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Research published today reveals a potential mechanism for migraine causation which could explain why women get more migraines than men. The study, in Frontiers in Molecular Biosciences, suggests that sex hormones affect cells around the trigeminal nerve and connected blood vessels in the head, with estrogens -- at their highest levels in women of reproductive age -- being particularly important for sensitizing these cells to migraine triggers. The finding provides scientists with a promising new route to personalized treatments for migraine patients.

"We can observe significant differences in our experimental migraine model between males and females and are trying to understand the molecular correlates responsible for these differences," explains Professor Antonio Ferrer-Montiel from the Universitas Miguel Hernández, Spain. "Although this is a complex process, we believe that modulation of the trigeminovascular system by sex hormones plays an important role that has not been properly addressed."

Ferrer-Montiel and his team reviewed decades of literature on sex hormones, migraine sensitivity and cells' responses to migraine triggers to identify the role of specific hormones. Some (like testosterone) seem to protect against migraines, while others (like prolactin) appear to make migraines worse. They do this by making the cells' ion channels, which control the cells' reactions to outside stimuli, more or less vulnerable to migraine triggers.

Some hormones need much more research to determine their role. However, estrogen stands out as a key candidate for understanding migraine occurrence. It was first identified as a factor by the greater prevalence of migraine in menstruating women and the association of some types of migraine with period-related changes in hormone levels. The research team's evidence now suggests that estrogen and changes in estrogen levels sensitize cells around the trigeminal nerve to stimuli. That makes it easier to trigger a migraine attack.

However, Ferrer-Montiel cautions that their work is preliminary. The role of estrogen and other hormones in migraine is complex and much more research is needed to understand it. The authors emphasize the need for longitudinal studies focusing on the relationship between menstrual hormones and migraines. Their current work relies on in vitro and animal models, which aren't easy to translate to human migraine sufferers.

Nonetheless, Ferrer-Montiel and his colleagues see a promising future for migraine medication in their current findings. They intend to continue their research using pre-clinical, human-based models which better reflect real patients.

"If successful, we will contribute to better personalized medicine for migraine therapy," he says.

The research is part of a special article collection on cell membrane proteins as targets for drugs.

Blood platelets are like the sand bags of the body. Got a cut? Platelets pile in to clog the hole and stop the bleeding.

But genetic mutations, infections and even radiation from cancer treatments can slash platelet numbers, leading to a condition called thrombocytopenia and putting people at risk for internal bleeding.

Now scientists at Scripps Research have uncovered a new approach for treating thrombocytopenia. As reported in the journal Proceedings of the National Academy of Sciences, they found that an enzyme can boost platelet production and may work as a future therapeutic.

"This opens up new options for treating diseases of the blood," says Paul Schimmel, PhD, professor at Scripps Research and co-senior author of the study with Professor Zaverio Ruggeri, MD, of Scripps Research.

Previous research had shown that while the enzyme YRSACT has a crucial role in decoding DNA (a process called translation), it appears to have additional jobs in the cell. YRSACT was abundant in blood platelets, the cells that let wounds clog and heal. So, the Schimmel and Ruggeri labs sought to uncover why.

Their study is the first to show that YRSACT is key to one method of platelet production. Schimmel, Ruggeri and their colleagues worked with a platelet-deficient mouse model. Animals injected with YRSACT showed a dramatic increase in platelet production, especially under stressful conditions, such as radiation similar to what cancer patients face.

"Our animal study indicated accelerated platelet recovery, not only in antibody-induced thrombocytopenia, but also in radiation-induced thrombocytopenia," says study first author Taisuke Kanaji, PhD, MD, an institute investigator at Scripps Research.

So how does YRSACT work? The researchers found that YRSACT increases the production of large bone marrow cells called megakaryocytes, which are the precursors to platelets.

Until this discovery, thrombopoietin (TPO) was previously the only other protein known to increase platelets. Schimmel says a version of TPO is currently used as a drug to treat some cases of thrombocytopenia. However, TPO has limitations, making it unsuitable and hazardous in some clinical settings.

Showing that YRSACT could be useful in human patients posed its own challenges. Congenital thrombocytopenia is rare, and even finding the right blood cells to test in thrombocytopenia patients is like finding a needle in a haystack.

Remarkably, the Scripps researchers were able to team up with a group at the Center for iPS Cell Research and Application at Kyoto University to test a stem cell line developed from a thrombocytopenia patient.

"I think this was a beautiful collaboration of groups having distinct expertise to work together to accomplish our goal," says study co-first author Sachiko Kanaji, PhD, MD, a staff scientist at Scripps Research.

Their findings in these human cells further confirmed that YRSACT can control a mechanism in cells to produce life-saving platelets.

Taisuke Kanaji says the next step in the research is to understand the conditions-from infections to radiation-that prompt the body to activate YRSACT on its own.

BUFFALO, N.Y. -- A class of proteins that has generated significant interest for its potential to treat diseases, has for the first time, been shown to be effective in reducing relapse, or drug-seeking behaviors, in a preclinical study.

Published online in July in Biological Psychiatry, the University at Buffalo research reveals important new information about the molecular changes that occur in the brain when an individual takes cocaine, and how these molecules can be targeted to reduce drug-seeking behaviors during withdrawal.

