Brain

CAMBRIDGE, MA -- A variety of medical devices can be inserted into the gastrointestinal tract to treat, diagnose, or monitor GI disorders. Many of these have to be removed by endoscopic surgery once their job is done. However, MIT engineers have now come up with a way to trigger such devices to break down inside the body when they are exposed to light from an ingestible LED.

The new approach is based on a light-sensitive hydrogel that the researchers designed. Incorporating this material into medical devices could avoid many endoscopic procedures and would give doctors a faster and easier way to remove devices when they are no longer needed or are not functioning properly, the researchers say.

"We are developing a set of systems that can reside in the gastrointestinal tract, and as part of that, we're looking to develop different ways in which we can trigger the disassembly of devices in the GI tract without the requirement for a major procedure," says Giovanni Traverso, an assistant professor of mechanical engineering, a gastroenterologist at Brigham and Women's Hospital, and the senior author of the study.

In a study in pigs, the researchers showed that devices made with this light-sensitive hydrogel can be triggered to break down after being exposed to blue or ultraviolet light from a small LED.

Ritu Raman, a postdoc at MIT's Koch Institute for Integrative Cancer Research, is the lead author of the paper, which appears today in Science Advances. Other authors of the paper are former technical associates Tiffany Hua, Jianlin Zhou, Tina Esfandiary, and Vance Soares; technical associates Declan Gwynne, Joy Collins, and Siddartha Tamang; graduate student Simo Pajovic; Division of Comparative Medicine veterinarian Alison Hayward; and David H. Koch Institute Professor Robert Langer.

Controlled breakdown

Over the past several years, Traverso and Langer have developed many ingestible devices designed to remain in the GI tract for extended periods of time. They have also worked on a variety of strategies to control the breakdown of such devices, including methods based on changes in pH or temperature, or exposure to certain chemicals.

"Given our interests in developing systems that can reside for prolonged periods in the gastrointestinal tract, we continue to investigate a range of approaches to facilitate the removal of these systems in the setting of adverse reaction or when they are no longer needed," Traverso says. "We're really looking at different triggers and how they perform, and whether we can apply them to different settings."

In this study, the researchers explored a light-based trigger, which they believed could offer some advantages over their earlier approaches. One potential advantage is that light can act at a distance and doesn't need to come into direct contact with the material being broken down. Also, light normally does not penetrate the GI tract, so there is no chance of accidental triggering.

To create the new material, Raman designed a light-sensitive hydrogel based on a material developed in the lab of Kristi Anseth, a former Langer lab postdoc who is now a professor of chemical and biological engineering at the University of Colorado at Boulder. This polymer gel includes a chemical bond that is broken when exposed to a wavelength of light between 405 and 365 nanometers (blue to ultraviolet).

Raman decided that instead of making a material composed exclusively of that light-sensitive polymer, she would use it to link together stronger components such as polyacrylamide. This makes the overall material more durable but still allows it to break apart or weaken when exposed to the right wavelength of light. She also constructed the material as a "double network," in which one polymer network surrounds another.

"You're forming one polymer network and then forming another polymer network around it, so it's really entangled. That makes it very tough and stretchy," Raman says.

The material's properties can be tuned by varying the composition of the gel. When the light-sensitive linker makes up a higher percentage of the material, it breaks down faster in response to light but is also mechanically weaker. The researchers can also control how long it takes to break down the material by using different wavelengths of light. Blue light works more slowly but poses less risk to cells that are sensitive to damage from ultraviolet light.

Deflated by light

The gel and its breakdown products are biocompatible, and the gel can be easily molded into a variety of shapes. In this study, the researchers used it to demonstrate two possible applications: a seal for a bariatric balloon and an esophageal stent. Standard bariatric balloons, which are sometimes used to help treat obesity, are inflated in a patient's stomach and filled with saline. After about six months, the balloon is removed by endoscopic surgery.

In contrast, the bariatric balloon that the MIT team designed can be deflated by exposing the seal to a tiny LED light, which would in principle be swallowed and then pass out of the body. Their balloon is made of latex and filled with sodium polyacrylate, which absorbs water. In this study, the researchers tested the balloons in pigs and found that the balloons swelled up as soon as they were placed in the stomach. When a small, ingestible LED emitting blue light was placed in the stomach for about six hours, the balloons slowly deflated. With a higher-power light, the material broke down within 30 minutes.

The researchers also molded the light-sensitive gel into an esophageal stent. Such stents are sometimes used to help treat esophageal cancer or other disorders that cause a narrowing of the esophagus. A light-triggerable version could be broken down and passed through the digestive tract when no longer needed.

In addition to those two applications, this approach could be used to create other kinds of degradable devices, such as vehicles for delivering drugs to the gastrointestinal tract, according to the researchers.

"This study is a proof of concept that we can create this kind of material, and now we're thinking about what are the best applications for it," Traverso says.

CHARLOTTESVILLE, Va. - The Association for Computing Machinery has named Matthew B. Dwyer, a University of Virginia professor of computer science, a fellow. Fellowships are conferred to association members for technological accomplishments that help define the digital age and improve professional and personal lives. Association for Computing Machinery Fellows comprise an elite group that represents less than 1% of the association's global membership.

Dwyer earned his Ph.D. in Computer Science from the University of Massachusetts at Amherst in 1995. He joined UVA Engineering in 2018 from the University of Nebraska, where he was the Leonard A. Lovell Professor and chair of the Department of Computer Science and Engineering. At UVA Engineering Dwyer is the John C. Knight Faculty Fellow and professor in the Department of Computer Science.

