Schapira A.H.V.,University College London |
Fox S.H.,University of Toronto |
Hauser R.A.,University of South Florida |
Jankovic J.,Baylor College of Medicine |
And 6 more authors.
JAMA Neurology | Year: 2017
IMPORTANCE Although levodopa remains the most effective oral pharmacotherapy for Parkinson disease (PD), its use is often limited by wearing off effect and dyskinesias. Management of such complications continues to be a significant challenge. OBJECTIVE To investigate the efficacy and safety of safinamide (an oral aminoamide derivative with dopaminergic and nondopaminergic actions) in levodopa-treated patients with motor fluctuations. DESIGN, SETTING, AND PARTICIPANTS From March 5, 2009, through February 23, 2012, patients from academic PD care centers were randomized (1:1 ratio) to receive double-blind adjunctive safinamide or placebo for 24 weeks. All patients had idiopathic PD with "off" time (time when medication effect has worn off and parkinsonian features, including bradykinesia and rigidity, return) of greater than 1.5 hours per day (excluding morning akinesia). Their pharmacotherapy included oral levodopa plus benserazide or carbidopa in a regimen that had been stable for 4 weeks or longer. During screening, each patient's regimen was optimized to minimize motor fluctuations. Study eligibility required that after 4 weeks of optimized treatment, the patients still have more than 1.5 hours per day of off time. Adverse events caused the premature study discontinuation of 12 individuals (4.4%) in the safinamide group and 10 individuals (3.6%) in the placebo group. INTERVENTIONS Patients took safinamide or placebo as 1 tablet daily with breakfast. If no tolerability issues arose by day 14, the starting dose, 50mg, was increased to 100mg. MAIN OUTCOMES AND MEASURES The prespecified primary outcomewas each treatment group's mean change from baseline to week 24 (or last "on" treatment value) in daily "on" time (relief of parkinsonian motor features) without troublesome dyskinesia, as assessed from diary data. RESULTS At 119 centers, 549 patients were randomized (mean [SD] age, 61.9 [9.0] years; 334 male [60.8%] and 371 white [67.6%]): 274 to safinamide and 275 to placebo. Among them, 245 (89.4%) receiving safinamide and 241 (87.6%) receiving placebo completed the study. Mean (SD) change in daily on time without troublesome dyskinesia was +1.42 (2.80) hours for safinamide, from a baseline of 9.30 (2.41) hours, vs +0.57 (2.47) hours for placebo, from a baseline of 9.06 (2.50) hours (least-squares mean difference, 0.96 hour; 95%CI, 0.56-1.37 hours; P < .001, analysis of covariance). The most frequently reported adverse event was dyskinesia (in 40 [14.6%] vs 15 [5.5%] and as a severe event in 5 [1.8%] vs 1 [0.4%]). CONCLUSIONS AND RELEVANCE The outcomes of this trial support safinamide as an effective adjunct to levodopa in patients with PD and motor fluctuations to improve on time without troublesome dyskinesia and reduce wearing off. © 2017 American Medical Association.
