Objectives Our goal was to assess the prevalence of complicated American Heart Association (AHA) lesion type VI plaques in the carotid arteries of patients with cryptogenic stroke. Background In up ...to 40% of ischemic stroke patients, no definite cause can be established despite extensive workup (i.e., cryptogenic stroke). To test the hypothesis if nonstenosing complicated carotid plaques may be the underlying etiology in some of these patients, we used high-resolution black-blood carotid magnetic resonance imaging (MRI), which can quantitatively assess plaque composition and morphology with good correlation to histopathology. Specifically, we focused on AHA type VI plaques, which are characterized by hemorrhage, thrombus, or fibrous cap rupture. Methods Thirty-two consecutive patients (22 male; mean age 71.7 ± 11.9 years) with cryptogenic stroke and nonstenosing (<50%) eccentric carotid plaques were recruited from a single stroke unit. All patients underwent extensive clinical workup (brain MRI, duplex sonography, electrocardiography and Holter monitoring, transthoracic and transesophageal echocardiography, and laboratory investigations) to exclude other causes of stroke. All patients received a black-blood carotid MRI at 3-T with fat-saturated pre- and post-contrast T-1–, proton density–, and T-2–weighted and time-of-flight images using surface coils and parallel imaging techniques. Prevalence of AHA type VI plaque was determined in both carotid arteries on the basis of previously published MRI criteria. Results AHA type VI plaques were found in 12 of 32 arteries (37.5%) ipsilateral to the stroke, whereas there were no AHA type VI plaques contralateral to the stroke (p = 0.001). The most common diagnostic feature of AHA type VI plaques was intraplaque hemorrhage (75%), followed by fibrous plaque rupture (50%) and luminal thrombus (33%). Conclusions This pilot study suggests that arterio-arterial embolism from complicated, nonstenosing carotid atherosclerotic plaques may play a role in a subgroup of patients previously diagnosed with cryptogenic stroke. To further evaluate the significance of AHA type VI plaques in cryptogenic stroke, future studies will have to analyze both clinical and imaging follow-up data, including event rates for secondary strokes.
ABSTRACT
Achieving a truly accurate wavelength calibration of high-dispersion echelle spectrographs is a challenging task but crucially needed for certain science cases, e.g. to test for a possible ...variation of the fine-structure constant in quasar spectra. One of the spectrographs best suited for this mission is Very Large Telescope/Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observation (ESPRESSO). Nevertheless, previous studies have identified significant discrepancies between the classical wavelength solutions and the one derived independently from the laser frequency comb. The dominant parts of these systematics were intra-order distortions, most-likely related to a deviation of the instrumental line-spread function from the assumed Gaussian shape. Here, we therefore present a study focused on a detailed modelling of the ESPRESSO instrumental line-spread function. We demonstrate that it is strongly asymmetric, non-Gaussian, different for the two slices and fibres, and varies significantly along the spectral orders. Incorporating the determined non-parametric model in the wavelength calibration process drastically improves the wavelength calibration accuracy, reducing the discrepancies between the two independent wavelength solutions from $50\,\rm{m\,s^{-1}}$ to about $10\, \rm{m\,s^{-1}}$. The most striking success is, however, that the different fibres and slices now provide fully consistent measurements with a scatter of just a couple m s−1. This demonstrates that the instrument-related systematics can be nearly eliminated over most of the spectral range by properly taking into account the complex shape of the instrumental line-spread function and paves the way for further optimizations of the wavelength calibration process.
