| 261. |
- Gatt, A, et al.
(författare)
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Importance of Proactive Treatment of Depression in Lewy Body Dementias: The Impact on Hippocampal Neurogenesis and Cognition in a Post-Mortem Study
- 2017
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 44:5-6, s. 283-293
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Objective:</i></b> To examine the impact of selective serotonin reuptake inhibitors (SSRIs) and depression on neurogenesis and cognition in dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). <b><i>Methods:</i></b> Late-stage progenitor cells were quantified in the subgranular zone (SGZ) of the hippocampal dentate gyrus of DLB/PDD patients (<i>n</i> = 41) and controls without dementia (<i>n</i> = 15) and compared between treatment groups (unmedicated, SSRIs, acetyl cholinesterase inhibitors [AChEIs], combined SSRIs and AChEIs). <b><i>Results:</i></b> DLB/PDD patients had more doublecortin-positive cells in the SGZ compared to controls. The doublecortin-positive cell count was higher in the SGZ of patients treated with SSRIs and correlated to higher cognitive scores. <b><i>Conclusion:</i></b> SSRI treatment was associated with increased hippocampal neurogenesis and preservation of cognition in DLB/PDD patients.
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| 262. |
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| 263. |
- Hegi, Monika E., et al.
(författare)
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No benefit from TMZ treatment in glioblastoma with truly unmethylated MGMT promoter : reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly glioblastoma patients
- 2024
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866.
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Tidskriftsartikel (refereegranskat)abstract
- Background: The treatment of elderly/ frail patients with glioblastoma is a balance between avoiding undue toxicity, while not withholding effective treatment. It remains debated, whether these patients should receive combined chemo-radiotherapy with temozolomide (RT/TMZ -> TMZ) regardless of the O6-methylguanine DNA methyltransferase gene promoter (MGMTp) methylation status. MGMT is a well-known resistance factor blunting the treatment effect of TMZ, by repairing the most genotoxic lesion. Epigenetic silencing of the MGMTp sensitizes glioblastoma to TMZ. For risk-adapted treatment, it is of utmost importance to accurately identify patients, who will not benefit from TMZ treatment.Methods: Here, we present a reanalysis of the clinical trials CE.6 and the pooled NOA-08 and Nordic trials in elderly glioblastoma patients that compared RT to RT/TMZ -> TMZ, or RT to TMZ, respectively. For 687 patients with available MGMTp methylation data, we applied a cutoff discerning truly unmethylated glioblastoma, established in a pooled analysis of 4 clinical trials for glioblastoma, with RT/TMZ -> TMZ treatment, using the same quantitative methylation-specific MGMTp PCR assay.Results: When applying this restricted cutoff to the elderly patient population, we confirmed that glioblastoma with truly unmethylated MGMTp derived no benefit from TMZ treatment. In the Nordic/NOA-08 trials, RT was better than TMZ, suggesting little or no benefit from TMZ.Conclusions: For evidence-based treatment of glioblastoma patients validated MGMTp methylation assays should be used that accurately identify truly unmethylated patients. Respective stratified management of patients will reduce toxicity without compromising outcomes and allow testing of more promising treatment options.
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| 264. |
- Illán-Gala, Ignacio, et al.
(författare)
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Plasma tau and neurofilament light in frontotemporal lobar degeneration and Alzheimer's disease.
- 2021
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Ingår i: Neurology. - 1526-632X. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically-diagnosed Alzheimer's disease (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses.We measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-Tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression and survival and cortical thickness.Plasma NfL, but not plasma t-tau discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-Tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone.Plasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S.This study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance than plasma t-tau in FTLD and AD.
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| 265. |
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| 266. |
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| 267. |
- Larsson, J, et al.
