64 research outputs found
Bruton's tyrosine kinase inhibition attenuates disease progression by reducing renal immune cell invasion in mice with hemolytic-uremic syndrome
Hemolytic-uremic syndrome (HUS) can occur as a complication of an infection with Shiga-toxin (Stx)-producing Escherichia coli . Patients typically present with acute kidney injury, microangiopathic hemolytic anemia and thrombocytopenia. There is evidence that Stx-induced renal damage propagates a pro-inflammatory response. To date, therapy is limited to organ-supportive strategies. Bruton’s tyrosine kinase (BTK) plays a pivotal role in recruitment and function of immune cells and its inhibition was recently shown to improve renal function in experimental sepsis and lupus nephritis. We hypothesized that attenuating the evoked immune response by BTK-inhibitors (BTKi) ameliorates outcome in HUS. We investigated the effect of daily oral administration of the BTKi ibrutinib (30 mg/kg) and acalabrutinib (3 mg/kg) in mice with Stx-induced HUS at day 7. After BTKi administration, we observed attenuated disease progression in mice with HUS. These findings were associated with less BTK and downstream phospholipase-C-gamma-2 activation in the spleen and, subsequently, a reduced renal invasion of BTK-positive cells including neutrophils. Only ibrutinib treatment diminished renal invasion of macrophages, improved acute kidney injury and dysfunction (plasma levels of NGAL and urea) and reduced hemolysis (plasma levels of bilirubin and LDH activity). In conclusion, we report here for the first time that BTK inhibition attenuates the course of disease in murine HUS. We suggest that the observed reduction of renal immune cell invasion contributes – at least in part – to this effect. Further translational studies are needed to evaluate BTK as a potential target for HUS therapy to overcome currently limited treatment options
No-go theorem for false vacuum black holes
We study the possibility of non-singular black hole solutions in the theory
of general relativity coupled to a non-linear scalar field with a positive
potential possessing two minima: a `false vacuum' with positive energy and a
`true vacuum' with zero energy. Assuming that the scalar field starts at the
false vacuum at the origin and comes to the true vacuum at spatial infinity, we
prove a no-go theorem by extending a no-hair theorem to the black hole
interior: no smooth solutions exist which interpolate between the local de
Sitter solution near the origin and the asymptotic Schwarzschild solution
through a regular event horizon or several horizons.Comment: 16 pages, 1 figure, Latex, some references added, to appear in
Classical and Quantum Gravit
Regular black holes and black universes
We give a comparative description of different types of regular static,
spherically symmetric black holes (BHs) and discuss in more detail their
particular type, which we suggest to call black universes. The latter have a
Schwarzschild-like causal structure, but inside the horizon there is an
expanding Kantowski-Sachs universe and a de Sitter infinity instead of a
singularity. Thus a hypothetic BH explorer gets a chance to survive. Solutions
of this kind are naturally obtained if one considers static, spherically
symmetric distributions of various (but not all) kinds of phantom matter whose
existence is favoured by cosmological observations. It also looks possible that
our Universe has originated from phantom-dominated collapse in another universe
and underwent isotropization after crossing the horizon. An explicit example of
a black-universe solution with positive Schwarzschild mass is discussed.Comment: 13 pages, 1 figure. 6 referenses and some discussion added, misprints
correcte
Scalar hairy black holes and solitons in asymptotically flat spacetimes
A numerical analysis shows that a class of scalar-tensor theories of gravity
with a scalar field minimally and nonminimally coupled to the curvature allows
static and spherically symmetric black hole solutions with scalar-field hair in
asymptotically flat spacetimes. In the limit when the horizon radius of the
black hole tends to zero, regular scalar solitons are found. The asymptotically
flat solutions are obtained provided that the scalar potential of the
theory is not positive semidefinite and such that its local minimum is also a
zero of the potential, the scalar field settling asymptotically at that
minimum. The configurations for the minimal coupling case, although unstable
under spherically symmetric linear perturbations, are regular and thus can
serve as counterexamples to the no-scalar-hair conjecture. For the nonminimal
coupling case, the stability will be analyzed in a forthcoming paper.Comment: 7 pages, 10 postscript figures, file tex, new postscript figs. and
references added, stability analysis revisite
Perception of High Alcohol Use of Peers Is Associated With High Personal Alcohol Use in First-Year University Students in Three Central and Eastern European Countries
