Children with HIV/AIDS falling through the cracks of treatment scale-up efforts

ScienceDaily (Dec. 1, 2011) — Less than one-quarter (23%) of children with HIV/AIDS who need treatment are getting it, according to a report released by the World Health Organization (WHO) on the occasion of World AIDS Day (1 December 2011). Although treatment coverage for adults has been steadily climbing and has now reached approximately half of those in need, coverage for children is lagging far behind, highlighted the Drugs for Neglected Diseases initiative (DNDi), a non-profit research and development organization that has recently launched a new paediatric HIV drug development programme.

'Children with HIV/AIDS are falling through the cracks', said Dr Bernard Pécoul, Executive Director of the DNDi. '250,000 children died of HIV-related complications in 2010 -- that's nearly 700 each day. This is simply unacceptable.'

There are several reasons for this situation -- including lack of access for pregnant women to antenatal care, HIV testing, and antiretrovirals (ARVs) to prevent mother-to-child transmission and treat expecting mothers, as well as difficulties diagnosing HIV in infants. But one of the most important, and overlooked, is the lack of suitable formulations of ARVs adapted for children, particularly babies and toddlers. The reason for this neglect lies, ironically, with the success of the virtual elimination of HIV among newborns in wealthy countries.

'There's little profit to be made from developing treatments for the millions of children with HIV/AIDS, 90% of whom are the poorest of the poor in sub-Saharan Africa, and the lack of market incentive means pharmaceutical companies do not develop ARVs adapted to their needs', Dr Pécoul continued. 'Without treatment, half of the children born with HIV die before their second birthday.'

WHO recommends immediate ART for all HIV-positive children less than two years old, but the safety and correct dosing have not been established in very young children for the majority of ARVs approved for adults. In addition, key existing paediatric ARV formulations taste bad, require impractical multiple liquid preparations and refrigeration, and have undesirable interactions with tuberculosis (TB) drugs.

DNDi's new paediatric HIV programme aims to develop an improved first-line therapy for children under three years of age. Ideally, this ARV combination therapy needs to be easy to administer and better tolerated by children than current drugs, as well as heat stable and easily dispersible (dissolvable in water or breast milk). It must also carry minimal risk for developing resistance and require minimum weight adjustments. Finally, any new formulations must be compatible with TB drugs.

'Given the current funding crisis, we are deeply concerned that children with HIV/AIDS -- who are already invisible and largely voiceless -- will fall even further down on the agenda', said Dr Marc Lallemant, Head of DNDi's Paediatric HIV Programme. 'And while everything possible needs to be done to achieve the long-term goal of "eliminating" new infections among infants, including through scale-up of prevention of mother-to-child transmission programmes, a more serious response is urgently needed for HIV-positive children today.'

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Earthquake friction effect demonstrated at the nanoscale

ScienceDaily (Nov. 30, 2011) — Earthquakes are some of the most daunting natural disasters that scientists try to analyze. Though Earth's major fault lines are well known, there is little scientists can do to predict when an earthquake will occur or how strong it will be. And, though earthquakes involve millions of tons of rock, a team of University of Pennsylvania and Brown University researchers has helped discover an aspect of friction on the nanoscale that may lead to a better understanding of the disasters.

Robert Carpick, a professor who chairs the Department of Mechanical Engineering and Applied Mechanics in Penn's School of Engineering and Applied Science, led the research in collaboration with Terry Tullis and David Goldsby, professors of geological science at Brown. The experimental and modeling work was conducted by first author Qunyang Li, a postdoctoral researcher in Carpick's group, who has recently been appointed an associate professor in the School of Aerospace at Tsinghua University, China.

Their work will be published in the journal Nature.

The team's research was spurred by an unusual phenomenon that has been observed in both natural and laboratory-simulated faults: materials become more resistant to sliding the longer they are in contact with one another. This trait is actually fundamental to why earthquakes happen at all. The longer materials are in contact, the stronger the resistance between them and the more violent and unstable the subsequent sliding is. Energy is stored over the time the materials are in contact and is then catastrophically released as an earthquake.

While geologists, physicists and mechanics researchers have studied this phenomenon for decades, the mechanism behind this increase of friction over time has only been hypothesized. There are two main theories as to why this "frictional aging" occurs.

"One hypothesis is that points of contact deform and grow over time -- that contact quantity increases," Carpick said. "The other is that bonding at the points of contact strengthens over time -- that contact quality increases."

