Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis

Cerebral edema (CED) is a severe complication of acute ischemic stroke. There is uncertainty regarding the predictors for the development of CED after cerebral infarction. We aimed to determine which baseline clinical and radiological parameters predict development of CED in patients treated with intravenous thrombolysis. We used an image-based classification of CED with 3 degrees of severity (less severe CED 1 and most severe CED 3) on postintravenous thrombolysis imaging scans. We extracted data from 42 187 patients recorded in the SITS International Register (Safe Implementation of Treatments in Stroke) during 2002 to 2011. We did univariate comparisons of baseline data between patients with or without CED. We used backward logistic regression to select a set of predictors for each CED severity. CED was detected in 9579/42 187 patients (22.7%: 12.5% CED 1, 4.9% CED 2, 5.3% CED 3). In patients with CED versus no CED, the baseline National Institutes of Health Stroke Scale score was higher (17 versus 10; P<0.001), signs of acute infarct was more common (27.9% versus 19.2%; P<0.001), hyperdense artery sign was more common (37.6% versus 14.6%; P<0.001), and blood glucose was higher (6.8 versus 6.4 mmol/L; P<0.001). Baseline National Institutes of Health Stroke Scale, hyperdense artery sign, blood glucose, impaired consciousness, and signs of acute infarct on imaging were independent predictors for all edema types. The most important baseline predictors for early CED are National Institutes of Health Stroke Scale, hyperdense artery sign, higher blood glucose, decreased level of consciousness, and signs of infarct at baseline. The findings can be used to improve selection and monitoring of patients for drug or surgical treatment

Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia

Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), that is, a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells. Little is known regarding the impact of such genotypes in untransplanted acute myeloid leukemia (AML). For this study, NK cell phenotypes and KIR/HLA genotypes were determined in 81 AML patients who received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention (NCT01347996). We observed that presence of unlicensed NK cells impacted favorably on clinical outcome, in particular among patients harboring functional NK cells reflected by high expression of the natural cytotoxicity receptor (NCR) NKp46. Genotype analyses suggested that the clinical benefit of high NCR expression was restricted to patients with a missing ligand genotype and/or a KIR B/x genotype. These data imply that functional NK cells are significant anti-leukemic effector cells in patients with KIR/HLA genotypes that favor NK cell autoreactivity

Spectroscopic Detection of Carbon Monoxide in Two Late-type T Dwarfs

M band spectra of two late-type T dwarfs, 2MASS J09373487+2931409, and Gliese 570D, confirm evidence from photometry that photospheric CO is present at abundance levels far in excess of those predicted from chemical equilibrium. These new and unambiguous detections of CO, together with an earlier spectroscopic detection of CO in Gliese 229B and existing M band photometry of a large selection of T dwarfs, suggest that vertical mixing in the photosphere drives the CO abundance out of chemical equilibrium and is a common, and likely universal feature of mid-to-late type T dwarfs. The M band spectra allow determinations of the time scale of vertical mixing in the atmosphere of each object, the first such measurements of this important parameter in late T dwarfs. A detailed analysis of the spectral energy distribution of 2MASS J09373487+2931409 results in the following values for metallicity, temperature, surface gravity, and luminosity: [M/H]~-0.3, T_eff=925-975K, log g=5.20-5.47, log L/L_sun=-5.308 +/- 0.027. The age is 3-10 Gyr and the mass is in the range 45-69 M_Jup.Comment: 36 pages incl. 12 figures and 3 tables, accepted by Ap

Basic physical parameters of a selected sample of evolved stars

We present the detailed spectroscopic analysis of 72 evolved stars, including the [Fe/H] determination for the whole sample. These metallicities, together with the Teff values and the absolute V magnitude derived from Hipparcos parallaxes, are used to estimate basic stellar parameters (ages, masses, radii, (B-V)o and log g using theoretical isochrones and a Bayesian estimation method. The (B-V)o values so estimated turn out to be in excellent agreement with the observed (B-V), confirming the reliability of the (Teff,(B-V)o) relation used in the isochrones. The estimated diameters have been compared with limb darkening-corrected ones measured with independent methods, finding an agreement better than 0.3 mas within the 1-10 mas interval. We derive the age-metallicity relation for the solar neighborhood; for the first time such a relation has been derived from observations of field giants rather than from open clusters and field dwarfs and subdwarfs. The age-metallicity relation is characterized by close-to-solar metallicities for stars younger than ~4 Gyr, and by a large [Fe/H] spread with a trend towards lower metallicities for higher ages. We find that the [Fe/H] dispersion of young stars (less than 1 Gyr) is comparable to the observational errors, indicating that stars in the solar neighbourhood are formed from interstellar matter of quite homogeneous chemical composition. The three giants of our sample which have been proposed to host planets are not metal rich, what is at odds with those for main sequence stars. However, two of these stars have masses much larger than a solar mass so we may be sampling a different stellar population from most radial velocity searches for extrasolar planets. We also confirm that the radial velocity variability tends to increase along the RGB.Comment: 17 pgs, 19 fig

Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis

BackgroundImatinib, a tyrosine kinase inhibitor, has been shown to restore bloodâ brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes.MethodsA phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS).ResultsFour serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400â mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (P = 0.02). For the 800â mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (P = 0.037) and 5 points (P = 0.012), respectively, versus controls. Functional independence (mRS 0â 2) increased by 18% versus controls (61 vs. 79; P = 0.296).ConclusionThis phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/1/joim12576_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/2/joim12576.pd

