Tech

WEST LAFAYETTE, Ind. -- A self-driving car has a hard time recognizing the difference between a toddler and a brown bag that suddenly appears into view because of limitations in how it senses objects using lidar.

The autonomous vehicle industry is exploring "frequency modulated continuous wave" (FMCW) lidar to solve this problem. Researchers have built a way that this type of lidar could achieve higher-resolution detection of nearby fast-moving objects through mechanical control and modulation of light on a silicon chip.

The work, published in Nature, was conducted by the OxideMEMS lab at Purdue University and the Laboratory of Photonics and Quantum Measurements at École polytechnique fédérale de Lausanne (EPFL), a research institute and university in Lausanne, Switzerland.

FMCW lidar detects objects by scanning laser light from the top of an autonomous vehicle. A single laser beam splits into a comb of other wavelengths, called a microcomb, to scan an area. Light bounces off of an object and goes to the detector through an optical isolator or circulator, which ensures all reflected light ends up at the detector array.

What Purdue and EPFL researchers developed uses acoustic waves to enable faster tuning of these components, which could bring higher-resolution FMCW lidar detection of nearby objects.

The technology integrates microelectromechanical systems (MEMS) transducers made of aluminum nitride to modulate the microcomb at high frequencies ranging from megahertz to gigahertz. The optical isolator that the team developed as part of this process is further described in a paper published in Nature Communications.

An array of phased MEMS transducers, also used in cellphones to discern cellular bands, stirs light at gigahertz frequencies by launching a corkscrew-like stress wave into a silicon chip.

"The stirring motion modulates light such that it can only travel in one direction," said Sunil Bhave, a Purdue professor of electrical and computer engineering.

Hao Tian, a Purdue Ph.D. candidate in electrical and computer engineering, built the MEMS transducers at the Scifres Nanofabrication Facility of Purdue's Birck Nanotechnology Center in Discovery Park. He integrated the transducers with a silicon nitride photonics wafer developed at EPFL.

"The tight vertical confinement of the bulk acoustic waves prevents cross-talk and allows for close placement of the actuators," Tian said.

Other transducers in the same technology excite an acoustic wave that shakes the chip at megahertz frequencies, demonstrating sub-microsecond control and tuning of the laser pulse microcomb or soliton.

"This achievement, bridging integrated photonics, MEMS engineering and nonlinear optics, represents a new milestone for the emerging chip-based microcomb technology," said Junqiu Liu, the first author on the Nature paper who leads the fabrication of silicon nitride photonics chips at the EPFL Center of MicroNanoTechnology.

This light modulation technique not only integrates mechanics with optics, but also the fabrication processes involved, making the technology more commercially viable, the researchers said. The MEMS transducers are simply fabricated on top of the silicon nitride photonics wafer with minimal processing.

"As yet unforeseen applications will follow up across multiple communities," said Tobias Kippenberg, a professor of physics at EPFL. "It's been shown time and again that hybrid systems can obtain advantages and functionality beyond those attained with individual constituents."

According to the researchers, the new technology could provide the impetus for microcomb applications in power-critical systems such as in space, data centers and portable atomic clocks, or in extreme environments such as those with cryogenic temperatures.

"Our results would not have been possible without this multidisciplinary and intercontinental collaboration," Bhave said.

In living organisms, DNA is the storage unit of all genetic information. It is with this information that proteins are encoded, which then enable biological systems to function as needed for the organism to survive. DNA's functioning is enabled by its structure: a double-stranded helix formed via the joining of specific pairs of molecules called 'nucleotides' in specific orders, called 'sequences'. In recent decades, scientists in the fields of DNA nanotechnology have been able to design DNA sequences to construct desired nanostructures and microstructures, which can be used to investigate biomolecular functions or create artificial cell systems.

The customization of the designs of sequences in DNA nanotechnology also enables the interactions among DNA molecules to be controlled and programmed. The inter-molecular interactions in cells cause various phenomena. A phenomenon called "liquid-liquid phase separation (LLPS)"--the separation of a liquid into a denser phase of droplets within a more dilute phase--plays an important role in many biological processes. LLPS artificially induced via DNA nanotechnology can help deepen our understanding of the applicability of LLPS and provide a methodology for controlling bio-macromolecular droplets.

Therefore, a team of scientists from Tokyo Tech, led by Professor Masahiro Takinoue, designed specific DNA-nanostructures to understand the influence of DNA sequences and demonstrate controllability on LLPS--into DNA-rich and DNA-poor phases--in artificially designed DNA nanostructures.

Their study, published in Science Advances, involved the construction of Y-shaped DNA nanostructures called "Y-motifs". Each side of a Y-motif comprises a short sticky end that interacts with other 'compatible' sticky ends (Fig. 1a). Upon progressively decreasing the temperature, the scientists found that the Y-motifs reversibly agglomerate to form droplets and then gels (Figs. 1b and 2a).

When they added another set of constructed Y-motifs with sticky ends that are incompatible with the previous set, two sets of droplets were formed for each type of Y-motif. This demonstrated that DNA sequences can be tailored to fuse exclusively with similar ones (Figs. 1c and 2b).

Prof Takinuoe and team then created a special DNA structure that can bridge together the incompatible Y-motifs. Upon adding this to the mixture of Y-motifs, droplets composed of both motifs were formed. Further construction of a cleavable variant of the special bridge DNA structure and subsequent addition of a certain cleaving enzyme caused the fission of droplets (Figs. 1d and 2c) and the mixed droplets to separate into Janus-shaped droplets with unmixable halves containing the two types of Y-motif (Figs. 1e and 2d). By conjugating cargo molecules with DNA strands compatible with either one type of Y-motif, the scientists were able to localize the cargo molecules exclusively on one half of the droplet (Figs. 1f and 2e).

Thus, the scientists were able to 'program' DNA and 'control' their behavior, opening doors to a new technique for creating artificial reaction environments to study biological systems and drug delivery. Prof Takinoue explains: "Living systems are well-organized dynamic structures whose behavior is regulated by the information encoded in biopolymers (such as DNA). Our DNA-based liquid-liquid phase separation system could provide a new basis for the development of artificial cell engineering."

Because precise DNA sequences can be readily produced using available bioengineering techniques, the potential applications of manipulating material behaviors through DNA sequences are far-reaching. Prof Takinoue concludes: "The phase behavior shown in this study could be expanded to other materials that can be modified with DNA, which may enable us to design phases and create droplets for various materials. Moreover, we envision that the observed autonomous behavior of macromolecular structures could one day serve for the development of robotic molecular systems comparable to those of living cells."

