698 research outputs found
Narrowband UVB phototherapy for clinically isolated syndrome: A trial to deliver the benefits of Vitamin D and other UVB-Induced molecules
Low vitamin D and insufficient sun exposure are additive independent risk factors for the development of multiple sclerosis (MS). The usual measure of vitamin D status, serum 25-hydroxy vitamin D [25(OH)D], is also a marker of recent exposure to the UVB rays of sunshine. The main evidence for a protective effect for MS development of higher 25(OH)D comes from observational studies, but this study design cannot separate out whether 25(OH)D is acting as a marker of vitamin D status, sun exposure, or both. In light of a lack of definitive outcomes in MS patients after trials of vitamin D supplementation and the ability of narrowband UVB to induce vitamin D, as well as other immune-regulatory molecules in skin, the Phototherapy for Clinically Isolated Syndrome (PhoCIS) trial was established to investigate the benefits of narrowband UVB, in addition to supplemented vitamin D, on MS development in individuals with Clinically Isolated Syndrome. We propose that the PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with MS development and progression
Real and imaginary chemical potential in 2-color QCD
In this paper we study the finite temperature SU(2) gauge theory with
staggered fermions for non-zero imaginary and real chemical potential. The
method of analytical continuation of Monte Carlo results from imaginary to real
chemical potential is tested by comparison with simulations performed {\em
directly} for real chemical potential. We discuss the applicability of the
method in the different regions of the phase diagram in the temperature --
imaginary chemical potential plane.Comment: 15 pages, 7 figures; a few comments added; version published on Phys.
Rev.
Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome
Objective
To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT).
Methods
sNfL levels were measured using a sensitive single-molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB-PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes.
Results
Baseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7â161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2â212.2) than in HC (10.7 pg/ml [IQR] 4.9â21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB-PT in the first 3 months (UVB-PT â10.6% vs non-UVB-PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall.
Conclusions
Our findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro-axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB-PT
IgG 3 + B cells are associated with the development of multiple sclerosis
Objectives
Diseaseâmodifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG3 antibodies and their uncharacterised Bâcell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG3+ B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically.
Methods
We designed a 31âparameter Bâcellâfocused mass cytometry panel to interrogate the role of peripheral blood IgG3+ B cells in MS progression of two different patient cohorts: one to investigate the Bâcell subsets involved in conversion from clinically isolated syndrome (CIS) to MS; and another to compare MS patients with inactive or active stages of disease. Each independent cohort included a group of nonâMS controls.
Results
Nine distinct CD20+IgDâIgG3+ Bâcell subsets were identified. Significant changes in the proportion of CD21+CD24+CD27âCD38â and CD27+CD38hiCD71hi memory Bâcell subsets correlated with changes in serum IgG3 levels and time to conversion from CIS to MS. The same CD38â doubleânegative Bâcell subset was significantly elevated in MS patients with active forms of the disease. A third CD21+CD24+CD27+CD38â subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switchedâmemory Bâcell subset.