Dwyer has published more than 130 articles in his research areas of software verification and validation, software engineering and program analysis. He has been supported by more than 35 external grants. He is exploring methods to assure the dependability of autonomous systems.

Dwyer has received numerous Association for Computing Machinery accolades. He was named a Distinguished Scientist and has received the Special Interest Group on Software Engineering Distinguished Service Award, three "test of time" awards and four distinguished paper awards.

Dwyer is also a National Science Foundation Faculty Early Development Career Award recipient, a Fulbright Research Scholar, an Institute of Electrical and Electronics Engineers Fellow and a David Lorge Parnas Fellow of the Irish Software Center.

"The research recognized by the selection committee is the product of collaborations with a wonderful set of mentors, colleagues and students I've been privileged to work with over the years," said Dwyer. "It is an honor to be named an ACM Fellow and to be in the company of my fellow professors at UVA," computer science professors Jack. W. Davidson, Madhav Marathe, John A. Stankovic, Mary Lou Soffa and Aidong Zhang; computer science professor and chair Kevin Skadron; and computer science professors emeritus Anita Jones and William Wulf.

"Computing technology has had a tremendous impact in shaping how we live and work today," said Association for Computing Machinery President Cherri M. Pancake. "All of the technologies that directly or indirectly influence us are the result of countless hours of collaborative and/or individual work, as well as creative inspiration and, at times, informed risk-taking. Each year, we look forward to welcoming some of the most outstanding individuals as Fellows. The ACM Fellows program is a cornerstone of our overall recognition effort. In highlighting the accomplishments of the ACM Fellows, we hope to give credit where it is due, while also educating the public about the extraordinary array of areas in which computing professionals work."

Sand crabs, a key species in beach ecosystems, were found to have increased adult mortality and decreased reproductive success when exposed to plastic microfibers, according to a new Portland State University study.

Dorothy Horn, a Ph.D. candidate in PSU's Earth, Environment and Society program, examined the effects of exposure to microfibers on adult mortality, reproductive output and embryonic development of the sand crab, a dominant organism on sandy beaches from British Columbia to Baja California, Mexico. Sand crabs, which eat by filtering small particles from the water, are considered indicator species because their health reflects the health of the ecosystem.

"When pollutants affect sand crabs, it's also affecting most organisms around it in that ecosystem," Horn said. "We don't eat them, but they're a bright blinking light for 'There's a problem in this area.'"

Horn found microplastics in all the sand samples analyzed from 19 beaches along the Oregon coast. She then conducted a lab experiment to mimic the concentrations of microfibers the crabs would be exposed to on the beach.

The study found that with an increasing number of microplastic fibers internalized, crab mortality increased while the number of days that a crab held live/viable eggs decreased. Exposure to microplastics also caused variability in a crab's embryonic development rates.

Horn said sand crabs are prey for shorebirds, nearshore fish and some marine mammals, and their increased mortality and decreased reproductive performance following exposure to microplastics could have potential effects on species higher up on the food chain.

"We've proved it's causing them harm, and it can have harmful effects on these other organisms," Horn said.

A new study from researchers at Western University and Queen's University definitively shows that regular exposure to THC, the main psychoactive ingredient in cannabis, during pregnancy has significant impact on placental and fetal development. With more than a year since the legalization of recreational cannabis in Canada, the effects of its use during pregnancy are only now beginning to be understood.

The study, published today in Scientific Reports, uses a rat model and human placental cells to show that maternal exposure to THC during pregnancy has a measurable impact on both the development of the organs of the fetus and the gene expression that is essential to placental function.

The researchers demonstrated in a rat model that regular exposure to a low-dose of THC that mimics daily use of cannabis during pregnancy led to a reduction in birth weight of 8 per cent and decreased brain and liver growth by more than 20 per cent.

"This data supports clinical studies that suggest cannabis use during pregnancy it is associated with low birth weight babies. Clinical data is complicated because it is confounded by other factors such as socioeconomic status," said Dan Hardy, PhD, Associate Professor at Western's Schulich School of Medicine & Dentistry and co-author on the paper. "This is the first study to definitively support the fact that THC alone has a direct impact on placental and fetal growth."

The research team was also able to characterize how THC prevents oxygen and nutrients from crossing the placenta into the developing fetus. By studying human placental cells, the researchers found that exposure to THC caused a decrease in a glucose transporter called GLUT-1. This indicates that the THC is preventing the placental transfer of glucose, a key nutrient, from the mother to the fetus. They also found a reduction in placental vasculature in the rat model suggesting reduced blood flow from the mother to the fetus.

The researchers say both of those factors are likely contributing to the growth restriction that they observed in the offspring.

The researchers point out that there are currently no clear guidelines from Health Canada on the use of cannabis in pregnancy and some studies have shown that up to one in five women are using cannabis during pregnancy to prevent morning sickness, for anxiety or for social reasons.

"Marjiuana has been legalized in Canada and in many states in the US, however, its use during pregnancy has not been well studied up until this point. This study is important to support clinicians in communicating the very real risks associated with cannabis use during pregnancy," said David Natale, PhD, Associate Professor at Queen's and co-author on the paper.