The difficulty in proving that either theory holds true lies in the fact that points of contact are necessarily embedded at the juncture of two materials and are therefore hard to observe. One of the original breakthrough experiments on these theories projected light through transparent materials held together to measure the growth of apparent contact points. While this lent credence to the contact quantity theory, there was not yet a way to assess the bond strengths at those individual points of contacts or to be sure that the observations were of single points of contacts or clusters of even smaller nanoscale contacts.

It was not until Carpick and Tullis met at a conference designed to bring physicists and mechanics researchers together with geologists that they realized that the tools of the former group could resolve the latter group's contact quality theory. The solution came from moving from the massive scale of earthquakes to the smallest scales imaginable.

"We want to simplify the case," Li said. "So in our experiment we look at only one point of contact: the tip of an atomic force microscope."

An atomic force microscope is an ideal tool for investigating bonding strength where two surfaces meet. Instead of using light, atomic force microscopes measure nanoscale details using an extremely sharp probe tip that is sensitive to the push and pull of individual atoms.

The researchers simulated rock-on-rock contact with silica, a major component in most geological materials. They pressed a silica tip against a silica surface for different lengths of time and then dragged it to measure the amount of friction it experienced. They repeated these experiments with surfaces made out of different materials: diamond and graphite. Critically, both diamond and graphite are chemically inert. As they don't easily form chemical bonds with silica, any frictional aging that occurred with them would necessarily be due to changing contact area and not increased bond strength.

The results showed a stark difference in the frictional aging between the materials.

"We saw a huge amount of aging with silica on silica. But with silica on diamond or graphite, even though the tip is experiencing about the same stress levels, we see almost no aging," Li said. "If the increasing contact area was responsible for the increase in frictional aging, you would see similar amounts in these cases. You might even see more aging with diamond because it is stiffer, leading to a slightly higher stress level in the silica, and this would cause more deformation on the tip."

The frictional aging seen in the silica-on-silica experiment was so intense that the researchers had another mystery on their hands: how to reconcile strong aging on the nanoscale with the weaker level seen on the macroscale where earthquakes actually occur.

The solution to that puzzle stems from the fact that not all contact points are created equal. Two different contact points on the same surface that are close to one another will sense each other's presence. This "elastic coupling," as it is known, means that only a few of the contact points within an area will be resisting the sliding motion at their full capacity; some will have started to slide earlier, and others will slide later. It is too difficult to make them all slide at once.

So, the overall level of resistance relies not only on the maximum resistance any contact point can provide, but also on the small fraction of contact points able to provide this resistance.

"When you take a lot of contact points,"Carpick said, "all of them could have this large amount of aging. But when you try to shear them, you see only a small fraction reach that very high value of friction at any given time. So, you need a very large effect on the level of a single contact point to get even a very modest effect on the macroscopic scale."

While showing that nansocale experiment can provide useful data for these kinds of applications was in itself an important finding for the research team, the ability to reconcile the laboratory data with geologists' observations will have a lasting effect on the field.

"If we can understand the fundamental physics," Tullis said, "then theories and equations based on that physics would have the capability of being extrapolated beyond the laboratory scale. Therefore we could use them with more confidence in all the earthquake modeling that's already being done."

"We're not ruling out the quantity argument, we're just ruling in the quality argument," Carpick said. "Future research will go to higher stress levels, where maybe contact quantity could start to come into play. We'd also like to look at different temperatures, which matter in the geological context, and do experiments where we can actually watch the contact in real time, using an electron microscope."

The research was supported by the National Science Foundation.

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Journal Reference:

Qunyang Li, Terry E. Tullis, David Goldsby, Robert W. Carpick. Frictional ageing from interfacial bonding and the origins of rate and state friction. Nature, 2011; DOI: 10.1038/nature10589

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Biologists deliver neutralizing antibodies that protect against HIV infection in mice

ScienceDaily (Nov. 30, 2011) — Over the past year, researchers at the California Institute of Technology (Caltech), and around the world, have been studying a group of potent antibodies that have the ability to neutralize HIV in the lab; their hope is that they may learn how to create a vaccine that makes antibodies with similar properties. Now, biologists at Caltech led by Nobel Laureate David Baltimore, president emeritus and Robert Andrews Millikan Professor of Biology, have taken one step closer to that goal: they have developed a way to deliver these antibodies to mice and, in so doing, have effectively protected them from HIV infection.

