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| 2. |
- Adamczuk, Katarzyna, et al.
(author)
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Amyloid imaging in cognitively normal older adults : comparison between F-18-flutemetamol and C-11-Pittsburgh compound B
- 2016
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:1, s. 142-151
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Journal article (peer-reviewed)abstract
- Purpose Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: F-18-flutemetamol and C-11-Pittsburgh compound B (PIB). Methods In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on F-18-flutemetamol versus C-11-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between F-18-flutemetamol and C-11-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. Results Binary classification based on semiquantitative assessment was concordant between F-18-flutemetamol and C-11-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between F-18-flutemetamol and C-11-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. Conclusion For the definition of preclinical AD based on F-18-flutemetamol, concordance with C-11-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region.
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| 3. |
- Adamczuk, Katarzyna, et al.
(author)
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Diagnostic value of cerebrospinal fluid A beta ratios in preclinical Alzheimer's disease
- 2015
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In: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 7
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Journal article (peer-reviewed)abstract
- Introduction: In this study of preclinical Alzheimer's disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) A beta ratios rather than A beta 42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). Methods: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65-80 years) underwent F-18-flutemetamol PET and CSF measurement of A beta 1-42, A beta 1-40, A beta 1-38, and total tau (ttau). F-18-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVRcomp) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVRcomp cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and F-18-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %. Results: Seven out of 38 subjects (18 %) were positive on amyloid PET. A beta 42/ttau, A beta 42/A beta 40, A beta 42/A beta 38, and A beta 42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC) >= 0.908). A beta 40 and A beta 38 had significantly lower discriminative power (AUC = 0.571). When specificity was fixed at 90 % and 95 %, A beta 42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of A beta 42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively). Conclusion: For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of A beta 42/ttau rather than using A beta 42 in isolation.
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| 4. |
- Delroisse, Jérôme, et al.
(author)
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High opsin diversity in a non-visual infaunal brittlestar
- 2014
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15
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Journal article (peer-reviewed)abstract
- Background In metazoans, opsins are photosensitive proteins involved in both vision and non-visual photoreception. Echinoderms have no well-defined eyes but several opsin genes were found in the purple sea urchin (Strongylocentrotus purpuratus) genome. Molecular data are lacking for other echinoderm classes although many species are known to be light sensitive. Results In this study focused on the European brittle star Amphiura filiformis, we first highlighted a blue-green light sensitivity using a behavioural approach. We then identified 13 new putative opsin genes against eight bona fide opsin genes in the genome of S. purpuratus. Six opsins were included in the rhabdomeric opsin group (r-opsins). In addition, one putative ciliary opsin (c-opsin), showing high similarity with the c-opsin of S. purpuratus (Sp-opsin 1), one Go opsin similar to Sp-opsins 3.1 and 3.2, two basal-branch opsins similar to Sp-opsins 2 and 5, and two neuropsins similar to Sp-opsin 8, were identified. Finally, two sequences from one putative RGR opsin similar to Sp-opsin 7 were also detected. Adult arm transcriptome analysis pinpointed opsin mRNAs corresponding to one r-opsin, one neuropsin and the homologue of Sp-opsin 2. Opsin phylogeny was determined by maximum likelihood and Bayesian analyses. Using antibodies designed against c- and r-opsins from S. purpuratus, we detected putative photoreceptor cells mainly in spines and tube feet of A. filiformis, respectively. The r-opsin expression pattern is similar to the one reported in S. purpuratus with cells labelled at the tip and at the base of the tube feet. In addition, r-opsin positive cells were also identified in the radial nerve of the arm. C-opsins positive cells, expressed in pedicellariae, spines, tube feet and epidermis in S. purpuratus were observed at the level of the spine stroma in the brittle star. Conclusion Light perception in A. filiformis seems to be mediated by opsins (c- and r-) in, at least, spines, tube feet and in the radial nerve cord. Other non-visual opsin types could participate to the light perception process indicating a complex expression pattern of opsins in this infaunal brittle star.
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| 5. |
- Goni, Maria Fernanda Sanchez, et al.
(author)
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The ACER pollen and charcoal database : a global resource to document vegetation and fire response to abrupt climate changes during the last glacial period
- 2017
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In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 9:2, s. 679-695
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Journal article (peer-reviewed)abstract
- Quaternary records provide an opportunity to examine the nature of the vegetation and fire responses to rapid past climate changes comparable in velocity and magnitude to those expected in the 21st-century. The best documented examples of rapid climate change in the past are the warming events associated with the Dansgaard-Oeschger (D-O) cycles during the last glacial period, which were sufficiently large to have had a potential feedback through changes in albedo and greenhouse gas emissions on climate. Previous reconstructions of vegetation and fire changes during the D-O cycles used independently constructed age models, making it difficult to compare the changes between different sites and regions. Here, we present the ACER (Abrupt Climate Changes and Environmental Responses) global database, which includes 93 pollen records from the last glacial period (73-15 ka) with a temporal resolution better than 1000 years, 32 of which also provide charcoal records. A harmonized and consistent chronology based on radiometric dating (C-14, U-234/Th-230, optically stimulated luminescence (OSL), Ar-40/Ar-39-dated tephra layers) has been constructed for 86 of these records, although in some cases additional information was derived using common control points based on event stratigraphy. The ACER database compiles metadata including geospatial and dating information, pollen and charcoal counts, and pollen percentages of the characteristic biomes and is archived in Microsoft Access (TM) at https://doi. org/10.1594/PANGAEA. 870867.