Skokie, IL - The ISSCR is updating its Guidelines for Stem Cell Research and Clinical Translation to respond to recent scientific advances that include the use of pluripotent stem cell (PSC) to create models of early human embryo development (see Stem Cell Reports 14:1-6). As the science continues to advance, it raises important scientific, clinical, ethical, and societal issues for researchers, regulators, and funding agencies. The ISSCR believes the scientific community must address these challenges to establish parameters for research in this area.

Stem cell-based models of early embryo development are important to enable researchers to study early human development without destroying human embryos. The ability to model early embryo development through the culture of stem cells may also make it possible to ethically study periods of human development that are poorly understood or difficult to model using animal embryos. This area of research could improve fertility treatment and prevent the development of certain congenital diseases.

The ISSCR will develop detailed guidance on this area of research in the updated ISSCR Guidelines that will be released in early 2021. Until the Guidelines are released, the ISSCR encourages researchers and institutions to observe the following principles and current recommendations when considering research in this area:

Research involving the culture of pluripotent stem cells (PSCs) to model the entire conceptus (the embryo and extraembryonic structures) should be overseen and authorized by a special committee capable of evaluating the ethical and scientific justification of proposed research according to the Embryo Research Oversight (EMRO) process described in ISSCR Guidelines Recommendation 2.1.1;

Multicellular structures derived from PSCs that do not model the entire conceptus (for example lacking extraembryonic structures and lack the potential to develop into an organism) are not embryos and should not be regulated as such. Proposed research using these models should be reported to an EMRO committee but does not require prior authorization;

Models of the entire conceptus that have the potential to develop into an organism should not be maintained in culture beyond 14 days or the time at which the primitive streak develops (ISSCR Guidelines, Recommendation 2.1.3.3 Category 3);?

Models of the entire conceptus that are cultured as individual components such as germ layers or extraembryonic structures before 14 days, or when the primitive streak develops, can continue in culture but should be reported to an EMRO committee;

Researchers using models involve combining human PSC-based embryo-like structures with other animal or human cells or tissues should endeavor to seek review by an EMRO process; and

Multicellular structures derived from PSCs that seek to model certain aspects of the conceptus or the entire conceptus should not be transferred into the uterus of a human or animal (ISSCR Guidelines, Recommendation 2.1.3.3 Category 3).

Washington, DC--Diagnosing EVALI--the e-cigarette, or vaping, product use associated lung injury illness that's recently garnered national attention--can be challenging. Initial symptoms may resemble pneumonia or go unrecognized, according to case analysis in the Journal of the American College of Emergency Physicians (JACEP) Open, a new open access journal.

"Electronic cigarettes and vaping products are sending thousands of smokers, especially teens, to emergency departments," said Kaitlyn Works, MD, an emergency physician with Vanderbilt University Medical Center and lead study author. "We must be crystal clear with young people: E-cigarettes and vaping products are not a healthy alternative to smoking. They can be dangerous, cause injuries and illnesses, or even death."

The analysis, "E-cigarette, or vaping, product use associated lung injury (EVALI): a case report of a pneumonia mimic with severe leukocytosis and weight loss," details the case of a 20-year-old male with no significant medical history who was hospitalized for four days then left against medical advice, only to return to the emergency department for chest pain, fever and shortness of breath. For two weeks leading up to his emergency, he had a productive cough, fever, diarrhea, nausea and significant weight loss.

"This flu season we are seeing an additional layer of complexity--EVALI symptoms may resemble pneumonia and become more dangerous or deadly when left untreated," Dr. Works said. "A patient with EVALI may have symptoms that vary and overlap with many illnesses, making it more complicated to diagnose."

Accurate diagnoses typically include the ruling out of other infections, autoimmune disorders or other conditions. In this case, negative tests were returned for strep, HIV, hepatitis and other diseases. A camera was inserted through the patient's airway to examine the lungs and a pulmonary consultation and CT scan confirmed EVALI.

The authors also note that nearly one-third of EVALI patients require intubation and mechanical breathing help.

As of January 2020, a total of 2,602 hospitalized EVALI cases have been reported in all 50 states, DC, Puerto Rico and U.S. Virgin Islands. Fifty-seven deaths have been confirmed.

CDC has identified vitamin E acetate, a thickening agent in many e-cigarette or vaping products with THC as a "chemical of concern" among EVALI cases. CDC recommends that people do not use e-cigarette or vaping products with THC.

"The simplest way to avoid EVALI is to avoid these products," Dr. Works said.

Less physical activity for infants below one year of age may lead to more fat accumulation which in turn may predispose them to obesity later in life, suggests a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

In the study, published January 16 in the journal Obesity, researchers tracked the physical activity levels of 506 infants using small ankle-worn accelerometers for four days per tracking period at ages 3, 6, 9, and 12 months. For each tracking period after 3, average physical activity increased by about four percent, in line with infants becoming generally more mobile and active over the course of their first year. Among infants, higher physical activity measured by the accelerometer was associated with lower central adiposity, a measure of lower-torso fat accumulation.

"This is the first study to demonstrate an association over time between higher levels of objectively measured physical activity and lower central adiposity in infancy," says study lead author Sara Benjamin-Neelon, PhD, JD, associate professor in the Department of Health, Behavior and Society and the Helaine and Sidney Lerner Professor of Public Health Promotion at the Bloomberg School.

There is evidence that infants who gain weight more rapidly in the first months of life are more likely to have obesity years later in middle childhood. About 40 percent of adults in the U.S.--more than 90 million people--are obese, up from 15 percent in 1970. Obesity brings a greater risk of diabetes, heart disease, certain cancers, autoimmune disorders, and many other ailments. Scientists suspect rising obesity rates are linked to higher-calorie diets and lower rates of physical activity, and that both can start promoting obesity in early life.