News Article | November 29, 2016
VANCOUVER, BC--(Marketwired - November 29, 2016) - Advanced Proteome Therapeutics Corporation ("APC" or the "Company") (TSX VENTURE: APC) ( : 0E8) is pleased to announce that it has invented a measurable basis for evaluating antibody labeling that provides key information on the pattern of labeling. The technology provides a means of sorting labeling entities according to the degree of selective labeling resulting from modification of a target antibody for conjugation. The methodology produces a rank order of candidate antibodies carrying antibody connectors for linkage to payloads such as drugs or toxins which should aid decision-making in ADC development. Immense growth is expected for the therapeutic antibody market which is estimated to reach nearly $125 Billion USD by the year 2020 (The therapeutic monoclonal antibody market: Ecker et al. MAbs 2015, Volume 7, ppgs 9-14.). This invention was developed to fulfil the Company's recently announced partnering initiatives with Wilex AG's subsidiary, Heidelberg Pharma GmbH and the Toronto Recombinant Antibody Centre (TRAC) at the University of Toronto. The method has been applied to measurements of the selectivity pattern that emerges from APC's experimental conditions for labeling commercially marketed antibody targets. Despite being prerequisites for a reliable assessment of performance of labeling technology, quantitative methods for the rapid determination of the purity of antibody-drug conjugates, and an analysis of the labeling pattern which produces them, have been lacking. APC's approach to impacting the field of antibody-drug conjugates is to design a labeling entity that places a handle on the antibody to which virtually any payload such as a drug or toxin can be attached. Since the Company is targeting "universal" sites on antibodies, the type that all IgG antibodies possess, it is important to emphasize that our approach could ultimately enable attaching drugs or toxins to any target antibody selectively, for which quantitative measurements are essential. (IgGs are the principal antibody carriers of ADCs.) Apropos of the above, APC is focusing on enabling technology, designed to link antibodies to drugs or toxins to produce pure and homogeneous antibody-drug conjugates. The field of antibody-drug conjugates affords numerous opportunities for improving the properties of therapeutic antibodies, but reliable methods for site-specifically attaching drugs or toxins to antibodies to give ADCs of high purity are needed to avoid the heterogeneity that currently limits applications of ADCs. The number of therapeutic antibodies and the companies producing them are legion, and growing, but comparatively few companies have capabilities for chemical modification of such antibodies aimed at producing "kinder and gentler" agents than classical chemotherapeutics. Advanced Proteome Therapeutics Corporation (APC) is advancing a site-specific protein modification technology platform to enable the development of superior protein therapeutics. Using this technology, APC has generated numerous and diverse modifications of annexin proteins with superior binding and stability properties, which are amenable to further labeling and conjugation for use in therapeutic applications. APC is now vigorously applying its technologies to achieve the site-specific labeling of therapeutic antibodies and provide the next generation of antibody-drug conjugates. Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. The forward-looking statements contained in this news release involve risks and uncertainties, and are subject to change based on various important factors including timely development and acceptance of new products, gaining product approval, successful entry into new markets, changes in financing conditions, and changes in FDA regulations.
Stocchi F.,IRCCS San Raffaele |
Borgohain R.,Nizam's Institute of Medical Sciences |
Onofrj M.,University of Chieti Pescara |
Schapira A.H.,University College London |
And 4 more authors.
Movement Disorders | Year: 2012
Safinamide is an α-aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add-on to dopamine agonist (DA) therapy in early-stage PD. In this 24-week, double-blind study, patients with early PD receiving a stable dose of a single DA were randomized to once-daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty-nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were -3.90 for safinamide 200 mg, -6.0 for safinamide 100 mg and -3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: -0.4; 95% confidence interval (CI): -2.3-1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: -1.9; 95% CI: -3.7 to -0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation. © 2011 Movement Disorder Society.
PubMed | University of Kansas Medical Center, Innsbruck Medical University, Autonomous University of Barcelona, Baylor College of Medicine and 6 more.
Type: | Journal: JAMA neurology | Year: 2016