This new approach to HIV prevention -- called Vectored ImmunoProphylaxis, or VIP -- is outlined in the November 30 advance online publication of the journal Nature.

Traditional efforts to develop a vaccine against HIV have been centered on designing substances that provoke an effective immune response -- either in the form of antibodies to block infection or T cells that attack infected cells. With VIP, protective antibodies are being provided up front.

"VIP has a similar effect to a vaccine, but without ever calling on the immune system to do any of the work," says Alejandro Balazs, lead author of the study and a postdoctoral scholar in Baltimore's lab. "Normally, you put an antigen or killed bacteria or something into the body, and the immune system figures out how to make an antibody against it. We've taken that whole part out of the equation."

Because mice are not sensitive to HIV, the researchers used specialized mice carrying human immune cells that are able to grow HIV. They utilized an adeno-associated virus (AAV) -- a small, harmless virus that has been useful in gene-therapy trials -- as a carrier to deliver genes that are able to specify antibody production. The AAV was injected into the leg muscle of mice, and the muscle cells then put broadly neutralizing antibodies into the animals' circulatory systems. After just a single AAV injection, the mice produced high concentrations of these antibodies for the rest of their lives, as shown by intermittent sampling of their blood. Remarkably, these antibodies protected the mice from infection when the researchers exposed them to HIV intravenously.

The team points out that the leap from mice to humans is large -- the fact that the approach works in mice does not necessarily mean it will be successful in humans. Still, the researchers believe that the large amounts of antibodies that the mice were able to produce -- coupled with the finding that a relatively small amount of antibody has proved protective in the mice -- may translate into human protection against HIV infection.

"We're not promising that we've actually solved the human problem," says Baltimore. "But the evidence for prevention in these mice is very clear."

The paper also notes that in the mouse model, VIP worked even in the face of increased exposure to HIV. To test the efficacy of the antibody, the researchers started with a virus dose of one nanogram, which was enough to infect the majority of the mice who received it. When they saw that the mice given VIP could withstand that dose, they continued to bump it up until they were challenging them with 125 nanograms of virus.

"We expected that at some dose, the antibodies would fail to protect the mice, but it never did -- even when we gave mice 100 times more HIV than would be needed to infect 7 out of 8 mice," says Balazs. "All of the exposures in this work were significantly larger than a human being would be likely to encounter."

He points out that this outcome likely had more to do with the properties of the antibody that was tested than the method, but adds that VIP is what enabled the large amount of this powerful antibody to circulate through the mice and fight the virus. Furthermore, VIP is a platform technique, meaning that as more potent neutralizing antibodies are isolated or developed for HIV or other infectious organisms, they can also be delivered using this method.

"If humans are like mice, then we have devised a way to protect against the transmission of HIV from person to person," says Baltimore. "But that is a huge if, and so the next step is to try to find out whether humans behave like mice."

He says the team is currently in the process of developing a plan to test their method in human clinical trials. The initial tests will ask whether the AAV vector can program the muscle of humans to make levels of antibody that would be expected to be protective against HIV.

"In typical vaccine studies, those inoculated usually mount an immune response -- you just don't know if it's going to work to fight the virus," explains Balazs. "In this case, because we already know that the antibodies work, my opinion is that if we can induce production of sufficient antibody in people, then the odds that VIP will be successful are actually pretty high."

The study, "Antibody-based Protection Against HIV Infection by Vectored ImmunoProphylaxis," was funded by the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Caltech-UCLA Joint Center for Translational Medicine. Caltech biology researchers Joyce Chen, Christin M. Hong, and Lili Yang also contributed to the paper, as well as Dinesh Rao, a hematologist from the University of California, Los Angeles.

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Journal Reference:

Alejandro B. Balazs, Joyce Chen, Christin M. Hong, Dinesh S. Rao, Lili Yang, David Baltimore. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature, 2011; DOI: 10.1038/nature10660

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New revolutionary material can be worked like glass

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Galaxies are the ultimate recyclers, NASA's Hubble confirms

ScienceDaily (Nov. 17, 2011) — Galaxies learned to "go green" early in the history of the universe, continuously recycling immense volumes of hydrogen gas and heavy elements to build successive generations of stars stretching over billions of years.