"Some evidence suggests that the earlier you can get infants crawling and walking, and providing them with opportunities to move freely throughout the day, the more you can help protect them against later obesity," says Benjamin-Neelon.

The study was part of a larger study of infant growth and obesity, called the Nurture study, which covered 666 mothers and their infants from the greater Durham, North Carolina, area during 2013 to 2016. Of this group, Benjamin-Neelon and her colleagues were able to get adequate accelerometer data for 506 infants. More than two thirds of the infants in the study were black, an underrepresented group in U.S.-based birth cohorts. Rates of obesity have been increasing faster among black children--as well as Native American and Latino children--compared to white children.

Studying infant physical activity levels has challenges. Accelerometers that track infant movement, much like Fitbits that adults wear, can in principle provide objective measures of activity, and have been used successfully in research on toddlers and preschoolers. For infants, movements that are initiated by a parent, such as carrying the infant, can complicate the data. The accelerometer measures all movement--regardless of whether it is initiated by infants or caregivers moving infants. Still, the results of the new study, the largest ever to use accelerometers to track infant activity over time, suggest that it is possible to overcome this limitation.

"We know that as infants grow older and start crawling and walking, their physical activity levels increase, and we saw such increases in our study--which makes me think there's some validity to the use of accelerometers for infants," Benjamin-Neelon says.

She and her colleagues found that among the infants in the study, an increase in recorded activity by one "standard deviation"--essentially a standard proportion of the range of the data--was associated with a small but significant decrease in central adiposity. The latter is a skinfold-thickness-based measurement that relates to abdominal fat levels and is thought to be a relatively good measure of obesity-related fat accumulation.

Benjamin-Neelon notes that larger, longer-term studies will be necessary to determine the sustained effect of infant physical activity, but that preventing extended periods of inactivity for infants will almost certainly be good for them.

"Even in infancy it's important for children to move freely," she says. "These days, infants are spending more and more sedentary time in car seats, high chairs, strollers--and perhaps we haven't thought enough about the developmental ramifications of these types of restrictive devices."

Letting infants move freely on a floor or in a crib is one solution, but Benjamin-Neelon emphasizes that it is also important for parents to create situations that nudge infants to develop more advanced motor skills, such as helping them grasp an adult's hands or other support in order to stand up--as well as the "tummy time" that promotes the development of neck and other upper-body muscles.

"Pediatricians have told me they've noticed anecdotally that infants appear to be developing less upper body strength than in the past, in part due to less time spent on their tummies," she says.

Benjamin-Neelon and her colleagues hope to keep following the children in this study to determine whether physical activity in the first year of life, and its relationship to adiposity, continues in early and middle childhood.

In the first study of its kind, published today in the Journal of the Royal Society Open Science, a team of experts from the School of Veterinary Medicine and Science at the University have been able to demonstrate the automated detection of lameness in sheep when standing, lying and walking, using a new prototype tagging and monitoring system.

The technology was developed by Dr Jasmeet Kaler, Associate Professor in Epidemiology and Farm Animal Health from the University, along with industry giant Intel and agricultural software developer Farm Wizard.

Lameness is the biggest health and welfare problem on sheep farms, costing the sector around £80m a year. More than 90% of farmers in the UK report lameness in their flocks, most of which is caused by foot rot - a bacterial infection. If spotted early enough, it can prevent the problem spreading in the flock.

As sheep are a 'prey' species they are likely to mask signs of lameness when they feel threatened, or enlivened by the presence of observing farmers and vets. It means that up to now, diagnosis has been difficult and relies on visual inspection because there are no validated commercial tools available.

The smart wearable technology consists of a sensing device worn on a sheep's ear tag that gathers accelerometer and gyroscope date effectively tracking the animal's behaviour and movement and its way of walking. The algorithms are used to create different alerts for farmers. What is particularly novel about the technology is that it uses edge processing which means it doesn't need to send all the data to the Cloud because it does the thinking on the device, which helps with battery life.

For all three activities (standing, walking and lying), the study has identified features that differed between lame and non-lame sheep. This is particularly novel in lying and standing, which has unobvious lameness related behaviors which it would be difficult to spot with the human eye previously.

The results suggest that instead of affecting how much of an activity lame sheep do, it shows that they actually carry out activities differently, leading to a change in acceleration and rotational movement.

Detecting features that significantly differentiate lame from non-lame was not surprising because of visual differences previously reported between the gait pattern of lame and non-lame sheep. Five out of the top six characteristics when walking, were frequency, linked to rhythm and pace. These differences could be linked to reduced mobility because of the disease in lame sheep, which also resulted in differences in the regularity and frequency of head movements.

Lame sheep also showed a change in gait with peculiar head nodding in line with stride compared to non-lame sheep which had a smoother stride pattern.

A particularly interesting find, was that the results for classification of lameness had a higher accuracy within lying and standing activities.

The top features include a mixture of frequency and time-domain features, this suggests differences in in the variability and smoothness of movements for both standing and lying down between lame and non-lame sheep. In lame sheep this could be an attempt by the animal to reduce discomfort caused by the lameness. Where they redistribute their body weight to an unaffected leg leading to postural changes when standing.

The research also suggests that lame sheep possibly lie differently than non-lame ones, this could once again be due to the animal's attempt to alleviate the pain.

