Brain

ITHACA, N.Y. - A common problem in diagnosing infectious disease is that the presence of a potential pathogen in the body does not necessarily mean the patient is sick. This can be particularly challenging for the treatment of organ transplant recipients, who often grapple with infection as well as complications related to immunosuppression.

A new Cornell study, "A Cell-Free DNA Metagenomic Sequencing Assay that Integrates the Host Injury Response to Infection," published Aug. 26 in Proceedings of the National Academy of Sciences, presents a technique to identify viruses and bacteria in the human body and quantify injuries to organs by using dead fragments of DNA, called cell-free DNA, that roam throughout the bloodstream and urine.

The resulting test is simple, fast, low cost and generalizable enough to identify thousands of bacteria and viruses.

"This really came about through collaboration with clinicians who explained to us this common problem in infectious disease diagnosis," said co-senior author Iwijn De Vlaminck, the Robert N. Noyce Assistant Professor in Life Science and Technology in the Meinig School of Biomedical Engineering. "So we developed an assay that would simultaneously inform us about the presence or absence of a wide range of pathogens, but at the same time would also tell us about the injury of different host tissues. The combined information enables us to more definitively say whether a person is dealing with disease or not."

De Vlaminck and his team partnered with researchers at Weill Cornell Medicine and focused on urinary tract infections in kidney transplant patients.

Lead author and Ph.D. student Alex Cheng used high-throughput DNA sequencing to identify any microorganisms that were present in clinical samples and distinguish them from the host DNA via bisulfite sequencing, a process in which the cell-free DNA is treated with salt to reveal methylation marks. These marks helped the researchers trace the cell-free DNA's tissues of origin and measure the degree of injury to different host tissues.

"In the field, doctors who try to diagnose infectious diseases and people who run microbiology labs are getting more and more excited about the use of genomic medicine approaches for diagnosis," De Vlaminck said. "But there was still a big gap to assess whether that organism is actually causing disease.

"That's really a critical question," he said. "Because some organisms are just commensals, they live side by side with the host. Our guts are filled with microbes, but those microbes may not be the reason you're suffering from disease. In a way, you're infected. You're colonized, but that's just part of normal biology."

The test is so generalizable that virtually any organism that has a DNA genome can be identified.

"Infectious diseases are a leading cause of disease burden worldwide," Cheng said. "They affect almost every single demographic, and they are not very easy to understand. So to have a test that can potentially help this large amount and wide range of people is exciting."

"Transplant recipients, because of the lifelong drug therapy needed to protect their transplanted organs, are ever at risk for infection-related complications," said co-author Dr. Manikkam Suthanthiran, chief of Nephrology, Hypertension and Transplantation Medicine and Stanton Griffis Ditinguished Professor of Medicine at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center. "A precise test that informs not only the presence of infectious agents but also the presence or absence of tissue injury is a major step toward personalizing therapy and making organ transplantation safer."

For co-senior author Dr. Darshana Dadhania, associate professor of medicine at Weill Cornell Medicine and a nephrologist at NewYork-Presbyterian/Weill Cornell Medical Center, the test is especially helpful in diagnosing damage due to BK polyomavirus (BKV) infection. While 25% to 30% of kidney transplant recipients have the virus in their blood or urine, only 5% experience nephropathy, or kidney disease, from the virus, Dadhania said.

"In this investigation, we were able to demonstrate that the kidney-specific urine cell-free DNA is higher in individuals with BKV nephropathy as compared to those with BKV replication alone and those with no BKV replication, suggesting a role for this assay to monitor kidney damage in the face of active viral replication and infection," Dadhania said. "This is particularly important because there is no specific therapy for active BKV replication."

Hurricane Dorian is packing heavy rain as it moves toward the Bahamas as predicted by NOAA's NHC or National Hurricane Center. NASA analyzed the storm and found heavy rainfall in the storm.

NASA has the ability to peer under the "hood" or clouds of a tropical cyclone and estimate the rainfall rates occurring. After looking into Dorian's clouds, imagery was generated using the Integrated Multi-satEllite Retrievals for GPM or IMERG "early run" product, at NASA's Goddard Space Flight Center in Greenbelt, Maryland. IMERG uses a constellation of satellites united by the GPM Core Observatory to provide global observations of Earth's precipitation every 30 minutes.

IMERG estimated rainfall accumulations for the region affected by Hurricane Dorian over the 24 hour period of August 27 at (7:59 a.m. EDT) 11:59 UTC to August 28 at (7:59 a.m. EDT) 11:59 UTC. "The data indicates that up to 120 mm (4.72 inches) of rainfall accumulated in certain regions during the 24 hour period," said Jacob Reed of NASA Disasters Program, GPM at NASA Goddard.

NHC said that Dorian is expected to produce the following rainfall accumulations this weekend into early next week: The central Bahamas...2 to 4 inches, isolated 6 inches; the northwestern Bahamas and coastal sections of the Southeastern United States...4 to 8 inches, isolated 12 inches. This rainfall may cause life-threatening flash flood.