Tulane University researchers are part of a team of scientists who have developed a hybrid solar energy converter that generates electricity and steam with high efficiency and low cost.

The work led by Matthew Escarra, associate professor of physics and engineering physics at Tulane, and Daniel Codd, associate professor of mechanical engineering at the University of San Diego, is the culmination of a U.S. Department of Energy ARPA-E project that began in 2014 with $3.3 million in funding and involved years of prototype development at Tulane and field testing in San Diego.

The research is detailed this month in the science journal Cell Reports Physical Science. Researchers from San Diego State University, Boeing-Spectrolab and Otherlab were also part of the project.

"Thermal energy consumption is a huge piece of the global energy economy - much larger than electricity use. There has been a rising interest in solar combined heat and power systems to deliver both electricity and process heat for zero-net-energy and greenhouse-gas-free development," said Escarra.

The hybrid converter utilizes an approach that more fully captures the whole spectrum of sunlight. It generates electricity from high efficiency multi-junction solar cells that also redirect infrared rays of sunlight to a thermal receiver, which converts those rays to thermal energy.

The thermal energy can be stored until needed and used to provide heat for a wide range of commercial and industrial uses, such as food processing, chemical production, water treatment, or enhanced oil recovery.

The team reports that the system demonstrated 85.1 percent efficiency, delivered steam at up to 248°C, and is projected to have a system levelized cost of 3 cents per kilowatt hour.

With follow-on funding from the Louisiana Board of Regents and Reactwell, a local commercialization partner, the team is continuing to refine the technology and move towards pilot-scale validation.

"We are pleased to have demonstrated high performance field operation of our solar converter," Escarra said, "and look forward to its ongoing commercial development."

University of Colorado Boulder researchers have used ultra-fast extreme ultraviolet lasers to measure the properties of materials more than 100 times thinner than a human red blood cell.

The team, led by scientists at JILA, reported its new feat of wafer-thinness this week in the journal Physical Review Materials. The group's target, a film just 5 nanometers thick, is the thinnest material that researchers have ever been able to fully probe, said study coauthor Joshua Knobloch.

"This is a record-setting study to see how small we could go and how accurate we could be," said Knobloch, a graduate student at JILA, a partnership between CU Boulder and the National Institute of Standards and Technology (NIST).

He added that when things get small, the normal rules of engineering don't always apply. The group discovered, for example, that some materials seem to get a lot softer the thinner they become.

The researchers hope that their findings may one day help scientists to better navigate the often-unpredictable nanoworld, designing tinier and more efficient computer circuits, semiconductors and other technologies.

"If you're doing nanoengineering, you can't just treat your material like it's a normal big material," said Travis Frazer, lead author of the new paper and a former graduate student at JILA. "Because of the simple fact that it's small, it behaves like a different material."

"This surprising discovery--that very thin materials can be 10 times more flimsy than expected--is yet another example of how new tools can helps us to understand the nanoworld better," said Margaret Murnane, a coauthor of the new research, professor of physics at CU Boulder and JILA fellow.

Nano wiggles

The research comes at a time when many technology firms are trying to do just that: go small. Some companies are experimenting with ways to build efficient computer chips that layer thin films of material one on top of the other--like a filo pastry, but inside your laptop.

The problem with that approach, Frazer said, is that scientists have trouble predicting how those flakey layers will behave. They're just too delicate to measure in any meaningful way with the usual tools.

To help in that goal, he and his colleagues deployed extreme ultraviolet lasers, or beams of radiation that deliver shorter wavelengths than traditional lasers--wavelengths that are well-matched to the nanoworld. The researchers developed a set-up that allows them to bounce those beams off of layers of material just a few strands of DNA thick, tracking the different ways those films can vibrate.

"If you can measure how fast your material is wiggling, then you can figure out how stiff it is," Frazer said.

Atomic disruption

The method has also revealed just how much the properties of materials can change when you make them very, very small.

In the most recent study, for example, the researchers probed the relative strength of two films made out of silicon carbide: one about 46 nanometers thick, and the other just 5 nanometers thick. The team's ultraviolet laser delivered surprising results. The thinner film was about 10 times softer, or less rigid, than its thicker counterpart, something the researchers weren't expecting.

Frazer explained that, if you make a film too thin, you can cut into the atomic bonds that hold a material together--a bit like unraveling a frayed rope.

"The atoms at the top of the film have other atoms underneath them that they can hold onto," Frazer said. "But above them, the atoms don't have anything they can grab onto."

But not all materials will behave the same way, he added. The team also reran the same experiment on a second material that was nearly identical to the first with one big difference--this one had a lot more hydrogen atoms added in. Such a "doping" process can naturally disrupt the atomic bonds within a material, causing it to lose strength.

When the group tested that second, flimsier material using their lasers, they found something new: this material was just as strong when it was 44 nanometers thick as it was at a meager 11 nanometers thick.

Put differently, the additional hydrogen atoms had already weakened the material--a bit of extra shrinking couldn't do anymore damage.

In the end, the team says that its new ultraviolet laser tool gives scientists a window into a realm that was previously beyond the grasp of science.

"Now that people are building very, very small devices, they're asking how properties like thickness or shape can change how their materials behave," Knobloch said. "This gives us a new way of accessing information about nanoscale technology."

Two daily fasting diets, also known as time-restricted feeding diets, are effective for weight loss, according to a new study published by researchers from the University of Illinois at Chicago.

The study reported results from a clinical trial that compared a 4-hour time-restricted feeding diet and a 6-hour time-restricted feeding diet to a control group.

"This is the first human clinical trial to compare the effects of two popular forms of time-restricted feeding on body weight and cardiometabolic risk factors," said Krista Varady, professor of nutrition at the UIC College of Applied Health Sciences and corresponding author of the story.

Participants in the 4-hour time-restricted feeding diet group were asked to eat only between the hours of 1 p.m. and 5 p.m. Participants in the 6-hour time-restricted feeding diet group were asked to eat only between the hours of 1 p.m. and 7 p.m.

In both the study groups, patients were allowed to eat whatever they wanted during the 4-hour or 6-hour eating period. During the fasting hours, participants were directed to only drink water or calorie-free beverages. In the control group, participants were directed to maintain their weight and not change their diet or physical activity levels.

