Monte Carlo simulations of infinitely dilute solutions of amphiphilic diblock star copolymers

Single-chain Monte Carlo simulations of amphiphilic diblock star copolymers were carried out in continuous space using implicit solvents. Two distinct architectures were studied: stars with the hydrophobic blocks attached to the core, and stars with the polar blocks attached to the core, with all arms being of equal length. The ratio of the lengths of the hydrophobic block to the length of the polar block was varied from 0 to 1. Stars with 3, 6, 9 or 12 arms, each of length 10, 15, 25, 50, 75 and 100 Kuhn segments were analysed. Four distinct types of conformations were observed for these systems. These, apart from studying the snapshots from the simulations, have been quantitatively characterised in terms of the mean-squared radii of gyration, mean-squared distances of monomers from the centre-of-mass, asphericity indices, static scattering form factors in the Kratky representation as well as the intra-chain monomer-monomer radial distribution functions.Comment: 12 pages, 11 ps figures. Accepted for publication in J. Chem. Phy

SDF1-A Facilitates Lin−/Sca1+ Cell Homing following Murine Experimental Cerebral Ischemia

Background Hematopoietic stem cells mobilize to the peripheral circulation in response to stroke. However, the mechanism by which the brain initiates this mobilization is uncharacterized. Methods Animals underwent a murine intraluminal filament model of focal cerebral ischemia and the SDF1-A pathway was evaluated in a blinded manner via serum and brain SDF1-A level assessment, Lin−/Sca1+ cell mobilization quantification, and exogenous cell migration confirmation; all with or without SDF1-A blockade. Results Bone marrow demonstrated a significant increase in Lin−/Sca1+ cell counts at 24 hrs (272±60%; P<0.05 vs sham). Mobilization of Lin−/Sca1+ cells to blood was significantly elevated at 24 hrs (607±159%; P<0.05). Serum SDF1-A levels were significant at 24 hrs (Sham (103±14), 4 hrs (94±20%, p = NS) and 24 hrs (130±17; p<0.05)). Brain SDF1-A levels were significantly elevated at both 4 hrs and 24 hrs (113±7 pg/ml and 112±10 pg/ml, respectively; p<0.05 versus sham 76±11 pg/ml). Following administration of an SDF1-A antibody, Lin−/Sca1+ cells failed to mobilize to peripheral blood following stroke, despite continued up regulation in bone marrow (stroke bone marrow cell count: 536±65, blood cell count: 127±24; p<0.05 versus placebo). Exogenously administered Lin−/Sca1+ cells resulted in a significant reduction in infarct volume: 42±5% (stroke alone), versus 21±15% (Stroke+Lin−/Sca1+ cells), and administration of an SDF1-A antibody concomitant to exogenous administration of the Lin−/Sca1+ cells prevented this reduction. Following stroke, exogenously administered Lin−/Sca1+ FISH positive cells were significantly reduced when administered concomitant to an SDF1-A antibody as compared to without SDF1-A antibody (10±4 vs 0.7±1, p<0.05). Conclusions SDF1-A appears to play a critical role in modulating Lin−/Sca1+ cell migration to ischemic brain

Symmetry Identification Using Partial Surface Matching and Tilt Correction in 3D Brain Images

We propose a novel method to automatically compute the symmetry plane and correct the 3D orientation of patient brain images. Many images of the brain are clinically unreadable because of the misalignment of the patient's head in the scanner. We proposed an algorithm that represents the brain volume as a re-parameterized surface point cloud where each location has been parameterized by its elevation (latitude), azimuth (longitude) and radius. The removal of the interior contents of the brain makes this approach perform robustly in the presence of the brain pathologies, e.g. tumor, stroke and bleed. Thus, we decompose the symmetry plane computation problem into a surface matching routine. The search for the best matching surface is implemented in a multi-resolution paradigm so as to decrease computational time considerably. Spatial affine transform then is performed to rotate the 3D brain images and align them within the coordinate system of the scanner. The corrected brain volume is re-sliced such that each planar image represents the brain at the same axial level

