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Bottom Line: National private insurance claims data were used to examine opioid prescribing patterns in children after tonsillectomy and return visits for complications. Opioids are commonly used after tonsillectomy, although American Academy of Otolaryngology clinical practice guidelines recommend nonopioids such as NSAIDs. This analysis included 2016 and 2017 claims data coded for tonsillectomy for nearly 16,000 children; nearly 60 percent of whom had one or more prescription drug claims for opioids between seven days before to one day after tonsillectomy. Having one or more prescription fills wasn't associated with return visits for pain or dehydration or bleeding compared with children not using opioids but it was associated with increased risk of return visits for constipation. The study authors suggest reducing opioid prescribing to children after tonsillectomy may be possible without increasing risk of complications. The study has several limitations, including that children may not use opioids even when prescriptions are filled.

Authors: Kao-Ping Chua, M.D., Ph.D., University of Michigan, Ann Arbor, and coauthors

(doi:10.1001/jamaoto.2019.2107)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Media advisory: To contact corresponding author Kao-Ping Chua, M.D., Ph.D., email Beata Mostafavi at bmostafa@med.umich.edu">bmostafa@med.umich.edu. The full study is linked to this news release.

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CAMBRIDGE, MA -- In recent years, MIT scientists have developed a new model for how key genes are controlled that suggests the cellular machinery that transcribes DNA into RNA forms specialized droplets called condensates. These droplets occur only at certain sites on the genome, helping to determine which genes are expressed in different types of cells.

In a new study that supports that model, researchers at MIT and the Whitehead Institute for Biomedical Research have discovered physical interactions between proteins and with DNA that help explain why these droplets, which stimulate the transcription of nearby genes, tend to cluster along specific stretches of DNA known as super enhancers. These enhancer regions do not encode proteins but instead regulate other genes.

"This study provides a fundamentally important new approach to deciphering how the 'dark matter' in our genome functions in gene control," says Richard Young, an MIT professor of biology and member of the Whitehead Institute.

Young is one of the senior authors of the paper, along with Phillip Sharp, an MIT Institute Professor and member of MIT's Koch Institute for Integrative Cancer Research; and Arup K. Chakraborty, the Robert T. Haslam Professor in Chemical Engineering, a professor of physics and chemistry, and a member of MIT's Institute for Medical Engineering and Science and the Ragon Institute of MGH, MIT, and Harvard.

Graduate student Krishna Shrinivas and postdoc Benjamin Sabari are the lead authors of the paper, which appears in Molecular Cell on Aug. 8.

"A biochemical factory"

Every cell in an organism has an identical genome, but cells such as neurons or heart cells express different subsets of those genes, allowing them to carry out their specialized functions. Previous research has shown that many of these genes are located near super enhancers, which bind to proteins called transcription factors that stimulate the copying of nearby genes into RNA.

About three years ago, Sharp, Young, and Chakraborty joined forces to try to model the interactions that occur at enhancers. In a 2017 Cell paper, based on computational studies, they hypothesized that in these regions, transcription factors form droplets called phase-separated condensates. Similar to droplets of oil suspended in salad dressing, these condensates are collections of molecules that form distinct cellular compartments but have no membrane separating them from the rest of the cell.

In a 2018 Science paper, the researchers showed that these dynamic droplets do form at super enhancer locations. Made of clusters of transcription factors and other molecules, these droplets attract enzymes such as RNA polymerases that are needed to copy DNA into messenger RNA, keeping gene transcription active at specific sites.

"We had demonstrated that the transcription machinery forms liquid-like droplets at certain regulatory regions on our genome, however we didn't fully understand how or why these dewdrops of biological molecules only seemed to condense around specific points on our genome," Shrinivas says.

As one possible explanation for that site specificity, the research team hypothesized that weak interactions between intrinsically disordered regions of transcription factors and other transcriptional molecules, along with specific interactions between transcription factors and particular DNA elements, might determine whether a condensate forms at a particular stretch of DNA. Biologists have traditionally focused on "lock-and-key" style interactions between rigidly structured protein segments to explain most cellular processes, but more recent evidence suggests that weak interactions between floppy protein regions also play an important role in cell activities.

In this study, computational modeling and experimentation revealed that the cumulative force of these weak interactions conspire together with transcription factor-DNA interactions to determine whether a condensate of transcription factors will form at a particular site on the genome. Different cell types produce different transcription factors, which bind to different enhancers. When many transcription factors cluster around the same enhancers, weak interactions between the proteins are more likely to occur. Once a critical threshold concentration is reached, condensates form.

"Creating these local high concentrations within the crowded environment of the cell enables the right material to be in the right place at the right time to carry out the multiple steps required to activate a gene," Sabari says. "Our current study begins to tease apart how certain regions of the genome are capable of pulling off this trick."

These droplets form on a timescale of seconds to minutes, and they blink in and out of existence depending on a cell's needs.

