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segunda-feira, 19 de maio de 2014

Sleeping pills increase cardiovascular events in heart failure patients

May 17, 2014

European Society of Cardiology (ESC)

Sleeping pills increase the risk of cardiovascular events in heart failure patients by 8-fold, according to research. The investigators concluded: "Our results need confirmation in larger, prospective studies before heart failure patients can be advised to stop taking sleeping pills. But (some) patients who use sleeping pills, particularly those who have sleep disordered breathing, should be carefully monitored."

Sleeping pills increase the risk of cardiovascular events in heart failure patients by 8-fold, according to research from Japan.

Sleeping pills increase the risk of cardiovascular events in heart failure patients by 8-fold, according to research from Japan. The study was presented today at the Heart Failure Congress 2014, held 17-20 May in Athens, Greece. The Congress is the main annual meeting of the Heart Failure Association of the European Society of Cardiology.

Dr Masahiko Setoguchi said: "Sleeping problems are a frequent side effect of heart failure and it is common for patients to be prescribed sleeping pills when they are discharged from hospital. They also have other comorbidities and may be prescribed diuretics, antiplatelets, antihypertensives, anticoagulants and anti-arrhythmics."

He added: "Cardiac function of heart failure patients worsens with repeated hospitalizations. We therefore decided it was important to investigate the relationships between drugs prescribed at discharge, rehospitalization and cardiovascular events in heart failure patients."

The researchers retrospectively examined the medical records of 111 heart failure patients admitted to Tokyo Yamate Medical Center from 2011 to 2013. Information was collected on the presence of coexisting cardiovascular and other medical conditions, medications administered during hospitalization and those prescribed at discharge, laboratory test results, electrocardiogram, echocardiogram and chest radiographic data and vital signs at admission and discharge.

Study participants were followed up for 180 days after they were discharged from hospital. The study endpoint was readmission for heart failure, or cardiovascular related death.

For the analysis, patients were divided into those who had heart failure with preserved ejection fraction (HFpEF) and those who had heart failure with reduced ejection fraction (HFrEF). Dr Setoguchi said: "Management and prognosis can vary between patients with HFpEF and HFrEF so we analysed the two groups separately."

Of the 47 HFpEF patients, 15 reached the study endpoint during the 180 day follow up period. The only differences between patients who had events and those who did not were prescription of sleeping pills (benzodiazepine hypnotics), blood sodium levels at admission and blood haemoglobin levels at discharge.

Multivariate analysis showed that HFpEF patients who were prescribed sleeping pills were at eight times greater risk of rehospitalisation for heart failure or cardiovascular related death than HFpEF patients who were not prescribed sleeping pills (hazard ratio [HR]=8.063, p=0.010).

Dr Setoguchi said: "Our study clearly shows that sleeping pills dramatically increase the risk of cardiovascular events in patients with HFpEF. The finding was consistent across univariate and multivariate analyses. Given that many heart failure patients have difficulty sleeping, this is an issue that needs further investigation in larger studies."

Of the 64 HFrEF patients, 24 reached the study endpoint during follow up. Multivariate analysis showed that HFrEF patients who were prescribed high blood pressure medications (ACE inhibitors or angiotensin receptor blockers) had less than one-quarter the risk of cardiovascular events compared to HFrEF patients not prescribed these drugs (HR=0.234, p=0.012).

Dr Setoguchi said: "The main finding of our study is that HFpEF patients prescribed sleeping pills have an increased risk of cardiovascular events. The number of HFpEF patients is increasing and becoming a larger proportion of heart failure patients overall. Our results therefore are of growing relevance to heart failure patients and the professionals who treat them."

He added: "Benzodiazepine hyptonics may have cardiodepressant actions. They may also exert respiratory depressant actions which could exacerbate sleep disordered breathing and lead to a worse prognosis."

Dr Setoguchi concluded: "Our results need confirmation in larger, prospective studies before heart failure patients can be advised to stop taking sleeping pills. But HFpEF patients who use sleeping pills, particularly those who have sleep disordered breathing, should be carefully monitored."

Story Source:

The above story is based on materials provided by European Society of Cardiology (ESC). Note: Materials may be edited for content and length.

Rotary sensors: Getting the right spin

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The polarization sensor that measures the angle of rotation mounted on the test board. On the left: A shaft with integrated polarizing film.

Rotary sensors can help determine the position of a moveable body in relation to an axis. They are essential to the smooth running of car engines in the automotive industry, for example. Fraunhofer researchers have developed a new kind of sensor that combines precision measurement with flexible handling, allowing it to be customized to specific measurement tasks. The scientists will be presenting their prototype at the Sensor + Test trade show in Nürnberg from June 3 to 5.

