EEG synchronization measures are early outcome predictors in comatose patients after cardiac arrest.

Outcome prognostication in comatose patients after cardiac arrest (CA) remains a major challenge. Here we investigated the prognostic value of combinations of linear and non-linear bivariate EEG synchronization measures. 94 comatose patients with EEG within 24h after CA were included. Clinical outcome was assessed at 3months using the Cerebral Performance Categories (CPC). EEG synchronization between the left and right parasagittal, and between the frontal and parietal brain regions was assessed with 4 different quantitative measures (delta power asymmetry, cross-correlation, mutual information, and transfer entropy). 2/3 of patients were used to assess the predictive power of all possible combinations of these eight features (4 measures×2 directions) using cross-validation. The predictive power of the best combination was tested on the remaining 1/3 of patients. The best combination for prognostication consisted of 4 of the 8 features, and contained linear and non-linear measures. Predictive power for poor outcome (CPC 3-5), measured with the area under the ROC curve, was 0.84 during cross-validation, and 0.81 on the test set. At specificity of 1.0 the sensitivity was 0.54, and the accuracy 0.81. Combinations of EEG synchronization measures can contribute to early prognostication after CA. In particular, combining linear and non-linear measures is important for good predictive power. Quantitative methods might increase the prognostic yield of currently used multi-modal approaches

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

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

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

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

Current understanding in climbing psychophysiology research

The sport of rock climbing places a significant physiological and psychological load on participants. Psychophysiological analysis provides a unique insight into affective states arising from the demands of climbing, and the impact that they have on performance. This review provides an overview of climbing psychophysiology research completed to date. To summarise, an on-sight lead ascent of a route elicits the greatest psychophysiological response in climbers; whilst, a red-point top-rope ascent produces the least. The affects of climbing stimuli on an individual’s performance appear to be conditional on their experience. In general, experienced climbers show superior performance and are less anxious than their less practiced counterparts, with significantly lower cognitive and somatic anxiety, increased self-confidence and lower values of the steroid stress hormone cortisol. It is likely that the experience-stressor-performance relationship is due to advanced climbers’ greater understanding of the risks associated with the sport, their habituation to the stressors gained through practice and their ability to perform well with higher levels of anxiety. This review outlines pertinent psychological climbing stimuli, summarise current methodologies and presents a detailed review of climbing psychophysiology research. It also concludes with suggestions for improving the depth and breadth of future research, including the need for the refinement of existing measures

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)

Top-Down Feedback in an HMAX-Like Cortical Model of Object Perception Based on Hierarchical Bayesian Networks and Belief Propagation

PubMed ID: 2313976

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Tetrazine-norbornene versus azide-norbornene ligation: evaluating the toolbox for polymer–polymer coupling

The selective ligation chemistry of the stable norbornene (Nb) with an asymmetric tetrazine (Tz), accessible in a one-pot reaction is adapted to the ligation of polymer segments yielding block copolymers. The Tz/Nb inverse electron-demand Diels–Alder reaction (IEDDA) is compared with the more classical azide (Az)-norbornene Huisgen 1,3-cycloaddition (CA) to ligate end-functionalized polymers. An endo/exo-norbornene end-functionalized polystyrene (PS1.5k-Nb) and polyethylene glycols with either tetrazine or aryl azido functionalities (PEG3k/5k-Tz, PEG3k/5k-Az) are synthesized. While the Tz/Nb IEDDA proceeds cleanly and leads to full conversion in stochiometric mixtures, the Az/Nb CA requires less effort but suffers from slower coupling kinetics and some side reactions. The coupling of PS1.5k-Nb with PEG3k/5k-Az requires 1H-NMR analysis to follow the kinetics and the products suffer from incomplete conversion as well as slight decomposition of the Az-moieties. In contrast, the ligation of PS1.5k-Nb with PEG3k/5k-Tz is robust. The reaction, which is conveniently monitored by UV/Vis spectroscopy, yields the desired PS-block-PEG in high yields and may offer potential for easy scale-up.Peer Reviewe