Comments on alternative calculations of the broadening of spectral lines of neutral sodium by H-atom collisions

With the exception of the sodium D-lines recent calculations of line broadening cross-sections for several multiplets of sodium by Leininger et al (2000) are in substantial disagreement with cross-sections interpolated from the tables of Anstee and O'Mara (1995) and Barklem and O'Mara (1997). The discrepancy is as large as a factor of three for the 3p-4d multiplet. The two theories are tested by using the results of each to synthesize lines in the solar spectrum. It is found that generally the data from the theory of Anstee, Barklem and O'Mara produce the best match to the observed solar spectrum. It is found, using a simple model for reflection of the optical electron by the potential barrier between the two atoms, that the reflection coefficient is too large for avoided crossings with the upper states of subordinate lines to contribute to line broadening, supporting the neglect of avoided ionic crossings by Anstee, Barklem and O'Mara for these lines. The large discrepancies between the two sets of calculations is a result of an approximate treatment of avoided ionic crossings for these lines by Leininger et al (2000).Comment: 18 pages, 5 ps figures included, to appear in J Phys B: At. Mol. Opt. Phy

Dynamic Measurements of Membrane Insertion Potential of Synthetic Cell Penetrating Peptides

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la403370p.Cell penetrating peptides (CPPs) have been established as excellent candidates for mediating drug delivery into cells. When designing synthetic CPPs for drug delivery applications, it is important to understand their ability to penetrate the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers at the air-water interface are used as model cell membranes to monitor the membrane insertion potential of synthetic CPPs. The insertion potential of CPPs having different cationic and hydrophobic amino acids were recorded using a Langmuir monolayer approach that records peptide adsorption to model membranes. Fluorescence microscopy was used to visualize alterations in phospholipid packing due to peptide insertion. All CPPs had the highest penetration potential in the presence of anionic phospholipids. In addition, two of three amphiphilic CPPs inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did. All the CPPs studied induced disruptions in phospholipid packing and domain morphology, which were most pronounced for amphiphilic CPPs. Overall, small changes to amino acids and peptide sequences resulted in dramatically different insertion potentials and membrane reorganization. Designers of synthetic CPPs for efficient intracellular drug delivery should consider small nuances in CPP electrostatic and hydrophobic properties

The ability of intermediate-band Stromgren photometry to correctly identify dwarf, subgiant, and giant stars and provide stellar metallicities and surface gravities

[Abridged] Several large scale photometric and spectroscopic surveys are being undertaken to provide a more detailed picture of the Milky Way. Given the necessity of generalisation in the determination of, e.g., stellar parameters when tens and hundred of thousands of stars are considered it remains important to provide independent, detailed studies to verify the methods used in the surveys. We evaluate available calibrations for deriving [M/H] from Stromgren photometry and develop the standard sequences for dwarf stars to reflect their metallicity dependence and test how well metallicities derived from ugriz photometry reproduce metallicities derived from the well-tested system of Stromgren photometry. We use a catalogue of dwarf stars with both Stromgren uvby photometry and spectroscopically determined iron abundances (in total 451 dwarf stars with 0.3<(b-y)_0<1.0). We also evaluate available calibrations that determine log g. A larger catalogue, in which metallicity is determined directly from uvby photometry, is used to trace metallicity-dependent standard sequences for dwarf stars. We derive new standard sequences in the c_1,0 versus (b-y)_0 plane and in the c_1,0 versus (v-y)_0 plane for dwarf stars with 0.40 < (b-y)_0 < 0.95 and 1.10 < (v-y)_0 < 2.38. We recommend the calibrations by Ramirez & Me'endez (2005) for deriving metallicities from Stromgren photometry and find that intermediate band photometry, such as Stromgren photometry, more accurately than broad band photometry reproduces spectroscopically determined [Fe/H]. Stromgren photometry is also better at differentiating between dwarf and giant stars. We conclude that additional investigations of the differences between metallicities derived from ugriz photometry and intermediate-band photometry, such as Stromgren photometry, are required.Comment: Accepted for publication in A&A, 34 pages, including on-line materia

Environmental differences between sites control the diet and nutrition of the carnivorous plant Drosera rotundifolia

Background and aims: Carnivorous plants are sensitive to small changes in resource availability, but few previous studies have examined how differences in nutrient and prey availability affect investment in and the benefit of carnivory. We studied the impact of site-level differences in resource availability on ecophysiological traits of carnivory for Drosera rotundifolia L. Methods: We measured prey availability, investment in carnivory (leaf stickiness), prey capture and diet of plants growing in two bogs with differences in N deposition and plant available N: Cors Fochno (0.62 g m−2 yr.−1, 353 μg l−1), Whixall Moss (1.37 g m−2 yr.−1, 1505 μg l−1). The total N amount per plant and the contributions of prey/root N to the plants’ N budget were calculated using a single isotope natural abundance method. Results: Plants at Whixall Moss invested less in carnivory, were less likely to capture prey, and were less reliant on prey-derived N (25.5% compared with 49.4%). Actual prey capture did not differ between sites. Diet composition differed – Cors Fochno plants captured 62% greater proportions of Diptera. Conclusions: Our results show site-level differences in plant diet and nutrition consistent with differences in resource availability. Similarity in actual prey capture may be explained by differences in leaf stickiness and prey abundance