Culture

LA JOLLA--(March 22, 2019) Similar to the dozens of Sherpas that guide hikers up treacherous Himalayan mountains to reach a summit, the nervous system relies on elaborate timing and location of guidance cues for neuronal axons--threadlike projections--to successfully reach their destinations in the body. Now, Salk Institute researchers discover how neurons navigate a tricky cellular environment by listening for directions, while simultaneously filtering out inappropriate instructions to avoid getting lost. The findings appeared in Neuron on March 19, 2019.

"There are 100 trillion connections in the nervous system governed by 20,000 genes, of which roughly 10 gene families are known to be involved in controlling axon guidance. We wanted to understand the clever genetic systems nature has employed to wire the most complicated biological machine in the universe," says Salk Professor Samuel Pfaff, senior author and a Howard Hughes Medical Institute investigator. "Thus, we set out to examine how motor neurons find their connections with muscles in the body, which is critical for our brain to relay information to our muscles to allow for movement."

The brain controls hundreds of different muscles to allow for precise movement. During development, motor neurons in the spinal cord extend their axons outside of the central nervous system to connect with muscle cells in the body. Every motor neuron relies on a set of genes to ensure the axon grows correctly to the muscle.

"In the broadest sense, we hoped that by identifying genes involved in abnormal motor neuron development we could better understand the intricacies of cell signaling in other contexts such as cancer," says first author Dario Bonanomi, a former postdoctoral fellow in the Pfaff lab, now a group leader at the San Raffaele Scientific Institute. "This work not only shows us how the nervous system develops, but also how cells, more generally, communicate, move and create structures in the body."

To find genes important for motor-neuron axon guidance, the team carried out a genetic screen and observed where the motor neurons grew their axons using green fluorescent proteins in a mouse model they engineered. The team then traced the axons to see when correct and incorrect growth decisions were made. Through this axon tracing, the scientists identified a gene mutation that caused motor axon misrouting. In this case, the motor neuron axons took detours and never connected properly to the muscles.

Upon closer investigation, the scientists found that these motor neurons climbed up the edge of the spinal cord rather than properly exiting to meet their muscle targets. The team pinpointed the gene causing this detrimental mutation as p190, which was previously known to play a role in cancer suppression, but had not been implicated in establishing neuronal connections during development.

The researchers set up a series of experiments to examine how p190 affects axons leaving the spinal cord. They found that, although axons are normally attracted to a protein in the spinal cord called netrin, during a short time window p190 acts as a blinder, so the axons disregard netrin and are led outside of the spinal cord. After the axons safely leave the central nervous system, this blinder is removed. Without p190, the axons are attracted to netrin and do not properly leave the spinal cord, so never connect with muscles.

Pfaff, holder of the Benjamin H. Lewis Chair, adds, "These results provide mechanistic insight into the unimagined complexity that cells use to communicate with one another."

The next step is to examine the control mechanism of p190, and what factors impact the timing of its activity, say the researchers.

CHAMPAIGN, Ill. -- A new study in mice suggests that consuming the chemical compounds found in thermally abused cooking oil may trigger genetic changes that promote the progression of late-stage breast cancer.

Thermally abused frying oil - cooking oil that has been repeatedly reheated to high temperatures - may act as a toxicological trigger that promotes tumor cell proliferation, metastases and changes in lipid metabolism, scientists at the University of Illinois found. They reported their findings in the journal Cancer Prevention Research.

After consuming a low-fat diet for one week, one group of the mice was fed unheated fresh soybean oil, while another group consumed thermally abused oil for the next 16 weeks. Soybean oil was used in the study because of its common use by the food service industry in deep frying.

The U. of I. scientists simulated late-stage breast cancer by injecting 4T1 breast cancer cells into a tibia of each mouse. The 4T1 cells are an aggressive form of the disease that can spontaneously metastasize to multiple distant sites in the body, including the lungs, liver and lymph nodes, according to the study.

Twenty days after inoculation with the tumor cells, the primary tumors in the tibias of the mice that consumed the thermally abused oil had more than four times as much metastatic growth as the mice that consumed the fresh soybean oil. And when the researchers examined the animals' lungs, they found more metastases among those that consumed the thermally abused oil.

"There were twice as many tumors in the lung, and they were more aggressive and invasive," said William G. Helferich, a professor of food science and human nutrition, who led the research.

Food chemistry professor Nicki J. Engeseth, the acting head of the department, co-wrote the paper. Graduate student Ashley W. Oyirifi and U. of I. alumnus Anthony Cam were the lead authors.

"I just assumed these nodules in the lungs were little clones - but they weren't. They'd undergone transformation to become more aggressive. The metastases in the fresh-oil group were there, but they weren't as invasive or aggressive, and the proliferation wasn't as extensive," Helferich said.

In examining both groups of mice, the scientists found that the metastatic lung tumors in those that consumed thermally abused frying oil expressed significantly more of a key protein, Ki-67, which is associated strictly with cell proliferation.

Gene expression in these animals' livers was altered as well. When the researchers conducted RNA sequencing analysis, they found 455 genes in which expression was at least two times greater - or, conversely, two times lower - than in mice that consumed the fresh oil.

The altered gene pathways were associated with oxidative stress and the metabolism of foreign substances, Oyirifi said.

When oil is repeatedly reused, triglycerides are broken apart, oxidizing free fatty acids and releasing acrolein, a toxic chemical that has carcinogenic properties.

Scientists have long known that thermally abused oil contains acrolein, and studies have linked the lipid peroxides in it with a variety of health problems, including atherosclerosis and heart disease.

As the oil degrades, polymer molecules also accumulate, raising nutritional and toxicological concerns, Engeseth said.

