Treadmill performance predicts mortality

                               Treadmill (stock image). Credit: © viktoriagavril / Fotolia

Analyzing data from 58,000 heart stress tests, Johns Hopkins cardiologists report they have developed a formula that estimates one's risk of dying over a decade based on a person's ability to exercise on a treadmill at an increasing speed and incline.

Several exercise-based risk scoring systems already in use are designed to measure short-term risk of dying but do so strictly among patients with established heart disease or overt signs of cardiovascular trouble. Such scores factor in multiple variables and incorporate results from additional tests, including electrocardiograms (EKGs).

By contrast, the new algorithm, dubbed the FIT Treadmill Score and described in the March 2 issue of the journal Mayo Clinic Proceedings, can gauge long-term death risk in anyone based solely on treadmill exercise performance. The score, the research team says, could yield valuable clues about a person's health and should be calculated for the millions of patients who undergo cardiac stress testing in the United States each year.

"The notion that being in good physical shape portends lower death risk is by no means new, but we wanted to quantify that risk precisely by age, gender and fitness level, and do so with an elegantly simple equation that requires no additional fancy testing beyond the standard stress test," says lead investigator Haitham Ahmed, M.D. M.P.H., a cardiology fellow at the Johns Hopkins University School of Medicine.

In addition to age and gender, the formula factors in peak heart rate reached during intense exercise and the ability to tolerate physical exertion as measured by so-called metabolic equivalents, or METs, a gauge of how much energy the body expends during exercise. More vigorous activities require higher energy output (higher METs), better exercise tolerance and higher fitness level. An activity such as slow walking equals two METs, compared with eight for running.

"The FIT Treadmill Score is easy to calculate and costs nothing beyond the cost of the treadmill test itself," says senior study author Michael Blaha, M.D., M.P.H., director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. "We hope the score will become a mainstay in cardiologists and primary clinicians' offices as a meaningful way to illustrate risk among those who undergo cardiac stress testing and propel people with poor results to become more physically active."

Exercise stress tests -- commonly used to determine who needs invasive cardiac testing and inform treatment decisions -- measure how well the heart and lungs respond to physical exertion while a person is walking on a treadmill at progressively higher speed and elevation. The test is stopped once a person reaches the point of exhaustion or develops chest pain, dizziness or heart rhythm abnormalities. Those who have abnormal findings on their EKG tracings during exercise or who develop symptoms suggestive of abnormal heart strain during the test are referred for angiography, an invasive procedure to examine the interior of the heart's main blood vessels. Those who have normal EKG readings and no alarming symptoms while exercising are said to have "normal" results and typically do not require further testing.
However, the researchers say, the new data show varying degrees of fitness among those with "normal" stress test results that reveal telling clues about cardiac and respiratory fitness and, therefore, overall death risk over time.

"Stress test results are currently interpreted as 'either/or' but we know that heart disease is a spectrum disorder," Ahmed says. "We believe that our FIT score reflects the complex nature of cardiovascular health and can offer important insights to both clinicians and patients."
For the study, the team analyzed information on 58,020 people, ages 18 to 96, from Detroit, Michigan, who underwent standard exercise stress tests between 1991 and 2009 for evaluation of chest pain, shortness of breath, fainting or dizziness. The researchers then tracked how many of the participants within each fitness level died from any cause over the next decade. The results reveal that among people of the same age and gender, fitness level as measured by METs and peak heart rate reached during exercise were the greatest indicators of death risk. Fitness level was the single most powerful predictor of death and survival, even after researchers accounted for other important variables such as diabetes and family history of premature death -- a finding that underscores the profound importance of heart and lung fitness, the investigators say.

Scores ranged from negative 200 to positive 200, with those above 0 having lower mortality risk and those in the negative range facing highest risk of dying. Patients who scored 100 or higher had a 2 percent risk of dying over the next 10 years, while those with scores between 0 and 100 faced a 3 percent death risk over the next decade. In other words, two of 100 people of the same age and gender with a score of 100 or higher would die over the next decade, compared with three out of 100 for those with a fitness score between 0 and 100. People with scores between negative 100 and 0 had an 11 percent risk of dying in the next 10 years, while those with scores lower than negative 100 had a 38 percent risk of dying.

