Researchers at Sunnybrook Health Sciences Centre have made a critical discovery in T cell development bringing immunologists one step closer to enabling the creation of tailored T cell therapy that could one day be used to treat patients with AIDS or other immune system deficiencies.
"For the first time we understand which sets of molecules are required to induce different types of T cells," says Canada Research Chair and principal investigator Dr. Juan Carlos Z--iga-Pfl-ckerr, a senior scientist at Sunnybrook Research Institute who is also a professor in the Department of Immunology at the University of Toronto.
The immune system uses two main types of T cells, alpha-beta and gamma-delta, each with unique roles in protecting us from disease. The findings show that T cell progenitors will develop into mature gamma-delta T cells despite the absence of the Notch molecule, a molecule that Z--iga-Pfl-cker's lab recently showed was essential for the early-stage development of both types of T cells.
Published today in the journal Immunity, the research is also the first to show at what developmental stage the two types of T cells become distinct lineages. The lead researcher, Maria Ciofani, a PhD student in Z--iga-Pfl-cker's lab, used precise cell isolation techniques to show which molecular cues are needed, and when for each lineage development. Collectively, the work clarifies how both T cell types can be generated in the laboratory, thereby enabling further study directed at tailoring their unique functions to specific clinical needs.
Gamma-delta T cells in particular hold exciting clinical promise for their ability to orchestrate immunity to a broad range of foreign molecules; experiments in mice have shown that gamma-delta T cell injections can eliminate cancerous tumours, although much work remains to translate this research into viable clinical therapy.
Z--iga-Pfl-cker was recently identified by the prestigious Thomson Scientific Essential Science Indicators as one of the most cited researchers in the field of immunology for his landmark December 2002 paper in Immunity, which showed how to generate T cells from stem cells in a Petri dish. In addition to enabling Z--iga-Pfl-cker's current work, this breakthrough discovery established a simple and effective way for other researchers to study T cell development, and has advanced this study in hundreds of labs around the world.
Sunnybrook Health Sciences Centre is transforming health care through the dedication of its more than 10,000 staff members who provide compassionate and innovative patient focused care. An internationally recognized leader in women's health, academic research and education and an affiliation with the University of Toronto distinguishes Sunnybrook as one of Canada's premier health sciences centres. Sunnybrook specializes in caring for newborns, adults and the elderly, treating and preventing cancer, heart problems, orthopaedic and arthritic conditions and traumatic injuries. Toronto Sunnybrook Regional Cancer Centre is the comprehensive cancer program at Sunnybrook, a Cancer Care Ontario partner and fully affiliated with the University of Toronto.
Contact:Jennifer White
Sunnybrook Health Sciences Centre
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суббота, 10 сентября 2011 г.
Caps On Medical Malpractice Damages Cut Doctors' Insurance Costs
Caps on medical malpractice damages mean lower insurance premiums for doctors, according to a new review from two Alabama universities. How these caps affect patient care or costs is less certain.
"There's been substantial controversy over whether caps do what they're supposed to reduce malpractice insurance premiums," said lead author Leonard J. Nelson III, of the Cumberland School of Law at Samford University in Birmingham. "The rates of increase in malpractice insurance premiums are lower in states that have caps."
In their analysis of 10 studies conducted since 1990, Nelson and co-authors from the Lister Hill Center for Health Policy at the University of Alabama found no evidence that caps affect consumers' health insurance costs.
However, they did say there is evidence of "small-to-modest effects" of damages caps on so-called defensive medicine and some evidence that more physicians will practice in areas where there are caps. Doctors practice defensive medicine when they avoid high-risk patients or procedures to reduce their exposure to malpractice suits.
The study appears in the latest issue of The Milbank Quarterly.
In one study that examined 12 years of data, researchers found that damages caps reduced premiums for general practitioners, general surgeons and OB/GYNs by 13.4 percent, 14.3 percent and 16.9 percent, respectively, in the short term and by 40 percent to 58 percent longer term.
Lower malpractice insurance premiums for physicians indirectly help patients, said David Studdert, adjunct professor at the Harvard School of Public Health.
"If doctors' fear of litigation, stimulated in part by pricey premiums, prompts them to deliver treatments and order tests designed to cover them not improve the patient's care then the patient may suffer," Studdert said. "Lower premiums may, and probably do, reduce the incidence of such defensiveness."
Nelson said that caps might have "some good effects," but that "they can be unfair because people who are severely injured don't get adequately compensated." One effect of caps, he said, is that they discourage lawsuits.