Countries in Europe and elsewhere regulate the amount of polar materials in frying oil, which are chemically altered triglycerides and fatty acids that are used as chemical markers of oils' decomposition. Typically, these standards permit restaurants to use oil containing up to 24-27 percent polar material.

By contrast, the thermally abused oil used in the current study contained about 15 percent polar material, while fresh oil contains 2-4 percent or less, Helferich said.

"Because there are no regulations in the U.S., it's really difficult for us to evaluate what's out there," Engeseth said. "But the important thing is, the food that's fried in these oils sucks up quite a bit of oil. Even though we're not consuming the oil directly, we're consuming oil that's brought into the food during the frying process."

Breast cancer survivors' biggest fear is recurrence, and the majority of these survivors have dormant tumor cells circulating in their blood, Helferich said.

"What wakes those cells up is anybody's guess, but I'm convinced that diet activates them and creates an environment in different tissues that's more fertile for them to grow," he said.

"Many cancer biologists are trying to understand what's happening at metastatic sites to prime them for tumor growth," Oyirifi said. "We're trying to add to this conversation and help people understand that it might not be just some inherent biological mechanism but a lifestyle factor. If diet provides an opportunity to reduce breast cancer survivors' risk, it offers them agency over their own health."

An international team of researchers has built a new sensor network that can monitor two crucial activities, namely biodiversity, or the variety of life, in a particular habitat or ecosystem, and identification of possible illegal activities such as logging or poaching in protected areas. This wireless recording network is capable of recording an ecosystem's sounds with the same quality as devices that have been used to date, but it is significantly more energy-efficient and cost-effective. This network is composed of edge computing recorders, or devices that sample and process data at the recording location, with power savings of up to 280%. It promises to significantly streamline the monitoring process of biodiversity and addresses the urgent global need for new assessment methods necessary to maintain the world's biodiversity balance.

"In this paper, we propose a low cost solution for an audio recorder with onboard audio processing, as part of a wireless sensor network. The developed audio recorder can be used in several different use cases for which no cost effective, scalable biodiversity monitoring solution currently exists, such as to monitor pollinating insects, or to assess the condition of tropical forests by observing vocal animals," says Victor C. M. Leung, Ph.D., corresponding author and Professor at the Department of Electrical and Computer Engineering, University of British Columbia. "Our tests demonstrate that a collection of acoustic sounds recorded in 1 minute can arrive at the server only 30 seconds after the recording has finished, affording near real-time performance which could be of great value in tracking endangered species, or identifying illegal activity such as logging or poaching in protected areas," Professor Leung adds.

The study was published in IEEE/CAA Journal of Automatica Sinica in January 2019.

Critical to understanding an ecosystem's structure and function and predicting future changes is knowing what species inhabit an ecosystem, and how many of each kind there are. A balanced ecosystem has healthy biodiversity levels and is therefore strong enough to withstand stresses such as climate change and predators. Ensuring the ecosystem's equilibrium is therefore vital to its survival. One way to track biodiversity and ensure its balance is by monitoring the sounds that animals emit as they communicate within their environment. This is also called passive acoustic monitoring, and it has emerged as a powerful method for preserving an ecosystem's survival. However, the amount of data that is collected requires automated methods that are capable of sampling the sounds across time and space and relaying the data to an accessible storage location. As this requires a lot of power, it remains a technical challenge. As such, there is currently an urgent need for new assessment methods that are both energy efficient as well as cost effective.

"Traditional biodiversity survey methods involve the identification and logging of species, by experts at the recording location, based on what they see and hear at locations of interest. This implies several disadvantages like the vast amount of time and money to get constant results over a long period of time and a wide geographical distance, lack of reliability due to human error. Based on the growing recognition of the ecological significance of the acoustic environment, passive acoustic monitoring is emerging as a promising solution to the urgent, global need for new biodiversity assessment methods," Professor Leung adds.

In the future, the researchers aim to optimize the system's versatility as well as efficiency. They also plan to increase battery life by implementing a system sleep mode as well as integrating solar as a second power source for a long-lasting operation. Furthermore, their aims are to improve the audio quality, further reduce costs, increase the number of nodes and install antennas between them so that they can cover a larger network. "A detailed analysis to identify the balance between range and power consumption might be an interesting topic for future enhancements of the wireless recorders," Professor Leung comments.

Adopting stricter state gun laws is linked to a safer school experience for students, finds research published in the Journal of Epidemiology & Community Health.

Strengthening gun laws at state level was associated with teens being less likely to report being threatened or injured with a weapon at school, miss at least one day of school due to feeling unsafe, or to carry a weapon at any location.

Among 1.3 million discipline incidents reported in US public schools during the 2013-2014 school year, 1 in 20 were related to weapon possession, write the authors. And a particularly dangerous part of school crime is gun violence, they add.

Previous studies have explored the effect of youth-orientated gun laws on non-fatal injuries, suicide rates, deaths from unintentional shootings and firearm homicides among teens.

But no conclusive evidence was found and little is known on the link between state-level gun laws and school safety.

So to shed some light on this, researchers looked at the associations of stricter gun laws with students' weapon carrying and their perception of school safety.

They used data from the Youth Risk Behaviors Surveys (YRBS) conducted between 1999-2015, which included information on 926,639 teens across 45 states, who were all in 9th to 12th grade.

Students reported on weapon carrying at school, the number of times they experienced weapon threats or injuries at school, the number of school days missed due to feeling unsafe, and weapon carrying at any location.

For each state and year, 133 gun laws were combined into an index of gun control strength, with higher scores corresponding to a stricter gun law environment.

The researchers controlled for individual and state characteristics, as well as year and state fixed events. This included age, sex and race, as well as sociodemographic characteristics such as the unemployment rate, crime rates and state anti-bullying policy.