"It's an on-demand biochemical factory that cells can form and dissolve, as and when they need it," Chakraborty says. "When certain signals happen at the right locus on a gene, the condensates form, which concentrates all of the transcription molecules. Transcription happens, and when the cells are done with that task, they get rid of them."

A new view

Weak cooperative interactions between proteins may also play an important role in evolution, the researchers proposed in a 2018 Proceedings of the National Academy of Sciences paper. The sequences of intrinsically disordered regions of transcription factors need to change only a little to evolve new types of specific functionality. In contrast, evolving new specific functions via "lock-and-key" interactions requires much more significant changes.

"If you think about how biological systems have evolved, they have been able to respond to different conditions without creating new genes. We don't have any more genes that a fruit fly, yet we're much more complex in many of our functions," Sharp says. "The incremental expanding and contracting of these intrinsically disordered domains could explain a large part of how that evolution happens."

Similar condensates appear to play a variety of other roles in biological systems, offering a new way to look at how the interior of a cell is organized. Instead of floating through the cytoplasm and randomly bumping into other molecules, proteins involved in processes such as relaying molecular signals may transiently form droplets that help them interact with the right partners.

"This is a very exciting turn in the field of cell biology," Sharp says. "It is a whole new way of looking at biological systems that is richer and more meaningful."

Some of the MIT researchers, led by Young, have helped form a company called Dewpoint Therapeutics to develop potential treatments for a wide variety of diseases by exploiting cellular condensates. There is emerging evidence that cancer cells use condensates to control sets of genes that promote cancer, and condensates have also been linked to neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Huntington's disease.

The NASA/ESA Hubble Space Telescope reveals the intricate, detailed beauty of Jupiter's clouds in this new image taken on 27 June 2019 [1]. It features the planet's trademark Great Red Spot and a more intense colour palette in the clouds swirling in the planet's turbulent atmosphere than seen in previous years.

Among the most striking features in the image are the rich colours of the clouds moving toward the Great Red Spot. This huge anticyclonic storm is roughly the diameter of Earth and is rolling counterclockwise between two bands of clouds that are moving in opposite directions toward it.

As with previous images of Jupiter taken by Hubble, and other observations from telescopes on the ground, the new image confirms that the huge storm which has raged on Jupiter's surface for at least 150 years continues to shrink. The reason for this is still unknown so Hubble will continue to observe Jupiter in the hope that scientists will be able to solve this stormy riddle. Much smaller storms appear on Jupiter as white or brown ovals that can last as little as a few hours or stretch on for centuries.

The worm-shaped feature located south of the Great Red Spot is a cyclone, a vortex spinning in the opposite direction to that in which the Great Red Spot spins. Researchers have observed cyclones with a wide variety of different appearances across the planet. The two white oval features are anticyclones, similar to small versions of the Great Red Spot.

The Hubble image also highlights Jupiter's distinct parallel cloud bands. These bands consist of air flowing in opposite directions at various latitudes. They are created by differences in the thickness and height of the ammonia ice clouds; the lighter bands rise higher and have thicker clouds than the darker bands. The different concentrations are kept separate by fast winds which can reach speeds of up to 650 kilometres per hour.

These observations of Jupiter form part of the Outer Planet Atmospheres Legacy (OPAL) programme, which began in 2014. This initiative allows Hubble to dedicate time each year to observing the outer planets and provides scientists with access to a collection of maps, which helps them to understand not only the atmospheres of the giant planets in the Solar System, but also the atmosphere of our own planet and of the planets in other planetary systems.

Researchers from the HSE Epilepsy Lighthouse Project and FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases hosted by RCSI, have developed a new genomics module in the Irish National Epilepsy Electronic Patient Record (EPR) system.

The work illustrates how an electronic health system can support the integration of genomic test results and new genetic knowledge into routine clinical care in the public health system. This new system will facilitate more personalised forms of medicine.

The research, funded by eHealth Ireland, the Health Service Executive (HSE) and Science Foundation Ireland, is published in the latest issue of the journal Epilepsia

Many adults and children with epilepsy of unknown cause now undergo genomic testing. An accurate genetic diagnosis can bring great value to the individual, their family and the clinical team. As a result of this research, many people now understand why they have epilepsy. For some, this has been a decades long journey of multiple treatments and no explanation or knowledge of the actual underlying cause for their condition.

"We now know that much of previously unexplained epilepsy is due, in part, to damaging variants in a person's genome," said Prof. Norman Delanty, Associate Professor at RCSI, FutureNeuro Investigator and Consultant Neurologist at Beaumont Hospital.

"The potential to understand the reason for a particular person's epilepsy at a molecular level, and to use this information to develop personalised therapies will become a significant advancement in the way we practice medicine."

