540 research outputs found
Advances in machine learning applications for cardiovascular 4D flow MRI
Four-dimensional flow magnetic resonance imaging (MRI) has evolved as a non-invasive imaging technique to visualize and quantify blood flow in the heart and vessels. Hemodynamic parameters derived from 4D flow MRI, such as net flow and peak velocities, but also kinetic energy, turbulent kinetic energy, viscous energy loss, and wall shear stress have shown to be of diagnostic relevance for cardiovascular diseases. 4D flow MRI, however, has several limitations. Its long acquisition times and its limited spatio-temporal resolutions lead to inaccuracies in velocity measurements in small and low-flow vessels and near the vessel wall. Additionally, 4D flow MRI requires long post-processing times, since inaccuracies due to the measurement process need to be corrected for and parameter quantification requires 2D and 3D contour drawing. Several machine learning (ML) techniques have been proposed to overcome these limitations. Existing scan acceleration methods have been extended using ML for image reconstruction and ML based super-resolution methods have been used to assimilate high-resolution computational fluid dynamic simulations and 4D flow MRI, which leads to more realistic velocity results. ML efforts have also focused on the automation of other post-processing steps, by learning phase corrections and anti-aliasing. To automate contour drawing and 3D segmentation, networks such as the U-Net have been widely applied. This review summarizes the latest ML advances in 4D flow MRI with a focus on technical aspects and applications. It is divided into the current status of fast and accurate 4D flow MRI data generation, ML based post-processing tools for phase correction and vessel delineation and the statistical evaluation of blood flow
Secondary prevention of venous thromboembolism: Predictors and outcomes of guideline adherence in a long-term prospective cohort study.
Background
Prevention of recurrent venous thromboembolism (VTE) is considered a main goal of VTE management. However, the extent to which physicians adhere to the recommendations from evidence-based guidelines is unknown.
Aim
From a large, prospective clinical cohort, we aimed to (1) quantify the adherence of treatment recommendations to evidence-based guidelines and establish its predictors, and (2) estimate its impact on clinical outcomes and costs in patients with VTE.
Methods
We included 6'243 consecutive patients with VTE treated at the university outpatient unit. Detailed clinical characteristics and treatment recommendations were recorded. Adherence of treatment recommendations to evidence-based guidelines at risk assessment was assessed in terms of duration of anticoagulant treatment. Data on death were obtained from the Swiss Central Compensation Office. Health care claims data recorded between 2014 and 2019 were retrieved from Helsana, one of the largest Swiss health insurance companies.
Results
The adherence to evidence-based guidelines was 36.1%. Among patients with non-adherence, overtreatment was present in 70.1%. Significant patient-related predictors of guideline adherence were (a) age above 50 years, (b) male sex, (c) pulmonary embolism, (d) unprovoked VTE, (e) multiple VTE, (f) laboratory tests not ordered, and (g) various cardiovascular comorbidities. Non-adherence was not significantly associated with mortality, hospitalization, admission to nursing home, and costs.
Conclusions
The adherence to evidence-based guidelines was low, and several unrelated predictors appeared. Although these results need to be confirmed in other settings, they highlight the need for implementation of evidence-based guidelines in clinical practice
Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features
Chromosomal breakpoints involving the MYC gene locus, frequently referred to as MYC rearrangements (MYC - R+), are a diagnostic hallmark of Burkitt lymphoma and recurrent in many other subtypes of B-cell lymphomas including follicular lymphoma, diffuse large B-cell lymphoma and other high-grade B-cell lymphomas and are associated with an aggressive clinical course. In remarkable contrast, in MCL, only few MYC - R+ cases have yet been described. In the current study, we have retrospectively analysed 16 samples (MYC - R+, n = 15, MYC - R-, n = 1) from 13 patients and describe their morphological, immunophenotypic and (molecular) genetic features and clonal evolution patterns. Thirteen out of fifteen MYC - R+ samples showed a non-classical cytology including pleomorphic (centroblastic, immunoblastic), anaplastic or blastoid. MYC translocation partners were IG-loci in 4/11 and non-IG loci in 7/11 analysed cases. The involved IG-loci included IGH in 3 cases and IGL in one case. PAX5 was the non-IG partner in 2/7 patients. The MYC - R+ MCL reported herein frequently displayed characteristics associated with an aggressive clinical course including high genomic-complexity (6/7 samples), frequent deletions involving the CDKN2A locus (7/10 samples), high Ki-67 proliferation index (12/13 samples) and frequent P53 expression (13/13 samples). Of note, in 4/14 samples, SOX11 was not or only focally expressed and 3/13 samples showed focal or diffuse TdT-positivity presenting a diagnostic challenge as these features could point to a differential diagnosis of diffuse large B-cell lymphoma and/or lymphoblastic lymphoma/leukaemia
Accretion of Planetary Material onto Host Stars
Accretion of planetary material onto host stars may occur throughout a star's
life. Especially prone to accretion, extrasolar planets in short-period orbits,
while relatively rare, constitute a significant fraction of the known
population, and these planets are subject to dynamical and atmospheric