Dr Kaler said: "Our study has shown conclusively that there are behavioural differences between lame and non-lame sheep when walking, standing and lying. This has been first report of its kind and given lameness classification is possible within all these activities this helps to improve the accuracy as well as flexibility in terms of energy requirements. This automated system for the lameness detection can help improve sheep health and welfare on farms."

Water is a mysterious substance. Understanding how it behaves at the atomic level is still a challenge for experimental physicists, as light hydrogen and oxygen atoms are difficult to observe using conventional experimental methods. This is especially true for any researcher looking to study the microscopic movements of individual water molecules that run off a surface in a matter of picoseconds. As they report in their paper, entitled 'Nanoscopic diffusion of water on a topological insulator', researchers from the Exotic Surfaces working group at TU Graz's Institute of Experimental Physics joined forces with counterparts from the Cavendish Laboratory at the University of Cambridge , the University of Surrey and Aarhus University. Together, they made significant advances, performing research into the behaviour of water on a material that is currently attracting particular interest: a topological insulator called bismuth telluride. This compound could be used to build quantum computers. Water vapour would be one of the environmental factors to which applications based on bismuth telluride might be exposed during operation.

In the course of their research, the team used a combination of a new experimental method called helium spin-echo spectroscopy and theoretical calculations. Helium spin-echo spectroscopy uses very low-energy helium atoms that allow isolated water molecules to be observed without influencing their motion in the process. The researchers discovered that water molecules behave completely differently on bismuth telluride compared with those on conventional metals. On such metals, attractive interactions between water molecules can be observed, leading to accumulations in the form of films. But the opposite is the case with topological insulators: the water molecules repel one another and remain isolated on the surface.

Bismuth telluride appears to be impervious to water, which is an advantage for applications exposed to typical environmental conditions. Plans are in place for further experiments on similarly structured surfaces, which are intended to clarify whether the movement of water molecules is attributable to specific features of the surface in question.

LAWRENCE -- As climate change threatens the world, governments and organizations from around the globe have banded together to fight its effects. Yet that collaboration has not always carried over into the online world, where technology is often assumed to connect people and break down barriers. Research from the University of Kansas has found that nongovernment organizations, or NGOs, dedicated to fighting climate change from rich countries and certain parts of the globe are dominating the online conversation, leaving others at risk of being left out.

Climate Change Action Network International is a worldwide network of 1,300 NGOs in more than 120 countries "working to promote government and individual action to limit human-induced climate change to economically sustainable levels." Despite their stated goal of collaboration for global good, a big-data analysis of their social media use found NGOs in the global north and Oceania are the most engaged, most connected and have the largest audience for their message about combating climate change.

KU researchers analyzed a year of activity on Twitter by 482 NGOs in 79 countries, members of the international alliance found to have active Twitter accounts. The analysis showed a stark divide in who is leading the international conversation on climate change among NGOs, which are in a unique position to reach world populations on the topic as a bridge between the scientific community and public.

"When we think about politics in general, and media, leaders and reporters tend to report to people within their borders, not as much of an international audience," said Hong Tien Vu, assistant professor of journalism & mass communications and lead author of the study. "That's where NGOs can come in, by connecting and helping to establish concerted efforts to tackle global issues. With the digital world of today, we need to collaborate not only in the real world but online as well. This was an ambitious project, because most research doesn't look at climate change communications from a global perspective."

The study, co-written by Hung Viet Do, computer science researcher at Trader Interactive; and KU researchers Hyunjin Seo, associate professor of journalism & mass communications, and Yuchen Liu, doctoral student, was published in the journal Environmental Communication.

The researchers analyze a years' worth of Twitter activity from the 482 NGOs with active accounts, analyzing which had the most followers, which posted most frequently, which were most connected to fellow NGOs and which amplified the messages of others through means such as retweets. Those with the most activity and followers were considered thought leaders and leading the conversation, the authors wrote. The analysis revealed that the conversation leaders were all located either in the global north -- or north of the equator -- or Oceania, the region including Australia, New Zealand, Micronesia and Polynesia. The least connected and active nearly uniformly were located in the global south, or south of the equator.

Those divides reflect economic disparities, as the majority of the world's richest economies are located in the global north and Oceania, while the inverse is true for the global south.

The differences were especially striking given the organizations' stated goals of working together to combat climate change, and collaboration through collectives such as the Climate Change Action Network International.

"These organizations, even though they had committed to connecting in the real world, rarely interacted on Twitter, or online," Vu said. "We found their digital interaction was not that great."

The conversation leaders generally had more followers than accounts they followed, produced the most tweets and, when connected to similar NGOs, tended to be connected to others in the global north or Oceania. That is troublesome, the authors wrote, because it leaves NGOs from the global south and their respective nations at risk of not only being excluded from the conversation but not reaching policymakers and people who can make a difference in their regions of the world. And while climate change is a global threat, it does not manifest itself the same way in every country or region, so actions or policies necessary in those being left out run the risk of not reaching those who most need to hear them.

"Climate change is a pretty abstract and broad term. Only by experiencing it can you tell what it means and how it affects your life," Vu said. "But without that type of larger communication, you can't pressure policymakers to have an impact on your nation. You can't tackle climate change as an individual, but without that greater interaction, you can't tell your story either."

Lack of resources may be one of the main factors driving the lack of interaction about climate change by NGOs in poorer nations, the researchers said. That can exacerbate the economic inequality across such regions, even though some of the nations most threatened by climate change are located in the global south. The findings echo those from KU that previously showed economic factors influence how media frame climate change coverage.

