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1.
  • 2017
  • swepub:Mat__t
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2.
  • Bousquet, J., et al. (författare)
  • Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
  • 2016
  • Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
  • Forskningsöversikt (refereegranskat)abstract
    • Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
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  • Brown, A. G. A., et al. (författare)
  • Gaia Data Release 2 Summary of the contents and survey properties
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. We present the second Gaia data release, Gaia DR2, consisting of astrometry, photometry, radial velocities, and information on astrophysical parameters and variability, for sources brighter than magnitude 21. In addition epoch astrometry and photometry are provided for a modest sample of minor planets in the solar system. Aims. A summary of the contents of Gaia DR2 is presented, accompanied by a discussion on the differences with respect to Gaia DR1 and an overview of the main limitations which are still present in the survey. Recommendations are made on the responsible use of Gaia DR2 results. Methods. The raw data collected with the Gaia instruments during the first 22 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into this second data release, which represents a major advance with respect to Gaia DR1 in terms of completeness, performance, and richness of the data products. Results. Gaia DR2 contains celestial positions and the apparent brightness in G for approximately 1.7 billion sources. For 1.3 billion of those sources, parallaxes and proper motions are in addition available. The sample of sources for which variability information is provided is expanded to 0 : 5 million stars. This data release contains four new elements: broad-band colour information in the form of the apparent brightness in the G(BP) (330-680 nm) and G(RP) (630-1050 nm) bands is available for 1.4 billion sources; median radial velocities for some 7 million sources are presented; for between 77 and 161 million sources estimates are provided of the stellar effective temperature, extinction, reddening, and radius and luminosity; and for a pre-selected list of 14 000 minor planets in the solar system epoch astrometry and photometry are presented. Finally, Gaia DR2 also represents a new materialisation of the celestial reference frame in the optical, the Gaia-CRF2, which is the first optical reference frame based solely on extragalactic sources. There are notable changes in the photometric system and the catalogue source list with respect to Gaia DR1, and we stress the need to consider the two data releases as independent. Conclusions. Gaia DR2 represents a major achievement for the Gaia mission, delivering on the long standing promise to provide parallaxes and proper motions for over 1 billion stars, and representing a first step in the availability of complementary radial velocity and source astrophysical information for a sample of stars in the Gaia survey which covers a very substantial fraction of the volume of our galaxy.
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  • Katz, D., et al. (författare)
  • Gaia Data Release 2 Mapping the Milky Way disc kinematics
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The second Gaia data release (Gaia DR2) contains high-precision positions, parallaxes, and proper motions for 1.3 billion sources as well as line-of-sight velocities for 7.2 million stars brighter than G(RVS) = 12 mag. Both samples provide a full sky coverage. Aims. To illustrate the potential of Gaia DR2, we provide a first look at the kinematics of the Milky Way disc, within a radius of several kiloparsecs around the Sun. Methods. We benefit for the first time from a sample of 6.4 million F-G-K stars with full 6D phase-space coordinates, precise parallaxes (sigma((omega) over bar)/(omega) over bar <= 20%), and precise Galactic cylindrical velocities (median uncertainties of 0.9-1.4 km s(-1) and 20% of the stars with uncertainties smaller than 1 km s(-1) on all three components). From this sample, we extracted a sub-sample of 3.2 million giant stars to map the velocity field of the Galactic disc from similar to 5 kpc to similar to 13 kpc from the Galactic centre and up to 2 kpc above and below the plane. We also study the distribution of 0.3 million solar neighbourhood stars (r < 200 pc), with median velocity uncertainties of 0.4 km s(-1), in velocity space and use the full sample to examine how the over-densities evolve in more distant regions. Results. Gaia DR2 allows us to draw 3D maps of the Galactocentric median velocities and velocity dispersions with unprecedented accuracy, precision, and spatial resolution. The maps show the complexity and richness of the velocity field of the galactic disc. We observe streaming motions in all the components of the velocities as well as patterns in the velocity dispersions. For example, we confirm the previously reported negative and positive galactocentric radial velocity gradients in the inner and outer disc, respectively. Here, we see them as part of a non-axisymmetric kinematic oscillation, and we map its azimuthal and vertical behaviour. We also witness a new global arrangement of stars in the velocity plane of the solar neighbourhood and in distant regions in which stars are organised in thin substructures with the shape of circular arches that are oriented approximately along the horizontal direction in the U - V plane. Moreover, in distant regions, we see variations in the velocity substructures more clearly than ever before, in particular, variations in the velocity of the Hercules stream. Conclusions. Gaia DR2 provides the largest existing full 6D phase-space coordinates catalogue. It also vastly increases the number of available distances and transverse velocities with respect to Gaia DR1. Gaia DR2 offers a great wealth of information on the Milky Way and reveals clear non-axisymmetric kinematic signatures within the Galactic disc, for instance. It is now up to the astronomical community to explore its full potential.
