Culture

UChicago scientists uncover secrets to designing brain-like devices

Even with decades of unprecedented development in computational power, the human brain still holds many advantages over modern computing technologies. Our brains are extremely efficient for many cognitive tasks and do not separate memory and computing, unlike standard computer chips.

In the last decade, the new paradigm of neuromorphic computing has emerged, inspired by neural networks of the brain and based on energy-efficient hardware for information processing.

To create devices that mimic what occurs in our brain's neurons and synapses, researchers need to overcome a fundamental molecular engineering challenge: how to design devices that exhibit controllable and energy-efficient transition between different resistive states triggered by incoming stimuli.

In a recent study, scientists at the Pritzker School of Molecular Engineering (PME) at the University of Chicago were able to predict design rules for such devices.

Published November 10 in npj Computational Materials, the study predicted new ways of engineering and triggering changes in electronic properties in several classes of transition metal oxides, which could be used to form the basis of neuromorphic computing architectures.

"We used quantum mechanical calculations to unravel the mechanism of the transition, highlighting exactly how it happens at the atomistic scale," said Giulia Galli, Liew Family Professor at Pritzker Molecular Engineering, professor of chemistry, and co-author of the study. "We further devised a model to predict how to trigger the transition, showing good agreement with available measurements."

The impact of defects on electronic properties

The researchers investigated oxide materials that exhibit a change of electronic properties from a metal - which conducts electricity - to an insulator - which does not allow electricity to pass through - with various concentrations of defects. Defects can be missing atoms or some impurities that substitute for the atoms present in a perfect crystal.

To understand how defects change the state of the material from a metal to an insulator, the authors calculated the electronic structure at different defect concentrations using methods based on quantum mechanics.

"Understanding the intricate interdependency of the charge of these defects, the way atoms rearrange in the material and the way spin properties vary is crucial to controlling and eventually triggering the desired transition," said Shenli Zhang, a UChicago postdoctoral researcher and first author of the paper.

"Compared to traditional semiconductors, the oxide materials we studied require much less energy to switch between two totally different states: from a metal to an insulator," Zhang continued. "This feature makes these materials promising candidates to be used as artificial neurons or artificial synapses for large-scale neuromorphic architectures."

The study, published by Zhang and Galli, was conducted within the Quantum Materials for Energy Efficient Neuromorphic Computing (QMEENC) research center, which is funded by the Department of Energy and led by Prof. Ivan Schuller at UC San Diego.

"Understanding quantum materials will provide the key solutions to many scientific and technological problems, including the reduction of energy consumption in computational devices," said Schuller. "Given the complexity of quantum materials, the Edisonian approach of trial and error is no longer feasible, and quantitative theories are needed."

Such high-level theories are computationally demanding and have been the target of a long line of work.

"First principles calculations are playing a key role in driving the molecular engineering of neuromorphic computing. It is exciting to see the methods that we have developed for years coming to fruition," said Galli.

Credit: 
University of Chicago

Two genes regulate social dominance

image: Beau Alward, assistant professor of psychology at the University of Houston with a joint appointment in biology and biochemistry, has discovered two genes in the cichlid fish regulate social dominance.

Image: 
University of Houston

Rank in social hierarchy is a condition not solely claimed by humans. In the animal kingdom, male peacocks exhibit brightly colored plumes to illustrate dominance, and underwater, male fish show pops of bright colors to do the same. Despite the links identified between social status, physiology and behavior, the molecular basis of social status has not been known, until now.

"We discovered that two paralogous androgen receptor genes control social status in African cichlid fish," reports Beau Alward in the Proceedings of the National Academy of Sciences. Alward is an assistant professor of psychology at the University of Houston with a joint appointment in biology and biochemistry. Paralogs are duplicate genes; androgens are hormones like testosterone necessary for male sexual development.

"Testosterone binds to androgen receptors to exert its effects. What we found through genome editing is that the two genes encoding these receptors are required for different aspects of social status," said Alward. "This type of coordination of social status may be fundamental across species that rely on social information to optimally guide physiology and behavior."

To make his discovery, Alward used CRISPR/Cas9 gene editing, often referred to as "genetic scissors." The developers of the CRISPR method recently won the Nobel Prize in Chemistry for their invention. The technique allowed Alward to test what regulates physiological and behavioral changes.

Alward found that the two androgen-receptor (AR) paralogs - AR alpha (ARα) and AR beta (ARβ) that exist in cichlid fish - regulate traits that determine their survival and mating opportunities.

"We've shown that ARβ controls coloration, a super key function because females prefer to mate with those that are brightly colored, and that ARα controls behavior, which can change rapidly due to social cues and also determines mating success," said Alward.

This independent regulation of changes in color and behaviors by two receptors suggests there are independent mechanisms in the brain, and that allows Alward and his team to study them in isolation.

"The fact that these are independent implies that this is how flexible social status could be regulated by similar independent mechanisms in other species, including humans," said Alward.

Credit: 
University of Houston

Frugal science--a low-cost way to decontaminate PPE equipment

image: Widely available materials found in hardware stores, like those shown here, can be combined with ultraviolet lights found in shuttered research labs to enable low-cost decontamination of personal protective equipment, UD researchers say.

Image: 
Photo by Evan Krape

As the weather turns cooler and people move activities indoors, the number of new coronavirus (COVID-19) cases being reported in the United States is rising. This mirrors COVID-19 activity already seen in Europe and elsewhere across the globe.

Meanwhile, supply-chain problems are likely to cause limited supplies of filtering facepiece respirators, such as N95 masks. Yet strategies to decontaminate personal protective equipment, or PPE, remain unresolved in many hospitals with limited resources, both in the United States and abroad.

University of Delaware researchers, led by biomedical engineer Jason Gleghorn, have devised a system for decontaminating N95 masks using off-the-shelf materials available at any hardware store combined with ultraviolet type C (UV-C) lights found in shuttered research laboratories.

The UD-developed method offers comparable decontamination to more expensive methods at an affordable cost of about $50 in materials.

"We focused on frugal science -- how do you decontaminate PPE in a very simple way that is easily scalable for high throughput so that any health care facility can use it globally," said Gleghorn, an associate professor of biomedical engineering at UD.