"One of the greatest challenges with addiction is the persistent vulnerability to relapse," said Craig Werner, PhD, first author on the paper and a postdoctoral fellow in the Department of Pharmacology and Toxicology in the Jacobs School of Medicine and Biomedical Sciences at UB. "We know that relapse rates have remained very stable despite many medical advancements, so the big question is, how can we better understand drug addiction so that we can reduce the risk of relapse? We wanted to look at withdrawal and to see what happens in the brain that maintains these relapse behaviors."

Werner is a researcher in the laboratory of David Dietz, PhD, senior author and chair of the Department of Pharmacology and Toxicology.

The publication focuses on a class of proteins called E3 ubiquitin ligases, which work by tagging other proteins to be degraded.

"We are the first group to look at this class of proteins in drug addiction," said Werner, noting that this class of proteins regulates the degradation of specific sets of other proteins in a highly selective manner. "If you indirectly affect a protein through one of these E3 ubiquitin ligases, you can modulate a signaling pathway without targeting it directly."

What is also exciting about these proteins, he said, is that they are changed in disease states. "So the goal is to figure out how to return expression back to what they are in non-disease states, or in this case, how to return the neuroadaptations back to the non-addicted state," he explained.

The targeted protein they studied is known as Smurf1, short for Smad ubiquitinylation regulatory factor 1. Werner and his colleagues found that cocaine addiction in lab animals caused a decrease in Smurf1 and that after addiction, during the withdrawal period when the animals were deprived of cocaine, there was a reduction in Smurf1 protein.

"We think the cell uses this protein, and those that it interacts with, to maintain vulnerability to relapse," he said. "So we hypothesized that if we increased Smurf1, we could make the animals less vulnerable to relapse and actually reduce cocaine-seeking behavior."

When the researchers used viral gene therapy to overexpress Smurf1 in the animals after they had been exposed to cocaine, it reduced the relapsing behavior.

"When we reversed what cocaine does to the brain, by reversing Smurf1 levels, the animal reduced their drug-seeking behaviors," D

Werner and Dietz said that the next step is to conduct more studies on the role of Smurf1 in addiction and other proteins in this class with the hope that such studies will provide the foundation for an effective therapeutic intervention for drug addiction.

New research, published in the European Heart Journal [1] today (Wednesday), has shown deaths from conditions that affect the blood supply to the brain, such as stroke, are declining overall in Europe but that in some countries the decline is levelling off or death rates are even increasing.

Cerebrovascular disease includes strokes, mini-strokes, and narrowing, blockage or rupturing of the blood vessels supplying blood to the brain, and it is the second single largest cause of death in Europe after heart disease, accounting for 9% of deaths in men and 12% of deaths in women each year.

The EHJ study used data from the World Health Organization (WHO) to examine mortality trends in three particular types of cerebrovascular disease in Europe for 37 years between 1980 and 2016: ischaemic stroke (a lack of blood flow to the brain), haemorrhagic stroke (bleeding in the brain) and sub-arachnoid haemorrhage (SAH), in which bleeding occurs between the brain and the surrounding membrane. Not all countries had data available for the full 37 years. [2]

The researchers, led by Dr Nick Townsend, associate professor in public health epidemiology at the University of Bath (UK), found that across the whole of the WHO European region for the most recent period for which data were available, there had been significant decreases in death rates from all three types of cerebrovascular disease in 33 (65%) countries for men and women. However, there had been increases in three countries (6%) for men (Azerbaijan, Georgia and Tajikistan) and in two countries (4%) for women (Azerbaijan and Uzbekistan).

There was evidence of a recent plateau in trends (where the rate of reductions in mortality in the most recent period was less pronounced than in the previous period) in seven countries in men (Austria, Denmark, France, Germany, Greece, Czech Republic and Hungary) and six countries in women (Austria, Belgium, France, Germany, Ireland and Switzerland). There were also a number of countries (eight in men and ten in women) in which death rates showed no change over the most recent period. This means that in both sexes, more than one third of countries showed either a slowing of the decrease in death rates, no decrease, or an increase in the most recent trend.

Age-standardised mortality rates from stroke, which adjust to take account of differences in population size and age structure, were higher in men than in women for all countries. For stroke, they were much lower in western Europe than the rest of the continent. In men, death rates in western Europe ranged from 49 per 100,000 of the population in France to 131 per 100,000 in San Marino. In central Europe, male death rates ranged from 110 per 100,000 in the Czech Republic to 391 per 100,000 in Bulgaria. In eastern Europe, male death rates ranged from 82 in Estonia to 331 in Russia per 100,000. In central Asia, they ranged from 152 in Armenia to 345 in Azerbaijan per 100,000. In the UK, the death rate was 68 per 100,000 in men and 65 per 100,000 in women.

When the researchers looked at each of the three types of stroke individually, data were only available by stroke subtype for 43 countries; most of the countries with missing data were in eastern Europe and central Asia. Over the whole period since 1980, more than half of countries with available data had significant decreases in age-standardised death rates from ischaemic stroke (56% of countries in men and 51% in women) and haemorrhagic stroke (58% and 67% of countries respectively). However, eight countries (19%) had increases in death rates from ischaemic stroke among men and nine countries (21%) in women, compared to none for haemorrhagic stroke. Although significant decreases in death rates from SAH occurred in 56% of countries for men they only did so in 42% of countries in women. Two countries (5%) showed increases in SAH among men and four countries (9%) did so for women.