More than half of the states have damages caps. Thirteen states and the District of Columbia never passed laws instituting caps and they were ruled unconstitutional in nine others states.
Nelson LJ, III, Morrisey MA, Kilgore ML. Damages caps in medical malpractice cases. The Milbank Quarterly 85(2), 2007.
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"There's been substantial controversy over whether caps do what they're supposed to reduce malpractice insurance premiums," said lead author Leonard J. Nelson III, of the Cumberland School of Law at Samford University in Birmingham. "The rates of increase in malpractice insurance premiums are lower in states that have caps."
In their analysis of 10 studies conducted since 1990, Nelson and co-authors from the Lister Hill Center for Health Policy at the University of Alabama found no evidence that caps affect consumers' health insurance costs.
However, they did say there is evidence of "small-to-modest effects" of damages caps on so-called defensive medicine and some evidence that more physicians will practice in areas where there are caps. Doctors practice defensive medicine when they avoid high-risk patients or procedures to reduce their exposure to malpractice suits.
The study appears in the latest issue of The Milbank Quarterly.
In one study that examined 12 years of data, researchers found that damages caps reduced premiums for general practitioners, general surgeons and OB/GYNs by 13.4 percent, 14.3 percent and 16.9 percent, respectively, in the short term and by 40 percent to 58 percent longer term.
Lower malpractice insurance premiums for physicians indirectly help patients, said David Studdert, adjunct professor at the Harvard School of Public Health.
"If doctors' fear of litigation, stimulated in part by pricey premiums, prompts them to deliver treatments and order tests designed to cover them not improve the patient's care then the patient may suffer," Studdert said. "Lower premiums may, and probably do, reduce the incidence of such defensiveness."
Nelson said that caps might have "some good effects," but that "they can be unfair because people who are severely injured don't get adequately compensated." One effect of caps, he said, is that they discourage lawsuits.
More than half of the states have damages caps. Thirteen states and the District of Columbia never passed laws instituting caps and they were ruled unconstitutional in nine others states.
Nelson LJ, III, Morrisey MA, Kilgore ML. Damages caps in medical malpractice cases. The Milbank Quarterly 85(2), 2007.
Health Behavior News Service
Center for the Advancement of Health 2000 Florida Ave. NW, Ste 210
Washington, DC 20009
United States
hbns
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Association of American Medical Colleges Supports Hospital Agreement On Health Care Reform
AAMC (Association of American Medical Colleges) President and CEO Darrell G. Kirch, M.D., issued the following statement on the agreement reached by the hospital community, the Obama administration, and the Senate Finance Committee in support of health care reform:
"The AAMC strongly supports the agreement announced today and believes it moves our nation closer to achieving meaningful health care reform. U.S. teaching hospitals provide 71 percent of all hospital-based charity care and are often the only source of specialized services in their communities. We greatly appreciate the thoughtful approach this agreement takes to guarantee that the safety net remains intact during the transition to a better system.
This accord helps to fulfill two key principles that the AAMC established for health care reform last year, namely that all Americans should have health care coverage, and that existing safety net mechanisms be supported and preserved until new ones are in place. By voluntarily accepting reduced market increases in hospital payments over the next decade, hospitals will contribute $100 billion toward the funding needed to provide all Americans with health insurance. We also are pleased that this agreement takes appropriate steps to ensure that new coverage mechanisms are in place before any reductions are made to Disproportionate Share payments. Congress and the administration will need to continually evaluate the effects of coverage expansion before making any cuts that could jeopardize the safety net for the uninsured and underinsured.
The nation's teaching hospitals are working hard to help expand access to health care while maintaining an environment where clinical care, discovery, and the training of the next generation of health professionals can occur-and will continue to make sacrifices as long as patient care comes first. As the Obama administration and Congress move forward with health care legislation, the AAMC and its members stand ready to make the positive changes needed for successful reform."
Source
Association of American Medical Colleges
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"The AAMC strongly supports the agreement announced today and believes it moves our nation closer to achieving meaningful health care reform. U.S. teaching hospitals provide 71 percent of all hospital-based charity care and are often the only source of specialized services in their communities. We greatly appreciate the thoughtful approach this agreement takes to guarantee that the safety net remains intact during the transition to a better system.