During the study period, many states strengthened their prohibitions of high-risk guns, and introduced laws preventing individuals with a history of domestic violence from owning or buying guns.

But 20 states allowed the use of a gun for self-defense without duty to retreat.

Stronger gun control (i.e. a 15-point increase in the score) was associated with a 0.8-percentage point decrease in the probability of being threatened or injured with a weapon at school (overall prevalence 7%), a 1.9-percentage point decrease in the probability of carrying a weapon at any location (overall prevalence 16%), and a 1.1-percentage point decrease in the probability of missing school due to feeling unsafe (overall prevalence 6.1%).

Overall, weapon carrying was more common among white students, compared with black and Hispanic students, while perceived threats were less common among white students compared with all other racial groups.

And stricter gun laws were more strongly associated with lower rates of weapon carrying among male students compared with female students.

Black students were more likely to carry weapons at school specifically in response to a strengthening in gun laws, but this may indicate a replacement for a firearm, say the authors.

This is an observational study, and may not be representative of all states. What's more, the information from students was volunteered, and the authors write that teens "might misreport certain behaviors due to social desirability."

But the research highlights that over the last two decades, 17 states experienced a weakening of gun control laws, which may facilitate teens' access to guns and increase levels of violence in schools, write the authors.

"With the prevalence of weapon threats and fights at school decreasing only slightly, and the percentage of students who miss school on the rise, school safety represents a policy priority across the fields of health and education," they conclude.

FINDINGS

A study has found that out-of-pocket health care spending and medical debt are substantially higher when adults have a history of adverse childhood experiences. The study showed that household medical costs were 30 percent higher, and the likelihood of medical debt was doubled, when an adult had lived through three or more adverse experiences during childhood.

BACKGROUND

Adverse childhood experiences include abuse, neglect and household dysfunction that occur before 18 years of age. The types of hardships can include divorce or separation from parents, violence in the home and parental mental illness. Such experiences in childhood are linked to higher rates of mental and physical illness in adulthood. Previous studies have shown that physical and sexual abuse were associated with higher out-of-pocket medical costs. This is the first study to look at the full range of adverse childhood experiences and their effect on later out-of-pocket health care costs, according to the researchers. For purposes of the study, out-of-pocket costs included spending on such items as coinsurance, deductibles and anything not covered by medical insurance.

METHOD

Researchers collected data on household out-of-pocket medical costs and information about adverse childhood experiences from the University of Michigan's Panel Study of Income Dynamics, a long-running U.S. household survey. Associations between adverse experiences and out-of-pocket household medical costs were then linked using statistical analyses, controlling for other factors such as income and demographic background.

IMPACT

About two out of three adults will experience one or more adverse experiences during childhood. Interventions to reduce childhood adversity could lead to a reduction of the costs associated with it. The next stage of research will examine the total cost to the health care system.

PITTSBURGH, March 21, 2019 - Social media has given those espousing anti-vaccination sentiments an effective medium to spread their message. However, an analysis of a viral Facebook campaign against a Pittsburgh pediatric practice reveals that the movement isn't "all about autism." Instead, the research from the University of Pittsburgh Center for Research on Media, Technology, and Health finds that anti-vaccination arguments center on four distinct themes that can appeal to diverse audiences.

The research, published today in the journal Vaccine, suggests a framework that pediatricians can use to open a conversation with parents who are hesitant to immunize their children, while also "inoculating" those parents with skills to resist anti-vaccination messages on social media.

"If we dismiss anybody who has an opposing view, we're giving up an opportunity to understand them and come to a common ground," said senior author Brian Primack, M.D., Ph.D., director of Pitt's Center for Research on Media, Technology, and Health, and dean of the Pitt Honors College. "That's what our research is about. We want to understand vaccine-hesitant parents in order to give clinicians the opportunity to optimally and respectfully communicate with them about the importance of immunization."

Vaccines are hailed as one of the greatest public health achievements of modern medicine and have prevented more than 100 million cases of serious childhood contagious diseases. However, in the U.S., only 70 percent of children ages 19 to 35 months receive all recommended immunizations, and, so far this year, hundreds of children in a dozen states have contracted measles, a disease that was declared eliminated in the U.S. nearly two decades ago due to high vaccination rates. In Europe, tens of thousands of children have been diagnosed with the vaccine-preventable disease, and dozens have died in the past year.

In 2017, Kids Plus Pediatrics, a Pittsburgh-based pediatric practice, posted a video on its Facebook page featuring its practitioners encouraging HPV vaccination to prevent cancer. Nearly a month after the video posted, it caught the attention of multiple anti-vaccination groups and, in an eight-day period, garnered thousands of anti-vaccination comments.

Elizabeth Felter, Dr.P.H., assistant professor of community and behavioral health sciences at Pitt's Graduate School of Public Health, connected Kids Plus Pediatrics with graduate student Beth Hoffman, B.Sc., and scientists at the Center for Research on Media, Technology, and Health. Hoffman led the team in partnering with the pediatrics practice to perform a systematic analysis to better understand the people behind the comments and how they cluster in the digitally-connected world of social media.

Hoffman's team analyzed the profiles of a randomly selected sample of 197 commenters and determined that, although Kids Plus Pediatrics is an independent practice caring for patients in the Pittsburgh region, the commenters in the sample were spread across 36 states and eight countries.

The team also found that the majority of commenters were mothers. In those for which it could be determined, the top two political affiliations of the commenters were divergent, with 56 percent expressing support for Donald Trump, and 11 percent expressing support for Bernie Sanders.