A simple solution

The project was inspired earlier this year by Rachel Gilbert, a doctoral candidate in the Gleghorn lab, after she learned that friends in the medical field were repeatedly donning the same N95 mask day after day.

"This is more widely known today, of course, thanks to media publicity around this issue, but it got me thinking," said Gilbert.

She knew that UV-C light was routinely used for sterilization of various materials and equipment found in research labs. She wondered if this technique could be repurposed to decontaminate specialized masks, specifically for front line workers, in a low-cost, scalable way.

Ultraviolet germicidal irradiation (UVGI) has been validated as an effective method to decontaminate masks between use. UVGI systems are routinely used to decontaminate work environments and surgical suites, equipment and ambulances, but not all healthcare facilities have access to this expensive commercial sterilization equipment. That said, many UV-C bulbs are sitting idle in biosafety cabinets in university labs and research facilities that may be empty due to restrictions arising from the pandemic.

"Being able to provide something that can be on-site, as opposed to other methods that require surgical-suite UV systems costing tens of thousands of dollars or shipping masks out for decontamination and relying on them coming back in a timely manner, was important," added Gilbert.

When she discussed the idea with Gleghorn, a former firefighter and critical care medic, he immediately agreed. Gilbert called the effort a "huge, collaborative team effort" with many lab members collectively reading the literature, figuring out a solution and then going to the hardware store and creating the setup in the peak of the pandemic in April, all while working from home.

It only took a few weeks to solve the problem and put the system together, but securing peer-review took longer.

"Peer-review is an important part of the process. And while we wish it could move faster, there is a reason that innovations are rigorously examined in the scientific community," said Gleghorn. "We need to make sure the science is sound and the methods we develop are safe for people."

Using basic resources

Now, more about how the method works.

Lay two N95 masks side-by-side and it is impossible to tell which mask, if either, is contaminated with the novel coronavirus SARS-CoV-2 that causes the disease COVID-19. It's not like dirt, which you can see.

The system the research team constructed modifies common fluorescent light fixtures to hold and power the specialized UVGI light bulbs. That, in addition to specific light placement arrangements and tin foil covered cardboard for reflectors, creates multiple decontamination arrangements people can make. To confirm the UV-C lights were effective, the researchers did copious mathematical calculations and modeling to make sure the intensity of UV radiation that the repurposed lights emit was correct and the N95 masks received the correct UV exposure to decontaminate the masks.

The team developed freely downloadable build instructions in simple, easy-to-understand language with a lot of pictures and made them freely available on the Gleghorn lab website. The directions emphasize UV safety and focus on use in healthcare because of the need for specialized equipment, like a UV-C intensity meter. They also include precautions to measure UV-C intensity to ensure confidence the system is delivering the correct degree of UV intensity for enough time to decontaminate.

The detailed setup instructions include granular information, too, such as how far apart to space the masks for maximum effectiveness. This is critical because placing them too close together can create shadows that prevent comprehensive UV-C decontamination.

It is important to note that this is not an at-home device.

"You need proper personal protective equipment to work with UV light, which can disrupt DNA and pose safety concerns," said Gilbert.

This disruptive feature, however, is exactly what makes the UV-C light useful for decontaminating PPE.

"The UV light causes the virus DNA to break up and become ineffective," explained Gleghorn.

"So, the virus -- that little spiky thing you've seen by now -- might still stick to you, but the genetic material inside will be fragmented and will not have the correct machinery to replicate."

The research team enlisted Kim Bothi, former global engineering director and now executive director of UD's Center for Hybrid, Active, and Responsive Materials, to help think through ways to scale the project. She, too, has firefighting and emergency medical technician experience, not to mention expertise in integrating new ideas across a global spectrum.

Bothi used her global expertise and relationships to recruit volunteers across the world to translate the build instructions into multiple languages with regional-specific information. So far, the directions have been translated in French, Spanish, Portuguese, Russian and German. To-date, the build plans have been accessed over 1,060 times from users in 52 countries.

She also is working on a policy brief to share the research team's method with Delaware's congressional delegation. Additionally, Bothi is passing information along to colleagues working with the Kenya Medical Research Institute and in other nongovernmental organizations across the world.

"Like any other technology or innovation, our off-the-shelf decontamination method will only have impact if people are aware of it," she said.

The researchers concede that mask re-use is not ideal, but they also recognize that not all hospitals or other patient care facilities are equipped with enough PPE to meet demand in a crisis, so first responders may be required to reuse masks in emergency situations.

This includes doctors, nurses and emergency response personnel, but also extends to staff behind-the-scenes who may be cleaning, disinfecting or preparing spaces for patient care. Beyond hospitals, PPE is worn in residential facilities and rural clinics around the globe that may have limited access to resources.

In a perfect world, Bothi would like to see academic and research institutions working hand-in-hand with hospital systems to collaboratively put these off-the-shelf systems in place where they are needed.

Kenya, for example, is a country in sub-Saharan Africa that has a fairly robust system for healthcare. Yet, the country is still facing incredible shortages of PPE just like here in the United States.

"The bigger benefit will be translating this to other areas of the world, where they don't have the resources," said Gleghorn.

Credit: 
University of Delaware

Psychological status rather than cognitive status is associated with incorrect perception of risk of falling in patients with moderate stage dementia

image: Dr. Klaus Hauer

Image: 
Dr. Klaus Hauer

Heidelberg, November 10, 2020: Dementia is associated with an impaired self-perception with potentially harmful consequences for health status and clinical risk classification in this patient group with an extraordinary high risk of falling. A new study published in the Journal of Alzheimer's Disease indicates that psychological factors such as anxiety or fear of falling, cognitive sub-performances such as executive functions, as well as behavioral strategies such as support seeking and interplay with other risk factors should be considered when risk of falling is documented in PWD.

"PwD show a threefold incidence of falls and a doubled incidences of severe falls as compared to peers without dementia and an inaccurate risk-perception and associated behavioral consequences may represent a link to this traumatic event in old age", explained lead investigator Klaus Hauer, PhD, Department of Geriatric Research at the Bethanien Hospital/Geriatric center at the Heidelberg University, Germany.

