Brain

New Haven, Conn. -- Yale Cancer Center (YCC) scientists have uncovered the workings of a metabolic pathway or "gauge" that lets cancer cells detect when they have enough nutrients around them to grow. The researchers hope that drugs designed to turn down the gauge may eventually aid in treating many forms of cancer. Their findings were published in the journal Oncogene.

"The cancer cell has an unlimited appetite for nutrients," said Xiaoyong Yang, Ph.D., associate professor of comparative medicine and of cellular and molecular physiology at YCC and senior author of the study. "But in many parts of the body, especially for solid tumors, nutrients and oxygen are often limited, so the cell has to make a decision to grow or survive. We have shown how the cell adapts to its microenvironment, detecting nutrient availability to make this decision."

Yang and his colleagues studied the role of a process called O-GlcNAc protein modification in cancer metabolism. O-GlcNAc modification alters the function of proteins by attaching certain kinds of sugar molecules and is thought to generally act as a nutrient sensor for the cell. Yang noted "we were interested in this modification because it is a common feature across many types of cancer."

The YCC team began by examining a wide range of human cancer tissue samples for signs of O-GlcNAc modification, including levels of expression for the OGT and OGA enzymes. They found that both OGT and OGA are expressed at higher levels in many cancers than in normal tissues. Next, the investigators discovered that OGA also promotes tumor growth and metabolic reprogramming in cancer cells. They followed up to show OGA does so by altering acetylation of a protein known as PKM2 (a key player in cell metabolism), and this activity increases along with levels of glucose available to the cell. OGT then inhibits PKM2 activity via O-GlcNAc modification, which drives metabolic reprogramming and promotes tumor growth.

The result was a surprise, since scientists previously thought that OGA and OGT directly work against each other. "People always thought they were foes, and our study identified how they can be friends," Yang said. "These two opposing enzymes work together in a nutrient-rich environment to drive cancer cells to grow and reproduce."

Yang now hopes to develop drugs that can mislead the OGA/OGT metabolic gauge, "so that cancer cells don't decide to turn on aerobic glycolysis and grow even when nutrients are flowing freely," he said.

This OGA/OGT biological pathway is also working at much lower levels in normal cells, so the drugs would aim to reduce the pathway rather than block it completely. Yang's team is collaborating with biochemist colleagues to investigate compounds that target the enzymes. The researchers hope to eventually see if such compounds can be combined effectively with other drugs to treat many forms of cancer.

Scientists have shown for the first time a link between two types of heart problems and one of the most commonly prescribed classes of antibiotics.

In a study published today in the Journal of the American College of Cardiology, researchers at the University of British Columbia (UBC) in partnership with the Provincial Health Services Authority's (PHSA) Therapeutic Evaluation Unit found that current users of fluoroquinolone antibiotics, such as Ciprofloxacin or Cipro, face a 2.4 times greater risk of developing aortic and mitral regurgitation, where the blood backflows into the heart, compared to patients who take amoxicillin, a different type of antibiotic. The greatest risk is within 30 days of use.

Recent studies have also linked the same class of antibiotics to other heart problems.

Some physicians favour fluoroquinolones over other antibiotics for their broad spectrum of antibacterial activity and high oral absorption, which is as effective as intravenous, or IV, treatment.

"You can send patients home with a once-a-day pill," said Mahyar Etminan, lead author and associate professor of ophthalmology and visual sciences in the faculty of medicine at UBC. "This class of antibiotics is very convenient, but for the majority of cases, especially community-related infections, they're not really needed. The inappropriate prescribing may cause both antibiotic resistance as well as serious heart problems."

The researchers hope their study helps inform the public and physicians that if patients present with cardiac issues, where no other cause has been discovered, fluoroquinolone antibiotics could potentially be a cause.

"One of the key objectives of the Therapeutic Evaluation Unit is to evaluate different drugs and health technologies to determine whether they enhance the quality of care delivered by our programs or improve patient outcomes," said Dr. Bruce Carleton, director of the unit and research investigator at BC Children's Hospital, a program of PHSA. "This study highlights the need to be thoughtful when prescribing antibiotics, which can sometimes cause harm. As a result of this work, we will continue working with the BC Antimicrobial Stewardship Committee to ensure the appropriate prescribing of this class of antibiotics to patients across British Columbia, and reduce inappropriate prescribing."

For the study, scientists analyzed data from the U.S. Food and Drug Administration's adverse reporting system. They also analyzed a massive private insurance health claims database in the U.S. that captures demographics, drug identification, dose prescribed and treatment duration. Researchers identified 12,505 cases of valvular regurgitation with 125,020 case-control subjects in a random sample of more than nine million patients. They defined current fluoroquinolone exposure as an active prescription or 30 days prior to the adverse event, recent exposure as within days 31 to 60, and past exposure as within 61 to 365 days prior to an incident. Scientists compared fluoroquinolone use with amoxicillin and azithromycin.

The results showed that the risk of aortic and mitral regurgitation, blood backflow into the heart, is highest with current use, followed by recent use. They saw no increased risk aortic and mitral regurgitation with past use.

Etminan hopes that if other studies confirm these findings, regulatory agencies would add the risk of aortic and mitral regurgitation to their alerts as potential side effects and that the results would prompt physicians to use other classes of antibiotics as the first line of defense for uncomplicated infections.

Athens, Ga. - A research team from the University of Georgia's Regenerative Bioscience Center has found that a compound molecule used for drug delivery of insulin could be used to treat glioblastoma, an aggressive, usually fatal form of brain cancer.