Published along with the study is a chart depicting death risk by age, gender and fitness level, which can be printed on placards for use in physician's offices to guide clinical advice.

For example, a 45-year-old woman with a fitness score in the bottom fifth percentile is estimated to have a 38 percent risk of dying over the next decade, compared with 2 percent for a 45-year-old woman with a top fitness score.
"We hope that illustrating risk that way could become a catalyst for patients to increase exercise and improve cardiovascular fitness," Blaha says.

Other Johns Hopkins investigators involved in the research included John McEvoy, Roger Blumenthal and Steven Jones.
Researchers from other institutions included Mouaz Al-Mallah, Clinton Brawner and Steven Keteyian of Henry Ford Hospital in Detroit and Khurram Nasir of Baptist Health Medical Group in Miami Beach, Fla.

Source: Johns Hopkins Medicine

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Stars found far from galaxy center - Nasa

The newfound young star clusters lie thousands of light-years below the plane of our Milky Way galaxy, a flat spiral disk seen in this artist's conception. If alien lifeforms were to develop on planets orbiting these stars, they would have views of a portion, or all, of the galactic disk. Credit: NASA/JPL-Caltech

Astronomers using data from NASA's Wide-field Infrared Survey Explorer, or WISE, have found a cluster of stars forming at the very edge of our Milky Way galaxy.

"A stellar nursery in what seems to be the middle of nowhere is quite surprising," said Peter Eisenhardt, the project scientist for the WISE mission at NASA's Jet Propulsion Laboratory in Pasadena, California. "But surprises turn up when you look everywhere, as the WISE survey did."
The discovery, led by Denilso Camargo of the Federal University of Rio Grande do Sul in Porto Alegre, Brazil, appears in a new study in the journal Monthly Notices of the Royal Astronomical Society.

The Milky Way, the galaxy we live in, has a barred spiral shape, with arms of stars, gas and dust winding out from a central bar. Viewed from the side, the galaxy would appear relatively flat, with most of the material in a disk and the central regions.

Using infrared survey images from WISE, the team discovered two clusters of stars thousands of light-years below the galactic disk. The stars live in dense clumps of gas called giant molecular clouds.

This is the first time astronomers have found stars being born in such a remote location. Clouds of star-forming material at very high latitudes away from the galactic plane are rare and, in general, are not expected to form stars.

"Our work shows that the space around the galaxy is a lot less empty that we thought," said Camargo. "The new clusters of stars are truly exotic. In a few million years, any inhabitants of planets around the stars will have a grand view of the outside of the Milky Way, something no human being will probably ever experience."

To learn more about the discovery, and what might have caused the stars to form at the edge of our galaxy, read the Royal Astronomical Society news release.

JPL managed and operated WISE for NASA's Science Mission Directorate. The spacecraft was put into hibernation mode in 2011, after it scanned the entire sky twice, completing its main objectives. Edward Wright was the principal investigator and is at UCLA. In September 2013, the WISE spacecraft was reactivated, renamed NEOWISE and assigned a new mission to assist NASA's efforts to identify the population of potentially hazardous near-Earth objects. Science operations and data processing take place at the Infrared Processing and Analysis Center at the California Institute of Technology in Pasadena.

The WISE mission was selected competitively under NASA's Explorers Program managed by the agency's Goddard Space Flight Center in Greenbelt, Maryland. The science instrument was built by the Space Dynamics Laboratory in Logan, Utah. The spacecraft was built by Ball Aerospace & Technologies Corp. in Boulder, Colorado. Caltech manages JPL for NASA.

