Khatri B.O.,Regional Center
Therapeutic Advances in Neurological Disorders | Year: 2016
Since the approval in 2010 of fingolimod 0.5 mg (Gilenya; Novartis Pharma AG, Basel, Switzerland) in the USA as an oral therapy for relapsing forms of multiple sclerosis, long-term clinical experience with this therapy has been increasing. This review provides a summary of the cumulative dataset from clinical trials and their extensions, plus postmarketing studies that contribute to characterizing the efficacy and safety profile of fingolimod in patients with relapsing forms of multiple sclerosis. Data from the controlled, phase III, pivotal studies [FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis), FREEDOMS II and TRANSFORMS (Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis)] in relapsing-remitting multiple sclerosis have shown that fingolimod has a robust effect on clinical and magnetic resonance imaging outcomes. The respective study extensions show that effects on annualized relapse rates are sustained with continued fingolimod treatment. Consistent, significant reductions in magnetic resonance imaging lesion counts and brain volume loss have also been sustained with long-term treatment. The safety profile of fingolimod is also examined, particularly in light of its long-term use. A summary of the adverse events of interest that are associated with fingolimod treatment and associated label guidelines are also considered, which include cardiac effects following first-dose administration, infections, lymphopenia, macular edema and pregnancy. Historic hurdles to the prescription of fingolimod and how these challenges are being met are also discussed. © The Author(s), 2016.
Gupta Choudhury S.,Indian Central Soil Salinity Research Institute |
Srivastava S.,Purbanchal University |
Singh R.,Indian Central Soil Salinity Research Institute |
Chaudhari S.K.,Indian Central Soil Salinity Research Institute |
And 3 more authors.
Soil and Tillage Research | Year: 2014
Conservation tillage and residue management are the options for enhancing soil organic carbon stabilization by improving soil aggregation in tropical soils. We studied the influence of different combinations of tillage and residue management on carbon stabilization in different sized soil aggregates and also on crop yield after 5 years of continuous rice-wheat cropping system on a sandy loam reclaimed sodic soil of north India. Compared to conventional tillage, water stable macroaggregates in conservation tillage (reduced and zero-tillage) in wheat coupled with direct seeded rice (DSR) was increased by 50.13% and water stable microaggregates of the later decreased by 10.1% in surface soil. Residue incorporation caused a significant increment of 15.65% in total water stable aggregates in surface soil (0-15cm) and 7.53% in sub-surface soil (15-30cm). In surface soil, the maximum (19.2%) and minimum (8.9%) proportion of total aggregated carbon was retained with >2mm and 0.1-0.05mm size fractions, respectively. DSR combined with zero tillage in wheat along with residue retention (T6) had the highest capability to hold the organic carbon in surface (11.57gkg-1 soil aggregates) with the highest stratification ratio of SOC (1.5). Moreover, it could show the highest carbon preservation capacity (CPC) of coarse macro and mesoaggregates. A considerable proportion of the total SOC was found to be captured by the macroaggregates (>2-0.25mm) under both surface (67.1%) and sub-surface layers (66.7%) leaving rest amount in microaggregates and 'silt+clay' sized particles. From our study, it has been proved that DSR with zero tillage in wheat (with residue) treatment (T6) has the highest potential to secure sustainable yield increment (8.3%) and good soil health by improving soil aggregation (53.8%) and SOC sequestration (33.6%) with respect to the conventional tillage with transplanted rice (T1) after five years of continuous rice-wheat cropping in sandy loam reclaimed sodic soil of hot semi-arid Indian sub-continent. © 2013 Elsevier B.V.
Cohen J.A.,Cleveland Clinic |
Barkhof F.,VU University Amsterdam |
Comi G.,Vita-Salute San Raffaele University |
Hartung H.-P.,Heinrich Heine University Dusseldorf |
And 13 more authors.