This accord helps to fulfill two key principles that the AAMC established for health care reform last year, namely that all Americans should have health care coverage, and that existing safety net mechanisms be supported and preserved until new ones are in place. By voluntarily accepting reduced market increases in hospital payments over the next decade, hospitals will contribute $100 billion toward the funding needed to provide all Americans with health insurance. We also are pleased that this agreement takes appropriate steps to ensure that new coverage mechanisms are in place before any reductions are made to Disproportionate Share payments. Congress and the administration will need to continually evaluate the effects of coverage expansion before making any cuts that could jeopardize the safety net for the uninsured and underinsured.
The nation's teaching hospitals are working hard to help expand access to health care while maintaining an environment where clinical care, discovery, and the training of the next generation of health professionals can occur-and will continue to make sacrifices as long as patient care comes first. As the Obama administration and Congress move forward with health care legislation, the AAMC and its members stand ready to make the positive changes needed for successful reform."
Source
Association of American Medical Colleges
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Bypass Procedure Used During Infant Heart Surgery Does Not Impair Later Neurological Outcomes
Congenital heart defects (CHD) are the most common birth defects in humans, affecting 8 per 1000 live births with one-third of affected children requiring intervention in early infancy. Increasing numbers of survivors combined with developmental expectations for independence, behavioral self-regulation and academic achievement have led to a growing identification of neurobehavioral symptoms in some survivors. A study now suggests that a cooling technique often used in heart operations does not impair neurological outcomes.
Congenital heart disease and its treatment were originally thought to potentially increase neurologic injury in these patients. The technique of deep hypothermic circulatory arrest (DHCA) is used in order to repair these congenital cardiac defects by providing a bloodless surgical field, which may facilitate completion of the best physiologic repair, and decrease the duration of blood exposure to the bypass circuit. However, it involves a period of reduced blood flow in the brain. Cooling is a protective mechanism to reduce metabolism of the brain and other organs during periods of low blood flow.
Stephanie Fuller, M.D., a cardiothoracic surgeon at The Children's Hospital of Philadelphia, presented these research findings yesterday in the prestigious J. Maxwell Chamberlain Lecture at the annual meeting of the Society of Thoracic Surgeons in Fort Lauderdale, Fla. According to the study, DHCA does not impair language skills, attention, and other neurocognitive abilities in school-age children.
Dr. Fuller and colleagues from Children's Hospital and the University of Washington assessed the use of DHCA as a predictor of neurodevelopmental outcomes in children who had cardiac surgery as infants. The infants were enrolled in a prospective study of apolipoprotein-E (APOE) polymorphisms and neurodevelopmental outcome after cardiac surgery and underwent formal neurodevelopmental testing at four years of age.
Neurodevelopmental testing was completed in 238 out of 307 eligible patients. The surgeons used DHCA in 92 of those infants as deemed necessary to provide better operative exposure with a bloodless and less cluttered surgical field and therefore a shorter total cardiopulmonary support time. Use of DHCA was not predictive of worse performance for any neurodevelopmental outcome. Significant predictors of worse outcome included lower socioeconomic status, preoperative mechanical ventilation and babies that were younger and smaller at the time of first operation. Neurodevelopmental assessment included cognition, language skills, attention, impulsivity, executive function, social competence, and visual-motor and fine-motor skills.
"Selective use of DHCA during cardiac surgery in infancy may facilitate operative repair and is not associated with impaired neurodevelopmental outcomes," said Dr. Fuller. "Despite added risk factors, the selective use of DHCA during infancy for repair of congenital heart disease without an obstruction in the aorta was not predictive of worse performance at four years of age."
Dr. Fuller added "use of DHCA as a support technique during cardiac surgery in infancy has many advantages; it is not necessary to sacrifice these advantages merely to avoid use of DHCA. Our study adds to the growing literature showing no adverse influence of limited periods of DHCA. New support techniques must be carefully evaluated prior to wide-spread acceptance to confirm they are not inferior to conventional management strategies."
Source
The Children's Hospital of Philadelphia
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Congenital heart disease and its treatment were originally thought to potentially increase neurologic injury in these patients. The technique of deep hypothermic circulatory arrest (DHCA) is used in order to repair these congenital cardiac defects by providing a bloodless surgical field, which may facilitate completion of the best physiologic repair, and decrease the duration of blood exposure to the bypass circuit. However, it involves a period of reduced blood flow in the brain. Cooling is a protective mechanism to reduce metabolism of the brain and other organs during periods of low blood flow.
Stephanie Fuller, M.D., a cardiothoracic surgeon at The Children's Hospital of Philadelphia, presented these research findings yesterday in the prestigious J. Maxwell Chamberlain Lecture at the annual meeting of the Society of Thoracic Surgeons in Fort Lauderdale, Fla. According to the study, DHCA does not impair language skills, attention, and other neurocognitive abilities in school-age children.
