Culture

SILVER SPRING, Md. - A team led by the Walter Reed Army Institute of Research has gained new insights into the mechanism of vaccine-induced T cell immunity utilizing single-cell RNA sequencing and metabolic profiling techniques. Though numerous vaccines induce and amplify T cells, a critical part of the body's adaptive immune system, there is still an information gap regarding what determines the magnitude, diversity and persistence of that response.

This study, published in Nature Communications, was conducted at the WRAIR Viral Diseases Branch in partnership with the Department of Cell and Molecular Biology, Institute for Immunology and Informatics at the University of Rhode Island. It utilized samples from a Phase 1 clinical trial for TAK-003, a live-attenuated tetravalent dengue vaccine.

Dengue virus, present in four distinct serotypes, infects up to 280-500 million individuals yearly around the world. Though many recover quickly from dengue infection, approximately 500,000 develop severe dengue disease, a condition with an approximately 2.5% mortality rate. Dengue is of particular concern for deploying Service Members, and the development of effective countermeasures to prevent dengue infection is a priority for the Department of Defense.

In cases where a patient experiences dengue infection from one serotype and is then re-infected with a distinct dengue serotype, the likelihood of developing severe disease increases significantly. This complicates development of a dengue vaccine, which needs to induce a protective response against all four serotypes and ensure that severe dengue is not induced as a result of the vaccine. A robust T cell response is considered a vital part of immunity to dengue and other viral diseases.

The TAK-003 vaccine, developed to protect against all four serotypes, has been shown to be safe and immunogenic in small animal models and non-human primates. In this study, techniques such as single-cell transcriptomic analysis, or the analysis of the RNA present within a cell, combined with more standard means of cellular immune monitoring shed significant light into the regulation, gene expression and metabolic pathways of T cells. Particularly notable was the discovery of a marker, transferrin receptor 1 (TfR1), to identify the differentiation potential of CD8+ cells, suggesting that T cell immunity is dependent on the availability of specific metabolites.

"The DoD Dengue Vaccine Program strives to understand mechanisms to enhance protection from diseases and to maximize the physical potential of the soldier. This collaborative effort with a partner's vaccine suggests that targeting the unique metabolic requirements of the immune cells thought to provide protection from dengue infection may contribute in the establishment of protective immunity following vaccination," said Lt. Col. Richard Jarman, an author on the paper and director of the Viral Diseases Branch. Though these discoveries took place in the context of a dengue vaccine trial, they are applicable to the development of vaccines for numerous viral diseases.

Frankfurt, Germany, August 14, 2019 - Several studies have recently focused on the association between migraine headaches and other headaches and dementia and found a positive migraine-dementia relationship. However, most of these studies have failed to simultaneously adjust for several common comorbidities, thus potentially introducing bias into their findings.

The goal of the present study, which will be published in the next issue of the Journal of Alzheimer's Disease, was to investigate the association between migraine diagnoses and dementia in patients followed in general practices in the United Kingdom.

This study was based on data from the Disease Analyzer database (IQVIA), which compiles drug prescriptions, diagnoses, and basic medical and demographic data obtained directly and in anonymous format from computer systems used in the practices of general practitioners and specialists.

The current study sample included patients who had received a migraine diagnosis in one of 67 general practices in the UK between January 1997 and December 2016 (index date). Inclusion criteria were as follows: an observation time of at least 12 months prior to the index date; a follow-up time of at least 12 months after the index date; aged between 60 and 80 years at the index date; and no diagnosis of dementia or mild cognitive impairment prior to or at the index date. After applying similar inclusion criteria, patients without migraine diagnoses were matched 1:1 to patients with migraine diagnoses based on propensity scores using a greedy algorithm and derived from the logistic regression using age, sex, index year, and co-diagnoses (i.e. diabetes mellitus, hyperlipidemia, coronary heart disease, stroke including transient ischemic attack, depression, intracranial injury, mental and behavioral disorders due to alcohol use, epilepsy, Parkinson's disease, osteoporosis). The index date for participants without migraine diagnoses was a randomly selected visit between January 1997 and December 2016. The main outcome of the study was the incidence of dementia as a function of migraine diagnosis within 10 years of the index date.

The present study included 3,727 individuals with and 3,727 individuals without a migraine diagnosis. Mean age was 67.7 years and 72.9% of patients were women. Within 10 years of the index date, 5.2% of the participants with and 3.7% of the participants without migraine diagnoses were diagnosed with dementia (p-value

However, a positive association between migraine diagnoses and all-cause dementia and Alzheimer's disease was only significant in women (Hazard Ratio (HR): 1.65; Alzheimer's disease: HR=2.27), not in men.

"Several biological and clinical hypotheses may explain the association between migraine headaches and dementia," explained Dr. Louis Jacob, PhD, from the University of Versailles Saint-Quentin-en-Yvelines. "For example, migraine headaches involve chronic pain, which has been found to substantially impact the risk of memory decline and dementia. As women usually have more severe migraine attacks, the risk of dementia in women with migraine could be higher than in men with migraine."

"We have conducted several studies focused on dementia in recent years," noted corresponding author Prof. Karel Kostev, PhD, from the Epidemiology Department of IQVIA (Germany). "We have been able to identify positive associations between osteoporosis and dementia and between epilepsy and dementia, but have also observed the negative association between some antiepileptic, antidepressant, and antihypertensive drugs and dementia incidence. Such findings demonstrate the significant role of anonymous patient data in epidemiology research for helping people recognize and avoid health risk factors in the future."

The authors of the study also noted that "further studies are warranted to gain a better understanding of the underlying mechanisms of the migraine-dementia relationship and the different sexes in the association between migraine and dementia."

The three major strengths of this study are the large number of patients available for analysis, the use of real-world data including several comorbidities, and the matched-pair design.

However, this study also has two major limitations. Although the prevalence of migraine headaches is the highest in young adults and tends to decrease with age, this study only included participants aged between 60 and 80 years, thus potentially introducing a bias into the statistical analyses. Furthermore, headaches related to an underlying ischemic cerebral lesion are frequently misdiagnosed as migraine headaches in the elderly, which may have affected the results of the present study.

CORVALLIS, Ore. - A new study provides evidence that increasing the abundance of a threatened or endangered species can deliver large benefits to the citizens of the Pacific Northwest.

The study, published today in the journal PLOS ONE, finds that a two-thirds increase in the average annual number of returning coho salmon to the Oregon coast would generate up to $518 million per year in non-market economic benefits to residents of the region.

