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Sökning: WFRF:(Lockhart T. G.)

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1.
  • Sweeney, M. D., et al. (författare)
  • Vascular dysfunction-The disregarded partner of Alzheimer's disease
  • 2019
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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  • Bacchus, E., et al. (författare)
  • Project 1640 observations of the white dwarf HD 114174 B
  • 2017
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 469:4, s. 4796-4805
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first near infrared spectrum of the faint white dwarf companion HD 114174 B, obtained with Project 1640. Our spectrum, covering the Y, J and H bands, combined with previous TaRgetting bENchmark-objects with Doppler Spectroscopy (TRENDS) photometry measurements, allows us to place further constraints on this companion. We suggest two possible scenarios; either this object is an old, low-mass, cool H atmosphere white dwarf with T-eff similar to 3800 K or a high-mass white dwarf with T-eff > 6000 K, potentially with an associated cool (T-eff similar to 700 K) brown dwarf or debris disc resulting in an infrared excess in the L' band. We also provide an additional astrometry point for 2014 June 12 and use the modelled companion mass combined with the radial velocity and direct imaging data to place constraints on the orbital parameters for this companion.
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3.
  • Hoenigl, M., et al. (författare)
  • Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study
  • 2023
  • Ingår i: Lancet. Infectious Diseases. - : Elsevier BV. - 1473-3099 .- 1474-4457. ; 23:6, s. 751-761
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes.Methods In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines.Findings 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1 & BULL;08 [95% CI 1 & BULL;04-1 & BULL;11; p<0 & BULL;0001] in patients with a central venous catheter and 1 & BULL;09 [1 & BULL;05-1 & BULL;13; p<0 & BULL;0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals.Interpretation Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay.
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4.
  • Wang, T, et al. (författare)
  • Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4932-
  • Tidskriftsartikel (refereegranskat)abstract
    • Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E−06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E−07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype–genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.
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  • Nilsson, Ricky, et al. (författare)
  • Project 1640 Observations of Brown Dwarf GJ 758 B : Near-infrared Spectrum and Atmospheric Modeling
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 838:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The nearby Sun-like star GJ 758 hosts a cold substellar companion, GJ 758 B, at a projected separation of l less than or similar to 30 au, previously detected in high-contrast multi-band photometric observations. In order to better constrain the companion's physical characteristics, we acquired the first low-resolution (R similar to 50) near-infrared spectrum of it using the high-contrast hyperspectral imaging instrument Project 1640 on Palomar Observatory's 5 m Hale telescope. We obtained simultaneous images in 32 wavelength channels covering the Y, J, and H bands (similar to 9521770 nm), and used data processing techniques based on principal component analysis to efficiently subtract chromatic background speckle-noise. GJ 758 B was detected in four epochs during 2013 and 2014. Basic astrometric measurements confirm its apparent northwest trajectory relative to the primary star, with no clear signs of orbital curvature. Spectra of SpeX/IRTF observed T dwarfs were compared to the combined spectrum of GJ 758 B, with chi(2) minimization suggesting a best fit for spectral type T7.0 +/- 1.0, but with a shallow minimum over T5T8. Fitting of synthetic spectra from the BT-Settl13 model atmospheres gives an effective temperature T-eff = 741 +/- 25 K and surface gravity log g=4.3 +/- 0.5 dex (cgs). Our derived best-fit spectral type and effective temperature from modeling of the low-resolution spectrum suggest a slightly earlier and hotter companion than previous findings from photometric data, but do not rule out current results, and confirm GJ 758 B as one of the coolest sub-stellar companions to a Sun-like star to date.
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11.
  • Follert, R., et al. (författare)
  • CRIRES plus : a cross-dispersed high-resolution infrared spectrograph for the ESO VLT
  • 2014
  • Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
  • Konferensbidrag (refereegranskat)abstract
    • High-resolution infrared spectroscopy plays an important role in astrophysics from the search for exoplanets to cosmology. Yet, many existing infrared spectrographs are limited by a rather small simultaneous wavelength coverage. The AO assisted CRIRES instrument, installed at the ESO VLT on Paranal, is one of the few IR (0.92-5.2 mu m) high-resolution spectrographs in operation since 2006. However it has a limitation that hampers its efficient use: the wavelength range covered in a single exposure is limited to similar to 15 nanometers. The CRIRES Upgrade project (CRIRES+) will transform CRIRES into a cross-dispersed spectrograph and will also add new capabilities. By introducing cross-dispersion elements the simultaneously covered wavelength range will be increased by at least a factor of 10 with respect to the present configuration, while the operational wavelength range will be preserved. For advanced wavelength calibration, new custom made absorption gas cells and etalons will be added. A spectro-polarimetric unit will allow one for the first time to record circularly polarized spectra at the highest spectral resolution. This will be all supported by a new data reduction software which will allow the community to take full advantage of the new capabilities of CRIRES+.