Source: NASA/Jet Propulsion Laboratory

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Beliefs can regulate effects of nicotine on the human brain

Two identical cigarettes led to a new discovery. Study participants inhaled nicotine, yet they showed significantly different brain activity. Why the difference? Some subjects were told their cigarettes were nicotine free. Credit: © Nomad_Soul / Fotolia
Two identical cigarettes led to a discovery by scientists at the Virginia Tech Carilion Research Institute. Study participants inhaled nicotine, yet they showed significantly different brain activity. Why the difference? Some subjects were told their cigarettes were nicotine free.

"Our research group has begun to show that beliefs are as powerful a physical influence on the brain as neuroactive drugs," said Read Montague, director of the Computational Psychiatry Unit at the Virginia Tech Carilion Research Institute and lead author of a study published this week in the Proceedings of the National Academy of Sciences.

Nicotine has formidable effects throughout the brain, especially in the reward-based learning pathways. Nicotine teaches the brain that smoking leads to reward. Once the brain learns that correlation, the addictive chemical cycle is difficult to break. In this study, scientists tracked the brain responses using functional magnetic resonance imaging.

"We suspected that we would be able to see neural signals based on the subjects' belief rather than their actual nicotine intake," said Montague, who is also a professor of physics in Virginia Tech's College of Science.

After smoking cigarettes, volunteers played a reward-based learning game while their brains were scanned. The subjects viewed a historical stock price graph, made an investment, and repeated the cycle multiple times.

Researchers used computational models of learning signals thought to be generated by the brain during these kinds of tasks. In each subject, the individually tracked signals were specifically influenced by beliefs about nicotine.

Montague and his team found that the people who believed they had smoked nicotine cigarettes made different choices and had different neural signals than the other participants, despite the fact that both groups had consumed the same substance.

The scientists also found people who believed they had smoked nicotine had significantly higher activity in their reward-learning pathways. Those who did not believe they had smoked nicotine did not exhibit those same signals.

"It was the belief alone that modulated activity in the learning pathway," Montague said. "This goes beyond the placebo effect."

Multiple studies support the placebo effect, showing sham treatments can improve a patient's condition simply because the person believed it would be helpful. In the current study, however, researchers found belief alone could actually erase or enhance the effects of nicotine in participants who were under the influence of the active drug.

The study was featured in an editorial commentary by Nora Volkow, director of the National Institute on Drug Abuse, in the Proceedings of the National Academy of Sciences.

"The current findings extend the relevance of dopamine-guided learning processes to the experience of how drug intoxication influences the way the human brain works and orchestrates our behaviors," Volkow wrote in the commentary.

Volkow suggested previously shrouded mechanisms behind beliefs and learned responses could be manipulated as a target for new addiction treatments.

"Nothing is more convincing than how a drug can make you feel differently," Montague said. "A drug can induce a belief state, which itself causes the change."

Scientists might be able to harness this belief system, capable of inducing physiological changes, to reverse-engineer addiction.

"Just as drugs micromanage the belief state," Montague said, "maybe we can micromanage beliefs to better effect behavior change in addiction."

Source: Virginia Tech

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Genetically speaking, mammals are more like their fathers

Newborn baby and his father's hand. Specifically, the research shows that although we inherit equal amounts of genetic mutations from our parents -- the mutations that make us who we are and not some other person -- we actually "use" more of the DNA that we inherit from our dads. Credit: © millaf / Fotolia

You might resemble or act more like your mother, but a novel research study from UNC School of Medicine researchers reveals that mammals are genetically more like their dads. Specifically, the research shows that although we inherit equal amounts of genetic mutations from our parents -- the mutations that make us who we are and not some other person -- we actually "use" more of the DNA that we inherit from our dads.

The research, published in the journal Nature Genetics, has wide implications for the study of human disease, especially when using mammalian research models. For instance, in many mouse models created for the study of gene expression related to disease, researchers typically don't take into account whether specific genetic expression originates from mothers or fathers. But the UNC research shows that inheriting a mutation has different consequences in mammals, depending on whether the genetic variant is inherited from the mother or father.