Ireland has a world-leading national EPR system designed specifically for epilepsy. This system captures, in great depth, the subtle patient features relevant to specialist care and allows for quicker access to key clinical data to better support people with complex chronic diseases such as epilepsy. In 2015, the HSE and eHealth Ireland designated the national Epilepsy EPR as a "Lighthouse" project for the country to help build an understanding of the quality, safety, and efficiency benefits of EPRs. The Lighthouse project combined the emerging fields of genomics and EPRs to promote personalised medicine and improved healthcare for people with epilepsy.

"The epilepsy EPR system is one of the largest, most detailed collections of active epilepsy eHealth records in the world," said Mary Fitzsimons, FutureNeuro Epilepsy eHealth Lead and Director of the Epilepsy Lighthouse Project at RCSI. "To our knowledge, the epilepsy genomics module we have developed is the first such specific system in the world. We believe the combined power of genomics and electronic patient records has the capability of enhancing, and in some cases transforming, the practice of medicine."

The new Epilepsy EPR module facilitates regular multidisciplinary meetings between clinicians, geneticists, bioinformaticians, and other team members, where they review data from genomic testing to determine if there is an identifiable genetic cause for a person's epilepsy.

"Diagnostic genomic testing is a rapidly growing area in clinical medicine, but there is much work to be done to understand the most effective way to integrate this powerful information into patient care. We hope this new eHealth technology can inform how genomics is integrated into the Irish healthcare system and act as an example for other diseases beyond epilepsy," said Gianpiero Cavalleri, FutureNeuro Deputy Director and Professor of Human Genetics at RCSI. "Having this data available in a person's secure electronic record enables multidisciplinary teams to quickly make better decisions about a person's treatment options."

Corals fascinate amateurs and experts alike: small polyps that extract calcium carbonate from seawater and use it to build their elaborate skeletons. But climate change, with rising water temperatures and increasing ocean acidification, is changing the living conditions of corals at an unprecedented rate. Whether they can keep pace with these changes and adapt is an open question. Now researchers from the GEOMAR Helmholtz Centre for Ocean Research Kiel and the University of California are providing new insights with a study published today in international journal Nature Communications. For this study, which was co-financed by the Austrian Science Fund FWF (Fonds zur Förderung der wissenschaftlichen Forschung) and the US NSF, the scientists investigated the response of the stony corals Porites astreoides to low pH and high dissolved carbon content in their natural environment.

Over millions of years of their evolution, corals have experienced and survived major environmental changes. Like tree rings, their skeletons are an environmental archive that allows researchers to gain insights into the past. From the smallest differences in the chemical composition of coral skeletons, conclusions can be drawn about former environmental conditions. However, many details on the control and regulation of skeletal formation processes of corals are still unknown.

To learn more about these processes, the researchers used a natural laboratory off the east coast of Mexico. There, groundwater seeps from almost circular holes in the seabed, so-called ojos. The water has previously dissolved calcium carbonate from the Yucatan peninsula rocks as well as high carbon dioxide from soil respiration. It is more acidic than normal seawater but contains more dissolved carbon and thus resembles the seawater of the distant future.

Despite these unfavorable conditions, the hard-coral Porites astreoides has settled at these ojos. However, the corals there grow more slowly than similar species outside the ojos. "Unlike corals that are exposed to such an acidic environment in laboratory experiments for only a few weeks to months, the corals we sampled live under such conditions for their whole life history," says Prof. Dr. Adina Paytan of the University of California Santa Cruz, co-author of the study..

For the study, samples were taken from corals living at different distances from the ojos. The researchers were thus able to study corals of the same species with varying degrees of change in seawater composition.

It is known from earlier research that the ratio of boron and carbon isotopes in coral skeletons provides information on the chemical properties of the calcifying fluid at the time of skeleton formation. "Kiel is one of the few locations where we have the necessary analytics to be able to measure these parameters simultaneously and with high resolution", explains Dr. Jan Fietzke, physicist at GEOMAR and co-author of the study, "We are thus able to measure two important parameters of coral calcification".

The investigations showed an almost constant chemical composition of all samples. "From this, we can conclude that each polyp creates a calcifying fluid that is largely independent of the seawater conditions surrounding it," explains GEOMAR marine biologist Dr. Marlene Wall, first author of the study, "yet even small changes in the two parameters studied can have an effect on calcification." Model calculations for coral growth based on these chemical data resembled the decline in growth measured in the field highlighting their importance to facilitate growth. In an environment with a lower pH, the corals at the ojos must put more effort to raise their pH to the observed level. This process is likely to cost them more energy.

Since the corals must distribute their energy reserves over many important functions such as food acquisition, digestion, reproduction or defense against diseases, they grow more slowly. Other influences, however, such as the calcium concentration in the calcifying fluid or the role of coral symbionts, offer potential for further research. "The study has also shown that we still have a long way to go before we understand all the interactions between changes in seawater and coral growth," summarizes Dr. Wall.