In factories, goods and products are transported from one processing station to the next via conveyor belt. For the transfer from one belt to the next to run smoothly, it must take place precisely at a specific position, which means knowing the relative position of objects on the conveyor belts as they move towards each other. This can be determined from the angle of rotation, which refers to the position of a moveable body to an axis. Rotation angles are also important within the automotive industry, where they provide information for engine feedback systems, for example, in which the rotational speed of the drive shaft must be precisely set. The angle of rotation is measured using special sensors. There are currently two types of such rotation angle sensors on the market, working according to either magnetic or optical measuring principles. Magnetic sensors are very durable and dirt resistant, giving them an advantage in harsh environments. They are, however not as precise as optical sensors. These in turn are not very flexible to use since they must be precisely mounted in a fixed position on the object being measured.

Researchers at the Fraunhofer Institute for Integrated Circuits IIS in Erlangen have now developed a new rotational angle sensor that combines the advantages of both solutions into one. "While our sensor also relies on optical measurement, its functional principle is completely different to other products currently available on the market," says Dr. Norbert Weber, group manager at the IIS. The researchers' development utilizes the polarization effect. Under normal conditions, light oscillates in all possible directions, meaning it is not polarized in its original state. With the help of special polarizing films, it is possible to steer these oscillations in a defined uniform direction, either horizontally or vertically. A good example of how polarizing films work is to be found in 3D glasses, which generate depth information because the viewer looks through lenses fitted with different polarizing filters for each eye. The researchers attach just such a polarization film to the test object -- the drive shaft, for example -- and direct a light beam at it. Polarized light is produced on the reverse side of the film. Should the drive shaft now rotate, the polarization vector rotates with it, thus serving as a kind of direction indicator.

Sensor can be fitted flexibly

The read-out module is then mounted in such a way that it is located in the beam of light. Several wire grids -- small microstructures -- are arranged in a matrix on the sensor chip. These lattices can be produced as part of the normal CMOS chip manufacturing process without any additional effort. The angular position of the shaft is calculated when the polarized light strikes the lattices. "In order to obtain a definite measurement of the angular position of a shaft, we need at least three grids that are each structured in different directions. Depending on the measuring task we can also add further grids, thus adapting the chip to suit the specific requirements of customers while increasing measurement accuracy, "explains Weber. With this design, the Erlanger researchers are not able to attain 100 percent of the precision of conventional optical sensors, but their sensor is significantly more robust and can be positioned relatively flexibly. "The chip does not even have to sit directly on the optical axis -- the only thing that matters is that it is located within the light beam," says Weber. Another advantage is that even if the shaft wobbles slightly, the result will not be affected as long as the beam is wide enough. At the SENSOR + TEST 2014 trade fair, researchers from Erlangen will present their solution on an exhibit which demonstrates rotation angle measurement on a hollow shaft. The measurement results are then displayed as a graph on the monitor.

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The above story is based on materials provided by Fraunhofer-Gesellschaft. Note: Materials may be edited for content and length.

Glasses-free 3-D projector

May 16, 2014

Massachusetts Institute of Technology

Researchers have steadily refined a design for a glasses-free, multiperspective, 3-D video screen, which they hope could provide a cheaper, more practical alternative to holographic video in the short term. Now they've designed a projector that exploits the same technology. The projector can also improve the resolution and contrast of conventional video, which could make it an attractive transitional technology as content producers gradually learn to harness the potential of multiperspective 3-D.

Multiperspective 3-D differs from the stereoscopic 3-D now common in movie theaters in that the depicted objects disclose new perspectives as the viewer moves about them, just as real objects would. This means it might have applications in areas like collaborative design and medical imaging, as well as entertainment.

Over the past three years, researchers in the Camera Culture group at the MIT Media Lab have steadily refined a design for a glasses-free, multiperspective, 3-D video screen, which they hope could provide a cheaper, more practical alternative to holographic video in the short term.

Now they've designed a projector that exploits the same technology, which they'll unveil at this year's Siggraph, the major conference in computer graphics. The projector can also improve the resolution and contrast of conventional video, which could make it an attractive transitional technology as content producers gradually learn to harness the potential of multiperspective 3-D.

The MIT researchers -- research scientist Gordon Wetzstein, graduate student Matthew Hirsch, and Ramesh Raskar, the NEC Career Development Associate Professor of Media Arts and Sciences and head of the Camera Culture group -- built a prototype of their system using off-the-shelf components. The heart of the projector is a pair of liquid-crystal modulators -- which are like tiny liquid-crystal displays (LCDs) -- positioned between the light source and the lens. Patterns of light and dark on the first modulator effectively turn it into a bank of slightly angled light emitters -- that is, light passing through it reaches the second modulator only at particular angles. The combinations of the patterns displayed by the two modulators thus ensure that the viewer will see slightly different images from different angles.