influences that can drive significant mass loss. Theoretical models frame
expectations regarding the rates and extent of this planetary accretion. For
instance, tidal interactions between planets and stars may drive complete
orbital decay during the main sequence. Many planets that survive their stars'
main sequence lifetime will still be engulfed when the host stars become red
giant stars. There is some observational evidence supporting these predictions,
such as a dearth of close-in planets around fast stellar rotators, which is
consistent with tidal spin-up and planet accretion. There remains no clear
chemical evidence for pollution of the atmospheres of main sequence or red
giant stars by planetary materials, but a wealth of evidence points to active
accretion by white dwarfs. In this article, we review the current understanding
of accretion of planetary material, from the pre- to the post-main sequence and
beyond. The review begins with the astrophysical framework for that process and
then considers accretion during various phases of a host star's life, during
which the details of accretion vary, and the observational evidence for
accretion during these phases.Comment: 18 pages, 5 figures (with some redacted), invited revie
Stellar Astrophysics and Exoplanet Science with the Maunakea Spectroscopic Explorer (MSE)
The Maunakea Spectroscopic Explorer (MSE) is a planned 11.25-m aperture
facility with a 1.5 square degree field of view that will be fully dedicated to
multi-object spectroscopy. A rebirth of the 3.6m Canada-France-Hawaii Telescope
on Maunakea, MSE will use 4332 fibers operating at three different resolving
powers (R ~ 2500, 6000, 40000) across a wavelength range of 0.36-1.8mum, with
dynamical fiber positioning that allows fibers to match the exposure times of
individual objects. MSE will enable spectroscopic surveys with unprecedented
scale and sensitivity by collecting millions of spectra per year down to
limiting magnitudes of g ~ 20-24 mag, with a nominal velocity precision of ~100
m/s in high-resolution mode. This white paper describes science cases for
stellar astrophysics and exoplanet science using MSE, including the discovery
and atmospheric characterization of exoplanets and substellar objects, stellar
physics with star clusters, asteroseismology of solar-like oscillators and
opacity-driven pulsators, studies of stellar rotation, activity, and
multiplicity, as well as the chemical characterization of AGB and extremely
metal-poor stars.Comment: 31 pages, 11 figures; To appear as a chapter for the Detailed Science
Case of the Maunakea Spectroscopic Explore
Long term outcome of adolescent and adult patients with pineal parenchymal tumors treated with fractionated radiotherapy between 1982 and 2003 -- a single institution's experience
Background: To evaluate the effectivity of fractionated radiotherapy in adolescent and adult patients with pineal parenchymal tumors (PPT). Methods: Between 1982 and 2003, 14 patients with PPTs were treated with fractionated radiotherapy. 4 patients had a pineocytoma (PC), one a PPT with intermediate differentiation (PPTID) and 9 patients a pineoblastoma (PB), 2 of which were recurrences. All patients underwent radiotherapy to the primary tumor site with a median total dose of 54 Gy. In 9 patients with primary PB treatment included whole brain irradiation (3 patients) or irradiation of the craniospinal axis (6 patients) with a median total dose of 35 Gy. Results: Median follow-up was 123 months in the PC patients and 109 months in the patients with primary PB. 7 patients were free from relapse at the end of follow-up. One PC patient died from spinal seeding. Among 5 PB patients treated with radiotherapy without chemotherapy, 3 developed local or spinal tumor recurrence. Both patients treated for PB recurrences died. The patient with PPTID is free of disease 7 years after radiotherapy. Conclusion: Local radiotherapy seems to be effective in patients with PC and some PPTIDs. Diagnosis and treatment of patients with more aggressive variants of PPTIDs as well as treatment of PB need to be further improved, since local and spinal failure even despite craniospinal irradiation (CSI) is common. As PPT are very rare tumors, treatment within multi-institutional trials remains necessary
Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation.
A progressive loss of protein homeostasis is characteristic of aging and a driver of neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain aging in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics and proteomics. We detected a progressive reduction in the correlation between protein and mRNA, mainly due to post-transcriptional mechanisms that account for over 40% of the age-regulated proteins. These changes cause a progressive loss of stoichiometry in several protein complexes, including ribosomes, which show impaired assembly/disassembly and are enriched in protein aggregates in old brains. Mechanistically, we show that reduction of proteasome activity is an early event during brain aging and is sufficient to induce proteomic signatures of aging and loss of stoichiometry in vivo. Using longitudinal transcriptomic data, we show that the magnitude of early life decline in proteasome levels is a major risk factor for mortality. Our work defines causative events in the aging process that can be targeted to prevent loss of protein homeostasis and delay the onset of age-related neurodegeneration
Npn-1 Contributes to Axon-Axon Interactions That Differentially Control Sensory and Motor Innervation of the Limb
The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1) in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG), we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs
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