Although levodopa remains the most effective oral pharmacotherapy for Parkinson disease (PD), its use is often limited by wearing off effect and dyskinesias. Management of such complications continues to be a significant challenge.To investigate the efficacy and safety of safinamide (an oral aminoamide derivative with dopaminergic and nondopaminergic actions) in levodopa-treated patients with motor fluctuations.From March 5, 2009, through February 23, 2012, patients from academic PD care centers were randomized (1:1 ratio) to receive double-blind adjunctive safinamide or placebo for 24 weeks. All patients had idiopathic PD with off time (time when medication effect has worn off and parkinsonian features, including bradykinesia and rigidity, return) of greater than 1.5 hours per day (excluding morning akinesia). Their pharmacotherapy included oral levodopa plus benserazide or carbidopa in a regimen that had been stable for 4 weeks or longer. During screening, each patients regimen was optimized to minimize motor fluctuations. Study eligibility required that after 4 weeks of optimized treatment, the patients still have more than 1.5 hours per day of off time. Adverse events caused the premature study discontinuation of 12 individuals (4.4%) in the safinamide group and 10 individuals (3.6%) in the placebo group.Patients took safinamide or placebo as 1 tablet daily with breakfast. If no tolerability issues arose by day 14, the starting dose, 50 mg, was increased to 100 mg.The prespecified primary outcome was each treatment groups mean change from baseline to week 24 (or last on treatment value) in daily on time (relief of parkinsonian motor features) without troublesome dyskinesia, as assessed from diary data.At 119 centers, 549 patients were randomized (mean [SD] age, 61.9 [9.0] years; 334 male [60.8%] and 371 white [67.6%]): 274 to safinamide and 275 to placebo. Among them, 245 (89.4%) receiving safinamide and 241 (87.6%) receiving placebo completed the study. Mean (SD) change in daily on time without troublesome dyskinesia was +1.42 (2.80) hours for safinamide, from a baseline of 9.30 (2.41) hours, vs +0.57 (2.47) hours for placebo, from a baseline of 9.06 (2.50) hours (least-squares mean difference, 0.96 hour; 95% CI, 0.56-1.37 hours; P<.001, analysis of covariance). The most frequently reported adverse event was dyskinesia (in 40 [14.6%] vs 15 [5.5%] and as a severe event in 5 [1.8%] vs 1 [0.4%]).The outcomes of this trial support safinamide as an effective adjunct to levodopa in patients with PD and motor fluctuations to improve on time without troublesome dyskinesia and reduce wearing off.clinicaltrials.gov Identifier NCT00627640.
Cai Z.-Y.,International School for Advanced Studies |
Cai Z.-Y.,Xiamen University |
Lapi A.,International School for Advanced Studies |
Lapi A.,University of Rome Tor Vergata |
And 10 more authors.
Astrophysical Journal | Year: 2013
We present a comprehensive investigation of the cosmological evolution of the luminosity function of galaxies and active galactic nuclei (AGNs) in the infrared (IR). Based on the observed dichotomy in the ages of stellar populations of early-type galaxies on one side and late-type galaxies on the other, the model interprets the epoch-dependent luminosity functions at z ≥ 1.5 using a physical approach for the evolution of proto-spheroidal galaxies and of the associated AGNs, while IR galaxies at z < 1.5 are interpreted as being mostly late-type "cold" (normal) and "warm" (starburst) galaxies. As for proto-spheroids, in addition to the epoch-dependent luminosity functions of stellar and AGN components separately, we have worked out, for the first time, the evolving luminosity functions of these objects as a whole (stellar plus AGN component), taking into account in a self-consistent way the variation with galactic age of the global spectral energy distribution. The model provides a physical explanation for the observed positive evolution of both galaxies and AGNs up to z ≃ 2.5 and for the negative evolution at higher redshifts, for the sharp transition from Euclidean to extremely steep counts at (sub-)millimeter wavelengths, as well as the (sub-)millimeter counts of strongly lensed galaxies that are hard to account for by alternative, physical or phenomenological, approaches. The evolution of late-type galaxies and z < 1.5 AGNs is described using a parametric phenomenological approach. The modeled AGN contributions to the counts and to the cosmic infrared background (CIB) are always sub-dominant. They are maximal at mid-IR wavelengths: the contribution to the 15 and 24 μm counts reaches 20% above 10 and 2 mJy, respectively, while the contributions to the CIB are of 8.6% and of 8.1% at 15 μm and 24 μm, respectively. The model provides a good fit to the multi-wavelength (from the mid-IR to millimeter waves) data on luminosity functions at different redshifts and on number counts (both global and per redshift slices). A prediction of the present model, useful to test it, is a systematic variation with wavelength of the populations dominating the counts and the contributions to the CIB intensity. This implies a specific trend for cross-wavelength CIB power spectra, which is found to be in good agreement with the data. © 2013. The American Astronomical Society. All rights reserved.
Stanciu C.,Nicolae Titulescu University of Bucharest |
Rissdorfer M.,APC |
Quality - Access to Success | Year: 2015
In a study realized by APC – Romania on 70 types of vegetable pate or paste from Romania, 19 producers (including 7 undeclared (?)), we found that only the big chains like Cora, Carrefour, Mega Image Hame says and that only some of vegetable products that are not genetically modified. Perhaps European legislation applies only to them in Romania. The remaining domestic producers (INEDIT, Glina, Prefera Foods, Production Transylvania, Regal Corp, Vascar, Scandia Food, Winny, Kaufland, Rewe, Billa, Profi, Auchan), violates the law on declaration of GMOs and no absolutely no information, although in the composition of their products appear soy protein, wheat flour, modified starch or corn or wheat. © 2015, SRAC - Societatea Romana Pentru Asigurarea Calitatii. All Rights Reserved.