The researchers also built a prototype of a new type of screen that widens the angle from which their projector's images can be viewed. The screen combines two lenticular lenses -- the type of striated transparent sheets used to create crude 3-D effects in, say, old children's books.

The MIT Media Lab's Camera Culture group introduces a novel approach to multiple-perspective, glasses-free 3-D.

Exploiting redundancy

For every frame of video, each modulator displays six different patterns, which together produce eight different viewing angles: At high enough display rates, the human visual system will automatically combine information from different images. The modulators can refresh their patterns at 240 hertz, or 240 times a second, so even at six patterns per frame, the system could play video at a rate of 40 hertz, which, while below the refresh rate common in today's TVs, is still higher than the 24 frames per second standard in film.

With the technology that has historically been used to produce glasses-free 3-D images -- known as a parallax barrier -- simultaneously projecting eight different viewing angles would mean allotting each angle one-eighth of the light emitted by the projector, which would make for a dim movie. But like the researchers' prototype monitors, the projector takes advantage of the fact that, as you move around an object, most of the visual change takes place at the edges. If, for instance, you were looking at a blue mailbox as you walked past it, from one step to the next, much of your visual field would be taken up by a blue of approximately the same shade, even though different objects were coming into view behind it.

Algorithmically, the key to the researchers' system is a technique for calculating how much information can be preserved between viewing angles and how much needs to be varied. Preserving as much information as possible enables the projector to produce a brighter image. The resulting set of light angles and intensities then has to be encoded into the patterns displayed by the modulators. That's a tall computational order, but by tailoring their algorithm to the architecture of the graphics processing units designed for video games, the MIT researchers have gotten it to run almost in real time. Their system can receive data in the form of eight images per frame of video and translate it into modulator patterns with very little lag.

Bridge technology

Passing light through two modulators can also heighten the contrast of ordinary 2-D video. One of the problems with LCD screens is that they don't enable "true black": A little light always leaks through even the darkest regions of the display. "Normally you have contrast of, let's say, values between 0 and 1," Wetzstein explains. "That's the full contrast, but in practice, all modulators have something like 0.1 to 1. So you get this 'black level.' But if you multiply two optically together, the black level goes down to 0.01. If you show black on one, which is 10 percent, and black on the other, which is also 10 percent, what you get through is 1 percent. So it's much more black."

By the same token, Hirsch explains, if the patterns displayed on the modulators are slightly offset from each other, the light passing through them will interfere with itself in ways that actually heighten the resolution of the resulting images. Again, the researchers have developed an algorithm that can calculate those patterns on the fly.

As content creators move to so-called "quad HD," video with four times the resolution of today's high-definition video, the combination of higher contrast and higher resolution could make a commercial version of the researchers' technology appealing to theater owners, which in turn could smooth the way for the adoption of multiperspective 3-D. "One thing you could do -- and this is what actual projector manufacturers have done in the recent past -- is take four 1080p modulators and put them next to each other and build some very complicated optics to tile them all seamlessly and then get a much nicer lens because you have to project a much smaller spot and bundle that all up together," Hirsch says. "We're saying you could take two 1080p modulators, stick them in your projector one after the other, then take your same old 1080p lens and project through it and use this software algorithm, and you end up with a 4k image. But not only that, it's got even higher contrast."

Spreading pixels

Oliver Cossairt, an assistant professor of electrical engineering and computer science at Northwestern University, once worked for a company that was attempting to commercialize glasses-free 3-D projectors. "What I consider the novelty of [the MIT researchers'] approach involves two things," Cossairt says. The first, he says, is "playing around with the parallax-barrier idea so that you can make it so that it (a) doesn't block as much light and (b) gets better resolution."

The second, he says, is the prototype screen. "There is this invariant of optical systems that says that if you take the area of the plane and the solid angle of light coming out from that plane, that is fixed," Cossairt says. "What that means is that if you take the 3-D image size and stretch it out to be, let's say, 10 times as large, then the field of view will decrease by a factor of 10. That's what we ran into. We couldn't figure out a way around that."

"They came up with a screen that instead of stretching the image -- which is what projection optics does -- essentially moved the pixels away from each other," Cossairt continues. "That allowed them to break this invariance."

Story Source:

The above story is based on materials provided by Massachusetts Institute of Technology. The original article was written by Larry Hardesty. Note: Materials may be edited for content and length.

Scientists discover how to turn light into matter after 80-year quest

In just one day over several cups of coffee in a tiny office in Imperial's Blackett Physics Laboratory, three physicists worked out a relatively simple way to physically prove a theory first devised by scientists Breit and Wheeler in 1934.