On Aug. 29 at 5 a.m. EDT (0900 UTC), NOAA's NHC said the center of Hurricane Dorian was located near latitude 20.5 degrees north and longitude 66.6 degrees west. That puts Dorian's center about 150 miles (240 km) north-northwest of San Juan, Puerto Rico and about 425 miles (685 km) east-southeast of the southeastern Bahamas.

Dorian is moving toward the northwest near 13 mph (20 kph), and this general motion is expected to continue through Friday. A west-northwestward motion is forecast to begin Friday night and continue into the weekend.

Maximum sustained winds are near 85 mph (140 kph) with higher gusts. Strengthening is forecast during the next few days, and Dorian is expected to become a major hurricane on Friday. The minimum central pressure based on earlier Air Force Reserve Hurricane Hunter data is 991 mb (29.27 inches).

NHC said "On this track, Dorian should move over the Atlantic well east of the southeastern and central Bahamas today and on Friday, and approach the northwestern Bahamas on Saturday."

Interests in the northwestern and central Bahamas should monitor the progress of Dorian. Swells are likely to begin affecting the east-facing shores of the Bahamas and the southeastern United States coast during the next few days. These swells are likely to cause life-threatening surf and rip current conditions.

MADISON -- In early mammalian development, timing is everything.

For healthy development to occur -- whether it be three weeks for a mouse or nine months for a human -- embryos follow the lead of oscillating genes, which turn on and off in precise cycles and trigger different development milestones. Oscillating genes are conductors keeping time in a symphony of growth.

Scientists at the Morgridge Institute for Research have created a new way to study this virtually unknowable process in humans, using human stem cells in the lab. Their "clock in a dish" not only opens new research avenues, it provides a way to replicate developmental disorders to better understand their cause.

Reporting online in this week's issue of Cell Reports, the team describes growing human stem cells that are programmed into a very early state, within the first month of development. Then, using CRISPR technology, they edited a specific gene known to be connected to timing so it would illuminate when expressed.

The result: The cells growing in a dish produce a burst of color every five hours, precisely when those faithful oscillating genes are repeating their instructions. This is the first confirmation of the exact timing of oscillating genes in early human development.

Li-Fang Chu, a scientist in the lab of Morgridge and University of Wisconsin-Madison stem cell research pioneer James Thomson, says most major oscillation findings to date have been with model organisms. The landmark paper 20 years ago described the oscillatory system in chickens, and following studies in zebrafish, mice and snakes have all added to knowledge.

"It is so early in the development states that in humans, there is no way you could even approach this process," Chu says. "That's why it was attractive for us to use stem cells to see if we can create it in the lab."

The project focuses on a specific phase of development called somitogenesis -- or the development of body segments -- which takes place around 20 days of development. It is a period when the 42-44 pairs of somites are forming, and they develop one after the other in a very precise pattern over a period of about two weeks.

Targeting this phase was valuable for two reasons, Chu says. First, it gives them a very distinct time frame to study where there are recognizable physiological signatures, making it easier to match the genetic activity with the development. Second, a well-known genetic mutation occurs during this process that leads to a rare and debilitating disease.

The gene HES7 has been implicated in spondylocostal dysotosis (SCDO), where vertebrae improperly form and become fused together. Because past research highlighted the importance of HES7 to the segmentation clock, the lab made that gene the focus for CRISPR editing.

When HES7 is expressing normally in the experiment, the genes oscillate around every five hours as expected. But when introducing into HES7 a specific mutation associated with SCDO, the oscillation was completely disrupted. Essentially, the team recreated the conditions that cause SCDO and potentially other congenital skeletal defects.

"Like an airplane crash, we really don't know what happened or what went wrong without the information in the black box," Chu says. "I believe our system provides that black box."

In real development, there are thousands of events happening simultaneously to create the complex organs in the body. To simplify their model, the researchers used only mesodermal cells -- those responsible for creating tissue like bones, arteries and muscle. This gave the team a clearer perspective on what was happening with or without HES7 activation.

Developmental timing is one of the big questions being addressed in the Thomson Lab. Without a better understanding of the hard-wired timing within cells, clinical applications are limited. For example, many cell types take 100-300 days to become mature and functional in the body, making them unlikely candidates for cell therapy.

One of the keys to unraveling the mystery is looking at differences across species. Now that they have strong evidence of a roughly five-hour clock for human somite formation, they can compare it to known rates of 30 minutes for zebrafish, 90 minutes, 120 minutes for mice, and other species. These differences might ultimately offer clues on how to accelerate cell development for clinical benefit.

"If we understand in this case why mouse cells oscillate faster and human ones slower, we could apply that principle to other cell lineages and potentially speed things up," he says.