The findings show that, despite the potential of social media and Twitter specifically, NGOs dedicated to fighting climate change have not harnessed it to collaborate globally and amplify their message.

"NGOs from richer countries were able to push their message the most and not only had the most resources but the most interest. We tend to think the internet would level the playing field, but that was not the case," Vu said. "We think NGOs should work together more functionally. They want to do more. That's why they became a part of this in the real world but also need to amplify their collaboration in the virtual world, and social media is a very powerful way to do that."

"When is my baby going home?" is one of the first questions asked by families of infants admitted to the neonatal intensive care unit (NICU). Now clinicians have a data-based answer. Moderate to late preterm babies (born at gestational age of 32 to 36 weeks) who have no significant medical problems on admission are likely to be discharged at 36 weeks of postmenstrual age (gestational age plus age since birth), according to a study published in the American Journal of Perinatology. Small for gestational age infants and those with specific diagnoses may stay longer.

"For the first time, practitioners have tangible data on length of stay to counsel parents at the time of their preterm baby's admission," says lead author Alanna Higgins Joyce, MD, MPH, a hospitalist at Ann & Robert H. Lurie Children's Hospital of Chicago and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Our results may decrease parent stress and help families prepare for their baby's arrival home."

Previously, length of stay predictors were signs of the infant's physiological maturity, which were only available near the end of the hospital stay. Infants born at less than 37 weeks of completed gestation comprise almost 10 percent of births in the United States. Most preterm infants are born between 32 and 36 weeks of gestation.

To establish a reliable length of stay estimate at the time of a preterm baby's admission, Dr. Higgins Joyce and colleagues from Lurie Children's conducted a retrospective chart review over six years, encompassing 3,240 moderate to late preterm infants born in a large, urban NICU. They found that the mean length of stay for these infants was 17 days, ranging from 30 days for infants born at 32 weeks of gestation to about a week for infants born at 36 weeks.

"While these results come from just our hospital, we hope other centers can confirm that many parents of premature infants can anticipate having their babies home with them earlier than previously expected," says senior author Patrick Myers, MD, neonatologist at Lurie Children's and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine.

Studies of animal movement and behavior--including those addressing disease spread and animal conservation--should monitor animals at both regular and irregular time points to improve understanding of animal movement behavior, according to a new study by Penn State statisticians. The study, which appears online this month in the journal Environmetrics, is the first to provide guidance about sampling regimes for these types of biological studies.

"Tracking animals is one of the major methods of data collection in ecology, but there has been little to no work on the relative benefits of different sampling schemes," said Elizabeth Eisenhauer, graduate student in statistics at Penn State and first author of the study. "In an ideal world, we could collect continuous or really fine-scale data about animal locations, but in reality researchers often have to make choices to balance their resources."

Researchers use a variety of tracking technology to study animal behavior, including GPS collars, radio telemetry, and even video cameras. These studies all provide information about an animal's location at a particular time, but due to limited resources usually provide an incomplete picture.

"For a GPS collar with limited battery life, for example, one could choose to record an animal's location very frequently over a short period of time or less frequently over a long period of time," said Ephraim Hanks, associate professor of statistics at Penn State and an author of the paper. "Even when we have videos of animal movement, such as in a laboratory setting, someone has to go in and manually record location data for every animal at regular time points. With these kinds of limitations being so prevalent, we wanted to know the best way to collect animal movement data to yield the most information."

The researchers propose a sampling regime inspired from the field of geostatistics--which analyzes position data, often over time--that they call lattice and random intermediate point sampling (LARI). LARI involves collecting location data at regular intervals, but also at a random time point between each of these intervals.

"Imagine we observed the location of a fox once every 24 hours," said Eisenhauer. "If the fox is asleep in its den every 24 hours, these regular location data aren't very interesting and, for example, wouldn't give us a good estimate of the animal's home range. If we checked in more frequently, maybe every hour, we might see more regular behaviors like how it forages for food, but might still miss interesting behaviors that happen more sporadically, like checking a disturbance outside of the den. If instead of every hour, we looked every two hours with a random point between each of these 2-hour periods, we might capture more of these fine-scale behaviors."

To assess the LARI sampling regime, the researchers looked at three different study systems that reflect different kinds of movement: ants moving between a nest entrance and the queen and brood at the back of the nest, guppies placed in a tank that usually swim toward shelter, and a simulated data set where the movement parameters were known. They first took very fine-scale data, for example sampling ant location once every second, to establish a gold standard or baseline. Then, the team compared a variety of less frequent regular and LARI sampling regimes to the standard. In nearly every case, the LARI sampling regime provided a better understanding of animal behavior--more accurate estimates of movement parameters--than a regular sampling regime with the same number of data points.

"Usually in animal movement studies, researchers use a variety of parameters to describe movement in order to get at the underlying behavior," said Eisenhauer. "In our examples, that might include how attracted a guppy is to a shelter object, or how quickly or in what directions ants are moving. Our models were more accurate and precise when estimating movement parameters when we used LARI versus regular sampling regimes."

Because movement observations provide an incomplete picture, researchers often use statistical modeling to fill in the gaps. When the researchers did so with the simulated data, results were closer to the known values when data was collected using the LARI sampling regime.

"When the number of time points collected remained the same, LARI yielded better results when filling in the gaps than regular sampling regimes," said Hanks. "Using LARI is a relatively easy change for biologists to integrate into their own studies. It's just a matter of tweaking when their observations occur."