Glioblastoma, also known as GBM, is a fast-growing, web-like tumor that arises from supportive tissue around the brain and resists surgical treatment. Described by some as "sand in grass," GBM cells are hard to remove and tend to reach out in a tentacle-like fashion through surrounding healthy brain tissue.

According to the National Foundation for Cancer Research, more than half of newly diagnosed GBM patients die within the first 15 months. Late U.S. Sens. John McCain and Ted Kennedy both died from GBM, raising national awareness of the deadly disease.

Surfen, a compound molecule first described in 1938, is a pharmaceutical agent used to optimize insulin delivery. The UGA researchers identified that surfen-treated cells were "blocked" from tumor growth, and the spread of tumor cells in the brain.

"This study shows that we can stifle the growth of invasive brain tumors with a compound that has a substantial clinical advantage, and can aid in the reduction or refinement of mainstream treatments, particularly radiation and/or chemo," said Lohitash Karumbaiah, associate professor of regenerative medicine in UGA's College of Agricultural and Environmental Sciences.

Published ahead of print in the FASEB Journal, the study is the first known use of surfen as an application to treat GBM. To test the approach, the research team first used cultured cells to observe binding properties of the surfen compound. Next, they introduced live rodent models with cells that could grow into invasive tumors. The researchers found that surfen-treated animals demonstrated smaller tumors and substantially reduced brain hemorrhage volume than control animals.

"In basic terms, surfen is highly positively charged and will bind to negatively charged things," said Meghan Logun, a graduate student working with Karumbaiah. "Since we study sugars in the brain, which are highly negatively charged, we then asked, 'Why not try using positive charges to block off the negative ones?'"

Logun is studying how brain cancer takes advantage of highly charged elements in brain tissue to aid in invasion. "In the surfen-treated animals, we saw that the tumors were actually much more constrained and had more defined boundaries," she said.

To explore the surfen molecule further, the team worked with Leidong Mao, associate professor in UGA's College of Engineering and co-developer of a microfluidic device used to examine glycosaminoglycans (GAGs)--highly negatively charged molecules produced by brain tumors. Designed to mimic the neural pathways of the brain, the device allows for real-time monitoring of tumor cell adhesion and growth.

"We did not expect to see such a robust response," Mao said. "Blocking off the charged GAGs from the tumor cells really did dampen their ability to invade."

Based on the study's discovery that surfen had isolated the tumor, the team also analyzed MRI images to gauge the treatment's effectiveness.

"In the MRI image you can see [the effects of the surfen treatment] pretty drastically, not in terms of killing the GBM but in blocking its prey," said Qun Zhao, associate professor of physics in the UGA Franklin College of Arts and Sciences and another RBC collaborator on the project. "In the non-treated image, you see rampant invasive growth, compared to the surfen-models where you see a nicely contained and almost circular-shaped tumor."

"The tumor may still grow, but at least now it doesn't have any invasive inroads to creep into other parts of the brain," said Karumbaiah. "That could be clinically beneficial for a surgeon wanting to remove the tumor and not having to worry about rogue cancer cells."

Looking ahead, Karumbaiah is hopeful that repurposing a compound known to be safe, with proven and beneficial binding properties, could help accelerate review and approval of this potential new therapeutic, and advance consideration in helping to expedite the drug approval process.

"Our hope is that, in the wake of this discovery, lives can be saved, and we can finally change the scope of this life-threatening disease," said Karumbaiah. "In my five years at UGA, this is the highest profile cancer paper I've ever had."

ITHACA, N.Y. - Lakes of liquid methane on the surface of Titan, Saturn's largest moon, were likely formed by explosive, pressurized nitrogen just under the moon's surface, according to new research.

"Titan has very distinctive topography. Its lakes show different kinds of shapes and in some cases sharp ridges," said paper co-author Jonathan Lunine, professor of physical sciences at Cornell University.

An international team of scientists examined lakes on Titan's surface that featured steep, cratered sharp edges, raised rims and ramparts. Some of the steep ridges tower far above the moon's natural liquid sea level.

"You either need gas that ignites explosively or a gas that builds up enough pressure so that it just pops like a cork from a champagne bottle," Lunine said. "On Titan, there is nothing that will create a fiery explosion because that moon has no free oxygen. Thus, a pressurized explosion model, we argue, is a better model for those kinds of lakes. Craters are created and they fill with liquid methane."

Besides Earth, Titan is the only other body in the solar system with a stable liquid - in this case, methane - on its surface. Titan's atmosphere is filled with vaporized nitrogen.

In Titan's geophysical history, that moon has seen epochs where methane becomes depleted, leaving a nitrogen atmosphere. The nitrogen cools, producing nitrogen liquid rain in its frigid climate, which then collects in pockets under Titan's crust.

While Titan is far from the sun, a slight amount of geologic heating might occur that causes this pressurized gas to explode, popping out to the surface. In the moon's natural cycling process, liquid methane returns and fills the craters to make lakes.

Images for this research were gathered by the radar data from the NASA Cassini mission's last close flyby of Titan, just months before the spacecraft's final plunge into Saturn two years ago.

Older adults are using cannabis at an unprecedented rate, yet research that informs policymakers on the topic is scarce, according to the latest issue of the journal Public Policy & Aging Report (PP&AR) from The Gerontological Society of America.

Titled "There's Something Happening Here: Exploring the Evolving Intersection between Cannabis and Older Persons," the journal highlights existing studies as well as recommended areas for further research.

"We largely remain in the dark regarding many important aspects about this rapidly evolving public health policy issue," wrote PP&AR Editor-in-Chief Brian Kaskie, PhD, in his introduction. "The United States is entering a period when states continue to operate as cannabis policymaking laboratories, the cannabis economy may grow five-fold, and the older adult population is projected to double."

Among the five articles that follow, the journal offers insights about a 2017 Academy of Medicine report on cannabis, the negative and positive outcomes experienced by older cannabis users, and the perspectives of health-care providers who increasingly encounter older patients who want to know about cannabis or may already be using it.

"There is an urgent need to provide policy makers, program administrators, and clinicians with empirically based answers to critical questions, such as: Why have some states extended cannabis program eligibility to persons with Alzheimer's disease, given meager amounts of clinical evidence? Is increasing cannabis use among older adults contributing to increasing cannabis use disorders, co-occurring substance use disorders, or related comorbidities?" Kaskie wrote.

The contents of the new PP&AR:

"There's Something Happening Here, But What It Is Ain't Exactly Clear," by Brian Kaskie, PhD

"The 2017 Cannabis Report of the National Academy of Medicine: A Summary of Findings and
Directions for Research Addressing Cannabis Use Among Older Persons," by Robert B. Wallace, MD, MSc

"Potential Harms of Marijuana Use Among Older Adults," by Namkee G. Choi, PhD, FGSA, Diana M. DiNitto, PhD, and Stephan Arndt, PhD

"The Role of Cannabis in Improving Pain and Symptom Management in End-of-Life Care," by J. Alton Croker III and Sara Sanders, PhD, MSW, FGSA

"Cannabis as an Alternative to Opioid Use by Older Adults: The Illinois Opioid Alternative Pilot
Program," by Julie Bobitt, PhD, and Conny Mueller Moody

"Medical Cannabis Policy: Considerations for Older Patients and Their Health-Care Providers," by Kenneth Brummel-Smith, MD, and Freddi Segal-Gidan, PhD

In 1886, female students at Vassar College put on a parody of the opera "The Mikado" by Gilbert and Sullivan. The work reveals notions about who can or cannot do math.

Laura Kasson Fiss accidentally discovered "The Mathematikado" as a graduating senior at Vassar College. She was perusing a local bookstore, the kind with used books that smell like history in the making, when she came across a thin paperback with a red-inked title. Together with Andrew Fiss, she gradually recognized it as one of the plays used in the Trig Ceremonies that Victorian students would write and produce at the end of sophomore mathematics courses. The addition of "math" to the title of one of the era's most popular operas caught her eye.

"These kinds of plays were quite common at the time," said Kasson Fiss, now the assistant director of the Honors Pathway Program in the Pavlis Honors College at Michigan Technological University, explaining that parodies of the classics and some contemporary performances were an important part of mid 19th-century college culture, especially about the rigors of math class. "To be able to joke -- and joke lightly -- is tied to the power of humor. It's saying you have the power to treat it lightly and laugh about it because you're that comfortable with it."

She shared the libretto with her math-major friend Fiss, now spouse and research partner, who is an assistant professor of technical and professional communication at Michigan Tech. Over the years, the two have adapted the music and thought deeply about its meaning. The team recently published a paper in Configurations, an expanded version of the team's lecture-performance of "The Mathematikado" at the 2017 British Science Festival alongside Amy Chambers from Manchester School of Art. (Listen to part of their performance on The Anthill podcast.)

The chapter leaders of Philaletheis, the Vassar College theater group, said in the 1870s that students works should be "...racy, witty, and spiced with common sense."

Some of the jokes are rusty to modern ears, but the "The Mathematikado" and its lineage of student-produced plays are full of tongue-in-cheek gibes at faculty, fellow students and their classes.

"I get asked all the time, were the Victorians actually funny?" Kasson Fiss said. (And adds, of course, they were.) "Gilbert and Sullivan's work was already complex and this adds new layers. Parody allows for fluidity and complexity in humor."

This is clear in the Vassar students' parody of "The Mikado," which was already a parody. The plotline, the characters, the setting are twisted and transposed to be closer to real-life college than the already warped portrayal of a fake Japanese village brought to London. One character, for example, speaks only in long passages from her trigonometry textbook while another character courts her (and he bemoans their equation-laden conversations like any post-finals student).

"The story looks like it's about math but is really about being a college student in a time when college was male-dominated," Kasson Fiss said. "In the script, the students played with gender pronouns, they pushed the edge with figuring out how to dress up in men's clothing while still wearing a skirt ... As a woman in a role that is often thought of as male, how do you behave? How much do you act like a man and how much do you act like a woman?"

While the conversation has evolved since the Victorian era, the Vassar students' experience of math class is not antiquated. Kasson Fiss and Fiss see opportunities for today's young women in "The Mathematikado" and Trig Ceremonies.

"Women are still underrepresented in math, " said Fiss, who brings a dual background in mathematics and technical communication. "There is a lot of talk about how to get out of the leaky pipeline in STEM education -- and part of it is through not calling it that any more -- and also what's exciting about this project is finding ways out by looking to what's been done in the past."

Specifically, Fiss sees plays and performance as one way to reframe math education -- that play and movement complement learning abstract mental concepts and opens more avenues for deeper and empowered learning.

"The play's math jokes and terminology showed that the students were in on the culture," Fiss said, adding that the parody shows there are alternatives to the status quo "that predate the conversations that people feel we're stuck in today."

Through the intersections of humor, literature, performance, math, music and college life, Fiss and Kasson Fiss see much potential for enlivening a traditional STEM classroom, just as the Vassar students did more than a century ago.

Researchers from Chalmers University of Technology and Politecnico di Milano have identified a crucial new aspect of charge density modulations in cuprate high critical temperature superconductors. They have identified a new electron wave which could help reveal some of the mysteries about superconducting materials. The findings are published in the journal Science.

High critical temperature superconductors have a variable charge density, meaning that their electrical charge is unevenly distributed. This partly results from what are known as 'charge density waves', which were discovered a few years ago. But these have only been observed to exist sporadically, under certain conditions. Therefore, they were not believed to be a contributing factor to the materials' superconducting properties.

What the researchers have now discovered, however, is an additional aspect to the variable charge density, which they term "charge density fluctuations". These have been identified as an additional charge modulation, collective and with a shorter correlation length. They are very pervasive, meaning that compared to the conventional charge density waves, they are present at a much greater range of temperatures, up to room temperature and beyond, and at different levels of oxygen doping.

"These charge density fluctuations could be a crucial ingredient of the highly unconventional room temperature properties of high critical temperature superconductors - something which challenges our common understanding of the charge transport in metals," says Riccardo Arpaia, postdoctoral researcher at the Department of Microtechnology and Nanoscience at Chalmers, who carried out the research.

"One could say the charge density waves, which were already very well known, were just the tip of the iceberg. The charge density fluctuations which we have now identified are like the hidden bulk of the iceberg." says Riccardo Arpaia. "The discoveries were possible thanks to the major developments of synchrotron-based x-ray scattering techniques, and to the quality of the samples we have used."

The samples were fabricated at the Italian National Research Council in Napoli, and in
the research group at Chalmers led by Professor Floriana Lombardi.

A further finding of the paper looks at how the charge density fluctuations evolve with the temperature of the material. While the previously-known charge density waves change abruptly as soon as the critical temperature is reached - meaning, dependent on whether the material is in a superconductive state or not, the newly-discovered charge density fluctuations are unaffected by the superconductivity. This indicates that the two characteristics are not 'in competition' with one another. This finding might strengthen the researchers' theory that the charge density fluctuations are the key to explaining the mystery of these materials.

Because superconductors operate at such low temperatures, they require cooling from liquid helium or liquid nitrogen, making them expensive and difficult to use outside of certain commercial applications. But if a superconductor could be made to work closer to room temperature, it could have enormous potential. Therefore, there is a lot of interest in improving our understanding of how this class of superconductors works.

Giacomo Ghiringhelli, Professor of Physics at Politecnico di Milano says about the research: "Since 2012, when charge density waves in cuprates were first observed, their importance had not been disputed - but their role had remained unclear. The newly observed charge density fluctuations appear to be a very general property of these materials, meaning they are likely playing a crucial role in the transport of electric current in cuprates."

Read the article "Dynamical charge density fluctuations pervading the phase diagram of a Cu-based high-Tc superconductor" in the journal Science.

More information about superconductors

Superconductors are materials which, when exposed to a certain temperature, known as the 'critical temperature', suddenly acquire incredible new properties - chiefly, that they can conduct electrical charge with zero resistance.

Most superconductors currently in commercial use are known as low critical temperature - typically meaning below about -240 degrees Celsius. High critical temperature superconductors meanwhile, are those which exhibit superconducting properties at a somewhat higher temperature - though still hundreds of degrees below zero. The most common type are known as 'cuprates', made from a mixture of copper and oxygen - it was this particular class of superconductors which the researchers investigated.

European collaboration for the research

Riccardo Arpaia, co-lead author of the paper, is a researcher from Chalmers University of Technology who, through the framework of the Swedish Research Council's international postdoc programme, also researches at Politecnico di Milano, in the group of Giacomo Ghiringhelli, who conceived the experiment.

Chalmers and Politecnico di Milano are both members of the IDEA league, an alliance of five leading European technological universities, that aims to encourage and elevate European research in science and technology by sharing academic resources and knowledge.

Experiments were performed at the European Synchrotron Radiation Facility in Grenoble, in collaboration with researchers of the Italian National Research Council (CNR) and of the Sapienza University of Rome.

Resonant inelastic X-ray scattering

The researchers identified the charge density fluctuations through the use of a technique known as resonant inelastic X-ray scattering. RIXS is a spectroscopy technique, where photons (X-ray radiation) get scattered from a material due to interaction with electronic clouds.

RIXS is, as suggested by the name, a resonant technique, since the energy of the incident photons coincides, and hence resonates, with a specific electronic transition (the Cu L3 edge at ?931 eV, in the case illustrated in the paper). This strongly enhances the signal. For this reason, RIXS currently represents the best technique for the detection of weak charge density modulations with particularly short correlation lengths, going even beyond previous limits set by neutron scattering and scanning tunnel microscopy techniques.

BOSTON - A new method for super-cooling human donor livers to subzero centigrade temperatures without freezing can triple the time that a donor organ stays safe and viable during transportation from the donor to the recipient. This development could greatly expand the availability of healthy livers for transplantation, improve organ utilization, and reduce some of the time pressure on procurement and transplantation teams.

This breakthrough addresses a dire need: because of the current donor organ shortage only about 36,500 of the 730,000 patients with fatal end-stage organ disease receive a life-saving organ transplant each year in the U.S.

The technique developed by Reiner J. de Vries, MD, Shannon N. Tessier, PhD, and Korkut Uygun, PhD from the Center for Engineering in Medicine at Massachusetts General Hospital (MGH) and Harvard Medical School, and their colleagues is described in Nature Biotechnology.

Currently, a donor human liver is kept only about nine hours outside the body -- stored on ice in a preservative solution at temperatures ranging from four to eight degrees C (39.2 to 46.4 degrees F) -- before the tissues become irreparably damaged and the organ has to be discarded. At colder, subzero temperatures the organ would survive longer; however freezing causes serious damage. This is similar to the damage deep frostbite can cause to skin and extremities and would make the organ not transplantable.

But as the MGH investigators previously demonstrated with rat livers, it's possible to "supercool" them to -6 °C (21.2 °F) without causing injury to the tissues, extending their preservation time from a matter of hours to a matter of days. The technique was hailed as an "awesome technology" by National Institutes of Health Director Francis Collins, MD, PhD in his "Director's Blog."

"With supercooling, as the volume increases it becomes exponentially more difficult to prevent ice formation at sub-zero temperatures," de Vries says. "So before, there were a lot of experts who said 'well this is amazing in small rats, but it will not work in human organs' and now we have successfully scaled it up 200 times from rat to human livers, using a combination of technologies."

Prior to supercooling, the livers are conditioned to protect them from the cold with a preservative "cocktail" that is delivered via machine perfusion, another technique already in use to improve organs for transplantation. The perfusion ensures that the preservative solution is evenly distributed throughout the organ.

The human livers can then be transported at -4 °C (24.8 °F), and at the transplantation site machine perfusion is again used to carefully warm the livers and bring them out of their state of suspended animation.

Using this technique, the investigators have been able to extend the out-of-body time for livers to 27 hours - long enough for a donated organ to be shipped virtually anywhere in the United States or beyond.

The extra time the technique can buy could make the difference between success and failure of a liver transplant, Tessier says.

"A lot of times when an organ becomes available, there may not be a good match nearby, so in terms of allocation, when you add that extra amount of time that means you can search a wider distance which means you have a better chance of not only finding a good match, but an excellent match," she says. "And that means that you have less organ discard, get more organs to recipients, and those organs are better matched to the recipients, meaning that organ can have a longer life within the recipient."

Positive childhood experiences, such as supportive family interactions, caring relationships with friends, and connections in the community, are associated with reductions in chances of adult depression and poor mental health, and increases in the chances of having healthy relationships in adulthood, a new study led by Johns Hopkins Bloomberg School of Public Health researchers suggests. This association was true even among those with a history of adverse childhood experiences.

The findings, to be published September 9 in JAMA Pediatrics, could encourage public health efforts and policies aimed at boosting positive childhood experiences in conjunction with reducing adverse childhood experiences.

Researchers have long known that adverse childhood experiences, such as physical or emotional abuse or neglect, substance abuse and mental health problems in the household, exposure to violence, parental incarceration or divorce, can have lifelong negative effects on physical and mental health, explains study leader Christina Bethell, PhD, MPH, MBA, professor in the Bloomberg School's Department of Population, Family and Reproductive Health and director of the Child and Adolescent Health Measurement Initiative.

The association between adverse childhood experiences and health effects is complex. Some individuals with multiple adverse childhood experiences thrive while others do not. And, many without adverse childhood experiences have health issues associated with adverse experiences, perhaps due to a lack of positive childhood experiences.

Positive childhood experiences are a key factor in influencing health and well-being, yet have not been sufficiently studied to date.

Bethell and her colleagues found a significant connection between positive childhood experiences and adult respondents' mental and emotional health. For those reporting six to seven positive childhood experiences, the odds of having depression or 14 or more poor mental health days in the previous months were 72 percent lower than for those reporting zero to two positive childhood experiences. Even for those reporting three to five positive childhood experiences, the odds of depression or poor mental health were 50 percent lower than those reporting zero to two positive childhood experiences. These associations held true even when respondents reported multiple adverse childhood experiences.

Additionally, the odds that respondents answered "always" on the question about getting the social and emotional support they need as adults was 3.53 times greater for those reporting six to seven positive childhood experiences compared to those reporting zero to two. Even among those with no adverse childhood experiences, only one-third reported always getting the social and emotional support they needed if they had zero to two positive childhood experiences. This was half the rate as those with six to seven such experiences. "Given the science linking social and emotional support to life expectancy, health and suicide, these findings have important implications," Bethell explains.

For their study, Bethell and her colleagues investigated the effects of positive childhood experiences analyzing data from the Wisconsin Behavioral Risk Factor Survey, a yearly random digit-dial telephone survey conducted in collaboration with the U.S. Centers for Disease Control and Prevention. The survey collects state-level data about health-related risk behaviors, chronic health conditions, and the use of preventive services.

In the 2015 Wisconsin survey, the state included seven extra questions related to positive childhood experiences. These included whether the respondents (1) were able to talk with their families about their feelings, (2) felt that their families stood by them during difficult times, (3) enjoyed participating in community traditions, (4) felt a sense of belonging in high school, (5) felt supported by friends, (6) had at least two non-parent adults who took genuine interest in them, and (7) felt safe and protected by an adult in their home.

The study designed, tested, and used a new positive childhood experiences measure that showed a dose-response relationship between how many positive experiences adults reported and their mental and relational health. This new "cumulative positive" design captures aggregate experiences in the same way adverse childhood experiences measure "cumulative risk."