Conclusion
We have identified previously uncharacterised subsets of IgG3+ B cells and shown them to correlate with autoimmune attacks on the central nervous system (CNS). These results highlight the potential for therapies that specifically target IgG3+ B cells to impact MS progression
Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome
Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1â4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to EpsteinâBarr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of âupstreamâ to âdownstreamâ IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS
Comparisons of Supergranule Characteristics During the Solar Minima of Cycles 22/23 and 23/24
Supergranulation is a component of solar convection that manifests itself on
the photosphere as a cellular network of around 35 Mm across, with a turnover
lifetime of 1-2 days. It is strongly linked to the structure of the magnetic
field. The horizontal, divergent flows within supergranule cells carry local
field lines to the cell boundaries, while the rotational properties of
supergranule upflows may contribute to the restoration of the poloidal field as
part of the dynamo mechanism that controls the solar cycle. The solar minimum
at the transition from cycle 23 to 24 was notable for its low level of activity
and its extended length. It is of interest to study whether the convective
phenomena that influences the solar magnetic field during this time differed in
character to periods of previous minima. This study investigates three
characteristics (velocity components, sizes and lifetimes) of solar
supergranulation. Comparisons of these characteristics are made between the
minima of cycles 22/23 and 23/24 using MDI Doppler data from 1996 and 2008,
respectively. It is found that whereas the lifetimes are equal during both
epochs (around 18 h), the sizes are larger in 1996 (35.9 +/- 0.3 Mm) than in
2008 (35.0 +/- 0.3 Mm), while the dominant horizontal velocity flows are weaker
(139 +/- 1 m/s in 1996; 141 +/- 1 m/s in 2008). Although numerical differences
are seen, they are not conclusive proof of the most recent minimum being
inherently unusual.Comment: 22 pages, 5 figures. Solar Physics, in pres
Comparison of large-scale flows on the Sun measured by time-distance helioseismology and local correlation tracking technique
We present a direct comparison between two different techniques time-distance
helioseismology and a local correlation tracking method for measuring mass
flows in the solar photosphere and in a near-surface layer: We applied both
methods to the same dataset (MDI high-cadence Dopplergrams covering almost the
entire Carrington rotation 1974) and compared the results. We found that after
necessary corrections, the vector flow fields obtained by these techniques are
very similar. The median difference between directions of corresponding vectors
is 24 degrees, and the correlation coefficients of the results for mean zonal
and meridional flows are 0.98 and 0.88 respectively. The largest discrepancies
are found in areas of small velocities where the inaccuracies of the computed
vectors play a significant role. The good agreement of these two methods
increases confidence in the reliability of large-scale synoptic maps obtained
by them.Comment: 14 pages, 6 figures, just before acceptance in Solar Physic
Protons in near earth orbit
The proton spectrum in the kinetic energy range 0.1 to 200 GeV was measured
by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at
an altitude of 380 km. Above the geomagnetic cutoff the observed spectrum is
parameterized by a power law. Below the geomagnetic cutoff a substantial second
spectrum was observed concentrated at equatorial latitudes with a flux ~ 70
m^-2 sec^-1 sr^-1. Most of these second spectrum protons follow a complicated
trajectory and originate from a restricted geographic region.Comment: 19 pages, Latex, 7 .eps figure
A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01
The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics
experiment that will study cosmic rays in the to range and will be installed on the International Space Station
(ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the
space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected
cosmic ray triggers. Part of the \emph{Mir} space station was within the
AMS-01 field of view during the four day \emph{Mir} docking phase of this
flight. We have reconstructed an image of this part of the \emph{Mir} space
station using secondary and emissions from primary cosmic rays
interacting with \emph{Mir}. This is the first time this reconstruction was
performed in AMS-01, and it is important for understanding potential
backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor
stylistic and grammer change
Subsurface Supergranular Vertical Flows as Measured Using Large Distance Separations in Time-Distance Helioseismology
As large--distance rays (say, 10\,-\,) approach the solar surface
approximately vertically, travel times measured from surface pairs for these
large separations are mostly sensitive to vertical flows, at least for shallow
flows within a few Mm of the solar surface. All previous analyses of
supergranulation have used smaller separations and have been hampered by the
difficulty of separating the horizontal and vertical flow components. We find
that the large separation travel times associated with supergranulation cannot
be studied using the standard phase-speed filters of time-distance
helioseismology. These filters, whose use is based upon a refractive model of
the perturbations, reduce the resultant travel time signal by at least an order
of magnitude at some distances. More effective filters are derived. Modeling
suggests that the center--annulus travel time difference
in the separation range \,-\, is insensitive to the
horizontally diverging flow from the centers of the supergranules and should
lead to a constant signal from the vertical flow. Our measurement of this
quantity, 5.1 \pm 0.1\secs, is constant over the distance range. This
magnitude of signal cannot be caused by the level of upflow at cell centers
seen at the photosphere of 10\ms extended in depth. It requires the vertical
flow to increase with depth. A simple Gaussian model of the increase with depth
implies a peak upward flow of 240\ms at a depth of 2.3\Mm and a peak
horizontal flow of 700\ms at a depth of 1.6\Mm.Comment: Solar Physics; 15 pages, 6 figure
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