Dr. Fuller and colleagues from Children's Hospital and the University of Washington assessed the use of DHCA as a predictor of neurodevelopmental outcomes in children who had cardiac surgery as infants. The infants were enrolled in a prospective study of apolipoprotein-E (APOE) polymorphisms and neurodevelopmental outcome after cardiac surgery and underwent formal neurodevelopmental testing at four years of age.
Neurodevelopmental testing was completed in 238 out of 307 eligible patients. The surgeons used DHCA in 92 of those infants as deemed necessary to provide better operative exposure with a bloodless and less cluttered surgical field and therefore a shorter total cardiopulmonary support time. Use of DHCA was not predictive of worse performance for any neurodevelopmental outcome. Significant predictors of worse outcome included lower socioeconomic status, preoperative mechanical ventilation and babies that were younger and smaller at the time of first operation. Neurodevelopmental assessment included cognition, language skills, attention, impulsivity, executive function, social competence, and visual-motor and fine-motor skills.
"Selective use of DHCA during cardiac surgery in infancy may facilitate operative repair and is not associated with impaired neurodevelopmental outcomes," said Dr. Fuller. "Despite added risk factors, the selective use of DHCA during infancy for repair of congenital heart disease without an obstruction in the aorta was not predictive of worse performance at four years of age."
Dr. Fuller added "use of DHCA as a support technique during cardiac surgery in infancy has many advantages; it is not necessary to sacrifice these advantages merely to avoid use of DHCA. Our study adds to the growing literature showing no adverse influence of limited periods of DHCA. New support techniques must be carefully evaluated prior to wide-spread acceptance to confirm they are not inferior to conventional management strategies."
Source
The Children's Hospital of Philadelphia
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Average Annual Deductible For Individual Employer-Sponsored PPO Now Over $1,000, According To Survey
The increasing cost of health care in the U.S. has prompted more U.S. employers to shift a larger portion of the expenses to their workers, pushing the average annual PPO deductible in 2008 for a single worker to more than $1,000, according to a study released on Wednesday by Mercer , the Los Angeles Times reports (Girion, Los Angeles Times, 11/20). The study was based on an annual survey of about 2,900 businesses nationwide that had at least 10 employees (Boulton, Milwaukee Journal Sentinel, 11/19).
The study found that the mean deductible for a traditional health plan increased from $859 last year to $1,001 this year, an increase of about 17%, because a large number of employers, especially those with fewer than 500 workers, raised their deductibles (Rubenstein, Wall Street Journal, 11/20). The study found that nearly half of all employers nationwide in 2000 offered health plans that did not require workers to pay a deductible, but in 2008, four in five businesses required a deductible, in addition to an average monthly premium of $124 for individuals under PPO plans (Raabe, Denver Post, 11/20). According to the Journal, from 2000 to 2007 the median deductible had stayed consistent at $500. Deductibles typically are raised in increments of $500, $1,000 or $1,500 (Wall Street Journal, 11/20).
The Denver Post reports that businesses have been able to maintain their annual cost increases at about 6% over the last four years by charging employees higher monthly premiums and deductibles. Health benefit costs for U.S. employees averaged $8,482 per employee, an increase of 6.3% on average, according to the Post (Denver Post, 11/20). Blaine Bos, the chief analyst for the survey, said, "Raising the deductible has become the fallback for employers faced with cost increases they can't handle," adding, "It's the easiest way to reduce cost without taking more out of every employee's paycheck" (Yee, Minneapolis Star Tribune, 11/19).
Laura Baker, a consultant for Mercer, said that companies are expecting further increases in 2009. "Historically, downturns in the economy have often correlated with higher medical trends," Baker said (Los Angeles Times, 11/20). However, Chris Watts, head of Mercer's health and benefits consulting office in Denver, said, "But these are different times, and history may not repeat itself," adding, "Higher employee cost-sharing -- like a $1,000 deductible -- could prevent that spike in utilization that we've seen in other recessions" (Denver Post, 11/20).
The study found that the mean deductible for a traditional health plan increased from $859 last year to $1,001 this year, an increase of about 17%, because a large number of employers, especially those with fewer than 500 workers, raised their deductibles (Rubenstein, Wall Street Journal, 11/20). The study found that nearly half of all employers nationwide in 2000 offered health plans that did not require workers to pay a deductible, but in 2008, four in five businesses required a deductible, in addition to an average monthly premium of $124 for individuals under PPO plans (Raabe, Denver Post, 11/20). According to the Journal, from 2000 to 2007 the median deductible had stayed consistent at $500. Deductibles typically are raised in increments of $500, $1,000 or $1,500 (Wall Street Journal, 11/20).