The participants were followed for 10 weeks as weight, insulin resistance, oxidative stress, blood pressure, LDL cholesterol, HDL cholesterol, triglycerides and inflammatory markers were tracked.

The study, published in Cell Metabolism, found that participants in both daily fasting groups reduced calorie intake by about 550 calories each day simply by adhering to the schedule and lost about 3% of their body weight. The researchers also found that insulin resistance and oxidative stress levels were reduced among participants in the study groups when compared with the control group. There was no effect on blood pressure, LDL cholesterol, HDL cholesterol or triglycerides.

There also was no significant difference in weight loss or cardiometabolic risk factors between the 4-hour and 6-hour diet groups.

"The findings of this study are promising and reinforce what we've seen in other studies -- fasting diets are a viable option for people who want to lose weight, especially for people who do not want to count calories or find other diets to be fatiguing," Varady said. "It's also telling that there was no added weight loss benefit for people who sustained a longer fast -- until we have further studies that directly compare the two diets or seek to study the optimal time for fasting, these results suggest that the 6-hour fast might make sense for most people who want to pursue a daily fasting diet."

Geoengineering - spraying sulfur dioxide into the atmosphere to combat global warming - would only temporarily and partially benefit apple production in northern India, according to a Rutgers co-authored study.

But abruptly ending geoengineering might lead to total crop failure faster than if geoengineering were not done, according to the study - believed to be the first of its kind - in the journal Climatic Change.

"This study reminds us that there is no perfect technical method to address the impacts of global warming, and that we need to mitigate global warming and adapt as best we can," said co-author Alan Robock, a Distinguished Professor in the Department of Environmental Sciences in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. "To reduce the impacts of global warming, in this case on the production of deciduous fruits such as apples, we need to leave the fossil fuels in the ground and move to powering society with wind and solar power as quickly as possible."

In a 2018 study, Robock and other researchers examined the biological impacts of starting and abruptly ending geoengineering efforts to cool Earth's climate. Society, responding to a climate emergency, may eventually spray sulfur dioxide into the stratosphere (upper atmosphere). Such geoengineering, or climate intervention, would create a massive sulfuric acid cloud to block some solar radiation and cool the Earth. But if the spraying were to suddenly cease, there would be a major impact on animals and plants, which would be forced to try to move to suitable habitat to survive. The airplane spraying technology may be developed within 10 or 20 years, and a geoengineered cloud would last only about a year if the airplanes stopped continuous spraying.

In their new study, scientists studied the impact of global warming and stratospheric geoengineering on the production of deciduous fruit in Himachal Pradesh, the second-largest apple-producing state in India. They used a climate model to project temperature changes and shifts in suitable habitat for apple orchards under a moderate greenhouse gas emissions scenario and efforts to limit warming.

"We found that global warming would reduce apple production by affecting the winter chill period necessary for the plants," Robock said. "Adaptation by moving to higher elevation cooler areas, would only partially be successful as the soil there is not as suitable and the overall area where apple production could succeed would be reduced. Geoengineering to counter some of the global warming would have limited benefits and could backfire if it ever ended suddenly."

Since the study was done with one global warming and geoengineering scenario for one crop in one part of the world, other studies are needed to see how robust the results are in general, Robock noted.

The work was done in collaboration with Jyoti Singh and Sandeep Sahany from the Indian Institute of Technology Delhi in India and the Centre for Climate Research Singapore.

July 15, 2020 - Smoking cessation initiatives notwithstanding, along with provocative public health campaigns and clinical guidance, quitting tobacco has remained elusive for many smokers. The American Thoracic Society's new clinical practice guideline on treatment for tobacco dependence in adults addresses how clinicians may deal with patients' reluctance to quit, one of a number of issues not previously assessed in the older guidelines.

The complete guideline detailing all the recommendations was posted online ahead of print in the July 15 issue of the American Journal of Respiratory and Critical Care Medicine.

An explainer video is available here.

This latest ATS practice guideline maintains the first principle of clinical practice that "all patients who use tobacco should receive treatment for their dependence, and not simply be encouraged to stop." It expands upon the last guidance by the U.S. Public Health Service, which was issued in 2008. In addition to addressing a reluctance to quit, the guideline "identifies an 'optimal controller' medication for clinicians to use as an initial pharmacotherapeutic choice and identifies a clinical strategy for amplifying the effectiveness of that controller," noted Frank T. Leone, MD, MS co-chair of the ATS guideline committee.

There is a clear consensus on the health consequences of smoking, including lung disorders like chronic obstructive pulmonary disorder and lung cancer, not to mention heart disease and mood disorders like anxiety and depression.

"At least among adults, the overwhelming majority of current smokers (including e-cigarette users) express an interest in quitting (over 70 percent) while only a very few follow through with some attempt," said Dr. Leone, associate professor medicine, University of Pennsylvania Medical Center and director, Comprehensive Smoking Treatment Program, Penn Lung Center.

But as Dr. Leone is quick to point out, "A willingness to quit is not a pre-requisite for achieving control over the compulsion to smoke." One main takeaway to the guidelines: "introducing the optimal controller to patients before they express willingness to quit results in an additional 308 patients achieving abstinence per 1000 patients treated."

The following recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation, or GRADE, approach:

1. For tobacco-dependent adults in whom treatment is being initiated, we recommend varenicline over a nicotine patch (strong recommendation, moderate certainty in the estimated effects).

2. For tobacco-dependent adults in whom treatment is being initiated, we recommend varenicline over bupropion (strong recommendation, moderate certainty in the estimated effects).

3. For tobacco-dependent adults in whom treatment is being initiated, we suggest varenicline plus a nicotine patch over varenicline alone (conditional recommendation, low certainty in the estimated effects).

4. For tobacco-dependent adults in whom treatment is being initiated, we suggest varenicline over electronic cigarettes (conditional recommendation, very low certainty in the estimated effects).

5. In tobacco-dependent adults who are not ready to discontinue tobacco use, we recommend that clinicians begin treatment with varenicline rather than waiting until they are ready to stop tobacco use (strong recommendation, moderate certainty in estimated effects).

6. For tobacco-dependent adults with co-morbid psychiatric conditions, including substance use disorder, depression, anxiety, schizophrenia and/or bipolar disorder, for whom treatment is being initiated, we recommend varenicline over a nicotine patch (strong recommendation, moderate certainty in estimated effects).