Breit and Wheeler suggested that it should be possible to turn light into matter by smashing together only two particles of light (photons), to create an electron and a positron -- the simplest method of turning light into matter ever predicted. The calculation was found to be theoretically sound but Breit and Wheeler said that they never expected anybody to physically demonstrate their prediction. It has never been observed in the laboratory and past experiments to test it have required the addition of massive high-energy particles.

The new research, published in Nature Photonics, shows for the first time how Breit and Wheeler's theory could be proven in practice. This 'photon-photon collider', which would convert light directly into matter using technology that is already available, would be a new type of high-energy physics experiment. This experiment would recreate a process that was important in the first 100 seconds of the universe and that is also seen in gamma ray bursts, which are the biggest explosions in the universe and one of physics' greatest unsolved mysteries.

The scientists had been investigating unrelated problems in fusion energy when they realised what they were working on could be applied to the Breit-Wheeler theory. The breakthrough was achieved in collaboration with a fellow theoretical physicist from the Max Planck Institute for Nuclear Physics, who happened to be visiting Imperial.

Demonstrating the Breit-Wheeler theory would provide the final jigsaw piece of a physics puzzle which describes the simplest ways in which light and matter interact (see image in notes to editors). The six other pieces in that puzzle, including Dirac's 1930 theory on the annihilation of electrons and positrons and Einstein's 1905 theory on the photoelectric effect, are all associated with Nobel Prize-winning research (see image).

Professor Steve Rose from the Department of Physics at Imperial College London said: "Despite all physicists accepting the theory to be true, when Breit and Wheeler first proposed the theory, they said that they never expected it be shown in the laboratory. Today, nearly 80 years later, we prove them wrong. What was so surprising to us was the discovery of how we can create matter directly from light using the technology that we have today in the UK. As we are theorists we are now talking to others who can use our ideas to undertake this landmark experiment."

The collider experiment that the scientists have proposed involves two key steps. First, the scientists would use an extremely powerful high-intensity laser to speed up electrons to just below the speed of light. They would then fire these electrons into a slab of gold to create a beam of photons a billion times more energetic than visible light.

The next stage of the experiment involves a tiny gold can called a hohlraum (German for 'empty room'). Scientists would fire a high-energy laser at the inner surface of this gold can, to create a thermal radiation field, generating light similar to the light emitted by stars.

They would then direct the photon beam from the first stage of the experiment through the centre of the can, causing the photons from the two sources to collide and form electrons and positrons. It would then be possible to detect the formation of the electrons and positrons when they exited the can.

Lead researcher Oliver Pike who is currently completing his PhD in plasma physics, said: "Although the theory is conceptually simple, it has been very difficult to verify experimentally. We were able to develop the idea for the collider very quickly, but the experimental design we propose can be carried out with relative ease and with existing technology. Within a few hours of looking for applications of hohlraums outside their traditional role in fusion energy research, we were astonished to find they provided the perfect conditions for creating a photon collider. The race to carry out and complete the experiment is on!"

The research was funded by the Engineering and Physical Sciences Research Council (EPSRC), the John Adams Institute for Accelerator Science, and the Atomic Weapons Establishment (AWE), and was carried out in collaboration with Max-Planck-Institut für Kernphysik.

Illuminating neuron activity in 3-D: New technique lets scientists monitor small worm's entire nervous system

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Researchers have created an imaging system that reveals neural activity throughout the brains of living animals. This technique, the first that can generate 3-D movies of entire brains at the millisecond timescale, could help scientists discover how neuronal networks process sensory information and generate behavior.

Researchers at MIT and the University of Vienna have created an imaging system that reveals neural activity throughout the brains of living animals. This technique, the first that can generate 3-D movies of entire brains at the millisecond timescale, could help scientists discover how neuronal networks process sensory information and generate behavior.

The team used the new system to simultaneously image the activity of every neuron in the worm Caenorhabditis elegans, as well as the entire brain of a zebrafish larva, offering a more complete picture of nervous system activity than has been previously possible.

"Looking at the activity of just one neuron in the brain doesn't tell you how that information is being computed; for that, you need to know what upstream neurons are doing. And to understand what the activity of a given neuron means, you have to be able to see what downstream neurons are doing," says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT and one of the leaders of the research team. "In short, if you want to understand how information is being integrated from sensation all the way to action, you have to see the entire brain."

The new approach, described May 18 in Nature Methods, could also help neuroscientists learn more about the biological basis of brain disorders. "We don't really know, for any brain disorder, the exact set of cells involved," Boyden says. "The ability to survey activity throughout a nervous system may help pinpoint the cells or networks that are involved with a brain disorder, leading to new ideas for therapies."

Boyden's team developed the brain-mapping method with researchers in the lab of Alipasha Vaziri of the University of Vienna and the Research Institute of Molecular Pathology in Vienna. The paper's lead authors are Young-Gyu Yoon, a graduate student at MIT, and Robert Prevedel, a postdoc at the University of Vienna.

