Low profile vascular plug for transarterial occlusion of patent ductus arteriosus in small dogs

Background: Minimally invasive transcatheter occlusion using Amplatz canine duct occluder (ACDO) is the treatment of choice for dogs with left-to-right shunting patent ductus arteriosus (PDA). However, in small dogs the femoral artery diameter is often too small to accommodate the guiding catheter required for ACDO deployment. Objective: Describe the effectiveness of transarterial implantation of Amplatzer Vascular Plug 4 (AVP-4), the only self-expandable nitinol mesh occlusion device which can be implanted through a 4 French diagnostic catheter, in small dogs with left-to-right shunting PDA. Animals: Seven client-owned dogs. Methods: Descriptive case series. Dogs with hemodynamically relevant left-to-right shunting PDA and a femoral artery diameter less than 2.0 mm measured preoperatively with ultrasonography were prospectively enrolled. Results: Angiography after releasing the device showed complete immediate PDA closure in 5 dogs, where the manufacturers' recommendation were strictly followed (30%-50% device oversizing of the ductal ampulla's diameter). Trivial residual flow on angiography in the 6th dog, whose device was slightly undersized, had resolved on echocardiography within 2 hours after placement. Marked device undersizing in the 7th dog resulted in severe residual shunting, which necessitated the addition of a coil. In this dog, the AVP-4 embolized into the pulmonary artery within 2 weeks after placement. Conclusions and Clinical Importance: Transarterial implantation of AVP-4 is a safe, effective and technically easy procedure for PDA occlusion in small dogs and offers a valuable alternative to coil implantation. Accurate PDA measurement and device sizing is essential to prevent residual shunting, inadvertent device embolization, and protrusion of the device into the aorta

Percolation Systems away from the Critical Point

This article reviews some effects of disorder in percolation systems even away from the critical density p_c. For densities below p_c, the statistics of large clusters defines the animals problem. Its relation to the directed animals problem and the Lee-Yang edge singularity problem is described. Rare compact clusters give rise to Griffiths singuraties in the free energy of diluted ferromagnets, and lead to a very slow relaxation of magnetization. In biassed diffusion on percolation clusters, trapping in dead-end branches leads to asymptotic drift velocity becoming zero for strong bias, and very slow relaxation of velocity near the critical bias field.Comment: Minor typos fixed. Submitted to Praman

Small heat shock proteins are induced during multiple sclerosis lesion development in white but not grey matter

INTRODUCTION: The important protective role of small heat-shock proteins (HSPs) in regulating cellular survival and migration, counteracting protein aggregation, preventing apoptosis, and regulating inflammation in the central nervous system is now well-recognized. Yet, their role in the neuroinflammatory disorder multiple sclerosis (MS) is largely undocumented. With the exception of alpha B-crystallin (HSPB5), little is known about the roles of small HSPs in disease. RESULTS: Here, we examined the expression of four small HSPs during lesion development in MS, focussing on their cellular distribution, and regional differences between white matter (WM) and grey matter (GM). It is well known that MS lesions in these areas differ markedly in their pathology, with substantially more intense blood-brain barrier damage, leukocyte infiltration and microglial activation typifying WM but not GM lesions. We analysed transcript levels and protein distribution profiles for HSPB1, HSPB6, HSPB8 and HSPB11 in MS lesions at different stages, comparing them with normal-appearing brain tissue from MS patients and non-neurological controls. During active stages of demyelination in WM, and especially the centre of chronic active MS lesions, we found significantly increased expression of HSPB1, HSPB6 and HSPB8, but not HSPB11. When induced, small HSPs were exclusively found in astrocytes but not in oligodendrocytes, microglia or neurons. Surprisingly, while the numbers of astrocytes displaying high expression of small HSPs were markedly increased in actively demyelinating lesions in WM, no such induction was observed in GM lesions. This difference was particularly obvious in leukocortical lesions covering both WM and GM areas. CONCLUSIONS: Since induction of small HSPs in astrocytes is apparently a secondary response to damage, their differential expression between WM and GM likely reflects differences in mediators that accompany demyelination in either WM or GM during MS. Our findings also suggest that during MS, cortical structures fail to benefit from the protective actions of small HSPs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0267-2) contains supplementary material, which is available to authorized users

