Multiple sclerosis is an inflammatory demyeli‐nating disease of the central nervous system. The hallmark of its pathology is the demyelinated plaque with reactive glial scar formation. However, a detailed analysis of the patterns of demyelination, oligodendroglia cell pathology and the reaction of other tissue components suggests that the pathogenesis of myelin destruction in this disease may be heterogeneous. In this review we present a new classification scheme of lesional activity on the basis of the molecular composition of myelin degradation products in macrophages. When these criteria are used, different patterns of demyelination can be distinguished, including demyelination with relative preservation of oligodendrocytes, myelin destruction with concomitant and complete destruction of oligodendrocytes or primary destruction or disturbance of myelinating cells with secondary demyelination. Furthermore, in some cases a primary selective demyelination may be followed by secondary oligodendrocyte loss in the established lesions. Finally, some extraordinarily severe conditions may result in destructive lesions with loss of myelin, oligodendrocytes, axons and astro‐cytes. This heterogeneity of plaque pathology is discussed in the context of recent experimental models of inflammatory demyelination, which show that different immunological pathways may lead to the formation of demyelinated plaques that reveal the diverse structural aspects described above. Our data indicate, that the demyelinated plaques of multiple sclerosis may reflect a common pathological end point of a variety of different immunological mechanisms of myelin destruction in this disease.
Objective Whole gland treatment of the prostate has known efficacy in treating many grades of prostate cancer. However, it is often associated with increased morbidity, including erectile dysfunction and urinary incontinence. Focal ablative therapies, including focal cryoablation (FC), are utilized to minimize the risk of tumor progression and preserve erectile and urinary function. There is little to no consensus on whether intermediate or high-risk prostate cancer should be treated with focal therapy. However, there is a growing body of literature on the effectiveness of FC as an effective means of prostate cancer control. We characterize our experience with 163 patients who underwent FC with a median follow-up of 39 months (IQR: 24-60). Methods A 163-patient retrospective cohort underwent FC of the prostate at a single clinic by a physician from November 2008 to December 2020. Each of these T1c patients in this single-tail study was monitored for biochemical recurrence (BCR) and oncologic outcomes. American Society for Radiation Oncology (ASTRO) definition of BCR is three consecutive prostate-specific antigens (PSA) increases of more than 0.5 ng/mL or, along with the utilization of the Phoenix definition, a PSA greater than nadir by 2 ng/mL was used to define BCR. This study's primary endpoint includes BCR or biochemical disease-free survival rates. Secondary endpoints include patient side effects, such as measuring for urinary incontinence and outcomes of salvage treatments. Cox proportional hazard analyses defined univariate HRs and 95% CIs for pre-operative PSA (POPSA), Decipher, and Gleason Grade Groups (GGGs) to determine the prognostic impact of pathologic factors. Statistical analysis and BCR timeline analysis also included logistic regression and the Kaplan-Meier method, with significance considered at p < 0.05. Select focal cryotherapy patients were monitored utilizing genomic sequencing tests. Results Our cohort included 27 patients (16.5%) with D'Amico low, 115 patients (70.5%) with intermediate, and 23 patients (14.1%) with high-risk prostate cancers. One month after FC, a 73% reduction in PSA resulted in a median post-operative PSA of 1.39 ng/mL (IQR: 0.46-2.80 ng/mL). At five years, our cohort yielded biochemical disease-free recurrence rates of 78%, 74%, and 55% for low, intermediate, and high-grade cancers, respectively. Genetic risk stratification results showed very similar BCR rates to patients whose tissues did not undergo genomic testing, at 27%, 26%, and 46% for low, intermediate, and high-grade cancers, respectively. Log-rank tests to map for BCR and HRs for pathologic factors did not yield any statistically significant predictive results. Urinary incontinence and erectile dysfunction were reported in 1.8% and 3.1% of patients in the focal cohort. Conclusions Our results add to the expanding body of literature around the efficacy of focal ablative therapies in contrast to whole gland treatment. The definitive extent of FC's efficacy still remains to be explored, but our conclusions demonstrate favorable PSA kinetics at five years follow-up.