The study comes the same week that the U.S. Department of Interior announced that it will implement a new rule that stipulates that economic impacts for listing a species be considered under the U.S. Endangered Species Act (ESA).

"When we think about actions to protect endangered and threatened species, we often focus on the costs," said David Lewis, an economist in OSU's College of Agricultural Sciences and corresponding author on the study. "The benefits of protecting threatened species are difficult to estimate since they are considered to be non-market and arise from the public's values for things like the existence of abundant salmon in the wild. This study gives us a way to evaluate the benefits."

"If an agency is considering a policy or program that would increase the number of salmon by a certain amount, our study translates the benefits for that amount of salmon to a dollar value," said Steven Dundas, study co-author and economist in OSU's College of Agricultural Sciences and Coastal Oregon Marine Experiment Station.

"This provides evidence of the economic value Pacific Northwest residents place on protecting threatened and endangered species," Dundas said. "We can compare it to how much we actually spend on salmon restoration activities, to see if there's a net benefit to more investment."

The study, a collaboration between OSU and the Alaska Fisheries Science Center in Seattle, also found that the public attaches a substantial value -- up to $277 million a year - to achieving conservation goals sooner rather than later.

"There are sizable benefits to achieving conservation goals quickly," Lewis said. "That has real implications for conservation programs, showing that there's significant value to the public in up-front investments."

Another key study finding: People benefit from Oregon Coast coho salmon conservation even if the fish aren't declared recovered and removed from listing under the ESA.

"That's an important concept," Lewis said. "This indicates that we shouldn't evaluate ESA activities only by whether a species is recovered or not. It's not all or nothing."

For the study, the researchers mailed surveys to 5,000 randomly selected households in Oregon, Washington, Idaho and northern California in the fall of 2017. The surveys included scenarios with levels of attributes associated with improving the abundance of Oregon Coast coho salmon: how many fish come back from the ocean, how quickly they come back and what their conservation status would be under the ESA.

Associated with these scenarios was an annual per-household cost from a combination of additional taxes and higher prices for lumber and agricultural products, ranging from $10 to $350 per year. Survey respondents then chose their preferred conservation scenario or a status quo option with $0 cost.

Twenty-one percent of the surveys were returned. By analyzing the responses, the researchers determined the public's average household willingness to pay for salmon conservation, which is then multiplied by the number of Pacific Northwest households to get the final benefit numbers.

"The surveys create a situation for someone to make a decision about a public good -- as if increases in salmon abundance were something they could choose off the shelf at the grocery store," Dundas said.

DES PLAINES, IL -- The results of a retrospective study on a pay-for-performance (P4P) program implemented in Vancouver, British Columbia suggest mixed consequences -- it can reduce access block for admitted patients but may also lead to discharges associated with return visits and admissions. The study is published in the August 2019 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM).

The lead author of the study is Yuren Wang MS, from the College of Systems Engineering, National University of Defense Technology, Changsha, China. The findings of the study are discussed in a recent AEM podcast, Do Financial Incentives Change Length-of-stay Performance in Emergency Departments? A Retrospective Study of the Pay-for-performance Program in Metro Vancouver

The study by Wang, et al., suggests that the pay?for?performance program implemented in British Columbia affected the timing of patient disposition in the participating emergency departments (EDs). Such influence includes reduction in the ED length of stay for admitted patients, but possibly higher return?and?admission rate for patients who were discharged right before the target time in certain EDs.

The authors concluded that these observations suggest that we may only include the admission time target in a length of stay-based pay?for?performance program for now. While implementing the discharge target calls for further justification, one may consider combining it with other measurements preventing the potential risk of discharging patients prematurely.

Keith E. Kocher, MD MPH, associate professor in the departments of emergency medicine and learning health sciences at the University of Michigan, had this to say:

"This study provides an excellent post-mortem on the outcomes from a centralized pay-for-performance program applied to emergency care. As is typical, the results are mixed and demonstrate some of the inherent tensions and trade-offs when designing these programs: Is the problem important? Are the targets specified correctly? Are unintended consequences considered? Are the incentives enough to change behavior? You make the call."

Children's savings accounts (CSAs), offered by elementary schools throughout San Francisco and in schools across the nation, were introduced to boost college-going rates, limit student debt and foster equal opportunity for low-income children. However, San Francisco State University Assistant Professor of Management Ian Dunham finds that geography -- particularly in neighborhoods that lack brick-and-mortar banks and credit unions -- may play a key role in how much families with CSAs actually save for college.

Dunham, who teaches in San Francisco State's Lam Family College of Business, and two collaborators are the first to study the connection between economic inequality, a neighborhood's financial service environment and the CSA savings rates at nearby schools, according to their recent study published in the Journal of Consumer Affairs.

They examined San Francisco's Kindergarten to College (K2C) Program, one of the nation's oldest and largest CSA programs. Since 2012, the San Francisco Unified School District (SFUSD) has been opening savings accounts and depositing $50 for each new kindergarten through sixth grade student. Family and friends are encouraged to contribute to a student's saving account throughout their education and they're offered different incentives such as financial matching.

In collaboration with the San Francisco Office of Financial Empowerment, Dunham and his co-authors analyzed data from more than 21,000 CSAs at SFUSD's 74 elementary schools and mapped all the banks, credit unions, elementary schools and alternative financial services institutions, such as payday lenders, in the city. What stood out to them was the relationship between schools with the lowest savings rates, neighborhood demographics and the number of check-cashing establishments.

"Our study finds that schools in comparatively low-income neighborhoods that have few brick-and-mortar banks and credit unions and more payday lenders, check-cashing outlets and pawn shops, have lower savings rates," said Dunham. He calls such neighborhoods "financial deserts" for their lack of mainstream banking options.

"Fringe" financial service providers seek to attract unbanked and underbanked consumers by advertising themselves as low-cost, easy to use and culturally sensitive, Dunham says. However, these providers are not always transparent about fees and long-term reliance upon them is not necessarily beneficial to the asset-building strategies of low- to moderate-income households, he adds. Mainstream banks and credit unions offer consumer protections, including things like FDIC insurance and transparency. Participation in the financial mainstream makes it easier for people to save for the future and build a credit history.

While his research doesn't explain why people in financial deserts have lower CSA savings rates, Dunham says it does highlight a need for improving and promoting financial inclusion and financial literacy school programs. "We want to shine a light on neighborhoods that have been historically marginalized -- be it through redlining, subprime mortgage lending, or other predatory financial practices -- and spur a debate about how to best move forward in a way that's empowering and complimentary to the nuanced needs of residents in these communities."