The researchers plan to test their model using other species, and to adapt their model to allow for data collected with considerable error--like data collected from marine mammals, where location data can sometimes be hundreds of kilometers off. They also plan to expand their models to account for animals switching between behavior types, for example changing from sleeping to foraging to migrating.

"Collecting more data, finer-scale data, is always better," said Hanks. "Improving technology, like miniaturization of GPS and solar panels, might make this feasible for large animals in the future, but we're also starting to track ants and bees, so these challenges are not going away anytime soon. Ecologists will always have to make decisions about sampling design given their technology, resources, and study system, and we have just begun to scratch the surface about what might be optimal. While just a first step, we hope our work provides useful guidance."

(BOSTON)--Low-income parents reported lower perceived parenting stress and better overall outcomes when parents participated in Parenting Journey, a community-delivered curriculum designed to increase resilience and support nurturing family relationships.

While previous studies have identified the positive impact that parenting programs have on outcomes in both children and families, in 2016 the National Academy of Sciences highlighted the need for further research on these programs in diverse populations.

The collaborative investigation was carried out in partnership with the Institute for Community Health, ABCD Head Start, the Parenting Journey, Boston University School of Medicine (BUSM) and Boston Medical Center (BMC). Participants in this study were predominantly female, identified as Black or Latino, reported an annual household income of less than $20,000 per year and had significantly higher perceived stress at baseline. Parents in the intervention group received 12, two-hour, weekly group sessions run by two trained facilitators.

During the sessions, caregivers were provided strategies to help them increase self-care, raise awareness of what influences their parenting styles, as well as identify their strengths to better support themselves, their children and their families Researchers found that parents participating in this program reported decreased parenting stress, greater insight into how their upbringing affects their current parenting behaviors and increased ability to access social networks when compared with parents that were not enrolled in this program.

According to the researchers, there is a need for effective, accessible, strength-based parenting supports for low income and diverse populations. "Parenting Journey has specifically been developed for delivery in the community in settings such as Head Start that primarily serve low-income families. In addition, the session content has been designed to engage parents and to develop trust among group participants," said corresponding author Caroline J Kistin, MD, MSc, assistant professor of pediatrics at BUSM and a pediatrician at BMC.

The researchers believe that community-delivered parenting curriculums like Parenting Journey may be one promising way in which family wellness and child development can be supported in low-income diverse populations. However, they note the need for further research examining the "long-term effects on parental mental health and child socioemotional development."

Acute myeloid leukemia (AML) is a deadly blood cancer that originates in the bone marrow and kills most of its victims within five years. Chemotherapy has been the standard AML treatment for over 40 years, and while it often causes the cancer to go into remission, it rarely completely eliminates the cancerous cells, which then lead to disease recurrence in nearly half of treated patients. Aggressive post-remission treatments, like high-dose chemotherapy or bone marrow transplants, can reduce the chance of recurrence, but many AML patients are not healthy enough to tolerate them.

Now, a new study presents an alternative treatment that has the potential to eliminate AML cells completely: an injectable, biomaterial-based vaccine that, when combined with standard chemotherapy, caused complete and lasting recovery from and immunity against AML in mice. The study was conducted by researchers from Harvard's Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences (SEAS), and Stem Cell Institute (SCI), and is published in Nature Biomedical Engineering.

"We have previously developed cancer vaccines against solid tumors, and we were curious to see if this technology would also be effective at treating a blood cancer like AML," said co-first author Nisarg Shah, Ph.D., a former Postdoctoral Fellow in the lab of Wyss Core Faculty member David Mooney, Ph.D. who is now an Assistant Professor at the University of California, San Diego. "The promising outcomes of the combination of this vaccine with chemotherapy may translate to human vaccines that can be personalized yet offer off-the-shelf convenience."

A crafty cryogel

Like other vaccines, the AML vaccine "teaches" the body's immune system to recognize a foreign invader (in this case, AML cancer cells) so that it can mount an effective attack when that invader appears. While traditional vaccines are typically liquid, this vaccine is a tiny, disk-shaped "cryogel" scaffold made primarily of two materials - polyethylene glycol and alginate - that have been cross-linked together to form a matrix. Two chemicals (GM-CSF and CpG-ODN) are embedded in the scaffold to attract the body's dendritic cells and activate them, along with antigens specific to AML cells (either contents from dead AML cells or a peptide from the protein WT-1). The activated dendritic cells take up the antigens from the vaccine site and present them to T cells, triggering them to seek and destroy AML cells and, hopefully, patrol the body long-term to destroy any disease recurrence.

To test whether their cryogel vaccine effectively primed the immune system to attack AML cells, the team injected it under the skin of healthy mice, and saw that it resulted in a much higher number of activated T cells when either AML cell contents or WT-1 was used as the antigen, compared with mice that received the activating chemicals via a traditional vaccine injection or a "blank" scaffold without any chemicals. They then "challenged" the mice by injecting them with WT-1-expressing AML cells to mimic the initial onset of the disease. The mice that received either the traditional vaccine or a blank scaffold succumbed to the disease within 60 days, while those that received the cryogel vaccine survived. The survivors were then re-challenged with a second dose of AML cells after 100 days and displayed no signs of disease, demonstrating that the vaccine successfully protected them against recurrence.