The survey also scored respondents' adverse childhood experiences and included questions about mental health, including diagnoses of depression and how many reported having poor mental health days in the past month. In addition, respondents were asked how often they got the social and emotional support they need (adult-reported social and emotional support). More than 6,000 adults ages 18 and older participated in the survey.

"This study offers the hopeful possibility that children and adults can thrive despite their accumulation of negative childhood experiences," say Bethell. "People assume eliminating adversity automatically results in good health outcomes, but many people reporting lower adversity in childhood still had poorer mental and relational health outcomes if they did not also report having had positive childhood experiences."

Treating preterm infants with antibiotics for more than 20 months appears to promote the development of multidrug-resistant gut bacteria, suggests a study funded by the National Institutes of Health. The research appears in Nature Microbiology.

Researchers used high-speed DNA sequencing and advanced computational analysis to study stool samples from 32 infants born very preterm who received antibiotic treatment for 21 months (in the neonatal intensive care unit and after discharge), nine infants born very preterm who received antibiotics for less than a week, and 17 healthy term and late preterm infants who hadn't received antibiotics. Infants who received prolonged antibiotic treatment had less diverse bacterial populations in their gut, compared to the other infants, and these bacteria contained more antibiotic resistance genes.

Moreover, the genomes of the high antibiotic use group contained genes for resistance to antibiotics typically not given to newborns, such as ciprofloxacin and chloramphenicol. One possible explanation is that these genes might originate in multidrug-resistant bacteria, so using a particular antibiotic may trigger resistance to other antibiotics, even if they were not used.

The researchers do not know the long-term effects of these genome changes, which they term "microbiota scars." They note that previous studies linked antibiotic treatment during infancy with allergies, psoriasis, obesity, diabetes and inflammatory bowel disease later in life. Their findings raise the possibility that early-life antibiotic use may promote these effects by reducing the diversity of microbial communities in the gut, encouraging the growth of injurious bacterial species and perhaps also suppressing the growth of beneficial microbes.

BUFFALO, N.Y. -- Superhard materials can slice, drill and polish other objects. They also hold potential for creating scratch-resistant coatings that could help keep expensive equipment safe from damage.

Now, science is opening the door to the development of new materials with these seductive qualities.

Researchers have used computational techniques to identify 43 previously unknown forms of carbon that are thought to be stable and superhard -- including several predicted to be slightly harder than or nearly as hard as diamonds. Each new carbon variety consists of carbon atoms arranged in a distinct pattern in a crystal lattice.

The study -- published on Sept. 3 in the journal npj Computational Materials -- combines computational predictions of crystal structures with machine learning to hunt for novel materials. The work is theoretical research, meaning that scientists have predicted the new carbon structures but have not created them yet.

"Diamonds are right now the hardest material that is commercially available, but they are very expensive," says University at Buffalo chemist Eva Zurek. "I have colleagues who do high-pressure experiments in the lab, squeezing materials between diamonds, and they complain about how expensive it is when the diamonds break.

"We would like to find something harder than a diamond. If you could find other materials that are hard, potentially you could make them cheaper. They might also have useful properties that diamonds don't have. Maybe they will interact differently with heat or electricity, for example."

Zurek, PhD, a professor of chemistry in UB College of Arts and Sciences, conceived of the study and co-led the project with Stefano Curtarolo, PhD, professor of mechanical engineering and materials science at Duke University.

The quest for hard materials

Hardness relates to a material's ability to resist deformation. As Zurek explains, it means that "if you try to indent a material with a sharp tip, a hole will not be made, or the hole will be very small."

Scientists consider a substance to be superhard if it has a hardness value of over 40 gigapascals as measured through an experiment called the Vickers hardness test.

All of the study's 43 new carbon structures are predicted to meet that threshold. Three are estimated to exceed the Vickers hardness of diamonds, but only by a little bit. Zurek also cautions that there is some uncertainty in the calculations.

The hardest structures the scientists found tended to contain fragments of diamond and lonsdaleite -- also called hexagonal diamond -- in their crystal lattices. In addition to the 43 novel forms of carbon, the research also newly predicts that a number of carbon structures that other teams have described in the past will be superhard.

Speeding up discovery of superhard materials

The techniques used in the new paper could be applied to identify other superhard materials, including ones that contain elements other than carbon.

"Very few superhard materials are known, so it's of interest to find new ones," Zurek says. "One thing that we know about superhard materials is that they need to have strong bonds. Carbon-carbon bonds are very strong, so that's why we looked at carbon. Other elements that are typically in superhard materials come from the same side of the periodic table, such as boron and nitrogen."

To conduct the study, researchers used XtalOpt, an open-source evolutionary algorithm for crystal structure prediction developed in Zurek's lab, to generate random crystal structures for carbon. Then, the team employed a machine learning model to predict the hardness of these carbon species. The most promising hard and stable structures were used by XtalOpt as "parents" to spawn additional new structures, and so on.

The machine learning model for estimating hardness was trained using the Automatic FLOW (AFLOW) database, a huge library of materials with properties that have been calculated. Curtarolo's lab maintains AFLOW and previously developed the machine learning model with Olexandr Isayev's group at the University of North Carolina at Chapel Hill.

"This is accelerated material development. It's always going to take time, but we use AFLOW and machine learning to greatly accelerate the process," Curtarolo says. "The algorithms learn, and if you have trained the model well, the algorithm will predict the properties of a material -- in this case, hardness -- with reasonable accuracy."

"You can take the best materials predicted using computational techniques and make them experimentally," says study co-author Cormac Toher, PhD, assistant research professor of mechanical engineering and materials science at Duke University.