Dunham said he hopes this research will also encourage the private sector and entrepreneurs to develop new technologies, be it an app or an online bank program with low fees, geared toward low- to moderate-income Americans. "Let's embrace technology and develop new financial services and products that reduce reliance on fringe financial services and make it easier to save and achieve personal financial goals," he said.

SF State could be on the forefront of this type of technology, Dunham says. The Lam Family College of Business recently received a $25 million gift from alumnus and digital currency entrepreneur Chris Larsen, his wife Lyna Lam and nonprofit Rippleworks that will launch a FinTech Initiative within the college. FinTech innovations aim to make every day financial transactions, such as money transfers and banking, cheaper and more accessible.

Bacteria, like people, have complicated relationships: they can either be friendly, neutral, or antagonistic toward each other, and those relationships can change depending on the situations in which they find themselves. As interest in identifying the bacterial species present in the human microbiome that contribute to health and disease has exploded in recent years, so too have efforts to understand how different species of bacteria interact. This knowledge could enable the creation of bacteria-based therapies and tools that could be used to improve human health, produce valuable substances, or repair microbial ecosystems. However, teasing out the relationships that occur simultaneously between multiple species within a consortium of bacteria in a complex environment like the human gut has proven to be a herculean challenge.

Now, science is one major step closer to that goal, thanks to the efforts of a team of researchers from the Wyss Institute for Biologically Inspired Engineering, Harvard Medical School (HMS), and Brigham and Women's Hospital (BWH). In a new paper published last week in mSystems, they report that they were able to successfully manipulate four different strains of bacteria in a consortium so that their interactions became beneficial rather than antagonistic and their respective numbers became more balanced in environments of varying complexity, including the gut of living mice.

"Whenever there are multiple species coexisting in the same space and using the same resources, they are likely to be antagonistic toward each other because they are both trying to be the one that survives," said first author Marika Ziesack, Ph.D., a Postdoctoral Researcher at the Wyss Institute and HMS. "By pushing the bacteria toward more mutually beneficial interactions, we can ultimately make the whole consortium of species more robust and resilient, and could hopefully one day develop synthetic consortia that are optimally tuned for various applications in human gut health and bioproduction."

To get the bacteria to play nicely with each other, the researchers modified their genomes so that each species was unable to produce three of the amino acids it needs to function and overproduced a fourth amino acid. Each species could therefore only thrive if the other three species were present in the community and producing the amino acids it lacked, which encouraged the bacteria to adopt a more live-and-let-live approach.

Such metabolite cross-feeding between species is common in nature - humans cannot produce nine of the 20 amino acids we need to maintain our bodies, so we have to consume a varied diet to get those essential building blocks. Many bacteria also depend on other species for compounds that they lack the ability to make, and such co-dependence is thought to help make bacterial consortia more diverse, which in turn helps them resist dominance by any one species or loss of a crucial member that could lead the consortium to collapse.

The four bacterial species the team chose to create their artificial consortium are all found in the mammalian gut: E. coli, S. Typhimurium, B. thetaiotaomicron, and B. fragilis. Each strain was genetically modified to overproduce either methionine, histidine, tryptophan, or arginine, and its ability to produce the other three amino acids was knocked out.

To evaluate whether each strain was able to "rescue" the other strains that were deficient in the amino acid that it overproduced, the researchers sequentially isolated the compounds secreted by each strain and grew the other strains in the presence of those compounds. Compared with a control group in which compounds from a non-overproducing strain were added, each of the overproducers was able to rescue the other strains to varying degrees, depending on how much of a given amino acid each strain needed to grow.

To see how the four modified strains interacted collectively as a consortium, the researchers cultured them all together and found that they grew in roughly the same proportions but at lower total numbers than non-engineered versions of the same strains grown together, showing that all of the deficient strains were able to get enough amino acids from the others to survive and reproduce. The team then repeated this experiment multiple times, each time reducing the starting population of one strain ten-fold to see how the consortium would react to losing one member. They found that in consortia of non-engineered bacteria the knocked down strain did not recover, while in consortia of engineered bacteria both S. Typhimurium and B. theta regrew to their normal levels after knockdown. Neither E. coli nor B. fragilis was able to recover after knockdown, and the loss of B. fragilis caused the whole consortium to grow to only half its normal size.

The knockdown experiments also revealed the relationships between the different strains in both non-engineered and engineered consortia. In the non-engineered consortium, the absence of certain strains resulted in the overgrowth of others, indicating that those strains are naturally in competition with each other. However, in the engineered consortium, knockdown of one species did not significantly alter the proportions of the remaining species, and in fact, the knockdown of B. fragilis had a negative impact on both S. Typhimurium and E. coli, indicating that the presence of B. fragilis had become beneficial to those species.

The researchers also found that the consortia of engineered bacteria displayed greater evenness - roughly similar amounts of each species - than non-engineered consortia, both in vitro and when the consortia were inoculated into the guts of bacteria-free mice. This trend was also present when the bacteria were grown in low-amino-acid environments, indicating that the engineered bacteria were successfully able to cross-feed each other amino acids to create a stable community.

"As expected in a complex network of species, not all of the bacterial strains interacted with each other equally; the engineered E. coli and S. Typhimurium seem to 'mooch' off of the Bacteroides species without providing as much of a benefit back to the other members, so future research could focus on optimizing how much each species overproduces its given amino acid and consumes others, to improve the overall fitness of the consortium without compromising species evenness," said co-corresponding author Pamela Silver, Ph.D., a Founding Core Faculty member of the Wyss Institute who is also the Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology at HMS.

Other potential directions for this research include introducing cascades of interactions so that each bacterial strain takes in a compound from another strain, modifies it, and "passes it on" to another strain for further processing, to create a more efficient bioproduction assembly line to create chemicals of pharmaceutical or industrial interest.

"We're ultimately interested in rationally designing consortia of beneficial bacteria that can function in complex environments, including the human gut, for medical applications. Introducing 'friendly' interactions among bacteria is an important step toward being able to control these consortia so that they don't exhibit overgrowth behaviors or losses of species and can carry out their intended functions," said co-corresponding author Georg Gerber, M.D., Ph.D., who is also chief of the Division of Computational Pathology at Brigham and Women's Hospital and an Assistant Professor at HMS, as well as co-director of the Massachusetts Host-Microbiome Center at the Brigham.

"Being able to convert one type of bacterial consortium into another stable community is one of the major challenges in microbiome-related medicine today, and this work by Pam Silver and her collaborators represents a major first step toward developing ways to engineer this switch in a controlled way," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences SEAS.