Axonal abnormalities in vanishing white matter

ObjectiveWe aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. MethodsAxons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, astrocyte-forebrain co-culture studies were performed. ResultsIn the corpus callosum of Eif2b5-mutant mice, myelin sheath thickness, axonal diameter, and G-ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G-ratio in Eif2b5-mutant mice. In more severely affected Eif2b4-Eif2b5 double-mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5-mutant mice. Co-cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal. InterpretationIn vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention

Early motor outcomes in infants with critical congenital heart disease are related to neonatal brain development and brain injury

Aim To assess the relationship between neonatal brain development and injury with early motor outcomes in infants with critical congenital heart disease (CCHD). Method Neonatal brain magnetic resonance imaging was performed after open-heart surgery with cardiopulmonary bypass. Cortical grey matter (CGM), unmyelinated white matter, and cerebellar volumes, as well as white matter motor tract fractional anisotropy and mean diffusivity were assessed. White matter injury (WMI) and arterial ischaemic stroke (AIS) with corticospinal tract (CST) involvement were scored. Associations with motor outcomes at 3, 9, and 18 months were corrected for repeated cardiac surgery. Results Fifty-one infants (31 males, 20 females) were included prospectively. Median age at neonatal surgery and postoperative brain magnetic resonance imaging was 7 days (interquartile range [IQR] 5-11d) and 15 days (IQR 12-21d) respectively. Smaller CGM and cerebellar volumes were associated with lower fine motor scores at 9 months (CGM regression coefficient=0.51, 95% confidence interval [CI]=0.15-0.86; cerebellum regression coefficient=3.08, 95% CI=1.07-5.09) and 18 months (cerebellum regression coefficient=2.08, 95% CI=0.47-5.12). The fractional anisotropy and mean diffusivity of white matter motor tracts were not related with motor scores. WMI was related to lower gross motor scores at 9 months (mean difference -0.8SD, 95% CI=-1.5 to -0.2). AIS with CST involvement increased the risk of gross motor problems and muscle tone abnormalities. Cerebral palsy (n=3) was preceded by severe ischaemic brain injury. Interpretation Neonatal brain development and injury are associated with fewer favourable early motor outcomes in infants with CCHD

Does Repeated Measurement of a 6-Min Walk Test Contribute to Risk Prediction in Children with Dilated Cardiomyopathy?

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients >= 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2-6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5-5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86-0.95 p <0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test

Search for Event Rate Modulation in XENON100 Electronic Recoil Data

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an un-binned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1 sigma for all periods suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8 sigma, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of WIMPs to electrons is excluded at 4.8 sigma.Comment: 6 pages, 4 figure

Search for Two-Neutrino Double Electron Capture of 124^{124}Xe with XENON100

Two-neutrino double electron capture is a rare nuclear decay where two electrons are simultaneously captured from the atomic shell. For $^{124}$Xe this process has not yet been observed and its detection would provide a new reference for nuclear matrix element calculations. We have conducted a search for two-neutrino double electron capture from the K-shell of $^{124}$Xe using 7636 kg$\cdot$d of data from the XENON100 dark matter detector. Using a Bayesian analysis we observed no significant excess above background, leading to a lower 90 % credibility limit on the half-life $T_{1/2}>6.5\times10^{20}$ yr. We also evaluated the sensitivity of the XENON1T experiment, which is currently being commissioned, and find a sensitivity of $T_{1/2}>6.1\times10^{22}$ yr after an exposure of 2 t$\cdot$yr.Comment: 6 pages, 4 figure

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN