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- Ingala, Silvia, et al.
(författare)
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Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort.
- 2021
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 17:7, s. 1189-1204
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Tidskriftsartikel (refereegranskat)abstract
- We classified non-demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles.From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut-offs of 1000 pg/mL for amyloid beta (Aß)1-42 and 27 pg/mL for p-tau181 were validated using Gaussian mixture models. Given strong correlation of p-tau and t-tau (R2 =0.98, P<0.001), neurodegeneration was defined by age-adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages.Age was 65 ± 7 years, with 58% females and 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A-T-N-, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non-Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (P<0.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T-N- compared to A-T-N- (P<0.001).In non-demented individuals along the AD continuum, p-tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.
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- Lorenzini, Luigi, et al.
(författare)
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The Open-Access European Prevention of Alzheimer?s Dementia (EPAD) MRI dataset and processing workflow
- 2022
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Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI pre-processing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features - i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features - Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) - were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses
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- Vreeswijk, Paul M., et al.
(författare)
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ON THE EARLY-TIME EXCESS EMISSION IN HYDROGEN-POOR SUPERLUMINOUS SUPERNOVAE
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 835:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the light curves of the hydrogen-poor superluminous supernovae (SLSNe I) PTF 12dam and iPTF 13dcc, discovered by the (intermediate) Palomar Transient Factory. Both show excess emission at early times and a slowly declining light curve at late times. The early bump in PTF 12dam is very similar in duration (similar to 10 days) and brightness relative to the main peak (2-3 mag fainter) compared to that observed in other SLSNe I. In contrast, the long-duration (>30 days) early excess emission in iPTF 13dcc, whose brightness competes with that of the main peak, appears to be of a different nature. We construct bolometric light curves for both targets, and fit a variety of light-curve models to both the early bump and main peak in an attempt to understand the nature of these explosions. Even though the slope of the late-time decline in the light curves of both SLSNe is suggestively close to that expected from the radioactive decay of Ni-56 and Co-56, the amount of nickel required to power the full light curves is too large considering the estimated ejecta mass. The magnetar model including an increasing escape fraction provides a reasonable description of the PTF 12dam observations. However, neither the basic nor the double-peaked magnetar model is capable of reproducing the light curve of iPTF 13dcc. A model combining a shock breakout in an extended envelope with late-time magnetar energy injection provides a reasonable fit to the iPTF 13dcc observations. Finally, we find that the light curves of both PTF 12dam and iPTF 13dcc can be adequately fit with the model involving interaction with the circumstellar medium.
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- Rudà, Roberta, et al.
(författare)
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Eano-Euracan-Sno Guidelines on Circumscribed Astrocytic GLIOMAS, Glioneuronal and Neuronaltumors.
- 2022
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Ingår i: Neuro-oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 24:12, s. 2015-2034
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Forskningsöversikt (refereegranskat)abstract
- In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, molecular workup is important for differential diagnosis, in particular DNA methylation profiling for the definitive classification of histologically unresolved cases. Molecular factors are increasingly of prognostic and predictive importance. MRI finding are non specific, but for some tumors are characteristic and suggestive. Gross total resection, when feasible, is the most important treatment in terms of prolonging survival and achieving long-term seizure control. Conformal radiotherapy should be considered in grade 3 and incompletely resected grade 2 tumors. In recurrent tumors reoperation and radiotherapy, including stereotactic radiotherapy, can be useful. Targeted therapies may be used in selected patients: BRAF and MEK inhibitors in pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas when BRAF altered, and mTOR inhibitor everolimus in subependymal giant cells astrocytomas .Sequencing to identify molecular targets is advocated for diagnostic clarification and to direct potential targeted therapies.
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