An unprecedented survey has revealed the loss of about 85 percent of historical tidal wetlands in California, Oregon, and Washington. The report, published today in PLOS ONE, also highlights forgotten estuary acreage that might now be targeted for restoration.

Where West Coast rivers reach the sea, estuaries serve as critical nurseries for juvenile salmon and steelhead as they make the transition from freshwater to the ocean. They are among the most dynamic and productive habitats known, also supporting migratory birds and a variety of other fish, shellfish, and terrestrial wildlife.

A team of scientists applied new technologies and data to identify and estimate the historic reach of nearly 450 West Coast estuaries. Their results show that the estuaries historically extended far beyond where they exist now. More than a century of development has erased roughly 85 percent of original vegetated estuarine wetlands, especially around major river deltas.

San Francisco Bay has lost about 85 percent of its original vegetated tidal wetlands, the study found. The Columbia River estuary has lost about 74 percent. While other scientists have estimated losses for these and other well-studied estuaries, this is the first time researchers have applied consistent methods across all 450 estuaries of the contiguous U.S. West Coast.

Mapping Reveals Restoration Opportunities

"Given how valuable estuaries are to so many different species, it's important to understand how much they have changed and what that means for fish and wildlife that depend on them," said Correigh Greene, research biologist at NOAA Fisheries' Northwest Fisheries Science Center in Seattle and coauthor of the new study.

The lost estuary habitat includes areas that were long ago diked and drained for agriculture, and forested wetlands that had not been widely recognized as estuary acreage, said Laura Brophy, lead author of the study and director of the Estuary Technical Group at the Institute for Applied Ecology in Corvallis, Oregon. Identifying such areas may open new opportunities for restoration of estuary habitat that otherwise might go overlooked.

"By folding in these areas that may not have been recognized as part of estuaries, we have a better idea of just how important and extensive these estuaries were," Brophy said. "Now we can see new restoration opportunities that people didn't realize existed."

The study's high-resolution mapping also highlights low-elevation areas at greatest risk of flooding as the sea level rises with climate change. Tidal wetland restoration in these vulnerable areas can re-establish natural processes like sediment delivery. This will help these wetlands remain productive into the future.

Estuaries Once Covered 2 Million Acres

The scientists combined precise elevation mapping known as LIDAR with NOAA water level modeling to establish the extent of tides that define estuary habitat. Based on these maps, they estimated that all West Coast estuaries once covered nearly 2 million acres. This is an area nearly three times the size of the state of Rhode Island.

Scientists have data on the historic and current wetlands in 55 of the larger estuaries. Those estuaries have lost about 85 percent of their original vegetated wetlands. These 55 estuaries represent about 97 percent of historical estuary area on the West Coast, so their losses reflect almost all of the estuary losses.

Since Brophy has studied estuaries for years, she found the losses "dismaying but not surprising." She said the good news is that fish and wildlife that live in estuaries must be adaptable because of the ever-changing tidal environment. She says "if you give them the chance to move back in, they will literally jump at the opportunity."

Although some studies have linked high levels of testosterone to immoral behavior, a new study published in Nature Human Behaviour finds testosterone supplements actually made people more sensitive to moral norms, suggesting that testosterone's influence on behavior is more complicated than previously thought.

Researchers at The University of Texas at Austin took a deeper look at the hormonal underpinnings of moral reasoning. Previous research has investigated moral judgment on the basis of behavioral responses and brain activity, but the current study goes beyond this to analyze the role of deep-seated biological factors, particularly testosterone.

"There's been an increasing interest in how hormones influence moral judgments in a fundamental way by regulating brain activity," said Bertram Gawronski, a psychology professor at UT Austin. "To the extent that moral reasoning is at least partly rooted in deep-seated biological factors, some moral conflicts might be difficult to resolve with arguments."

The researchers borrowed the paradigm of philosophy's trolley problem to test the influence of the hormone testosterone on moral judgments. In the problem, a runaway trolley will kill five people unless someone chooses to pull a lever, redirecting the trolley to another track, where it will kill one person instead.

Instead of the trolley problem itself, the researchers used 24 dilemmas associated with real-life events to simulate a situation that pits utilitarian decisions, which focus on the greater good (saving a large group of people) against deontological decisions, which focus on moral norms (avoiding action that would harm someone).

Prior studies on how hormones influence moral judgment suggest that higher levels of testosterone are associated with stronger utilitarian preferences. So, the researchers put the hypothesis to the test in a double-blind study that administered testosterone to a group of 100 participants and a placebo to another 100 participants.

"The study was designed to test whether testosterone directly influences moral judgments and how," said Skylar Brannon, a psychology graduate student at UT Austin. "Our design also allowed us to examine three independent aspects of moral judgment, including sensitivity to consequences, sensitivity to moral norms and general preference for action or inaction."

Unlike previous studies where heightened testosterone was linked to utilitarian judgments, the researchers were surprised to find that those who received testosterone supplements were less likely to act for the greater good, and instead became more sensitive to moral norms. However, participants with high levels of naturally occurring testosterone showed the opposite, making judgments that were less sensitive to moral norms.

The study's authors think naturally occurring testosterone may be associated with certain moral judgments because people with particular personality traits tend to have different levels of testosterone. For example, people with high levels of psychopathy tend to have high levels of naturally occurring testosterone and exhibit lower sensitivity to moral norms. But this does not mean that testosterone is the cause of psychopaths' insensitivity to moral norms. If anything, testosterone seems to have the opposite effect, increasing people's sensitivity to moral norms, as found in the current study.

"The current work challenges some dominant hypotheses about the effects of testosterone on moral judgments," Gawronski said. "Our findings echo the importance of distinguishing between causation and correlation in research on neuroendocrine determinants of human behavior, showing that the effects of testosterone supplements on moral judgments can be opposite to association between naturally occurring testosterone and moral judgments."

It's unlikely that someone born today could independently think up all the necessary steps it would take to send a rocket to the moon. They would need to learn from those who came before them.

"There are so many things you would need to learn, engineering and chemistry and astronomy," says Marco Smolla, an evolutionary biologist and postdoctoral researcher in the Department of Biology in Penn's School of Arts and Sciences. "It's the 'standing on the shoulders of giants' idea."

Individuals can innovate, coming up with their own ways to advance a society's knowledge, but, perhaps more often, they learn from those with whom they are connected.

In a new paper in Science Advances, Smolla and theoretical biologist Erol Akçay, an assistant professor of biology, show how this learning process triggers a feedback that affects the network structure of societies. Societies in an environment that favors generalists, who have a wide range of skills, are less well-connected than those societies that favor specialists, who are highly skilled at a smaller number of traits.

While other researchers have studied how a society's social structure could influence its cultural dynamics, this is the first time that researchers have shown how cultural selection could impact how the group's social network was formed and maintained.

Putting these theoretical societies under certain pressures--such as changing a generalist-leaning environment so it favors specialists and then goes back to favoring generalists--revealed a tendency for densely networked clusters of specialists to arise, forming "echo chambers" resistant to learning new skills. Such societies can get stuck being highly specialized in a few skills, even when the environment requires a larger variety of skills.

The findings could inform how businesses and even academic fields encourage networking, the authors say.

"There's an idea in business and science and so on where people say networking and more connectivity is important because you get more diverse traits in the network," says Akçay. "What we show is the opposite, that in fact if you get more networked and well-connected, you amplify this echo chamber. You learn what you observe, and if everybody is connected that means everybody learns the same things."

Smolla and Akçay set out to create a simple model of cultural evolutionary dynamics, working off the idea that cultural practices are passed through a social network. They focused on the trade-off between a generalist culture that favors a wide range of skills, for example a hunter-gatherer society in which everyone may be comfortable with a number of practices, versus a specialist-favoring culture, for example a fishing society, in which everyone specializes in that livelihood.

"We asked, how does the thing you need to learn affect how you interact with others," says Smolla. "If you're a generalist where you have a lot of different skillsets to acquire, or you're a specialist who learns one thing but learns it really well, how does that affect the networks?"

The researchers used a social-network model borrowed from a previous study by Akçay and his former postdoc Amiyaal Ilany based on hyena societies in which social ties are passed through generations. They also borrowed a feature of social-network analysis by Penn's Damon Centola known as "complex contagion," which assumes that a person requires multiple exposures to a skill or behavior to learn it.

Their first main finding, that specialists formed efficient, dense networks, while generalists formed sparser networks, came as something of a surprise.

"We had thought it might be the other way around," says Smolla, "that if you wanted to be a generalist with a broad spectrum of skills you would interact with a broad spectrum of individuals. But the reason that's not the case is complex contagion, the fact that you have to observe traits repeatedly. In the dense network of specialists, you're more likely to learn a specific skill that everyone around you is specializing on as well."

Also surprising to the team was the fact that generalists developed repertoire sizes that were only slightly larger than those of specialists. But again, it depends on complex contagion: The generalists were less likely to encounter others with the same trait multiple times, which means they had lower rates of learning overall. Specialists, on the other hand, had far higher proficiencies than the generalists, thanks to a combination of individuals innovating and then learning from their highly-skilled friends and neighbors.

Smolla and Akçay also observed that being subject to environmental changes can harm specialists, sealing them off from opportunities to learn. They point to examples of this on, for instance, social media where groups tend to be highly connected, or even in tight-knit specialties of science.

"There is even an interesting recent paper that shows that, in scientific communities where everybody coauthors with the same people, those scientific fields are less likely to produce replicable findings," says Akçay.

Looking ahead, the researchers are continuing to example cultural evolution by adding complexity to their model. In one line of study, they're examining what happens when there are different values placed on the various skills learned and taught in a group.

"Let's say right now it's better to be a scientist, but later it might be better to be a farmer," says Smolla. "We're interested in how that affects a society's networks."

Depending on the temperature, a plant may synthesize the hormone auxin. Depending on the pathogens present, a plant may synthesize auxin. Depending on the available nutrients, water, stressors or development cues: auxin.

When a plant bends toward the light as it grows, the underlying chemical that regulates that movement?

Auxin.

Depending on the situation, the presence of this hormone can be a signal that kicks DNA transcription into gear, promoting growth and development, or it can keep transcription from happening.

An interdisciplinary team comprising members of Arts & Sciences and the McKelvey School of Engineering at Washington University in St. Louis has recently uncovered a mechanism by which a plant can be affected in a myriad of ways based on the presence of the same hormone.

The research was published Aug. 14 in the journal Molecular Cell.

"You can have any cue," said lead researcher Lucia Strader, associate professor of biology in Arts & Sciences and associate director of the Center for Science & Engineering of Living Systems. "Light, temperature, different nutrients ... the plant makes auxin in response to all of these things." What follows as a result of that auxin release can also vary, from stress responses to leaf development to changes in the root system architecture.

Those responses are all results of Auxin Response Factors (ARFs), proteins which bind to DNA in a cell's nucleus to facilitate growth and development in one way, or another.

The question Strader's lab was investigating: how can ARFs do the right thing, in the right place, at the right time while at the same time preventing inappropriate responses?

The answer began with an updated understanding of the fundamental nature of ARFs.

They are always present in a plant, but ARFs are often impotent because they are bound by Aux/IAA repressor proteins, which keep the ARFs inactive, until auxin chemically uncouples them. A new understanding of the structure of the ARFs led to a new understanding about the way they connect.

The change centered on the PB1 domain, on the opposite end of the ARF protein from the DNA binding domain (where the ARF, once in the nucleus of a cell, will bind to DNA during the transcription process).

As opposed to being bound to repressor or ARF proteins in pairs, "ARF PB1 domains are like miniature bar magnets, with a plus side and a minus side, free on two ends to pair with other proteins," Strader said. "There's the potential for them to grow into long chains."

Outliers in the cytoplasm

It turns out that ARF PB1 domain chain formation plays an unexpected role.

While researching ARFs, Samantha Powers, a graduate student in the lab, was tasked with tagging one of the 23 Arabidopsis ARFs as part of her research. The image she came back with was unusual. Instead of finding the ARFs in the nuclei of plant cells, they were showing up in the cytoplasm, the gel-like substance that surrounds the nucleus. "Which is weird," Strader said.

Looking in the literature for studies showing the location of ARFs in plant cells, the team found one. Just one. And it looked much different than what Powers saw in her research: the ARFs were mostly where they "should" be, in the nuclei of the cells, with a couple of outliers in the cytoplasm.

An interdisciplinary team comprising members of Arts & Sciences and the McKelvey School of Engineering at Washington University in St. Louis has recently uncovered a mechanism by which a plant can be affected in a myriad of ways based on the presence of the same hormone.

Powers, it turned out, had been looking at ARFs in the plant's mature root, while the study they found had looked at the meristematic root tip, the area where young cells divide.