O desenvolvimento intelectual acerca da formação de buracos negros possui uma história muito rica, pois não envolve apenas questões técnicas particulares à teoria da relatividade geral. O pleno entendimento do colapso gravitacional tanto discorre sobre diversos temas da astrofísica relativística, assim como evidencia a participação de muitos dos maiores físicos da história da ciência. Este artigo visa tratar, de forma introdutória e conceitual, as principais características da formação dos buracos negros, numa linha cronológica de inicial rejeição, seguida de sua inevitável aceitação.
We describe a large simulation of the stars to be observed by the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST). The simulation is based on the TRILEGAL code, which resorts to large databases of stellar evolutionary tracks, synthetic spectra, and pulsation models, added to simple prescriptions for the stellar density and star formation histories of the main structures of the Galaxy, to generate mock stellar samples through a population synthesis approach. The main bodies of the Magellanic Clouds are also included. A complete simulation is provided for single stars, down to the r = 27.5 mag depth of the coadded Wide–Fast–Deep survey images. A second simulation is provided for a fraction of the binaries, including the interacting ones, as derived with the BinaPSE module of TRILEGAL. We illustrate the main properties and numbers derived from these simulations, including: comparisons with real star counts; the expected numbers of Cepheids, long-period variables, and eclipsing binaries; the crowding limits as a function of seeing and filter; the star-to-galaxy ratios. Complete catalogs are accessible through the NOIRLab Astro Data Lab, while the stellar density maps are incorporated in the LSST metrics analysis framework.
L. Fiorini, Luigi Coviello, Alessandra Sorrentino
et al.
Socially Assistive Robots (SARs) are designed to support us in our daily life as a companion, and assistance but also to support the caregivers’ work. SARs should show personalized and human-like behavior to improve their acceptance and, consequently, their use. Additionally, they should be trustworthy by caregivers and professionals to be used as support for their work (e.g. objective assessment, decision support tools). In this context the aim of the paper is dual. Firstly, this paper aims to present and discuss the robot behavioral model based on sensing, perception, decision support, and interaction modules. The novel idea behind the proposed model is to extract and use the same multimodal features set for two purposes: (i) to profile the user, so to be used by the caregiver as a decision support tool for the assessment and monitoring of the patient; (ii) to fine-tune the human–robot interaction if they can be correlated to the social cues. Secondly, this paper aims to test in a real environment the proposed model using a SAR robot, namely ASTRO. Particularly, it measures the body posture, the gait cycle, and the handgrip strength during the walking support task. Those collected data were analyzed to assess the clinical profile and to fine-tune the physical interaction. Ten older people (65.2 ± 15.6 years) were enrolled for this study and were asked to walk with ASTRO at their normal speed for 10 m. The obtained results underline a good estimation ( p < 0.05) of gait parameters, handgrip strength, and angular excursion of the torso with respect to most used instruments. Additionally, the sensory outputs were combined in the perceptual model to profile the user using non-classical and unsupervised techniques for dimensionality reduction namely T-distributed Stochastic Neighbor Embedding (t-SNE) and non-classic multidimensional scaling (nMDS). Indeed, these methods can group the participants according to their residual walking abilities.
: Simulation is a valuable technique used by the military to support personnel training. A trend in current military training is the combination of different types of simulation in an integrated setup. Observing this trend, the Brazilian Army is making efforts to develop integrated simulation solutions. This paper presents the conception of an integrated simulation system of the Brazilian Army Artillery called SIS-ASTROS. Besides the integrated setup connecting different types of simulators, a major contribution in the scope of the SIS-ASTROS is the presentation of the virtual tactical simulator to train mid-rank officers in activities regarding the coordinated deployment of ASTROS artillery batteries on the battlefield. This simulator not only addresses constructive simulation aspects but also virtual ones. Due to its design, the conception of this simulator on its own is already an important innovation. This paper presents the key components of the integrated simulation system, highlighting the main contributions in the research and development of the virtual tactical simulator.
