Abstract
In this contribution, we achieve the primary goal of the active galactic nucleus (AGN)
STORM
campaign by recovering velocity–delay maps for the prominent broad emission lines (Ly
α
, C
iv
, ...He
ii
, and H
β
) in the spectrum of NGC 5548. These are the most detailed velocity–delay maps ever obtained for an AGN, providing unprecedented information on the geometry, ionization structure, and kinematics of the broad-line region. Virial envelopes enclosing the emission-line responses show that the reverberating gas is bound to the black hole. A stratified ionization structure is evident. The He
ii
response inside 5–10 lt-day has a broad single-peaked velocity profile. The Ly
α
, C
iv
, and H
β
responses extend from inside 2 to outside 20 lt-day, with double peaks at ±2500 km s
−1
in the 10–20 lt-day delay range. An incomplete ellipse in the velocity–delay plane is evident in H
β
. We interpret the maps in terms of a Keplerian disk with a well-defined outer rim at
R
= 20 lt-day. The far-side response is weaker than that from the near side. The line-center delay
τ
=
(
R
/
c
)
(
1
−
sin
i
)
≈
5
days gives the inclination
i
≈ 45°. The inferred black hole mass is
M
BH
≈ 7 × 10
7
M
⊙
. In addition to reverberations, the fit residuals confirm that emission-line fluxes are depressed during the “BLR Holiday” identified in previous work. Moreover, a helical “Barber-Pole” pattern, with stripes moving from red to blue across the C
iv
and Ly
α
line profiles, suggests azimuthal structure rotating with a 2 yr period that may represent precession or orbital motion of inner-disk structures casting shadows on the emission-line region farther out.
The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the ...nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, based on structural and functional features of auditory brain organization that confer vulnerability to neurodegeneration, the extensive, reciprocal interplay between 'peripheral' and 'central' hearing dysfunction, and recently characterized auditory signatures of canonical neurodegenerative dementias (Alzheimer's disease, Lewy body disease and frontotemporal dementia). Moving beyond any simple dichotomy of ear and brain, we argue for a reappraisal of the role of auditory cognitive dysfunction and the critical coupling of brain to peripheral organs of hearing in the dementias. We call for a clinical assessment of real-world hearing in these diseases that moves beyond pure tone perception to the development of novel auditory 'cognitive stress tests' and proximity markers for the early diagnosis of dementia and management strategies that harness retained auditory plasticity.
More than twenty years following the end of the 1990-1991 Gulf War it is estimated that approximately 300,000 veterans of this conflict suffer from an unexplained chronic, multi-system disorder known ...as Gulf War Illness (GWI). The etiology of GWI may be exposure to chemical toxins, but it remains only partially defined, and its case definition is based only on symptoms. Objective criteria for the diagnosis of GWI are urgently needed for diagnosis and therapeutic research.
This study was designed to determine if blood biomarkers could provide objective criteria to assist diagnosis of GWI.
A surveillance study of 85 Gulf War Veteran volunteers identified from the Department of Veterans Affairs Minnesota Gulf War registry was performed. All subjects were deployed to the Gulf War. Fifty seven subjects had GWI defined by CDC criteria, and 28 did not have symptomatic criteria for a diagnosis of GWI. Statistical analyses were performed on peripheral blood counts and assays of 61 plasma proteins using the Mann-Whitney rank sum test to compare biomarker distributions and stepwise logistic regression to formulate a diagnostic model.
Lymphocyte, monocyte, neutrophil, and platelet counts were higher in GWI subjects. Six serum proteins associated with inflammation were significantly different in GWI subjects. A diagnostic model of three biomarkers-lymphocytes, monocytes, and C reactive protein-had a predicted probability of 90% (CI 76-90%) for diagnosing GWI when the probability of having GWI was above 70%.
The results of the current study indicate that inflammation is a component of the pathobiology of GWI. Analysis of the data resulted in a model utilizing three readily measurable biomarkers that appears to significantly augment the symptom-based case definition of GWI. These new observations are highly relevant to the diagnosis of GWI, and to therapeutic trials.
Electron acceleration by dispersive scale Alfvén waves at Jupiter is investigated using a Gyrofluid‐Kinetic‐Electron model. Specifically, the simulations consider the propagation of an Alfvén wave ...perturbation from the center of the Io plasma torus to high‐latitude regions that are consistent with recent Juno satellite observations (e.g., Allegrini et al., 2017, https://doi.org/10.1002/2017GL073180; Mauk, et al., 2017a, https://doi.org/10.1038/nature23648; Mauk, et al., 2017b, https://doi.org/10.1002/2016GL072286; Szalay et al., 2018, https://doi.org/10.1029/2018JE005752). As in those observations, the energized electron spectra is broadband in nature and the majority of the energization is under the interaction of inertial Alfvén waves at high latitudes. The extent of the energization associated with these waves is proportional to both the magnitude of the wave perturbation and the ratio of the torus to high‐latitude density.
Plain Language Summary
Recent observations of the Juno satellite at Jupiter illustrate that the electron energy spectrum at high latitudes is observed to be broadband—that is, ranging in energies from tens of electron volts to tens and hundreds of kiloelectron volts. At Earth, such electron spectra are associated with electron energization by Alfvén waves—which are transverse waves that travel along magnetic field lines in close analogy to waves on a string. In particular, at small scales (e.g., perpendicular scale lengths on the order of the ion orbit around the field line), kinetic effects allow for significant electric field generation that can efficiently accelerate electrons parallel to the field line. At these scales, the waves are known as dispersive Alfvén waves. In this work, we, for the first time, present global‐scale (entire dipolar field line) kinetic simulations of electron energization at Jupiter. We illustrate that these dispersive Alfvén waves, sourced in the Io plasma torus, lead to broadband electron energization close to the Jupiter ionosphere that is qualitatively consistent with the Juno observations. We additionally illustrate how the presence of the Io plasma torus (which is a feature unique to the Jupiter ionosphere) affects the characteristics of this broadband energization.
