302 research outputs found
Remote sensing of cloud liquid water during ICE'89
The cloud liquid water path, LWP, over the North
Sea during the International Cirrus Experiment 1989 (ICE'89) is derived from measurements of the microwave radiometer SSM/I on board.of the polar orbiting satellite DMSP and from measurements of a ground-based 33-GHz-radiometer operating on board of the German research vessel 'Poseldon'. Comparisons of maps of LWP compiled from the SSM/I data with time series computed from the ground-based system show no significant bias and agree within the range of uncertainty caused by the different sampling characteristics of the observing systems. Using a combination of SSM/I data and almost simultaneously recorded METEOSAT-IR data offers the possibility to identify different cloud types, e.g. to seperate cirrus clouds and cirrus with underlying water clouds. Both types may have the same IR-brightness temperature but different microwave brightness temperature because ice clouds have a negligible influence on the microwave radiances
NGC 6738: not a real open cluster
A photometric, astrometric and spectroscopic investigation of the poorly
studied open cluster NGC 6738 has been performed in order to ascertain its real
nature. NGC 6738 is definitely not a physical stellar ensemble: photometry does
not show a defined mean sequence, proper motions and radial velocities are
randomly distributed, spectro-photometric parallaxes range between 10 and 1600
pc, and the apparent luminosity function is identical to that of the
surrounding field. NGC 6738 therefore appears to be an apparent concentration
of a few bright stars projected on patchy background absorption.Comment: A&A, in press (compared with first submission to astro-ph, now Table
2 and Figure 4 are replaced with corrected versions
Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin
Background Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have
been suggested to play a role in a subset of patients with neuromyelitis
optica and related disorders. Objective To assess (i) the frequency of MOG-IgG
in a large and predominantly Caucasian cohort of patients with optic neuritis
(ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive
patients and vice versa; (iii) the origin and frequency of MOG-IgG in the
cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and
(v) the influence of disease activity and treatment status on MOG-IgG titers.
Methods 614 serum samples from patients with ON and/or myelitis and from
controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples
were tested for MOG-IgG using a live cell-based assay (CBA) employing full-
length human MOG-transfected HEK293A cells. Results MOG-IgG was detected in 95
sera from 50 patients with ON and/or myelitis, including 22/54 (40.7%)
patients with a history of both ON and myelitis, 22/103 (21.4%) with a history
of ON but no myelitis and 6/45 (13.3%) with a history of longitudinally
extensive transverse myelitis but no ON, and in 1 control patient with
encephalitis and a connective tissue disorder, all of whom were negative for
AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients
with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with
multiple sclerosis (MS). MOG-IgG was found in 12/18 (67%) CSF samples from
MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was
negative in all cases, indicating a predominantly peripheral origin of CSF
MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1
subclass. MOG-IgG was present already at disease onset. The antibodies
remained detectable in 40/45 (89%) follow-up samples obtained over a median
period of 16.5 months (range 0–123). Serum titers were higher during attacks
than during remission (p < 0.0001), highest during attacks of simultaneous
myelitis and ON, lowest during acute isolated ON, and declined following
treatment. Conclusions To date, this is the largest cohort studied for IgG to
human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a
substantial subset of patients with ON and/or myelitis, but not in classical
MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of
extrathecal origin. Serum MOG-IgG is present already at disease onset and
remains detectable in the long-term course. Serum titers depend on disease
activity and treatment status
Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study
Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothesis-free mixed networks and associations between clinical disease with neuroimaging markers in 40 aquaporin-4-immunoglobulin G antibody seropositive patients (age = 48.16 ± 14.3 years, female:male = 36:4) and 31 healthy controls (age = 45.92 ± 13.3 years, female:male = 24:7). Magnetic resonance imaging measures included total brain and deep grey matter volumes, cortical thickness and spinal cord atrophy. Optical coherence tomography measures of the retina and clinical measures comprised of clinical attack types and expanded disability status scale were also utilized. For multimodal network analysis, all measures were introduced as nodes and tested for directed connectivity from clinical attack types and disease duration to systematic imaging and clinical disability measures. Analysis of variance, with group interactions, gave weights and significance for each nodal association (hyperedges). Connectivity matrices from 80% and 95% F-distribution networks were analyzed and revealed the number of combined attack types and disease duration as the most connected nodes, directly affecting changes in several regions of the central nervous system. Subsequent multivariable regression models, including interaction effects with clinical parameters, identified associations between decreased nucleus accumbens (β = −0.85, P = 0.021) and caudate nucleus (β = −0.61, P = 0.011) volumes with higher combined attack type count and longer disease duration, respectively. We also confirmed previously reported associations between spinal cord atrophy with increased number of clinical myelitis attacks. Age was the most important factor associated with normalized brain volume, pallidum volume, cortical thickness and the expanded disability status scale score. The identified imaging biomarker candidates warrant further investigation in larger-scale studies. Graph theory-based multimodal networks allow for connectivity and interaction analysis, where this method may be applied in other complex heterogeneous disease investigations with different outcome measures
Uncovering convolutional neural network decisions for diagnosing multiple sclerosis on conventional MRI using layer-wise relevance propagation
Machine learning-based imaging diagnostics has recently reached or even
superseded the level of clinical experts in several clinical domains. However,
classification decisions of a trained machine learning system are typically
non-transparent, a major hindrance for clinical integration, error tracking or
knowledge discovery. In this study, we present a transparent deep learning
framework relying on convolutional neural networks (CNNs) and layer-wise
relevance propagation (LRP) for diagnosing multiple sclerosis (MS). MS is
commonly diagnosed utilizing a combination of clinical presentation and
conventional magnetic resonance imaging (MRI), specifically the occurrence and
presentation of white matter lesions in T2-weighted images. We hypothesized
that using LRP in a naive predictive model would enable us to uncover relevant
image features that a trained CNN uses for decision-making. Since imaging
markers in MS are well-established this would enable us to validate the
respective CNN model. First, we pre-trained a CNN on MRI data from the
Alzheimer's Disease Neuroimaging Initiative (n = 921), afterwards specializing
the CNN to discriminate between MS patients and healthy controls (n = 147).
Using LRP, we then produced a heatmap for each subject in the holdout set
depicting the voxel-wise relevance for a particular classification decision.
The resulting CNN model resulted in a balanced accuracy of 87.04% and an area
under the curve of 96.08% in a receiver operating characteristic curve. The
subsequent LRP visualization revealed that the CNN model focuses indeed on
individual lesions, but also incorporates additional information such as lesion
location, non-lesional white matter or gray matter areas such as the thalamus,
which are established conventional and advanced MRI markers in MS. We conclude
that LRP and the proposed framework have the capability to make diagnostic
decisions of..
Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination
Background Antibodies to the myelin oligodendrocyte glycoprotein (MOG) are
associated with a subset of inflammatory demyelinating diseases of the central
nervous system such as acute disseminated encephalomyelitis and neuromyelitis
optica spectrum disorders. However, whether human MOG antibodies are
pathogenic or an epiphenomenon is still not completely clear. Although MOG is
highly conserved within mammals, previous findings showed that not all human
MOG antibodies bind to rodent MOG. We therefore hypothesized that human MOG
antibody-mediated pathology in animal models may only be evident using
species-specific MOG antibodies. Methods We screened 80 human MOG antibody-
positive samples for their reactivity to mouse and rat MOG using either a live
cell-based assay or immunohistochemistry on murine, rat, and human brain
tissue. Selected samples reactive to either human MOG or rodent MOG were
subsequently tested for their ability to induce complement-mediated damage in
murine organotypic brain slices or enhance demyelination in an experimental
autoimmune encephalitis (EAE) model in Lewis rats. The MOG monoclonal antibody
