224 research outputs found

    The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

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    © 2019, The Author(s). The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology

    Preliminary survey of polychlorinated biphenyls (PCBs) in aquatic habitats and Great Blue Herons on the Hanford Site. [Ardea herodias]

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    Polychlorinated biphenyls (PCBs), constituents of insulating fluids used in electrical transformers and capacitors, were identified during a preliminary survey of waters, sediments, and fish from five locations on the Hanford Site in southeastern Washington State: Gable Mountain Pond, B Pond, West Pond, White Bluffs Slough on the Columbia River, and a pond on the Wahluke Slope. These aquatic areas are all within the foraging range of great blue herons (Ardea herodias) that nest on the Hanford Site. Of those waters that contained PCBs, concentrations were found to be somewhat over 1 ng/L, but less than 20 ng/L, and equal to or less than concentrations reported for other freshwater regions of the United States. The PCBs in sediments and fish closely resembled the chromatographic profile of Aroclor 1260, a commercial PCB mixture produced in the United States by the Monsanto Company. Concentrations of PCBs detected in the sediments were 10 to 100 times lower than those found in soils and sediments from other areas of the nation. Concentrations of PCBs in fat from Hanford great blue herons ranged from 3.6 to 10.6 ppM, while PCB concentrations in herons from other areas of the Pacific Northwest ranged from 0.6 to 15.6 ppM. Great blue herons at Hanford contained PCB isomer distributions closely matching that of Aroclor 1260; great blue herons from other locations contained isomer distributions indicating the presence of a mixture of aroclors. 21 refs., 13 figs., 8 tabs

    Ariel stellar characterisation: I -- homogeneous stellar parameters of 187 FGK planet host stars Description and validation of the method

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    In 2020 the European Space Agency selected Ariel as the next mission to join the space fleet of observatories to study planets outside our Solar System. Ariel will be devoted to the characterisation of a thousand planetary atmospheres, for understanding what exoplanets are made of, how they formed and how they evolve. To achieve the last two goals all planets need to be studied within the context of their own host stars, which in turn have to be analysed with the same technique, in a uniform way. We present the spectro-photometric method we have developed to infer the atmospheric parameters of the known host stars in the Tier 1 of the Ariel Reference Sample. Our method is based on an iterative approach, which combines spectral analysis, the determination of the surface gravity from {\em Gaia} data, and the determination of stellar masses from isochrone fitting. We validated our approach with the analysis of a control sample, composed by members of three open clusters with well-known ages and metallicities. We measured effective temperature, Teff, surface gravity, logg, and the metallicity, [Fe/H], of 187 F-G-K stars within the Ariel Reference Sample. We presented the general properties of the sample, including their kinematics which allows us to separate them between thin and thick disc populations. A homogeneous determination of the parameters of the host stars is fundamental in the study of the stars themselves and their planetary systems. Our analysis systematically improves agreement with theoretical models and decreases uncertainties in the mass estimate (from 0.21+/-0.30 to 0.10+/-0.02 M_sun), providing useful data for the Ariel consortium and the astronomical community at large.Comment: Accepted for publication in A&A, 13 pages, 14 figures, Tables A1 and A2 in the Appendix will be available at CDS and can be requested by email to: [email protected]

    A retrospective analysis of noise-induced hearing loss in the Dutch construction industry

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    Purpose Noise exposure is an important and highly prevalent occupational hazard in the construction industry. This study examines hearing threshold levels of a large population of Dutch construction workers and compares their hearing thresholds to those predicted by ISO-1999. Methods In this retrospective study, medical records of periodic occupational health examinations of 29,644 construction workers are analysed. Pure-tone audiometric thresholds of noise-exposed workers are compared to a non-exposed control group and to ISO-1999 predictions. Regression analyses are conducted to explore the relationship between hearing loss and noise intensity, noise exposure time and the use of hearing protection. Results Noise-exposed workers had greater hearing losses compared to their non-noise-exposed colleagues and to the reference population reported in ISO-1999. Noise exposure explained only a small proportion of hearing loss. When the daily noise exposure level rose from 80 dB(A) towards 96 dB(A), only a minor increase in hearing loss is shown. The relation of exposure time and hearing loss found was similar to ISO-1999 predictions when looking at durations of 10 years or more. For the first decade, the population medians show poorer hearing than predicted by ISO-1999. Discussion Duration of noise exposure was a better predictor than noise exposure levels, probably because of the limitations in noise exposure estimations. In this population, noise-induced hearing loss was already present at the beginning of employment and increased at the same rate as is predicted for longer exposure duration

    Expanding the frontiers of cool-dwarf asteroseismology with ESPRESSO:Detection of solar-like oscillations in the K5 dwarf ϵ Indi

