Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing-remitting multiple sclerosis in a real-world clinical setting: PROTEC.

Ensaio clínico PROTEC, Protocolo nº 109MS408Abstract BACKGROUND: Patient-reported outcomes (PRO) and clinical outcomes give a broad assessment of relapsing-remitting multiple sclerosis (RRMS) disease. OBJECTIVE: The aim is to evaluate the effectiveness of delayed-release dimethyl fumarate (DMF) on disease activity and PROs in patients with RRMS in the clinic. METHODS: PROTEC, a phase 4, open-label, 12-month observational study, assessed annualized relapse rate (ARR), proportion of patients relapsed, and changes in PROs. Newly diagnosed and early MS (≤3.5 EDSS and ≤1 relapse in the prior year) patient subgroups were evaluated. RESULTS: Unadjusted ARR at 12 months post-DMF versus 12 months before DMF initiation was 75% lower (0.161 vs. 0.643, p < 0.0001) overall (n = 1105) and 84%, 77%, and 71% lower in newly diagnosed, ≤3.5 EDSS, and ≤1 relapse subgroups, respectively. Overall, 88% of patients were relapse-free 12 months after DMF initiation (84%, newly diagnosed; 88%, ≤3.5 EDSS; 88%, ≤1 relapse). PRO measures for fatigue, treatment satisfaction, daily living, and work improved significantly over 12 months of DMF versus baseline. CONCLUSION: At 12 months after versus 12 months before DMF initiation, ARR was significantly lower, the majority of patients were relapse-free, and multiple PRO measures showed improvement (overall and for subgroups), suggesting that DMF is effective based on clinical outcomes and from a patient perspective.Clinical trial: A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes (PROTEC), NCT01930708,info:eu-repo/semantics/publishedVersio

On the number of limit cycles of the Lienard equation

In this paper, we study a Lienard system of the form dot{x}=y-F(x), dot{y}=-x, where F(x) is an odd polynomial. We introduce a method that gives a sequence of algebraic approximations to the equation of each limit cycle of the system. This sequence seems to converge to the exact equation of each limit cycle. We obtain also a sequence of polynomials R_n(x) whose roots of odd multiplicity are related to the number and location of the limit cycles of the system.Comment: 10 pages, 5 figures. Submitted to Physical Review

Laccase-Carrying Polylactic Acid Electrospun Fibers, Advantages and Limitations in Bio-Oxidation of Amines and Alcohols

Laccases are oxidative enzymes that could be good candidates for the functionalization of biopolymers with several applications as biosensors for the determination of bioactive amine and alcohols, for bioremediation of industrial wastewater, and for greener catalysts in oxidation reactions in organic synthesis, especially used for non-phenolic compounds in combination with redox mediators in the so-called Laccase Mediator System (LMS). In this work, we describe the immobilization of Laccase from Trametes versicolor (LTv) in poly-L-lactic acid (PLLA) nanofibers and its application in LMS oxidation reactions. The PLLA-LTv catalysts were successfully produced by electrospinning of a water-in-oil emulsion with an optimized method. Different enzyme loadings (1.6, 3.2, and 5.1% (w)/(w)) were explored, and the obtained mats were thoroughly characterized. The actual amount of the enzyme in the fibers and the eventual enzyme leaching in different solvents were evaluated. Finally, the PLLA-LTv mats were successfully applied as such in the oxidation reaction of catechol, and in the LMS method with TEMPO as mediator in the oxidation of amines with the advantage of easier work-up procedures by the immobilized enzyme. However, the PLLA-LTv failed the oxidation of alcohols with respect to the free enzyme. A tentative explanation was provided

An analytical approximation scheme to two point boundary value problems of ordinary differential equations

A new (algebraic) approximation scheme to find {\sl global} solutions of two point boundary value problems of ordinary differential equations (ODE's) is presented. The method is applicable for both linear and nonlinear (coupled) ODE's whose solutions are analytic near one of the boundary points. It is based on replacing the original ODE's by a sequence of auxiliary first order polynomial ODE's with constant coefficients. The coefficients in the auxiliary ODE's are uniquely determined from the local behaviour of the solution in the neighbourhood of one of the boundary points. To obtain the parameters of the global (connecting) solutions analytic at one of the boundary points, reduces to find the appropriate zeros of algebraic equations. The power of the method is illustrated by computing the approximate values of the ``connecting parameters'' for a number of nonlinear ODE's arising in various problems in field theory. We treat in particular the static and rotationally symmetric global vortex, the skyrmion, the Nielsen-Olesen vortex, as well as the 't Hooft-Polyakov magnetic monopole. The total energy of the skyrmion and of the monopole is also computed by the new method. We also consider some ODE's coming from the exact renormalization group. The ground state energy level of the anharmonic oscillator is also computed for arbitrary coupling strengths with good precision.Comment: 5 pages, 3 tables, Late

Performance of Irradiated Thin Edgeless N-on-P Planar Pixel Sensors for ATLAS Upgrades