In the last 150 years, engineers have developed and mastered ways to stabilize dynamic systems, without lag or overshoot, using what's known as control theory. Now, a team of University of Arizona researchers has shown that cells and organisms evolved complex biochemical circuits that follow the principles of control theory, millions of years before the first engineer put pencil to paper.

Consider your home air conditioner, for example. You set the temperature to 82 degrees and leave for work. When you return after a long, hot day, you set the temperature to 72 degrees. Your air conditioner then blasts cold air into your home until the thermostat reaches 72. This is an analog for what's called feedforward control - your thermostat sets a goal, gets as close to 72 degrees as fast as it can, and turns off when it meets the goal.

The remainder of the evening, your air conditioner senses when the temperature deviates from 72 and turns on in small bursts to maintain a stable temperature. This is an analog for a feedback control, where small fluctuations away from the set temperature feedback onto the controller and cause the system to adjust.

A UA team discovered that the coupling of two interconnected biochemical circuits within a cell - the TOR and PKA pathways - work like a thermostat to control the growth of cells in response to the availability of nutrients. For decades, it has been known that mutations in both PKA and TOR cause disease; The new research found that each pathway has its own distinct role and teased out exactly how and why the two pathways work together.

The study, published today in Nature Communications, was led by associate professor of molecular and cellular biology and BIO5 Institute member Andrew Capaldi. He and his team wanted to know, if TOR and PKA both activate genes that cause cells to grow and turn on and off in response to nutrients, then why does the cell need both pathways to control growth?

Cells are constantly adapting to what's available in their environment. They discovered that when a cell has a steady availability of nutrients, the TOR pathway makes sure the cell chugs along at an appropriate (matched) pace. But when a cell suddenly gets rich in a certain nutrient, the PKA pathway shifts into gear and triggers a 25-fold increase in gene production before turning itself off and letting the far more precise TOR controller take over again. Without PKA, TOR's response to the influx of nutrients would lag.

"If you just have the TOR pathway, you'd always replicate at a good pace. The problem would be that when the conditions change, it would take a cell hours to adjust its growth rate. So nature added PKA," Capaldi said. When you run out of nutrient, PKA can also quickly shut things down to let TOR take over again. "What's happening is you have two controls - one whose job it is to speed up the response, and the other to keep it exactly right."

Chemical engineers use the same principle to tightly control temperature.

"Often, chemicals must maintain a certain temperature or you'll end up with unwanted side reactions. So, engineers include a thermostat inside the chemical mixing chamber," Capaldi said. "Let's say the next stage of a reaction is going to create a ton of heat. They use a feedforward control like PKA to quickly adjust the temperature, and then feedback control takes over to keep it steady like TOR."

Because cells must be incredibly precise, cellular pathways are numerous and complex.

"Our cells have 30,000 proteins, and biologists have shown that if there's anything wrong in one of a few thousand that control growth, then you can get a disease," Capaldi said. "That is because these pathways do not work as simple on-and-off switches. As we have shown in our new study, they act like complex circuits, even computers."

In fact, like computers, signaling networks have what are called hubs. The TOR and PKA pathways act as hubs because they are highly connected to each other, as well as hundreds of other proteins and pathways in the cell. As a result, when either of these hubs get broken the whole system goes down, just as we find with the internet.

For example, an underproductive TOR can result in clinical depression. Overactive TOR results in epilepsy, and overactive TOR or PKA results in cancer.

"The most important take-home message is to think about all the different pathways in a cell in this way - that is, think about how pathways work together to provide precise control. We won't be able to design truly effective drugs until we do," he said.

"I want our research to continue along the same theme," Capaldi added. "We'll keep trying to figure out how different pieces of the growth-control network work together. There are hundreds and hundreds of signaling pathways that are interconnected, but we still don't know how or why they talk to each other. There is just so much we still have to learn."

Approximately one in every thousand children develops a urethral stricture, sometimes even when they are still a foetus in the womb. In order to prevent life-threatening levels of urine from accumulating in the bladder, paediatric surgeons like Gaston De Bernardis at the Kantonsspital Aarau have to surgically remove the affected section of the urethra and sew the open ends of the tube back together again. It would be less damaging to the kidneys, however, if a stent could be inserted to widen the constriction while the foetus is still in the womb.

Stents have been used to treat blocked coronary vessels for some time now, but the urinary tract in foetuses is much narrower in comparison. It's not possible to produce stents with such small dimensions using conventional methods, which is why De Bernardis approached the Multi-Scale Robotics Lab at ETH Zurich. The lab's researchers have now developed a new method that enables them to produce highly detailed structures measuring less than 100 micrometres in diameter, as they report in a recently published journal article.