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6.
  • Spoto, F., et al. (författare)
  • Gaia Data Release 2 : Observations of solar system objects
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims: We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods: To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results: The overall astrometric performance is close to the expectations, with an optimal range of brightness G similar to 12 - 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G similar to 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.
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7.
  • Eyer, L., et al. (författare)
  • Gaia Data Release 2 Variable stars in the colour-absolute magnitude diagram
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The ESA Gaia mission provides a unique time-domain survey for more than 1.6 billion sources with G less than or similar to 21 mag. Aims. We showcase stellar variability in the Galactic colour-absolute magnitude diagram (CaMD). We focus on pulsating, eruptive, and cataclysmic variables, as well as on stars that exhibit variability that is due to rotation and eclipses. Methods. We describe the locations of variable star classes, variable object fractions, and typical variability amplitudes throughout the CaMD and show how variability-related changes in colour and brightness induce "motions". To do this, we use 22 months of calibrated photometric, spectro-photometric, and astrometric Gaia data of stars with a significant parallax. To ensure that a large variety of variable star classes populate the CaMD, we crossmatched Gaia sources with known variable stars. We also used the statistics and variability detection modules of the Gaia variability pipeline. Corrections for interstellar extinction are not implemented in this article. Results. Gaia enables the first investigation of Galactic variable star populations in the CaMD on a similar, if not larger, scale as was previously done in the Magellanic Clouds. Although the observed colours are not corrected for reddening, distinct regions are visible in which variable stars occur. We determine variable star fractions to within the current detection thresholds of Gaia. Finally, we report the most complete description of variability-induced motion within the CaMD to date. Conclusions. Gaia enables novel insights into variability phenomena for an unprecedented number of stars, which will benefit the understanding of stellar astrophysics. The CaMD of Galactic variable stars provides crucial information on physical origins of variability in a way that has previously only been accessible for Galactic star clusters or external galaxies. Future Gaia data releases will enable significant improvements over this preview by providing longer time series, more accurate astrometry, and additional data types (time series BP and RP spectra, RVS spectra, and radial velocities), all for much larger samples of stars.
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  • Babusiaux, C., et al. (författare)
  • Observational Hertzsprung-Russell diagrams
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 16:A10
  • Tidskriftsartikel (refereegranskat)
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  • Bousquet, J., et al. (författare)
  • MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation
  • 2015
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY-BLACKWELL. - 0105-4538 .- 1398-9995. ; 70:11, s. 1372-1392
  • Tidskriftsartikel (refereegranskat)abstract
    • Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
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  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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  • Zamora, Juan Carlos, et al. (författare)
  • Considerations and consequences of allowing DNA sequence data as types of fungal taxa
  • 2018
  • Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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17.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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  • Guerreiro, R., et al. (författare)
  • Heritability and genetic variance of dementia with Lewy bodies
  • 2019
  • Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 127, s. 492-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants. © 2019 Elsevier Inc.
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  • Guerreiro, R., et al. (författare)
  • Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study
  • 2018
  • Ingår i: Lancet Neurology. - 1474-4422. ; 17:1, s. 64-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also only in participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2.40, 95% CI 2.14-2.70; p=1.05 x 10-48), SNCA (rs7681440; OR 0.73, 0.66-0.81; p=6.39 x 10(-10)), and GBA (rs35749011; OR 2.55, 1.88-3.46; p=1.78 x 10(-9)). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1.51, 1.27-1.79; p=2.32 x 10(-6)); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease.
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  • van Doorn, Ljcv, et al. (författare)
  • Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
  • 2017
  • Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.
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24.
  • Blanton, Michael R., et al. (författare)
  • Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
  • 2017
  • Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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25.