In view of the LHC upgrade phases towards the High Luminosity LHC (HL-LHC), the ATLAS experiment plans to upgrade the Inner Detector with an all-silicon system. Because of its radiation hardness and cost effectiveness, the n-on-p silicon technology is a promising candidate for a large area pixel detector. The paper reports on the joint development, by LPNHE and FBK of novel n-on-p edgeless planar pixel sensors, making use of the active trench concept for the reduction of the dead area at the periphery of the device. After discussing the sensor technology, a complete overview of the electrical characterization of several irradiated samples will be discussed. Some comments about detector modules being assembled will be made and eventually some plans will be outlined.Comment: 6 pages, 13 figures, to appear in the proceedings of the 2013 Nuclear Science Symposium and Medical Imaging Conference. arXiv admin note: text overlap with arXiv:1311.162

Electrical Characterization of a Thin Edgeless N-on-p Planar Pixel Sensors For ATLAS Upgrades

In view of the LHC upgrade phases towards the High Luminosity LHC (HL-LHC), the ATLAS experiment plans to upgrade the Inner Detector with an all-silicon system. Because of its radiation hardness and cost effectiveness, the n-on-p silicon technology is a promising candidate for a large area pixel detector. The paper reports on the joint development, by LPNHE and FBK of novel n-on-p edgeless planar pixel sensors, making use of the active trench concept for the reduction of the dead area at the periphery of the device. After discussing the sensor technology, and presenting some sensors' simulation results, a complete overview of the electrical characterization of the produced devices will be given.Comment: 9 pages, 9 figures, to appear in the proceedings of the 15th International Workshops on Radiation Imaging Detector

Development of Edgeless n-on-p Planar Pixel Sensors for future ATLAS Upgrades

The development of n-on-p "edgeless" planar pixel sensors being fabricated at FBK (Trento, Italy), aimed at the upgrade of the ATLAS Inner Detector for the High Luminosity phase of the Large Hadron Collider (HL-LHC), is reported. A characterizing feature of the devices is the reduced dead area at the edge, achieved by adopting the "active edge" technology, based on a deep etched trench, suitably doped to make an ohmic contact to the substrate. The project is presented, along with the active edge process, the sensor design for this first n-on-p production and a selection of simulation results, including the expected charge collection efficiency after radiation fluence of $1 \times 10^{15} {\rm n_{eq}}/{\rm cm}^2$ comparable to those expected at HL-LHC (about ten years of running, with an integrated luminosity of 3000 fb$^{-1}$) for the outer pixel layers. We show that, after irradiation and at a bias voltage of 500 V, more than 50% of the signal should be collected in the edge region; this confirms the validity of the active edge approach.Comment: 20 pages, 9 figures, submitted to Nucl. Instr. and Meth.

Novel Silicon n-on-p Edgeless Planar Pixel Sensors for the ATLAS upgrade

In view of the LHC upgrade phases towards HL-LHC, the ATLAS experiment plans to upgrade the Inner Detector with an all-silicon system. The n-on-p silicon technology is a promising candidate for the pixel upgrade thanks to its radiation hardness and cost effectiveness, that allow for enlarging the area instrumented with pixel detectors. We report on the development of novel n-in-p edgeless planar pixel sensors fabricated at FBK (Trento, Italy), making use of the "active edge" concept for the reduction of the dead area at the periphery of the device. After discussing the sensor technology and fabrication process, we present device simulations (pre- and post-irradiation) performed for different sensor configurations. First preliminary results obtained with the test-structures of the production are shown.Comment: 6 pages, 5 figures, to appear in the proceedings of the 9th International Conference on Radiation Effects on Semiconductor Materials Detectors and Device

Dating long thrust systems on Mercury: new clues on the thermal evolution of the planet

The global tectonics of Mercury is dominated by contractional features mainly represented by lobate scarps, high relief ridges, and wrinkle ridges. These structures are the expression of thrust faults and are linear or arcuate features widely distributed on Mercury. Locally, these structures are arranged in long systems characterized by a preferential orientation and non-random spatial distribution. In this work we identified five thrust systems, generally longer than 1000 km. They were named after the main structure or crater encompassed by the system as: Thakur, Victoria, Villa Lobos, Al-Hamadhani, and Enterprise. In order to gain clues about their formation, we dated them using the buffered crater counting technique, which can be applied to derive the ages of linear landforms such as faults, ridges and channels. To estimate the absolute age for the end of the thrust system's activity, we applied both Le Feuvre and Wieczorek Production Function and Neukum Production Functions. Moreover, to further confirm the results obtained with the buffered crater counting method, the classic stratigraphic approach has been adopted, in which a faulted and an unfaulted craters were dated for each system. The results gave consistent ages and suggested that the most movements along major structures all over Mercury most likely ended at about 3.6–3.8 Ga. This gives new clues to better understand the tectonics of the planet and, therefore, its thermal evolution. Indeed, the early occurrence of tectonic activity in the planet's history, well before than predicted by the thermophysical models, coupled with the orientation and spatial distribution of the thrust systems, suggests that other processes beside global contraction, like mantle downwelling or tidal despinning, could have contributed to the first stage of the planet's history. Keywords: Mercury, Thrust systems, Crater counting, Thermal evolution, Planetary geology, Structural geolog