The He ii transverse proximity effect-enhanced He ii Ly transmission in a background sightline caused by the ionizing radiation of a foreground quasar-offers a unique opportunity to probe the ...emission properties of quasars, in particular the emission geometry (obscuration, beaming) and the quasar lifetime. Building on the foreground quasar survey published in Schmidt et al., we present a detailed model of the He ii transverse proximity effect, specifically designed to include light travel time effects, finite quasar ages, and quasar obscuration. We post-process outputs from a cosmological hydrodynamical simulation with a fluctuating He ii ultraviolet background model, with the added effect of the radiation from a single bright foreground quasar. We vary the age tage and obscured sky fractions obsc of the foreground quasar, and explore the resulting effect on the He ii transverse proximity effect signal. Fluctuations in intergalactic medium density and the ultraviolet background, as well as the unknown orientation of the foreground quasar, result in a large variance of the He ii Ly transmission along the background sightline. We develop a fully Bayesian statistical formalism to compare far-ultraviolet He ii Ly transmission spectra of the background quasars to our models, and extract joint constraints on tage and obsc for the six Schmidt et al. foreground quasars with the highest implied He ii photoionization rates. Our analysis suggests a bimodal distribution of quasar emission properties, whereby one foreground quasar, associated with a strong He ii transmission spike, is relatively old (22 Myr) and unobscured ( obsc < 35 % ), whereas three others are either younger than 10 Myr or highly obscured ( obsc > 70 % ).
The He ii transverse proximity effect-enhanced He ii transmission in a background sightline caused by the ionizing radiation of a foreground quasar-offers a unique opportunity to probe the morphology ...of quasar-driven He ii reionization. We conduct a comprehensive spectroscopic survey to find quasars in the foreground of 22 background quasar sightlines with Hubble Space Telescope/COS He ii transmission spectra. With our two-tiered survey strategy, consisting of a deep pencil-beam survey and a shallow wide-field survey, we discover 131 new quasars, which we complement with known SDSS/BOSS quasars in our fields. Using a restricted sample of 66 foreground quasars with inferred He ii photoionization rates greater than the expected UV background at these redshifts ( ) we perform the first statistical analysis of the He ii transverse proximity effect. Our results show qualitative evidence for a large object-to-object variance: among the four foreground quasars with the highest only one (previously known) quasar is associated with a significant He ii transmission spike. We perform a stacking analysis to average down these fluctuations, and detect an excess in the average He ii transmission near the foreground quasars at significance. This statistical evidence for the transverse proximity effect is corroborated by a clear dependence of the signal strength on . Our detection places a purely geometrical lower limit on the quasar lifetime of . Improved modeling would additionally constrain quasar obscuration and the mean free path of He ii-ionizing photons.
As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased ...individuals
. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer
, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19
. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.
The study of 21 cm line observations of atomic hydrogen allows detailed insight into the kinematics of spiral galaxies. We use sensitive high-resolution Very Large Array data from The H i Nearby ...Galaxy Survey (THINGS) to search for radial gas flows primarily in the outer parts (up to 3 × r
25) of 10 nearby spiral galaxies. Inflows are expected to replenish the gas reservoir and fuel star formation under the assumption that galaxies evolve approximately in steady state. We carry out a detailed investigation of existing tilted ring fitting schemes and discover systematics that can hamper their ability to detect signatures of radial flows. We develop a new Fourier decomposition scheme that fits for rotational and radial velocities and simultaneously determines position angle and inclination as a function of radius. Using synthetic velocity fields we show that our novel fitting scheme is less prone to such systematic errors and that it is well suited to detect radial inflows in discs. We apply our fitting scheme to 10 THINGS galaxies and find clear indications of, at least partly previously unidentified, radial gas flows, in particular for NGC 2403 and NGC 3198 and to a lesser degree for NGC 7331, NGC 2903 and NGC 6946. The mass flow rates are of the same order but usually larger than the star formation rates. At least for these galaxies a scenario in which continuous mass accretion feeds star formation seems plausible. The other galaxies show a more complicated picture with either no clear inflow, outward motions or complex kinematic signatures.