Indirect 4D printing

"We've printed the world's smallest stent with features that are 40 times smaller than any produced to date," says Carmela De Marco, lead author of the study and Marie Sk?odowska-Curie fellow in Bradley Nelson's research group. The group calls the method they've developed indirect 4D printing. They use heat from a laser beam to cut a three-dimensional template - a 3D negative - into a micromould layer that can be dissolved with a solvent. Next, they fill the negative with a shape-memory polymer and set the structure using UV light. In the final step, they dissolve the template in a solvent bath and the three-dimensional stent is finished.

It's the stent's shape-memory properties that give it its fourth dimension. Even if the material is deformed, it remembers its original shape and returns to this shape when warm. "The shape-memory polymer is suitable for treating urethral strictures. When compressed, the stent can be pushed through the affected area. Then, once in place, it returns to its original shape and widens the constricted area of the urinary tract," De Bernardis says.

But the stents are still a long way from finding real-world application. Before human studies can be conducted to show whether they are suitable for helping children with congenital urinary tract defects, the stents must first be tested in animal models. However the initial findings are promising, "We firmly believe that our results can open the door to the development of new tools for minimally invasive surgery," De Marco says.

WASHINGTON, Aug. 08, 2019 -- WASHINGTON, Aug. 08, 2019 — Every year, around half a million people in the United States get sick from C. diff bacteria, often after taking antibiotics. Sounds counterintuitive? This week on Reactions, we break down why that happens, and how an unlikely hero could save the day: https://youtu.be/0dw7WZsmkjQ.

Magnetic resonance imaging (MRI) visualizes internal body structures, often with the help of contrast agents to enhance sensitivity. A Belgian team of scientists has now developed a bimodal contrast agent suited for two imaging techniques at once, namely, MRI and a technique called photoacoustic imaging. The use of only one contrast agent for two imaging techniques improves the sensitivity of both, with only little impact on the patient's body.

MRI is a widely used technique in medicine and research and is known for its good resolution. Structures down to a hundredth of a millimeter can be resolved. However, sensitivity, the ability to detect something at all, is sometimes an issue. Therefore, contrast agents are often administered to improve the clarity by which the structures can be seen.

The results of MRI can also be improved in combination with complementary imaging methods, which focus on different aspects. However, most imaging tools require the presence of probes and dyes, but applying first a contrast agent, and then a second drug may cause more risks for the patient. This inspired Sophie Laurent, a professor at the University of Mons, Belgium, and her team to develop so-called bimodal contrast agents - agents that would serve both tools at once.

MRI contrast agents typically contain gadolinium, a paramagnetic element that enhances the signal of the elements nearby. Free gadolinium can be harmful, but it is held tightly within the structure of an organic molecule. Laurent's idea was to directly join the gadolinium agent with the probe used for the second imaging technique.

The team chose photoacoustic imaging (PAI), a highly sensitive and rather new imaging method that measures the heat response in a tissue to laser pulses. The method is, like MRI, non-invasive, but a special organic dye must be present that absorbs laser light applied from the outside. This technique would clearly enhance MRI sensitivity, the authors thought. Dysfunctions in the skin and below would be detected with unprecedented clarity.

To join the gadolinium agent with the organic dye, the scientists chose the natural amino acid lysin as a linker. Lysin is special among the amino acids. It is a rather long molecule that can bind to two other molecules at both ends. The scientists successfully linked an MRI agent called Gd-PCTA with a PAI probe with the name ZW800-1. And there is another option. Apart from the two connections, lysin owns a third connectivity, which could be of use in the future. The scientists imagine adding an additional biovector, for example, a peptide that recognizes specifically a biological disorder--this would make the now bimodal probe trimodal.

The bimodal probe enhanced the MRI contrast as strongly as a commercial MRI agent. And it gave the same photoacoustic signal as the original PAI probe. This means the probe is a two-in-one agent, which facilitates the combination of MRI and other medical imaging techniques. The next step would be to test it in real organisms.

The beginning of this project dates back to 2012-2013, when team leader Ayrat Dimiev was working at Rice University, Houston, TX, USA, with Professor James Tour. Together with Natnael Behabtu, at that time a PhD student of Professor Matteo Pasquali, they discovered a phenomenon that could be observed in optical microscope during the stage transitions in graphite intercalation compounds. It took Dr. Dimiev six years of further research, including additional experiments at Kazan Federal University, to fully comprehend the driving forces behind the observed phenomena. The experiments were conducted with participation from PhD graduate Ksenia Shukhina. An important breakthrough came from the use of a new unique equipment, manufactured by the Belarusian company SOL Instruments, that allowed ultrafast Raman mapping of the graphite surface during the stage transitions.