"The beautiful thing about plants as a developmental model is that in a single individual, at a single time point, you have every stage of development present," Strader said. The youngest cells are at the beginning of the root system and since plant cells don't move, they simply divide upward, building upon each other; the cells get older the farther away they are from the tip.

Powers's finding, then, was a clue: In the younger cells, ARFs were in the nucleus, transcribing mRNA, but in the older cells, they were stuck in the cytoplasm, not doing much of anything. And in the intermediate regions, there was a mix.

Strader discussed these findings at a biophysics seminar, after which Alex Holehouse -- then a PhD student working in the lab of Rohit Pappu, the Edwin H. Murty Professor of Engineering in the McKelvey School of Engineering -- approached her with a specific proposal.

"He said, 'While you were giving the talk, I downloaded the sequences of all 23 ARFs and analyzed them. I have data for you,'" Strader said.

Holehouse is currently a postdoctoral fellow in the Pappu lab and is slated to start his own lab in the Department of Biochemistry & Molecular Biophysics in early 2020. He proposed that the ARFs that Powers and Strader were seeing in the cytoplasm were in fact protein condensates driven, in part by the "intrinsically disordered regions" of ARF proteins, the regions that lie between the DNA binding and the PB1 domains.

Holehouse postulated that the ARF proteins were transitioning from dispersed to condensed states to accumulate in the cytoplasm; similar to the way water molecules condense to form droplets.

"Conventional wisdom says that proteins have to adopt specific three-dimensional shapes to recognize their molecular targets; IDRs are different in that they are shape shifters," Pappu said. "They can adopt different shapes depending on their contexts and these features make them ideal drivers of condensates providing they have the requisite sticky regions.

"Alex analyzed the sequences and found a very clear compositional distinction," Pappu said.

The IDRs (intrinsically disordered regions) of particular ARFs had all the features of molecules that readily stick to themselves. Coupled with the ability for the ARFs to connect and form repeating structures -- or oligomerize -- via the PB1 domain, ARFs in the older cells condensed into assemblies that ensure that they remain stuck in the cytoplasm.

And when ARFs are stuck in the cytoplasm, they cannot initiate DNA transcription. "It is that simple," Pappu said.

"We think this is a way of keeping that pathway from being active in a certain cell type without turning it off completely," Strader said.

Plants as model systems

Guided by Holehouse's detective work, Powers went on to mutate certain ARFs so they would all make their way into the nucleus. They found that, as long as the ARFs can make it into the nucleus to bind DNA, when auxin is present, transcription will occur, no matter the cell type.

"It's really exciting because we have shown that forming condensates in the cytoplasm is a way of attenuating auxins," Strader said. "Every cell is responsive to auxin when there is an ARF variant that's constitutively nuclear, whereas unresponsive cells sequester ARFs in their cytoplasm." A constitutively nuclear variant be able to activate genes in all cell types.

"Engineers routinely try to design biomaterials that can form depots within cells so as to control the release of material that gets tied up in the depots," Pappu said. "What is fascinating is the level of control afforded to the localization of ARF proteins by making cytoplasmic depots, the condensates, via sticky IDRs in older cells. The depot making apparatus, comprising of molecules with sticky IDRs can tell older from younger cells. Being able to replicate this type of molecular control to make active matter would be a dream for bioengineers."

The continuing collaboration between the Strader and Pappu labs is focused on adapting plants as model systems to study molecular and cellular processes that are tied to neurodegeneration.

That's because this research shows a strong, positive biological role for protein condensation which, Strader pointed out, is the same process often associated with disease such as Alzheimer's , ALS, and other prion-related disorders.

For plants, this research illustrates how condensation is a mechanism that can prevent them from transcribing genes by keeping transcription factors out of the nucleus in certain contexts, ensuring auxin does the right thing, at the right time, in the right place.

It is well known that men benefit reproductively from having multiple spouses, but the reasons why women might benefit from multiple marriages are not as clear. Women, as a result of pregnancy and lactation, can't reproduce as fast as males.

But new research by the University of California, Davis, challenges evolutionary-derived sexual stereotypes about men and women, finding that multiple spouses can be good for women too.

"We can't pin down the exact reasons for this finding, but our work (together with suggestions of others) suggests that marrying multiply may be a wise strategy for women where the necessities of life are hard, and where men's economic productivity and health can vary radically over their lifetime due to the challenging environmental conditions," said the lead researcher, Monique Borgerhoff Mulder, UC Davis professor of anthropology.

Women can buffer themselves against effects of the economy

Researchers infer that by acquiring multiple spouses, women can buffer themselves against economic and social crises, and more effectively keep their children alive.

Borgerhoff Mulder collected data on births, deaths, marriages and divorces of all households in a western Tanzanian village over two decades. A longitudinal study like this is "much more reliable than records collected retrospectively," said the study's co-author, Cody Ross, currently a postdoctoral fellow at the Max Planck Institute for Evolutionary Anthropology, Leipzig.

Working with the demographic data, Ross found that women who moved from spouse to spouse tended to have more surviving children, controlling for the number of years they had been married. Men by contrast, again controlling for their number of married years, tended to produce fewer surviving children with the individual women they married over their lives.

Researchers collected data on nearly 2,000 individuals living in a small village at the north end of the Rukwa Valley, in an area adjacent to floodplains and woodlands now designated as Katavi National Park. The people who live there are of Pimbwe and related Bantu ethnicity. The Pimbwe people have a long history of hunting, fishing, and farming cassava and maize. They also gather honey, brew beer and conduct small business. But crop yields are unreliable owing to unpredictable rainfall, poor soil conditions, agricultural pests and theft.

The latest paper, published Aug. 14 in Proceedings of the Royal Society B, represents a culmination of two decades of work by Borgerhoff Mulder, who has written extensively about the lives of men and women in this small village in western Tanzania where she conducts anthropological and demographic research.

"As evolutionary biologists we measure benefit in terms of numbers of surviving children produced -- still a key currency in rural Africa," explained Borgerhoff Mulder. "... it bears emphasizing that in many parts of rural Africa reproductive inequality among women emerges not from reproductive suppression as in some other highly social mammals ... but more likely from direct competition among women for access to resources." These resources include high-quality spouses, multiple caretakers to help around the house and farm, and (at least in this particular cultural context) helpful in-laws, she said.

Marriage in the Pimbwe culture is informal -- defined as sexual partners living together. Accordingly, "divorce is easy, and can be initiated by either partner," as both Borgerhoff Mulder and early 20th century missionary visitors to the area have observed. Both men and women may have more sexual partners than marriage partners, but sexual partnerships are quickly recognized as marriages, researchers said.