Asymmetry Analysis in Rodent Cerebral Ischemia Models

Rationale and Objectives: An automated method for identification and segmentation of acute/subacute ischemic stroke, using the inherent bi-fold symmetry in brain images, is presented. An accurate and automated method for localization of acute ischemic stroke could provide physicians with a mechanism for early detection and potentially faster delivery of effective stroke therapy. Materials and Methods: Segmentation of ischemic stroke was performed on magnetic resonance (MR) images of subacute rodent cerebral ischemia. Eight adult male Wistar rats weighing 225–300 g were anesthetized with halothane in a mix of 70% nitrous oxide/30% oxygen. Animal core temperature was maintained at 37°C during the entire surgical procedure, including occlusion of the middle cerebral artery (MCA) and the 90-minute post-reperfusion period. To confirm cerebral ischemia, transcranial measurements of cerebral blood flow were performed with laser-Doppler flowmetry, using 15-mm flexible fiberoptic Doppler probes attached to the skull over the MCA territory. Animal MR scans were performed at 1.5 T using a knee coil. Three experts performed manual tracing of the stroke regions for each rat, using the histologic-stained slices to guide delineation of stroke regions. A strict tracing protocol was followed that included multiple (three) tracings of each stroke region. The volumetric MR image data were processed for each rat by computing the axis of symmetry and extracting statistical dissimilarities. A nonparametric Wilcoxon rank sum test operating on paired windows in opposing hemispheres identified seeds in the pixels exhibiting statistically significant bi-fold mirror asymmetry. Two brain reference maps were used for analysis: an absolute difference map (ADM) and a statistical difference map (SDM). Although an ADM simply displays the absolute difference by subtracting one brain hemisphere from its reflection, SDM highlights regions by labeling pixels exhibiting statistically significant asymmetry. Results: To assess the accuracy of the proposed segmentation method, the surrogate ground truth (the stroke tracing data) was compared to the results of our proposed automated segmentation algorithm. Three accuracy segmentation metrics were utilized: true-positive volume fraction (TPVF), false-positive volume fraction (FPVF), and false-negative volume fraction (FNVF). The mean value of the TPVF for our segmentation method was 0.8877; 95% CI 0.7254 to 1.0500; the mean FPVF was 0.3370, 95% CI –0.0893 to 0.7633; the mean FNVF was 0.1122, 95% CI –0.0502 to 0.2747. Conclusions: Unlike most segmentation methods that require some degree of manual intervention, our segmentation algorithm is fully automated and highly accurate in identifying regions of brain asymmetry. This approach is attractive for numerous neurologic applications where the operator's intervention should be minimal or null

Chandra Detection of a TypeII Quasar at z=3.288

We report on observations of a TypeII quasar at redshift z=3.288, identified as a hard X-ray source in a 185 ks observation with the Chandra X-ray Observatory and as a high-redshift photometric candidate from deep, multiband optical imaging. CXOJ084837.9+445352 (hereinafter CXO52) shows an unusually hard X-ray spectrum from which we infer an absorbing column density N(H) = (4.8+/-2.1)e23 / cm2 (90% confidence) and an implied unabsorbed 2-10 keV rest-frame luminosity of L(2-10) = 3.3e44 ergs/s, well within the quasar regime. Hubble Space Telescope imaging shows CXO52 to be elongated with slight morphological differences between the WFPC2 F814W and NICMOS F160W bands. Optical and near-infrared spectroscopy of CXO52 show high-ionization emission lines with velocity widths ~1000 km/s and flux ratios similar to a Seyfert2 galaxy or radio galaxy. The latter are the only class of high-redshift TypeII luminous AGN which have been extensively studied to date. Unlike radio galaxies, however, CXO52 is radio quiet, remaining undetected at radio wavelengths to fairly deep limits, f(4.8GHz) < 40 microJy. High-redshift TypeII quasars, expected from unification models of active galaxies and long-thought necessary to explain the X-ray background, are poorly constrained observationally with few such systems known. We discuss recent observations of similar TypeII quasars and detail search techniques for such systems: namely (1) X-ray selection, (2) radio selection, (3) multi-color imaging selection, and (4) narrow-band imaging selection. Such studies are likely to begin identifying luminous, high-redshift TypeII systems in large numbers. We discuss the prospects for these studies and their implications to our understanding of the X-ray background.Comment: 28 pages, 5 figures; to appear in The Astrophysical Journa

Post-carotid endarterectomy neurocognitive decline is associated with cerebral blood flow asymmetry on post-operative magnetic resonance perfusion brain scans

Objective: Up to 25% of patients experience subtle declines in post-operative neurocognitive function following, otherwise uncomplicated, carotid endarterectomy (CEA). We sought to determine if post-CEA neurocognitive deficits are associated with cerebral blood flow (CBF) abnormalities on post-operative MR perfusion brain scans. Methods: We enrolled 22 CEA patients to undergo a battery of neuropsychometric tests pre-operatively and on post-operative day 1 (POD 1). Neurocognitive dysfunction was defined as a two standard deviation decline in performance in comparison to a similarly aged control group of lumbar laminectomy patients. All patients received MR perfusion brain scans on POD 1 that were analysed for asymmetries in CBF distribution. One patient experienced a transient ischemic attack within 24 hours before the procedure and was excluded from our analysis. Results: Twenty-nine percent of CEA patients demonstrated neurocognitive dysfunction on POD 1. One hundred percent of those patients with cognitive deficits demonstrated CBF asymmetry, in contrast to only 27% of those patients without cognitive impairment. Post-CEA cognitive dysfunction was significantly associated with CBF abnormalities (RR=3.75, 95% CI: 1.62-8.67, p=0.004). Conclusion: Post-CEA neurocognitive dysfunction is significantly associated with post-operative CBF asymmetry. These results support the hypothesis that post-CEA cognitive impairment is caused by cerebral hemodynamic changes. Further work exploring the relationship between CBF and post-CEA cognitive dysfunction is needed