"When we looked at the type of stroke and for the most recent period for which data were available, the trends could be quite different," said Dr Townsend. "This shows that considering all cerebrovascular disease over the whole period hides a lot of the story. In the most recent period, there were increases in ischaemic stroke in eight countries among men and nine for women, increases in haemorrhagic stroke in three countries in men and one for women, and increases in SAH in five countries for men and eight countries for women." [3]

He continued: "Over the last 35 years there have been large overall declines in deaths from cerebrovascular disease in the majority of European countries. While these declines have continued in more than half of the countries, these have not been consistent across Europe and our analysis has revealed evidence of recent plateauing and even increases in stroke deaths in certain countries. We have seen this in both sexes and in countries across the whole of Europe, particularly in eastern and central Europe and central Asia. We have also found differences in death rates by stroke type. Therefore, it is not enough to consider cerebrovascular disease as just one condition and we must consider each individual stroke type.

"Our findings highlight a need to counter inequalities by understanding local contexts in disease occurrence and treatment. In particular, we need to encourage the implementation of evidence-based recommendations in the prevention and treatment of stroke in all countries. Many countries have been able to reduce the mortality burden from stroke in recent years. We must understand why this is not happening in all countries and identify barriers to the implementation of evidence-based recommended practice in countries that are slow to adopt them. In addition, we only studied between-country inequalities, but we must consider within-country inequalities as well if we are to have an impact on the disease."

The researchers say that SAH amongst women was the only type of stroke for which more countries demonstrated plateauing or increasing trends than decreases in recent years. A less pronounced decrease, no significant change, or a significant increase in death rates from SAH, was found in 25 countries for women.

"General risk factors for SAH include familial predisposition and disorders of the blood vessels, leading to aneurysms. Smoking, hypertension and heavy drinking have also been found to be significant risk factors, as with other stroke types and cardiovascular disease," said Dr Townsend. "Interestingly, when we compare mortality from stroke sub-type by age we find that death from SAH is more common at younger ages. In the UK, for example, around 60% of deaths from SAH in women occur before the aged of 75, commonly termed premature. This is much lower in cerebral haemorrhage, which is closer to 25%, and lower still in ischaemic haemorrhage, which is around 15%. Despite SAH being much less common than the other stroke subtypes, this greater mortality at younger age groups need further investigation and intervention."

Although this study did not look at the reason behind these changes, he said it was unlikely that there was a single reason for the overall decline in cerebrovascular disease. Improvements in treating the disease, including new drugs and improved surgical techniques, played a role, as did prevention strategies that encouraged people to improve their lifestyles by stopping smoking, drinking less alcohol, improving their diet and taking more physical exercise. Possible reasons why the trends towards lower death rates might be levelling off or even increasing in some countries could include the increasing prevalence of obesity, diabetes and higher cholesterol levels in recent years.

Limitations of the study include the fact that the researchers used data submitted to the WHO by individual countries, and which were either absent or incomplete from some countries and of variable quality; the analytical approach used to identify trends is a simplified method and may not give the full picture of plateauing in some countries over some periods; and the study describes the trends but cannot give reasons for them.

Scientists in Norfolk, VA (USA) have developed a new method of making collagen microfibres, which could have applications in research, medical devices and clinical treatments ranging from ligament damage to skin burns.

While collagen fibre manufacturing methods such as electrospinning and extrusion exist for biomedical applications, they have seen limited clinical success. This is partially due to challenges of scalability, cost, and complexity.

The research team, from Eastern Virginia Medical School, The Frank Reidy Research Center for Bioelectrics at Old Dominion University and Embody LLC developed a new method called pneumatospinning.

Writing in Biofabrication, they describe how it uses a high-speed air-based technique to form collagen microfibres from clinical-grade calf skin collagen.

Lead author Dr. Michael Francis said: "Existing methods for making collagen fibre produce low volumes of material, and are very complicated and expensive. Our aim with this research was to explore a cheaper, simpler method that could produce more material faster, ultimately moving towards clinical translation."

The researchers dissolved clinical grade type-1 collagen in acetic acid. They then used a common airbrush to spray the solution (pneumatospinning), polymerizing it into cytocompatible sub-micron fibres. After stabilising the resulting collagen scaffolds, the team examined them using Fourier-transform infrared spectroscopy, circular dichroism, mechanical testing and scanning electron microscopy to show the assembly of native collagen fibre from the molecular to microscales, through mesoscale and into macroscale.

Dr Francis said: "We found the pneumatospun collagen fibres had significantly higher tensile strength compared to electrospun collagen. Also, stem cells cultured on the pneumatospun collagen showed strong cell attachment and compatibility, providing opportunities for more advanced combination therapies."

"Using dimethyl sulfoxide (DMSO) as a solvent, we were also able to make a blended, microfibrous biomaterial by pneumatospinning it with poly(d,l-lactide) This enables even more possible applications of this collagen microfibre-based manufacturing technology for other therapeutic indications with varying requirements, such as higher tensile strength and tailorable degradation kinetics, as based on clinical need."

