Frontotemporal Lobar Degeneration (FTLD) is a clinically, pathologically and genetically heterogeneous group of disorders that affect principally the frontal and temporal lobes of the brain. There ...are three major associated clinical syndromes, behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non‐fluent aphasia (PNFA); three principal histologies, involving tau, TDP‐43 and FUS proteins; and mutations in three major genes, MAPT, GRN and C9orf72, along with several other less common gene mutations. All three clinical syndromes can exist separately or in combination with Amyotrophic Lateral Sclerosis (ALS). SD is exclusively a TDP‐43 proteinopathy, and PNFA may be so, with both showing tight clinical, histological and genetic inter‐relationships. bvFTD is more of a challenge with overlapping histological and genetic features, involvement of any of the three aggregating proteins, and changes in any of the three major genes. However, when ALS is present, all cases show a clear histological phenotype with TDP‐43 aggregated proteins, and familial forms are associated with expansions in C9orf72. TDP‐43 and FUS are nuclear carrier proteins involved in the regulation of RNA metabolism, whereas tau protein – the product of MAPT – is responsible for the assembly/disassembly of microtubules, which are vital for intracellular transport. Mutations in TDP‐43 and FUS genes are linked to clinical ALS rather than FTLD (with or without ALS), suggesting that clinical ALS may be a disorder of RNA metabolism. Conversely, the protein products of GRN and C9orf72, along with those of the other minor genes, appear to form part of the cellular protein degradation machinery. It is possible therefore that FTLD is a reflection of dysfunction within lysosomal/proteasomal systems resulting in failure to remove potentially neurotoxic (TDP‐43 and tau) aggregates, which ultimately overwhelm capacity to function. Spread of aggregates along distinct pathways may account for the different clinical phenotypes, and patterns of progression of disease.
Semantic dementia is a focal clinical syndrome, resulting from degeneration of the temporal lobes and characterized by progressive loss of conceptual knowledge about the world. Because of the highly ...circumscribed nature of the disorder it is a natural model for improving understanding of how semantic information is cerebrally represented. There is currently a lack of consensus. One view proposes the existence of modality specific meaning systems, in which visual and verbal information are stored separately. An opposing view assumes that information is represented by a unitary, amodal semantic system. The present study explores these alternatives in an examination of famous face and name knowledge in 15 patients with semantic dementia. The study of face recognition in patients with an established semantic disorder also permits an examination of the relationship between semantic dementia and the focal clinical syndrome of progressive prosopagnosia. The semantic dementia patients were profoundly impaired on both face and name identification and familiarity judgement tasks compared with amnesic patients with Alzheimer’s disease and healthy controls. However, whereas the two reference groups performed better for names than faces, the semantic group showed the opposite pattern. This overall profile masked individual differences: semantic dementia patients with predominant left temporal lobe atrophy showed better recognition of names than faces, whereas patients with right temporal predominance showed the reverse pattern. Relative superiority for names or faces was mirrored by corresponding superiority for words or pictures on a standard semantic test. We interpret the findings as inconsistent with a unitary, amodal model of semantic memory. However, the data are not wholly compatible with a strict multiple system account. The data favour a model of semantic memory comprising a single interconnected network, with dedicated brain regions representing modality specific information. The data emphasize the importance of the anterior, inferolateral parts of the left temporal lobe for the representation of names and the corresponding parts of the right temporal lobe for faces. Dissociations between face and name knowledge provide a challenge for existing models of face processing. Moreover, they lead us to argue that the focal syndrome of progressive prosopagnosia is one of the clinical presentations of semantic dementia and not a separate clinical entity.
Context.To analyze diffuse emission that fills the field of view, one must accurately characterize the instrumental backgrounds. For the XMM-Newton EPIC-MOS instrument these backgrounds include a ...temporally variable “quiescent” component, as well as the strongly variable soft proton contamination. Aims.We have characterized the spectral and spatial response of the EPIC-MOS detectors to these background components and have developed tools to remove these backgrounds from observations. Methods.The “quiescent” component was characterized using a combination of the filter-wheel-closed data and a database of unexposed-region data. The soft proton contamination was characterized by differencing images and spectra taken during flared and flare-free intervals. Results.After application of our modeled backgrounds, the differences between independent observations of the same region of blank sky are consistent with the statistical uncertainties except when there is clear spectral evidence of solar wind charge exchange emission. Using a large sample of blank sky data, we show that strong magnetospheric SWCX emission requires elevated solar wind fluxes; observations through the densest part of the magnetosheath are not necessarily strongly contaminated with SWCX emission.