High-speed 3-D imaging

Neurons encode information -- sensory data, motor plans, emotional states, and thoughts -- using electrical impulses called action potentials, which provoke calcium ions to stream into each cell as it fires. By engineering fluorescent proteins to glow when they bind calcium, scientists can visualize this electrical firing of neurons. However, until now there has been no way to image this neural activity over a large volume, in three dimensions, and at high speed.

Scanning the brain with a laser beam can produce 3-D images of neural activity, but it takes a long time to capture an image because each point must be scanned individually. The MIT team wanted to achieve similar 3-D imaging but accelerate the process so they could see neuronal firing, which takes only milliseconds, as it occurs.

The new method is based on a widely used technology known as light-field imaging, which creates 3-D images by measuring the angles of incoming rays of light. Ramesh Raskar, an associate professor of media arts and sciences at MIT and an author of this paper, has worked extensively on developing this type of 3-D imaging. Microscopes that perform light-field imaging have been developed previously by multiple groups. In the new paper, the MIT and Austrian researchers optimized the light-field microscope, and applied it, for the first time, to imaging neural activity.

With this kind of microscope, the light emitted by the sample being imaged is sent through an array of lenses that refracts the light in different directions. Each point of the sample generates about 400 different points of light, which can then be recombined using a computer algorithm to recreate the 3-D structure.

"If you have one light-emitting molecule in your sample, rather than just refocusing it into a single point on the camera the way regular microscopes do, these tiny lenses will project its light onto many points. From that, you can infer the three-dimensional position of where the molecule was," says Boyden, who is a member of MIT's Media Lab and McGovern Institute for Brain Research.

Prevedel built the microscope, and Yoon devised the computational strategies that reconstruct the 3-D images.

Aravinthan Samuel, a professor of physics at Harvard University, says this approach seems to be an "extremely promising" way to speed up 3-D imaging of living, moving animals, and to correlate their neuronal activity with their behavior. "What's very impressive about it is that it is such an elegantly simple implementation," says Samuel, who was not part of the research team. "I could imagine many labs adopting this."

Neurons in action

The researchers used this technique to image neural activity in the worm C. elegans, the only organism for which the entire neural wiring diagram is known. This 1-millimeter worm has 302 neurons, each of which the researchers imaged as the worm performed natural behaviors, such as crawling. They also observed the neuronal response to sensory stimuli, such as smells.

The downside to light field microscopy, Boyden says, is that the resolution is not as good as that of techniques that slowly scan a sample. The current resolution is high enough to see activity of individual neurons, but the researchers are now working on improving it so the microscope could also be used to image parts of neurons, such as the long dendrites that branch out from neurons' main bodies. They also hope to speed up the computing process, which currently takes a few minutes to analyze one second of imaging data.

The researchers also plan to combine this technique with optogenetics, which enables neuronal firing to be controlled by shining light on cells engineered to express light-sensitive proteins. By stimulating a neuron with light and observing the results elsewhere in the brain, scientists could determine which neurons are participating in particular tasks.

Other co-authors at MIT include Nikita Pak, a PhD student in mechanical engineering, and Gordon Wetzstein, a research scientist at the Media Lab. The work at MIT was funded by the Allen Institute for Brain Science; the National Institutes of Health; the MIT Synthetic Intelligence Project; the IET Harvey Prize; the National Science Foundation (NSF); the New York Stem Cell Foundation-Robertson Award; Google; the NSF Center for Brains, Minds, and Machines at MIT; and Jeremy and Joyce Wertheimer.

Video: http://www.youtube.com/watch?v=8Dotiqbtvoo

Story Source:

The above story is based on materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton. Note: Materials may be edited for content and length.

Journal Reference:

Robert Prevedel, Young-Gyu Yoon, Maximilian Hoffmann, Nikita Pak, Gordon Wetzstein, Saul Kato, Tina Schrödel, Ramesh Raskar, Manuel Zimmer, Edward S Boyden, Alipasha Vaziri. Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy. Nature Methods, 2014; DOI: 10.1038/nmeth.2964

New technology simplifies production of biotech medicines

May 14, 2014

The final step in the production of a biotech medicine is finishing with the correct sugar structure. This step is essential for the efficacy of the medicine, but it also makes the production process very complex and expensive. Researchers have developed a technology that shortens the sugar structures whilst retaining the therapeutic efficiency. This technology has the potential to make the production of biotech medicines significantly simpler and cheaper.

Nico Callewaert, who says: "This technology has allowed us to solve an old biotech problem. Since the 1990s, nearly everyone has been working to make the sugar synthesis in biotech production cells as similar to human cells as possible."

