Intravenous magnesium in subarachnoid hemorrhage

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Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3-year prospective follow-up study

Various signs on routine brain MRI can help differentiate between Parkinson’s disease (PD) and the various forms of atypical parkinsonism (AP). Here, we evaluate what routine brain MRI contributes to the clinical diagnosis, in both early and advanced disease stages. We performed a prospective observational study in 113 patients with parkinsonism, but without definite diagnosis upon inclusion. At baseline, patients received a structured interview, comprehensive and standardized neurological assessment, and brain MRI. The silver standard diagnosis was made after 3 years of follow-up (PD n = 43, AP n = 57), which was based on disease progression, repeat standardized neurological examination and response to treatment. The clinical diagnosis was classified as having either ‘low certainty’ (lower than 80%) or ‘high certainty’ (80% or higher). The added diagnostic yield of baseline MRI results were then studied relative to clinical neurological evaluation at presentation, and at follow-up. Sensitivity and specificity for separating AP from PD were calculated for all potentially distinguishing MRI abnormalities described previously in the literature. MRI abnormalities showed moderate to high specificity but limited sensitivity for the diagnosis of AP. These MRI abnormalities contributed little over and above the clinically based diagnosis, except when the clinical diagnosis was uncertain. For these patients, presence of putaminal or cerebellar atrophy was particularly indicative of AP. Routine brain MRI has limited added value for differentiating between PD and AP when clinical certainty is already high, but has some diagnostic value when the clinical diagnosis is still uncertain

External Validation of the DCD-N Score and a Linear Prediction Model to Identify Potential Candidates for Organ Donation After Circulatory Death:A Nationwide Multicenter Cohort Study

Donation after circulatory death (DCD) is a procedure in which after planned withdrawal of life-sustaining treatment (WLST), the dying process is monitored. A DCD procedure can only be continued if the potential organ donor dies shortly after WLST. This study performed an external validation of 2 existing prediction models to identify potentially DCD candidates, using one of the largest cohorts. METHODS. This multicenter retrospective study analyzed all patients eligible for DCD donation from 2010 to 2015. The first model (DCD-N score) assigned points for absence of neurological reflexes and oxygenation index. The second model, a linear prediction model (LPDCD), yielded the probability of death within 60 min. This study determined discrimination (c-statistic) and calibration (Hosmer and Lemeshow test) for both models. RESULTS. This study included 394 patients, 283 (72%) died within 60 min after WLST. The DCD-N score had a c-statistic of 0.77 (95% confidence intervals, 0.71-0.83) and the LPDCD model 0.75 (95% confidence intervals, 0.68-0.81). Calibration of the LPDCD 60-min model proved to be poor (Hosmer and Lemeshow test, P < 0.001). CONCLUSIONS. The DCD-N score and the LPDCD model showed good discrimination but poor calibration for predicting the probability of death within 60 min. Construction of a new prediction model on a large data set is needed to obtain better calibration

Human in vivo neuroimaging to detect reprogramming of the cerebral immune response following repeated systemic inflammation

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Precision Immunotherapy for Sepsis

Decades of sepsis research into a specific immune system-targeting adjunctive therapy have not resulted in the discovery of an effective compound. Apart from antibiotics, source control, resuscitation and organ support, not a single adjunctive treatment is used in current clinical practice. The inability to determine the prevailing immunological phenotype of patients and the related large heterogeneity of study populations are regarded by many as the most important factors behind the disappointing results of past clinical trials. While the therapeutic focus has long been on immunosuppressive strategies, increased appreciation of the importance of sepsis-induced immunoparalysis in causing morbidity and mortality in sepsis patients has resulted in a paradigm shift in the sepsis research field towards strategies aimed at enhancing the immune response. However, similar to immunosuppressive therapies, precision medicine is imperative for future trials with immunostimulatory compounds to succeed. As such, identifying those patients with a severely suppressed or hyperactive immune system who will most likely benefit from either immunostimulatory or immunosuppressive therapy, and accurate monitoring of both the immune and treatment response is crucial. This review provides an overview of the challenges lying ahead on the path towards precision immunotherapy for patients suffering from sepsis

Constraints on the Cosmic-Ray Density Gradient beyond the Solar Circle from Fermi gamma-ray Observations of the Third Galactic Quadrant

We report an analysis of the interstellar $\gamma$-ray emission in the third Galactic quadrant measured by the {Fermi} Large Area Telescope. The window encompassing the Galactic plane from longitude 210\arcdeg to 250\arcdeg has kinematically well-defined segments of the Local and the Perseus arms, suitable to study the cosmic-ray densities across the outer Galaxy. We measure no large gradient with Galactocentric distance of the $\gamma$-ray emissivities per interstellar H atom over the regions sampled in this study. The gradient depends, however, on the optical depth correction applied to derive the \HI\ column densities. No significant variations are found in the interstellar spectra in the outer Galaxy, indicating similar shapes of the cosmic-ray spectrum up to the Perseus arm for particles with GeV to tens of GeV energies. The emissivity as a function of Galactocentric radius does not show a large enhancement in the spiral arms with respect to the interarm region. The measured emissivity gradient is flatter than expectations based on a cosmic-ray propagation model using the radial distribution of supernova remnants and uniform diffusion properties. In this context, observations require a larger halo size and/or a flatter CR source distribution than usually assumed. The molecular mass calibrating ratio, $X_{\rm CO} = N({\rm H_{2}})/W_{\rm CO}$, is found to be $(2.08 \pm 0.11) \times 10^{20} {\rm cm^{-2} (K km s^{-1})^{-1}}$ in the Local-arm clouds and is not significantly sensitive to the choice of \HI\ spin temperature. No significant variations are found for clouds in the interarm region.Comment: Corresponding authors: I. A. Grenier ([email protected]); T. Mizuno ([email protected]); L. Tibaldo ([email protected]) accepted for publication in Ap

Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3-year prospective follow-up study

Abstract Various signs on routine brain MRI can help differentiate between Parkinson&apos;s disease (PD) and the various forms of atypical parkinsonism (AP). Here, we evaluate what routine brain MRI contributes to the clinical diagnosis, in both early and advanced disease stages. We performed a prospective observational study in 113 patients with parkinsonism, but without definite diagnosis upon inclusion. At baseline, patients received a structured interview, comprehensive and standardized neurological assessment, and brain MRI. The silver standard diagnosis was made after 3 years of follow-up (PD n = 43, AP n = 57), which was based on disease progression, repeat standardized neurological examination and response to treatment. The clinical diagnosis was classified as having either &apos;low certainty&apos; (lower than 80%) or &apos;high certainty&apos; (80% or higher). The added diagnostic yield of baseline MRI results were then studied relative to clinical neurological evaluation at presentation, and at follow-up. Sensitivity and specificity for separating AP from PD were calculated for all potentially distinguishing MRI abnormalities described previously in the literature. MRI abnormalities showed moderate to high specificity but limited sensitivity for the diagnosis of AP. These MRI abnormalities contributed little over and above the clinically based diagnosis, except when the clinical diagnosis was uncertain. For these patients, presence of putaminal or cerebellar atrophy was particularly indicative of AP. Routine brain MRI has limited added value for differentiating between PD and AP when clinical certainty is already high, but has some diagnostic value when the clinical diagnosis is still uncertain

The relative and absolute timing accuracy of the EPIC-pn camera on XMM-Newton, from X-ray pulsations of the Crab and other pulsars

Reliable timing calibration is essential for the accurate comparison of XMM-Newton light curves with those from other observatories, to ultimately use them to derive precise physical quantities. The XMM-Newton timing calibration is based on pulsar analysis. However, as pulsars show both timing noise and glitches, it is essential to monitor these calibration sources regularly. To this end, the XMM-Newton observatory performs observations twice a year of the Crab pulsar to monitor the absolute timing accuracy of the EPIC-pn camera in the fast Timing and Burst modes. We present the results of this monitoring campaign, comparing XMM-Newton data from the Crab pulsar (PSR B0531+21) with radio measurements. In addition, we use five pulsars (PSR J0537-69, PSR B0540-69, PSR B0833-45, PSR B1509-58 and PSR B1055-52) with periods ranging from 16 ms to 197 ms to verify the relative timing accuracy. We analysed 38 XMM-Newton observations (0.2-12.0 keV) of the Crab taken over the first ten years of the mission and 13 observations from the five complementary pulsars. All the data were processed with the SAS, the XMM-Newton Scientific Analysis Software, version 9.0. Epoch folding techniques coupled with \chi^{2} tests were used to derive relative timing accuracies. The absolute timing accuracy was determined using the Crab data and comparing the time shift between the main X-ray and radio peaks in the phase folded light curves. The relative timing accuracy of XMM-Newton is found to be better than 10^{-8}. The strongest X-ray pulse peak precedes the corresponding radio peak by 306\pm9 \mus, which is in agreement with other high energy observatories such as Chandra, INTEGRAL and RXTE. The derived absolute timing accuracy from our analysis is \pm48 \mus.Comment: 16 pages, 9 figures. Accepted for publication on A&

Magnetic fields in supernova remnants and pulsar-wind nebulae

We review the observations of supernova remnants (SNRs) and pulsar-wind nebulae (PWNe) that give information on the strength and orientation of magnetic fields. Radio polarimetry gives the degree of order of magnetic fields, and the orientation of the ordered component. Many young shell supernova remnants show evidence for synchrotron X-ray emission. The spatial analysis of this emission suggests that magnetic fields are amplified by one to two orders of magnitude in strong shocks. Detection of several remnants in TeV gamma rays implies a lower limit on the magnetic-field strength (or a measurement, if the emission process is inverse-Compton upscattering of cosmic microwave background photons). Upper limits to GeV emission similarly provide lower limits on magnetic-field strengths. In the historical shell remnants, lower limits on B range from 25 to 1000 microGauss. Two remnants show variability of synchrotron X-ray emission with a timescale of years. If this timescale is the electron-acceleration or radiative loss timescale, magnetic fields of order 1 mG are also implied. In pulsar-wind nebulae, equipartition arguments and dynamical modeling can be used to infer magnetic-field strengths anywhere from about 5 microGauss to 1 mG. Polarized fractions are considerably higher than in SNRs, ranging to 50 or 60% in some cases; magnetic-field geometries often suggest a toroidal structure around the pulsar, but this is not universal. Viewing-angle effects undoubtedly play a role. MHD models of radio emission in shell SNRs show that different orientations of upstream magnetic field, and different assumptions about electron acceleration, predict different radio morphology. In the remnant of SN 1006, such comparisons imply a magnetic-field orientation connecting the bright limbs, with a non-negligible gradient of its strength across the remnant.Comment: 20 pages, 24 figures; to be published in SpSciRev. Minor wording change in Abstrac