Temporal lobe epilepsy is a widespread chronic disorder that manifests as spontaneous seizures and is often characterized by refractoriness to drug treatment. Temporal lobe epilepsy can be caused by a primary brain injury; therefore, the prevention of epileptogenesis after a primary event is considered one of the best treatment options. However, a preventive treatment for epilepsy still does not exist. Neuroinflammation is directly involved in epileptogenesis and neurodegeneration, leading to the epileptic condition and cognitive decline. In the present study, we aimed to clarify the effect of treatment with a recombinant form of the Interleukin-1 receptor antagonist (anakinra) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that anakinra administration during the latent phase of the model significantly suppressed the duration and frequency of spontaneous recurrent seizures in the chronic phase. Moreover, anakinra administration prevented some behavioral impairments, including motor hyperactivity and disturbances in social interactions, during both the latent and chronic periods. Histological analysis revealed that anakinra administration decreased neuronal loss in the CA1 and CA3 areas of the hippocampus but did not prevent astro- and microgliosis. The treatment increased the expression level of the solute carrier family 1 member 2 gene (Slc1a2, encoding excitatory amino acid transporter 2 (EAAT2)) in the hippocampus, potentially leading to a neuroprotective effect. However, the increased gene expression of proinflammatory cytokine genes (Interleukin-1β (Il1b) and tumor necrosis factor α (Tnfa)) and astroglial marker genes (glial fibrillary acidic protein (Gfap) and inositol 1,4,5-trisphosphate receptor type 2 (Itpr2)) in experimental rats was not affected by anakinra treatment. Thus, our data demonstrate that the administration of anakinra during epileptogenesis has some beneficial disease-modifying effects.
We apply a new deep learning technique to detect, classify, and deblend sources in multiband astronomical images. We train and evaluate the performance of an artificial neural network built on the Mask Region-based Convolutional Neural Network image processing framework, a general code for efficient object detection, classification, and instance segmentation. After evaluating the performance of our network against simulated ground truth images for star and galaxy classes, we find a precision of 92 per cent at 80 per cent recall for stars and a precision of 98 per cent at 80 per cent recall for galaxies in a typical field with ∼30 galaxies arcmin−2. We investigate the deblending capability of our code, and find that clean deblends are handled robustly during object masking, even for significantly blended sources. This technique, or extensions using similar network architectures, may be applied to current and future deep imaging surveys such as Large Synoptic Survey Telescope and Wide-Field Infrared Survey Telescope. Our code, astro r-cnn, is publicly available at https://github.com/burke86/astro_rcnn.
More than 20% of patients undergoing initial breast-conserving surgery (BCS) for cancer require reoperation. To address this concern, the American Society of Breast Surgeons (ASBrS) endorsed 10 processes of care (tools) in 2015 to be considered by surgeons to de-escalate reoperations. In a planned follow-up, we sought to determine which tools were associated with fewer reoperations. A cohort of ASBrS member surgeons prospectively entered data into the ASBrS Mastery® registry on consecutive patients undergoing BCS in 2017. The association between tools and reoperations was estimated via multivariate and hierarchical ranking analyses. Seventy-one surgeons reported reoperations in 486 (12.3%) of 3954 cases (mean 12.7% [standard deviation (SD) 7.7%], median 11.5% [range 0–32%]). There was an eightfold difference between surgeons in the 10th and 90th percentile performance groups. Actionable factors associated with fewer reoperations included routine planned cavity side-wall shaves, surgeon use of ultrasound (US), neoadjuvant chemotherapy, intra-operative pathologic margin assessment, and use of a pre-operative diagnostic imaging modality beyond conventional 2D mammography. For patients with invasive cancer, ≥ 24% of those who underwent reexcision did so for reported margins of < 1 or 2 mm, representing noncompliance with the SSO-ASTRO margin guideline. Although ASBrS member surgeons had some of the lowest rates of reoperation reported in any registry, significant intersurgeon variability persisted. Further efforts to lower rates are therefore warranted. Opportunities to do so were identified by adopting those processes of care, including improved compliance with the SSO-ASTRO margin guideline, which were associated with fewer reoperations.
