. Glucose is a source of energy for all living things. That could explain why the system's specificity for the molecule evolved, say study lead authors Hwei Ee Tan and Alexander Sisti, who are graduate students in Zuker's lab.

Previously, scientists speculated that sugar's energy content, or calories, explained its appeal, since many artificial sweeteners lack calories. However, Zuker's study showed this is not the case, since calorie-free, glucose-like molecules can also activate the gut-to-brain sugar-sensing pathway.

To better understand how the brain's strong preference for sugar develops, his group is now studying the connections between this gut-brain sugar circuit and other brain systems, like those involved in reward, feeding, and emotions. Although his studies are in mice, Zuker believes that essentially the same glucose-sensing pathway exists in humans.

"Uncovering this circuit helps explain how sugar directly impacts our brain to drive consumption," he says. "It also exposes new potential targets and opportunities for strategies to help curtail our insatiable appetite for sugar."