"This is an exceptional new research finding that opens the door to an entirely new area of exploration in human genetics," said Fernando Pardo-Manuel de Villena, PhD, professor of genetics and senior author of the paper. "We've known that there are 95 genes that are subject to this parent-of-origin effect. They're called imprinted genes, and they can play roles in diseases, depending on whether the genetic mutation came from the father or the mother. Now we've found that in addition to them, there are thousands of other genes that have a novel parent-of-origin effect."

These genetic mutations that are handed down from parents show up in many common but complex diseases that involve many genes, such as type-2 diabetes, heart disease, schizophrenia, obesity, and cancers. Studying them in genetically diverse mouse models that take parent-of-origin into account will give scientists more precise insights into the underlying causes of disease and the creation of therapeutics or other interventions.

The key to this research is the Collaborative Cross -- the most genetically diverse mouse population in the world, which is generated, housed, and distributed from UNC. Traditional lab mice are much more limited in their genetic diversity, and so they have limited use in studies that try to home in on important aspects of diseases in humans. The Collaborative Cross bred together various wild type mice to create wide diversity in the mouse genome. Pardo-Manuel de Villena said that this diversity is comparable to the variation found in the human genome. This helps scientists study diseases that involve various levels of genetic expression across many different genes.

Gene expression connects DNA to proteins, which then carry out various functions inside cells. This process is crucial for proper human health. Mutations that alter gene expression are called regulatory mutations.

"This type of genetic variation is probably the most important contributor -- not to simple Mendelian diseases where there's just one gene mutation [such as cystic fibrosis] -- but to much more common and complex diseases, such as diabetes, heart disease, neurological conditions, and a host of others," Pardo-Manuel de Villena said. "These diseases are driven by gene expression, not of one gene but of hundreds or thousands of genes.

"The Collaborative Cross and the expertise we have at UNC allow us to look at different gene expression for every gene in the genome of every kind of tissue," said Pardo-Manuel de Villena, who directs the Collaborative Cross.

For the Nature Genetics study, Pardo-Manuel de Villena's team, including first author James Crowley, PhD, assistant professor of genetics, selected three genetically diverse inbred strains of mice that were descended from a subspecies that evolved on different continents. These mice were bred to create nine different types of hybrid offspring in which each strain was used as both father and mother. When the mice reached adulthood, the researchers measured gene expression in four different kinds of tissue, including RNA sequencing in the brain. They then quantified how much gene expression was derived from the mother and the father for every single gene in the genome.

"We found that the vast majority of genes -- about 80 percent -- possessed variants that altered gene expression," Crowley said. "And this was when we discovered a new, genome-wide expression imbalance in favor of the dad in several hundred genes. This imbalance resulted in offspring whose brain gene expression was significantly more like their father's."

For every gene a scientist is interested in, Pardo-Manuel de Villena's team can create mice that have low, intermediate, or high expression of genes. And they can explore if that expression is associated with a specific disease.

"This expression level is dependent on the mother or the father," Pardo-Manuel de Villena said. "We now know that mammals express more genetic variance from the father. So imagine that a certain kind of mutation is bad. If inherited from the mother, the gene wouldn't be expressed as much as it would be if it were inherited from the father. So, the same bad mutation would have different consequences in disease if it were inherited from the mother or from the father."

These types of genetic mutations across hundreds of genes are hard to study and a major bottleneck to realizing the promises of the post-genome era. But Pardo-Manuel de Villena said, "Thanks to the Collaborative Cross, the mouse can be used to model how these genes work and how they impact health and disease in any kind of tissue in the body."