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| 6. |
- Renard, Jean-Baptiste, et al.
(author)
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LOAC : a small aerosol optical counter/sizer for ground-based and balloon measurements of the size distribution and nature of atmospheric particles - Part 1
- 2016
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:4, s. 1721-1742
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Journal article (peer-reviewed)abstract
- The study of aerosols in the troposphere and in the stratosphere is of major importance both for climate and air quality studies. Among the numerous instruments available, optical aerosol particles counters (OPCs) provide the size distribution in diameter range from about 100 nm to a few tens of mu m. Most of them are very sensitive to the nature of aerosols, and this can result in significant biases in the retrieved size distribution. We describe here a new versatile optical particle/sizer counter named LOAC (Light Optical Aerosol Counter), which is light and compact enough to perform measurements not only at the surface but under all kinds of balloons in the troposphere and in the stratosphere. LOAC is an original OPC performing observations at two scattering angles. The first one is around 12 degrees, and is almost insensitive to the refractive index of the particles; the second one is around 60 degrees and is strongly sensitive to the refractive index of the particles. By combining measurement at the two angles, it is possible to retrieve the size distribution between 0.2 and 100 mu m and to estimate the nature of the dominant particles (droplets, carbonaceous, salts and mineral particles) when the aerosol is relatively homogeneous. This typology is based on calibration charts obtained in the laboratory. The uncertainty for total concentrations measurements is +/- 20% when concentrations are higher than 1 particle cm 3 (for a 10 min integration time). For lower concentrations, the uncertainty is up to about +/- 60% for concentrations smaller than 10 2 particle cm(-3). Also, the uncertainties in size calibration are +/- 0.025 mu m for particles smaller than 0.6 mu m, 5% for particles in the 0.7-2 mu m range, and 10% for particles greater than 2 mu m. The measurement accuracy of sub-micronic particles could be reduced in a strongly turbid case when concentration of particles > 3 mu m exceeds a few particles cm(-3). Several campaigns of cross-comparison of LOAC with other particle counting instruments and remote sensing photometers have been conducted to validate both the size distribution derived by LOAC and the retrieved particle number density. The typology of the aerosols has been validated in well-defined conditions including urban pollution, desert dust episodes, sea spray, fog, and cloud. Comparison with reference aerosol mass monitoring instruments also shows that the LOAC measurements can be successfully converted to mass concentrations.
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| 7. |
- Renard, Jean-Baptiste, et al.
(author)
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LOAC : a small aerosol optical counter/sizer for ground-based and balloon measurements of the size distribution and nature of atmospheric particles - Part 2
- 2016
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:8, s. 3673-3686
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Journal article (peer-reviewed)abstract
- In the companion (Part I) paper, we have described and evaluated a new versatile optical particle counter/sizer named LOAC (Light Optical Aerosol Counter), based on scattering measurements at angles of 12 and 60A degrees. That allows for some typology identification of particles (droplets, carbonaceous, salts, and mineral dust) in addition to size-segregated counting in a large diameter range from 0.2aEuro-A mu m up to possibly more than 100aEuro-A mu m depending on sampling conditions (Renard et al., 2016). Its capabilities overpass those of preceding optical particle counters (OPCs) allowing the characterization of all kind of aerosols from submicronic-sized absorbing carbonaceous particles in polluted air to very coarse particles (> 10-20aEuro-A mu m in diameter) in desert dust plumes or fog and clouds. LOAC's light and compact design allows measurements under all kinds of balloons, on-board unmanned aerial vehicles (UAVs) and at ground level. We illustrate here the first LOAC airborne results obtained from a UAV and a variety of scientific balloons. The UAV was deployed in a peri-urban environment near Bordeaux in France. Balloon operations include (i) tethered balloons deployed in urban environments in Vienna (Austria) and Paris (France), (ii) pressurized balloons drifting in the lower troposphere over the western Mediterranean (during the Chemistry-Aerosol Mediterranean Experiment - ChArMEx campaigns), (iii) meteorological sounding balloons launched in the western Mediterranean region (ChArMEx) and from Aire-sur-l'Adour in south-western France (VOLTAIRE-LOAC campaign). More focus is put on measurements performed in the Mediterranean during (ChArMEx) and especially during African dust transport events to illustrate the original capability of balloon-borne LOAC to monitor in situ coarse mineral dust particles. In particular, LOAC has detected unexpected large particles in desert sand plumes.