"As a robust and rapid method of collagen microfibre synthesis, this method has many applications in medical device manufacturing. That includes those benefiting from anisotropic microstructures, such as ligament, tendon and nerve repair, for topical meshes such as ocular or wound dressings, or even for applying microfibrous collagen-based coatings to other materials, such as polymers and metals to enhance graft integration and compatibility."

PROVIDENCE, R.I. [Brown University] -- Polyploidal cancer cells--cells that have more than two copies of each chromosome--are much larger than most other cancer cells, are resistant to chemotherapy and radiation treatments and are associated with disease relapse. A new study by Brown University researchers is the first to reveal key physical properties of these "giant" cancer cells.

The research, published Aug. 9 in Scientific Reports, shows that the giant cells are stiffer and have the ability to move further than other cancer cells, which could help explain why they're associated with more serious disease.

"I think these polyploidal giant cancer cells are the missing link for why tumors become so complex and heterogeneous so quickly," said Michelle Dawson, an assistant professor of molecular pharmacology, physiology and biotechnology at Brown and the study's corresponding author. "By understanding the physical properties of this weird population of cells we might identify a new way to eliminate them. Patients will benefit from that."

Dawson, who is also an assistant professor of engineering with an appointment in Brown's Center for Biomedical Engineering, worked with graduate student Botai Xuan and two undergraduate students on the study, which focused on a common strain of triple negative breast cancer, an extremely aggressive and hard-to-eradicate kind of breast cancer.

They found that 2-5 percent of cells from this breast cancer strain were polyploidal giant cancer cells with four, eight or sixteen copies of each chromosome, instead of the normal two. The cells with more chromosomes were proportionally larger, which is similar to polyploidal cells in other organisms. Commercially available strawberries, for example, tend to be much larger than wild strawberries because the cells of commercial varieties have eight copies of each chromosome. After treating the breast cancer cells with a common chemotherapy, the team found three to 10 times more giant cancer cells. This both confirmed that the giant cells were more drug resistant and gave the researchers more giant cells to study.

Then Xuan, first author on the paper, injected nano-sized fluorescent beads into the cancer cells ¾ both polyploidal giant cells and normal ¾ using a specialized technique involving high pressure helium gas. He found that the beads moved about twice as slow inside the giant cells, indicating the cells were stiffer. This stiffness allows the giant cells to get so big, Dawson said.

The research also found that giant cells had more actin, a biopolymer that forms wire-cable-like structures inside cells to help give the cells their shape and allow them to move. When cancer cells move, they can spread or metastasize, a word no patient wants to hear. Giant cancer cells move differently than standard cancer cells too. Like the allegorical tortoise, they move slower than other cancer cells, but go further.

The Dawson Lab tested a drug that interferes with actin and found it softened the giant cancer cells, but Dawson cautioned this would not be a possible treatment for triple negative breast cancer, as it would turn a hypothetical patient into mush. However, a next step for her research is to look at the giant cancer cells at the molecular level to try to find specific differences in order to develop a targeted treatment.

"This first paper really just gave us a lot of structural information," Dawson said, adding they need to do more research to understand any differences between polyploidal giant cancer cells found before chemotherapy, polyploidal giant cancer cells formed during treatment and the daughter cells they "bud off" in a very atypical manner.

They are also going to look for polyploidal giant cancer cells in samples from patients.

Though the study focused on giant cancer cells found in a strain of triple negative breast cancer, they have found giant cancer cells in other kinds of breast cancer, as well as strains of ovarian and prostate cancer.

"The giant cancer cells break all the cancer rules -- they are stiffer, they are larger, they have a very abnormal and non-polarized cell structure -- and they can move a long way," Dawson said. "Without basic science research, we don't get creative new ideas that lead to breakthrough treatments for patients."

SAN FRANCISCO -- When people are rude to their coworkers or treat them badly, they probably don't realize the unintended victims in that encounter could be the coworkers' children. Women who experience incivility in the workplace are more likely to engage in stricter, more authoritarian parenting practices that can have a negative impact on their children, according to research presented at the annual convention of the American Psychological Association.

"These findings reveal some previously undocumented ways that women, in particular, suffer as a result of workplace aggression," said researcher Angela Dionisi, PhD, of Carleton University. "In uncovering how this mistreatment in the workplace interferes with positive mother-child interactions, this research also speaks to a previously unacknowledged group of indirect incivility victims, namely children."

Workplace incivility is any behavior that is rude, disrespectful, impolite or otherwise violates workplace norms of respect. This behavior shows a lack of concern for others, according to co-author Kathryne Dupre, PhD, of Carleton University. Some examples of workplace incivility include ignoring or making derogatory remarks about someone, taking credit for the work of others, passing blame for your own mistakes, avoiding someone or shutting people out of a network or team.

"We now know, based on much empirical evidence, that the outcomes of workplace incivility are vast and negative," said Dupre. "For example, being on the receiving end of workplace incivility has been linked to lower levels of effort and performance on the job, higher levels of stress, and impaired attention, information processing and decision-making."