Because AML originates in the bone marrow and cancerous cells can "hide" there to escape chemotherapy treatment, the team analyzed the mice's bone marrow. They found large numbers of active T cells and no trace of AML cells in the cryogel-vaccinated mice's marrow. When they transplanted bone marrow from those mice into healthy mice that were then challenged with AML cells, all of the transplant recipients survived while a control group of mice succumbed to AML within 30 days, indicating that the immune protection against AML was sustained and transferable.

Unexpected results, better-than-expected outcomes

To more closely mimic the clinical scenario of a human patient developing AML, the team injected their cryogel vaccine into mice that had AML along with the standard chemotherapy regimen that AML patients receive, which causes AML cells to die in large numbers. The activated T cell response in mice that received the combo therapy was six-fold higher than in mice that received chemo plus a traditional liquid vaccine, suggesting that the cryogel was a much more effective vehicle for delivering the activating chemicals to the immune system.

To test the durability of the immune response generated by the combo treatment, they harvested bone marrow from mice that were given the cryogel vaccine with WT-1 peptide along with chemotherapy and transplanted it into healthy mice that were then challenged with AML. None of the recipient mice developed AML up to 14 days after transplant, indicating that the combo-treated mice did not have residual AML cells in their marrow, and all the recipient mice survived a later challenge with AML cells while untreated mice died within 31 days.

But, when the researchers started to tinker with the vaccine's components to investigate why it worked so well, they saw something completely unexpected: vaccines that had no AML antigen in them were just as effective at providing protection as vaccines containing either AML cell contents or WT-1 peptide.

"We were definitely surprised and really didn't expect this result, because we initially thought that including the antigen in the vaccine was critical. That led us down some research avenues we hadn't previously considered to try and understand what was going on," said co-first author Alex Najibi, a graduate student in the Mooney lab. "We found that AML cells actually enter the cryogels over time, right where dendritic cells are already concentrated and activated. When the chemo causes large numbers of AML cells to die, the dendritic cells can pick up their remains as antigens and generate a strong signal to activate T cells against AML."

To further evaluate the efficacy of their antigen-free vaccine and chemotherapy combo, the team analyzed the bone marrow of mice with AML that received either the combo or the antigen-free vaccine alone. They found that the antigen-free vaccine alone did not effectively reduce the amount of AML cells in the marrow or increase the number of active T cells, but the combo therapy achieved both of those goals. The combo also caused a decline in the number of regulatory T cells (Tregs) in the marrow, which suppress immune function and are thought to be a major reason why AML cells in the marrow can evade immune detection.

Work on the cryogel vaccine is continuing along multiple threads of inquiry. Mooney's team is examining how it could be combined with sequencing technology to identify antigens that are specific to a single patient's cancer and create a highly personalized vaccine, and also exploring potential synergies with T cell and other adoptive transfer techniques. Other members of the lab are researching antigen-free vaccines in the context of breast cancer, as well as further investigating the response they observed in AML.

"We are very excited about the performance of our AML vaccine, because it could finally provide long-term, relapse-free survival for AML patients, either to 'clean up' residual AML cells in the bone marrow following a stem cell transplant, or in older patients who cannot tolerate either transplants or high-dose chemo," said Mooney, who is also the Founding Core Faculty & Lead of the Immuno-Materials platform at the Wyss Institute at Harvard University and the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

New research from McGill University and the University of California, Santa Cruz has found that the local streets of the world's cities are becoming less connected, a global trend that is driving urban sprawl and discouraging the use of public transportation.

The new study published in Proceedings of the National Academy of Sciences is the first global history of sprawl as measured by local connectivity of street networks. The research relied on publicly available data sourced from OpenStreetMap, the Wikipedia of maps, and satellite-derived data.

"We wanted to take a systematic approach that identifies cities--which might not be household names beyond their country's borders--where sprawl is rapidly worsening," said co-author Christopher Barrington-Leigh, an associate professor at McGill's Institute for Health and Social Policy. "We also wanted to identify the cities that, often with little fanfare, have been working to grow in an efficient, connected pattern for decades."

The result of a 7 year collaboration, the study was able to show that in large parts of the world, recent urban growth has increasingly resulted in inflexible and disconnected street networks. Different forms of gated communities were also found to be on the rise globally.

Barrington-Leigh and collaborator Adam Millard-Ball, an associate professor in the Environmental Studies Department at the University of California Santa Cruz, built a Street-Network Disconnectedness Index to create a global street connectivity map. Their data showed that southeast Asia is now home to some of the most sprawling cities on the planet - and sprawl is getting worse. Gridded street networks, on the other hand, promote efficient, dense urban form in Bolivia, Argentina and Peru. Germany, Denmark and the UK have been able to maintain moderate levels of street connectivity thanks to pedestrian and bicycle pathways, offering greater connectivity to non-motorized travel.

In conjunction with the study's publication, the authors are launching an online interactive map through which visitors can explore street connectivity around the world.

Past research has shown that the increased accessibility offered by gridded street networks makes walking, cycling and the use of public transit much simpler while cul-de-sacs tend to encourage the use of personal motorized vehicles. Barrington-Leigh said urban planners thus need to think about connectivity at the most local scale when designing and planning new streets in order to make cities more sustainable.

"Streets and roads represent an essentially permanent backbone that shapes all other dimensions of urban form and land use," he said. "Policy makers should look to cities like Tokyo and Buenos Aires for inspiration on how to limit sprawl. On our current path, choices that limit street connectivity may restrict future resilience and lock in pathways of energy use, CO2 emissions, health outcomes, and other aspects of our lifestyle for a century or more."