The final step in the production of a biotech medicine is finishing with the correct sugar structure. This step is essential for the efficacy of the medicine, but it also makes the production process very complex and expensive. Leander Meuris, Francis Santens and Nico Callewaert (VIB/UGent) have developed a technology that shortens the sugar structures whilst retaining the therapeutic efficiency. This technology has the potential to make the production of biotech medicines significantly simpler and cheaper.

Sugar structures are essential for the mechanism of biotech medicines

Nearly all biotech medicines are proteins. Most of these medicines contain a mixture of complicated sugar structures that are attached to the protein. These sugars are important for the mechanism of the medicine on the one hand, but on the other hand their complicated structure also causes problems during production. This makes the process expensive and often results in a mixture of the same protein with different sugars attached. In some cases, only a few of the many sugar forms are ideal for the treatment and others are not, meaning that a part of the production and treatment efficiency is lost.

Optimizing production cells
The proteins that are used as biotech medicines are produced by living cells. Leander Meuris and Nico Callewaert have altered these production cells so that they truncate the sugar structures to a smaller shape. In order to achieve this they added an enzyme obtained from a fungus, which truncates complex sugars, to the production cells. The stump that remains after truncation is then expanded by the cells to form two similar structures that are very suitable for therapeutic applications. Surprisingly, these production cells do not mind: they grow perfectly and continue to produce the therapeutic proteins.

A satisfying discovery

Nico Callewaert(VIB/UGent): "This technology has allowed us to solve an old biotech problem. Since the 1990s, nearly everyone has been working to make the sugar synthesis in biotech production cells as similar to human cells as possible. This is a very difficult task, because there are so many steps in this synthesis pathway. We have been able to create a 'detour' in this synthesis pathway in a fairly simple manner, making the pathway much shorter and simpler."

Leander Meuris (VIB/UGent): "You can compare it to a pollard willow. The branches of willows are pruned to keep the tree more functional, just like our technology in which we removed the complex branches to make biotech medicines more manageable and in some cases more efficient."

Story Source:

The above story is based on materials provided by VIB. Note: Materials may be edited for content and length.

Journal Reference:

Leander Meuris, Francis Santens, Greg Elson, Nele Festjens, Morgane Boone, Anaëlle Dos Santos, Simon Devos, François Rousseau, Evelyn Plets, Erica Houthuys, Pauline Malinge, Giovanni Magistrelli, Laura Cons, Laurence Chatel, Bart Devreese, Nico Callewaert. GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins. Nature Biotechnology, 2014; 32 (5): 485 DOI: 10.1038/nbt.2885

domingo, 18 de maio de 2014

Magnets and kids: A dangerous duo

Magnet ingestions by children have received increasing attention over the past 10 years. With the growing availability of new and stronger neodymium-iron-boron magnets being sold as "toys," there has been an increase of cases of ingestion, resulting in serious injury and, in some cases, death. In a new study scheduled for publication in The Journal of Pediatrics, researchers studied the trends of magnetic ingestions at The Hospital for Sick Children (SickKids), Canada's largest children's hospital.

Matt Strickland, MD, and colleagues reviewed all cases of foreign body ingestion seen in the emergency department from April 1, 2002 through December 31, 2012. Inclusion criteria included being less than 18 years of age, with suspected or confirmed magnetic ingestion. According to Dr. Strickland, "We chose to limit our scope to the alimentary tract because the majority of serious harm from magnets arises from perforations and fistulae of the stomach, small bowel, and colon." To reflect the introduction of small, spherical magnet sets in 2009, the study was divided into two time periods, visits during 2002-2009 and those during 2010-2012.

Of 2,722 patient visits for foreign body ingestions, 94 children met the inclusion criteria. Of those, 30 children had confirmed ingestion of multiple magnets. Overall magnet ingestions tripled from 2002-2009 to 2010-2012; the incidence of injuries involving multiple magnets increased almost 10-fold between the two time periods. Six cases required surgery for sepsis or potential for imminent bowel perforation, all of which occurred in 2010-2012. The average size of the magnets also decreased approximately 70% between 2002-2009 and 2010-2012.

This study shows a significant increase in the rate of multiple magnet-related injuries between 2002 and 2012. "More concerning, however," notes Dr. Strickland, "is the increased number of high-risk injuries featuring multiple, smaller magnets." Despite new magnet-specific toy standards, labeling requirements, product recalls, and safety advisories issued in the past 10 years, continuing efforts should focus on educating parents and children on the dangers inherent in magnetic "toys."

Story Source:

The above story is based on materials provided by Elsevier. Note: Materials may be edited for content and length.

Cameras and displays: Organic photodiodes for sensor applications

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Organic photodiodes are extremely lightweight and also inexpensive to produce.