The Denver Post reports that businesses have been able to maintain their annual cost increases at about 6% over the last four years by charging employees higher monthly premiums and deductibles. Health benefit costs for U.S. employees averaged $8,482 per employee, an increase of 6.3% on average, according to the Post (Denver Post, 11/20). Blaine Bos, the chief analyst for the survey, said, "Raising the deductible has become the fallback for employers faced with cost increases they can't handle," adding, "It's the easiest way to reduce cost without taking more out of every employee's paycheck" (Yee, Minneapolis Star Tribune, 11/19).
Laura Baker, a consultant for Mercer, said that companies are expecting further increases in 2009. "Historically, downturns in the economy have often correlated with higher medical trends," Baker said (Los Angeles Times, 11/20). However, Chris Watts, head of Mercer's health and benefits consulting office in Denver, said, "But these are different times, and history may not repeat itself," adding, "Higher employee cost-sharing -- like a $1,000 deductible -- could prevent that spike in utilization that we've seen in other recessions" (Denver Post, 11/20).
Small Businesses Experience Biggest Deductible Increases
A separate employer survey by the Kaiser Family Foundation and the Health Research and Education Trust found that businesses with three to 199 workers had experienced the largest increase in deductibles, with at least one in three workers paying a minimum of $1,000 for single PPO coverage (Los Angeles Times, 11/20). The study also projected potential increases in employee deductibles, copayments and other fees in 2009, the Raleigh News & Observer reports (Wolf, Raleigh News & Observer, 11/20).
Survey co-author Gary Claxton, a Kaiser Family Foundation vice president and director of the Foundation's Health Care Marketplace Project -- said deductibles likely would continue to increase over the next couple of years. "When unemployment goes up, workers just have less ability to push for good benefits," he said (Wall Street Journal, 11/20). He said that a deductible "discourages people from using services," adding, "The more cost-sharing there is, the more it's going to be discouraged. And when they are already worried economically, that's got to amplify the effect" (Los Angeles Times, 11/20).
The Mercer study is available online.
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.
© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
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Video Camera That Records At The Speed Of Thought
European researchers who created an ultra-fast, extremely high-resolution video camera have enabled dozens of medical applications, including one scenario that can record 'thought' processes travelling along neurons. This is ingenious science.
The Megaframe project scored a staggering number of breakthroughs to create the world's first 1024 pixel, photon-resolution, million-frame-per-second CMOS camera that puts Europe firmly in the lead for ultra-high speed video cameras.
Their work has pushed the boundaries of CMOS (a type of semiconductor) miniaturisation and sophistication. But it is in the application of their technology that the most stunning impacts of the Megaframe project will be seen, particularly in medical applications.
That is because the camera can detect a single photon at a million times a second, and so it can record molecular processes in unprecedented detail. "We need this sort of detail because biomedical scientists are studying processes at the intra-cellular and molecular levels," underlines Edoardo Charbon, coordinator of the EU-funded Megaframe project.
Ingenious
Scientists have developed extremely ingenious ways to infer or deduce what is happening at the molecular level, and Megaframe could make that process even more detailed. Essentially, scientists use a variety of emissive materials to see what is happening in microscopic biomedical processes.
Take Fluorescence Lifetime Imaging Microscopy (FLIM). Here, a fluorescent material is introduced to the area of interest. Fluorescence has some interesting properties, for example a particular spectrum of emission and a rate of decay.
One particular fluorophore, Oregon Green Bapta (OGB-1), decays at a rate proportionate to the presence of calcium. Interestingly, calcium is an important indicator of neuron activity.
"So it is possible, for example, to go inside neurons and look at their ion channels. These are the channels that allow neurons to communicate with other neurons. And you can basically see the amount of calcium that is present. You can probe optically how neurons communicate with other neurons just by looking at the concentrations of calcium in real time," explains Charbon.
So scientists can use the OGB-1 to indicate the presence and concentration of calcium, and the whole process can be recorded in ultra-fine detail thanks to single-photon detectors, such as the ones present in the Megaframe camera. The camera is recording at the speed of thought.
"Biomedical scientists could in principle use this microscopic information about calcium to learn about macroscopic conditions like Parkinson's, or Alzheimer's or epilepsy," Charbon stresses.