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    Fuelled by space photometry, asteroseismology is vastly benefitting the study of cool main-sequence stars, which exhibit convection-driven solar-like oscillations. Even so, the tiny oscillation amplitudes in K dwarfs continue to pose a challenge to space-based asteroseismology. A viable alternative is offered by the lower stellar noise over the oscillation timescales in Doppler observations. In this Letter we present the definite detection of solar-like oscillations in the bright K5 dwarf ϵ Indi based on time-intensive observations collected with the ESPRESSO spectrograph at the VLT, thus making it the coolest seismic dwarf ever observed. We measured the frequencies of a total of 19 modes of degree ℓ = 0–2 along with νmax = 5305 ± 176 μHz and Δν = 201.25 ± 0.16 μHz. The peak amplitude of radial modes is 2.6 ± 0.5 cm s−1, or a mere ∼14% of the solar value. Measured mode amplitudes are ∼2 times lower than predicted from a nominal L/M scaling relation and favour a scaling closer to (L/M)1.5 below ∼5500 K, carrying important implications for our understanding of the coupling efficiency between pulsations and near-surface convection in K dwarfs. This detection conclusively shows that precise asteroseismology of cool dwarfs is possible down to at least the mid-K regime using next-generation spectrographs on large-aperture telescopes, effectively opening up a new domain in observational asteroseismology

    Evaluation of the endoplasmic reticulum-stress response in eIF2B-mutated lymphocytes and lymphoblasts from CACH/VWM patients

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    <p>Abstract</p> <p>Background</p> <p>Eukaryotic translation initiation factor 2B (eIF2B), a guanine nucleotide exchange factor (GEF) and a key regulator of translation initiation under normal and stress conditions, causes an autosomal recessive leukodystrophy of a wide clinical spectrum. EBV-immortalised lymphocytes (EIL) from eIF2B-mutated patients exhibit a decrease in eIF2B GEF activity. eIF2B-mutated primary fibroblasts have a hyper-induction of activating transcription factor 4 (ATF4) which is involved in the protective unfolded protein response (UPR), also known as the ER-stress response. We tested the hypothesis that EIL from eIF2B-mutated patients also exhibit a heightened ER-stress response.</p> <p>Methods</p> <p>We used thapsigargin as an ER-stress agent and looked at polysomal profiles, rate of protein synthesis, translational activation of <it>ATF4</it>, and transcriptional induction of stress-specific mRNAs (<it>ATF4, CHOP, ASNS, GRP78</it>) in normal and eIF2B-mutated EIL. We also compared the level of stress-specific mRNAs between EIL and primary lymphocytes (PL).</p> <p>Results</p> <p>Despite the low eIF2B GEF activity in the 12 eIF2B-mutated EIL cell lines tested (range 40-70% of normal), these cell lines did not differ from normal EIL in their ATF4-mediated ER-stress response. The absence of hyper-induction of ATF4-mediated ER-stress response in eIF2B-mutated EIL in contrast to primary fibroblasts is not related to their transformation by EBV. Indeed, PL exhibited a higher induction of the stress-specific mRNAs in comparison to EIL, but no hyper-induction of the UPR was noticed in the eIF2B-mutated cell lines in comparison to controls.</p> <p>Conclusions</p> <p>Taken together with work of others, our results demonstrate the absence of a major difference in ER-stress response between controls and eIF2B-mutated cells. Therefore, components of the ER-stress response cannot be used as discriminantory markers in eIF2B-related disorders.</p

    Monte Carlo study of the effects of system geometry and antiscatter grids on cone-beam CT scatter distributions