Patients with neurodegenerative diseases often present with poor self-awareness that may exacerbate their already jeopardized decision-making and behavior. With respect to risk of falling and functional capacities, deficits in specific cognitive sub-performances such as executive function/working memory showed significant discriminative validity for fallers vs. non-fallers and documented restricted judgement in own motor planning while executive function also influenced overestimation of own functional abilities among fallers suggesting a potential mechanism for falling already in persons without cognitive impairment.

However other factors such as psychological- or functional status or adaptive behavioral strategies have shown high associations with incorrect fall risk perception in study samples without cognitive impairment or unspecified cognitive status and those factors may interfere with, facilitate, compensate or even superimpose the effects of impaired cognition. Studies on mismatch of subjective vs objective risk with focus on falls have so far not been published in PWD representing a highest risk group for falls.

"Although 2/3 of the study participants had a mismatch between subjective and objective risk, study results indicate that cognitive impairment per se does not lead to underestimation of risk of falling while results of specific cognitive subdomains such as less impaired executive and memory function was only associated with overestimation of risk in this group of persons with beginning to moderate stage dementia.

Other factors such as anxiety, concerns about falling, activity avoidance, history of falls, or support seeking strategies represented more relevant parameters to discriminate between match or mismatch of objective vs subjective risk of falling", commented co-investigator Ilona Dutzi, PhD, Department of Geriatric Research at the Bethanien Hospital/ Geriatric center at the Heidelberg University, Germany.

Results, especially so in the largest subgroup with underestimation of risk, may indicate a rather less negative view on life perspectives and less emotional and behavioral reactivity to adverse events such as falls, leading to a higher quality of life and allowing to be more physically active thus counterbalancing objective risks. Results seem encouraging, as they translate mismatch classification (inadequate perception) into a positive direction, documenting unexpected remaining resources in a large subgroup of persons with moderate dementia.

While traumatic fall events are associated to fear of falling, the study findings indicate that a mismatch of subjective and objective risk seems not to be a general and high impact factor for risk or falling even in PwD, allowing fewer concerns to motivate such persons to take part in active prevention programs with increased risk exposure such as exercise programs.

Credit: 
IOS Press

Induced liver regeneration enhances CRISPR/Cas9-mediated gene repair

image: journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications.

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, November 9, 2020--Use of thyroid hormone to boost hepatocyte proliferation enhanced the efficiency of CRISPR/Cas9-mediated gene correction in the mouse liver. This dietary induction of hepatocyte regeneration may be a viable clinical strategy to enhance gene repair in the liver, according to the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free through December 9, 2020.

The study was done in a mouse model of tyrosinemia type 1. "In neonatal mice, a gene correction frequency of ~10.8% of hepatocytes was achieved," said Qing-Shuo Zhang, Oregon Health & Science University and coauthors. "The efficiency in adult mice was significantly lower at ~1.6%."

Use of thyroid hormone T3 to temporarily induce hepatocyte division in the adult mice led to a significant increase in the gene correction efficiency to 3.5%.

"The promise of gene editing for human gene therapy is being realized initially with ex vivo manipulation of stem cells and lymphocytes and in small organ targets like the retina. If gene editing becomes efficient enough to correct genetic defects in vivo in the liver, it could then be used to treat a much wider variety of disorders. The work in this paper moves the field closer to that goal," according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

Getting single-crystal diamond ready for electronics

image: Shape of mosaic single crystal diamond substrate before and after plasma-assisted polishing.

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Osaka University

Osaka, Japan - Silicon has been the workhorse of electronics for decades because it is a common element, is easy to process, and has useful electronic properties. A limitation of silicon is that high temperatures damage it, which limits the operating speed of silicon-based electronics. Single-crystal diamond is a possible alternative to silicon. Researchers recently fabricated a single-crystal diamond wafer, but common methods of polishing the surface—a requirement for use in electronics—are a combination of slow and damaging.

In a study recently published in Scientific Reports, researchers from Osaka University and collaborating partners polished a single-crystal diamond wafer to be nearly atomically smooth. This procedure will be useful for helping diamond replace at least some of the silicon components of electronic devices.

Diamond is the hardest known substance and essentially does not react with chemicals. Polishing it with a similarly hard tool damages the surface and conventional polishing chemistry is slow. In this study, the researchers in essence first modified the quartz glass surface and then polished diamond with modified quartz glass tools.

"Plasma-assisted polishing is an ideal technique for single-crystal diamond," explains lead author Nian Liu. "The plasma activates the carbon atoms on the diamond surface without destroying the crystal structure, which lets a quartz glass plate gently smooth away surface irregularities."

The single-crystal diamond, before polishing, had many step-like features and was wavy overall, with an average root mean square roughness of 0.66 micrometers. After polishing, the topographical defects were gone, and the surface roughness was far less: 0.4 nanometers.

"Polishing decreased the surface roughness to near-atomic smoothness," says senior author Kazuya Yamamura. "There were no scratches on the surface, as seen in scaife mechanical smoothing approaches."

Furthermore, the researchers confirmed that the polished surface was unaltered chemically. For example, they detected no graphite—therefore, no damaged carbon. The only detected impurity was a very small amount of nitrogen from the original wafer preparation.

"Using Raman spectroscopy, the full width at half maximum of the diamond lines in the wafer were the same, and the peak positions were almost identical," says Liu. "Other polishing techniques show clear deviations from pure diamond."

With this research development, high-performance power devices and heat sinks based on single-crystal diamond are now attainable. Such technologies will dramatically lower the power use and carbon input, and improve the performance, of future electronic devices.

Credit: 
Osaka University

New research identifies 'triple trouble' for mangrove coasts

image: Mangroves with dense roots trap mud more effectively.

Image: 
Barend van Maanen

Some of the world's most valuable ecosystems are facing a "triple threat" to their long-term durability and survival, new research shows.

The study found that mangrove forests, their large biodiversity and the coastal protection they provide are under pressure from three distinct threats - sea-level rise, lack of mud and squeezed habitats.

The research, conducted by an international team of experts including Dr Barend van Maanen from the University of Exeter, identifies not only how these coastal forests get pushed against their shores, but also what causes the loss of their diversity.

It shows the negative effects of river dams that decrease the supply of mud that could otherwise raise mangrove soils, while buildings and seawalls largely occupy the space that mangroves require for survival.

The study is published in Environmental Research Letters.

Coastal mangrove forests are valuable, highly biodiverse ecosystems that protect coastal communities against storms.