By delving into the messages that each commenter had publicly posted in the previous two years, the team found that they clustered into four distinct subgroups:

"trust," which emphasized suspicion of the scientific community and concerns about personal liberty;

"alternatives," which focused on chemicals in vaccines and the use of homeopathic remedies instead of vaccination;

"safety," which focused on perceived risks and concerns about vaccination being immoral; and

"conspiracy," which suggested that the government and other entities hide information that this subgroup believes to be facts, including that the polio virus does not exist.

"The presence of these distinct subgroups cautions against a blanket approach to public health messages that encourage vaccination," Hoffman said. "For example, telling someone in the 'trust' subgroup that vaccines don't cause autism may alienate them because that isn't their concern to begin with. Instead, it may be more effective to find common ground and deliver tailored messages related to trust and the perception mandatory vaccination threatens their ability to make decisions for their child."

Todd Wolynn, M.D., chief executive officer of Kids Plus Pediatrics and a co-author of the research paper, said that although the negative comments in reaction to the practice's video were disheartening, he's glad it turned into a learning experience that may benefit other clinicians.

"We're focused on keeping kids healthy and preventing disease whenever possible. In this age of social media disinformation, evidence-based recommendations from a trusted health care provider are more important than ever," he said. "We're thrilled to play such a key role in research that empowers pediatricians worldwide to meet parents where they are, appreciate their concerns, and communicate the incredible power and value of vaccination."

Seychelles warblers live and breed in family groups on the tiny island of Cousin. In each group, a dominant female and male reproduce. When helpers assist the with incubation and feeding of chicks, the dominant female breeders age more slowly and live longer, a study by biologists from the University of Groningen and colleagues from the Universities of East Anglia, Leeds, Sheffield, and Wageningen shows. The results, which are published in the journal Nature Communications on 21 March, indicate how cooperative breeding - which also occurs in other species, including humans - can increase life span.

The Seychelles warbler lives on Cousin Island in the Indian Ocean, measuring just 500 by 700 meters. Some fifty years ago, only a handful of birds survived. However, conservation efforts have led to a spectacular increase in the population, and new populations have been established by translocating birds to four other islands nearby. 'There are about one hundred breeding territories on Cousin, each with a dominant male and female and a number of subordinates, which are often the offspring of the dominant pair', explains University of Groningen biologist Martijn Hammers, lead author of the study.

Survival

Inside the groups, some - often female - subordinates may help the dominant female with the demanding tasks of incubation and raising chicks. 'Not all dominant females get help', explains Hammers. That is why the Seychelles warbler is well suited to investigate the effect of having helpers on aging in dominant breeders.

Ever since the 1990s, the Seychelles warblers on Cousin Island have been fitted with colored rings, so scientists are able to follow them over time. Hammers and his colleagues used data on survival and breeding success collected over fifteen years. In addition, they measured the shortening of telomeres, which can be used as a marker of condition and aging. Telomeres are repetitive DNA sequences at the end of chromosomes, which shorten in response to stress. Telomere shortening is a sign of biological aging, and in the Seychelles warbler, telomere length predicts survival.

Positive feedback

'Our analysis showed that in dominant females who get help from subordinates, the shortening of the telomeres is slower than in birds who do not get help. Also, for the older dominant females, this help results in much better survival.' Dominant males do not appear to benefit as much from having helpers, probably because they invest much less energy in breeding.

Hammers and his colleagues also discovered a positive feedback system: 'Birds who get more help age more slowly and live longer. But older birds also tend to be more social and recruit more helpers.' The helping subordinates are often daughters of the dominant female. In helping their mother, they raise siblings with whom they share genes.

Humans

The study shows how cooperative breeding could increase an individual's lifespan. 'Of course, the effects we have measured were within one generation, not between generations.' Nevertheless, it supports a long-held hypothesis that cooperative breeding - which also is the norm in humans - can reduce the cost of raising young and may slow down the negative effects of aging. 'It provides an explanation for why more social species tend to have longer lifespans', Hammers concludes.

New research suggests that targeted use of behavioural 'nudges' can encourage people to conserve water.

Researchers at the University of East Anglia (UEA) found that rather than giving people general information about the importance of saving water, emphasising the water conserving actions of others in the same social group - for example university students or local residents - encourages similar behaviour changes and reduces water demand.

Water scarcity is a growing global issue and within the UK water shortages are recognised as one of the greatest climate change-related threats. This week the UK's Environment Agency warned that England will not have enough water to meet demand within 25 years.

The new study explored the use of social norms in campaigns to motivate people to save water. Previous research has found that these behavioural-based approaches, or 'nudges' can impact on other pro-environmental behaviours, for example around saving energy and encouraging recycling.

The findings, published in the Journal of Environmental Psychology, demonstrate that existing interventions can be enhanced by focusing on a specific, psychologically meaningful social identity - a technique known as an 'ingroup norms appeal'.

Social identities describe our sense of attachment to a place or a group of people (our 'ingroups'). These identities influence our attitudes, emotions, and behaviour, sometimes even when we are not aware of their effects. Therefore, if we provide information about the behaviour of others who share an important social identity with us, our attitudes and behaviours will change accordingly.

Lead researcher Ellin Lede carried out the work as part of her PhD with the School of Environmental Sciences.

"Ensuring a sustainable water supply requires a multifaceted approach, and this will become increasingly important as demand for water continues to rise and climate change alters water availability," said Dr Lede.

"Our findings have implications for the design of environmental campaigns. Traditionally, water conservation communication campaigns deliver general water saving information. However, campaigns informed by behavioural science can increase their effectiveness and should form an integral part of demand reduction strategies.

"Activating a sense of regional identity, such as a local city, neighbourhood or community, and communicating credible information about the behaviour and practices of other group members should strengthen perceived norms regarding water conservation, resulting in increased water-savings efforts among community members."