PHILADELPHIA - Giving trauma patients with severe blood loss the hormone arginine vasopressin (AVP) cut the volume of blood products required to stabilize them by half, according to results of a new, first-of-its-kind clinical trial from Penn Medicine. The finding, published online this week in JAMA Surgery, suggests that administering AVP to trauma patients with severe bleeding could become standard practice in trauma care, reducing the use of blood products and their adverse side effects. The authors say the study is particularly important for the treatment of patients with gun-related injuries. Each year, there are over 100,00 firearm-related injuries with over 36,000 deaths.

"Unintentional traumatic injuries are the leading cause of death in the United States for people younger than 45, and the injuries often involve severe blood loss. We can replace a patient's lost blood with blood products such as packed red blood cells, fresh frozen plasma, and platelets, but use of these options can lead to serious complications and they may not fully replace key molecules in blood that are needed to support blood pressure and the normal function of vital organs," said Carrie A. Sims, MD, PhD, an associate professor of Surgery and Laboratory Director of the Penn Acute Research Collaboration. "The results of this trial suggest a promising way to reduce the amount of blood needed to save the lives of patients with life-threatening injuries."

In the trial, 100 trauma patients were treated using low-dose AVP, a small protein produced in the hypothalamus and stored in the pituitary gland. AVP is secreted into the bloodstream when blood pressure is too low, and has the effect of constricting some blood vessels to bring blood pressure back up to the normal range. Treating trauma patients with AVP significantly decreased the need for blood products without increasing complications.

Prior studies have shown that patients with severe blood loss--a condition called hemorrhagic shock--may have lost most of their stores of AVP and/or their ability to secrete it into the circulation. For that reason, restoring an adequate blood pressure in these patients often requires the infusion of more blood products, involving more potential complications, than would otherwise be needed if AVP were present. Replacing AVP artificially in hemorrhagic shock patients may be a good way to reduce unnecessary blood product-use and improve patient outcomes. Experiments in animal models have suggested that is the case, but Sims and colleagues are the first to test the idea with a rigorous clinical trial design.

From May 2013 through May 2017 at a Penn Medicine trauma center, they enrolled 100 trauma patients who had been brought in with hemorrhagic shock and otherwise met the study criteria. All but seven were male victims of gunshot or knife wounds. The researchers randomized 49 of the patients to receive AVP in an initial moderate dose plus a slow infusion--during the first 48 hours of care--and the other 51 to receive the placebo equivalent.

The researchers found that the patients treated with AVP for 48 hours ended up receiving an average of 1.4 liters of blood products - less than half the average amount given to those treated with the placebo (2.9 liters).

The AVP group also had a markedly lower rate (11 percent vs. 34 percent) of deep-vein thrombosis--blood clot in a leg vein--which is a common complication in trauma patients. Rates of complications within 30 days for the AVP and placebo groups were otherwise similar (55 percent vs. 64 percent), and the numbers of deaths in that period were the same (six in each group). Other findings showed that although the AVP group had shorter average stays in the hospital compared to the placebo group, the relatively small number of patients in the study meant that these length-of-stay differences were not statistically significant.

With the promising results from this initial study in hand, the researchers hope to initiate a larger study that would help determine whether AVP could save lives affected by severe trauma.

ITHACA, N.Y. - Ever-widening divisions between Democrats and Republicans are believed to reflect deeply rooted ideological differences, but a new study points to a radically different interpretation: it may be mostly a matter of luck.

It's a phenomenon that Michael Macy, Cornell University professor and director of the Social Dynamics Laboratory, calls an "opinion cascade" - in which partisans pile onto whatever emerging position they identify with their party. Macy is author of "Opinion Cascades and the Unpredictability of Partisan Polarization," published Aug. 28 in Science Advances.

Social scientists have long wondered how political partisanship develops, and even more confusing is the tendency of U.S. political parties to radically shift platforms.

Macy asks: "Why have the major political parties shifted positions on issues like free trade, balanced budgets, legalization of marijuana, same-sex marriage and trust in science? And how is it that voters on both sides often have contradictory positions on abortion rights and capital punishment?"

Macy's team looked for answers by conducting an experiment in which they re-created the early days of opinion formation to see how the cards might have fallen differently had early movers held different arbitrary opinions.

The researchers split more than 2,000 Democratic and Republican volunteers into 10 "parallel worlds," each isolated from the others. Within each world, participants took turns filling out an online survey to indicate whether they agreed or disagreed with a series of unfamiliar political and cultural issues. In two of the 10 worlds, the survey was private, but in the other eight, whenever a partisan took a position on a given issue, all other participants in their world saw a real-time update of how each party was leaning.

The results showed how a handful of early movers can trigger a cascade in which later partisans pile on to their party's newly emerging position, leading eventually to large political differences. The big surprise was that the party that supported the issue in one world was just as likely to oppose the issue in another world.

"In one world, it was Democrats who favored using AI to spot online criminals, and in another world it was Republicans," he said. "In one world, Democrats favored classic books, and in another world, Republicans favored the classics. In one world, Democrats were more optimistic about the future and in another world, it was Republicans."

Macy hopes that these findings might help civilize the political discourse.

"In our world, political divisions are so fiercely defended," Macy said. "The two sides get very worked up, which would seem to indicate that positions are deeply rooted fundamental divisions. But our study suggests that these positions may just be identity markers, like bumper stickers, the result of opinion cascades that propelled people into a position with which they came to emotionally identify.

"Learning that the two parties could just as easily have switched sides," he said, "might encourage people to re-examine their positions and listen to the views of people with whom they sharply disagree."

COLUMBUS, Ohio - They may all be in the same classroom together, but each child in preschool may have a very different experience, a new study suggests.

The researchers documented these different experiences using a novel technique in the classroom: They had children wear a video camera on their head for two hours on one day to see what the class was like from the child's perspective.

In this study, published recently in PLOS ONE, the researchers were interested in the linguistic environment - how were children exposed to language in the class?

"We found that the duration and frequency of kids' interactions with teachers and peers was very different among kids," said Leydi Johana Chaparro-Moreno, lead author of the study and a doctoral student in educational psychology at The Ohio State University.

"Overall, children interacted more with the teacher than their peers, but for some kids their peers were an additional source of hearing language."

This was something that researchers could not easily learn from traditional studies, she said.

Most previous studies observed how teachers behaved in the class, such as how they talked to kids.

"What was missing was the perspective of the kids. Especially in preschool classrooms, each child may not be listening to the teacher at the same time or interacting in the same way," Chaparro-Moreno said.

The study involved 13 children, ages 3 and 4, who attended an urban nonprofit childcare center full-day preschool located in an urban community.

The children, whose parents agreed to let them join the study, wore the wireless head-mounted camera on a randomly assigned day during a four-day period. They wore it for one hour in the morning, during which they participated in different kinds of activities: some involving the whole class, and some where the kids were free to choose what to do in various centers around the classroom.

Four children wore a camera each day, as did the master teacher.

Afterward, the researchers analyzed the videos to see how many times each child interacted with the teacher or a peer, how long each interaction lasted, and a variety of aspects of the interaction.

Overall, about 60 percent of the interactions caught on video were with the teacher. And the total duration of interactions with teachers was almost three times longer than the interactions with peers.

But there was wide variation. Six of the 13 children interacted with their peers almost as many times as they interacted with their teachers. In addition, four children interacted for longer periods of time with their peers, relative to the average interaction length among all the children.

When someone was talking directly to a child wearing a camera in class, 81 percent of the time it was the teacher.

Kids also heard nearly all sophisticated language from their teachers - 92 percent of all complex sentences came from teachers.

But again, there was a lot of variability, Chaparro-Moreno said.

For example, for every type of word and complex sentence that one child heard per minute from teachers, another child heard five types of words and four complex sentences.

"Teachers may adapt how they interact with kids to meet the students' learning needs," she said.

"It is also possible that children's language ability and personality may play a role in how they interact with the teacher and their peers."

This study is part of a larger five-year, $4.5 million project called Early Learning Ohio funded by the federal Institute of Education Sciences, said Laura Justice, co-author of the PLOS ONE paper and principal investigator for the project.

The project, which involves students from preschool to grade 3, is "trying to identify those aspects of the classroom experience that are most important to academic development and social development," said Justice, who is also director of Ohio State's Crane Center for Early Childhood Research and Policy.

The data from the camera study will be used in future studies to model the social network in the classroom and examine how kids resolve conflicts with each other.

Researchers participating in the project are experimenting with other technologies, such as location sensors to see how kids move around classrooms and interact with their peers.

"Our goal is to map the dimensions of the classroom experience, including relationships with teachers and peers, how much kids enjoy school and whether they are victimized by other children," Justice said.

In a new study, scientists led by the U.S. Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research identified a transcriptional signature in B cells associated with protection from SIV or HIV infection in five independent trials of HIV-1 vaccine candidates. The gene expression signature was found to correlate with protection in the only human HIV vaccine trial that previously showed modest efficacy, RV144. Results from the study were published today in Science Translational Medicine.

This signature and specific genes were previously shown to be induced in response to influenza and yellow fever vaccination in humans. "We think this B cell signature is a broad indicator of effective responses after vaccination and could potentially be used to help design effective vaccines against HIV and other pathogens," said Dr. Rasmi Thomas, MHRP's Chief of Host Genomics and senior author of the publication. More broadly, Thomas said the RNA-Sequencing (RNA-Seq) methods used in this study could prove to be a valuable tool to discover protective correlates in other clinical and preclinical trials.

The study examined RNA-Seq data from preclinical HIV-1 vaccine candidate trials. Researchers hypothesized that partial efficacy observed in those studies could be due to variations in host gene expression elicited by the investigational vaccines. Using for the first time in HIV trials a next-generation sequencing method called RNA-Seq, they observed a common protective gene signature in the non-human primates.