Mangroves withstand flooding by tides and capture mud to raise their soils. But as the mangrove trees cannot survive if they are under water for too long, the combination of sea-level rise and decreasing mud supply from rivers poses a serious threat.

New computer simulations show how coastal forests retreat landward under sea-level rise, especially in coastal areas where mud in the water is declining. The simulations include interactions among tides, mud transport and, for the first time, multiple mangrove species.

Dr van Maanen, senior lecturer at the University of Exeter and supervisor of the project, said: "Both mangrove coverage loss and diversity loss go hand in hand when that landward retreat is limited by expanding cities, agriculture or flood protection works."

The model also shows that mangrove trees with dense roots trap mud more effectively and can stop it from reaching forest areas further inland.

Danghan Xie, PhD researcher at Utrecht University and lead author of the study said: "This makes the more landward-located trees flood for longer periods of time, an effect that is intensified by sea-level rise.

"Increasing landward flooding then seriously reduces biodiversity.

"Human land use prevents the mangroves 'escaping' flooding by migrating inland, narrowing the mangrove zone and further endangering biodiversity."

A narrow mangrove zone is much less effective in protecting the coast against storms, or in the worst case loses its protective properties altogether.

Co-author Dr Christian Schwarz, environmental scientist at the University of Delaware, added: "The loss of mangrove species will have dramatic ecological and economic implications, but fortunately there are ways to help safeguarding these ecosystems.

"It is essential to secure or restore mud delivery to coasts to counter negative effects of sea-level rise.

"For coasts where mud supply remains limited, removal of barriers that obstruct inland migration is of utmost importance to avoid loss of mangrove forests and biodiversity."

Credit: 
University of Exeter

Empathy and perspective taking: How social skills are built

Understanding what other people want, how they feel, and how they see the world is becoming increasingly important in our complex, globalised society. Social skills enable us to make friends and create a network of people who support us. But not everyone finds it easy to interact with other people. One of the main reasons is that two of the most important social skills - empathy, i.e. being able to empathise with the other person's emotions, and the ability to take a perspective, i.e. being able to gain an information by adopting another person's point of view - are developed to different degrees.

Researchers have long been trying to find out what helps one to understand others. The more you know about these two social skills, the better you can help people to form social relationships. However, it still not exactly clear what empathy and perspective taking are (the latter is also known as "theory of mind"). Being able to read a person's emotions through their eyes, understand a funny story, or interpret the action of another person--in everyday life there are always social situations that require these two important abilities. However, they each require a combination of different individual subordinate skills. If it is necessary to interpret looks and facial expressions in one situation, in another it may be necessary to think along with the cultural background of the narrator or to know his or her current needs.

To date, countless studies have been conducted that examine empathy and perspective taking as a whole. However, it has not yet been clarified what constitutes the core of both competencies and where in the brain their bases lie. Philipp Kanske, former MPI CBS research group leader and currently professor at the TU Dresden, together with Matthias Schurz from the Donders Institute in Nijmegen, Netherlands, and an international team of researchers, have now developed a comprehensive explanatory model.

"Both of these abilities are processed in the brain by a 'main network' specialised in empathy or changing perspective, which is activated in every social situation. But, depending on the situation, it also involves additional networks," Kanske explains, referring to the results of the study, which has just been published in the journal Psychological Bulletin. If we read the thoughts and feelings of others, for example, from their eyes, other additional regions are involved than if we deduce them from their actions or from a narrative. "The brain is thus able to react very flexibly to individual requirements."

For empathy, a main network that can recognise acutely significant situations, for example, by processing fear, works together with additional specialised regions, for example, for face or speech recognition. When changing perspective, in turn, the regions that are also used for remembering the past or fantasising about the future, i.e., for thoughts that deal with things that cannot be observed at the moment, are active as the core network. Here too, additional brain regions are switched on in each concrete situation.

Through their analyses, the researchers have also found out that particularly complex social problems require a combination of empathy and a change of perspective. People who are particularly competent socially seem to view the other person in both ways­--­on the basis of feelings and on the basis of thoughts. In their judgement, they then find the right balance between the two.

"Our analysis also shows, however, that a lack of one of the two social skills can also mean that not this skill as a whole is limited. It may be that only a certain factor is affected, such as understanding facial expressions or speech melody," adds Kanske. A single test is therefore not sufficient to certify a person's lack of social skills. Rather, there must be a series of tests to actually assess them as having little empathy, or as being unable to take the other person's point of view.

The scientists have investigated these relationships by means of a large-scale meta-analysis. They identified, on the one hand, commonalities in the MRI pattern of the 188 individual studies examined when the participants used empathy or perspective taking. This allowed the localisation of the core regions in the brain for each of the two social skills. However, results also indicated how the MRI patterns differed depending on the specific task and, therefore, which additional brain regions were used.

Credit: 
Max Planck Institute for Human Cognitive and Brain Sciences

Efforts needed to better integrate family caregivers into health care teams

Integrating family caregivers into a patient's health care team can help improve care quality and the quality of life for both patients and their families, yet family caregivers face significant barriers coordinating their efforts with the formal health care team, according to a new RAND Corporation study.

New policies and approaches may be needed to overcome those hurdles, such as rules to identify and record information on family caregivers, and incentives to encourage providers to engage with family caregivers.

Additional efforts suggested by researchers are investing in programs that provide supportive services for family caregivers, as well as expanding access to and funding for care coordinators to support caregivers and connect them to a family member's clinical information.

"Family caregivers too often are treated as secondary members of the care team, with little direct access to the formal health care providers," said Esther M. Friedman, lead author of the report and a sociologist at RAND, a nonprofit research organization. "We hope our research helps start a conversation about ways to better integrate family caregivers into the health care team."

Other strategies recommended by researchers are implementing training programs for providers and caregivers to facilitate effective communication, and encouraging leaders to develop technologies that foster caregiver-provider care integration and information sharing.

An estimated 53 million family and friends provide care assistance to loved ones in the United States, an increase of 9.5 million caregivers from 2015 to 2020. These family members typically provide assistance with everyday activities such as eating, bathing, dressing, driving and taking medications.

Family caregivers have direct and frequent access to loved ones with caregiving needs. More than one-third of care recipients live with their family caregiver and 55 percent of caregivers visit the care recipient more than once a week.