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    Purpose: The proliferation of cone-beam CT (CBCT) has created interest in performance optimization,with x-ray scatter identifie among the main limitations to image quality. CBCT often contends with elevated scatter, but the wide variety of imaging geometry in different CBCT configuration suggests that not all configuration are affected to the same extent. Graphics processing unit (GPU) accelerated Monte Carlo (MC) simulations are employed over a range of imaging geometries to elucidate the factors governing scatter characteristics, effica y of antiscatter grids, guide system design, and augment development of scatter correction. Methods: A MC x-ray simulator implemented on GPU was accelerated by inclusion of variance reduction techniques (interaction splitting, forced scattering, and forced detection) and extended to include x-ray spectra and analytical models of antiscatter grids and flat-pane detectors. The simulator was applied to small animal (SA), musculoskeletal (MSK) extremity, otolaryngology (Head), breast, interventional C-arm, and on-board (kilovoltage) linear accelerator (Linac) imaging, with an axis-todetector distance (ADD) of 5, 12, 22, 32, 60, and 50 cm, respectively. Each configuratio was modeled with and without an antiscatter grid and with (i) an elliptical cylinder varying 70–280 mm in major axis; and (ii) digital murine and anthropomorphic models. The effects of scatter were evaluated in terms of the angular distribution of scatter incident upon the detector, scatter-to-primary ratio (SPR), artifact magnitude, contrast, contrast-to-noise ratio (CNR), and visual assessment. Results: Variance reduction yielded improvements in MC simulation efficien y ranging from ∼17-fold (for SA CBCT) to ∼35-fold (for Head and C-arm), with the most significan acceleration due to interaction splitting (∼6 to ∼10-fold increase in efficien y). The benefi of a more extended geometry was evident by virtue of a larger air gap—e.g., for a 16 cm diameter object, the SPR reduced from 1.5 for ADD = 12 cm (MSK geometry) to 1.1 for ADD = 22 cm (Head) and to 0.5 for ADD = 60 cm (C-arm). Grid efficien y was higher for configuration with shorter air gap due to a broader angular distribution of scattered photons—e.g., scatter rejection factor ∼0.8 for MSK geometry versus ∼0.65 for C-arm. Grids reduced cupping for all configuration but had limited improvement on scatterinduced streaks and resulted in a loss of CNR for the SA, Breast, and C-arm. Relative contribution of forward-directed scatter increased with a grid (e.g., Rayleigh scatter fraction increasing from ∼0.15 without a grid to ∼0.25 with a grid for the MSK configuration) resulting in scatter distributions with greater spatial variation (the form of which depended on grid orientation). Conclusions: A fast MC simulator combining GPU acceleration with variance reduction provided a systematic examination of a range of CBCT configuration in relation to scatter, highlighting the magnitude and spatial uniformity of individual scatter components, illustrating tradeoffs in CNR and artifacts and identifying the system geometries for which grids are more beneficia (e.g., MSK) from those in which an extended geometry is the better defense (e.g., C-arm head imaging). Compact geometries with an antiscatter grid challenge assumptions of slowly varying scatter distributions due to increased contribution of Rayleigh scatter.The research was supported by academic-industry partnership with Carestream Health Inc. (Rochester, NY) and National Institutes of Health (NIH) Grant No. 2R01-CA-112163. A. Sisniega is supported by FPU grant (Spanish Ministry of Education), AMIT project, RECAVA-RETIC Network, Project Nos. TEC2010-21619- C04-01, TEC2011-28972-C02-01, and PI11/00616 (Spanish Ministry of Science and Education), ARTEMIS program (Comunidad de Madrid), and PreDiCT-TB partnership.Publicad

    The Noise Exposure Structured Interview (NESI): an instrument for the comprehensive estimation of lifetime noise exposure

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    Lifetime noise exposure is generally quantified by self report. The accuracy of retrospective self report is limited by respondent recall, but is also bound to be influenced by reporting procedures. Such procedures are of variable quality in current measures of lifetime noise exposure, and off-the-shelf instruments are not readily available. The Noise Exposure Structured Interview (NESI) represents an attempt to draw together some of the stronger elements of existing procedures and to provide solutions to their outstanding limitations. Reporting is not restricted to pre-specified exposure activities, and instead encompasses all activities that the respondent has experienced as noisy (defined based on sound level estimated from vocal effort). Changing exposure habits over time are reported by dividing the lifespan into discrete periods in which exposure habits were approximately stable, with life milestones used to aid recall. Exposure duration, sound level, and use of hearing protection are reported for each life period separately. Simple-to-follow methods are provided for the estimation of free-field sound level, the sound level emitted by personal listening devices, and the attenuation provided by hearing protective equipment. An energy-based means of combining the resulting data is supplied, along with a primarily energy-based method for incorporating firearm-noise exposure. Finally, the NESI acknowledges the need of some users to tailor the procedures; this flexibility is afforded and reasonable modifications are described. Competency needs of new users are addressed through detailed interview instructions (including troubleshooting tips) and a demonstration video. Limited evaluation data are available and future efforts at evaluation are proposed

    Optimality of Human Contour Integration

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    For processing and segmenting visual scenes, the brain is required to combine a multitude of features and sensory channels. It is neither known if these complex tasks involve optimal integration of information, nor according to which objectives computations might be performed. Here, we investigate if optimal inference can explain contour integration in human subjects. We performed experiments where observers detected contours of curvilinearly aligned edge configurations embedded into randomly oriented distractors. The key feature of our framework is to use a generative process for creating the contours, for which it is possible to derive a class of ideal detection models. This allowed us to compare human detection for contours with different statistical properties to the corresponding ideal detection models for the same stimuli. We then subjected the detection models to realistic constraints and required them to reproduce human decisions for every stimulus as well as possible. By independently varying the four model parameters, we identify a single detection model which quantitatively captures all correlations of human decision behaviour for more than 2000 stimuli from 42 contour ensembles with greatly varying statistical properties. This model reveals specific interactions between edges closely matching independent findings from physiology and psychophysics. These interactions imply a statistics of contours for which edge stimuli are indeed optimally integrated by the visual system, with the objective of inferring the presence of contours in cluttered scenes. The recurrent algorithm of our model makes testable predictions about the temporal dynamics of neuronal populations engaged in contour integration, and it suggests a strong directionality of the underlying functional anatomy
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