Abstract
The intense radiation emitted by luminous quasars dramatically alters the ionization state of their surrounding IGM. This so-called proximity effect extends out to tens of Mpc, and manifests ...as large coherent regions of enhanced Ly
α
(Ly
α
) forest transmission in absorption spectra of background sightlines. Here, we present a novel method based on Ly
α
forest tomography, which is capable of mapping these quasar “light echoes” in three dimensions. Using a dense grid (10–100) of faint (
) background galaxies as absorption probes, one can measure the ionization state of the IGM in the vicinity of a foreground quasar, yielding detailed information about the quasar’s radiative history and emission geometry. An end-to-end analysis—combining cosmological hydrodynamical simulations post-processed with a quasar emission model, realistic estimates of galaxy number densities, and instrument + telescope throughput—is conducted to explore the feasibility of detecting quasar light echoes. We present a new, fully Bayesian statistical method that allows one to reconstruct quasar light echoes from thousands of individual low-S/N transmission measurements. Armed with this tool, we undertake an exhaustive parameter study and show that light echoes can be convincingly detected for luminous (
M
1450
< −27.5 mag, corresponding to
m
1450
< 18.4 mag at
) quasars at redshifts 3 <
z
QSO
< 5, and that a relative precision better than 20% on the quasar age can be achieved for individual objects in the expected range of ages between 1 and 100 Myr. The observational requirements are relatively modest: moderate-resolution (
R
≳ 750), multiobject spectroscopy at a low signal-to-noise ratio (S/N > 5) is sufficient, requiring three-hour integrations using existing instruments on 8 m class telescopes.
The molecular organization of presynaptic active zones during calcium influx-triggered neurotransmitter release is the focus of intense investigation. The Drosophila coiled-coil domain protein ...Bruchpilot (BRP) was observed in donut-shaped structures centered at active zones of neuromuscular synapses by using subdiffraction resolution STED (stimulated emission depletion) fluorescence microscopy. At brp mutant active zones, electron-dense projections (T-bars) were entirely lost, Ca²⁺ channels were reduced in density, evoked vesicle release was depressed, and short-term plasticity was altered. BRP-like proteins seem to establish proximity between Ca²⁺ channels and vesicles to allow efficient transmitter release and patterned synaptic plasticity.
TDP‐43 is an RNA/DNA‐binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP‐43 are hallmarks of frontotemporal dementia and amyotrophic lateral sclerosis. ...Besides aggregation of TDP‐43, loss of nuclear localization is observed in disease. To identify relevant targets of TDP‐43, we performed expression profiling. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered on TDP‐43 silencing and confirmed at the mRNA and protein level in human embryonic kidney HEK293E and neuronal SH‐SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl‐tubulin. HDAC6 levels were restored by re‐expression of TDP‐43, dependent on RNA binding and the C‐terminal protein interaction domains. Moreover, TDP‐43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP‐43 knockout Drosophila melanogaster confirmed the specific downregulation of HDAC6. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, HDAC6‐dependent reduction of cellular aggregate formation and increased cytotoxicity of polyQ‐expanded ataxin‐3 were found in TDP‐43 silenced cells. In conclusion, loss of functional TDP‐43 causes HDAC6 downregulation and might thereby contribute to pathogenesis.
ABSTRACT Ground-based astronomy is unavoidably subject to the adverse effect of atmospheric turbulence, a.k.a. the seeing, which blurs the images and limits the achievable spatial resolution. For ...spectroscopic observations, it leads to slit or fibre-injection losses, since not all photons distributed over the extended seeing disc can be captured. These losses might have a very substantial impact on the overall efficiency of a spectrograph and are naturally highly variable. Assessing the fibre-injection losses requires accurate information about the image quality (IQ) delivered by the telescope to the instrument over the course of the observations, which, however, is often not directly available. ESPRESSO provides acquisition and field-stabilization images attached to the science data and thus offers the opportunity for a post-processing analysis. Here, we present a novel method to infer the IQ profile and fibre-injection losses from the integrated field-stabilization images, utilizing the spill-over light that does not get injected into the fibre. We validate these measurements against the IQ observed in the acquisition images and determine that our method delivers unbiased estimates with a scatter of 0.11 arcsec for the FWHM of the profile and $15~{{\ \rm per\ cent}}$ in terms of fibre-injection losses. This compares favourably to the estimates derived from either the differential image motion monitor or the telescope guide probe sensors and therefore represents a valuable tool to characterize the instrument efficiency and to correct raw spectra for fibre-injection losses.
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