Next, researchers investigated whether or not this B-cell signature was associated with protection from HIV infection in the only clinical human HIV vaccine study to show modest efficacy: the RV144 trial conducted by MHRP and its partners in Thailand. RV144 used a completely different vaccine Pox-protein regimen than what was used in the non-human primate studies.

The B cell signature that correlated with protection in the preclinical studies also correlated with protection in the RV144 human vaccine efficacy trial, and in 2 additional Pox-protein vaccines in NHP. This B cell signature also associated with higher levels of a functional antiviral antibody response called antibody-dependent cellular phagocytosis, or ADCP that could shed some light on why the vaccine was protective.

"We're excited because the identified gene signature associates with protective efficacy for the two vaccine regimens that are currently being tested in human efficacy trials in Africa, the Imbokodo study and HVTN702," said Thomas of the findings. "This new correlate of protection provides a clue as to why the vaccines were partially protective previously and may help to understand the mechanisms of efficacy in these new studies."

Scientists have found evidence that the horizontal circulation of carbon-rich ocean water in the subpolar Southern Ocean works in tandem with vertical circulation, together controlling how much carbon the region stores in the deep ocean or releases to the atmosphere. These findings contradict the conventional framework for carbon cycling in Antarctic waters, which primarily attributes carbon uptake to vertical circulation while overlooking the contribution of large systems of swirling ocean current called gyres. Reframing the carbon cycle in the Southern Ocean is an essential step to better shape predictions for how future climate change will impact processes such as acidification and sea-ice cover shift. Graeme A. MacGilchrist et al. zeroed in on the Weddell Gyre - an important representative region of the subpolar Southern Ocean - using data obtained from cruises around the outer perimeter of the gyre along with accompanying satellite observations. They discovered that the gyre transports carbon-containing phytoplankton from the open ocean out of the region at a rate of about 80 trillion grams per year, indicating that the gyre plays a key role in Southern Ocean carbon transport. This result suggests that processes far removed from vertical circulation affect the carbon content of deep ocean waters, further hinting that future research efforts should be more broadly focused to include horizontal circulation. Such studies could begin to answer intensely debated questions about the past and future of Earth's climate, including causes of glacial climate periods and future projections of CO2 in the atmosphere, the authors say.

New research from the University of North Carolina at Chapel Hill compares the growth rates between nearshore and offshore corals in the Belize Mesoamerican Barrier Reef System, the world's second-largest reef system. While nearshore corals have historically grown faster than those offshore, over the past decade there was a decline in the growth rates of two types of nearshore corals, while offshore coral growth rates in the same reef system stayed the same.

Coral reefs are a critical source of food, income and storm protection for millions of people worldwide. Nearshore corals grow in warmer and more nutrient-rich waters than their offshore counterparts and, because of their warmer temperatures, are believed to give a glimpse into the coral reefs of the future. This growth decline leads researchers to believe that any previous environmental advantage that came from corals being located closer to shore has now diminished. This is likely due to climate change and human activities, like coastal development that introduces excess sediment and nutrients to the water, subjecting corals close to shore to higher levels of stress. The findings also suggest that over time climate change will slow the growth of nearshore and offshore corals throughout the world.

"This research leaves us with troubling questions, like whether or not corals will be able to adapt to future conditions, and, if not, how that will impact the health and well-being of the millions of people around the world who rely on reefs for their food, income and protection from storms," said Justin Baumann, postdoctoral researcher in marine sciences and biology at the University of North Carolina at Chapel Hill. "Since we don't know the answer to these questions, it remains crucial that we carefully manage and protect reefs so that they will have the best possible chance to acclimate, adapt, and, hopefully, survive the impacts of climate change."

Baumann is lead author of the paper, which was published in Global Change Biology on Aug. 28.

The research team looked at the relationship between growth rates and specific acute stress events, such as coral bleaching. Coral bleaching happens when corals become stressed by pollution or increased ocean temperature and the colorful algae living inside of coral tissue are expelled, causing the coral to turn white. They found that while coral bleaching events can slow the growth of coral, the long-term declines in nearshore coral growth appear to be driven by the chronic stress of rising water temperatures due to climate change combined with increasing land-based stresses like development along the coast.

The study evaluated corals that were located along a 300-kilometer stretch of the Belize portion of the Mesoamerican Barrier Reef System. The nearshore coral reefs were within 10 kilometers of Belize's coast and the offshore coral reefs were 30-60 kilometers away from mainland Belize. Scuba divers collected 124 coral core samples for the study. A coral's core has growth bands that show its age, similar to the rings on a tree. The cores were taken from 19 sites, providing a sample size large enough to represent the entire reef system.

In the lab, the research team performed CT scans on the cores to measure the yearly vertical growth rate of the coral skeletons for each core. Reefs that have lower vertical growth rates are expected to be less diverse and complex. They also offer less protection to the shoreline and provide less area for fish and other invertebrates to live. The extent to which these reef changes will harm the communities that rely on them for food, income and protection against storms is yet to be seen.