Abstract The MAGIC telescopes are two Imaging Atmospheric Cherenkov Telescopes (IACTs) located on the Canary island of La Palma. The telescopes are designed to measure Cherenkov light from air showers initiated by gamma rays in the energy regime from around 50 GeV to more than 50 TeV. The two telescopes were built in 2004 and 2009, respectively, with different cameras, triggers and readout systems. In the years 2011–2012 the MAGIC collaboration undertook a major upgrade to make the stereoscopic system uniform, improving its overall performance and easing its maintenance. In particular, the camera, the receivers and the trigger of the first telescope were replaced and the readout of the two telescopes was upgraded. This paper (Part I) describes the details of the upgrade as well as the basic performance parameters of MAGIC such as raw data treatment, linearity in the electronic chain and sources of noise. In Part II, we describe the physics performance of the upgraded system.
It is common practice in cosmology to model large-scale structure observables as lognormal random fields, and this approach has been successfully applied in the past to the matter density and weak lensing convergence fields separately. We argue that this approach has fundamental limitations which prevent its use for jointly modelling these two fields since the lognormal distribution's shape can prevent certain correlations to be attainable. Given the need of ongoing and future large-scale structure surveys for fast joint simulations of clustering and weak lensing, we propose two ways of overcoming these limitations. The first approach slightly distorts the power spectra of the fields using one of two algorithms that minimises either the absolute or the fractional distortions. The second one is by obtaining more accurate convergence marginal distributions, for which we provide a fitting function, by integrating the lognormal density along the line of sight. The latter approach also provides a way to determine directly from theory the skewness of the convergence distribution and, therefore, the parameters for a lognormal fit. We present the public code Full-sky Lognormal Astro-fields Simulation Kit (FLASK) which can make tomographic realisations on the sphere of an arbitrary number of correlated lognormal or Gaussian random fields by applying either of the two proposed solutions, and show that it can create joint simulations of clustering and lensing with sub-per-cent accuracy over relevant angular scales and redshift ranges.
M. C. S. Ansoldi, L. A. Antonelli, P. Antoranz
et al.
Aims. We investigate the extension of the very high-energy spectral tail of the Crab Pulsar at energies above 400 GeV. Methods. We analyzed ~320 h of good-quality Crab data obtained with the MAGIC telescope from February 2007 to April 2014. Results. We report the most energetic pulsed emission ever detected from the Crab Pulsar reaching up to 1.5 TeV. The pulse profile shows two narrow peaks synchronized with those measured in the GeV energy range. The spectra of the two peaks follow two different power-law functions from 70 GeV up to 1.5 TeV and connect smoothly with the spectra measured above 10 GeV by the Large Area Telescope (LAT) on board the Fermi satellite. When making a joint fit of the LAT and MAGIC data above 10 GeV the photon indices of the spectra differ by 0.5 ± 0.1. Conclusions. Using data from the MAGIC telescopes we measured the most energetic pulsed photons from a pulsar to date. Such TeV pulsed photons require a parent population of electrons with a Lorentz factor of at least 5 × 106. These results strongly suggest IC scattering off low-energy photons as the emission mechanism and a gamma-ray production region in the vicinity of the light cylinder.
M. C. J. Aleksi'c, S. Ansoldi, L. A. Antonelli
et al.