These regular interactions allow family caregivers to monitor changes in health and care needs on a more regular basis than would be possible for formal health care providers.

To better understand the barriers that face family caregivers and how to mitigate those obstacles, RAND researchers reviewed the research literature and interviewed 13 experts from diverse stakeholder groups. The study is among the first to focus in depth on integrating family caregivers into the health care team by incorporating interviews with payers, providers and caregiver advocates.

RAND researchers defined family caregiver integration to include communication, collaboration and coordination with providers, broadly defined as individuals or organizations that deliver care or health care services or help coordinate care for people with caregiving needs. The health care team may include physicians, nurses, social workers, care coordinators, and private sector health and care service providers.

"The goal of this study is to identify promising policy directions and provide a blueprint for assessing, developing and implementing policies to improve integration of family caregivers into the health care team," said study co-author Patricia K. Tong, a RAND economist.

The report found that barriers to integration fell under four themes: identifying caregivers, communication and information-sharing, time limitations and competing demands, and trust and cultural barriers.

Researchers say that future work is needed to expand and assess policy approaches through stakeholder engaged consensus methods, assess the availability of evidence-based research, assess each approach on metrics of feasibility and impact, evaluate approaches for their cost effectiveness, and build consensus on how best to implement the most-promising choices.

Credit: 
RAND Corporation

Do consumers enjoy events more when commenting on them?

Researchers from Rutgers University and New York University published a new paper in the Journal of Marketing that explores the phenomenon of user-generated content during experiences.

The study, forthcoming in the Journal of Marketing, is titled "Generating Content Increases Enjoyment by Immersing Consumers and Accelerating Perceived Time" and is authored by Gabriela Tonietto and Alixandra Barasch.

"Enjoy the moment. Put down your phone." The media is full of headlines telling consumers that to truly enjoy themselves and their experiences, the first step is to ditch their cellphones. Yet this advice often appears to fall on deaf ears. Major events routinely coincide with huge surges in social media posts as millions tweet during experiences like the Super Bowl and World Cup. This poses something of a conundrum. People clearly generate large amounts of content--remarking on what they are currently doing, hearing, and seeing--as experiences unfold, but is this behavior helpful or harmful?

The research team systematically examined the effect of generating content on people's feelings of immersion in their experiences and discovered that this common behavior can actually improve experiences. Across a series of nine studies, results indicate that when people create content about unfolding experiences, they ultimately enjoy the experience more, because creating content increases engagement and makes time feel like it is "flying." Tonietto explains that, "In contrast to popular press advice, this research uncovers an important benefit of technology's role in our daily lives ... by generating content relevant to ongoing experiences, people can use technology in a way that complements, rather than interferes with, their experiences."

The researchers tested the potential benefits of generating content across a variety of experiences including the Super Bowl halftime show, holiday celebrations, a dance performance, virtual safaris and bus tours, and a horror film. During all these experiences, which differed in their pleasantness and duration (from a few minutes to multiple hours), they consistently found that generating content led people to feel more immersed in their experiences and to feel as though time was passing more quickly. Interestingly, this occurred whether people tended to say positive or negative things about the experience. Moreover, generating content generating content increased people's enjoyment of positive experiences, though this effect did not occur for negative experiences.

Importantly, just because a consumer is on her phone does not mean that she's distracted or unable to become absorbed in her experience. Barasch says "We found that when people choose to generate content, they tend to do so in a constructive way. On average, people create content that is directly relevant to their current experience, with positive effects on their evaluations of the experience. However, when people use their technology to generate irrelevant content, this behavior is no longer beneficial. That is, only when people communicate about the unfolding experience itself does content creation increase immersion and enjoyment."

Interestingly, marketers often encourage consumers to communicate about their events and experiences. For example, companies may use branded hashtags, offer discounts and rewards tied to posting on social media, or use sharing platforms customized for individual events. The study tested two potential strategies for firms to encourage content creation: 1) an incentive (i.e., reward) for generating content; and 2) a norm nudge, where consumers are informed of how common this behavior is among other consumers. As expected, both strategies effectively increased content creation. Even more importantly, consumers who were incentivized or motivated by social norms to generate content reaped the same experiential benefits as those who created content organically. That is, content generation in response to a firm's encouragement can still lead consumers to feel more immersed in the experience and to enjoy it more. These findings illustrate how leveraging consumer content creation can mutually benefit marketers and consumers alike by improving experiences.

So, the next time you're advised to put down your phone in order to truly live "in the moment," remember that this depends on how you're using your phone. If you're posting about the last movie you saw while ignoring the person across the dinner table from you, then this could potentially detract from your current experience. But if you're using your device to comment, joke, or even complain about your current experience, then this research indicates you may be more engaged and enjoy that experience more than if you kept your phone in your pocket.

Credit: 
American Marketing Association

Microbe "rewiring" technique promises a boom in biomanufacturing

image: A two-liter bioreactor containing an P. putida culture that has undergone metabolic rewiring to produce indigoidine all the time.

Image: 
Berkeley Lab

Researchers from Lawrence Berkeley National Laboratory (Berkeley Lab) have achieved unprecedented success in modifying a microbe to efficiently produce a compound of interest using a computational model and CRISPR-based gene editing.

Their approach could dramatically speed up the research and development phase for new biomanufacturing processes, and get cutting-edge bio-based products such as sustainable fuels and plastic alternatives on the shelves faster.

The process uses computer algorithms - based on real-world experimental data - to identify what genes in a "host" microbe could be switched off to redirect the organism's energy toward producing high quantities of a target compound, rather than its normal soup of metabolic products.

Currently, many scientists in this field still rely on ad hoc, trial-and-error experiments to identify what gene modifications lead to improvements. Additionally, most microbes used in biomanufacturing processes that produce a nonnative compound - meaning the genes to make it have been inserted into the host genome - can only generate large quantities of the target compound after the microbe has reached a certain growth phase, resulting in slow processes that waste energy while incubating the microbes.

The team's streamlined metabolic rewiring process, coined "product/substrate pairing," makes it so the microbe's entire metabolism is linked to making the compound at all times.