"Local action to mitigate stress from coastal development and global action to reduce greenhouse gas emissions will both be necessary to ensure a sustainable future for both nearshore and offshore coral reefs," said Baumann.

Infants and young children with epilepsy due to a confirmed genetic abnormality had a better response to treatment with ketogenic diet compared to patients with other types of epilepsy, according to a review of 10-year experience at Ann & Robert H. Lurie Children's Hospital of Chicago. Results were published in Scientific Reports.

"Overall, we observed that ketogenic diet continues to be a safe, effective and well-tolerated treatment for patients under 3 years of age with drug-resistant epilepsy," says study author John Millichap, MD, an epilepsy specialist at Lurie Children's and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Based on our experience, clinicians could consider offering ketogenic diet earlier to infants diagnosed with genetic epilepsy, perhaps even before it becomes clear that the patient is not responding to anticonvulsant medication."

Ketogenic diet is a high fat, low carbohydrate and protein restricted diet that is rigorously medically supervised. It is widely recognized as an effective treatment for epilepsy that does not respond to medications.

"The ketogenic diet helps control seizures by reducing fluctuations of blood sugar, which reduces hyper-excitability in the brain," explains Dr. Millichap. "At Lurie Children's we have used it since 1963."

Generally, it is only in the last few years that epilepsy specialists began offering ketogenic diet to younger kids, and most studies in infants have only included babies with infantile spasms. The current report from Lurie Children's describes experience using ketogenic diet with a large and expanded population of young patients who had various types of epilepsy that began in infancy. In their review, the youngest patient to start ketogenic diet was only 3 weeks old.

Out of 109 children in the study, close to 20 percent achieved complete seizure control after three months on ketogenic diet and nearly 40 percent had significant seizure reduction (more than 50 percent). In children with genetic causes of epilepsy, outcomes were even more favorable, with nearly half experiencing more than 50 percent seizure reduction. Dr. Millichap and colleagues found that the age of seizure onset or age at the ketogenic diet initiation were not related to the eventual seizure outcome.

Only about 10 percent of the children included in the study withdrew early. Among these, there were no critical adverse events related to the ketogenic diet.

"The ketogenic diet is challenging to maintain and parents need extensive multidisciplinary support, especially during the complicated period of solid food introduction," says Dr. Millichap. "At Lurie Children's, our team includes nurse practitioners, dieticians and a social worker, all focused on making the ketogenic diet work for the child and family."

Lurie Children's also offers a genetic testing clinic for infants and children with suspected genetic causes of epilepsy.

"Genetic testing should be performed as early as possible so that we can provide the most precise treatments right away," says Dr. Millichap. "Large, multicenter studies are needed for us to establish which genetic epilepsy syndromes respond best to the ketogenic diet so that we can add it to our precision medicine toolkit."

Social network users risk becoming more and more addicted to social media platforms even as they experience stress from their use.

Social networking sites (SNS) such as Facebook and Instagram are known to cause stress in users, known as technostress from social media. However, when faced with such stress, instead of switching off or using them less, people are moving from one aspect of the social media platforms to another - escaping the causes of their stress without leaving the medium on which it originated.

Research into the habits of 444 Facebook users revealed they would switch between activities such as chatting to friends, scanning news feeds and posting updates as each began to cause stress. This leads to an increased likelihood of technology addiction, as they use the various elements of the platform over a greater timespan.

Researchers from Lancaster University, the University of Bamberg and Friedrich-Alexander Univeristät Erlangen-Nürnberg, writing in Information Systems Journal, found that users were seeking distraction and diversion within the Facebook platform as a coping mechanism for stress caused by the same platform, rather than switching off and undertaking a different activity.

Professor Monideepa Tarafdar, Professor of Information Systems and Co-Director of the Centre for Technological Futures at Lancaster University Management School, who co-authored the study, said: "While it might seem counter-intuitive, social media users are continuing to use the same platforms that are causing them stress rather than switching off from them, creating a blurring between the stress caused and the compulsive use".

Assistant Professor Christian Maier, of the University of Bamberg, who collected the data from the Facebook users along with Professor Sven Laumer, Schöller Endowed Professor and Chair of Information Systems and the Deputy Director of the Dr. Theo und Friedl Schöller Research Center. said: "Because social network sites offer such a wide range of features, users can find they act both as stressors and as a distraction from that stress".

"Even when users are stressed from SNS use, they are using the same platforms to cope with that stress, diverting themselves through other activities on the SNS, and ultimately building compulsive and excessive behaviour. As a result, they embed themselves in the social network environment rather than getting away from it, and an addiction is formed."

The research team looked at various different forms of technostress caused by using social media, such users feeling that SNS were invading their personal life, adapting their SNS use to conform to that of their friends, experiencing excessive social demands and too much social information, and facing constant changes and updates to the SNS platform.