7. For tobacco-dependent adults for whom treatment is being initiated with a controller, we recommend using extended duration (greater than 12 weeks) over standard duration (6-12 weeks) (strong recommendation, moderate certainty in estimated effects).

Mobile phones and other electronic devices made from an organic material that is thin, bendable and more powerful are now a step closer thanks to new research led by scientists at The Australian University (ANU).

Lead researchers Dr Ankur Sharma and Associate Professor Larry Lu say it would help create the next generation of ultra-fast electronic chips, which promise to be much faster than current electronic chips we use.

"Conventional devices run on electricity - but this material allows us to use light or photons, which travels much faster," Dr Sharma said.

"The interesting properties we have observed in this material make it a contender for super-fast electronic processors and chips.

"We now have the perfect building block, to achieve flexible next generation electronics."

Associate Professor Lu said they observed interesting functions and capabilities in their organic material, previously unseen.

"The capabilities we observed in this material that can help us achieve ultra-fast electronic devices," said Associate Professor Lu.

The team were able to control the growth of a novel organic semiconductor material - stacking one molecule precisely over the other.

"The material is just one carbon atom thick, a hundred times thinner than a human hair, which gives it the flexibility to be bent into any shape. This will lead to its application in flexible electronic devices."

In 2018 the same team developed a material that combined both organic and inorganic elements.

Now, they've been able to improve the organic part of the material, allowing them to completely remove the inorganic component.

"It's made from just carbon and hydrogen, which would mean devices can be biodegradable or easily recyclable, thus avoiding the tonnes of e-waste generated by current generation electronic devices," Dr Sharma said.

Dr Sharma says while the actual devices might still be some way off, this new study is an important next step, and a key demonstration of this new material's immense capabilities.

What would conversations with Alexa be like if she was a regular at The Second City?

Jonathan May, research lead at the USC Information Sciences Institute (ISI) and research assistant professor of computer science at USC's Viterbi School of Engineering, is exploring this question with Justin Cho, an ISI programmer analyst and prospective USC Viterbi Ph.D. student, through their Selected Pairs Of Learnable ImprovisatioN (SPOLIN) project. Their research incorporates improv dialogues into chatbots to produce more engaging interactions.

The SPOLIN research collection is made up of over 68,000 English dialogue pairs, or conversational dialogues of a prompt and subsequent response. These pairs model yes-and dialogues, a foundational principle in improvisation that encourages more grounded and relatable conversations. After gathering the data, Cho and May built SpolinBot, an improv agent programmed with the first yes-and research collection large enough to train a chatbot.

The project research paper, "Grounding Conversations with Improvised Dialogues," was presented on July 6 at the Association of Computational Linguistics conference, held July 5-10.

Finding Common Ground

May was looking for new research ideas in his work. His love for language analysis had led him to work on Natural Language Processing (NLP) projects, and he began searching for more interesting forms of data he could work with.

"I'd done some improv in college and pined for those days," he said. "Then a friend who was in my college improv troupe suggested that it would be handy to have a 'yes-and' bot to practice with, and that gave me the inspiration--it wouldn't just be fun to make a bot that can improvise, it would be practical!"

The deeper May explored this idea, the more valid he found it to be. Yes-and is a pillar of improvisation that prompts a participant to accept the reality that another participant says ("yes") and then build on that reality by providing additional information ("and"). This technique is key in establishing a common ground in interaction. As May put it, "Yes-and is the improv community's way of saying 'grounding.'"

Yes-ands are important because they help participants build a reality together. In movie scripts, for example, maybe 10-11% of the lines can be considered yes-ands, whereas in improv, at least 25% of the lines are yes-ands. This is because, unlike movies, which have settings and characters that are already established for audiences, improvisers act without scene, props, or any objective reality.

"Because improv scenes are built from almost no established reality, dialogue taking place in improv actively tries to reach mutual assumptions and understanding," said Cho. "This makes dialogue in improv more interesting than most ordinary dialogue, which usually takes place with many assumptions already in place (from common sense, visual signals, etc.)."

But finding a source to extract improv dialogue from was a challenge. Initially, May and Cho examined typical dialogue sets such as movie scripts and subtitle collections, but those sources didn't contain enough yes-ands to mine. Moreover, it can be difficult to find recorded, let alone transcribed, improv.

The Friendly Neighborhood Improv Bot

Before visiting USC as an exchange student in Fall 2018, Cho reached out to May, inquiring about NLP research projects that he could participate in. Once Cho came to USC, he learned about the improv project that May had in mind.

"I was interested in how it touched on a niche that I wasn't familiar with, and I was especially intrigued that there was little to no prior work in this area," Cho said. "I was hooked when Jon said that our project will be answering a question that hasn't even been asked yet: the question of how modeling grounding in improv through the yes-and act can contribute to improving dialogue systems."

Cho investigated multiple approaches to gathering improv data. He finally came across Spontaneanation, an improv podcast hosted by prolific actor and comedian Paul F. Tompkins that ran from 2015 to 2019.

With its open-topic episodes, about a good 30 minutes of continuous improvisation, high quality recordings, and substantial size, Spontaneanation was the perfect source to mine yes-ands from for the project. The duo fed their Spontaneanation data into a program, and SpolinBot was born.

"One of the cool parts of the project is that we figured out a way to just use improv," May explained. "Spontaneanation was a great resource for us, but is fairly small as data sets go; we only got about 10,000 yes-ands from it. But we used those yes-ands to build a classifier (program) that can look at new lines of dialogue and determine whether they're yes-ands."

Working with improv dialogues first helped the researchers find yes-ands from other sources as well, as most of the SPOLIN data comes from movie scripts and subtitles. "Ultimately, the SPOLIN corpus contains more than five times as many yes-ands from non-improv sources than from improv, but we only were able to get those yes-ands by starting with improv," May said.

SpolinBot has a few controls that can refine its responses, taking them from safe and boring to funny and wacky, and also generates five response options that users can choose from to continue the conversation.

SpolinBot #Goals

The duo has a lot of plans for SpolinBot, along with extending its conversational abilities beyond yes-ands. "We want to explore other factors that make improv interesting, such as character-building, scene-building, 'if this (usually an interesting anomaly) is true, what else is also true?,' and call-backs (referring to objects/events mentioned in previous dialogue turns)," Cho said. "We have a long way to go, and that makes me more excited for what I can explore throughout my PhD and beyond."