This ongoing recycling keeps galaxies from emptying their "fuel tanks" and therefore stretches out their star-forming epoch to over 10 billion years. However, galaxies that ignite a rapid firestorm of star birth can blow away their remaining fuel, essentially turning off further star-birth activity.

This conclusion is based on a series of Hubble Space Telescope observations that flexed the special capabilities of its comparatively new Cosmic Origins Spectrograph (COS) to detect otherwise invisible mass in the halo of our Milky Way and a sample of more than 40 other galaxies. Data from large ground-based telescopes in Hawaii, Arizona, and Chile also contributed to the studies by measuring the properties of the galaxies.

This invisible mass is made up of normal matter -- hydrogen, helium, and heavier elements such as carbon, oxygen, nitrogen, and neon -- as opposed to dark matter that is an unknown exotic particle pervading space.

The results are being published in three papers in the November 18 issue of Science magazine. The leaders of the three studies are Nicolas Lehner of the University of Notre Dame in South Bend, Ind.; Jason Tumlinson of the Space Telescope Science Institute in Baltimore, Md.; and Todd Tripp of the University of Massachusetts at Amherst.

The Key Findings

The color and shape of a galaxy is largely controlled by gas flowing through an extended halo around it. All modern simulations of galaxy formation find that they cannot explain the observed properties of galaxies without modeling the complex accretion and "feedback" processes by which galaxies acquire gas and then later expel it after processing by stars. The three studies investigated different aspects of the gas-recycling phenomenon.

"Our results confirm a theoretical suspicion that galaxies expel and can recycle their gas, but they also present a fresh challenge to theoretical models to understand these gas flows and integrate them with the overall picture of galaxy formation," Tumlinson says.

The team used COS observations of distant stars to demonstrate that a large mass of clouds is falling through the giant corona halo of our Milky Way, fueling its ongoing star formation. These clouds of ionized hydrogen reside within 20,000 light-years of the Milky Way disk and contain enough material to make 100 million suns. Some of this gas is recycled material that is continually being replenished by star formation and the explosive energy of novae and supernovae, which kicks chemically enriched gas back into the halo; the remainder is gas being accreted for the first time. The infalling gas from this vast reservoir fuels the Milky Way with the equivalent of about a solar mass per year, which is comparable to the rate at which our galaxy makes stars. At this rate the Milky Way will continue making stars for another billion years by recycling gas into the halo and back onto the galaxy. "We now know where is the missing fuel for galactic star formation," Lehner concludes. "We now have to find out its birthplace."

One goal of the studies was to study how other galaxies like our Milky Way accrete mass for star making. But instead of widespread accretion, the team found nearly ubiquitous halos of hot gas surrounding vigorous star-forming galaxies. These galaxy halos, rich in heavy elements, extend as much as 450,000 light-years beyond the visible portions of their galactic disks. The surprise was discovering how much mass in heavy elements is far outside a galaxy. COS measured 10 million solar masses of oxygen in a galaxy's halo, which corresponds to about 1 billion solar masses of gas -- as much as in the entire interstellar medium between stars in a galaxy's disk. They also found that this gas is nearly absent from galaxies that have stopped forming stars. This is evidence that widespread outflows, rather than accretion, determine a galaxy's fate. "We didn't know how much mass was there in these gas halos, because we couldn't do these observations until we had COS," Tumlinson says. "This stuff is a huge component of galaxies but can't be seen in any images."

He points out that because so much of the heavy elements has been ejected into the halos instead of sticking around in the galaxies, the formation of planets, life, and other things requiring heavy elements could have been delayed in these galaxies.

The COS data also demonstrate that those galaxies forming stars at a very rapid rate, perhaps a hundred solar masses per year, can drive 2-million-degree gas very far out into intergalactic space at speeds of up to 2 million miles per hour. That's fast enough for the gas to escape forever and never refuel the parent galaxy. While hot plasma "winds" from galaxies have been known for some time, the new COS observations reveal that hot outflows extend to much greater distances than previously thought and can carry a tremendous amount of mass out of a galaxy. Some of the hot gas is moving more slowly and could eventually be recycled. The Hubble observations show how gas-rich star-forming spiral galaxies can evolve to quiescent elliptical galaxies that no longer have star formation. "So not only have we found that star-forming galaxies are pervasively surrounded by large halos of hot gas," says Tripp, "we have also observed that hot gas in transit -- we have caught the stuff in the process of moving out of a galaxy and into intergalactic space."