A fisherman's curiosity led to identification of the correlation between microbial communities in recreational freshwater locales and seasonal environmental changes, according to a team of researchers from Penn State.

Zachary Weagly, a 2018 graduate of Penn State Berks and an avid fisherman, noticed that the quality of the water where he fished changed with the local environment. He asked Tami Mysilwiec, associate professor of biology and one of his teachers, if he could use some of her laboratory's Biolog Ecoplates to test the water and a three-site, multiyear project to test freshwater in the Blue Marsh watershed in Pennsylvania began.

"Zach came to me because he is an avid fisherman and our campus abuts a tributary of the Schuylkill River, Tulpehocken Creek," said Mysilwiec. "When he went fishing he noticed changes in the water and the fish at various times.

Biolog Ecoplates are commercially available and contain three sets of identical wells that test for 31 different forms of carbon-containing chemicals. Bacterial communities have identifiable reaction patterns on these plates and researchers can characterize the communities and track changes in them through time and environmental change.

The first site tested is on a creek that receives runoff from agricultural land. The second site is a lake with an artificial dam that is unusual because water empties from the lake from below rather than falling over a spillway. The third site is downstream in an area with industrial complexes, a hospital and an airport.

"The three sites are in three different environmental areas," said Mysilwiec. "The water quality changes on a seasonal basis, which leads to the question of what happens to potential pathogens."

The testing plates can provide an idea of what the microbes in the water like to eat, and from that, a profile of the bacteria is possible. Some of the chemicals tested are antibiotics, nutrients, growth factors and other metabolites.

The researchers, including Jill M. Felker, research technologist at Penn State Berks and graduate student at Antioch New England, and Katherine H. Baker, associate professor emerita in the School of Science, Engineering and Technology at Penn State Harrisburg, looked at E. coli and Enterococci bacterial counts, because those are the two bacteria the U.S. Environmental Protection Agency uses to decide if recreational waterways are safe.

"We found that the lake near the survey was over the acceptable amounts 93% of the time," said Felker. "We also found that depending on the season, E. coli could be 36 percent higher than previously measured and Enterococci could be 86 percent higher than previously measured.

"We do not know why this happens," she continued. The researchers wonder if it is phosphates and nitrates in runoff from agriculture from livestock or fertilizer.

The researchers also used 16S ribosomal sequencing to capture a snapshot of the pathogenic bacteria in the samples. The 16S rRNA gene is present in all bacteria and differences in this gene can identify the bacterial types.The researchers report today (Aug. 14) at the annual meeting of the Ecological Society of America in Louisville, Kentucky, that there were seasonal differences at all three sites and between the three sites. Levels of nitrate and phosphate increased in late fall and mid-spring. They found that microbial populations varied among the three sites, with numbers of colonies increasing in warmer months and peaking when human waterway use was highest.

Signs of human use were the levels of chemicals used in personal care products and agricultural practices.

The researchers noted that "common human practices can potentially change a waterway's chemistry, leading to the preferential selection of pathogenic microbial communities."

Over the past several years, microplastic particles have repeatedly been detected in sea-water, drinking water, and even in animals. But these minute particles are also transported by the atmosphere and subsequently washed out of the air, especially by snow - and even in such remote regions as the Arctic and the Alps. This was demonstrated in a study conducted by experts at the Alfred Wegener Institute and a Swiss colleague, recently published in the journal Science Advances.

The fact that our oceans are full of plastic litter has by now become common knowledge: year after year, several million tonnes of plastic litter find their way into rivers, coastal waters, and even the Arctic deep sea. Thanks to the motion of waves, and even more to UV radiation from the sun, the litter is gradually broken down into smaller and smaller fragments - referred to as microplastic. This microplastic can be found in marine sediment, in seawater, and in marine organisms that inadvertently ingest it. In comparison, there has been little research to date on whether, and if so, to what extent, microplastic particles are transported by the at-mosphere. Only a handful of works are available, e.g. from researchers who were able to confirm the particles' presence in the Pyrenees and near major urban centres in France and China.

A team of experts from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) has now found that microplastic particles can apparently be transported over tremendous distances by the atmosphere and are later washed out of the air by precipitation, particularly snow. As the team led by Dr Melanie Bergmann and Dr Gunnar Gerdts report in the journal Science Advances, the analyses they conducted on snow samples from Helgo-land, Bavaria, Bremen, the Swiss Alps and the Arctic confirm that the snow at all sites con-tained high concentrations of microplastic - even in remote reaches of the Arctic, on the is-land Svalbard, and in snow on drifting ice floes. "It's readily apparent that the majority of the microplastic in the snow comes from the air," says Melanie Bergmann. Her hypothesis is supported by past research conducted on grains of pollen, in which experts confirmed that pollen from the middle latitudes is transported by the air to the Arctic. These grains are rough-ly the same size as the microplastic particles; similarly, dust from the Sahara can cover dis-tances of 3,500 km or more, reaching the northeast Atlantic.

The AWI researchers found the highest concentration in samples gathered near a rural road in Bavaria - 154,000 particles per litre. Even the snow in the Arctic contained up to 14,400 particles per litre. The types of plastic found also varied greatly between sampling sites: in the Arctic, the researchers chiefly found nitrile rubber, acrylates and paint, which are used in a host of applications. Given its resistance to various types of fuel and broad temperature range, nitrile rubber is often used in gaskets and hoses. Paints containing plastic are used in several different areas, e.g. to coat the surfaces of buildings, ships, cars and offshore oil rigs. Near the rural road in Bavaria, the samples especially contained various types of rubber, which is used in countless applications, such as automotive tyres.

One intriguing aspect of the AWI study: the microplastic concentrations found are considera-bly higher than those in studies conducted by other researchers, e.g. on dust deposits. Ac-cording to Gunnar Gerdts, this could be due to one of two reasons: "First of all, snow is ex-tremely efficient when it comes to washing microplastic out of the atmosphere. Secondly, it could be due to the infrared spectroscopy we used, which allowed us to detect even the smallest particles - down to a size of only 11 micrometres." Gerdts and his colleagues melt the snow and pour the meltwater through a filter; the residue trapped in the filter is then exam-ined with an infrared microscope. Depending on the type of plastic, different wavelengths of the infrared light are absorbed and reflected; in this way, an optical fingerprint can be used to determine what type of plastic they've found.