The research involved four studies carried out in Norfolk, in the East of England, a region prone to water shortages. The first two, involving UEA students and Norwich residents, provided initial evidence that using an ingroup norms appeal message can increase individuals' intentions to engage in water conservation behaviours.

Study three was conducted in a UEA halls of residence. Stickers with water conservation messages were placed in shower rooms, in an attempt to get students to reduce their shower time by one or two minutes - a saving of seven to 14 litres of water per shower.

The social norms message aimed to encourage this behaviour by suggesting it represented a common water saving strategy used by other people generally. In the ingroup norms message, saving water was presented as something that was normal among other students at the university. An illustration of a university mascot also accompanied the text to reinforce social identity. No sticker was placed in rooms assigned to a control group.

After a two-week trial, the ingroup norms message was found to be more effective than the social norms one, with students reducing their time in the shower by more than a minute.

The fourth study was conducted with Anglian Water through the Anglian Centre for Water Studies at UEA, a collaboration between the university and water company. It aimed to increase sign-ups to a free residential retrofitting service, whereby a plumber fits water efficiency devices in customers' homes.

An ingroup norms appeal message was added to the beginning of a letter sent to 1148 households, stating that people in Norfolk care about the environment and saving water, and other residents had already signed up to the programme. It also included an image of a windmill, a historic feature of the area. After six weeks, sign-up rates were significantly higher among households who received the amended letter, compared to the 1158 who received a standard letter without the additional messaging.

Vittoria Danino, Anglian Water's head of the Centre for Water Studies at UEA, said: "The significant increase in customers signing up to receive our water efficiency devices shows how successful the study by UEA was. We are continually encouraging our customers to become more water efficient and are always looking into a variety of ways to communicate this.

"Our customers in the East of England are already some of the most water savvy in the country. On average each of us use 133 litres each per day compared to the national average of about 140-145 litres. That equates to the difference of about 4million toilet flushes every day. There is always more we can all do to use water wisely, all year round."

Co-author Dr Rose Meleady, of UEA's School of Psychology, said: "Across four studies conducted in a water scarce region in England we demonstrated the ways in which the social identity approach can maximize the power of behaviour-based interventions and encourage a shift in intentions and behaviour to promote household water conservation.

"As shown in the study with Anglian Water, just integrating the ingroup norms appeal text in the letter increased the rate of sign-up to a water conserving initiative. Something as simple as changing the form of messaging, and in a way that doesn't cost any more, can make messaging more effective and lead to behaviour change."

A new study published in Infant and Child Development indicates that complications during birth may increase the risk that children will develop social anxiety by their pre-teen years.

For the study, 149 children aged nine to 12 years were screened for behavioral inhibition--a tendency to exhibit a fearful disposition and withdrawal in unfamiliar contexts and situations--and assessed for social anxiety symptoms using parent- and child-reports. Investigators found that perinatal complications were associated with higher levels of behavioral inhibition and social anxiety symptoms.

Additionally, analyses suggested that behavioral inhibition acted as a pathway between birth complications and social anxiety symptoms.

"This study sets the stage for future longitudinal work examining whether childhood temperament is a developmental path by which birth complications lead to social anxiety symptoms," said lead author Dr. Santiago Morales, of the University of Maryland.

MINNEAPOLIS - Some studies have suggested that people who are younger when they enter puberty are more likely to later develop multiple sclerosis (MS). But a new study attributes that link to body mass index (BMI). The study is published in the March 20, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Previous studies have shown that children with higher body weight tend to enter puberty earlier than children with normal body weight, and increased BMI is also linked to a greater risk of MS," said study author J. Brent Richards, MD, MSc, of McGill University in Montreal, Canada. "It appears that earlier age at puberty is associated with an increased risk of MS, but this association is influenced by BMI. Our findings do not support a substantial role for the effect of the timing of puberty on the risk of MS independent of BMI."

For the study, researchers looked at a genome-wide association study of 329,245 women and 372 genetic variants that are strongly associated with the age when girls have their first menstrual cycle. Previous studies have shown that the genes related to the timing of puberty are well-correlated in girls and boys.

Then researchers looked at another genetic study that included 14,802 people with MS and compared them to 26,703 people who did not have the disease to examine whether the age of puberty was associated with risk of MS.

Richards said they did find that people with an earlier age of puberty were more likely to develop MS, but once they factored in BMI, the results were no longer significant.

"More research is needed to determine whether decreasing rates of obesity could help to reduce the prevalence of MS," he said. "If so, this could be another important reason for public health initiatives to focus on lowering obesity rates."

A limitation of the study was that researchers were not able to analyze results for men and women separately.

The prognosis for older patients with acute myeloid leukemia (AML) is poor: very few achieve remission and for those that don't the option is largely palliative.

Every year almost 1000 Australians die of the disease and clinical trials into new therapies for older patients have largely failed.

A new Australian drug trial has achieved a remarkable result, clearing the bone marrow of leukaemia in almost 60% of patients.

The trial was considered so effective that the US Food and Drug Administration approved its use last November for the treatment of AML.

Kaye Oliver, 74, was the first patient in the world enrolled on this trial at the Alfred Hospital in 2015 - the results of which are published today in the Journal of Clinical Oncology.

Given little hope of survival beyond a few months at diagnosis, Kaye remains well and without evidence of the cancer four years later.

Associate Professor Andrew Wei, from the Alfred Hospital and Monash University Clinical School, commenced research in this area almost two decades ago at the Walter and Eliza Hall Institute of Medical Research. He is now the lead clinician/researcher on the international trial of the cancer drug, currently combined with cytarabine to treat older adults with AML.

Taken separately these drugs achieve little, according to Associate Professor Wei. Venetoclax alone led to a 19% response rate in a US trial and cytarabine had a similar result, he said.