Key Points
The first full flux tube kinetic simulations of electron energization in dispersive Alfven waves at Jupiter are presented
The resulting electron energization is broadband in nature—consistent with recent Juno observations
The ratio of the torus to high‐latitude density plays an important role in regulating the magnitude of the energization
Background and objectives
Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of ...alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis.
Methods
Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases.
Results
We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system.
Conclusions
Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.
Objectives
An obstetric comorbidity index has been developed recently with superior performance characteristics relative to general comorbidity measures in an obstetric population. This study aimed ...to externally validate this index and to examine the impact of including hospitalisation/delivery records only when estimating comorbidity prevalence and discriminative performance of the obstetric comorbidity index.
Design
Validation study.
Setting
Alberta, Canada.
Population
Pregnant women who delivered a live or stillborn infant in hospital (n = 5995).
Methods
Administrative databases were linked to create a population‐based cohort. Comorbid conditions were identified from diagnoses for the delivery hospitalisation, all hospitalisations and all healthcare contacts (i.e. hospitalisations, emergency room visits and physician visits) that occurred during pregnancy and 3 months pre‐conception. Logistic regression was used to test the discriminative performance of the comorbidity index.
Main outcome measures
Maternal end‐organ damage and extended length of stay for delivery.
Results
Although prevalence estimates for comorbid conditions were consistently lower in delivery records and hospitalisation data than in data for all healthcare contacts, the discriminative performance of the comorbidity index was constant for maternal end‐organ damage all healthcare contacts area under the receiver operating characteristic curve (AUC) = 0.70; hospitalisation data AUC = 0.67; delivery data AUC = 0.65 and extended length of stay for delivery (all healthcare contacts AUC = 0.60; hospitalisation data AUC = 0.58; delivery data AUC = 0.58).
Conclusions
The obstetric comorbidity index shows similar performance characteristics in an external population and is a valid measure of comorbidity in an obstetric population. Furthermore, the discriminative performance of the comorbidity index was similar for comorbidities ascertained at the time of delivery, in hospitalisation data or through all healthcare contacts.
Dietary changes associated with industrialization increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease. This relationship is often attributed to ...an 'evolutionary mismatch' between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout human evolutionary history (e.g. simple sugars and saturated fats) promote inflammation and disease relative to diets more akin to ancestral human hunter-gatherer diets, such as a Mediterranean diet. Peripheral blood monocytes, precursors to macrophages and important mediators of innate immunity and inflammation, are sensitive to the environment and may represent a critical intermediate in the pathway linking diet to disease. We evaluated the effects of 15 months of whole diet manipulations mimicking Western or Mediterranean diet patterns on monocyte polarization in a well-established model of human health, the cynomolgus macaque (
). Monocyte transcriptional profiles differed markedly between diets, with 40% of transcripts showing differential expression (FDR < 0.05). Monocytes from Western diet consumers were polarized toward a more proinflammatory phenotype. The Western diet shifted the co-expression of 445 gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans, and dramatically altered behavior. For example, Western-fed individuals were more anxious and less socially integrated. These behavioral changes were also associated with some of the effects of diet on gene expression, suggesting an interaction between diet, central nervous system activity, and monocyte gene expression. This study provides new molecular insights into an evolutionary mismatch and uncovers new pathways through which Western diets alter monocyte polarization toward a proinflammatory phenotype.
During the Space Telescope and Optical Reverberation Mapping Project observations of NGC 5548, the continuum and emission-line variability became decorrelated during the second half of the ...six-month-long observing campaign. Here we present Swift and Chandra X-ray spectra of NGC 5548 obtained as part of the campaign. The Swift spectra show that excess flux (relative to a power-law continuum) in the soft X-ray band appears before the start of the anomalous emission-line behavior, peaks during the period of the anomaly, and then declines. This is a model-independent result suggesting that the soft excess is related to the anomaly. We divide the Swift data into on- and off-anomaly spectra to characterize the soft excess via spectral fitting. The cause of the spectral differences is likely due to a change in the intrinsic spectrum rather than to variable obscuration or partial covering. The Chandra spectra have lower signal-to-noise ratios, but are consistent with the Swift data. Our preferred model of the soft excess is emission from an optically thick, warm Comptonizing corona, the effective optical depth of which increases during the anomaly. This model simultaneously explains all three observations: the UV emission-line flux decrease, the soft-excess increase, and the emission-line anomaly.
IgG antibodies cause inflammation and organ damage in autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the metabolic profile of macrophages isolated from inflamed ...tissues in immune complex (IC)-associated diseases, including SLE and rheumatoid arthritis, and following IgG Fcγ receptor cross-linking. We found that human and mouse macrophages undergo a switch to glycolysis in response to IgG IC stimulation, mirroring macrophage metabolic changes in inflamed tissue in vivo. This metabolic reprogramming was required to generate a number of proinflammatory mediators, including IL-1β, and was dependent on mTOR and hypoxia-inducible factor (HIF)1α. Inhibition of glycolysis, or genetic depletion of HIF1α, attenuated IgG IC-induced activation of macrophages in vitro, including primary human kidney macrophages. In vivo, glycolysis inhibition led to a reduction in kidney macrophage IL-1β and reduced neutrophil recruitment in a murine model of antibody-mediated nephritis. Together, our data reveal the molecular mechanisms underpinning FcγR-mediated metabolic reprogramming in macrophages and suggest a therapeutic strategy for autoantibody-induced inflammation, including lupus nephritis.
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