But that's just the beginning. Megaframe could have a significant impact on any medical science that uses visible light emissive scanning technologies like FLIM. But it can even have an impact where visible light is not present.
Other apps
Other applications currently under exploration by Megaframe include intracellular DNA sequencing and proteomics, two huge areas for drug discovery, as well as basic scientific research for gene sequencing and protein-folding.
"For example, the camera could be used to detect and display the impact of certain drugs, or certain combinations of drugs, in animal or human models," Charbon says, adding that they are currently looking at oligonucleotides, which are "very short sequences of DNA mounted directly onto the detectors for labelled and label-free monitoring of the hybridisation process."
Other areas where Megaframe's work could boost research results include cell membrane scanning, to discover what bacteria or other material are present, and this research could be extended to look at issues like water purity, and waterborne bacteria.
Exploring further potential
Another very promising technique is the combination of fluorescence imaging with MRI, or magnetic resonance imaging. "In MRI you need very strong magnetic fields in the cavity where you are performing the imaging, up to 10 Tesla, but conventional fluorescence technology won't work in these conditions," says Charbon.
But Megaframe's choice of photo detector the Single-Photon Avalanche Diode (SPAD) have been tested successfully in fields up to 9.4 Tesla, he reveals.
"Thus, it can be envisaged to have a system where fluorescence-enhanced imaging and functional MRI may be used simultaneously," Charbon enthuses. "This is very useful in a number of biomedical applications, where one wants to monitor the correlation between the presence of certain molecules in organs, such as the brain, and their function."
Again, pharmacology could benefit from this technique enormously, as well as epidemiological research.
"Our preliminary tests were conducted in an animal MRI, which in general has much higher fields than a human MRI. Human MRI tests will follow," reveals Charbon, adding that the technique has been tested with other SPAD-based microsensors and has yielded good results.
"Even though we have not tested it with the Megaframe chip, it is a guaranteed success because the technology is in principle the same," Charbon predicts.
The Megaframe project has just begun to explore the potential for their camera in biomedical applications, and the list just keeps on growing as their research continues. And that is just in the biomedical field. There are dozens of potential applications in fields as diverse as high-energy physics, entertainment and automotive diagnostics.
The Megaframe project received funding from the FET-Open scheme of the EU's Sixth Framework Programme for research.
This is the second of a three-part special feature on the Megaframe project appearing on ICT Results.
Source: ICT Results
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The Megaframe project scored a staggering number of breakthroughs to create the world's first 1024 pixel, photon-resolution, million-frame-per-second CMOS camera that puts Europe firmly in the lead for ultra-high speed video cameras.
Their work has pushed the boundaries of CMOS (a type of semiconductor) miniaturisation and sophistication. But it is in the application of their technology that the most stunning impacts of the Megaframe project will be seen, particularly in medical applications.
That is because the camera can detect a single photon at a million times a second, and so it can record molecular processes in unprecedented detail. "We need this sort of detail because biomedical scientists are studying processes at the intra-cellular and molecular levels," underlines Edoardo Charbon, coordinator of the EU-funded Megaframe project.
Ingenious
Scientists have developed extremely ingenious ways to infer or deduce what is happening at the molecular level, and Megaframe could make that process even more detailed. Essentially, scientists use a variety of emissive materials to see what is happening in microscopic biomedical processes.
Take Fluorescence Lifetime Imaging Microscopy (FLIM). Here, a fluorescent material is introduced to the area of interest. Fluorescence has some interesting properties, for example a particular spectrum of emission and a rate of decay.
One particular fluorophore, Oregon Green Bapta (OGB-1), decays at a rate proportionate to the presence of calcium. Interestingly, calcium is an important indicator of neuron activity.
"So it is possible, for example, to go inside neurons and look at their ion channels. These are the channels that allow neurons to communicate with other neurons. And you can basically see the amount of calcium that is present. You can probe optically how neurons communicate with other neurons just by looking at the concentrations of calcium in real time," explains Charbon.
So scientists can use the OGB-1 to indicate the presence and concentration of calcium, and the whole process can be recorded in ultra-fine detail thanks to single-photon detectors, such as the ones present in the Megaframe camera. The camera is recording at the speed of thought.
"Biomedical scientists could in principle use this microscopic information about calcium to learn about macroscopic conditions like Parkinson's, or Alzheimer's or epilepsy," Charbon stresses.