Kumar V.,NIMS University |
Sharma U.K.,KVK Inc |
Annals of Agri Bio Research | Year: 2012
Marketing system for honey is spread in the North-Eastern Zone of Haryana state. The marketing of honey is done mainly by two channels : (1) Producer-Consumer (sale at farm) and (2) Producer-Wholesaler-Retailer-Consumer. The net share of producer in the consumer's rupee was 83.53, 84.29 and 88.87%, respectively, in small, medium and large categories. This relative share of the producer in consumer's rupee was worked out when there was no middleman involved in distributing the honey. In overall beekeepers categories, the net share in price paid by the consumer was 54.52% in Production-Wholesaler-Retailer-Consumer channel. The whole analysis of marketing costs and margins indicated that though main marketing channel revealed that the expenses incurred by wholesaler decreased as increase in size of beekeeping and decreased as increase in size of beekeeping and the margin of enterprise. But the retailer margin decreased as the increase in quantum of the product.
2009 CERN-Latin-American School of High-Energy Physics, CLASHEP 2009 - Proceedings | Year: 2010
In these three lectures I discuss the present status of high-energy astroparticle physics including Ultra-High-Energy Cosmic Rays (UHECR), high-energy gamma rays, and neutrinos. The first lecture is devoted to ultra-high-energy cosmic rays. After a brief introduction to UHECR I discuss the acceleration of charged particles to highest energies in the astrophysical objects, their propagation in the intergalactic space, recent observational results by the Auger and HiRes experiments, anisotropies of UHECR arrival directions, and secondary gamma rays produced by UHECR. In the second lecture I review recent results on TeV gamma rays. After a short introduction to detection techniques, I discuss recent exciting results of the H.E.S.S., MAGIC, and Milagro experiments on the point-like and diffuse sources of TeV gamma rays. A special section is devoted to the detection of extragalactic magnetic fields with TeV gammaray measurements. Finally, in the third lecture I discuss Ultra-High-Energy (UHE) neutrinos. I review three different UHE neutrino detection techniques and show the present status of searches for diffuse neutrino flux and point sources of neutrinos.
EngineerIT | Year: 2011
Neil Rasmussen, APC, informs about terms, such as power factor, crest factor, and surge factor, which refer to completely different and unrelated phenomena. Power factor is a quantity which has important implications when implementing a UPS system and power distribution equipment. Power is a measure of the delivery rate of energy and in direct current (DC) electrical circuits is expressed as the mathematical product of volts and amps. Crest factor is the ratio between the instantaneous peak current required by the load and the root mean square (RMS) current. Most common electrical appliances exhibit a crest factor of 1,4, while computers and IT equipment with power factor corrected power supplies exhibit a crest factor of 1,4. Surge factor relates to the momentary overload capacity of the UPS and is a measure of the ability of the UPS to startup loads, which temporarily require extra power when they start-up.
Binetruy P.,APC |
Bohe A.,APC |
Hertog T.,APC |
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2010
Junctions on cosmic string loops give rise to the proliferation of sharp kinks. We study the effect of this proliferation on the gravitational wave (GW) signals emitted from string networks with junctions, assuming a scaling solution. We calculate the rate of occurrence and the distribution in amplitude of the GW bursts emitted at cusps and kinks in the frequency bands of LIGO/VIRGO and LISA as a function of the string tension, the number of sharp kinks on loops with junctions, and the fraction of loops in the cosmological network which have junctions. Combining our results with current observational constraints, we find that pulsar data rule out a significant number of kinks on loops for strings with tensions Gμ10⊃-12. By contrast, for smaller tensions current observations allow for a large number of kinks on loops. If this is the case, the incoherent superposition of small bursts emitted at kink-kink encounters leads to an enhanced GW background that hides the strong individual bursts from kinks and cusps. © 2010 The American Physical Society.