New England Journal of Medicine | Year: 2010
Background: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. Methods: In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a (an established therapy for multiple sclerosis) at a weekly dose of 30 μg. The primary end point was the annualized relapse rate. Key secondary end points were the number of new or enlarged lesions on T2-weighted magnetic resonance imaging (MRI) scans at 12 months and progression of disability that was sustained for at least 3 months. Results: A total of 1153 patients (89%) completed the study. The annualized relapse rate was significantly lower in both groups receiving fingolimod - 0.20 (95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg group and 0.16 (95% CI, 0.12 to 0.21) in the 0.5-mg group - than in the interferon group (0.33; 95% CI, 0.26 to 0.42; P<0.001 for both comparisons). MRI findings supported the primary results. No significant differences were seen among the study groups with respect to progression of disability. Two fatal infections occurred in the group that received the 1.25-mg dose of fingolimod: disseminated primary varicella zoster and herpes simplex encephalitis. Other adverse events among patients receiving fingolimod were nonfatal herpesvirus infections, bradycardia and atrioventricular block, hypertension, macular edema, skin cancer, and elevated liver-enzyme levels. Conclusions: This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as compared with intramuscular interferon beta-1a. Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year. Copyright © 2010 Massachusetts Medical Society. All rights reserved.
News Article | December 14, 2015
If you want to book a trip to visit (or come back to) the United States, Homeland Security might soon be asking you for your Twitter handle along with your passport. According to the Wall Street Journal, the federal department wants to parse social media posts to determine if visa candidates might pose a threat to national security. The visa review proposal comes mere weeks after a Dec. 2 shooting at the Inland Regional Center in San Bernadino, Calif., which resulted in 14 casualties, with 22 wounded on the scene. The Los Angeles Times has called the massacre "the worst terrorist attack on American soil since Sept. 11, 2001." One of the assailants, Tashfeen Malik, came to the U.S. from Pakistan on a visa, despite undergoing three separate background checks to do so. Currently, it is illegal for Homeland Security agents to scrutinize an applicant's social media pages or accounts. A similar proposal to revert this ruling was dismissed in 2014 by Homeland Security Secretary Jeh Johnson. At the time of her visa review, Malik's social media accounts were not checked for suspicious activity, despite the fact that she frequently posted pro-jihadist sentiments. In a statement following the attack, President Barack Obama exhorted "high-tech and law enforcement leaders to make it harder for terrorists to use technology to escape from justice."
The new mass-spectral imaging system is the first of its kind in the world and its applications are just beginning to surface, said Carmen Menoni, a University Distinguished Professor in the Department of Electrical and Computer Engineering. A special issue of Optics and Photonics News last month highlights the CSU research among "the most exciting peer-reviewed optics research to have emerged over the past 12 months." Editors identified the imaging device among global "breakthroughs of interest to the optics community." Menoni's group, in collaboration with an interdisciplinary group of faculty, devised and built the instrument with help from students. She found a partner in CSU's renowned Mycobacteria Research Laboratories, which seek new treatments for the global scourge of tuberculosis. The partners described the system in a paper published earlier this year in Nature Communications. Dean Crick, a professor who researches tuberculosis, collaborated with Menoni to refine the mass spectrometer imaging system. He said the instrument will allow him to examine cells at a level 1,000 times smaller than that of a human hair - about 100 times more detailed than was earlier possible. This will give researchers the ability to observe how well experimental drugs penetrate and are processed by cells as new medications are developed to combat disease. Crick's primary research interest is tuberculosis, an infectious respiratory disease that contributes to an estimated 1.5 million deaths around the world each year. "We've developed a much more refined instrument," Crick said. "It's like going from using a dull knife to using a scalpel. You could soak a cell in a new drug and see how it's absorbed, how quickly, and how it affects the cell's chemistry." The earlier generation of laser-based mass-spectral imaging could identify the chemical composition of a cell and could map its surface in two dimensions at the microscale, but could not chart cellular anatomy at the more detailed nanoscale and in 3-D, Crick said. In addition to observing how cells respond to