"But combining LDAC with venetoclax in older patients led to a 54% response rate, with half the study population surviving longer than 10 months," he added.

The trial tested 82 patients with a median age of 74 years and was conducted in Australia, Europe and the USA.

The current research is supported by another trial in older AML patients, which combined venetoclax with another drug, azacytidine and led to a 71% remission rate with an average life expectancy of almost 17 months.

Based on the early results of these two studies, the Food and Drug Administration in the US approved the use of these combination drug therapies in older people with AML on November 21 last year.

The drug combination acts on a protein prevalent in leukaemia cells called BCL-2 which controls the survival of the cells. Venetoclax acts by effectively switching off the protein and activating a self-destruct program in the cell.

Associate Professor Wei said that a randomised trial of the therapy, where patients on the therapy are compared to those who are not, has recently been completed and the results are awaited to support a submission to the Therapeutic Goods Association in Australia.

The findings are important not just because of the success of the treatment in a disease that, previously, was fatal, but because with an aging population AML is likely to become more prevalent in the future.

"AML arises due to mutations accumulating in the bone marrow over time. It also arises in patients who have previously had chemotherapy. With an expected doubling in the number of over people over 65 in the next 30 years, the need to find more effective treatments for this disease is paramount," Associate Professor Wei said.

"AML research used to be likened to a 'clinical trial graveyard' because trials of new drugs into AML were rarely successful," Associate Professor Wei said.

"It was widely seen as an untreatable and inevitably fatal condition for older patients by most doctors. These two new trials have given real hope to patients who previously had little."

The center of our galaxy is a frenzy of activity. A behemoth black hole -- 4 million times as massive as the sun -- blasts out energy as it chows down on interstellar detritus while neighboring stars burst to life and subsequently explode.

Now, an international team of astronomers has discovered two exhaust channels -- dubbed "galactic center chimneys" -- that appear to funnel matter and energy away from the cosmic fireworks in the Milky Way's center, about 28,000 light-years from Earth.

Mark Morris, a UCLA professor of astronomy and astrophysics, contributed to the research, which will be published March 21 in the journal Nature.

"We hypothesize that these chimneys are exhaust vents for all the energy released at the center of the galaxy," Morris said.

All galaxies are giant star-forming factories, but their productivity can vary widely -- from one galaxy to the next and even over the course of each galaxy's lifetime. One mechanism for throttling the rate of star production is the fountain of matter and energy whipped up by the heavyweight black hole that lurks at a galaxy's center.

"Star formation determines the character of a galaxy," Morris said. "And that's something we care about because stars produce the heavy elements out of which planets -- and life -- are made."

To better understand what becomes of that outflow of energy, Morris and his colleagues pointed the European Space Agency's XMM-Newton satellite, which detects cosmic X-rays, toward the center of the Milky Way. Because X-rays are emitted by extremely hot gas, they are especially useful for mapping energetic environments in space.

In images they collected from 2016 to 2018 and in 2012, the researchers found two plumes of X-rays -- the galactic center chimneys -- stretching in opposite directions from the central hub of the galaxy. Each plume originates within about 160 light-years of the supermassive black hole and spans over 500 light-years.

The chimneys hook up to two gargantuan structures known as the Fermi bubbles, cavities carved out of the gas that envelops the galaxy. The bubbles, which are filled with high-speed particles, straddle the center of the galaxy and stretch for 25,000 light-years in either direction. Some astronomers suspect that the Fermi bubbles are relics of massive eruptions from the supermassive black hole, while others think the bubbles are blown out by hordes of newly born stars. Either way, the chimneys could be the conduits through which high-speed particles get there.

Understanding how energy makes its way from a galaxy's center to its outer limits could provide insights into why some galaxies are bursting with star formation whereas others are dormant.

"In extreme cases, that fountain of energy can either trigger or shut off star formation in the galaxy," Morris said.

Our galaxy isn't quite that extreme -- other galaxies have fountains powered by central black holes weighing a thousand times more than ours -- but the Milky Way's center provides an up-close look at what might be happening in galaxies that are more energetic.

"We know that outflows and winds of material and energy emanating from a galaxy are crucial in sculpting and altering that galaxy's shape over time -- they're key players in how galaxies, and other structures, form and evolve throughout the cosmos," said lead author Gabriele Ponti of the Max Planck Institute for Extraterrestrial Physics in Garching, Germany. "Luckily, our galaxy gives us a nearby laboratory to explore this in detail, and probe how material flows out into the space around us."

Morris said the centers of the nearest galaxies are hundreds to thousands of times farther away than our own. "The amount of energy coming out of the center of our galaxy is limited, but it's a really good example of a galactic center that we can observe and try to understand," he said.

Irvine, Calif., March 20, 2019 - Here's something to chew on: One in four people are impacted by defects of the temporomandibular - or jaw - joint. Despite the pervasiveness of this affliction, treatments are lacking, and many sufferers resort to palliative measures to cope with the pain and debilitation it causes.

"The TMJ is central to chewing, talking and so many other daily activities, so when this crucial joint is impaired, there are significant negative effects on quality of life," said Kyriacos A. Athanasiou, Distinguished Professor of biomedical engineering at the University of California, Irvine. "The problem may start with slight pain and clicking and get progressively worse to the point where it's not just impacting the jaw but the entire body."

Athanasiou is senior author on a paper published recently in the Cell Press journal Trends in Molecular Medicine that examines the causes of temporomandibular disorders, past failures in treating them, and new approaches based on tissue-engineering innovations developed in his laboratory. Co-authors are Ryan Donahue, UCI graduate student researcher in biomedical engineering, and Jerry Hu, UCI principal development engineer in biomedical engineering.

