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 $V(\phi)$ 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