Supermassive black holes with masses of millions to billions of solar masses are commonly found in the centers of galaxies. Astronomers seek to image jet formation using radio interferometry but still suffer from insufficient angular resolution. An alternative method to resolve small structures is to measure the time variability of their emission. Here we report on gamma-ray observations of the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes, revealing variability with doubling time scales faster than 4.8 min. Causality constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole. We suggest that the emission is associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the radio jet. Gamma rays that vary on a several-minute time scale suggest an origin within a supermassive black hole’s event horizon. Timing tells the structure of the unseen Nothing can move faster than the speed of light, but some gamma rays seem to break that rule. Powerful jets that balance the angular momentum of accreting black holes are difficult to discern in images, so astronomers often resort to timing their emission to reveal the physics at work. Aleksić et al. found that gamma rays from the active galaxy IC 310 varied faster than the time required for light to cross the event horizon of the supermassive black hole at its nucleus. Particle acceleration at the base of the jet may enable this apparent speed, adding a piece to the puzzle of how jets form at supermassive black holes. Science, this issue p. 1080
We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the γ-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV tohard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the γ-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios. Aims. The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the “single-curve SSC model adjustment” typically reported in the literature. Methods. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (>100 GeV, VHE) γ rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE γ rays). Results. The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE γ rays do not make a dominant contribution to the ~1 keV emission. Alternatively, there could be a very variable component contributing to the VHE γ-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed γ-ray flaring activity, with the EVPA rotation coincident with the first γ-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties.
Astrocytes, once considered passive support cells, are increasingly appreciated as dynamic regulators of neuronal development and function, in part via secreted factors. The extent to which they similarly regulate oligodendrocytes or proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) is less understood. Here, we generated astrocytes from human pluripotent stem cells (hiPSC-Astros) and demonstrated that immature astrocytes, as opposed to mature ones, promote oligodendrogenesis in vitro. In the PVL mouse model of neonatal hypoxic/ischemic encephalopathy, associated with cerebral palsy in humans, transplanted immature hiPSC-Astros promoted myelinogenesis and behavioral outcome. We further identified TIMP-1 as a selectively upregulated component secreted from immature hiPSC-Astros. Accordingly, in the rat PVL model, intranasal administration of conditioned medium from immature hiPSC-Astros promoted oligodendrocyte maturation in a TIMP-1-dependent manner. Our findings suggest stage-specific developmental interactions between astroglia and oligodendroglia and have important therapeutic implications for promoting myelinogenesis.
According to the no-hair theorem, astrophysical black holes are fully characterized by their masses and spins and are described by the Kerr metric. This theorem can be tested observationally by measuring (at least) three different multipole moments of the spacetimes of black holes. In this paper, we calculate the profiles of fluorescent iron lines emitted from the accretion flows around black hole candidates within a framework that allows us to perform the calculation as a function of its mass and spin as well as of a free parameter that measures potential deviations from the Kerr metric. We show that such deviations lead to line profiles that are significantly altered and may exhibit a modified flux ratio of the two peaks in their characteristic double-peaked shape. We also show that the disk inclination can be measured independently of the spin and the deviation parameter at low to intermediate inclination angles, as in the case of Kerr black holes. We estimate the precision that near-future X-ray missions such as Astro-H and ATHENA+ are required to achieve in order to resolve deviations from the Kerr metric in iron line profiles and show that constraints on such deviations will be strongest for rapidly spinning black holes. More generally, we show that measuring the line profile with a precision of ∼5% at disk inclinations of 30° or 60° constrains the deviation parameter to order unity for values of the spin a ≳ 0.5M.
We present the results from deep Suzaku observations of the central region of the Perseus cluster. Bulbul et al. (2014) reported the detection by XMM-Newton instruments of an unidentified X-ray emission line at an energy around 3.5keV in spectra for the Perseus and other clusters. They argued for a possibility of the decay of sterile neutrino, a dark matter candidate. We examine Suzaku X-ray Imaging Spectrometer (XIS) spectra of the Perseus cluster for evidence in the 3.5keV line and other possible dark matter features in the 2-6keV energy band. In order to search for and constrain a weak line feature with the XIS, observations of the Crab nebula are used to evaluate the system's effective area. We found no line feature at the claimed position with a systematic line flux upper limit at a half (1.5eV in line equivalent width) of the claimed best-fit value by Bulbul et al. We discuss this inconsistency in terms of instrumental calibration errors and modeling of continuum emission. Future prospects for high-energy resolution spectroscopy with ASTRO-H are presented.