To test product/substrate pairing, the team performed experiments with a promising emerging host - a soil microbe called Pseudomonas putida - that had been engineered to carry the genes to make indigoidine, a blue pigment. The scientists evaluated 63 potential rewiring strategies and, using a workflow that systematically evaluates possible outcomes for desirable host characteristics, determined that only one of these was experimentally realistic. Then, they performed CRISPR interference (CRISPRi) to block the expression of 14 genes, as guided by their computational predictions.

"We were thrilled to see that our strain produced extremely high yields of indigoidine after we targeted such a large number of genes simultaneously," said co-lead author Deepanwita Banerjee, a postdoctoral researcher at the Joint BioEnergy Institute (JBEI), which is managed by Berkeley Lab. "The current standard for metabolic rewiring is to laboriously target one gene at a time, rather than many genes all at once," she said, noting that before this paper there was only one previous study in metabolic engineering in which the authors targeted six genes for knockdown. "We have substantially raised the upper limit on simultaneous modifications by using powerful CRISPRi-based approaches. This now opens up the field to consider computational optimization methods even when they necessitate a large number of genetic modifications, because they can truly lead to transformative output," said Banerjee.

Co-lead author Thomas Eng, a JBEI research scientist, added, "With product/substrate pairing, we believe we can significantly reduce the time it takes to develop a commercial-scale biomanufacturing process with our rationally designed process. It's daunting to think of the sheer number of research years and people hours spent on developing artemisinin (an antimalarial) or 1-3,butanediol (a chemical used to make plastics) - about five to 10 years from the lab notebook to pilot plant. Dramatically reducing R&D time scales is what we need to make tomorrow's bioeconomy a reality," he said.

Examples of target compounds under investigation at Berkeley Lab include isopentenol, a promising biofuel; components of flame-retardant materials; and replacements for petroleum-derived starter molecules used in industry, such as nylon precursors. Many other groups use biomanufacturing to produce advanced medicines.

Principal investigator Aindrila Mukhopadhyay explained that the team's success came from its multidisciplinary approach. "Not only did this work require rigorous computational modeling and state-of-the-art genetics, we also relied on our collaborators at the Advanced Biofuels and Bioproducts Process Development Unit (ABPDU) to demonstrate that our process could hold its desirable features at higher production scales," said Mukhopadhyay, who is the vice president of the biofuels and bioproducts division and director of the host engineering group at JBEI. "We also collaborated with the Department of Energy (DOE) Joint Genome Institute to characterize our strain. Not surprisingly, we anticipate many such future collaborations to examine the economic value of the improvements we obtained, and to delve deeper in characterizing this drastic metabolic rewiring."

Credit: 
DOE/Lawrence Berkeley National Laboratory

Uncovering novel genomes from earth's microbiomes

image: Artistic interpretation of how microbial genome sequences from the GEM catalog can help fill in gaps of knowledge about the microbes that play key roles in the Earth's microbiomes. This image complements a public repository of 52,515 microbial draft genomes generated from environmental samples around the world, expanding the known diversity of bacteria and archaea by 44%, is now available and described November 9, 2020 in Nature Biotechnology. Work on this catalog of genomes from Earth's microbiomes catalog results from a collaboration involving more than 200 scientists, researchers at the DOE Joint Genome Institute (JGI) and the DOE Systems Biology Knowledgebase (KBase).

Image: 
Rendered by Zosia Rostomian/Berkeley Lab

Despite advances in sequencing technologies and computational methods in the past decade, researchers have uncovered genomes for just a small fraction of Earth's microbial diversity. Because most microbes cannot be cultivated under laboratory conditions, their genomes can't be sequenced using traditional approaches. Identifying and characterizing the planet's microbial diversity is key to understanding the roles of microorganisms in regulating nutrient cycles, as well as gaining insights into potential applications they may have in a wide range of research fields.

A public repository of 52,515 microbial draft genomes generated from environmental samples around the world, expanding the known diversity of bacteria and archaea by 44%, is now available and described November 9, 2020 in Nature Biotechnology. Known as the GEM (Genomes from Earth's Microbiomes) catalog, this work results from a collaboration involving more than 200 scientists, researchers at the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), and the DOE Systems Biology Knowledgebase (KBase).

Metagenomics is the study of the microbial communities in the environmental samples without needing to isolate individual organisms, using various methods for processing, sequencing and analysis. "Using a technique called metagenome binning, we were able to reconstruct thousands of metagenome-assembled genomes (MAGs) directly from sequenced environmental samples without needing to cultivate the microbes in the lab," noted Stephen Nayfach, the study's first author and research scientist in Nikos Kyrpides' Microbiome Data Science group. "What makes this study really stand out from previous efforts is the remarkable environmental diversity of the samples we analyzed."

Emiley Eloe-Fadrosh, head of the JGI Metagenome Program and senior author on the study elaborated on Nayfach's comments. "This study was designed to encompass the broadest and most diverse range of samples and environments, including natural and agricultural soils, human- and animal-host associated, and ocean and other aquatic environments - that's pretty remarkable."

Adding Value Beyond Genome Sequences

Much of the data had been generated from environmental samples sequenced by the JGI through the Community Science Program and was already available on the JGI's Integrated Microbial Genomes & Microbiomes (IMG/M) platform. Eloe-Fadrosh noted that it was a nice example of "big-data" mining to gain a deeper understanding of the data and enhancing the value by making data publicly available.

To acknowledge the efforts of the investigators who had done the sampling, Eloe-Fadrosh reached out to more than 200 researchers around the world in accordance with the JGI data use policy. "I felt it is important to acknowledge the significant efforts to collect and extract DNA from these samples, many of which come from unique, difficult to access environments, and invited these researchers to be co-authors as part of IMG data consortium," she said.

Using this massive dataset, Nayfach clustered the MAGs into 18,000 candidate species groups, 70% of which were novel compared over 500,000 existing genomes available at that time. "Looking across the tree of life, it's striking how many uncultivated lineages are only represented by MAGs," he said. "While these draft genomes are imperfect, they can still reveal a lot about the biology and diversity of uncultured microbes."