  • Costa, C, et al. (författare)
  • Population Health Inequalities Across and Within European Metropolitan Areas through the Lens of the EURO-HEALTHY Population Health Index
  • 2019
  • Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 16:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The different geographical contexts seen in European metropolitan areas are reflected in the uneven distribution of health risk factors for the population. Accumulating evidence on multiple health determinants point to the importance of individual, social, economic, physical and built environment features, which can be shaped by the local authorities. The complexity of measuring health, which at the same time underscores the level of intra-urban inequalities, calls for integrated and multidimensional approaches. The aim of this study is to analyse inequalities in health determinants and health outcomes across and within nine metropolitan areas: Athens, Barcelona, Berlin-Brandenburg, Brussels, Lisbon, London, Prague, Stockholm and Turin. We use the EURO-HEALTHY Population Health Index (PHI), a tool that measures health in two components: Health Determinants and Health Outcomes. The application of this tool revealed important inequalities between metropolitan areas: Better scores were found in Northern cities when compared with their Southern and Eastern counterparts in both components. The analysis of geographical patterns within metropolitan areas showed that there are intra-urban inequalities, and, in most cities, they appear to form spatial clusters. Identifying which urban areas are measurably worse off, in either Health Determinants or Health Outcomes, or both, provides a basis for redirecting local action and for ongoing comparisons with other metropolitan areas.
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  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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  • Jansen, Willemijn J, et al. (författare)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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29.
  • Miambo, Regina D., et al. (författare)
  • Prevalence of Giardia and Cryptosporidium in young livestock and dogs in Magude District of Maputo Province, Mozambique
  • 2019
  • Ingår i: Onderstepoort Journal of Veterinary Research. - : AOSIS. - 0030-2465 .- 2219-0635. ; 86:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Giardia and Cryptosporidium species are significant zoonotic parasites of humans and domesticated animals. Objectives: The study aimed to determine the prevalence of Giardia and Cryptosporidium in livestock and dogs of the Magude District. Method: The flotation technique (Willis), modified Ziehl-Neelsen (mZN) and direct and indirect immunofluorescence (DIF and IIF) techniques were applied to determine the prevalence of Giardia and Cryptosporidium species in faecal samples of dog pups (156), goat kids (60) and calves (480) from the Magude District of Mozambique from February to September 2015. Results: Using Willis, IIF and DIF, the prevalence of Giardia in calves was 0%, 8.1%, and 6.0%; in dogs 0.6%, 8.3% and 5.7% and for goats 0% and 13.3% (IIF was not performed), respectively. The prevalence of Cryptosporidium in calves using Willis, mZN, IIF and DIF was 0%, 3.8%, 4.7% and 0.4% and in dogs 0%, 0.6%, 6.4% and 0.6%, respectively. The parasite was not detected in goats. Conclusion: Results from the present study showed that IIF performed better diagnosis of Giardia and Cryptosporidium, and that the mZN can be used as an alternative for Cryptosporidium because of the high cost of IIF. There is a need for identification of genotypes or subtypes of these parasites through application of molecular techniques in order to determine their zoonotic potential, and we advocate a 'one health' approach in the control and prevention of these parasites.
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30.
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31.
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32.
  • Boj, Sylvia F, et al. (författare)
  • Organoid models of human and mouse ductal pancreatic cancer
  • 2015
  • Ingår i: Cell. - : Cell press. - 0092-8674 .- 1097-4172. ; 160:1-2, s. 324-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.
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33.
  • Bos, Isabelle, et al. (författare)
  • The frequency and influence of dementia risk factors in prodromal Alzheimer's disease
  • 2017
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 56, s. 33-40
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.
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34.
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35.
  • Guerzoni, R., et al. (författare)
  • Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures : An architectural survey
  • 2017
  • Ingår i: Transactions on Emerging Telecommunications Technologies. - : Wiley-Blackwell. - 2161-5748 .- 2161-3915. ; 28:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the last couple of years, industry operators' associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This article provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi-operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisation.
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36.