To better understand the effects of workplace incivility spillover at home, the researchers conducted an online survey of 146 working mothers and their spouses. Mothers were asked about their experience with incivility in the workplace as well as feelings of effectiveness as a parent. Their spouses were asked to report on the mothers' negative parenting behaviors, both authoritarian (strict and controlling) and permissive. They found a significant association between experiencing rude behavior at work and authoritarian parenting by working mothers at home. There was no association found with permissive parenting.

Survey results also showed that incivility in the workplace was associated with mothers feeling less effective as parents, which could help explain the increased need to engage in strict, controlling parenting behaviors, said Dupre.

Authoritarian parents have high expectations of their children, with rules that they expect their children to follow unconditionally. At the same time, though, they provide very little in the way of feedback and nurturance and harshly punish any mistakes, said Dupre. They tend to have lots of regulations and micromanage almost every aspect of their children's lives, valuing discipline over fun.

"Research suggests that authoritarian parenting is more of a negative style of parenting as compared to other parenting styles. This style of parenting has been associated with a variety of negative child outcomes, including associating obedience and success with love, exhibiting aggressive behavior outside the home, being fearful or overly shy around others, having difficulty in social situations due to a lack of social competence, suffering from depression and anxiety, and struggling with self-control," she said.

One of the most interesting aspects of the findings was how widespread the negative effects of workplace incivility were, especially given that, unlike extreme acts of aggression and violence, these behaviors are generally considered to be low-intensity deviant behaviors, according to Dionisi. "This is a form of mistreatment that many likely dismiss as non-effectual. It's unpleasant, it's frustrating, but it may boil down to one seeing a coworker behaving as a jerk. Our findings, however, suggest that this low-intensity behavior can actually erode one's sense of parental competence, and as a result, may also be harming one's children in a vicarious way."

Dionisi and Dupre hope that providing evidence that what happens at work influences the way people parent will provide the impetus for organizations to better understand and control a form of workplace mistreatment that may sometimes not be taken seriously.

"This research tells us much about the nature and scope of workplace incivility, specifically its detrimental impact on mothering well-being and specific negative parenting behavior. The vicarious impact of incivility on children should be used to inform choices about where and to whom to direct organizational interventions and supports," said Dionisi.

Session 3257: "Uncivil Workplace, Uncivil Home: Workplace Incivility and Harmful Parenting Behavior," Poster Session, Saturday, Aug. 11, 1-1:50 p.m. PDT, Exhibition Halls ABC - South Building, Moscone Center, 747 Howard St., San Francisco, Calif.

Presentations are available from the APA Public Affairs Office.

LAWRENCE -- Younger generations of religious Americans tend to closely harbor concerns for the environment via stewardship more so than older parishioners, according to a study by a University of Kansas researcher.

"The best way to account for this upsurge from about 1980 and on is that a lot of religious groups have actually started to talk to their parishioners about creation care -- a term used to avoid the political context attached to environmentalism," said Lukas Szrot, a KU doctoral candidate in sociology. "Leaders felt that religious groups and churches needed to address this problem, and their members likely wanted to talk more about these issues."

Szrot examined data from the 1973-2014 General Social Survey to determine whether and to what extent environmental concern has been fostered among diverse religious groups in the United States.

He will present his findings on Aug. 11 at the American Sociological Association's Annual Meeting in Philadelphia.

The important background behind the study is the 1967 argument from influential historian Lynn White Jr. who identified Western Christianity as the most anthropocentric religion that has ever existed. Recently, others have also criticized the United States for abdicating its global leadership on environmental issues in recent decades.

Szrot said recent research suggests that environmentalism in the United States has religious roots dating back to the Puritans via an emphasis on environmental stewardship -- the idea that humans bear a special responsibility to care for creation that comes from God. However, researchers have traditionally had difficulty quantifying the connection between environmental concern and those Americans who consider themselves religious.

"Religious groups have said there really is a part of Christianity that isn't anthropocentric," he said. "They have seemed to get a dialogue going."

The dataset accounted for various Judeo-Christian religious traditions, including Protestant denominations, Catholics and Jews.

The environmental concern by age cohort was the starkest finding, Szrot said, indicating that the idea of stewardship has grown, particularly among younger generations of Christians.

This finding likely represents the influence of the heyday for the environmentalism movement in the United States that began in the late 1970s and lasted through the mid-1990s, he said. This focus likely led religious groups to begin to discuss environmental stewardship and care in light of their religious duties, he said.

The findings can be viewed positively, especially in such a divisive and partisan American political climate today, Szrot said.

"I think that there are people on both sides of the party line who want to reach out on environmental issues right now," he said.

Religious groups and settings also might present a favorable forum for people with diverse political views to come together, he added.

"It's been rather uneven so far in a lot of ways. Environmental issues are much more polarized than the 1970s," Szrot said. "There are definitely some challenges, but there is also the idea that church has a sort of social-networking function as well. People who wouldn't normally associate with each other could instead get together. It is possible that in the long run, this will lead to new conversations about environmental issues in the United States."