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12.
  • Oliva, E., et al. (författare)
  • Concept and optical design of the cross-disperser module for CRIRES
  • 2014
  • Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
  • Konferensbidrag (refereegranskat)abstract
    • CRIRES, the ESO high resolution infrared spectrometer, is a unique instrument which allows astronomers to access a parameter space which up to now was largely uncharted. In its current setup, it consists of a single-order spectrograph providing long-slit, single-order spectroscopy with resolving power up to R=100,000 over a quite narrow spectral range. This has resulted in sub-optimal efficiency and use of telescope time for all the scientific programs requiring broad spectral coverage of compact objects (e.g. chemical abundances of stars and intergalactic medium, search and characterization of extra-solar planets). To overcome these limitations, a consortium was set-up for upgrading CRIRES to a cross-dispersed spectrometer, called CRIRES+. This paper presents the updated optical design of the cross-dispersion module for CRIRES+. This new module can be mounted in place of the current pre-disperser unit. The new system yields a factor of >10 increase in simultaneous spectral coverage and maintains a quite long slit (10"), ideal for observations of extended sources and for precise sky-background subtraction.
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13.
  • Roberts, Lewis C., et al. (författare)
  • CHARACTERIZATION OF THE COMPANION mu HER
  • 2016
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 151:6
  • Tidskriftsartikel (refereegranskat)abstract
    • mu Her is a nearby quadruple system with a G-subgiant primary and several low-mass companions arranged in a 2+2 architecture. While the BC components have been well characterized, the Ab component has been detected astrometrically and with direct imaging but there has been some confusion over its nature, in particular, whether the companion is stellar or substellar. Using near-infrared spectroscopy, we are able to estimate the spectral type of the companion as an M4 +/- 1V star. In addition, we have measured the astrometry of the system for over a decade. We combined the astrometry with archival radial velocity measurements to compute an orbit of the system. From the combined orbit, we are able to compute the mass sum of the system. Using the estimated mass of the primary, we estimate the mass of the secondary as 0.32 MG, which agrees with the estimated spectral type. Our computed orbit is preliminary due to the incomplete orbital phase coverage, but it should be sufficient to predict ephemerides over the next decade.
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14.
  • Roberts, Lewis C., et al. (författare)
  • KNOW THE STAR, KNOW THE PLANET. V. CHARACTERIZATION OF THE STELLAR COMPANION TO THE EXOPLANET HOST STAR HD 177830
  • 2015
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 150:4
  • Tidskriftsartikel (refereegranskat)abstract
    • HD 177830 is an evolved K0IV star with two known exoplanets. In addition to the planetary companions it has a late-type stellar companion discovered with adaptive optics imagery. We observed the binary star system with the PHARO near-IR camera and the Project 1640 coronagraph. Using the Project 1640 coronagraph and integral field spectrograph we extracted a spectrum of the stellar companion. This allowed us to determine that the spectral type of the stellar companion is a M4 +/- 1 V. We used both instruments to measure the astrometry of the binary system. Combining these data with published data, we determined that the binary star has a likely period of approximately 800 years with a semimajor axis of 100-200 AU. This implies that the stellar companion has had little or no impact on the dynamics of the exoplanets. The astrometry of the system should continue to be monitored, but due to the slow nature of the system, observations can be made once every 5-10 years.
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15.
  • Seemann, U., et al. (författare)
  • Wavelength calibration from 1-5 mu m for the CRIRES plus high-resolution spectrograph at the VLT
  • 2014
  • Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
  • Konferensbidrag (refereegranskat)abstract
    • CRIRES at the VLT is one of the few adaptive optics enabled instruments that offer a resolving power of 10 5 from 1 - 5 mu m. An instrument upgrade (CRIRES+) is proposed to implement cross-dispersion capabilities, spectro-polarimetry modes, a new detector mosaic, and a new gas absorption cell. CRIRES+ will boost the simultaneous wavelength coverage of the current instrument (similar to lambda/70 in a single-order) by a factor of greater than or similar to 10 in the cross-dispersed configuration, while still retaining a 10 arcsec slit suitable for long-slit spectroscopy. CRIRES+ dramatically enhances the instrument's observing efficiency, and opens new scientific opportunities. These include high-precision radial-velocity studies on the 3m/s level to characterize extra-solar planets and their athmospheres, which demand for specialized, highly accurate wavelength calibration techniques. In this paper, we present a newly developed absorption gas-cell to enable high-precision wavelength calibration for CRIRES+. We also discuss the strategies and developments to cover the full operational spectral range (1-5 mu m), employing hollow-cathode emission lamps, Fabry-Perot etalons, and absorption gas-cells.
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