1,259 research outputs found
International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome
Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763
Manipulating the Mouse Genome to Engineer Precise Functional Syntenic Replacements with Human Sequence
SummaryWe have devised a strategy (called recombinase-mediated genomic replacement, RMGR) to allow the replacement of large segments (>100 kb) of the mouse genome with the equivalent human syntenic region. The technique involves modifying a mouse ES cell chromosome and a human BAC by inserting heterotypic lox sites to flank the proposed exchange interval and then using Cre recombinase to achieve segmental exchange. We have demonstrated the feasibility of this approach by replacing the mouse α globin regulatory domain with the human syntenic region and generating homozygous mice that produce only human α globin chains. Furthermore, modified ES cells can be used iteratively for functional studies, and here, as an example, we have used RMGR to produce an accurate mouse model of human α thalassemia. RMGR has general applicability and will overcome limitations inherent in current transgenic technology when studying the expression of human genes and modeling human genetic diseases
Association between active genes occurs at nuclear speckles and is modulated by chromatin environment
Genes on different chromosomes can be spatially associated in the nucleus in several transcriptional and regulatory situations; however, the functional significance of such associations remains unclear. Using human erythropoiesis as a model, we show that five cotranscribed genes, which are found on four different chromosomes, associate with each other at significant but variable frequencies. Those genes most frequently in association lie in decondensed stretches of chromatin. By replacing the mouse α-globin gene cluster in situ with its human counterpart, we demonstrate a direct effect of the regional chromatin environment on the frequency of association, whereas nascent transcription from the human α-globin gene appears unaffected. We see no evidence that cotranscribed erythroid genes associate at shared transcription foci, but we do see stochastic clustering of active genes around common nuclear SC35-enriched speckles (hence the apparent nonrandom association between genes). Thus, association between active genes may result from their location on decondensed chromatin that enables clustering around common nuclear speckles
The Muonium Atom as a Probe of Physics beyond the Standard Model
The observed interactions between particles are not fully explained in the
successful theoretical description of the standard model to date. Due to the
close confinement of the bound state muonium () can be used as
an ideal probe of quantum electrodynamics and weak interaction and also for a
search for additional interactions between leptons. Of special interest is the
lepton number violating process of sponteanous conversion of muonium to
antimuonium.Comment: 15 pages,6 figure
DT/T beyond linear theory
The major contribution to the anisotropy of the temperature of the Cosmic
Microwave Background (CMB) radiation is believed to come from the interaction
of linear density perturbations with the radiation previous to the decoupling
time. Assuming a standard thermal history for the gas after recombination, only
the gravitational field produced by the linear density perturbations present on
a universe can generate anisotropies at low z (these
anisotropies would manifest on large angular scales). However, secondary
anisotropies are inevitably produced during the nonlinear evolution of matter
at late times even in a universe with a standard thermal history. Two effects
associated to this nonlinear phase can give rise to new anisotropies: the
time-varying gravitational potential of nonlinear structures (Rees-Sciama RS
effect) and the inverse Compton scattering of the microwave photons with hot
electrons in clusters of galaxies (Sunyaev-Zeldovich SZ effect). These two
effects can produce distinct imprints on the CMB temperature anisotropy. We
discuss the amplitude of the anisotropies expected and the relevant angular
scales in different cosmological scenarios. Future sensitive experiments will
be able to probe the CMB anisotropies beyong the first order primary
contribution.Comment: plain tex, 16 pages, 3 figures. Proceedings of the Laredo Advance
School on Astrophysics "The universe at high-z, large-scale structure and the
cosmic microwave background". To be publised by Springer-Verla
Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj
Nuclear shadowing is observed in the per-nucleon cross-sections of positive
muons on carbon, calcium and lead as compared to deuterium. The data were taken
by Fermilab experiment E665 using inelastically scattered muons of mean
incident momentum 470 GeV/c. Cross-section ratios are presented in the
kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are
consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj
decreases, the size of the shadowing effect, as well as its A dependence, are
found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.
Gravitational Lensing at Millimeter Wavelengths
With today's millimeter and submillimeter instruments observers use
gravitational lensing mostly as a tool to boost the sensitivity when observing
distant objects. This is evident through the dominance of gravitationally
lensed objects among those detected in CO rotational lines at z>1. It is also
evident in the use of lensing magnification by galaxy clusters in order to
reach faint submm/mm continuum sources. There are, however, a few cases where
millimeter lines have been directly involved in understanding lensing
configurations. Future mm/submm instruments, such as the ALMA interferometer,
will have both the sensitivity and the angular resolution to allow detailed
observations of gravitational lenses. The almost constant sensitivity to dust
emission over the redshift range z=1-10 means that the likelihood for strong
lensing of dust continuum sources is much higher than for optically selected
sources. A large number of new strong lenses are therefore likely to be
discovered with ALMA, allowing a direct assessment of cosmological parameters
through lens statistics. Combined with an angular resolution <0.1", ALMA will
also be efficient for probing the gravitational potential of galaxy clusters,
where we will be able to study both the sources and the lenses themselves, free
of obscuration and extinction corrections, derive rotation curves for the
lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on
"Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be
published by Springer-Verlag 2002. Paper with full resolution figures can be
found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g
Diagnosis and management of Guillain-Barré syndrome in ten steps
Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae
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