Temporomandibular disorders can be the result of sudden injuries or wear and tear over time. The cartilage disc between the mandible and the temporal bone is subject to thinning or perforation. The condition usually affects patients between the ages of 20 and 50. Most strikingly, premenopausal women are eight times more likely to experience jaw joint problems than men - which Athanasiou calls the TMJ gender paradox.

Typical treatments include physical therapy, splints and adjustments, corticosteroid injections and pain medications. Only about 5 percent of sufferers are candidates for surgical interventions. The TMJ is a joint like many others in the body, and surgeries to repair knees, elbows, hips and shoulders are commonplace, so why are operations on the jaw so rare?

"It has to do with the proximity of the TMJ to the brain," Athanasiou said. "Back in the 1980s, many patients - primarily women - came forward with issues they had with the TMJ. The solution at the time was to insert a spacer between the two bones articulated in the jaw."

The spacer was made of Teflon, a material approved by the U.S. Food and Drug Administration.

"It turns out that Teflon was an absolute catastrophe for all of those women," Athanasiou said. "Because of the large mechanical forces generated in the jaw, the Teflon broke up into pieces, and because of the proximity of the TMJ to the brain, those pieces somehow found their way into the brain."

This fiasco set back therapies for temporomandibular disorders for decades, but now Athanasiou and his colleagues in UCI's Department of Biomedical Engineering are working on new approaches that eschew synthetic materials entirely. They're developing biological TMJ discs in the laboratory that will be suitable for implantation in humans.

"The end product that we aspire to use for treating afflictions of TMJ discs is a tissue-engineered product that's fully alive, biological and mechanically comparable to the real thing," Donahue said. "So even if it breaks down, it will be like any other biological component, without having pieces of foreign material entering the brain."

In work detailed in a study published in Science Translational Medicine in June 2018, Athanasiou's team successfully took cells from the rib cartilage of a Yucatan miniature pig, grew them in their laboratory and implanted the tissue-engineered construct into a separate animal.

Whereas some researchers may place bioengineered cells in some other part of an animal's body - on the back of a mouse, for example - Athanasiou said a key aspect of his group's work is to put the new disc in the exact place as the old one so it will be subject to all the normal stresses of the joint.

"In eight weeks, we saw complete functionality of the TMJ disc, whereas the ones we left untreated deteriorated completely, developing full osteoarthritis in the joint," Hu said. "So we were able to show that by using our tissue-engineering approach in a large-animal model, we could achieve exceptional healing."

Athanasiou said his team's goal now is to conduct trials in more large-animal models to determine if their solution will ultimately work in humans. A major hurdle will be gaining regulatory approval from the FDA, but Athanasiou recently received some encouraging signals from the agency.

"The FDA has asked if we could help them figure out how to go about developing processes for bringing TMJ products to the market," he said. "We would be delighted to help create that pathway."

March 20, 2019 - Salads were recently in the news--and off America's dinner tables--when romaine lettuce was recalled nationwide. Outbreaks of intestinal illness were traced to romaine lettuce contaminated with Escherichia coli (E. coli) bacteria.

These bacteria occur naturally in the intestines of warm-blooded animals. Because crops are grown in the natural environment, E.coli may get into the fields, contaminating produce. The results are potentially deadly for people who eat that produce.

Cooking kills E. coli, removing the danger. But lettuce and other leafy greens are generally eaten raw, so they present special safety issues. To protect the public, strict rules require producers to test their irrigation water to see if it is contaminated with E. coli or other microorganisms that can cause illness. The produce industry implements these food safety measures to keep people safe and grow a reliable, nutritious product for consumers.

Are the irrigation water tests consistent enough to prevent future widespread recalls? Researchers are comparing tests to see.

In 2011, the U.S. Food and Drug Administration proposed ten EPA-approved tests to detect generic E.coli in irrigation water. One of these methods, mTEC®, is an excellent test for generic E. coli but has not been commonly used in the water testing industry. A commercially available test kit, Colilert®, is much simpler to use. It is also offered by hundreds of water quality testing laboratories nationwide, compared to only a handful of laboratories that offer the mTEC® assay.

Research scientist Jean E. McLain and colleagues at the University of Arizona felt it was important to discover how good laboratories are at using these tests, and whether test results are consistent from lab to lab. Each month, a technician collected a water sample from irrigation canals at the university's research farms near Yuma and Maricopa, AZ. Each water sample was divided into thirds: one-third was delivered to McLain's lab and the remainder was delivered to two collaborating labs for testing.

"This study used a side-by-side comparison of both methods, across three laboratories, to test how well the method results were reproduced across labs," says McLain. "Both methods have shown excellent results as long as water samples are clean. But because these methods were developed for drinking water, they may not work as well with environmental water samples, which can contain salts, sediments, and naturally-occurring microbes."

Field samples of irrigation water can include salts and sediments when rivers are muddied from rain. Because the Arizona water samples were usually very clean, the researchers sometimes added sediment, salts or bacteria like E. coli to the samples before sending them off for testing.

Each lab put its samples through the two certified methods to identify the amount of generic E. coli in the sample. Both tests performed very well when there were no additions to the water as well as when salts and sediments were added.

"But when microbes were added, the consistency fell apart," McLain reported. "For both the mTEC® and Colilert® tests, two labs found the levels of generic E. coli were very high--way above the safety standard. But for each test, one of the three labs showed that the water quality was within the safety threshold."

"The Colilert® test is so straightforward that labs generally get same results," McLain said. "But in this study comparing the two methods, we are not seeing the same results with each test and each lab. Why would labs have such disparate results? That will be the focus of the rest of the study."