The progressive aging of the world’s population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally ...invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ε4 genotype (APOE ε4) information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson’s disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias.
Frontotemporal lobar degeneration (FTLD) is the umbrella term encompassing a heterogeneous group of pathological disorders. With recent discoveries, the FTLDs have been show to classify nicely into ...three main groups based on the major protein deposited in the brain: FTLD-tau, FTLD-TDP and FTLD-FUS. These pathological groups, and their specific pathologies, underlie a number of well-defined clinical syndromes, including three frontotemporal dementia (FTD) variants behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia, and semantic dementia (SD), progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS). Understanding the neuropathological background of the phenotypic variability in FTD, PSPS and CBS requires large clinicopathological studies. We review current knowledge on the relationship between the FTLD pathologies and clinical syndromes, and pool data from a number of large clinicopathological studies that collectively provide data on 544 cases. Strong relationships were identified as follows: FTD with motor neuron disease and FTLD-TDP; SD and FTLD-TDP; PSPS and FTLD-tau; and CBS and FTLD-tau. However, the relationship between some of these clinical diagnoses and specific pathologies is not so clear cut. In addition, the clinical diagnosis of bvFTD does not have a strong relationship to any FTLD subtype or specific pathology and therefore remains a diagnostic challenge. Some evidence suggests improved clinicopathological association of bvFTD by further refining clinical characteristics. Unlike FTLD-tau and FTLD-TDP, FTLD-FUS has been less well characterized, with only 69 cases reported. However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies. Clinical diagnosis is therefore promising in predicting molecular pathology.
Aims. We present our analysis of a local (z = 0.04−0.2) sample of 31 galaxy clusters with the aim of measuring the density of the X-ray emitting gas in cluster outskirts. We compare our results with ...numerical simulations to set constraints on the azimuthal symmetry and gas clumping in the outer regions of galaxy clusters. Methods. We have exploited the large field-of-view and low instrumental background of ROSAT/PSPC to trace the density of the intracluster gas out to the virial radius. We stacked the density profiles to detect a signal beyond r200 and measured the typical density and scatter in cluster outskirts. We also computed the azimuthal scatter of the profiles with respect to the mean value to look for deviations from spherical symmetry. Finally, we compared our average density and scatter profiles with the results of numerical simulations. Results. As opposed to some recent Suzaku results, and confirming previous evidence from ROSAT and Chandra, we observe a steepening of the density profiles beyond ~r500. Comparing our density profiles with simulations, we find that bibradiative runs predict density profiles that are too steep, whereas runs including additional physics and/or treating gas clumping agree better with the observed gas distribution. We report high-confidence detection of a systematic difference between cool-core and non cool-core clusters beyond ~0.3r200, which we explain by a different distribution of the gas in the two classes. Beyond ~r500, galaxy clusters deviate significantly from spherical symmetry, with only small differences between relaxed and disturbed systems. We find good agreement between the observed and predicted scatter profiles, but only when the 1% densest clumps are filtered out in the ENZO simulations. Conclusions. Comparing our results with numerical simulations, we find that bibradiative simulations fail to reproduce the gas distribution, even well outside cluster cores. Although their general behavior agrees more closely with the observations, simulations including cooling and star formation convert a large amount of gas into stars, which results in a low gas fraction with respect to the observations. Consequently, a detailed treatment of gas cooling, star formation, AGN feedback, and consideration of gas clumping is required to construct realistic models of the outer regions of clusters.
THE STRUCTURE OF THE LOCAL HOT BUBBLE Liu, W.; Chiao, M.; Collier, M. R. ...