  • Hernández-Moreno, Laura, et al. (författare)
  • The Portuguese version of the activity inventory
  • 2015
  • Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To characterize interventions needed by the population with visual impairment or to assess interventions in vision rehabilitation validated and standardized instruments used in different cultural contexts are necessary. The aim of this work was to characterize the functional status of a sample of people with visual impairment with the Portuguese version of the activity inventory (AI)Methods: A group of participants in the study Prevalence and Costs of Visual Impairment in Portugal (PC-VIP) was recruit to face-to-face interviews and the activity inventory was administered. The AI examines 50 goals split between three objectives: social functioning, recreation and daily living. Goals rated ‘not important’ were skipped, but for all other goals the participant was asked to rate its difficulty on a five point scale ranging from ‘not difficult’ to ‘impossible without help’. The difficulty responses were Rasch analysed (Winsteps v3.81.0) to produce a continuous measure of visual ability (AI score). Additional information about distance and near visual acuity (ETDRS scale), contrast sensitivity (MARS test) and critical print size (MNREAD test) was collected.Results: A total of 94 persons participated in this study. Some participants were not able to read or recognize letters due to their poor vision or poor literacy and were excluded from further analysis. Data reported here are from 62 participants, median age 63y (range=12-85) and the most common cause of visual impairment were retinal diseases. Mean presenting acuity in the better eye was 0.93logMAR (SD=0.5). The mean difficulty (item measure) in the AI was -0.33 logits (SD=0.96). The most difficult items were "sew or do needlework", "read the newspaper", "drive" and the easiest items were "provide care for a pet", "eat your meals", "use the restroom in a public place". The mean ability score (person measures) was 1.11 logits (SD=2.04). The ability measures in the AI were correlated with distance visual acuity (r=-0.57, p<.001), near visual acuity (r=-0.66, p<0.001), contrast sensitivity (r=0.62, p<.001) and critical print size (r=-0.60, p<.001).Conclusions: Our results indicate that the AI scores in a sample of people Portuguese people with visual impairment were in line with what has been found in other cultural contexts. The visual ability measured by the AI was correlated with visual function assessed by different visual tests, which shows that this instrument can be used with confidence.
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37.
  • Hu, Yannan, et al. (författare)
  • Trends in socioeconomic inequalities in self-assessed health in 17 European countries between 1990 and 2010
  • 2016
  • Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 70:7, s. 644-652
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Between the 1990s and 2000s, relative inequalities in all-cause mortality increased, whereas absolute inequalities decreased in many European countries. Whether similar trends can be observed for inequalities in other health outcomes is unknown. This paper aims to provide a comprehensive overview of trends in socioeconomic inequalities in self-assessed health (SAH) in Europe between 1990 and 2010.METHODS: Data were obtained from nationally representative surveys from 17 European countries for the various years between 1990 and 2010. The age-standardised prevalence of less-than-good SAH was analysed by education and occupation among men and women aged 30-79 years. Socioeconomic inequalities were measured by means of absolute rate differences and relative rate ratios. Meta-analysis with random-effects models was used to examine the trends of inequalities.RESULTS: We observed declining trends in the prevalence of less-than-good SAH in many countries, particularly in Southern and Eastern Europe and the Baltic states. In all countries, less-than-good SAH was more prevalent in lower educational and manual groups. For all countries together, absolute inequalities in SAH were mostly constant, whereas relative inequalities increased. Almost no country consistently experienced a significant decline in either absolute or relative inequalities.CONCLUSIONS: Trends in inequalities in SAH in Europe were generally less favourable than those found for inequalities in mortality, and there was generally no correspondence between the two when we compared the trends within countries. In order to develop policies or interventions that effectively reduce inequalities in SAH, a better understanding of the causes of these inequalities is needed.
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38.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
  • 2018
  • Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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39.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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40.
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41.
  • Oliveira, F., et al. (författare)
  • Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of A beta species
  • 2018
  • Ingår i: Neuroimage-Clinical. - : Elsevier BV. - 2213-1582. ; 20, s. 603-610
  • Tidskriftsartikel (refereegranskat)abstract
    • Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid beta (A beta) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of A beta(38), A beta(40) and A beta(42) were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF A beta concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than A beta concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. A beta(38) and A beta(40) correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with A beta(42), the A beta(42)/A beta(40) or A beta(42)/A beta(38) ratios were found compared to normalization based on cerebellar gray matter.
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42.
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43.
  • Rocha De Sousa, Amandio, et al. (författare)
  • Hospital prevalence of visual of visual impairment caused by diabetic retinopathy
  • 2015
  • Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 93:S255
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeTo investigate cases of visual impairment caused by diabetic retinopathy (DR) in a hospital population.MethodsAs part of an observational study to estimate the prevalence and costs of visual impairment in Portugal (PCVIP study), clinical records of all patients attending the ophthalmology department of a tertiary hospital were analysed looking for patients meeting the inclusion criteria. Inclusion criteria were: (i) presenting visual acuity in the better eye <5/10 (20/40) and/or (ii) visual field <20°. Diagnosis of cases with VI were classified according with ICD9. Results reported here were selected from the total number of patients with VI by filtering ICD9 codes staring by 362.ResultsIn 12 weeks, 1920 cases of VI were detected, 586 (31%) caused by any type of DR. From those: 54% were caused by non-proliferative-DR, 40% by proliferative-DR and 6% by diabetic macular oedema. The mean age of the patients with VI caused by DR was 69.4 (sd = 9.5) years and 57% were female. The estimated hospital prevalence (for 52 weeks) of VI caused by DR is 39% (95%CI = 38–41).ConclusionsOur results show that DR remains the leading cause of VI in the population attending our hospital. Information about the number of patients reaching VI will be fundamental to assess the cost-benefits of treatments and public health campaigns to reduce the burden of diabetic retinopathy in Portugal.