Powerful, inexpensive and even flexible when they need to be, organic photodiodes are a promising alternative to silicon-based photodetectors. They are used to improve light sensitivity in cameras and to check displays for homogeneous color composition. Fraunhofer scientists are developing just this kind of component to fit customer-specific requirements and will be presenting a color sensor demonstrator at this year's SENSOR + TEST trade fair in Nuremberg from June 3 to 5.

We have Mother Nature and her ingenious brand of technology to thank for our ability to see -- our eyes capture light from our environment and our retinas transform it into an electronic signal that is passed on to the brain as information. Optical components -- like photodetectors -- work according to the same principle. They can be found in digital cameras and are also used in automation technology, bioanalytics and medical imaging diagnostics. Optical components are typically made from inorganic materials such as silicon. But scientists at the Fraunhofer Research Institution for Organics, Materials and Electronic Devices COMEDD in Dresden are now also developing organic photodiodes (OPD) that rely on organic materials such as dyes or pigments. "These kinds of OPD offer a range of advantages compared with inorganic components -- they're extremely lightweight, cheap to produce and can be used for flexible applications," explains COMEDD head of department Dr. Olaf R. Hild.

The choice of which material to use is determined primarily by the wavelength spectrum customers select for their applications. Organic materials are each sensitive only to a particular wavelength range -- for instance, they may react only to green light. So by choosing the right material, scientists can control and tailor the spectral sensitivity of their optical sensors. The available materials already cover a broad wavelength spectrum. For special applications, for instance in the UV or near-infrared range, the Dresden-based scientists are also developing compact micro-sensors that combine organic semiconductors with silicon technology.

Increased light sensitivity using photodiodes

Uses vary from tiny sensor elements for cameras or for bioanalytics to large-scale, quality control applications. In lab-on-chip applications, for instance, OPDs can detect certain DNA sequences that have been tagged with fluorescent markers. Hild explains how photodiodes help to increase a high-end camera's light sensitivity: "Integrating our organic photodiodes increases the light sensitivity of today's CCD chips by providing a larger usable surface." OPDs can also be used to check the homogeneity of the color composition or the brightness distribution of luminescent surfaces such as displays.

Unlike their silicon-based counterparts, OPDs also allow for flexible components. Here photodiodes are integrated into polymer films that can be applied to concave or curved surfaces. This could be used to develop quality control systems specially shaped to the product to be placed inside them so that whole car doors could be examined for scratches or any quality inconsistencies in the paintwork. And it is particularly in such large-scale applications that OPDs offer a cheaper alternative to traditional technologies: whereas it is very difficult and expensive to cover large surfaces with silicon, OPDs can be applied to comparatively inexpensive materials using simple coating techniques. This means that the scientists can utilize established manufacturing techniques such as those used to manufacture organic photovoltaics, for example. At this year's SERSOR + TEST the scientists will be presenting a color sensor featuring four organic photodiodes, each one with its own spectral sensitivity.

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The above story is based on materials provided by Fraunhofer-Gesellschaft. Note: Materials may be edited for content and length.

Silently among us: Scientists worry about milder cases of MERS

(Reuters) - Scientists leading the fight against Middle East Respiratory Syndrome say the next critical front will be understanding how the virus behaves in people with milder infections, who may be spreading the illness without being aware they have it.

Establishing that may be critical to stopping the spread of MERS, which emerged in the Middle East in 2012 and has so far infected more than 500 patients in Saudi Arabia alone. It kills about 30 percent of those who are infected.

It is becoming increasingly clear that people can be infected with MERS without developing severe respiratory disease, said Dr David Swerdlow, who heads the MERS response team at the U.S. Centers for Disease Control and Prevention.

"You don't have to be in the intensive care unit with pneumonia to have a case of MERS," Swerdlow told Reuters. "We assume they are less infectious (to others), but we don't know."

The CDC has a team in Saudi Arabia studying whether such mild cases are still capable of spreading the virus. Swerdlow is overseeing their work from Atlanta.

They plan to test the family members of people with mild MERS, even if these relatives don't have any symptoms, to help determine whether the virus can spread within a household.

Cases of the disease, which causes coughing, fever and sometimes fatal pneumonia, have nearly tripled in the past month and a half, and the virus is moving out of the Arabian peninsula as infected individuals travel from the region.

Since late April, the first two cases of MERS have been reported on U.S. soil. Dutch officials reported their first two cases this week. Infections have also turned up in Britain, Greece, France, Italy, Malaysia and elsewhere.

Since MERS is an entirely new virus, there are no drugs to treat it and no vaccines capable of preventing its spread. It is a close cousin of the virus that caused Severe Acute Respiratory Syndrome or SARS, which killed around 800 people worldwide after it first appeared in China in 2002.

Because MERS patients can have "mild and unusual symptoms," the World Health Organization advises healthcare workers to apply standard infection control precautions for all patients, regardless of their diagnosis, at all times.