WHAT:

Despite promising advances, important scientific questions remain unanswered in the effort to develop a safe and effective Ebola vaccine, according to members of an international Ebola research consortium. In a Viewpoint published in The Lancet, the experts review the current field of Ebola vaccine candidates and clinical trials and highlight key gaps in knowledge that need to be addressed by future research.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, are among the Viewpoint's authors. All authors are with the Partnership for Research on Ebola VACcination (PREVAC). In addition to NIAID, the partnership, established in 2017, comprises experts from the French National Institute of Health and Medical Research (Inserm), the London School of Hygiene & Tropical Medicine (LSHTM), the West African Clinical Research Consortium and their collaborators. PREVAC is currently conducting a Phase 2 clinical trial in Guinea, Liberia, Sierra Leone and Mali to evaluate three Ebola vaccination strategies in people one year and older.

Ebola virus disease remains a public health threat--the Democratic Republic of the Congo (DRC) already has experienced two Ebola outbreaks in 2018--underscoring the need for continued efforts to develop an effective vaccine. The authors note that 36 trials of Ebola vaccine candidates have been completed and another 14 are active, according to clinicaltrials.gov. The rVSV-ZEBOV experimental vaccine, which has been deployed in the DRC, is the only candidate with some clinical efficacy data, which were obtained in a clinical trial in Guinea conducted during the 2014-2016 Ebola outbreak in Guinea.

After reviewing the status of four additional vaccine candidates under study (Ad26.ZEBOV, MVA-BN-Filo, chAd3-EBO-Z, and the GamEvac-Combi vaccine), the authors highlight areas where more research is required. Specifically, they note the need for more data in pregnant women, children and immunocompromised populations, including people infected with HIV and the elderly. Additionally, they say more research is needed on the durability and rapidity of immune responses generated by various vaccine approaches. The experts also call for studies to identify reliable correlates of protection (the specific and measurable part of an immune response that would indicate a person is protected from Ebola) as well as large-scale trials to fully evaluate the safety and efficacy of experimental vaccines.

The authors conclude by underscoring the value of embedding social science research in clinical trial design to help build trust and engagement with the affected communities. They note that in addition to the need to investigate various vaccines and vaccination strategies to respond more effectively to future outbreaks, improving the global capacity to conduct clinical research and forming collaborative partnerships, such as PREVAC, are crucial for success.

OAK RIDGE, Tenn., Aug.10, 2018 -- The first full characterization measurement of an accelerator beam in six dimensions will advance the understanding and performance of current and planned accelerators around the world.

A team of researchers led by the University of Tennessee, Knoxville conducted the measurement in a beam test facility at the Department of Energy's Oak Ridge National Laboratory using a replica of the Spallation Neutron Source's linear accelerator, or linac. The details are published in the journal Physical Review Letters.

"Our goal is to better understand the physics of the beam so that we can improve how accelerators operate," said Sarah Cousineau, group leader in ORNL's Research Accelerator Division and UT joint faculty professor. "Part of that is related to being able to fully characterize or measure a beam in 6D space--and that's something that, until now, has never been done."

Six-dimensional space is like 3D space but includes three additional coordinates on the x, y, and z axes to track motion or velocity.

"Right away we saw the beam has this complex structure in 6D space that you can't see below 5D--layers and layers of complexities that can't be detangled," Cousineau said. "The measurement also revealed the beam structure is directly related to the beam's intensity, which gets more complex as the intensity increases."

Previous attempts to fully characterize an accelerator beam fell victim to "the curse of dimensionality," in which measurements in low dimensions become exponentially more difficult in higher dimensions. Scientists have tried to circumvent the issue by adding three 2D measurements together to create a quasi-6D representation. The UT-ORNL team notes that approach is incomplete as a measurement of the beam's initial conditions entering the accelerator, which determine beam behavior farther down the linac.

As part of efforts to boost the power output of SNS, ORNL physicists used the beam test facility to commission the new radio frequency quadrupole, the first accelerating element located at the linac's front-end assembly. With the infrastructure already in place, a research grant from the National Science Foundation to the University of Tennessee enabled outfitting the beam test facility with the state-of-the-art 6D measurement capability. Conducting 6D measurements in an accelerator has been limited by the need for multiple days of beam time, which can be a challenge for production accelerators.

"Because we have a replica of the linac's front-end assembly at the beam test facility, we don't have to worry about interrupting users' experiment cycles at SNS. That provides us with unfettered access to perform these time-consuming measurements, which is something we wouldn't have at other facilities," said lead author Brandon Cathey, a UT graduate student.

"This result shows the value of combining the freedom and ingenuity of NSF-funded academic research with facilities available through the broad national laboratory complex," said Vyacheslav Lukin, the NSF program officer who oversees the grant to the University of Tennessee. "There is no better way to introduce a new scientist--a graduate student--to the modern scientific enterprise than by allowing them to lead a first-of-a-kind research project at a facility that uniquely can dissect the particles that underpin what we know and understand about matter and energy."

The researchers' ultimate goal is to model the entire beam, including mitigating so-called beam halo, or beam loss--when particles travel to the outer extremes of the beam and are lost. The more immediate challenge, they say, will be finding software tools capable of analyzing the roughly 5 million data points the 6D measurement generated during the 35-hour period.

"When we proposed making a 6D measurement 15 years ago, the problems associated with the curse of dimensionality seemed insurmountable," said ORNL physicist and coauthor Alexander Aleksandrov. "Now that we've succeeded, we're sure we can improve the system to make faster, higher resolution measurements, adding an almost ubiquitous technique to the arsenal of accelerator physicists everywhere."