They further examined two separate ways of coping with the stress. The first included users creating a diversion by partaking in other activities away from social media, which is the more obvious path. They would switch off, talk to friends or family about issues they were experiencing and spend less time on the platform.

However, the other method consisted of diversion through engaging in different activities within the same SNS app itself, and potentially moving on a pathway towards SNS addiction. This method was more prevalent among those social media users who used the sites more regularly.

Professor Sven Laumer said: "We found that those users who had a greater social media habit- needed less effort to find another aspect of the platforms, and were thus more likely to stay within the SNS rather than switch off when they needed to divert themselves. The stronger the user's SNS habit, the higher the likelihood they would keep using it as a means of diversion as a coping behaviour in response to stressors, and possibly develop addiction to the SNS."

"Users go to different areas of the platform which they see as being separate and that they use in different ways. With Facebook, there are features that take you into different worlds within the same platform. You can be in many different places all from the same application, for example following friends' activities, posting pictures about daily activities, switching to a chat feature or playing games".

Professor Monideepa Tarafdar added: "The idea of using the same environment that is causing the stress as means of coping with that stress is novel. It is an interesting phenomenon that seems distinctive to technostress from social media".

The research group of Nuno Maulide from the Faculty of Chemistry of the University of Vienna has, in cooperation with the Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, achieved the synthesis of a potential immunosuppressive agent by modification of a naturally occurring compound. In this endeavour, the researchers have employed a masking trick to "hide" a reactive species inside the target molecule. The results were recently published in the renowned Journal of the American Chemical Society.

The Chemical fascination of Natural products

Chemists have long had a fascination with Nature. "Nature is an amazing Chemist", explains Nuno Maulide, Professor of Organic Chemistry at the University of Vienna and Austrian Scientist of the Year 2018, "especially since it has had millions of years to perfect a chemical machinery which is unrivalled in its complexity and efficiency".

Particularly fascinating are the so-called "Natural products". These are substances produced by living organisms, for the most diverse functions: defense, sensing, signaling, among others. For example, a plant which is threatened by a certain parasite might develop, through evolution over a period of many thousands of years, the ability to produce certain classes of chemicals that can either kill or at least repel the said parasite. Natural products often possess very sophisticated chemical structure and are species-specific - meaning, they are produced only by a selected species of organisms.

The FR-molecules: natural products with special properties

In 2003, a Japanese company reported the isolation of 3 natural products from the microorganism Pseudomonas fluorescens, the so-called "FR Molecules" (cf. Figure 1). Noteworthy was their complex chemical structure but also their very interesting immunosuppressive properties. Immunosuppressive drugs are widely used in the treatment of allograft repulsions and autoimmune-associated diseases. Although a range of such drugs have been developed and are used clinically, almost all of them carry severe side effects and limitations. The search for new immunosuppressants with a distinct mode of action is therefore an urgent need to improve the safety and efficiency of immunosuppressive therapy.

Several research groups have attempted the laboratory synthesis of the FR molecules in the years that followed - with mitigated sucess. "They all struggled with the molecule's Achiles' Heel: the macrocyclic ring with three consecutive double bonds", explains Nuno Maulide, who since November 2018 is also Adjunct PI at CeMM.

A solution to a long-standing problem

Maulide and his team have now developed a novel chemical reaction that allows the preparation of such macrocyclic structures in high efficiency and from simple precursors. "We simply hide the double bonds in a 'secured' form, so that they can be revealed at a later stage. Very much like a 'Trojan horse'", jokes Yong Chen, first author of the paper.

For this goal the researchers install a smaller ring with only 4 carbon atoms, termed a "cyclobutene", as "masked" form for the double bonds of the natural product (cf. Figure 2). This approach results in a very short access to the FR molecules.

"We are now in a position to make grams of these compounds; the natural source delivered at best milligrams - a considerable advance. Furthermore, the compounds we prepare in the lab are indistinguishable from those isolated from Pseudomonas fluorescens", enthuses Maulide.

Variations lead to a better drug

As the researchers are now able to reproduce these complex structures in the lab, they are in a position to introduce non-natural variations and modifications of those structures. They already found an "analogue" (i.e, a new molecule resembling the original natural product but possessing small structural modifications) that is almost 100 times more potent than the compounds produced by Nature. "The joint collaboration between University of Vienna and CeMM has resulted in true synergies", explains Stefan Kubicek from the Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM), and coauthor of the study.

"There are so many open questions: what is the mode of action of these molecules? Can we improve the activity even further? Research at its best always generates more questions than answers", ends Maulide.

ITHACA, N.Y. - Children who grow up in disadvantaged neighborhoods are nearly one-third more likely to experience obesity as adults, according to new research from Cornell University.

The research, which offers a more precise and longer-term view than previously available of the lasting influence a neighborhood can have on unhealthy weight gain, shows the risk of obesity is strongest for teens.