May echoed Cho's sentiments. "Ultimately, we want to build a good conversational partner and a good creative partner," he said, noting that even in improv, yes-ands only mark the beginning of a conversation. "Today's bots, SpolinBot included, aren't great at keeping the thread of the conversation going. There should be a sense that both participants aren't just establishing a reality, but are also experiencing that reality together."

That latter point is key, because, as May explained, a good partner should be an equal, not subservient in the way that Alexa and Siri are. "I'd like my partner to be making decisions and brainstorming along with me," he said. "We should ultimately be able to reap the benefits of teamwork and cooperation that humans have long benefited from by working together. And the virtual partner has the added benefit of being much better and faster at math than me, and not actually needing to eat!"

PITTSBURGH, July 15, 2020 - Blocking a newly identified "immune memory checkpoint" in immune cells could improve immunotherapy and help prevent cancers from recurring, according to new findings in mice and human samples by researchers at the UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine. The research was published this week in Nature Immunology.

Immunotherapy drugs that harness the body's own immune system to fight cancer have revolutionized the treatment of many cancers. They work by blocking checkpoint inhibitor proteins like PD1, removing the brakes from cancer-killing T cells in the immune system. However, only about a third of patients respond to these drugs.

"There is still much work to be done to improve cancer immunotherapy because only a small group of people benefit, and even among those, we see many tumors relapsing," said Dario A.A. Vignali, Ph.D., who holds the Frank Dixon Chair in Cancer Immunology at Pitt's School of Medicine and is the co-leader of the Cancer Immunology and Immunotherapy program at the UPMC Hillman Cancer Center. "Our findings point to an important new biological anti-tumor mechanism that we can exploit to provide durable, long-term immune response against tumors."

Vignali and his colleagues discovered that a protein called Neuropilin-1 (NRP1) plays an important role in suppressing immune responses to cancer.

"We knew NRP1 was present on the surface of other T cells, but we wondered whether it somehow altered the function of the killer T cells," said Chang "Gracie" Liu, Ph.D., a postdoctoral researcher in Vignali's lab and first author of the publication. "We thought it might function like any other immune checkpoint molecule and that blocking it would prevent tumors from growing."

Liu and her colleagues created a genetically modified mouse that had NRP1 removed specifically from the surface of only killer T cells. When they grafted tumor cells to this mouse model, they expected that the tumors would not grow or grow more slowly when compared to normal animals, as they had seen when blocking other checkpoint proteins. Instead, they saw no difference at all.

"We were a bit disappointed and thought we had hit a dead end because it looked like removing NRP1 did not impact anti-tumor immunity," said Liu. "But instead of giving up, we asked a different question -- does NRP1 change the capability of the immune system to remember the tumor?"

They removed the tumor, waited and grafted cancer cells again in a different location, mimicking how a tumor might come back in a patient who had surgery. They saw a dramatic effect. Mice that had NRP1 genetically deleted on killer T cells were better protected against the secondary tumor and responded more positively to anti-PD1 immunotherapy when compared to normal mice.

Further experiments revealed that neuropilin was controlling the fate of how T cells develop and establish immune memory. Having NRP1 caused the killer T cells to become exhausted and ineffective in fighting cancer cells, particularly long-term, while removing NRP1 resulted in T cells having an increased immune memory -- the ability of the immune response to respond more potently when it "sees" a tumor again.

These findings in mice also correlated with studies of T cells isolated from the blood of patients with skin cancer or head and neck cancer. Patients with advanced stage head and neck cancer had higher levels of NRP1 on a subset of "memory" killer T cells and fewer of these cells compared to those with earlier stage disease. In patients with advanced skin cancer treated with various immunotherapies, higher NRP1 levels on killer T cells were associated with a poorer response to treatment and a smaller pool of memory T cells.

"This is a completely new area of understanding of how anti-tumor immunity is controlled and will present new therapeutic opportunities to promote and enhance a more durable, long-term anti-tumor response in cancer patients," says Vignali.

Drugs that target NRP1 are already being tested in the clinic in combination with anti-PD1 immunotherapies, and these clinical trials will reveal much more about the role of immune memory in fighting cancer, says Vignali. "This is why persistence pays off. When our initial hypothesis turned out to be incorrect, we kept pursuing other possibilities and ended up with an important new discovery."

Making the transition to a renewable energy future will have environmental and long-term economic benefits and is possible in terms of energy return on energy invested (EROI), UNSW Sydney researchers have found.

Their research, published in the international journal Ecological Economics recently, disproves the claim that a transition to large-scale renewable energy technologies and systems will damage the macro-economy by taking up too large a chunk of global energy generation.

Honorary Associate Professor Mark Diesendorf, in collaboration with Prof Tommy Wiedmann of UNSW Engineering, analysed dozens of studies on renewable electricity systems in regions where wind and/or solar could provide most of the electricity generation in future, such as Australia and the United States.

The Clean Energy Australia report states that renewable energy's contribution to Australia's total electricity generation is already at 24 per cent.

Lead author A/Prof Diesendorf is a renewable energy researcher with expertise in electricity generation, while co-author Prof Tommy Wiedmann is a sustainability scientist.

A/Prof Diesendorf said their findings were controversial in light of some fossil fuel and nuclear power supporters, as well as some economists, rejecting a transition to large-scale electricity renewables.

"These critics claim the world's economy would suffer because they argue renewables require too much lifecycle energy to build, to the point of diverting all that energy away from other uses," he said.

"Our paper shows that there is no credible scientific evidence to support such claims, many of which are founded upon a study published in 2014 that used data up to 30 years old.

"There were still research papers coming out in 2018 using the old data and that prompted me to examine the errors made by those perpetuating the misconception."

A/Prof Diesendorf said critics' reliance on outdated figures was "ridiculous" for both solar and wind technology.

"It was very early days back then and those technologies have changed so dramatically just in the past 10 years, let alone the past three decades," he said.

"This evolution is reflected in their cost reductions: wind by about 30 per cent and solar by 85 to 90 per cent in the past decade. These cost reductions reflect increasing EROIs."

A/Prof Diesendorf said fears about macro-economic damage from a transition to renewable energy had been exaggerated.

"Not only did these claims rely on outdated data, but they also failed to consider the energy efficiency advantages of transitioning away from fuel combustion and they also overestimated storage requirements," he said.

"I was unsurprised by our results, because I have been following the literature for several years and doubted the quality of the studies that supported the previous beliefs about low EROIs for wind and solar."

