A case study in the history of neurology

We review the case of a young man who developed a constellation of symptoms and signs—bizarre behavior, seizures, abnormal movements, and autonomic instability—that evaded diagnosis at the time of presentation. We use this case to explore the way medical knowledge changes over time. Despite the dramatic advances in our understanding of neurological diseases in recent decades, physicians tend to approach diseases and diagnoses as if they were immutable. Our case reinforces how the diagnosis and treatment of disease are determined by an ever-changing historical context driven by the rapid expansion of medical knowledge. We discuss the implications of this realization and present strategies for navigating the boundaries of knowledge, both in practice and in principle

Multidimensional relativistic MHD simulations of Pulsar Wind Nebulae: dynamics and emission

Pulsar Wind Nebulae, and the Crab nebula in particular, are the best cosmic laboratories to investigate the dynamics of magnetized relativistic outflows and particle acceleration up to PeV energies. Multidimensional MHD modeling by means of numerical simulations has been very successful at reproducing, to the very finest details, the innermost structure of these synchrotron emitting nebulae, as observed in the X-rays. Therefore, the comparison between the simulated source and observations can be used as a powerful diagnostic tool to probe the physical conditions in pulsar winds, like their composition, magnetization, and degree of anisotropy. However, in spite of the wealth of observations and of the accuracy of current MHD models, the precise mechanisms for magnetic field dissipation and for the acceleration of the non-thermal emitting particles are mysteries still puzzling theorists to date. Here we review the methodologies of the computational approach to the modeling of Pulsar Wind Nebulae, discussing the most relevant results and the recent progresses achieved in this fascinating field of high-energy astrophysics.Comment: 29 pages review, preliminary version. To appear in the book "Modelling Nebulae" edited by D. Torres for Springer, based on the invited contributions to the workshop held in Sant Cugat (Barcelona), June 14-17, 201

Comparative Pro-cognitive and Neurochemical Profiles of Glycine Modulatory Site Agonists and Glycine Reuptake Inhibitors in the Rat: Potential Relevance to Cognitive Dysfunction and Its Management

© 2020, The Author(s). Frontocortical NMDA receptors are pivotal in regulating cognition and mood, are hypofunctional in schizophrenia, and may contribute to autistic spectrum disorders. Despite extensive interest in agents potentiating activity at the co-agonist glycine modulatory site, few comparative functional studies exist. This study systematically compared the actions of the glycine reuptake inhibitors, sarcosine (40–200mg/kg) and ORG24598 (0.63–5mg/kg), the agonists, glycine (40–800mg/kg), and D-serine (10–160mg/kg) and the partial agonists, S18841 (2.5mg/kg s.c.) and D-cycloserine (2.5–40mg/kg) that all dose-dependently prevented scopolamine disruption of social recognition in adult rats. Over similar dose ranges, they also prevented a delay-induced impairment of novel object recognition (NOR). Glycine reuptake inhibitors specifically elevated glycine but not D-serine levels in rat prefrontal cortical (PFC) microdialysates, while glycine and D-serine markedly increased levels of glycine and D-serine, respectively. D-Cycloserine slightly elevated D-serine levels. Conversely, S18841 exerted no influence on glycine, D-serine, other amino acids, monamines, or acetylcholine. Reversal of NOR deficits by systemic S18841 was prevented by the NMDA receptor antagonist, CPP (20mg/kg), and the glycine modulatory site antagonist, L701,324 (10mg/kg). S18841 blocked deficits in NOR following microinjection into the PFC (2.5–10μg/side) but not the striatum. Finally, in rats socially isolated from weaning (a neurodevelopmental model of schizophrenia), S18841 (2.5 and 10mg/kgs.c.) reversed impairment of NOR and contextual fear-motivated learning without altering isolation-induced hyperactivity. In conclusion, despite contrasting neurochemical profiles, partial glycine site agonists and glycine reuptake inhibitors exhibit comparable pro-cognitive effects in rats of potential relevance to treatment of schizophrenia and other brain disorders where cognitive performance is impaired

Localized structures of electromagnetic waves in hot electron-positronplasmas

The dynamics of relativistically strong electromagnetic (EM) wave propagation in hot electron-positron plasma is investigated. The possibility of finding localized stationary structures of EM waves is explored. It is shown that under certain conditions the EM wave forms a stable localized soliton-like structures where plasma is completely expelled from the region of EM field location.Comment: 14 pages, LaTeX, 1 figure can be obtained upon request through email to [email protected]

On the kinematics of a corotating relativistic plasma stream in the perpendicular rotator model of a pulsar magnetosphere