"Asymptomatic carriers of diseases can represent a major route for a pathogen to spread," said Dr Amesh Adalja of the University of Pittsburgh Medical Center.

"Just think of Typhoid Mary," he said, referring to the asymptomatic cook who spread typhoid fever to dozens of people in the early 20th century.

NOT EVEN A COUGH

Milder symptoms played a role in the second U.S. case of MERS, a man who started having body aches on a journey from Jeddah on Saudi Arabia's Red Sea coast to the United States.

It took the patient more than a week before he sought help in an emergency department in Orlando, Florida. Once he arrived, he waited nearly 12 hours in the ER before staff recognized a MERS link and placed him in an isolation room. The patient did not have signs of a respiratory infection, not even a cough.[ID:nL1N0O002W]

Dr Kevin Sherin, director of the Florida Department of Health for Orange County, believes that made it less likely that he could spread the infection. Hospital workers have tested negative, but the health department and the CDC are still checking on hundreds of people who might have been in contact with the patient.

A CDC study published earlier this week looked at some of the first cases of MERS that occurred in Jordan in 2012.

Initially, only two people in that outbreak were thought to have MERS. When CDC disease detectives used more sensitive tests that looked for MERS antibodies among hospital workers, they found another seven people had contracted MERS and survived it.

That suggests there may be people with mild cases "that can serve as a way for the virus to spread to other individuals, which makes it a lot harder to control," Adalja said.

Scientists are especially concerned because a lot of recent cases of MERS are among people who did not have contact with animals such as camels or bats that are believed to be reservoirs for the virus.

"If they don't have animal contact, where do they pick it up? Potentially, asymptomatic cases," said Dr Michael Osterholm, an infectious disease expert from the University of Minnesota.

Herpes-loaded stem cells used to kill brain tumors

Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.

The work, led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member, is published in the Journal of the National Cancer Institute. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.

Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors but with limited success. In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells. However, the therapy hasn't translated as well for human patients. The problem previous researchers couldn't overcome was how to keep the herpes viruses at the tumor site long enough to work.

Shah and his team turned to mesenchymal stem cells (MSCs) -- a type of stem cell that gives rise to bone marrow tissue -- which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilized to carry oncolytic viruses. Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors developed in mice. Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumor cells and subsequently into all of the tumor cells.

"So, how do you translate this into the clinic?" asked Shah, who also is an Associate Professor at Harvard Medical School.

"We know that 70-75 percent of glioblastoma patients undergo surgery for tumor debulking, and we have previously shown that MSCs encapsulated in biocompatible gels can be used as therapeutic agents in a mouse model that mimics this debulking," he continued. "So, we loaded MSCs with oncolytic herpes virus and encapsulated these cells in biocompatible gels and applied the gels directly onto the adjacent tissue after debulking. We then compared the efficacy of virus-loaded, encapsulated MSCs versus direct injection of the virus into the cavity of the debulked tumors."

Using imaging proteins to watch in real time how the virus combated the cancer, Shah's team noticed that the gel kept the stem cells alive longer, which allowed the virus to replicate and kill any residual cancer cells that were not cut out during the debulking surgery. This translated into a higher survival rate for mice that received the gel-encapsulated stem cells.

"They survived because the virus doesn't get washed out by the cerebrospinal fluid that fills the cavity," Shah said. "Previous studies that have injected the virus directly into the resection cavity did not follow the fate of the virus in the cavity. However, our imaging and side-by-side comparison studies showed that the naked virus rarely infects the residual tumor cells. This could give us insight into why the results from clinical trials with oncolytic viruses alone were modest."

The study also addressed another weakness of cancer-killing viruses, which is that not all brain tumors are susceptible to the therapy. The researchers' solution was to engineer oncolytic herpes viruses to express an additional tumor-killing agent, called TRAIL. Again, using mouse models of glioblastoma -- this time created from brain tumor cells that were resistant to the herpes virus -- the therapy led to increased animal survival.

"Our approach can overcome problems associated with current clinical procedures," Shah said. "The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors."

Further preclinical work will be needed to use the herpes-loaded stem cells for breast, lung and skin cancer tumors that metastasize to the brain. Shah predicts the approach will enter clinical trials within the next two to three years.

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The above story is based on materials provided by Harvard University. Note: Materials may be edited for content and length.

Journal Reference:

Matthias Duebgen, Jordi Martinez-Quintanilla, Kaoru Tamura, Shawn Hingtgen, Navid Redjal, Hiroaki Wakimoto And Khalid Shah. Stem Cells Loaded With Multimechanistic Oncolytic Herpes Simplex Virus Variants for Brain Tumor Therapy. Journal of the National Cancer Institute, May 2014 DOI: 10.1093/jnci/dju090