"Growing up in a disadvantaged neighborhood sticks with you, and can have a negative impact on one's health through increasing one's chance of obesity in adulthood," said lead author Steven Alvarado, professor of sociology.

Among respondents followed in the data across different age ranges, that chance is 13% greater among children up to age 10 who live in disadvantaged neighborhoods, and 29% higher for kids aged 11 to 18. Overall, the odds rose 31%.

Alvarado defined "disadvantaged" neighborhoods based on seven variables, including median income and home values and the percentage of residents who were living in poverty, unemployed or had earned bachelor's degrees. But measuring a neighborhood's association with adult outcomes including obesity is complex. Researchers must consider "unobserved" factors not included in their data that might explain any association between childhood neighborhoods and obesity in adulthood.

Genes, for example, or high parental stress level associated with household instability might be more responsible for children's later weight gain.

The study accounted for these factors by comparing siblings. The siblings largely shared the same genes and parenting habits but may have experienced different neighborhood circumstances growing up, because their families moved or their neighborhoods changed over time between sibling births.

Alvarado's study is the first to adjust for criteria such as grandparents' experiences in segregated schools and neighborhoods, while exploring the link between growing up in tough neighborhoods and adult obesity.

"We must continue to consider the context in which individuals are making decisions, the neighborhood resources that could serve as catalysts or suppressors for any genetic predispositions toward obesity in adulthood," he said.

Glacier-fed rivers in northern Canada may be consuming significant amounts of carbon dioxide from the atmosphere, according to new research by University of Alberta biologists.

The study examined the Lake Hazen watershed in Quttinirpaaq National Park on Ellesmere Island in Nunavut as a model system to study the impact of melting glaciers on freshwater systems.

"We observed that concentrations of carbon dioxide in the rivers were much lower than in the atmosphere, meaning that rivers are actively consuming carbon dioxide from the atmosphere," explained Kyra St. Pierre,former PhD student in the Department of Biological Sciences and Vanier scholar.

This is due to a process called chemical weathering, which is a series of chemical reactions that occur as materials like rocks, sediment, and soil come into contact with water and gases from our atmosphere.

"Glacial landscapes are special in that they have huge expanses of finely ground sediments created by the glaciers themselves as they advance and retreat," said St. Pierre, who conducted the study under the supervision of Professor Vincent St. Louis. "As these sediments mix with melt waters, which in turn mix with the atmosphere, they can undergo a number of potential chemical weathering reactions, some of which consume carbon dioxide."

But while reducing levels of atmospheric carbon dioxide may sound like good news, it comes at the high and yet unknown cost of melting glaciers.

"The melting of glaciers in mountain and polar regions is one of the most striking consequences of climate warming, but it's not always clear what this means," said St Pierre. "Many of the world's rivers, including the Athabasca and Fraser Rivers here in Western Canada, originate from glaciers and yet, despite their importance in our everyday lives, we actually know very little about how glacier-fed freshwaters function."

Future research will investigate just how common this weathering phenomenon is around the world, and how it differs between different regions with glaciers. Work in national parks in Jasper and Banff is already underway, with plans to expand to other glacier-covered areas in Canada and around the world.

COLUMBIA, Mo. - With school in full swing, many parents might be considering how to get more involved with their child's schooling. Parent involvement and support can be beneficial for students of all ages, but new research shows that family-school involvement has specific perks for young students.

After surveying more than 3,170 students and 200 teachers, researchers at the University of Missouri found that families are less engaged with their child's schooling in middle school than they are when their child is in elementary school. However, the researchers also found a silver lining: Both elementary school children and middle school children are less likely to have concentration problems and behavioral issues at the end of a school year if their parents made a greater effort to be engaged with their schooling earlier in the year.

"In addition to being less likely to have emotional or behavioral issues in class, we also found that students with engaged parents ended the year with better social skills and were able to focus on tasks easier," said Tyler Smith, a senior research associate in the College of Education. "This means that when parents are more involved at school, the benefits to their child grow over time."

The researchers said that family-school engagement often drops from elementary to middle school for several reasons, including a change in student-teacher ratio and a desire to respect their child's growing sense of independence.

"Keeping in contact with multiple teachers can be more challenging for parents with children in middle school, but our study shows evidence that parents and teachers should continue to make an effort to connect," said Keith Herman, a professor in the College of Education and co-author on the study. "There are many options for parents to become more involved at both levels without feeling intrusive."

Herman suggests that parents can explore getting involved with their child's schooling in a variety of ways. Options outside of the home include attending school functions, volunteering at events and joining parent groups. However, parents and family members can also take a more active role by helping with homework and keeping in touch with the child's teacher(s).

Smith adds that teachers can also do their part in encouraging families to get more involved by providing opportunities for parents to connect with them.

"Teachers have a lot on their hands, obviously, but even small efforts to help build better family-teacher relationships can have big payoffs for everyone involved," Smith said. "Teachers might consider inviting parents to special events or giving students assignments that involve their parents so that the students can help begin to build that relationship naturally."