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44.
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45.
  • Travassos, M., et al. (författare)
  • Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-beta Levels in Patients with Alzheimer's Disease?
  • 2015
  • Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 47:4, s. 1069-1078
  • Tidskriftsartikel (refereegranskat)abstract
    • Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-beta (A beta) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly A beta. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A beta(1-42), total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other A beta species, A beta(X-38), A beta(X-40), and A beta(X-42), with the MSD A beta Triplex assay. The concentration of caffeine was 0.79 +/- 1.15 mu g/mL in the CSF and 1.20 +/- 1.88 mu g/mL in the plasma. No correlation was found between caffeine consumption and A beta(42) in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with A beta(42) in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable A beta profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.
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46.
  • Vornhagen, J., et al. (författare)
  • Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection
  • 2018
  • Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 128:5, s. 1985-1999
  • Tidskriftsartikel (refereegranskat)abstract
    • Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS induces vaginal epithelial exfoliation by activation of integrin and beta-catenin signaling. However, exfoliation did not diminish GBS vaginal colonization as reported for other vaginal microbes. Rather, vaginal exfoliation increased bacterial dissemination and ascending GBS infection, and abrogation of exfoliation reduced ascending infection and improved pregnancy outcomes. Thus, for some vaginal bacteria, exfoliation promotes ascending infection rather than preventing colonization. Our study provides insight into mechanisms of ascending infection by vaginal microbes.
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47.
  • Vornhagen, J., et al. (författare)
  • Human Cervical Mucus Plugs Exhibit Insufficiencies in Antimicrobial Activity Towards Group B Streptococcus
  • 2018
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 217:10, s. 1626-1636
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth is a leading cause of neonatal mortality and lacks an effective therapy. Ascending microbial infections from the lower genital tract lead to infection of the placenta, amniotic fluid, and fetus causing preterm birth or stillbirth. Directly in the path of an ascending infection is the cervical mucus plug (CMP), a dense mucoid structure in the cervical canal with potential antimicrobial properties. In this study, we aimed to define the components of CMP responsible for antimicrobial activity against a common lower genital tract organism associated with preterm birth and stillbirths, namely, group B streptococcus (GBS). Using a quantitative proteomic approach, we identified antimicrobial factors in CMPs that were collected from healthy human pregnancies. However, we noted that the concentration of antimicrobial peptides present in the human CMPs were insufficient to directly kill GBS, and antimicrobial activity, when observed, was due to antibiotics retained in the CMPs. Despite this insufficiency, CMP proteins were able to activate leukocytes in whole blood resulting in increased rates of bacterial killing, suggesting a role for the CMP in enhancing complement-mediated killing or leukocyte activation. This study provides new insight into how the human CMP may limit ascending bacterial infection.
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48.
  • Waldorf, Kristina M. Adams, et al. (författare)
  • Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain
  • 2018
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:3, s. 368-374
  • Tidskriftsartikel (refereegranskat)abstract
    • Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.
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49.
  • Zerr, Inga, et al. (författare)
  • Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.
  • 2018
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:6, s. 751-763
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown.Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n=122), mild cognitive impairment (n=48), Alzheimer's disease (n=108), dementia with Lewy bodies/Parkinson's disease dementia (n=53), vascular dementia (n=46), frontotemporal dementia (n=41), sporadic Creutzfeldt-Jakob disease (sCJD, n=132), and genetic prion diseases (n=182).The highest NFL levels were detected in sCJD, followed by vascular dementia, frontotemporal dementia, dementia with Lewy bodies/Parkinson's disease dementia, Alzheimer's disease, and mild cognitive impairment. In sCJD, NFL levels correlated with cerebrospinal fluid tau and disease duration. NFL levels were able to differentiate sCJD from nonprimarily neurodegenerative neurological and psychiatric diseases (area under the curve=0.99, 95% confidence interval: 0.99-1) and from the other diagnostic groups showing cognitive impairment/dementia of a non-CJD etiology (area under the curve=0.90, 95% confidence interval: 0.87-0.92). Compared to nonprimarily neurodegenerative neurological and psychiatric diseases, NFL was also elevated in genetic prion diseases associated with the E200K, V210I, P102L, and D178N prion protein gene mutations.Increased NFL levels are a common feature in neurodegenerative dementias.
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