The light emitted by this hot plasma is invisible, so the researchers used COS to detect the presence of the gas by the way it absorbs certain colors of light from background quasars. The brightest objects in the universe, quasars are the brilliant cores of active galaxies that contain rapidly accreting supermassive black holes. The quasars serve as distant lighthouse beacons that shine through the gas-rich "fog" of hot plasma encircling galaxies. At ultraviolet wavelengths, COS is sensitive to absorption from many ionized heavy elements, such as nitrogen, oxygen, and neon. COS's high sensitivity allows many galaxies that happen to lie in front of the much more distant quasars to be studied. The ionized heavy elements serve as proxies for estimating how much mass is in a galaxy's halo.

"Only with COS can we now address some of the most crucial questions that are at the forefront of extragalactic astrophysics," Tumlinson says.

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Journal References:

T. M. Tripp, J. D. Meiring, J. X. Prochaska, C. N. A. Willmer, J. C. Howk, J. K. Werk, E. B. Jenkins, D. V. Bowen, N. Lehner, K. R. Sembach, C. Thom, J. Tumlinson. The Hidden Mass and Large Spatial Extent of a Post-Starburst Galaxy Outflow. Science, 2011; 334 (6058): 952 DOI: 10.1126/science.1209850N. Lehner, J. C. Howk. A Reservoir of Ionized Gas in the Galactic Halo to Sustain Star Formation in the Milky Way. Science, 2011; 334 (6058): 955 DOI: 10.1126/science.1209069J. Tumlinson, C. Thom, J. K. Werk, J. X. Prochaska, T. M. Tripp, D. H. Weinberg, M. S. Peeples, J. M. O'Meara, B. D. Oppenheimer, J. D. Meiring, N. S. Katz, R. Dave, A. B. Ford, K. R. Sembach. The Large, Oxygen-Rich Halos of Star-Forming Galaxies Are a Major Reservoir of Galactic Metals. Science, 2011; 334 (6058): 948 DOI: 10.1126/science.1209840

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Training in 'concrete thinking' can be self-help treatment for depression, study suggests

ScienceDaily (Nov. 17, 2011) — New research provides the first evidence that depression can be treated by only targeting an individual's style of thinking through repeated mental exercises in an approach called cognitive bias modification.

The study suggests an innovative psychological treatment called 'concreteness training' can reduce depression in just two months and could work as a self-help therapy for depression in primary care.

Led by the University of Exeter and funded by the Medical Research Council, the research shows how this new treatment could help some of the 3.5 million people in the UK living with depression.

People suffering from depression have a tendency towards unhelpful abstract thinking and over-general negative thoughts, such as viewing a single mistake as evidence that they are useless at everything. Concreteness training (CNT) is a novel and unique treatment approach that attempts to directly target this tendency. Repeated practice of CNT exercises can help people to shift their thinking style.

CNT teaches people how to be more specific when reflecting on problems. This can help them to keep difficulties in perspective, improve problem-solving and reduce worry, brooding, and depressed mood. This study provided the first formal test of this treatment for depression in the NHS.

121 individuals who were currently experiencing an episode of depression were recruited from GP practices. They took part in the clinical trial and were randomly allocated into three groups. A third received their usual treatment from their GP, plus CNT, while some were offered relaxation training in addition to their usual treatment and the remainder simply continued their usual treatment. All participants were assessed by the research team after two months and then three and six months later to see what progress they had made.

The CNT involved the participants undertaking a daily exercise in which they focused on a recent event that they had found mildly to moderately upsetting. They did this initially with a therapist and then alone using an audio CD that provided guided instructions. They worked through standardised steps and a series of exercises to focus on the specific details of that event and to identify how they might have influenced the outcome.

CNT significantly reduced symptoms of depression and anxiety, on average reducing symptoms from severe depression to mild depression during the first two months and maintaining this effect over the following three and six months. On average, those individuals who simply continued with their usual treatment remained severely depressed.

Although concreteness training and relaxation training both significantly reduced depression and anxiety, only concreteness training reduced the negative thinking typically found in depression. Moreover, for those participants who practised it enough to ensure it became a habit, CNT reduced symptoms of depression more than relaxation training.