Doctors have found that children who have been in Intensive Care Units (ICUs) for sepsis have a significantly increased risk of Post-Traumatic Stress Disorder (PTSD), with around 1/3 showing PTSD symptoms. In some young people, these may persist for years following discharge. There is some evidence that these children have altered immune responses during their stay in ICU and this may be a risk factor for later PTSD symptom development, but this needs to be confirmed.

Sepsis is a potentially life-threatening condition caused by the body's immune system reacting to overwhelming to infection. It can lead to septic shock, damage to major organs, a rapid and potentially fatal blood pressure drop, and needs immediate hospital treatment.

Between 2010 and 2017, researchers from St Mary's Hospital and Imperial College in London followed up 69 young patients (all older than 3 years, average age of 4.2 years, 48% male) who had been admitted to intensive care for treatment of sepsis. When reviewed at an average follow up time of 4.6 years later, 31% of the children showed signs of PTSD. In some cases PTSD symptoms were still evident up to 7 years after discharge. The results from the study also indicated that children who had experienced rapid increases in inflammation during their stay were at higher risk. The data was controlled for potentially misleading (confounding) factors, such as length of stay in intensive care, medications, etc.

Lead researcher, Dr Georgina Corbet Burcher (Imperial College, London) said, "Young people survive critical illness at greater rates than ever before, but in some there is a high psychological price. PTSD symptoms can lead to long term effects on their mental health and wellbeing which persist in the absence of 'physical' after-effects. It appears that those who suffer from sepsis may be at particular risk for subsequent PTSD symptom development.

Recent studies indicate that PTSD affects around 7% of young people in the UK. On average, the risk is increased if a child has to spend time in an Intensive Care Unit, with around 20-30% of children overall showing symptoms at 3-12 months following discharge. This is the first study to look at the longer term endurance of symptoms after sepsis, indicating that they may persist in some children.

There's many questions still unanswered-in particular why it is that sepsis might be a risk factor for later development of PTSD symptoms, which children are at risk of longer term symptoms and the potential mechanism behind the brain's response to high levels of inflammation. . We also need to bear in mind that this is a small study in a single centre, so these findings need to be confirmed in other settings".

The World Health organisation estimates that around 3 million newborns and 1.2 million children suffer from sepsis globally each year. In the general population, they estimate that 30 million suffer each year, with around 6 million deaths (https://www.who.int/news-room/fact-sheets/detail/sepsis). In the US, around 75,000 children contract sepsis every year, while the UK's Sepsis Trust estimated that 25,000 children contract sepsis every year, although not all are admitted to ICU.

WASHINGTON -- Regular screening mammograms are unlikely to benefit women 75 and older who have chronic illnesses such as cardiovascular disease or diabetes. New data suggest they would likely die due to other health conditions before they developed breast cancer.

That is the finding of a new study based on data from more than 220,000 women that was published September 6, 2019, in JNCI.

"Our findings shed light on what age may be the best stopping point for mammography. If you have chronic illnesses after age 75, our findings do not support continuing mammograms," said senior author Dejana Braithwaite, PhD, an associate professor of epidemiology and oncology at Georgetown Lombardi Comprehensive Cancer Center.

Using data from Medicare claims and the Breast Cancer Surveillance Consortium -- which gathers the largest set of data in the world on older women who receive mammograms as the United States is one of the few countries to continue screening women into their 80s and sometimes 90s -- the researchers found that for women who lived past age 75, fewer cases of new invasive breast cancer and ductal carcinoma in situ (DCIS), a non-invasive pre-malignant growth, occurred.

"This study examined who is not likely to benefit from screening mammography after 75 years of age," said co-author, Karla Kerlikowske, MD, a professor of medicine at UCSF and physician at UCSF-affiliated San Francisco VA Medical Center. "We hope that future research efforts can build on our evidence and inform discussions about optimal screening strategies for older women."

The investigators looked at breast cancer incidence (new cases) and death from breast cancer and other causes over a period of 10 years among 222,088 women who had one or more mammograms between 66 and 94 years of age; they found that 7,583 women were diagnosed with invasive breast cancer and 1,742 with DCIS. Over the 10 years, 471 women died from breast cancer and 42,229 died from other causes, a nearly 90-fold difference.

The investigators also noted:

Women ages 75 to 84 were 123 times more likely to die of causes other than breast cancer; this estimate was even higher among women age 85 and older.

The risk of dying from breast cancer stayed steady as the risk of dying from non-breast cancer causes increased; conversely, the risk of being diagnosed with breast cancer decreased slightly after age 75 regardless of women's overall health status.

The 10-year risk of dying from breast cancer was small and did not vary by age; it stayed about the same from age 66 to 94, accounting for just 0.2% -0.3% of all deaths.

The United States Preventive Services Task Force notes that there is not enough evidence to recommend for or against screening women age 75 or older. Many breast cancer programs in Europe stop screening women between the ages of 69 and 74.

"Our research underscores the need to individualize screening decisions among older women," said first author, Joshua Demb, PhD, a postdoctoral researcher at the University of California San Diego. "To that end, we hope that our analyses contribute to developing effective tools that older women can use in consultation with their health care providers to decide a screening strategy that is best for them."

EAST LANSING, Mich. - Grasslands make up more than 40% of the world's ice-free land and have sustained humanity and thousands of other species for eons. In addition to providing food for cattle and sheep, grasslands are home to animals found nowhere else in the wild, such as the bison of North America's prairies or the zebras and giraffes of the African savannas. Grasslands also can hold up to 30% of the world's carbon, making them critical allies in the fight against climate change.