(författare)
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The occurrence of refractoriness and mast cell mediator release following mannitol-induced bronchoconstriction
- 2011
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 110:4, s. 1029-1035
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Tidskriftsartikel (refereegranskat)abstract
- For several hours after exercise-induced bronchoconstriction, there is diminished responsiveness to repeated challenge. The mechanism causing this refractoriness is unclear. Inhalation of dry powder mannitol is a new bronchial provocation test that has been suggested as a surrogate for an exercise challenge. Refractoriness to repeated mannitol challenge has however not been established. Our objective was to investigate if repeated challenge with mannitol is associated with refractoriness and diminished release of mast cell mediators of bronchoconstriction. Sixteen subjects with asthma underwent repeated inhalation of mannitol 90 min apart. Lung function was assessed by forced expiratory volume in 1 s (FEV1). The urinary excretion (ng/mmol creatinine) of the mediators 9α,11β-prostaglandin (PG) F2 and leukotriene (LT) E4 were measured. The group mean fall in FEV1 after the second challenge was 48.5 ± 5.8% of the first ( P < 0.001). The protection afforded by the initial challenge, however, varied considerably between subjects (range 88–0%). Furthermore, the urinary excretion of the two mediators was increased after both challenges. The average excretion of mediators after the challenges was significantly higher for the six most refractory subjects. This was observed both for LTE4 (95.6 ± 5.2 vs. 58.0 ± 2.4 for the 6 least refractory) ( P < 0.001) and for 9α,11β-PGF2 (137.6 ± 6.7 vs. 50.1 ± 1.1 for the 6 least refractory) ( P = 0.002). As occurs with exercise-induced bronchoconstriction, repeated inhalation of mannitol induced refractoriness. We propose that refractoriness is due to tachyphylaxis at the level of the airway smooth muscle responsiveness to mediators of bronchoconstriction rather than due to fatigue of their release from mast cells.
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| 268. |
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| 269. |
- Le Duigou, J., et al.
(författare)
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Optimization and lifecycle engineering for design and manufacture of recycled aluminium parts
- 2016
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Ingår i: CIRP Annals - Manufacturing Technology. - : Elsevier BV. - 1726-0604 .- 0007-8506. ; 65:1, s. 149-152
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Tidskriftsartikel (refereegranskat)abstract
- Aluminium alloys components are numerous in aeronautic and automobile structures. Despite having interesting mechanical properties for lightweight solutions, the extraction of virgin aluminium still has negative impacts on the environment. A solution is to use an increased rate of recycled aluminium in structural parts. This requires a global optimization of the part design and manufacture. The proposed work details the advanced optimization techniques used for product and process design integrating environmental concerns. The methodology is implemented and tested on an industrial case that results in a recycling rate of 75% in high-end structural component based on wrought aluminium alloys. (C) 2016 CIRP.
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| 270. |
- Lester, Mark, et al.
(författare)
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The Impact of Energetic Particles on the Martian Ionosphere During a Full Solar Cycle of Radar Observations: Radar Blackouts
- 2022
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Ingår i: Journal of Geophysical Research - Space Physics. - : John Wiley & Sons. - 2169-9380 .- 2169-9402. ; 127:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first long-term characterization of ionization layers in the lower ionosphere of Mars (below ∼90 km), a region inaccessible to orbital in-situ observations, based on an analysis of radar echo blackouts observed on Mars Express and the Mars Reconnaissance Orbiter from 2006 to 2017. A blackout occurs when the expected surface reflection is partly or totally attenuated for portions of an observation. Enhanced ionization at altitudes of 60–90 km, below the main ionospheric electron density peak, leads to increased absorption of the radar signal, resulting in the blackouts. We find that (a) MARSIS, operating at frequencies between 1.8 and 5 MHz, suffered more blackouts than SHARAD, which has a higher carrier frequency (20 MHz), (b) there is a clear correlation of blackout occurrence with solar cycle, (c) there is no apparent relationship between blackout occurrence and crustal magnetic fields, and (d) blackouts occur during both nightside and dayside observations, although the peak occurrence is deep on the nightside. Analysis of Mars Atmosphere and Volatile EvolutioN Solar Energetic Particle electron counts between 20 and 200 keV demonstrates that these electrons are likely responsible for attenuating the radar signals. We investigate the minimum SEP electron fluxes required to ionize the lower atmosphere and produce measurable attenuation. When both radars experience a blackout, the SEP electron fluxes are at their highest. Based on several case studies, we find that the average SEP spectrum responsible for a blackout is particularly enhanced at its higher energy end, that is, above 70 keV.
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