Teams of researchers worked on multiple analyses harnessing the genome repository, and the IMG/M team developed several updates and features to mine the GEM catalog. (Watch this IMG webinar on Metagenome Bins to learn more.) One group mined the dataset for novel secondary metabolites of secondary metabolite biosynthetic gene clusters (BGCs), increasing these BGCs in IMG/ABC (Atlas of Biosynthetic Gene Clusters) by 31%. (Listen to this JGI Natural Prodcast episode on genome mining.) Nayfach also worked with another team on predicting host-virus connections between all viruses in IMG/VR (Virus) and the GEM catalog, associating 81,000 viruses - 70% of which had not already been associated with a host - with 23,000 MAGs.

Modeling A New Path for Metagenomics Researchers

Building upon these resources, KBase, a multi-institutional collaborative knowledge creation and discovery environment designed for biologists and bioinformaticians, developed metabolic models for thousands of MAGs. The models are now available in a public Narrative, which provides shareable, reproducible workflows. "Metabolic modeling is a routine analysis for isolate genomes, but has not been done at scale for uncultivated microbes," said Eloe-Fadrosh, "and we felt that the collaboration with KBase would add value beyond clustering and analysis of these MAGs."

"Just bringing this dataset into KBase has immediate value because people can find the high-quality MAGs and use them to inform future analyses," said José P. Faria, a KBase computational biologist at Argonne National Laboratory. "The process of building a metabolic model is simple: you just select a genome or MAG and press a button to build a model from our database of mappings between biochemical reactions and annotations. We look at what was annotated in the genome and at the resulting model to assess the metabolic capabilities of the organism." (Watch this KBase webinar on metabolic modeling.)

KBase User Engagement lead Elisha Wood-Charlson added that by demonstrating the ease with which metabolic models were generated from the GEM dataset, metagenomics researchers might consider branching into this space. "Most metagenomics researchers might not be willing to dive into an entirely new research field [metabolic modeling], but they might be interested in how biochemistry impacts what they work on. The genomics community can now explore metabolism using KBase's easy path from genomes or MAGs to modeling that may not have been considered," she said.

A Community Resource for Facilitating Research

Kostas Konstantinidis of Georgia Institute of Technology, one of the co-authors whose data were part of the catalog, "I don't think there are many institutions that can do this kind of large-scale metagenomics and that have the capacity for large scale analyses. The beauty of this study is that it's done at this scale that individual labs cannot do, and it gives us new insights into microbial diversity and function."

He is already finding ways to utilize the catalog in his own research on how microbes respond to climate change. "With this dataset I can see where every microbe is found, and how abundant it is. That's very useful for my work and for others doing similar research." Additionally, he's interested in expanding the diversity of the reference database he's developing called the Microbial Genomes Atlas to allow for more robust analyses by adding the MAGs.

"This is a great resource for the community," Konstantinidis added. "It's a dataset that is going to facilitate many more studies subsequently. And I hope JGI and other institutions continue to do this kind of projects."

Credit: 
DOE/Lawrence Berkeley National Laboratory

'Diseases of despair' have soared over past decade in US

'Diseases of despair', such as substance abuse, alcohol dependency, and suicidal thoughts and behaviours, have soared in the US over the past decade, reveals an analysis of health insurance claims data published in the online journal BMJ Open.

And they now affect all ages, with suicidal thoughts and behaviours among the under 18s rocketing by 287% between 2009 and 2018, and by 210% among 18-34 year olds, the analysis shows.

Between 2015 and 2017, life expectancy fell year on year in the USA, the longest sustained decline since 1915-18. And deaths among middle-aged white non-Hispanic men and women rose sharply between 1999 and 2015.

These premature deaths are largely attributable to accidental overdose, alcohol-related disease, and suicide.

Such 'deaths of despair' have coincided with decades of economic decline for workers, particularly those with low levels of educational attainment; loss of social safety nets; and stagnant or falling wages and family incomes in the US, all of which are thought to have contributed to growing feelings of despair.

Despair may in turn trigger emotional, behavioural and even biological changes, increasing the likelihood of diseases that can progress and ultimately culminate in deaths of despair, say the researchers.

To characterise trends in diseases of despair over the past decade and identify associated demographic risk factors, they drew on detailed claims data extracted from Highmark, a large US-based health insurance company.

Highmark members are concentrated in states that have been disproportionately affected by deaths of despair: Pennsylvania; West Virginia; and Delaware.

In all, the researchers analysed information for 12 million people enrolled in a Highmark health insurance plan between 2007 and 2018, and who had valid details on file.

Diseases of despair were defined as diagnoses related to alcohol dependency, substance misuse, and suicidal thoughts/behaviours, and analysed among the following age groups: under the age of 12 months; 1-17 year olds; 18-34 year olds; 35-54 year olds; 55-75 year olds; and those aged 75+.

Overall, 1 in 20 (515,830; just over 4%) of those insured were diagnosed with at least one disease of despair at some point during the monitoring period. Some 58.5% were male, with an average age of 36.

Of these, over half (54%) were diagnosed with an alcohol-related disorder; just over 44% with a substance related disorder; and just over 16% with suicidal thoughts/behaviours. Just under 13% were diagnosed with more than one type of disease of despair.

Between 2009 and 2018, the rate of diseases of despair diagnoses increased by 68%. The rate of alcohol-related, substance-related, and suicide-related diagnoses rose by 37%, 94%, and 170%, respectively.

The largest increase in alcohol and substance-related diagnoses was seen among 55-74 year olds: 59% and 172%, respectively.

Among infants, substance-related diagnoses, which were attributable to neonatal abstinence syndrome linked to maternal drug abuse--for example opioid addiction--rose by 114%.

While the absolute numbers of suicide-related diagnoses were lower than for other types of diseases of despair, the relative increases were large. Among 1-17 year olds, the rate increased by 287%, and by 210% among 18-34 year olds. A relative increase of at least 70% occurred in all other age groups.

Diseases of despair diagnoses were associated with significantly higher scores for coexisting conditions, higher rates of anxiety and mood disorders, and schizophrenia for both men and women across all age groups.

The researchers acknowledge that it wasn't possible to find out about potentially influential social determinants of health from the claims data, added to which, given that an estimated 87 million working adults in the US are uninsured or underinsured, it is hard to gauge the true scope of the diseases of despair, they say.

Nevertheless, they urge: "While the opioid crisis remains a top public health priority, parallel rises in alcohol-related diagnoses and suicidality must be concurrently addressed."

Credit: 
BMJ Group

Severe COVID-19 infection rare in newborns

Severe COVID-19 infection appears rare in newborn babies, suggests a new study.