Climate change is causing grasslands to shift beneath our feet, putting these benefits at risk. Global change--which includes climate change, pollution and other widespread environmental alterations--is transforming grasslands and the plant species in them. A new study from researchers at Michigan State University shows what these changes to grassland plant communities look like, and reveal they are not always in ways scientists expect.

"Here in the Midwest, grasslands have been reduced to less than 1% of what they were at the time of European settlement and understanding what drove these changes is important to managing and restoring these systems" said Kay Gross, a plant ecologist at MSU's Kellogg Biological Station, or KBS, and one of the authors of the study. "Our research at the KBS Long Term Ecological Research site and Allegan State Game Area had provided important information on these processes, but including our data into this larger synthesis reveals insights that are not apparent in site-specific research."

The new paper, published in the Proceedings of the National Academy of Sciences, offers the most comprehensive evidence to date on how human activities are changing grassland plants.

The team looked at 105 grassland experiments around the world, including other sites from the National Science Foundation's Long Term Ecological Research program and other research done at KBS. Each experiment tested at least one global change factor--such as rising carbon dioxide, hotter temperatures, extra nutrient pollution or drought. Some experiments looked at two or more of these factors. The team was led by Kimberly Komatsu, a grassland ecologist at the Smithsonian Environmental Research Center, and included researchers from around the world--including former KBS graduate students Emily Grman and Greg Houseman. Team members contributed data from a wide range of grasslands, and developed analyses to determine whether global change was altering the composition of grasslands, both in the total number and kinds of plant species present.

They discovered grasslands can be surprisingly tough--to a point. And it can take time for these changes to be detected. In general, grasslands resisted the effects of global change for the first decade of exposure. But after 10 years of exposure to a climate change factor, species began to shift. Half of the experiments lasting 10 years or more found a change in the total number of plant species, and nearly three-fourths found changes in the types of species. By contrast, only 20% of the experiments that lasted less than 10 years picked up any species changes at all. Experiments that examined three or more aspects of global change were also more likely to detect grassland transformation.

"I think grasslands are very, very resilient," said Meghan Avolio, co-author and assistant professor of ecology at Johns Hopkins University. "But when conditions arrive that they do change, the change can be really important."

To the scientists' surprise, the identity of grassland species can change drastically, without altering the number of species. In half the plots where individual plant species changed, the total amount of species remained the same. In some plots, nearly all the species had changed.

For the team, this is a sign of hope that most grasslands could resist the experimentally induced global changes for at least 10 years. And that maybe grasslands are changing slowly enough that we can prevent catastrophic changes in the future.

However, time may not be on our side. In some experiments, the current pace of global change transformed even the "control plots" that were not exposed to experimentally higher global change pressures. Eventually, many of those plots looked the same as the experimental plots.

"Working collectively to understand how climate change is affecting grasslands is critical so that we can better restore and manage this important habitat that we and many other species depend on," Gross said. "Long-term experiments and data sets are crucial for these efforts."

One of the first studies of its kind focusing on South African children's language ability and mental health outcomes, has found clear evidence for a link between low language ability and depression in young people.

The study, published today in the journal PLOS One from researchers at the University of Bath (UK) and Stellenbosch University (South Africa) studied language ability and outcomes for 200 13-year-olds in Khayelitsha - a semi-urban, impoverished township outside Cape Town.

Their results highlight a strong relationship between lower language ability and ADHD-type attention problems and also show a more general association between high language ability and better self-esteem in young people. Adolescents with low language ability additionally had higher levels of depressive symptoms. These findings mirror previous research carried out mainly in the UK and US, yet this study is one of the first to focus on the issue in the context of a low-middle income country.

Lead author Dr Michelle St Clair from the University of Bath's Department of Psychology, said: "Children and adolescents with delayed or disordered language development are at increased risk of a number of negative outcomes, including social and emotional problems and mental health difficulties. Yet, in low- and middle- income countries, where risk factors for compromised language development are known to be prevalent, there is a lack of research on the association between child and adolescent language ability and mental health outcomes.

"I hope these findings raise awareness of how important good language skills are for so many different aspects of our lives. These findings highlight the importance of early parental engagement in supporting their child's language development." The team suggests that more needs to be done to highlight the benefits of developing early language skills for behaviour, academic and mental health outcomes to parents in communities, such as Khayelitsha.

"This is a very simple intervention. Better awareness of how easily parents can enhance their children's language abilities in early life may in time help to reduce behaviour problems and mental health difficulties," added Dr St Clair.

Dr Sarah Skeen of the Institute for Life Course Health Research, Department of Global Health, Stellenbosch University explained: "Language development is central to many aspects of children's lives. Language skills are essential for successful communication of emotions, needs and thoughts, and to maintain relationships with others. Language also underpins the development of a range of psychological processes, such as emotional self-regulation which in turn predicts a range of positive outcomes, including better interpersonal relationships and academic achievement.

"When children or adolescents have delayed or disordered language development, there is a long-term negative impact on their well-being. They are more likely to perform poorly at school and be unemployed as adults. They are less likely to have good social skills and tend to exhibit withdrawn behaviour. Poor language skills are linked with problems in peer relationships and difficulties with friendship development

"We need to factor this new knowledge into our education programmes and do more to ensure locally accessible support for children with reduced language ability is available, given the longer-term consequences of poorer mental health."