The Astrophysical journal,
01/2017, Letnik:
834, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT Diffuse X-rays from the Local Galaxy (DXL) is a sounding rocket mission designed to quantify and characterize the contribution of Solar Wind Charge eXchange (SWCX) to the Diffuse X-ray ...Background and study the properties of the Local Hot Bubble (LHB). Based on the results from the DXL mission, we quantified and removed the contribution of SWCX to the diffuse X-ray background measured by the ROSAT All Sky Survey. The "cleaned" maps were used to investigate the physical properties of the LHB. Assuming thermal ionization equilibrium, we measured a highly uniform temperature distributed around kT = 0.097 keV 0.013 keV (FWHM) 0.006 keV (systematic). We also generated a thermal emission measure map and used it to characterize the three-dimensional (3D) structure of the LHB, which we found to be in good agreement with the structure of the local cavity measured from dust and gas.
We present an XMM-Newton spectrum of diffuse X-ray emission from within the solar system. The spectrum is dominated by probable C VI lines at 0.37 and 0.46 keV, an O VII line at 0.56 keV, O VIII ...lines at 0.65 and approx0.8 keV, Ne IX lines at approx0.92 keV, and Mg XI lines at approx1.35 keV. This spectrum is consistent with that expected from charge exchange emission between the highly ionized solar wind and either interstellar neutrals in the heliosphere or material from Earth's exosphere. The emission is clearly seen as a low-energy (E < 1.5 keV) spectral enhancement in one of a series of four observations of the Hubble Deep Field-North. The X-ray enhancement is concurrent with an enhancement in the solar wind measured by Advanced Composition Explorer, Wind, and Solar and Heliospheric Observatory spacecraft. The solar wind enhancement reaches a flux level an order of magnitude more intense than typical fluxes at 1 AU and has a significantly enhanced O+7/O+6 ratio. Besides being of interest in its own right for studies of the solar system, this emission can have significant consequences for observations of cosmological objects. It can provide emission lines at zero redshift, which are of particular interest in studies of diffuse thermal emission (e.g. O VII and O VIII), and which can therefore act as contamination in the spectra of objects that cover the entire detector field of view. We propose the use of solar wind monitoring data as a diagnostic to screen for such possibilities.
We aimed to determine the extent to which patients with progressive language impairment conform to 2011 primary progressive aphasia (PPA) classification and to examine clinicopathologic correlations ...within PPA variants.
Sixty-two consecutive patients with pathologically confirmed dementia who presented clinically with aphasia were identified. Patients with insufficient clinical information were excluded. PPA classifications were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis.
The final cohort comprised 52 patients, 30 of whom met basic PPA criteria. Twenty-five patients met one of the 3 PPA classifications (13 logopenic, 8 nonfluent/agrammatic, and 4 semantic). Five patients did not meet the criteria for any of the PPA variants. All patients who met semantic variant PPA and 75% of patients who met nonfluent/agrammatic variant PPA classifications had frontotemporal lobar degeneration spectrum pathology. Pathologies were heterogeneous in patients who met logopenic variant PPA criteria (46% Alzheimer disease AD, 8% AD mixed with dementia with Lewy bodies, 23% frontotemporal lobar degeneration, and 23% other).
The 2011 PPA recommendations classify a large proportion of patients who meet basic PPA criteria. However, some patients had aphasic syndromes that could not be classified, suggesting that the 2011 recommendations do not cover the full range of PPA variants. Classification of semantic variant PPA provides a good prediction of underlying pathology. Classification of logopenic variant does not successfully differentiate PPA due to AD from PPA due to other pathologies.
Aims.We present a uniform catalog of the images and radial profiles of the temperature, abundance, and brightness for 70 clusters of galaxies observed by XMM-Newton. Methods.We use a new “first ...principles” approach to the modeling and removal of the background components; the quiescent particle background, the cosmic diffuse emission, the soft proton contamination, and the solar wind charge exchange emission. Each of the background components demonstrate significant spectral variability, several have spatial distributions that are not described by the photon vignetting function, and all except for the cosmic diffuse emission are temporally variable. Because these backgrounds strongly affect the analysis of low surface brightness objects, we provide a detailed description our methods of identification, characterization, and removal. Results.We have applied these methods to a large collection of XMM-Newton observations of clusters of galaxies and present the resulting catalog. We find significant systematic differences between the Chandra and XMM-Newton temperatures.
PDF