The UK-wide analysis, led by researchers from Imperial College London and the Nuffield Department of Population Health at the University of Oxford, is the first study analysing COVID-19 infections in newborns across the whole UK.

The study, published in the journal The Lancet Child and Adolescent Health, traced all babies less than 29 days old with COVID-19 across the UK, who needed to be admitted into hospital.

The analysis, which was funded by the National Institute for Health Research, traced these babies with COVID-19 between the beginning of March and end of April, at the peak of the first wave of the UK COVID-19 pandemic. Babies were tracked using a national system called the British Paediatric Surveillance Unit that all paediatricians in the UK contribute to.

The study found 66 babies required hospital treatment for COVID-19 infection in this period. This is the equivalent of 1 in 1785 births, or 0.06 per cent of births.

Nearly half (45 per cent) of the babies who developed severe infection were from Black, Asian or minority ethnic groups. Around one in four of the babies (24 per cent) were born prematurely (defined as being born before 37 weeks). These are both higher than would be expected from the UK birth population.

Only 17 babies, out of the 66 newborns in the study, were suspected to have caught COVID-19 from their mother in the first seven days after birth. Seven of these 17 babies developed COVID-19 despite being separated from their mother immediately after birth. This supports UK and international guidance to keep mother and baby together even when the mother is suspected or known to have COVID-19, say the team. Six babies were thought to have contracted COVID-19 while in hospital.

None of the babies in the group died from COVID-19 (although one baby sadly died, this was not linked to COVID-19 infection).

When the data were analysed nearly 90 per cent of the babies had fully recovered from the infection, and had been discharged from hospital.

The study suggests a higher proportion of newborns who develop severe disease will need intensive care or breathing support (36 per cent), compared with older children (13 per cent). However, the study authors add that severe infection in newborn babies is still very rare.

The researchers add that, overall, this study suggests a small proportion of babies caught COVID-19 from their mother. They explain that, in light of this, if a mother tests positive for COVID-19, her baby does not need to be separated from her at birth. They add that seven babies who were separated from their mother at birth in the current study still contracted the virus.

Dr Chris Gale, co-lead author of the study from Imperial's School of Public Health said: "Parents, and expectant parents, are understandably worried about their babies becoming ill with COVID-19. This study will hopefully provide some reassurance, as it suggests severe COVID-19 infection in newborns is very rare. Most babies only develop mild symptoms when infected with the virus and make a full recovery. This research also supports UK and international guidance to keep mother and baby together even when the mother is known or suspected to have COVID-19."

Dr Gale added: "Although this study did show that six babies may have contracted hospital-acquired COVID-19, this data was from the beginning of the pandemic, and infection control measures on neonatal and paediatric units have improved dramatically over the past six months."

The team say urgent investigation is needed to understand why so many of the babies hospitalised with severe COVID-19 were from Black, Asian or minority ethnic groups.

Professor Jenny Kurinczuk, co-lead author from the Nuffield Department of Population Health at the University of Oxford, said: "As in our recent study of pregnant women with COVID-19, and the general population, we found a higher than expected proportion of the babies were from Black, Asian and ethnic minority backgrounds, which clearly needs further investigation. In the meantime however, parents may find some reassurance that severe COVID-19 infection, even in the first wave of the pandemic, was rare in babies from the BAME community."

The study revealed 17 of the babies were suspected to have caught the infection from their mother, with two of these babies potentially contracting COVID-19 in the womb.

The main symptoms of COVID-19 infection in the babies in the study included high temperature, poor feeding, vomiting, a runny nose, cough and lethargy.

Credit: 
Imperial College London

Loneliness a leading cause of depression in older adults

Loneliness is responsible for 18% of depression among people over 50 in England, according to a new study led by UCL researchers.

The findings, published in The Lancet Psychiatry, suggest that almost one in five depression cases among older adults could be prevented if loneliness were eliminated.

The researchers found that people's subjective experiences of loneliness contributed to depression up to 12 years later, independent of more objective measures of social isolation.

Senior author Dr Gemma Lewis (UCL Psychiatry) said: "We found that whether people considered themselves to be lonely was a bigger risk factor for depression than how many social contacts and support they had. The findings suggest that it's not just spending time with other people that matters, but having meaningful relationships and companionship."

The researchers reviewed data from 4,211 participants of the English Longitudinal Study of Ageing, aged 52 and over, who had answered questions at regular intervals over a 12-year period about their experiences of loneliness, social engagement and social support, as well as depressive symptoms.

To measure loneliness, participants were asked three questions about lacking companionship, feeling left out, and feeling isolated, and their answers combined into a loneliness score on a seven-point scale.

Each one-point increase on the loneliness scale corresponded to a doubling of the odds of depression (based on a clinical threshold of depressive symptoms rather than a diagnosis). The researchers accounted for depression and loneliness levels at the start of the study to reduce the possibility that depression was responsible for the increasing feelings of loneliness that were reported.

The researchers found that depressive symptoms increased over time among people with greater loneliness, suggesting that loneliness was leading to future depression.

As part of their analysis, the researchers investigated the proportion of depression that was due to loneliness, and found that 18% of depression cases could be attributed to loneliness (as measured one year earlier).

First author Siu Long Lee, who led the study as part of an MSc degree in UCL Psychiatry, said: "Health professionals working with older people who report being lonely should know that they are at risk of depression. Interventions such as social prescribing, social skills training, and psychological therapies that target negative feelings of loneliness, may be important for the mental health of lonely older adults."

Dr Lewis added: "Our study has important public health implications, as it suggests that community-based approaches designed to reduce loneliness could reduce depression rates. Building relationships, meaningful connections and a sense of belongingness may be more important than just increasing how much time people spend with others."

Robin Hewings, Director of Campaigns, Policy and Research at the Campaign to End Loneliness said: "This important study adds to our understanding of the very serious impacts of loneliness on our mental and physical health. The author's findings that nearly one in five cases of depression in older people could potentially be prevented if loneliness were eliminated only adds to the case for comprehensive action across society. In our day-to-day lives that can mean reaching out to those around us.

"At the same time it's vitally important that we implement the Government's ground-breaking loneliness strategy and ensure that services to combat loneliness have the funding they need."

Credit: 
University College London