8-18-C5 was used as a positive control. Results Overall, we found that only a
subset of human MOG antibodies are reactive to mouse (48/80, 60%) or rat
(14/80, 18%) MOG. Purified serum antibodies from 10 human MOG antibody-
positive patients (8/10 reactive to mouse MOG, 6/10 reactive to rat MOG), 3
human MOG-negative patients, and 3 healthy controls were tested on murine
organotypic brain slices. Purified IgG from one patient with high titers of
anti-human, mouse, and rat MOG antibodies and robust binding to myelin tissue
produced significant, complement-mediated myelin loss in organotypic brain
slices, but not in the EAE model. Monoclonal 8-18-C5 MOG antibody caused
complement-mediated demyelination in both the organotypic brain slice model
and in EAE. Conclusion This study shows that a subset of human MOG antibodies
can induce complement-dependent pathogenic effects in a murine ex vivo animal
model. Moreover, a high titer of species-specific MOG antibodies may be
critical for demyelinating effects in mouse and rat animal models. Therefore,
both the reactivity and titer of human MOG antibodies must be considered for
future pathogenicity studies
Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome
Background A subset of patients with neuromyelitis optica spectrum disorders
(NMOSD) has been shown to be seropositive for myelin oligodendrocyte
glycoprotein antibodies (MOG-IgG). Objective To describe the epidemiological,
clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological
features of a large cohort of MOG-IgG-positive patients with optic neuritis
(ON) and/or myelitis (n = 50) as well as attack and long-term treatment
outcomes. Methods Retrospective multicenter study. Results The sex ratio was
1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease
followed a multiphasic course in 80% (median time-to-first-relapse 5 months;
annualized relapse rate 0.92) and resulted in significant disability in 40%
(mean follow-up 75 ± 46.5 months), with severe visual impairment or functional
blindness (36%) and markedly impaired ambulation due to paresis or ataxia
(25%) as the most common long-term sequelae. Functional blindness in one or
both eyes was noted during at least one ON attack in around 70%. Perioptic
enhancement was present in several patients. Besides acute tetra-/paraparesis,
dysesthesia and pain were common in acute myelitis (70%). Longitudinally
extensive spinal cord lesions were frequent, but short lesions occurred at
least once in 44%. Fourty-one percent had a history of simultaneous ON and
myelitis. Clinical or radiological involvement of the brain, brainstem, or
cerebellum was present in 50%; extra-opticospinal symptoms included
intractable nausea and vomiting and respiratory insufficiency (fatal in one).
CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in
only 13%, and blood-CSF-barrier dysfunction in 32%. Intravenous
methylprednisolone (IVMP) and long-term immunosuppression were often
effective; however, treatment failure leading to rapid accumulation of
disability was noted in many patients as well as flare-ups after steroid
withdrawal. Full recovery was achieved by plasma exchange in some cases,
including after IVMP failure. Breakthrough attacks under azathioprine were
linked to the drug-specific latency period and a lack of cotreatment with oral
steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was
associated with ongoing or increasing disease activity. Rituximab and
ofatumumab were effective in some patients. However, treatment with rituximab
was followed by early relapses in several cases; end-of-dose relapses occurred
9-12 months after the first infusion. Coexisting autoimmunity was rare (9%).
Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald
criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%,
respectively; MS had been suspected in 36%. Disease onset or relapses were
preceded by infection, vaccination, or pregnancy/delivery in several cases.
Conclusion Our findings from a predominantly Caucasian cohort strongly argue
against the concept of MOG-IgG denoting a mild and usually monophasic variant
of NMOSD. The predominantly relapsing and often severe disease course and the
short median time to second attack support the use of prophylactic long-term
treatments in patients with MOG-IgG-positive ON and/or myelitis
Pain in AQP4-IgG-positive and MOG-IgG-positive neuromyelitis optica spectrum disorders
Background: Pain is a frequent symptom in aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorders (AQP4-IgG-pos. NMOSD). Data on pain in myelin-oligodendrocyteglycoprotein- immunoglobulin-G autoimmunity with a clinical NMOSD phenotype (MOG-IgG-pos. NMOSD) are scarce.
Objective: The objective of this paper is to investigate pain in MOG-IgG-pos. NMOSD, AQP4-IgG-pos. NMOSD and NMOSD without AQP4/MOG-IgG detection (AQP4/MOG-IgG-neg. NMOSD).