Whereas other experts sort out microplastic from their samples by hand under the micro-scope, which can easily cause some particles to be overlooked, Gerdts uses his infrared microscope to test all of the residue, ensuring that he and his team hardly miss a thing. "We've automated and standardised the technique so as to rule out the errors that can creep in when manual analysis is used." As such, it's hardly surprising that the analyses conducted at the AWI yielded especially high particle concentrations.

In light of the meteorological realities, the AWI experts are convinced that a major portion of the microplastic in Europe, and even more so in the Arctic, comes from the atmosphere and snow. According to Melanie Bergmann: "This additional transport route could also explain the high amounts of microplastic that we've found in the Arctic sea ice and the deep sea in previ-ous studies."

Lastly, there's another key question that motivates her work. "To date there are virtually no studies investigating the extent to which human beings are subject to microplastic contamina-tion." In addition, most research has focused on how animals or human beings absorb micro-plastic from what they eat. As Bergmann explains: "But once we've determined that large quantities of microplastic can also be transported by the air, it naturally raises the question as to whether and how much plastic we're inhaling. Older findings from medical research offer promising points of departure for work in this direction." Yet another aspect that warrants a closer look in the future.

Individual and systemic challenges specific to female family physicians in their first five years of practice create obstacles that can result in disproportionate rates of burnout and negative impacts on career trajectories, according to a new paper co-authored by Dr. Tali Bogler of St. Michael's Hospital's Academic Family Health Team.

The article, to be published on August 14, 2019 in Canadian Family Physician, is authored by three female family physicians nearing the end of their first five years of practice and outlines practical strategies to achieve gender equity and work-life integration.

The paper highlights systemic challenges including implicit and overt bias, a shortage of women in leadership positions, a lack of supportive and comprehensive leave policies, and gender-based pay inequities. Individual challenges include imposter syndrome, balancing personal and professional responsibilities, and restrictive gender norms.

"The 2017 Canadian Medical Association National Physician Health Survey demonstrated that that female physicians and early career physicians reported the highest levels of burnout," says Dr. Bogler.

"What we didn't know was why. This paper aimed to explore that from a first-person perspective and provide practical strategies to specifically support female family physicians."

The paper calls for implicit bias and sexual harassment training for physicians of all career stages, more flexibility in scheduling to respect work-life responsibilities, and a review of which payment models widen or lessen the gender-pay gap. Female family physicians typically spend longer with patients and give more attention to psychosocial issues, putting them at an earning disadvantage compared to their male counterparts, who typically see a larger volume of patients for shorter visits, the paper states. The authors advocate for remuneration systems that adequately compensate family physicians for time spent with patients and complexity of care.

The authors also called for the development of comprehensive family, caregiving, and medical leave policies, citing that a lack of these policies disproportionately affects women and those in early career.

There are solutions that female family physicians can individually initiate, including exploring peer-to-peer support groups, mentorship and by setting boundaries. The paper notes that the development of electronic medical records have created an expectation of 24-7 availability for physicians.

The paper also recounts the authors' personal moments of gender bias and disparity, including a time in which Dr. Bogler and her husband, also a physician, were standing side by side both wearing stethoscopes. A stranger referred to her husband as a doctor and to Dr. Bogler as a nurse.

While the paper largely explores the challenges for early-career female family physicians, Dr. Bogler notes that these challenges may be amplified for women with intersecting forms of social positions such as race and sexual orientation.

For children and teens with migraine, the pain and symptoms that accompany migraine attacks can be debilitating, resulting in missed school days, absence from social or sporting events, and affected home activities. Now the American Academy of Neurology (AAN) and the American Headache Society have developed two guidelines that include recommendations for preventing and treating migraine in children and teens. The guidelines are published in the August 14, 2019, online issue of Neurology®, the medical journal of the AAN, and are endorsed by the American Academy of Pediatrics and the Child Neurology Society as well as the American Headache Society. The guidelines update the 2004 AAN guideline on drug treatment of migraine in children and teens.

Migraine is a common neurologic disease marked by irregular attacks of moderate to severe headaches and related symptoms, including nausea, vomiting and sensitivity to light and sound.

The guidelines looked at two areas: acute treatments to stop or lessen the pain and other symptoms during an attack and also treatments to prevent or reduce how often the migraine attacks occur and lower the impact of the disease on school, home and social functioning.

"We reviewed all of the available evidence, and the good news is that there are evidence-based treatments for children and teens that are effective for treating migraine attacks when they occur," said guideline lead author Maryam Oskoui, MD, MSc, of McGill University in Montreal, Canada, and a Fellow of the American Academy of Neurology. "However, most medications that are designed to prevent recurrent migraine attacks are only as good as placebo when used in children and there is little evidence to guide treatment of related symptoms such as nausea and sensitivity to light. It should be noted that these medications, as well as placebo, were effective in more than 50 percent of the patients."

The guidelines recommend that children and teens have a detailed history and physical examination, including a neurological examination that may need to be conducted by a neurologist or headache medicine specialist. The guidelines also recommend that children and teens, along with their parents, be educated about migraine, including potential identification of factors associated with migraine, such as lack of physical activity, being overweight, excessive caffeine intake, poor sleep habits and dehydration.

Additionally, migraine may occur alongside mood disorders such as depression and anxiety that can worsen the disability and delay recovery. Development of healthy lifestyle habits to include healthy eating, regular exercise, adequate hydration and getting enough regular sleep can address many of these issues.

Doctors should discuss the risks and benefits of preventive medication and appropriate acute treatment. The combination of cognitive behavioral therapy (CBT) and amitriptyline was more beneficial than amitriptyline and headache education in reducing migraine attack frequency and migraine-related disability, however, it is important to note that amitriptyline may increase the risk of suicidal thoughts and behavior.

CBT uses a combination of coping skills, positive thinking strategies, adherence management, barrier reduction and biofeedback-assisted relaxation, which is computer-aided feedback of relaxation techniques, to empower the children and teens to counter the effects of migraine.

Oskoui said, "The benefit of CBT alone or in combination with other treatments in migraine prevention warrants further study."

The guidelines recommend treating attacks as soon as the child or teen becomes aware of an attack starting. Medications such as ibuprofen, triptans and combination sumatriptan/naproxen can help relieve pain during an attack.

Another treatment outlined in the guidelines was botulinum toxin for prevention of migraine. While the drug is effective in preventing migraine in adults, it has not shown the same effectiveness in children and teens.

Finally, the guidelines did not address some of the newest treatments, including calcitonin gene-related peptide (CGRP) antibodies, other similar drugs, and devices for migraine in children and teens, because while there has been research showing these treatments may work well for preventing migraine in adults, the study of these treatments in children and teens is only beginning.