Spotlight on wind and solar

A/Prof Diesendorf said the study focused on wind and solar renewables which could provide the vast majority of electricity, and indeed almost all energy, for many parts of the world in future.

"Wind and solar are the cheapest of all existing electricity generation technologies and are also widely available geographically," he said.

"We critically examined the case for large-scale electricity supply-demand systems in regions with high solar and/or high wind resources that could drive the transition to 100 per cent renewable electricity, either within these regions or where power could be economically transmitted to these regions.

"In these regions - including Australia, the United States, Middle East, North Africa, China, parts of South America and northern Europe - variable renewable energy (VRE) such as wind and/or solar can provide the major proportion of annual electricity generation.

"For storage, we considered hydroelectricity, including pumped hydro, batteries charged with excess wind and/or solar power, and concentrated solar thermal (CST) with thermal storage, which is a solar energy technology that uses sunlight to generate heat."

Energy cost/benefit ratio approach

Co-author Prof Wiedmann said the researchers used Net Energy Analysis as their conceptual framework within which to identify the strengths and weaknesses of past studies in determining the EROI of renewable energy technologies and systems.

"We used the established Net Energy Analysis method because it's highly relevant to the issue of EROI: it aims to calculate all energy inputs into making a technology in order to understand the full impact," Prof Wiedmann said.

"From mining the raw materials and minerals processing, to building and operating the technology, and then deconstructing it at the end of its life. So, it's a lifecycle assessment of all energy which humans use to make a technology."

Renewable transition possible

A/Prof Diesendorf said their findings revealed that a transition from fossil fuels to renewable energy was worthwhile, contradicting the assumptions and results of many previous studies on the EROIs of wind and solar.

"We found that the EROIs of wind and solar technologies are generally high and increasing; typically, solar at a good site could generate the lifecycle primary energy required to build itself in one to two years of operation, while large-scale wind does it in three to six months," he said.

"The impact of storage on EROI depends on the quantities and types of storage adopted and their operational strategies. In the regions we considered, the quantity of storage required to maintain generation reliability is relatively small.

"We also discovered that taking into account the low energy conversion efficiency of fossil-fuelled electricity greatly increases the relative EROIs of wind and solar.

"Finally, we found the macro-economic impact of a rapid transition to renewable electricity would at worst be temporary and would be unlikely to be major."

A more sustainable future

A/Prof Diesendorf said he hoped the study's results would give renewed confidence to businesses and governments considering or already making a transition to more sustainable electricity technologies and systems.

"This could be supported by government policy, which is indeed the case in some parts of Australia - including the ACT, Victoria and South Australia - where there's strong support for the transition," he said.

"A number of mining companies in Australia are also going renewable, such as a steel producer which has a power purchase agreement with a solar farm to save money, while a zinc refinery built its own solar farm to supply cheaper electricity."

A/Prof Diesendorf said the Australian Government, however, could help with more policies to smooth the transition to renewable energy.

"In Australia the transition is happening because renewable energy is much cheaper than fossil fuels, but there are many roadblocks and potholes in the way," he said.

"For example, wind and solar farms have inadequate transmission lines to feed power into cities and major industries, and we need more support for storage to better balance the variability of wind and solar.

"So, I hope our research will help bolster support to continuing with the transition, because we have discredited the claim that the EROIs of electricity renewables are so low that a transition could displace investment in other sectors."

Over the last decade, the field of condensed matter physics has experienced a golden age with the discovery of new materials and properties, and related technologies being developed at breakneck speed thanks to the arrival of topological physics. Topological physics took off in 2008 with the discovery of topological insulator, a type of material that is electrically insulating in the bulk but metallic on the surface.

Since then, scientists have found more exotic topological phases including Dirac semimetals, Weyl semimetals and Axionic insulators. But most recently, materials that are insulating in the bulk, on surfaces and edges but are metallic only on the hinges or at the corners have been theoretically predicted. These bizarre new materials called higher-order topological insulators are extremely rare and only the element bismuth has been experimentally proven to possibly belong to this category so far.

What is a hinge state anyway? Imagine a box - longer and wider than tall - with flaps on top and bottom that you can open to put things inside. The space inside the box would be called the bulk. Most materials which conduct electricity do so in the bulk. However, in topological insulators, the bulk of the box is electrically insulating but the top and bottom - the flaps - are metallic and maintain surface states. For some materials, the bulk, the top and bottom of the box are insulating but the sides (edges) are metallic. These have edge states which have been demonstrated in magnetic topological insulators. Finally, in higher-order topological insulators, the bulk, top, bottom and sides of the box are all insulating but the hinges and corners of the box are metallic and have disparate hinge or corner states. These hinge states have also been predicted to exist in topological semimetals like bismuth. The hinge states in particular are expected to be promising for the study of spintronics because the direction of their propagation is tied to their spin as well as for Majorana fermions which are actively being investigated for their applications to fault-tolerant quantum computing.

Now an international team of scientists from the United States, Hong Kong, Germany, and South Korea have identified a new higher-order topological insulator. It is a layered two-dimensional transition metal dichalcogenide (TMDC) called WTe2. This is a famous material in condensed matter physics that displays a variety of exotic properties from titanic magnetoresistance to quantized spin hall effect. It was the first example of a Type-II Weyl semimetal that can be made into devices that are only one layer in thickness and is exfoliatable like graphene. WTe2 has also shown to superconduct under pressure which means electrons form pairs and a supercurrent travels through it without any resistance.

Adding to this carnival of properties, theoretical physicists in 2019 envisioned WTe2 and its sister material MoTe2 to be higher-order topological insulators with metallic hinge states. Many research teams around the world have since searched for evidence of these exotic states in WTe2 and MoTe2 and some recent results have shown that there are extra conductive states at their edges. But the researchers were unable to identify if these were truly edge states or the highly sought-after hinge states.

In a study published in Nature Materials on July 6, 2020, the team led by Kin Chung Fong (Raytheon BBN Technologies), Mazhar N. Ali (Max Plank Institute of Microstructure Physics and also Material Mind Inc.), Kam Tuen Law (Hong Kong University of Science and Technology) and Gil-Ho Lee (Pohang University of Science and Technology, and the Asia Pacific Center for Theoretical Physics) took a new approach by using the Josephson junctions to spatially resolve the supercurrent flow and to show that WTe2 does indeed appear to have hinge states and be a higher-order topological insulator (Link to paper).