Professor Edward Watkins of the University of Exeter said: "This is the first demonstration that just targeting thinking style can be an effective means of tackling depression. Concreteness training can be delivered with minimal face-to-face contact with a therapist and training could be accessed online, through CDs or through smartphone apps. This has the advantage of making it a relatively cheap form of treatment that could be accessed by large numbers of people. This is a major priority in depression treatment and research, because of the high prevalence and global burden of depression, for which we need widely available cost-effective interventions."

The researchers are now calling for larger effectiveness clinical trials so that the feasibility of CNT as part of the NHS's treatment for depression can be assessed.

Published in the journal Psychological Medicine, this study was carried out by a team from the Mood Disorders Centre, which is a partnership between the NHS and the University of Exeter and the Peninsula College of Medicine and Dentistry, a joint entity of the Universities of Exeter and Plymouth and the NHS in the South West.

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Great Plains river basins threatened by pumping of aquifers

ScienceDaily (Nov. 18, 2011) — Suitable habitat for native fishes in many Great Plains streams has been significantly reduced by the pumping of groundwater from the High Plains aquifer -- and scientists analyzing the water loss say ecological futures for these fishes are "bleak."

Results of their study have been published in the journal Ecohydrology.

Unlike alluvial aquifers, which can be replenished seasonally with rain and snow, these regional aquifers were filled by melting glaciers during the last Ice Age, the researchers say. When that water is gone, it won't come back -- at least, until another Ice Age comes along.

"It is a finite resource that is not being recharged," said Jeffrey Falke, a post-doctoral researcher at Oregon State University and lead author on the study. "That water has been there for thousands of years, and it is rapidly being depleted. Already, streams that used to run year-round are becoming seasonal, and refuge habitats for native fishes are drying up and becoming increasingly fragmented."

Falke and his colleagues, all scientists from Colorado State University where he earned his Ph.D., spent three years studying the Arikaree River in eastern Colorado. They conducted monthly low-altitude flights over the river to map refuge pool habitats and connectivity, and compared it to historical data.

They conclude that during the next 35 years -- under the most optimistic of circumstances -- only 57 percent of the current refuge pools would remain -- and almost all of those would be isolated in a single mile-long stretch of the Arikaree River. Water levels today already are significantly lower than they were 40 and 50 years ago.

Though their study focused on the Arikaree, other dryland streams in the western Great Plains -- composed of eastern Colorado, western Nebraska and western Kansas -- face the same fate, the researchers say.

Falke said the draining of the regional aquifers lowers the groundwater input to alluvial aquifers through which the rivers flow, creating the reduction in streamflow. He and his colleagues estimate that it would require a 75 percent reduction in the rate of groundwater pumping to maintain current water table levels and refuge pools, which is "not economically or politically feasible," the authors note in the study.

Dryland streams in the Great Plains host several warm-water native fish species that have adapted over time to harsh conditions, according to Falke, who is with the Department of Fisheries and Wildlife at Oregon State University. Brassy minnows, orange-throat darters and other species can withstand water temperatures reaching 90 degrees, as well as low levels of dissolved oxygen, but the increasing fragmentation of their habitats may impede their life cycle, limiting the ability of the fish to recolonize.

"The Arikaree River and most dryland streams are shallow, with a sandy bottom, and often silty," Falke said. "The water can be waist-deep, and when parts of the river dry up from the pumping of groundwater, it is these deeper areas that become refuge pools. But they are becoming scarcer, and farther apart each year."

Falke said the changing hydrology of the system has implications beyond the native fishes. The aquifer-fed stream influences the entire riparian area, where cottonwood trees form their own ecosystem and groundwater-dependent grasses support the grazing of livestock and other animals.

Pumping of regional aquifers is done almost entirely for agriculture, Falke said, with about 90 percent of the irrigation aimed at corn production, with some alfalfa and wheat.

"The impact goes well beyond the Arikaree River," Falke said. "Declines in streamflow are widespread across the western Great Plains, including all 11 headwaters of the Republican River. Ultimately, the species inhabiting these drainages will decline in range and abundance, and become more imperiled as groundwater levels decline and climate changes continue."

Other authors on the study include Kurt Fausch, Robin Magelky, Angela Aldred, Deanna Durnford, Linda Riley and Ramchand Oad, all of Colorado State University. The study was supported by the Colorado Division of Wildlife and the Colorado Agricultural Experiment Station.

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