Evaluating resective surgery targets in epilepsy patients: a comparison of quantitative EEG methods.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.BACKGROUND: Quantitative analysis of intracranial EEG is a promising tool to assist clinicians in the planning of resective brain surgery in patients suffering from pharmacoresistant epilepsies. Quantifying the accuracy of such tools, however, is nontrivial as a ground truth to verify predictions about hypothetical resections is missing. NEW METHOD: As one possibility to address this, we use customized hypotheses tests to examine the agreement of the methods on a common set of patients. One method uses machine learning techniques to enable the predictive modeling of EEG time series. The other estimates nonlinear interrelation between EEG channels. Both methods were independently shown to distinguish patients with excellent post-surgical outcome (Engel class I) from those without improvement (Engel class IV) when assessing the electrodes associated with the tissue that was actually resected during brain surgery. Using the AND and OR conjunction of both methods we evaluate the performance gain that can be expected when combining them. RESULTS: Both methods' assessments correlate strongly positively with the similarity between a hypothetical resection and the corresponding actual resection in class I patients. Moreover, the Spearman rank correlation between the methods' patient rankings is significantly positive. COMPARISON WITH EXISTING METHOD(S): To our best knowledge, this is the first study comparing surgery target assessments from fundamentally differing techniques. CONCLUSIONS: Although conceptually completely independent, there is a relation between the predictions obtained from both methods. Their broad consensus supports their application in clinical practice to provide physicians additional information in the process of presurgical evaluation.This work was supported by the Swiss National Science Foundation (SNF) (Project No: SNF 32003B 155950). M.G. gratefully acknowledges the financial support of the EPSRC via grant EP/N014391/1. The contribution of M.G. was generously supported by a Wellcome Trust Institutional Strategic Support Award (WT105618MA)

Low-Temperature Orientation Dependence of Step Stiffness on {111} Surfaces

For hexagonal nets, descriptive of {111} fcc surfaces, we derive from combinatoric arguments a simple, low-temperature formula for the orientation dependence of the surface step line tension and stiffness, as well as the leading correction, based on the Ising model with nearest-neighbor (NN) interactions. Our formula agrees well with experimental data for both Ag and Cu{111} surfaces, indicating that NN-interactions alone can account for the data in these cases (in contrast to results for Cu{001}). Experimentally significant corollaries of the low-temperature derivation show that the step line tension cannot be extracted from the stiffness and that with plausible assumptions the low-temperature stiffness should have 6-fold symmetry, in contrast to the 3-fold symmetry of the crystal shape. We examine Zia's exact implicit solution in detail, using numerical methods for general orientations and deriving many analytic results including explicit solutions in the two high-symmetry directions. From these exact results we rederive our simple result and explore subtle behavior near close-packed directions. To account for the 3-fold symmetry in a lattice gas model, we invoke a novel orientation-dependent trio interaction and examine its consequences.Comment: 11 pages, 8 figure

Anomalous layering at the liquid Sn surface

X-ray reflectivity measurements on the free surface of liquid Sn are presented. They exhibit the high-angle peak, indicative of surface-induced layering, also found for other pure liquid metals (Hg, Ga and In). However, a low-angle peak, not hitherto observed for any pure liquid metal, is also found, indicating the presence of a high-density surface layer. Fluorescence and resonant reflectivity measurements rule out the assignment of this layer to surface-segregation of impurities. The reflectivity is modelled well by a 10% contraction of the spacing between the first and second atomic surface layers, relative to that of subsequent layers. Possible reasons for this are discussed.Comment: 8 pages, 9 figures; to be submitted to Phys. Rev. B; updated references, expanded discussio

Portable auricular device for real-time swallow and chew detection

Monitoring a person’s nutritional consumption is costly and complex. To solve this problem a new technique is proposed to draw conclusions of a person’s food intake. The air pressure signal, recorded in the external acoustic meatus, is used to detect swallow and chew events. A portable device has been developed to record this pressure signal. Due to the constraint of running on a low-power microcontroller, real-time algorithms, used in pattern and speech recognition, were used to develop methods to automatically detect swallow and chew events. A binary classifier was trained by means of manually annotated data sets. Direct comparisons with state of the art technology and tests with several subjects are provided for evaluation purposes

Changes in Electronic Structure and Chemical Bonding upon Crystallization of the Phase Change Material GeSb₂Te₄

High-resolution photoelectron spectroscopy of in situ prepared films of GeSb₂Te₄ reveals significant differences in electronic and chemical structure between the amorphous and the crystalline phase. Evidence for two different chemical environments of Ge and Sb in the amorphous structure is found. This observation can explain the pronounced property contrast between both phases and provides new insight into the formation of the amorphous state