Source: University of North Carolina Health Care

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Old-looking galaxy in a young universe: Astronomers find dust in the early universe

This spectacular view from the NASA/ESA Hubble Space Telescope shows the rich galaxy cluster Abell 1689. The huge concentration of mass bends light coming from more distant objects and can increase their total apparent brightness and make them visible. One such object, A1689-zD1, is located in the box -- although it is still so faint that it is barely seen in this picture. New observations with ALMA and ESO's VLT have revealed that this object is a dusty galaxy seen when the Universe was just 700 million years old.  Credit: NASA; ESA; L. Bradley (Johns Hopkins University); R. Bouwens (University of California, Santa Cruz); H. Ford (Johns Hopkins University); and G. Illingworth (University of California, Santa Cruz)

Dust plays an extremely important role in the universe -- both in the formation of planets and new stars. But dust was not there from the beginning and the earliest galaxies had no dust, only gas. Now an international team of astronomers, led by researchers from the Niels Bohr Institute, has discovered a dust-filled galaxy from the very early universe. The discovery demonstrates that galaxies were very quickly enriched with dust particles containing elements such as carbon and oxygen, which could form planets. The results are published in the scientific journal, Nature.

Cosmic dust are smoke-like particles made up of either carbon (fine soot) or silicates (fine sand). The dust is comprised primarily of elements such as carbon, silicon, magnesium, iron and oxygen. The elements are synthesised by the nuclear combustion process in stars and driven out into space when the star dies and explodes. In space, they gather in clouds of dust and gas, which form new stars, and for each generation of new stars, more elements are formed. This is a slow process and in the very earliest galaxies in the history of the universe, dust had not yet formed.

But now a team of researchers have discovered a very distant galaxy that contains a large amount of dust, changing astronomers' previous calculations of how quickly the dust was formed.

"It is the first time dust has been discovered in one of the most distant galaxies ever observed -- only 700 million years after the Big Bang. It is a galaxy of modest size and yet it is already full of dust. This is very surprising and it tells us that ordinary galaxies were enriched with heavier elements far faster than expected," explains Darach Watson, an astrophysicist with the Dark Cosmology Centre at the Niels Bohr Institute at the University of Copenhagen.

Darach Watson led the project, with Lise Christensen from the Dark Cosmology Centre and researchers from Sweden, Scotland, France and Italy.

Lucky location

Because the galaxy is very distant and therefore incredibly faint, it would not usually be detectable from Earth. But a fortunate circumstance means the light from it has been amplified. This is because a large cluster of galaxies called Abell 1689, lies between the galaxy and Earth. The light is refracted by the gravity of the galaxy cluster, thus amplifying the distant galaxy. The phenomenon is called gravitational lensing and it works like a magnifying glass.

"We looked for the most distant galaxies in the universe. Based on the colours of the light observed with the Hubble Space Telescope we can see which galaxies could be very distant. Using observations from the very sensitive instrument, the X-shooter spectrograph on the Large Telescope, VLT in Chile, we measured the galaxy's spectrum and from that calculated its redshift, i.e. the change in the light's wavelength as the object recedes from us. From the redshift we can calculate the galaxy's distance from us and it turned out to be, as we suspected, one of the most distant galaxies we know of to date," explains Lise Christensen, an astrophysicist at the Dark Cosmology Centre at the Niels Bohr Institute.

Early planet formation

Darach Watson explains that they then studied the galaxy with the ALMA telescopes, which can observe far-infrared wavelengths and then it became really interesting, because now they could see that the galaxy was full of dust. He explains that young stars in early galaxies emit hot ultraviolet light. The hot ultraviolet radiation heats the surrounding ice-cold dust, which then emits light in the far-infrared.

"It is this far-infrared light, which tells us that there is dust in the galaxy. It is very surprising and it is the first time that dust has been found in such an early galaxy. The process of star formation must therefore have started very early in the history of the universe and be associated with the formation of dust. The detection of large amounts of solid material shows that the galaxy was enriched very early with solids which are a prerequisite for the formation of complex molecules and planets," explains Darach Watson.

Now the researchers hope that future observations of a large number of distant galaxies using the ALMA telescopes could help unravel how frequently such evolved galaxies occur in this very early epoch of the history of the universe.

Source: University of Copenhagen - Niels Bohr Institute

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