Josephson junctions are an incredibly important device and tool in physics. They are used in a variety of technological applications including magnetic resonance imaging (MRI) machines as well as in qubits, which are building blocks of quantum computers. These junctions are formed when two superconducting electrodes like niobium (Nb) are connected by a non-superconducting bridge like a high-quality WTe2 in a thin film device. When the temperature is lowered enough, the supercurrent that is injected from one Nb electrode can travel across the bridge without resistance to the other Nb electrode. Therefore the overall device shows zero resistance and is said to be superconducting.

However, no infinite amount of supercurrent can be sent across the bridge while retaining superconductivity. When the injected current exceeds a critical current, the junction turns into a normal state and exhibits finite resistance. The Josephson effect states that as a function of the applied magnetic field, the critical current will oscillate in a Fraunhofer pattern between high and low values due to the changing phase of the superconducting wave-function across the sample.

The team realized that hidden in this oscillation is location information of the supercurrent while it travels in the sample. By taking an inverse Fourier transform of the Fraunhofer pattern, the researchers were able to visualize the supercurrent flow in the sample and found that it indeed travels on the sides of the WTe2 device. However, this was not enough to distinguish the edge states from the hinge states.

As shown in the figure below, due to a quirk in the symmetry-based origin of the hinge states, not all hinges are identical on the WTe2 sample. For example, there are metallic hinge states on top left and bottom right hinges on the sample but not on the top right or bottom left. This is different from an edge state, which would simply be existing on the entirety of the left and right sides of the sample. Regarding this, Kin Chung Fong of Raytheon BBN Technologies explains, "We used this difference to our advantage. By connecting superconducting electrodes on just the top half of the sample and not the bottom half, we realized we would see a different Fraunhofer pattern if hinge states existed and not edge states." He further commented, "In this configuration, electrodes would connect to only one of the hinge states (i.e. top left and not bottom right), which would show a distinct Fraunhofer pattern. If there were edge states, this configuration wouldn't be any different than connecting to both the bottom and top halves of the sample and the Fraunhofer would look the same." When they carried out this challenging experiment, they observed the hallmark of the hinge state, not the edge state.

"But that's not all. WTe2 is a fairly low-symmetry orthorhombic material with high crystalline anisotropy. The different directions in the crystal are not equivalent and we also theorized and confirmed that the hinge states existing in WTe2 aren't all equivalent either. In some directions, they mix into the bulk while in other directions they don't," explained Kam Tuen Law at Hong Kong University of Science and Technology.

"There is a variety of exciting physics to be explored in these compounds in the near future now that hinge states have been found in WTe2," remarked Gil Ho Lee of Pohang University of Science and Technology. He added, "The possibility for dissipationless interconnections, true 1D superconducting nano-wires and spintronics devices, topological superconductivity, Majorana fermions and correspondingly topological quantum computers are all on the horizon."

Mazhar N. Ali at the Max Plank Institute of Microstructure Physics explained, "WTe2 may be the second material shown to host hinge states, but it is very different from the other candidate, bismuth. Being 2D, WTe2 is easily fabricable into nano-devices with controlled surfaces, and can be layered on top of other 2D materials in heterostructures and even on top of itself when slightly twisted to form a Moire superlattice." He added, "Its sister material MoTe2 is expected to exhibit the same hinge states but it is an intrinsic superconductor at low temperatures." He questioned excitedly, "How can these hinge states be modified, controlled, and used? There are a lot of exciting research opportunities ahead."

For most of us, our closest encounter with the element fluorine is likely to be our toothpaste or a municipal water supply with added fluoride.

But excess fluorine can be a problem. For example, high levels of fluorine in the soil can hurt plants. Fluorine in soils may also affect microbes and other organisms higher along the food chain.

A new study explored whether soil fluorine levels in New Zealand are high enough to hurt a specific microbe called Rhizobium.

Rhizobium bacteria live in root nodules of legume plants, like beans and lentils. These bacteria 'fix' atmospheric nitrogen, making the nutrients into a form the host plant can use.

Nitrogen fixation by Rhizobia means farmers need to use less nitrogen fertilizer. That can save significant costs.

If soil fluorine levels become high enough to hurt Rhizobia, it could impact the legume crops the bacteria help support.

In addition, pastures for grazing livestock often contain clover, another legume. High fluorine levels could harm Rhizobia living in clover root nodules. Ultimately, that could impact the livestock that eat the clover.

But there are a lot of unknowns about fluorine and its specific effects on microbes. "No one has investigated the potential impact of fluorine on Rhizobia," says Christopher Anderson, a researcher at Massey University in New Zealand.

In the study, Anderson and colleagues found that high levels of fluorine are toxic to Rhizobia and white clover.

In laboratory studies, fluorine levels above 100 mg per liter hampered Rhizobia growth. High fluorine concentrations also led to changes in the shape and metabolic activity of the bacteria.

These high fluorine levels also impacted white clover. At fluorine concentrations above 100 mg per liter, white clover seedlings did not survive.

Fortunately, there's some good news as well. The concentration of fluorine at which it is toxic is much greater than the concentration the researchers found in New Zealand soils.

"This means that there is no problem, right now, of fluorine levels in soil affecting Rhizobia in New Zealand's soils," says Anderson.

This finding gives confidence to agencies in New Zealand that are tasked with ensuring sustainable farming systems. "Without our research, they would still be in the dark," says Anderson.

Rhizobia - and one of the host plants, white clover - are key parts of the New Zealand way of animal husbandry.

"In New Zealand, we are fortunate that we can grow grass year-round," says Anderson. "Our livestock are kept on pasture all year."

Rhizobium bacteria associated with clover fixes nitrogen from the atmosphere. When clover plants die, they break down in the soil. The fixed nitrogen becomes available to other plants.

"So, we don't need to apply as much synthetic nitrogen fertilizers, such as urea, to our pastures with clover" says Anderson.

But farmers need to apply other fertilizers to New Zealand's pastures, including phosphorus fertilizers. That's where concerns about fluorine levels come in.

Fluorine is a fairly common element in Earth's crust. It is concentrated in some materials, like phosphate rocks. These rocks are the main ingredient in many fertilizers with phosphorus.

In areas where phosphorus fertilizers are applied year after year, fluorine can accumulate in soils over time. This accumulated fluorine can become a soil contaminant.

"But in some cases, biological systems are very tolerant of contaminants," says Anderson.