21. Yüzyıl İçin İstenen/Gerekli Kütüphaneci Becerileri ve Kariyer Planlaması

21. yüzyılın değişen koşullarında kütüphane bir kütüphanecinin eleştirel düşünme ve çözüm bulma, iletişim, takım çalışması ve işbirliği ve yaratıcılık ve yenilikçi olma gibi özelliklere sahip olması gerektiği dikkat çekmektedir. Kütüphanecinin bu yeni koşullara uyum sağlaması son derece büyük bir önem taşımaktadır

Simultaneous determination of natural and synthetic steroid estrogens and their conjugates in aqueous matrices by liquid chromatography / mass spectrometry

An analytical method for the simultaneous determination of nine free and conjugated steroid estrogens was developed with application to environmental aqueous matrices. Solid phase extraction (SPE) was employed for isolation and concentration, with detection by liquid chromatography/mass spectrometry (LC/MS) using electrospray ionisation (ESI) in the negative mode. Method recoveries for various aqueous matrices (wastewater, lake and drinking water) were determined, recoveries proving to be sample dependent. When spiked at 50 ng/l concentrations in sewage influent, recoveries ranged from 62-89 % with relative standard deviations (RSD) < 8.1 %. In comparison, drinking water spiked at the same concentrations had recoveries between 82-100 % with an RSD < 5%. Ion suppression is a known phenomenon when using ESI; hence its impact on method recovery was elucidated for raw sewage. Both ion suppression from matrix interferences and the extraction procedure has bearing on the overall method recovery. Analysis of municipal raw sewage identified several of the analytes of interest at ng/l concentrations, estriol (E3) being the most abundant. Only one conjugate, estrone 3-sulphate (E1-3S) was observe

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis

Trimethylation of histone H3 lysine 27 (H3K27me3) plays critical roles in regulating animal development, and in several cases, H3K27me3 is also required for the proper expression of developmentally important genes in plants. However, the extent to which H3K27me3 regulates plant genes on a genome-wide scale remains unknown. In addition, it is not clear whether the establishment and spreading of H3K27me3 occur through the same mechanisms in plants and animals. We identified regions containing H3K27me3 in the genome of the flowering plant Arabidopsis thaliana using a high-density whole-genome tiling microarray. The results suggest that H3K27me3 is a major silencing mechanism in plants that regulates an unexpectedly large number of genes in Arabidopsis (~4,400), and that the maintenance of H3K27me3 is largely independent of other epigenetic pathways, such as DNA methylation or RNA interference. Unlike in animals, where H3K27m3 occupies large genomic regions, in Arabidopsis, we found that H3K27m3 domains were largely restricted to the transcribed regions of single genes. Furthermore, unlike in animals systems, H3K27m3 domains were not preferentially associated with low-nucleosome density regions. The results suggest that different mechanisms may underlie the establishment and spreading of H3K27me3 in plants and animals

Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring

BACKGROUND: The ABC transporter P-glycoprotein (P-gp) is recognized as a site for drug-drug interactions and provides a mechanistic explanation for clinically relevant pharmacokinetic interactions with digoxin. The question of whether several P-gp inhibitors may have additive effects has not yet been addressed. METHODS: We evaluated the effects on serum concentrations of digoxin (S-digoxin) in 618 patients undergoing therapeutic drug monitoring. P-gp inhibitors were classified as Class I, with a known effect on digoxin kinetics, or Class II, showing inhibition in vitro but no documented effect on digoxin kinetics in humans. Mean S-digoxin values were compared between groups of patients with different numbers of coadministered P-gp inhibitors by a univariate and a multivariate model, including the potential covariates age, sex, digoxin dose and total number of prescribed drugs. RESULTS: A large proportion (47%) of the digoxin patients undergoing therapeutic drug monitoring had one or more P-gp inhibitor prescribed. In both univariate and multivariate analysis, S-digoxin increased in a stepwise fashion according to the number of coadministered P-gp inhibitors (all P values < 0.01 compared with no P-gp inhibitor). In multivariate analysis, S-digoxin levels were 1.26 ± 0.04, 1.51 ± 0.05, 1.59 ± 0.08 and 2.00 ± 0.25 nmol/L for zero, one, two and three P-gp inhibitors, respectively. The results were even more pronounced when we analyzed only Class I P-gp inhibitors (1.65 ± 0.07 for one and 1.83 ± 0.07 nmol/L for two). CONCLUSIONS: Polypharmacy may lead to multiple drug-drug interactions at the same site, in this case P-gp. The S-digoxin levels increased in a stepwise fashion with an increasing number of coadministered P-gp inhibitors in patients taking P-gp inhibitors and digoxin concomitantly. As coadministration of digoxin and P-gp inhibitors is common, it is important to increase awareness about P-gp interactions among prescribing clinicians