But that's just the beginning. Megaframe could have a significant impact on any medical science that uses visible light emissive scanning technologies like FLIM. But it can even have an impact where visible light is not present.
Other apps
Other applications currently under exploration by Megaframe include intracellular DNA sequencing and proteomics, two huge areas for drug discovery, as well as basic scientific research for gene sequencing and protein-folding.
"For example, the camera could be used to detect and display the impact of certain drugs, or certain combinations of drugs, in animal or human models," Charbon says, adding that they are currently looking at oligonucleotides, which are "very short sequences of DNA mounted directly onto the detectors for labelled and label-free monitoring of the hybridisation process."
Other areas where Megaframe's work could boost research results include cell membrane scanning, to discover what bacteria or other material are present, and this research could be extended to look at issues like water purity, and waterborne bacteria.
Exploring further potential
Another very promising technique is the combination of fluorescence imaging with MRI, or magnetic resonance imaging. "In MRI you need very strong magnetic fields in the cavity where you are performing the imaging, up to 10 Tesla, but conventional fluorescence technology won't work in these conditions," says Charbon.
But Megaframe's choice of photo detector the Single-Photon Avalanche Diode (SPAD) have been tested successfully in fields up to 9.4 Tesla, he reveals.
"Thus, it can be envisaged to have a system where fluorescence-enhanced imaging and functional MRI may be used simultaneously," Charbon enthuses. "This is very useful in a number of biomedical applications, where one wants to monitor the correlation between the presence of certain molecules in organs, such as the brain, and their function."
Again, pharmacology could benefit from this technique enormously, as well as epidemiological research.
"Our preliminary tests were conducted in an animal MRI, which in general has much higher fields than a human MRI. Human MRI tests will follow," reveals Charbon, adding that the technique has been tested with other SPAD-based microsensors and has yielded good results.
"Even though we have not tested it with the Megaframe chip, it is a guaranteed success because the technology is in principle the same," Charbon predicts.
The Megaframe project has just begun to explore the potential for their camera in biomedical applications, and the list just keeps on growing as their research continues. And that is just in the biomedical field. There are dozens of potential applications in fields as diverse as high-energy physics, entertainment and automotive diagnostics.
The Megaframe project received funding from the FET-Open scheme of the EU's Sixth Framework Programme for research.
This is the second of a three-part special feature on the Megaframe project appearing on ICT Results.
Source: ICT Results
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Putting A Bull's-Eye On The Flu: Science Paper Details Influenza's Structure For Future Drug Targeting
Beating the flu has always been tough, but it has gotten even more difficult in recent years. Two of the four antiviral drugs used to treat a nasty case of the influenza A virus no longer work.
Fortunately, scientists at the National High Magnetic Field Laboratory and Institute of Molecular Biophysics at Florida State University and researchers at Brigham Young University in Utah are close to understanding why these drugs have become less effective - and how new drugs might take their place. Their findings appear this week in the journal Science.
"Resistance to drugs is a fundamental problem that develops from their misuse, overuse and underuse," said Timothy A. Cross, the Earl Frieden Professor of Chemistry and Biochemistry at Florida State and director of the Magnet Lab's Nuclear Magnetic Resonance Program, as well as one of the Science article's senior authors. Compounding the problem is that "the development of new drugs to take their place is a decade-long process with infrequent success."
The two drugs no longer recommended by the U.S. Centers for Disease Control - amantadine (brand names Symadine and Symmetrel) and rimantadine (Flumadine) - have been used to fight the flu since 1969. For decades, they worked by preventing an essential protein function during viral infection of healthy cells. The protein, called the M2 channel, plays a key role in the virus' ability to reproduce. But the M2 channel mutated just enough to allow the virus to resist both drugs.
"Our work provides a blueprint on how protons are moved through a passageway inside the M2 channel," said Huan-Xiang Zhou, an FSU physics professor and the other senior co-author of the Science article. Interfering with that passageway is "an obvious route for drug development."
To study the M2 channel, researchers enlisted the help of one of the magnet lab's crown jewels: the 900-megahertz, nuclear magnetic resonance magnet. The 40-ton magnet was used to map the protein's structure by giving it the equivalent of an MRI scan. The detailed images allowed the research groups of Cross and Zhou to chart the tiniest, previously unknown aspects of the protein's atomic structure.
"Now that we have a much more refined view of M2 - going all the way down to the atomic level, the level that includes protons going through the channel - we can draw conclusions about how to block it," said David Busath, a biophysicist at Brigham Young University and a co-author of the Science paper.