Graphite intercalation compounds (GICs) are formed by insertion of certain atomic and molecular species between the graphene layers of graphite. The resulting compounds possess a range of unique properties, which are not specific for the parent materials. Among the most intriguing properties of GIC is its superconductivity, a discovery that triggered much interest. Depending on the electrochemical potential of the intercalant, and the respective charge on the graphene layers, graphite forms structures where one, two or more graphene layers are sandwiched between the two layers of intercalant. The resulting compounds are referred to as stage-1, stage-2, and stage-3 GICs, respectively. Despite intensive and long-lasting research on GICs, the mechanism of the stage transitions remains obscure.

In this study, authors used optical and Raman microscopy to perform direct real time monitoring of stage transitions in H2SO4-GIC made from highly oriented pyrolytic graphite (HOPG). They observed that stage transitions in HOPG-based GIC occur very differently from those in GIC made from the natural flake graphite. During the stage-2 to stage-1 transition, formation of the stage-2 phase begins nearly simultaneously over the entire graphite surface that is exposed to the media. This was attributed to the movement of the small intercalant portions toward the points of attraction, thus growing continuous islands. However, during the reverse process, the stage-1 to stage-2 transition begins strictly from the edges of the graphite sample and propagates toward its center. The most striking observation was that the deintercalation front was discontinuous; namely, the selected micrometer-sized domains of the graphite surface deintercalate preferentially to release the strain that had been induced by the intercalation. The intercalant dynamics in the 2D graphite galleries, occurring at the speed of >240 μm/s, has fast kinetics. The initial intercalation process is different from the rest of the reintercalation cycles. The difference in the mechanisms of the stage transitions in natural flake graphite-based GICs and in the HOPG-based GICs exemplifies the role of the graphite structure for the intercalant dynamics in 2D graphite galleries.

The findings made in this study advance the field of graphene and have several potential applications. GICs can be considered as stacks of doped graphene which can be easily prepared by fully reversible reactions; the doping level can be easily controlled by the reaction conditions. Secondly, intercalation weakens the adhesive forces between the adjacent graphene layers, thus, GICs serve as precursors for obtaining single-layer graphene and graphene nanoplatelets via liquid phase exfoliation. Third, GICs serve as important and unavoidable intermediates en route to covalent functionalization of graphene due to the charged condition of carbon atoms. Finally and most importantly, Li-ion battery operation is based on the cyclic intercalation-deintercalation of lithium ions with graphite. Understanding the stage transition mechanism will help in advancing all these applications.

Ayrat Dimiev concludes, "The studied stage transitions in the H2SO4-GICs are accompanied by the transfer of protons to and from the intercalated sulfuric acid that occurs by the Grotthuss mechanism, i.e. it is ultrafast and "frictionless". We are thinking of checking if that is true. If yes, these systems can be used as proton conductors in the hydrogen fuel cells. Another direction is developing an efficient and high-throughput procedure for the liquid phase exfoliation of graphite to mono-layer graphene."

The work of federal scientists is essential to support the health, security, and well-being of people in Canada, from exploring the high Arctic, to safeguarding the effective and ethical use of AI, to ensuring the food that ends up on our dinner plates is safe to eat. Their work takes place across a variety of departments and agencies with diverse mandates.

"Federal science happens in close to 200 laboratories and other major facilities across Canada, most of which are showing their age," said Wendy Watson-Wright, PhD, Chair of the Expert Panel. "This report is timely and necessary if Canada is to become a leader in transforming science for society through the next generation of science and technology infrastructure."

In Budget 2018, the federal government committed $2.8 billion to renew its science laboratories through an infrastructure initiative. One of the goals of this initiative is to support the construction of multi?purpose facilities that bring together scientists and engineers from across different departments and sectors. Beginning in 2019, the federal government will consider approaches to assess infrastructure investment opportunities that reflect a new vision for the federal science and technology (S&T) enterprise as collaborative, adaptive, and efficient.

Public Services and Procurement Canada asked the Council of Canadian Academies (CCA) to assess the evidence on leading practices for federal S&T infrastructure investment decisions.

Building Excellence synthesizes key theoretical and practical considerations for evaluating S&T infrastructure investment opportunities. The Panel identifies and explores four principles that can guide evaluations of proposed S&T infrastructure investments. The report also considers how the design of decision-making processes and advisory structures might support these principles.

"The challenges involved in renewing the federal government's S&T facilities are as diverse as they are complex" said Eric M. Meslin, PhD, FCAHS, President and CEO of the CCA. "This report aims to provide thoughtful, objective information to support decisions about the future of these important resources."

Technology that can help interpret inaudible calls from laboratory mice has been developed in a bid to improve research.

The computer tool can reveal valuable insights into rodents' communication patterns and is more reliable than existing methods, which rely on human interpretation.

The system analyses audio recordings of ultrasonic vocalisations - beyond the range of human hearing. Researchers say it could support research involving mice, which play a crucial role in testing new therapies for human diseases.

Monitoring rodent communications can reveal important information about how diseases progress, particularly for neurological disorders such as Parkinson's disease and autism.