Methods: Forty-nine MOG-IgG-pos. (n=14), AQP4-IgG-pos. (n=29) and AQP4/MOG-IgG-neg. (n=6) NMOSD patients were included in this cross-sectional baseline analysis from an ongoing observational study. We identified spinal cord lesions on magnetic resonance imaging, assessed pain by the painDETECT and McGill Pain questionnaires, quality of life by Short Form Health Survey, and depression by Beck Depression Inventory.
Results: Twelve MOG-IgG-pos. NMOSD patients (86%), 24 AQP4-IgG-pos. NMOSD patients (83%), and all AQP4/MOG-IgG-neg. NMOSD patients (100%) suffered from pain. MOG-IgG-pos. NMOSD patients had mostly neuropathic pain and headache; AQP4-IgG-pos. and AQP4/MOG-IgG-neg. NMOSD patients had mostly neuropathic pain. A history of myelitis was less frequent in MOG-IgGpos. NMOSD than in AQP4-IgG-pos. NMOSD patients. Pain influenced quality of life in all patients. Thirty-six percent of patients with pain received pain medication; none of them were free of pain.
Conclusions: Pain is a frequent symptom of patients with MOG-IgG-pos. NMOSD and is as important as in AQP4-IgG-pos. and AQP4/MOG-IgG-neg. NMOSD. Despite its impact on quality of life, pain is insufficiently alleviated by medication
Standardization of T1w/T2w Ratio Improves Detection of Tissue Damage in Multiple Sclerosis
Normal appearing white matter (NAWM) damage develops early in multiple sclerosis (MS) and continues in the absence of new lesions. The ratio of T1w and T2w (T1w/T2w ratio), a measure of white matter integrity, has previously shown reduced intensity values in MS NAWM. We evaluate the validity of a standardized T1w/T2w ratio (sT1w/T2w ratio) in MS and whether this method is sensitive in detecting MS-related differences in NAWM. T1w and T2w scans were acquired at 3 Tesla in 47 patients with relapsing-remitting MS and 47 matched controls (HC). T1w/T2w and sT1w/T2w ratios were then calculated. We compared between-group variability between T1w/T2w and sT1w/T2w ratio in HC and MS and assessed for group differences. We also evaluated the relationship between the T1w/T2w and sT1w/T2w ratios and clinically relevant variables. Compared to the classic T1w/T2w ratio, the between-subject variability in sT1w/T2w ratio showed a significant reduction in MS patients (0 <. 0.001) and HC < 0.001). However, only sT1w/T2w ratio values were reduced in patients compared to HC (p < 0.001). The sT1w/T2w ratio intensity values were significantly influenced by age, T2 lesion volume and group status (MS vs. HC) (adjusted R-2 = 0.30, p 0.001). We demonstrate the validity of the sT1w/T2w ratio in MS and that it is more sensitive to MS-related differences in NAWM compared to T1w/T2w ratio. The sT1w/T2w ratio shows promise as an easily-implemented measure of NAWM in MS using readily available scans and simple post-processing methods
TACTIC : The TRIUMF Annular Chamber for Tracking and Identification of Charged particles
An in-depth characterization of the TACTIC detector was performed using data from a 148Gd alpha source and some test runs with a stable ion beam. The detector is an active target time-projection chamber with a blind central region for maximizing beam tolerance and GEM-based electron amplification, equipped with a modern digitizing data acquisition system allowing the recording of full signals. The system was developed to study the reaction 8Li(α,n)11B, which is important for bridging the mass 8 gap in scenarios of low 4He density like Inhomogeneous Big Bang Nucleosynthesis and the production of r-process seeds in supernovae. Both energy resolution and tracking accuracy were found to agree with theoretical predictions and Geant4 simulations. The 8Li beam rate capability of the system is predicted to be of the order of 105s-1, several orders of magnitude higher than most previous measurements of the same reaction, while still maintaining a high detection efficiency of 70% to 80 %
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