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| 8. |
- Vandenberghe, Rik, et al.
(author)
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Binary classification of F-18-flutemetamol PET using machine learning: Comparison with visual reads and structural MRI
- 2013
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In: NeuroImage. - : Elsevier BV. - 1095-9572 .- 1053-8119. ; 64, s. 517-525
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Journal article (peer-reviewed)abstract
- F-18-flutemetamol is a positron emission tomography (PET) tracer for in vivo amyloid imaging. The ability to classify amyloid scans in a binary manner as 'normal' versus 'Alzheimer-like', is of high clinical relevance. We evaluated whether a supervised machine learning technique, support vector machines (SVM), can replicate the assignments made by visual readers blind to the clinical diagnosis, which image components have highest diagnostic value according to SVM and how F-18-flutemetamol-based classification using SVM relates to structural MRI-based classification using SVM within the same subjects. By means of SVM with a linear kernel, we analyzed F-18-flutemetamol scans and volumetric MRI scans from 72 cases from the F-18-flutemetamol phase 2 study (27 clinically probable Alzheimer's disease (AD), 20 amnestic mild cognitive impairment (MCI), 25 controls). In a leave-one-out approach, we trained the F-18-flutemetamol based classifier by means of the visual reads and tested whether the classifier was able to reproduce the assignment based on visual reads and which voxels had the highest feature weights. The F-18-flutemetamol based classifier was able to replicate the assignments obtained by visual reads with 100% accuracy. The voxels with highest feature weights were in the striatum, precuneus, cingulate and middle frontal gyrus. Second, to determine concordance between the gray matter volume- and the F-18-flutemetamol-based classification, we trained the classifier with the clinical diagnosis as gold standard. Overall sensitivity of the F-18-flutemetamol- and the gray matter volume-based classifiers were identical (85.2%), albeit with discordant classification in three cases. Specificity of the F-18-flutemetamol based classifier was 92% compared to 68% for MRI. In the MCI group, the F-18-flutemetamol based classifier distinguished more reliably between converters and non-converters than the gray matter-based classifier. The visual read-based binary classification of F-18-flutemetamol scans can be replicated using SVM. In this sample the specificity of F-18-flutemetamol based SVM for distinguishing AD from controls is higher than that of gray matter volume-based SVM. (C) 2012 Elsevier Inc. All rights reserved.
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| 9. |
- Vinarov, Zahari, et al.
(author)
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Current challenges and future perspectives in oral absorption research : An opinion of the UNGAP network
- 2021
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In: Advanced Drug Delivery Reviews. - : Elsevier. - 0169-409X .- 1872-8294. ; 171, s. 289-331
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Research review (peer-reviewed)abstract
- Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research.
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| 10. |
- Wouters, Anke, et al.
(author)
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Association between the perfusion/diffusion and diffusion/FLAIR mismatch: data from the AXIS2 trial.
- 2015
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In: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 35:10, s. 1681-1686
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Journal article (peer-reviewed)abstract
- The perfusion-/diffusion-weighted imaging (PWI/DWI) mismatch and the diffusion/fluid attenuated inversion recovery (DWI/FLAIR) mismatch are magnetic resonance imaging (MRI) markers of evolving brain ischemia. We examined whether the DWI/FLAIR mismatch was independently associated with the PWI/DWI mismatch. Furthermore, we determined whether the presence of the DWI/FLAIR mismatch in patients with the PWI/DWI mismatch would provide additional information regarding last seen normal time (LTM). We used data from the 'AX200 for ischemic stroke' trial (AXIS 2 study NCT00927836). We studied the association between the presence of the DWI/FLAIR and PWI/DWI mismatch, baseline National Institute of Health Stroke Scale (NIHSS), age, ischemic-core volume, gender, intravenous (IV) tissue plasminogen activator (tPA), and perfusion-mismatch volume in univariate analysis. Significant variables (P<0.05) were added into the final multivariate model. We analyzed 197 patients. Seventy-two (37%) had both the PWI/DWI and the DWI/FLAIR mismatch. Patients with the double mismatch pattern had a shorter LTM than patients with the PWI/DWI mismatch alone (Median difference 90 minutes, P<0.01). Multivariate analysis confirmed the independent association between the two mismatch patterns (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.2 to 5.4). Our study implies that the DWI/FLAIR mismatch and PWI/DWI mismatch are strongly associated, independent from LTM. Furthermore, in the presence of the PWI/DWI mismatch, the DWI/FLAIR pattern indicates a shorter LTM. This could have implications in selecting patients for reperfusion therapy.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 June 2015; doi:10.1038/jcbfm.2015.108.
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