The PRL paper is titled "First Six Dimensional Phase Space Measurement of an Accelerator Beam." The paper's coauthors also include ORNL's Alexander Zhukov.

"This research is vital to our understanding if we're going to build accelerators capable of reaching hundreds of megawatts," Cousineau said. "We'll be studying this for the next decade, and SNS is better positioned to do this than any other facility in the world."

NASA's Aqua satellite found strong storms circling the center of Tropical Storm Kristy.

On Aug. 10. Infrared data from NASA's Aqua satellite provided forecasters with temperature data that showed strong storms.

On Aug. 10 at 4:45 a.m. EDT (0845 UTC) the Moderate Resolution Imaging Spectroradiometer, or MODIS, instrument aboard NASA's Aqua satellite analyzed Tropical Storm Kristy's cloud top temperatures in infrared light. MODIS found cloud top temperatures of strongest thunderstorms around Kristy's low-level center were as cold as or colder than minus 70 degrees Fahrenheit (minus 56.6 degrees Celsius). Cloud top temperatures that cold indicate strong storms that have the capability to create heavy rain.

The National Hurricane Center (NHC) noted at 5 a.m. EDT (0900 UTC), the center of Tropical Storm Kristy was located near 18.2 degrees north latitude and 129.8 degrees west longitude. Kristy is far from land areas and about 1,325 miles (2,135 km) west of the southern tip of Baja California, Mexico.

Kristy is moving toward the north-northeast near 9 mph (15 km/h). A turn toward the north-northeast is expected later today, followed by a turn back to the north with a decrease in forward speed on Saturday, Aug. 11. The estimated minimum central pressure is 991 millibars.

Maximum sustained winds are near 70 mph (110 kph) with higher gusts. While little change in strength is expected today, there is still a chance that Kristy could become briefly become a hurricane this morning. Gradual weakening is expected to begin by tonight and continue through the weekend.

A new LSU Pennington Biomedical Research Center study reveals that a novel biomarker might give us new answers necessary to creating a diagnostic tool for hypoglycemia-associated autonomic failure (HAAF). No objective diagnostic tool currently exists for this condition which, if left untreated, can lead to ever-worsening and possibly life-threatening episodes of dangerously low blood sugar.

Low blood sugar, or hypoglycemia, is a major complication of type 1 and type 2 diabetes. People with diabetes can have difficulty self-administering the exact insulin dose at the correct time to keep blood sugar levels in healthy ranges. If a low blood sugar episode occurs, individuals usually begin to feel a range of symptoms such as dizziness, headaches and nausea that trigger them to seek immediate, potentially life-saving, medical care.

But when people with diabetes have too many hypoglycemic episodes, their senses may become blunted. They may stop experiencing the physical symptoms that serve as cues to seek medical attention. They may not even realize they are having one or multiple hypoglycemic episodes until it is too late. This condition is more commonly known as hypoglycemia-associated autonomic failure (HAAF).

"There is currently no objective way for a health care provider to measure whether a patient has experienced repeated episodes of low blood sugar and therefore may be suffering from HAAF," said David McDougal, PhD, assistant professor-research and head of Pennington Biomedical's Neurobiology of Metabolic Dysfunction Laboratory. One-third of older adults with diabetes who had experienced a severe low blood sugar episode died within three years of the incident, according to a Johns Hopkins Bloomberg School of Public Health study.

LSU Pennington Biomedical researchers set out to discover ways that biomedical imaging might be able to offer new solutions as to how to measure exposure to glucose level crashes. They decided to focus not on glucose uptake in the brain directly, but on how the brain adapts following an episode of low glucose levels.

Blood glucose is the brain's essential metabolic fuel. If glucose isn't available because a person has hypoglycemia, the brain can adapt by increasing the rate at which it uses alternative energy sources, such as acetate.

"The results of our study suggest that this adaptation may still be present after exposure to times of low blood sugar and therefore can be used to measure how frequently a person experiences low blood sugar," McDougal said. "We believe that by measuring how well a person's brain uses acetate, we might one day be able to determine if they are suffering from HAAF or are at increased risk for developing the condition in the near future."

This would allow doctors to provide treatment for reducing this risk by changing the medication the person takes or advising them to use a continuous glucose monitoring device, McDougal said.

The research significantly advances our understanding of the scope and importance of the relationship between brain metabolism and hypoglycemia, McDougal said.

However, he cautions that "more studies will have to be conducted in order to demonstrate if this biomarker can be of practical clinical use."

McDougal has filed a provisional patent application for his discovery.

A quality-improvement project to standardize feeding practices for micro preemies--preterm infants born months before their due date-- helped to boost their weight and nearly quadrupled the frequency of lactation consultations ordered in the neonatal intensive care unit (NICU), a multidisciplinary team from Children's National Health System finds.

According to the Centers for Disease Control and Prevention, about 1 in 10 infants in 2016 was preterm, born prior to completing 37 gestational weeks of pregnancy. Micro preemies are the tiniest infants in that group, weighing less than 1,500 grams and born well before their brain, lungs and organs like the liver are fully developed.