new drugs, he said, researchers could use the technology to identify the sources of pathogens propagated for bioterrorism. The instrument might also be used to investigate new ways to overcome antibiotic resistance among patients with surgical implants. "You might be able to customize treatments for specific cell types in specific conditions," Crick said. The CSU instrument would cover the average dining room table. Its central features are mass-spectral imaging technology and an extreme ultraviolet laser. Jorge Rocca, also a University Distinguished Professor in the Department of Electrical and Computer Engineering, created the laser attached to the spectrometer. Its beam is invisible to the human eye and is generated by an electrical current 20,000 times stronger than that of regular fluorescent tubes in ceiling lights, resulting in a tiny stream of plasma that is very hot and dense. The plasma acts as a gain medium for generating extreme ultraviolet laser pulses. The laser may be focused to shoot into a cell sample; each time the laser drills a tiny hole, miniscule charged particles, or ions, evaporate from the cell surface. These ions then may be separated and identified, allowing scientists to determine chemical composition. The microscopic shrapnel ejected from each hole allows scientists to chart the anatomy of a cell piece by piece, in three dimensions, at a scale never seen before, the scientists said. The project was funded with $1 million from the National Institutes of Health as part of an award to the Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research. The optical equipment that focuses the laser beam was created by the Center for X-Ray Optics at the Lawrence Berkeley National Laboratory in Berkeley, Calif. The CSU system recently received support for system engineering design from Siemens. The company gave the CSU team an academic grant for its NX software package, including 30 seat licenses, valued at $37 million. Other CSU faculty involved in the project include Feng Dong and Elliot Bernstein from the Department of Chemistry. The lead author on the paper published in Nature Communications is Ilya Kuznetsov, a CSU doctoral student in Electrical and Computer Engineering. "The whole system was built by students and post-docs," Menoni said. "This is something we pride ourselves on, that the students get an interdisciplinary experience. Having access to design software such as the Siemens NX package is critical for creating these instruments and for training students." Key to the project has been collaboration among scientists who build high-tech devices and those who use them to solve global problems. "It's been very interesting learning how to communicate with engineers," Crick said. "We don't think alike. They understand the biology about as well as I understand the engineering. But over the years we've learned how to talk to each other, which is nice. I can see the need for the instrument, but I have no idea how to build it. They do." At one end of the instrument is a special laser created in an argon gas-filled tube when a pulse of 60 kilovolts is discharged. "It's like a lightning strike in a nanosecond," said Carmen Menoni, University Distinguished Professor in the Department of Electrical and Computer Engineering. The laser is guided through chambers using mirrors and special lenses that focus it down to a diameter of less than 100 nanometers. In a chamber at the far side of the spectrometer, the laser hits a sample cell placed with the aid of a microscope. "When you're trying to hit a single bacterium with a laser, it's tricky. You have to aim well," said Dean Crick, a CSU professor in the Department of Microbiology, Immunology and Pathology. Once the laser drills a miniscule hole in the cell, charged ions emitted after the tiny explosion are drawn into a side tube using electrostatic fields. The larger mass the charged particle has, the slower it moves down the tube; the time it takes an ion to reach a detector gives scientists information about its mass. "It's like you have a sports car and a big truck," said Ilya Kuznetsov, a doctoral student in Electrical and Computer Engineering. "Imagine you put the same motor in both—they will move at different speeds. And the more you allow them to go, the more they separate. That's why our tube is so long, to allow for that differentiation." A set of special pumps creates high vacuum that sucks all air from the tube, to remove any foreign particles the sample might collide with and to ensure equally smooth sailing for all the ions. "If you want to have a car race, you need to remove all traffic from the roads," Kuznetsov explained. By keeping the charge and amount of energy applied to each particle consistent, the mass becomes the key signature that provides researchers with every ion's chemical identity. A computer program developed in-house generates the data in a color spectrum of masses, which is then used to create a kind of topographical cell composition map. Explore further: Research team refrigerates liquids with a laser for the first time