An investigation of the kinematics of a rotating relativistic plasma stream in the perpendicular rotator model of the pulsar magnetosphere is presented. It is assumed that the plasma (ejected from the pulsar) moves along the pulsar magnetic field lines and also corotates with them. The field lines are considered to be radial straight lines, located in the plane which is perpendicular to the pulsar rotation axis. The necessity of taking particle inertia into account is discussed. It is argued that the "massless" ("force-free") approximation cannot be used for the description of this problem. The frame selection is discussed and it is shown that it is convenient to discuss the problem in the noninertial frame of ZAMOs (Zero Angular Momentum Observers). The equation of motion and the exact set of equations describing the behaviour of a relativistic plasma stream in the pulsar magnetosphere is obtained. The possible relevance of this investigation for the understanding of the formation process of a pulsar magnetosphere is discussed.Comment: Plain LaTe

Le magmatisme de la région de Kwyjibo, Province\ud du Grenville (Canada) : intérêt pour les\ud minéralisations de type fer-oxydes associées

The granitic plutons located north of the Kwyjibo property in Quebec’s Grenville Province are of\ud Mesoproterozoic age and belong to the granitic Canatiche Complex . The rocks in these plutons are calc-alkalic, K-rich,\ud and meta- to peraluminous. They belong to the magnetite series and their trace element characteristics link them to\ud intraplate granites. They were emplaced in an anorogenic, subvolcanic environment, but they subsequently underwent\ud significant ductile deformation. The magnetite, copper, and fluorite showings on the Kwyjibo property are polyphased\ud and premetamorphic; their formation began with the emplacement of hydraulic, magnetite-bearing breccias, followed by\ud impregnations and veins of chalcopyrite, pyrite, and fluorite, and ended with a late phase of mineralization, during\ud which uraninite, rare earths, and hematite were emplaced along brittle structures. The plutons belong to two families:\ud biotite-amphibole granites and leucogranites. The biotite-amphibole granites are rich in iron and represent a potential\ud heat and metal source for the first, iron oxide phase of mineralization. The leucogranites show a primary enrichment in\ud REE (rare-earth elements), F, and U, carried mainly in Y-, U-, and REE-bearing niobotitanates. They are metamict and\ud underwent a postmagmatic alteration that remobilized the uranium and the rare earths. The leucogranites could also be\ud a source of rare earths and uranium for the latest mineralizing events

Design and modeling of a transistor vertical-cavity surface-emitting laser

A multiple quantum well (MQW) transistor vertical-cavity surface-emitting laser (T-VCSEL) is designed and numerically modeled. The important physical models and parameters are discussed and validated by modeling a conventional VCSEL and comparing the results with the experiment. The quantum capture/escape process is simulated using the quantum-trap model and shows a significant effect on the electrical output of the T-VCSEL. The parameters extracted from the numerical simulation are imported into the analytic modeling to predict the frequency response and simulate the large-signal modulation up to 40 Gbps

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis:An ENIGMA Working Group Mega-analysis

IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (rho = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (rho = 0.43; 95% CI, 0.20 to 0.61; P = .001).CONCLUSIONS AND RELEVANCE This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.Question How are brain morphometric features associated with later psychosis conversion in individuals at clinical high risk (CHR) for developing psychosis?Findings In this case-control study including 3169 participants, lower cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in individuals at CHR in a manner highly consistent with thinner cortex in individuals with established psychosis. Regions that displayed lower cortical thickness in individuals at CHR who later developed a psychotic disorder additionally displayed abnormal associations with age.Meaning In this study, CHR status and later transition to psychosis was robustly associated with lower cortical thickness; abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in individuals at CHR, including pruning and myelination.This case-control study investigates baseline structural magnetic resonance imaging (MRI) differences between individuals at clinical high risk and healthy controls as well as between participants at clinical high risk who later developed a psychotic disorder and those who did not

High Energy Processes in Pulsar Wind Nebulae

Young pulsars produce relativistic winds which interact with matter ejected during the supernova explosion and the surrounding interstellar gas. Particles are accelerated to very high energies somewhere in the pulsar winds or at the shocks produced in collisions of the winds with the surrounding medium. As a result of interactions of relativistic leptons with the magnetic field and low energy radiation (of synchrotron origin, thermal, or microwave background), the non-thermal radiation is produced with the lowest possible energies up to $\sim$100 TeV. The high energy (TeV) gamma-ray emission has been originally observed from the Crab Nebula and recently from several other objects. Recent observations by the HESS Cherenkov telescopes allow to study for the first time morphology of the sources of high energy emission, showing unexpected spectral features. They might be also interpreted as due to acceleration of hadrons. However, theory of particle acceleration in the PWNe and models for production of radiation are still at their early stage of development since it becomes clear that realistic modeling of these objects should include their time evolution and three-dimensional geometry. In this paper we concentrate on the attempts to create a model for the high energy processes inside the PWNe which includes existence not only relativistic leptons but also hadrons inside the nebula. Such model should also take into account evolution of the nebula in time. Possible high energy expectations based on such a model are discussed in the context of new observations.Comment: 9 pages, 1 figure, Proc. Multimessenger approach to high energy gamma-ray source