Experts previously categorised mouse communications into nine call types by manually deciphering visual representations of the soundwaves, known as spectrograms.

Researchers have now developed an automated tool that can accurately extract characteristics of the ultrasonic vocalisations to determine these different types of sounds.

The new approach used machine learning techniques to make analysis faster, more reliable, and less subjective than human interpretation, the researchers say.

It will standardise interpretations of mouse communication, helping researchers to directly compare their results between labs, types of mice, and over time, they add.

The research was led by the Universities of Edinburgh and Melbourne and the Istituto Superiore di Sanità in Rome. It is published in the journal Scientific Reports.

Dr Athanasios Tsanas, of the University of Edinburgh's Usher Institute, who co-led the research, said: "We developed a fully automated system that uses signal processing and statistical machine learning techniques to extract a range of diverse patterns from rodents' ultrasonic vocalisations. We then mapped those patterns onto the widely accepted types of vocalisations that experts understand.

"We hope these tools may find further use in animal model studies investigating, for example, the effect of neurological effects on communication patterns."

Associate Professor Adam Vogel, of the University of Melbourne's Centre for Neuroscience of Speech, said: "These new methods will help scientists better measure mouse behaviour, improving how we test new medicines and how we measure changes in health and behaviour in different diseases and conditions."

People with familial chylomicronemia syndrome are born with a genetic mutation that means they can't produce an enzyme called lipoprotein lipase. Without the enzyme, their bodies can't break down dietary-derived fat in the blood. Instead, fat-carrying molecules called chylomicrons build up in the blood, causing many life-threatening symptoms, most notably pancreatitis. People living with this condition must follow a strict low-fat diet, but there is no treatment.

Joseph Witztum, MD, professor of medicine at University of California San Diego School of Medicine, recently helped lead a global research team that tested how well the drug volanesorsen reduces fat accumulation in the blood (triglycerides) of participants with familial chylomicronemia syndrome. In a randomized, double-blind Phase III clinical trial, 33 participants received the drug and 33 received a placebo.

Volanesorsen reduced triglyceride levels by an average of 77 percent. In contrast, for participants who received a placebo, triglyceride levels increased by an average of 18 percent.

These results will publish August 8, 2019 in the New England Journal of Medicine.

Chylomicrons carry dietary triglycerides from the gut into the blood, where they are normally broken down by the enzyme lipoprotein lipase. Without that enzyme, chylomicrons accumulate and thicken the blood of people with familial chylomicronemia syndrome.

"Chylomicrons are what you see when you see cream form on the top of milk," Witztum said. "For most people, when you eat a fatty meal for dinner at 6:00 p.m., the triglycerides are transported into the blood by chylomicrons and then lipoprotein lipase clears those out of the blood by 9:00 p.m. That's definitely not the case for patients with familial chylomicronemia syndrome."

Triglyceride levels are regulated by a molecule called apolipoprotein C-III, which is made in the liver, and then secreted into the blood. Volanesorsen, an antisense drug developed by Ionis Pharmaceuticals, is designed to block the mRNA in the liver that encodes apolipoprotein C-III. Reducing apolipoprotein C-III in the blood in turn reduces triglyceride levels. Triglycerides are often used as a measure for heart health, as high levels are associated with heart disease, even in otherwise healthy people.

Trial participants began by receiving 300 milligrams of volanesorsen under the skin once a week. The most common side effects were skin reactions at the injection site (20 of 33 participants who received volanesorsen vs. none in the placebo group) and thrombocytopenia (15 of 33 participants who received volanesorsen vs. none in the placebo group). Thrombocytopenia, or low levels of blood cells known as platelets, can limit the body's ability to form blood clots. Later in the trial, the doses were reduced to once every other week to reduce these side effects. The trial lasted for one year. Participants were aged 20 to 75 years old, 80 percent were white and 55 percent were female.

Volanesorsen was recently approved for clinical use in Europe, as an adjunct to diet in adult patients who have genetically confirmed familial chylomicronemia syndrome and are at high risk for pancreatitis, and who haven't responded to diet and triglyceride-lowering therapy. The team is now waiting for Food and Drug Administration approval to market the drug in the United States.

According to Witztum, this clinical trial also helped unravel some of the basic biology underlying dietary fat processing. Researchers had previously thought that lipoprotein lipase was a necessary intermediate that allowed apolipoprotein C-III to raise triglycerides levels. This trial revealed that that's not always the case -- apolipoprotein C-III has a second role independent of lipoprotein lipase, in which it inhibits the liver from taking up triglyceride-carrying particles.

"This is the sort of information that could help inform better prevention methods and treatments for many types of heart disease, not just this particular rare condition," Witztum said.