Cardiac Arrhythmias after Subarachnoid Hemorrhage: Risk Factors and Impact on Outcome

Objective: Serious cardiac arrhythmias have been described in approximately 5% of patients after subarachnoid hemorrhage (SAH). The aim of this study was to identify the frequency, risk factors and clinical impact of cardiac arrhythmia after SAH. Methods: We prospectively studied 580 spontaneous SAH patients and identified risk factors and complications associated with the development of clinically significant arrhythmia. Multiple logistic regression analysis was used to calculate adjusted odds ratios for the effect of arrhythmia on hospital complications and 3-month outcome, as measured by the modified Rankin Scale, after controlling for age, neurological grade, APACHE-2 physiologic subscore, brain herniation and aneurysm size. Results: Arrhythmia occurred in 4.3% (n = 25) of patients. Atrial fibrillation and flutter were the most common arrhythmias, occurring in 76% (n = 19) of these patients. Admission predictors of cardiac arrhythmia included older age, history of arrhythmia and abnormal admission electrocardiogram (all p < 0.05). After adjusting for length of stay, hospital complications associated with arrhythmia included myocardial ischemia, hyperglycemia, and herniation (all p < 0.05). Arrhythmia was associated with an excess ICU stay of 5 days (p = 0.002). After adjusting for other predictors of outcome, arrhythmia was associated with an increased risk of death (adjusted OR 8.0, 95% confidence interval 1.9–34.0, p = 0.005), and death or severe disability (adjusted OR 6.9, 95% confidence interval 1.5–32.0, p = 0.014). Conclusions: Clinically important arrhythmias, most often atrial fibrillation or flutter, occurred in 4% of SAH patients. Arrhythmias are associated with an increased risk of cardiovascular comorbidity, prolonged hospital stay and poor outcome or death after SAH, after adjusting for other predictors of poor outcome

Toward Objective Quantification of Perfusion-weighted Computed Tomography in Subarachnoid Hemorrhage: Quantification of Symmetry and Automated Delineation of Vascular Territories

Rationale and Objectives: Perfusion-weighted computed tomography (CTP) is a relatively recent innovation that estimates a value for cerebral blood flow (CBF) using a series of axial head CT images tracking the time course of a signal from an intravenous contrast bolus. Materials and Methods: CTP images were obtained using a standard imaging protocol and were analyzed using commercially available software. A novel computer-based method was used for objective quantification of side-to-side asymmetries of CBF values calculated from CTP images. Results: Our method corrects for the inherent variability of the CTP methodology seen in the subarachnoid hemorrhage (SAH) patient population to potentially aid in the diagnosis of cerebral vasospasm (CVS). This method analyzes and quantifies side-to-side asymmetry of CBF and presents relative differences in a construct termed a Relative Difference Map (RDM). To further automate this process, we have developed a unique methodology that enables a computer to delineate vascular territories within a brain image, regardless of the size and shape of the brain. Conclusions: While both the quantification of image symmetry using RDMs and the automated assignment of vascular territories were initially designed for the analysis of CTP images, it is likely that they will be useful in a variety of applications

Systemic glucose variability predicts cerebral metabolic distress and mortality after subarachnoid hemorrhage: a retrospective observational study

Introduction: Cerebral glucose metabolism and energy production are affected by serum glucose levels. Systemic glucose variability has been shown to be associated with poor outcome in critically ill patients. The objective of this study was to assess whether glucose variability is associated with cerebral metabolic distress and outcome after subarachnoid hemorrhage. Methods: A total of 28 consecutive comatose patients with subarachnoid hemorrhage, who underwent cerebral microdialysis and intracranial pressure monitoring, were studied. Metabolic distress was defined as lactate/pyruvate ratio (LPR) >40. The relationship between daily glucose variability, the development of cerebral metabolic distress and hospital outcome was analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes. Results: Daily serum glucose variability was expressed as the standard deviation (SD) of all serum glucose measurements. General linear models were used to relate this predictor variable to cerebral metabolic distress and mortality at hospital discharge. A total of 3,139 neuromonitoring hours and 181 days were analyzed. After adjustment for Glasgow Coma Scale (GCS) scores and brain glucose, SD was independently associated with higher risk of cerebral metabolic distress (adjusted odds ratio = 1.5 (1.1 to 2.1), P = 0.02). Increased variability was also independently associated with in hospital mortality after adjusting for age, Hunt Hess, daily GCS and symptomatic vasospasm (P = 0.03). Conclusions: Increased systemic glucose variability is associated with cerebral metabolic distress and increased hospital mortality. Therapeutic approaches that reduce glucose variability may impact on brain metabolism and outcome after subarachnoid hemorrhage