Objectives: The objectives of this study were to assess discrepancies between estimated peer and personal drinking behavior and to determine associations between perceptions of peer and personal drinking behavior among university students from Hungary (HU), Lithuania (LT), and the Slovak Republic (SK). Methods: 2,554 freshman university students completed an online questionnaire on the frequency of their personal alcohol use, the number of heavy drinking occasions and on their perception concerning the corresponding drinking behavior of a typical student. Associations between perceived peer and personal use were analyzed by means of logistic regression, adjusting for sex. Results: The majority of students across all countries thought their peers drink more frequently and are more often involved in heavy drinking occasions than themselves. Students who perceived the frequency of peer alcohol use to be higher were more likely to drink alcohol twice a week or more often (SR: OR = 3.81, 95% CI = 2.51–5.79; LT: OR = 3.16, 95% CI = 2.11–4.75; HU: OR = 2.10, 95% CI = 1.53–2.87) compared with students who drink alcohol monthly or less. Those who perceived the number of peer heavy drinking occasions as high were more likely to report heavy drinking weekly or more often (SR: OR = 3.16, 95% CI = 1.92–5.20; LT:OR = 3.56, 95% CI = 2.14–5.94; HU:OR = 1.41, 95% CI = 0.79–2.51) compared with students who report heavy drinking less than monthly. Conclusions/Importance: University students perceived peer alcohol use to be higher than their personal use. Given the association between perceptions and personal alcohol use, future research should investigate if targeting perceptions in the surveyed countries may have an impact on alcohol use
On the stability of scalar-vacuum space-times
We study the stability of static, spherically symmetric solutions to the
Einstein equations with a scalar field as the source. We describe a general
methodology of studying small radial perturbations of scalar-vacuum
configurations with arbitrary potentials V(\phi), and in particular space-times
with throats (including wormholes), which are possible if the scalar is
phantom. At such a throat, the effective potential for perturbations V_eff has
a positive pole (a potential wall) that prevents a complete perturbation
analysis. We show that, generically, (i) V_eff has precisely the form required
for regularization by the known S-deformation method, and (ii) a solution with
the regularized potential leads to regular scalar field and metric
perturbations of the initial configuration. The well-known conformal mappings
make these results also applicable to scalar-tensor and f(R) theories of
gravity. As a particular example, we prove the instability of all static
solutions with both normal and phantom scalars and V(\phi) = 0 under spherical
perturbations. We thus confirm the previous results on the unstable nature of
anti-Fisher wormholes and Fisher's singular solution and prove the instability
of other branches of these solutions including the anti-Fisher "cold black
holes".Comment: 18 pages, 5 figures. A few comments and references added. Final
version accepted at EPJ
Species identification by experts and non-experts: comparing images from field guides
Accurate species identification is fundamental when recording ecological data. However, the ability to correctly identify organisms visually is rarely questioned. We investigated how experts and non-experts compared in the identification of bumblebees, a group of insects of considerable conservation concern. Experts and non-experts were asked whether two concurrent bumblebee images depicted the same or two different species. Overall accuracy was below 60% and comparable for experts and non-experts. However, experts were more consistent in their answers when the same images were repeated, and more cautious in committing to a definitive answer. Our findings demonstrate the difficulty of correctly identifying bumblebees using images from field guides. Such error rates need to be accounted for when interpreting species data, whether or not they have been collected by experts. We suggest that investigation of how experts and non-experts make observations should be incorporated into study design, and could be used to improve training in species identification
Unimodular bimode gravity and the coherent scalar-graviton field as galaxy dark matter
The explicit violation of the general gauge invariance/relativity is adopted
as the origin of dark matter and dark energy of the gravitational nature. The
violation of the local scale invariance alone, with the residual unimodular
one, is considered. Besides the four-volume preserving deformation mode -- the
transverse-tensor graviton -- the metric comprises a compression mode -- the
scalar graviton, or the systolon. A unimodular invariant and general covariant
metric theory of the bimode/scalar-tensor gravity is consistently worked out.
To reduce the primordial ambiguity of the theory a dynamical global symmetry is
imposed, with its subsequent spontaneous breaking revealed. The static
spherically symmetric case in the empty, but possibly for the origin, space is
studied. A three-parameter solution describing a new static space structure --
the dark lacuna -- is constructed. It enjoys the property of gravitational
confinement, with the logarithmic potential of gravitational attraction at the
periphery, and results in the asymptotically flat rotation curves. Comprising a
super-massive dark fracture (a scalar-modified black hole) at the origin
surrounded by a cored dark halo, the dark lacunas are proposed as a prototype
model of galaxies, implying an ultimate account for the distributed
non-gravitational matter and a putative asphericity or rotation.Comment: 38 pages, 10 figures; exposition improved, remarks added, accepted
for publicatio
Huntington disease in a nonagenarian mistakenly diagnosed as normal pressure hydrocephalus
In the absence of family history or overt chorea, the protean manifestations (cognitive, motor and behavioral) of Huntington disease (HD) may suggest alternative disease processes, particularly in elderly patients. Herein, we report on a nonagenarian with HD who did not manifest overt chorea until 91 years of age and was mistakenly diagnosed with normal pressure hydrocephalus at 89 years of age. The gait abnormalities seen in early HD should be readily distinguished from those of normal pressure hydrocephalus. © 2010 Elsevier Ltd. All rights reserved
Interprofessionelles Lernen curricular verankern am Beispiel interprofessioneller Tutorien fĂĽr Auszubildende und Studierende der Humanmedizin, Pflege, Physio- und Ergotherapie
- …