Anderson aims to determine fluorine levels at which it is toxic to animals. "In particular we would like to look at earthworms," says Anderson. "Earthworms are very useful ecological indicators."

Researchers also want to look at grazing animals, which can eat a considerable amount of soil. When animals ingest too much fluorine, they can develop fluorosis. That can cause bone, teeth, and kidney problems.

"We have to make sure the science is looking after all aspects of the pastoral system - soil, microorganisms, plants, and animals," says Anderson.

A Korean research team has developed a technology that enables the effective control of fine particulate matter and nanoplastics, which are major causes of human toxicity and ecosystem disturbances. This technology, which allows for real-time sorting, purification, and concentration of nanoparticles invisible to the human eye, has great potential application, not only for the removal of toxic particles from the natural environment, but also for removing viruses and detecting dementia-related proteins and cancer diagnostic markers. Due to its vast range of applicability, this technology is attracting much attention in scientific and academic circles.

The research team, led by Dr. Yong-sang Ryu of the Sensor System Research Center in the National Agenda Research Division at the Korea Institute of Science and Technology (KIST), working with a team led by Dr. Sin-Doo Lee of the Department of Electrical and Computer Engineering at Seoul National University (SNU, President Se-Jung Oh), announced its successful development of a '*nanogap electrode' able to effectively capture ultra-fine floating particles as small as 20 nanometers (nm, 1/1000 the thickness of a human hair). The research team used the newly developed electrode in successful selective concentration and positioning experiments for **extracellular vesicles (exosomes), which have recently been gaining much attention in the new drug development field and as new diagnostic markers for cancer as well as dementia-related proteins (***Amyloid-beta).

*Nanogap electrode: Electrode with a nanometer-scale gap between two electrodes.

**Extracellular vesicle: Also called an exosome. A single-membraneparticle released from a cell, in the shape of a flattened pocket.

***Amyloid-beta: A representative dementia-causing protein, usually found in the brain cells of dementia patients.

Researchers around the world have shown a keen interest in developing techniques to manipulate nano-size particles without damaging them. The optical tweezers technology, which received the Nobel Prize in Physics in 2018, is representative of such technologies. However, it has proven difficult to go beyond individual particle-level manipulation/measurement and to realize commercialization on a massive scale. Researchers have repeatedly run into technical limitations in scaling mechanisms for collecting, sorting, purifying, and concentrating particles that are 100 nm or less in size; however, such mechanisms are needed to work in large-scale atmospheric and water environments.

The joint KIST-SNU research team, through centimeter (cm) scale device production for particle concentration and purification experiments, was able to overcome these limitations and successfully scaled up the nanogap electrodes by sandwiching nanoscaled insulator film between two electrodes in a vertical alignment, allowing the 'dielectrophoretic tweezer' technology to be applied to large areas. Dielectrophoresis is a technology wherein wavelengths vibrating several hundred to several thousand times per second are applied to two electrodes to form an non-uniform electrical field distribution around the electrodes. These electrodes are then used to attract or repel particles in the vicinity of the nanogaps.

The joint research team conducted experiments to find technologies that could use universally available semiconductor processes, rather than expensive equipment used only by select companies. During the experiment process, the team found that the dielectrophoretic force produced by electrodes in an asymmetric electrode-arranged vertical array was over 10 times greater than that of a conventional horizontally-aligned nanogap array. This discovery simultaneously solved the problems of scaling up and reduced the costs associated with the nanogap technology. Using the conventional horizontal electrode array production method, it costs a minimum of several hundreds of thousands of won to produce enough nanogap electrodes to cover the area of a fingernail. Using the new dielectrophoresis technology, it takes only KRW 5,000 to produce enough nanogap electrodes to cover the area of an LP disc.

The vertical nanogap technology developed by the KIST research team makes it possible to scale up the nanogap electrode technology, produce nanogap electrodes in numerous shapes and sizes, and radically reduces unit production costs. As such, the technology has a broad range of potential applications. According to the research team, when used in air or water filters, the nanogap electrodes can function under low voltage (such as that of an ordinary AA cell) to detect and remove, in real time, various microscopic floating particles such as fine dust, nanoplastics, viruses, germs, and bacteria.

Dr. Eui-Sang Yu, the principle author of the study, commented, "The achievement has future application for the sorting and purifying of nano-sized particles, regardless of type of particle or the environment." Dr. Yong-Sang Ryu of the KIST, the corresponding author of the study, added, "We hope that the study can make broad contributions to solving various social problems and enhance the general quality of human life."

Early life stress is associated with youth-onset depression for some types of stress but not others

Results support an association between eight different types of early life stress and the development of depression in youth

Washington, DC, July 15, 2020 - A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that individuals exposed to early life stress (ELS) were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.

Examining the association between eight different types of ELS and youth-onset depression, the authors found that while some types of ELS (e.g., poverty) were not associated with MDD, other types of stress, including emotional abuse, were associated more strongly with MDD than a broader assessment of ELS.

"Researchers have documented that early life stress increases the risk for developing depression in adulthood. We wanted to know the degree to which it was associated with depression earlier in life--specifically during childhood or adolescence," said lead author Joelle LeMoult, PhD, a researcher at the University of British Columbia, Vancouver, Canada. "Given that earlier onsets of depression often mean a more recurrent course across the lifespan. We found that exposure to early life stress more than doubled the likelihood someone will develop youth-onset depression.

"These findings indicate that there is a narrow window between adversity and depression during which we have the opportunity to intervene."

The findings are based on a meta-analysis of data from 62 journal articles and over 44,000 unique participants. Studies that assessed early life stress and the presence or absence of MDD before the age of 18 years were also included.

Compared to youth who were not exposed to ELS, youth who were exposed to ELS were 2.5 times more likely to develop MDD (OR=2.50; 95% CI [2.08, 3.00]).

The authors also conducted eight additional meta-analyses to examine the association between different types of ELS and a diagnosis of MDD during childhood or adolescence. Sexual abuse, physical abuse, death of a family member, domestic violence, and emotional abuse were associated with significantly higher risk for youth-onset MDD; in contrast, poverty, illness/injury, and exposure to a natural disaster were not.

Several variables moderated the association between ELS and youth-onset MDD. For example, studies that used interview-based assessments or included larger sample sizes reported stronger associations between ELS and depression.

Taken together, findings provide evidence that the adverse effects of ELS on risk for MDD manifests early in development, before adulthood, and varies by type of ELS. Further, findings support recommendations to use best-practice methods in early life stress research.