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- Comi, G, et al.
(författare)
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Effects of early treatment with glatiramer acetate in patients with clinically isolated syndrome
- 2013
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:8, s. 1074-1083
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Tidskriftsartikel (refereegranskat)abstract
- The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome and brain lesions on MRI. Objective: To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe. Methods: Patients with a clinically isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were randomized to receive glatiramer acetate 20 mg/d (early-treatment, n=198) or placebo (delayed-treatment, n=211) for 36 months or until conversion to CDMS, followed by open-label glatiramer acetate treatment for two years. Results: Early glatiramer acetate treatment reduced CDMS conversion risk by 41% (hazard ratio 0.59, 95% confidence interval 0.44–0.80; p=0.0005) versus delayed-treatment, and was associated with a 972-day delay (185%) in conversion to CDMS, less brain atrophy (−28%, p=0.0209), fewer new T2 lesions/year (−42%, <0.0001) and lower T2 lesion volume (−22%, p=0.0005) versus delayed treatment. Adverse events were consistent with the established safety profile of glatiramer acetate. Conclusions: Effects of early glatiramer acetate treatment on the rate of conversion to CDMS and on MRI measures of disease activity and lesion burden support initiating glatiramer acetate treatment soon after the first clinical symptoms suggestive of MS and continuing treatment to sustain benefits.
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- Lemcke, S., et al.
(författare)
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Nerve conduction velocity is regulated by the inositol polyphosphate-4-phosphatase II gene
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 184:9, s. 2420-2429
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Tidskriftsartikel (refereegranskat)abstract
- Impairment of nerve conduction is common in neurodegenerative and neuroinflammatory diseases such as multiple sclerosis (MS), and measurement of evoked potentials (visual, motor, or sensory) has been widely used for diagnosis and recently also as a prognostic marker for MS. We used a classical genetic approach to identify novel genes controlling nerve conduction. First, we used quantitative trait mapping in F2 progeny of B10/SJL mice to identify EAE31, a locus controlling latency of motor evoked potentials (MEPs) and clinical onset of experimental autoimmune encephalomyelitis. Then, by combining congenic mapping, in silico haplotype analyses, and comparative genomics we identified inositol polyphosphate-4-phosphatase, type II (Inpp4b) as the quantitative trait gene for EAE31. Sequence variants of Inpp4b (C/A, exon 13; A/C, exon 14) were identified as differing among multiple mouse strains and correlated with individual cortical MEP latency differences. To evaluate the functional relevance of the amino acid exchanges at positions S474R and H548P, we generated transgenic mice carrying the longer-latency allele (Inpp4b(474R/548P)) in the C57BL/6J background. Inpp4b(474R/548P) mice exhibited significantly longer cortical MEP latencies (4.5 +/- 0.22 ms versus 3.7 +/- 0.13 ms; P = 1.04 x 10(-9)), indicating that INPP4B regulates nerve conduction velocity. An association of an INPP4B polymorphism (rs13102150) with MS was observed in German and Spanish MS cohorts (3676 controls and 911 cases) (P = 8.8 x 10(-3)).
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- Rauer, H., et al.
(författare)
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The PLATO 2.0 mission
- 2014
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 38:1-2, s. 249-330
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Tidskriftsartikel (refereegranskat)abstract
- PLATO 2.0 has recently been selected for ESA's M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s cadence) providing a wide field-of-view (2232 deg(2)) and a large photometric magnitude range (4-16 mag). It focuses on bright (4-11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4-10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2-3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e. g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such a low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmospheres. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA's Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.
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- Sorensen, PS, et al.
(författare)
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Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab
- 2012
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 18:2, s. 143-152
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Tidskriftsartikel (refereegranskat)abstract
- Natalizumab is a highly effective immunomodulator in the treatment of multiple sclerosis (MS). Treatment with natalizumab has been associated with progressive multifocal leukoencephalopathy (PML), an infection of the central nervous system (CNS) caused by a pathogenic form of the normally benign JC virus (JCV). We searched PubMed and used current data from the natalizumab global safety database to assess risk factors and quantify the risk of PML. Natalizumab treatment duration and prior use of immunosuppressive therapies are established risk factors for development of PML in natalizumab-treated patients. With the development of a reliable and validated assay for detection of antibodies in patients with MS directed against JCV, it is now possible to identify persons who are carriers of JCV. The availability of this assay provides an additional option for risk stratification of PML in patients using or considering natalizumab therapy. Recommendations for clinical management of patients with MS and use of natalizumab are provided based on the presence of these three risk factors. The identification of risk factors that increase the likelihood of PML in natalizumab-treated patients can facilitate benefit–risk discussions between health care professionals and patients. Continued research and data collection will further develop our understanding of PML and the mechanisms by which these risk factors contribute to its development.
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