The approach adopted by the team of the University of Trento, led by Anna Cereseto, opens new perspectives in the treatment of cystic fibrosis, a genetic disease for which no cure is currently available. The research work was carried out in collaboration with KU Leuven, in Belgium. The research project ("A new gene therapy approach: repairing splicing mutations in the Cftr gene through genome editing") benefited from two years funding amounting to 90,000 euro from the Italian foundation for research on cystic fibrosis (Fondazione ricerca fibrosi cistica), with the participation of the Cystic fibrosis association of Trentino (Associazione trentina fibrosi cistica). The results of the study were published today in Nature Communications, an open access journal.

The disease is caused by a mutation of the gene that produces Cftr (the cystic fibrosis transmembrane conductance regulator), whose malfunctioning affects multiple organs, especially the lungs. The UniTrento/KU Leuven research team adapted the Crispr-Cas system, the molecular scissors that are revolutionising biomedicine, to permanently edit at least two types of the mutation that cause cystic fibrosis. In particular, the technique is called "SpliceFix" because it fixes the gene and restores the protein production mechanism at the same time.

Giulia Maule, doctoral student in Biomolecular sciences at the University of Trento and first author of the article, explained: "We have devised a genome editing strategy based on Crispr-Cas to permanently remove two different mutations that cause the disease. Crispr-Cas works like a genomic scalpel to cut out the mutated elements with extreme accuracy. We demonstrated that our repair strategy works on patient-derived organoids and with a high level of precision: it targets only the mutated sequences, leaving non-mutated DNA untouched".

The young researcher underlines a novel aspect of the study: "Instead of animal models, we have used organoids that we developed from the patients' cells, a choice that allowed us to verify the efficacy of the molecular strategy in a context that is very similar to that of the patients with cystic fibrosis".

Cystic fibrosis is also called the invisible disease because it doesn't show on the outside, and yet it takes a huge toll on the lives of the people it affects. Most of all, they have lung and digestive problems. The disease is inherited from parents. In Italy, about one in 25 people is a carrier. This means that a couple of carriers has one chance in four to have a child with the disease. There are about 6,000 people with cystic fibrosis in Italy, and 200 new cases every year.

Washington, DC - There are longstanding debates in the United States about how society should distribute resources and support, from education to public health. Examining fairness through the lens of Moral Foundation Theory, researchers show that people on the political left (Democrats and liberals) tend to focus on equity, or need based on where people start, more than people on the political right (Republicans and conservatives). When it comes to proportionality, or the idea that people's outcomes should be proportional to their effort (sometimes viewed as the "Protestant work ethic"), the link between a person's political leaning and their concern for proportionality isn't as strong.

"Even though people on the political left are somewhat less likely to buy into the belief that 'you get what you give' than those on the political right," says Christofer Skurka (Cornell University), "it seems that concerns about meritocracy, and what some have called the Protestant Work Ethic, are interwoven into the fabric of American principles."

The research appears in the journal Social Psychological and Personality Science.

They studied a national sample of U.S. adults recruited through Nielsen's Harris Panel, randomly split into calibration (N=1,499) and replication samples (N=1,499).

Moral Foundations Theory (MFT) is a well-known psychological framework that unpacks why people judge moral situations in different ways. In terms of politics, differing moral views are linked to support and opposition for various policies.

"For a while, there has been discussion about expanding MFT to include other foundations aside from the original five foundations described by the theory and to refine our understanding of the original foundations," says Skurka.

The participants completed a moral foundations questionnaire, measuring their views on various moral principles including Harm/Care (involving empathy and the desire to limit the suffering of others), Fairness/Reciprocity (the desire to minimize unjust treatment), Ingroup/Loyalty (obligation to the groups of which one is a member), Authority/Respect (reflecting the need to maintain social order by respecting hierarchical relationships), and Purity/Sanctity. Participants also reported their political leanings and party affiliations, if they had any.

They looked at two new possible "foundations" on which people in the U.S. base their judgments about what is right and wrong: Equity, that people should receive support based on their starting point in order to ensure that all people have equal success, and Proportionality, that people should receive support in proportion to how much effort they give.

Both Equity and Proportionality emerged as significant predictors of party affiliation in their first and second study. Specifically, for a one-unit increase on the Equity scale, the odds of being a Democrat increased by 54-82%. For a one-unit increase on the Proportionality scale, the odds of being a Democrat decreased by 31-34%. However, when they looked at Equity and Proportionality as predictors of political ideology (on a scale from extremely conservative to extremely liberal), Equity consistently predicted a person's ideology, but Proportionality only predicted a person's ideology in the first study.

Skurka notes that they only interviewed adults in the United States for this study, so these results may not hold for other groups of people or cultures.

They are also still parsing out if their findings reflect two possible new foundations, Equity and Proportionality, for MFT or if these are "simply values that shape how we view the world around us."

"If we get a better sense of how these foundations play out in cultural contexts outside the U.S., we will have a much better idea of whether Equity and Proportionality are inherent to all of our moral evaluations," summarizes Skurka.