Evaluation of C-reactive protein and its kinetics as a prognostic indicator in canine leptospirosis.

OBJECTIVE To evaluate C-reactive protein at presentation and during hospitalisation in dogs with acute kidney injury resulting from leptospirosis to compare C-reactive protein at presentation in dogs with acute kidney injury of different aetiology and to study its correlation with markers of inflammation, azotaemia and survival. MATERIALS AND METHODS Prospective observational study of 41 dogs with acute kidney injury secondary to leptospirosis and 15 control dogs with acute kidney injury of different aetiology. C-reactive protein was measured at presentation in both groups and daily for 7 days in a subgroup of 28 dogs with leptospirosis. The associations of C-reactive protein with neutrophil count, albumin, urea, creatinine and survival were analysed. RESULTS C-reactive protein was increased at presentation in all dogs with leptospirosis but was not significantly different from dogs with acute kidney injury of different cause. It was associated with markers of inflammation (neutrophil count, albumin) but not with azotaemia (creatinine, urea). It decreased gradually from presentation to day 4, with significantly lower concentrations in survivors than non-survivors. Initial C-reactive protein was only weakly associated with outcome, but its average concentration from presentation to day 2 was more strongly associated. Absolute and relative changes in C-reactive protein during hospitalisation and creatinine at presentation were not associated with survival. CLINICAL SIGNIFICANCE Serial assessment of C-reactive protein may improve outcome prediction in dogs with leptospirosis compared with a single measurement at presentation or with markers of renal function

Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells

High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPs; particles < 0.1 μm). Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 μm) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential

Shapes of polyhedra, mixed volumes and hyperbolic geometry

We generalize to higher dimensions the Bavard–Ghys construction of the hyperbolic metric on the space of polygons with fixed directions of edges. The space of convex d -dimensional polyhedra with fixed directions of facet normals has a decomposition into type cones that correspond to different combinatorial types of polyhedra. This decomposition is a subfan of the secondary fan of a vector configuration and can be analyzed with the help of Gale diagrams. We construct a family of quadratic forms on each of the type cones using the theory of mixed volumes. The Alexandrov–Fenchel inequalities ensure that these forms have exactly one positive eigenvalue. This introduces a piecewise hyperbolic structure on the space of similarity classes of polyhedra with fixed directions of facet normals. We show that some of the dihedral angles on the boundary of the resulting cone-manifold are equal to π/2

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration

NME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia

Author summary Motile cilia are required for clearing mucous, infectious agents and inhaled dust from the airways. Primary ciliary dyskinesia (PCD) is a hereditary defect of motile cilia. Clinical findings may include recurrent airway infections, fertility problems, and sometimes hydrocephalus. We analyzed an Alaskan Malamute family, in which two out of six puppies were affected by an autosomal recessive form of PCD. Whole genome sequencing of an affected dog identified a one base pair deletion in the NME5 gene, c.43delA, leading to an early frame-shift and premature stop codon. Later in the study, we became aware of a previously published Alaskan Malamute with PCD involving respiratory infections and hydrocephalus. We observed perfect concordance of the NME5 genotypes with the PCD phenotype in all three affected Alaskan Malamutes and more than 1000 controls. The fact that the third case, which had no documented close relationship to the initial two cases, was homozygous for the same rare mutant NME5 allele, strongly supports our hypothesis that NME5:c.43delA causes the PCD phenotype. We confirmed absence of NME5 protein expression in nasal epithelium of an affected dog. Our results enable genetic testing in dogs and identify NME5 as novel candidate gene for unsolved human PCD cases.Peer reviewe

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Mucociliary and long-term particle clearance in airways of patients with immotile cilia

Spherical monodisperse ferromagnetic iron oxide particles of 1.9 μm geometric and 4.2 μm aerodynamic diameter were inhaled by seven patients with primary ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13 healthy non-smokers (NS) from a previous study. The bolus penetration front depth was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/-8 % after 8 s breath holding time. Particle retention was measured by the magnetopneumographic method over a period of nine months. Particle clearance from the airways showed a fast and a slow phase. In PCD patients airway clearance was retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact mucociliary clearance. There was no difference in the slow clearance phase between PCD patients and healthy NS. Despite non-functioning cilia the effectiveness of airway clearance in PCD patients is comparable to healthy NS, with a prolonged kinetics of one week, which may primarily reflect the effectiveness of cough clearance. This prolonged airway clearance allows longer residence times of bacteria and viruses in the airways and may be one reason for increased frequency of infections in PCD patients

Human Flt3L Generates Dendritic Cells from Canine Peripheral Blood Precursors: Implications for a Dog Glioma Clinical Trial

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads) encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L) and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK). This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs), in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF.Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-alpha and IFN-gamma. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation.These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials

Internet-based, culturally sensitive, problem-solving therapy for turkish migrants with depression: Randomized controlled trial

Background: Turkish migrants living in the Netherlands have a high prevalence of depressive disorders, but experience considerable obstacles to accessing professional help. Providing easily accessible Internet treatments may help to overcome these barriers. Objective: The aim of this study was to evaluate the effectiveness of a culturally sensitive, guided, self-help, problem-solving intervention through the Internet for reducing depressive symptoms in Turkish migrants. Methods: A two-armed randomized controlled trial was conducted. The primary outcome measure was the severity of depressive symptoms; secondary outcome measures were somatic symptoms, anxiety, quality of life, and satisfaction with the treatment. Participants were assessed online at baseline, posttest (6 weeks after baseline), and 4 months after baseline. Posttest results were analyzed on the intention-to-treat sample. Missing values were estimated by means of multiple imputation. Differences in clinical outcome between groups were analyzed with a t test. Cohen's d was used to determine the between-groups effect size at posttreatment and follow-up. Results: Turkish adults (N=96) with depressive symptoms were randomized to the experimental group (n=49) or to a waitlist control group (n=47). High attrition rates were found among the 96 participants of which 42% (40/96) did not complete the posttest (6 weeks) and 62% (59/96) participants did not complete the follow-up assessment at 4 months. No significant difference between the experimental group and the control group was found for depression at posttest. Recovery occurred significantly more often in the experimental group (33%, 16/49) than in the control group (9%, 4/47) at posttest (P=.02). Because of the high attrition rate, a completers-only analysis was conducted at follow-up. The experimental group showed significant improvement in depression compared to the control group both at posttest (P=.01) and follow-up (P=.01). Conclusions: The results of this study did not show a significant effect on the reduction of depressive symptoms. However, the effect size at posttest was high, which might be an indicator of the possible effectiveness of the intervention when assessed in a larger sample and robust trial. Future research should replicate our study with adequately powered samples. © Burçin Ünlü Ince, Pim Cuijpers, Edith van 't Hof, Wouter van Ballegooijen, Helen Christensen, Heleen Riper