Busath and his team have already begun screening millions of compounds, looking for drugs that will bind to the channel and block its reproductive role.
And FSU "has been awarded two patents for drug screening," Cross said. "We'll continue to use the 900-megahertz magnet for these drug-screening activities."
As to why the longtime flu drugs have become ineffective, the massive misuse of amantadine in poultry may have played a role, Cross said.
In the West, amantadine can only be given to humans. But starting in 2005, the Chinese began feeding it to chickens and other poultry to prevent them from getting avian flu. In all, China administered 2.6 billion doses of amantadine to its domestic birds.
"It's terrible to utilize these miracle drugs that can save thousands, if not millions, of lives and dramatically reduce hospitalizations in that fashion," Cross said.
The flu project headed up by Cross, Zhou and Busath is paid for by a 10-year, multimillion-dollar grant from the National Institutes of Health. Additional contributors to the Science article are lead author Mukesh Sharma, Myunggi Yi, Hao Dong and Huajun Qin, all of FSU, and Emily Peterson of BYU.
The National High Magnetic Field Laboratory develops and operates state-of-the-art, high-magnetic-field facilities that faculty and visiting scientists and engineers use for research. The laboratory is sponsored by the National Science Foundation and the state of Florida. To learn more, visit here.
Source:
Florida State University
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Fortunately, scientists at the National High Magnetic Field Laboratory and Institute of Molecular Biophysics at Florida State University and researchers at Brigham Young University in Utah are close to understanding why these drugs have become less effective - and how new drugs might take their place. Their findings appear this week in the journal Science.
"Resistance to drugs is a fundamental problem that develops from their misuse, overuse and underuse," said Timothy A. Cross, the Earl Frieden Professor of Chemistry and Biochemistry at Florida State and director of the Magnet Lab's Nuclear Magnetic Resonance Program, as well as one of the Science article's senior authors. Compounding the problem is that "the development of new drugs to take their place is a decade-long process with infrequent success."
The two drugs no longer recommended by the U.S. Centers for Disease Control - amantadine (brand names Symadine and Symmetrel) and rimantadine (Flumadine) - have been used to fight the flu since 1969. For decades, they worked by preventing an essential protein function during viral infection of healthy cells. The protein, called the M2 channel, plays a key role in the virus' ability to reproduce. But the M2 channel mutated just enough to allow the virus to resist both drugs.
"Our work provides a blueprint on how protons are moved through a passageway inside the M2 channel," said Huan-Xiang Zhou, an FSU physics professor and the other senior co-author of the Science article. Interfering with that passageway is "an obvious route for drug development."
To study the M2 channel, researchers enlisted the help of one of the magnet lab's crown jewels: the 900-megahertz, nuclear magnetic resonance magnet. The 40-ton magnet was used to map the protein's structure by giving it the equivalent of an MRI scan. The detailed images allowed the research groups of Cross and Zhou to chart the tiniest, previously unknown aspects of the protein's atomic structure.
"Now that we have a much more refined view of M2 - going all the way down to the atomic level, the level that includes protons going through the channel - we can draw conclusions about how to block it," said David Busath, a biophysicist at Brigham Young University and a co-author of the Science paper.
Busath and his team have already begun screening millions of compounds, looking for drugs that will bind to the channel and block its reproductive role.
And FSU "has been awarded two patents for drug screening," Cross said. "We'll continue to use the 900-megahertz magnet for these drug-screening activities."
As to why the longtime flu drugs have become ineffective, the massive misuse of amantadine in poultry may have played a role, Cross said.
In the West, amantadine can only be given to humans. But starting in 2005, the Chinese began feeding it to chickens and other poultry to prevent them from getting avian flu. In all, China administered 2.6 billion doses of amantadine to its domestic birds.
"It's terrible to utilize these miracle drugs that can save thousands, if not millions, of lives and dramatically reduce hospitalizations in that fashion," Cross said.
The flu project headed up by Cross, Zhou and Busath is paid for by a 10-year, multimillion-dollar grant from the National Institutes of Health. Additional contributors to the Science article are lead author Mukesh Sharma, Myunggi Yi, Hao Dong and Huajun Qin, all of FSU, and Emily Peterson of BYU.
The National High Magnetic Field Laboratory develops and operates state-of-the-art, high-magnetic-field facilities that faculty and visiting scientists and engineers use for research. The laboratory is sponsored by the National Science Foundation and the state of Florida. To learn more, visit here.
Source:
Florida State University
Buy Chloroquine Without Prescription
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