| 1. |
- Devos, David, et al.
(författare)
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Trial of Deferiprone in Parkinson’s Disease
- 2022
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 387:22, s. 2045-2055
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
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| 2. |
- Runnholm, Axel, 1992-, et al.
(författare)
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On the evolution of the size of Lyman alpha haloes across cosmic time : no change in the circumgalactic gas distribution when probed by line emission
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 522:3, s. 4275-4293
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Tidskriftsartikel (refereegranskat)abstract
- Lyman alpha (Ly alpha) is now routinely used as a tool for studying high-redshift galaxies, and its resonant nature means it can trace neutral hydrogen around star-forming galaxies. Integral field spectrograph measurements of high-redshift Ly alpha emitters indicate that significant extended Ly alpha halo emission is ubiquitous around such objects. We present a sample of redshift 0.23 to 0.31 galaxies observed with the Hubble Space Telescope selected to match the star formation properties of high-z samples while optimizing the observations for detection of low surface brightness Ly alpha emission. The Ly alpha escape fractions range between 0.7 and 37 per cent, and we detect extended Ly alpha emission around six out of seven targets. We find Ly alpha halo to UV scale length ratios around 6:1, which is marginally lower than high-redshift observations, and halo flux fractions between 60 and 85 per cent - consistent with high-redshift observations - when using comparable methods. However, our targets show additional extended stellar UV emission: we parametrize this with a new double exponential model. We find that this parametrization does not strongly affect the observed Ly alpha halo fractions. We find that deeper H alpha data would be required to firmly determine the origin of Ly alpha halo emission; however, there are indications that H alpha is more extended than the central FUV profile, potentially indicating conditions favourable for the escape of ionizing radiation. We discuss our results in the context of high-redshift galaxies, cosmological simulations, evolutionary studies of the circumgalactic medium in emission, and the emission of ionizing radiation.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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