As staff reviewed charts for very low birth weight preterm infants admitted to Children's NICU, they found dramatic variation in nutritional practices among clinicians and a mean decline in delta weight Z-scores, a more sensitive way to monitor infants' weight gain along growth percentiles for their gestational age. A multidisciplinary team that included dietitians, nurses, neonatologists, a lactation consultant and a quality-improvement leader evaluated nutrition practices and determined key drivers for improving nutrition status.

"We tested a variety of strategies, including standardizing feeding practices; maximizing intended delivery of feeds; tracking adequacy of calorie, protein and micronutrient intake; and maximizing use of the mother's own breast milk," says Michelande Ridoré, MS, a Children's NICU quality-improvement lead who will present the group's findings during the Virginia Neonatal Nutrition Association conference this fall. "We took nothing for granted: We reeducated everyone in the NICU about the importance of the standardized feeding protocol. We shared information about whether infants were attaining growth targets during daily rounds. And we used an infographic to help nursing moms increase the available supply of breastmilk," Ridoré says.

On top of other challenges, very low birth weight preterm infants are born very lean, with minimal muscle. During the third trimester, pregnant women pass on a host of essential nutrients and proteins to help satisfy the needs of the fetus' developing muscles, bones and brain. "Because preterm infants miss out on that period in utero, we add fortification to provide preemies with extra protein, phosphorus, calcium and zinc they otherwise would have received from mom in the womb," says Victoria Catalano, RDN, LD, CNSC, CLC, a pediatric clinical dietitian in Children's NICU and study co-author. Babies' linear growth is closely related to neurocognitive development, Catalano says. A dedicated R.N. is assigned to length boards for Children's highest-risk newborns to ensure consistency in measurements.

Infants who were admitted within the first seven days of life and weighed less than 1,500 grams were included in the study. At the beginning of the quality-improvement project, the infants' mean delta Z-score for weight was -1.8. By December 2018, that had improved to -1.3. And the number of lactation consultation ordered weekly increased from 1.1 to four.

"We saw marked improvement in micro preemies' nutritional status as we reduced the degree of variation in nutrition practices," says Mary Revenis, M.D., NICU medical lead on nutrition and senior author for the research. "Our goal was to increase mean delta Z-scores even more. To that end, we will continue to test other key drivers for improved weight gain, including zinc supplementation, updating infants' growth trajectories in the electronic medical record and advocating for expanded use of birth mothers' breast milk," Dr. Revenis says.

Why does the egg size of house sparrows vary so much? Isn't it always an advantage to be big?

Perhaps not surprisingly, baby sparrows that hatch from large eggs are consistently bigger their small egg counterparts. They can store up more reserves if food becomes scarce. So you would think that it's always a good idea to lay big eggs because your offspring would seem to have a greater chance of survival.

But what really set research biologists to wondering is that the difference in volume from the smallest to the largest egg can vary by 50 per cent.

Between 2003 and 2009, biologists from the Norwegian University of Science and Technology (NTNU) examined the egg sizes of an insular population of house sparrows on Hestmannøy in Nordland county. Now the results have been published - and they may surprise you.

Bigger is better if it rains

"We looked at the survival of the young and the chances of recruitment," says postdoctoral fellow Thomas Kvalnes at NTNU's Centre for Biodiversity Dynamics (CBD).

What that means is that researchers didn't simply look at whether the young survived, but also whether they survived to be able to produce their own young when they became old enough.

The researchers found two main attributes:

First of all, yes, big eggs are advantageous if you're looking at short-term survival of the young - when there's a lot of rain. That's when the parents rarely venture out to get food, because insects are less accessible. In that case, it's an advantage for the nestlings to have more energy reserves from the egg.

But researchers also found another connection.

Temperature affects whether it is advantageous to hatch from large or small eggs. In higher temperatures, the young are better off if they hatch from smaller eggs.

Why in the world would that be?

Disadvantage to grow too fast

"At low temperatures, extra reserves from large eggs are important, while at high temperatures, the same reserves probably lead to faster growth than is optimal for long-term survival," says Kvalnes.

So it's possible to grow too fast. This can happen when greater egg reserves, plenty of food and higher temperatures all coincide.

"Previous research has shown that too rapid growth can lead to a lower survival rate over time," Kvalnes says.

This may be due to something called oxidative stress. Rapid growth increases the production of what is known as reactive oxygen species. The body's defence against these degradative compounds cannot always keep up if an organism grows too fast.

This stress can lead to shorter telomeres, which are the caps at the end of each strand of DNA that prevent the genes from being damaged during cell division. Biologists have previously found a connection between telomere length and length of life.

Variable egg size in every clutch

It's no easy matter to predict the weather, either for people or for house sparrows. If the advantage of different egg sizes depends on the weather, the birds have a challenge if they want their offspring to have the greatest possibility of surviving long enough to produce their own young. So how do they solve it?

"We see that every female lays eggs of varying sizes in the same clutch," says Kvalnes.

House sparrows can produce up to three clutches during a season, from early spring to August. The eggs come in assorted sizes within each of these clutches.

"This variation increases the chance that some eggs are always close to the optimal size depending on the weather conditions," Kvalnes says.

Research results also show that the eggs in the last clutch tend to be consistently smaller than eggs early in the season. This may not be so strange, since the average temperature in August is usually higher than early in the spring.

The house sparrow may put all her eggs in the same nest, but she still ensures species security through their varied sizes.