One suggestion is that some of these methods are very subjective, requiring highly-trained technicians to evaluate the test results. All water testing completed by the leafy greens industry must be conducted at a certified laboratory, and any presumptive positive results for pathogens must be tested a second time to confirm their presence.

In the next phase of research, McLain and her collaborators will gather more data about the varying conditions that may affect test results, including environmental factors and technician training. The team's goal is to develop a user-friendly guide for industry that will help ensure consistently accurate test results.

Each year, approximately 265,000 Americans have a stroke that causes visual impairment. New research, which appears in the journal Proceedings of the Royal Society B, sheds light on how the damage in the brain caused by a stroke can lead to permanent vision impairment. The findings could provide researchers with a blueprint to better identify which areas of vision are recoverable, facilitating the development of more effective interventions to encourage vision recovery.

"This study breaks new ground by describing the cascade of processes that occur after a stroke in the visual center of the brain and how this ultimately leads to changes in the retina," said senior study author Brad Mahon, an associate professor at Carnegie Mellon University and the University of Rochester. "By more precisely understanding which connections between the eye and brain remain intact after a stroke, we can begin to explore therapies that encourage neuroplasticity with the ultimate goal of restoring more vision in more patients."

When a stroke occurs in the primary visual cortex, the neurons responsible for processing vision can be damaged. Depending upon the extent of the damage, this can result in blind areas in the field of vision. While some patients spontaneously recover vision over time, for most the loss is permanent. A long-known consequence of damage to neurons in this area of the brain is the progressive atrophy of cells in the eyes, called retinal ganglion cells.

"While the eye is not injured in the stroke, cells in the retina that send projections to parts of the brain that are damaged will degenerate over time," Mahon said. "Once this occurs, it becomes more and more unlikely for vision to recover at that location."

The new research sought to understand the mechanisms of vision loss after stroke and whether it was possible to identify areas in the field of vision that could be recovered. The study involved 15 patients treated at Strong Memorial and Rochester General hospitals for a stroke that affected the primary visual processing area of the brain. The participants took vision tests, underwent scans in an MRI to identify areas of brain activity and were administered a test that evaluated the integrity of cells in their retina.

The team found that the survival of the retinal ganglion cells depended upon whether or not the primary visual area of the brain to which they are connected remained active. Eye cells that were connected to areas of visual cortex that were no longer active would atrophy and degenerate, leading to permanent visual impairment.

However, the researchers observed that some cells in the eye remained healthy, even though the patient could not see at the corresponding field of vision. This finding suggests that these eye cells remain connected to unscathed neurons in the visual cortex and that visual information was making its way from the eyes to the visual cortex, even though this information was not being interpreted by the brain in a manner that allowed sight.

"The integration of a number of cortical regions of the brain is necessary in order for visual information to be translated into a coherent visual representation of the world," said study co-author Dr. Bogachan Sahin, an assistant professor in the University of Rochester Medical Center (URMC) Department of Neurology. "And while the stroke may have disrupted the transmission of information from the visual center of the brain to higher order areas, these findings suggest that when the primary visual processing center of the brain remains intact and active, clinical approaches that harness the brain's plasticity could lead to vision recovery."

The research has formed the basis of a new clinical trial for stroke patients with vision loss that is now under way at URMC and lead by Sahin. The study involves a class of drugs called selective serotonin reuptake inhibitors, the most common of which is the antidepressant Prozac, which are known to enhance neuroplasticity - the brain's ability to rewire itself and form new connections to restore function after damage. The hypothesis is that the drug will help restore vision by fostering the development of new connections between areas of the brain necessary for interpreting signals from the healthy eye cells.

The study also suggests new clinical approaches to maximize the potential for recovery by more effectively targeting blind regions in the field of vision. URMC researchers Krystel Huxlin and Dr. James V. Aquavella have developed a visual training regime that has been shown to help with vision recovery after stroke and the new study could help refine how this technology is employed.

"These findings suggest a treatment protocol that involves a visual field test and an eye exam to identify discordance between the visual deficit and retinal ganglion cell degeneration," said Colleen Schneider, an M.D./Ph.D. student at the University of Rochester School of Medicine and Dentistry and the first author of the study. "This could identify areas of vision with intact connections between the eyes and the brain and this information could be used to target visual retraining therapies to regions of the blind field of vision that are most likely to recover."

Data from this study is openly available in KiltHub, CMU's comprehensive institutional repository hosted within figshare. In the future, it will be incorporated into The Open Brain Project, a new, digital platform for exploration of the human brain. Ana Van Gulick, research liaison for psychology and brain sciences and program director for Open Science at Carnegie Mellon University Libraries, is a key contributor to this joint effort of CMU and the University of Rochester.

"The field of neuroscience is currently undergoing a dramatic shift toward open science that will encourage new collaborations and methods of research inspired by data science," Van Gulick said. "A cornerstone of this is providing open access to datasets in a standard format so that they can be aggregated and reused to extend scientific discovery. The data currently available in KiltHub and the larger collection that will later be discoverable through The Open Brain Project will provide a rich open access resource for education and research in neuroscience."

This study also is part of a larger research program being carried out by the Translational Brain Mapping Program at the University of Rochester Medical Center. Mahon and Sahin were recently awarded a $1.7 million grant from National Eye Institute to continue their investigations into vision loss after stroke. The funding will support a multi-institution research effort that includes CMU, URMC, Rochester Regional Health and the University of Pittsburgh Medical Center.

Additional co-authors of the study include Emily Prentiss, Ania Busza and Zoe Williams with URMC and Kelly Matmati and Nabil Matmati with Rochester Regional Health. The study was supported with funding from the National Institute of Neurological Disorders and Stroke, the National Eye Institute, the Schmitt Program on Integrative Brain Research and Research to Prevent Blindness.