Effects of scopolamine on matching to sample paradigm and related tests in human subjects

This was a double-blind placebo-controlled study with a cross-over design to examine the effects of scopolamine on cognitive functions in young healthy subjects. Scopolamine hydrobromide was administered subcutaneously to 12 subjects (mean +/- SD age 23.8 +/- 2.2 years) at doses of 0.3 and 0.6 mg in comparison with two placebo conditions. Scopolamine at both doses produced marked sedation as rated by subjects and an observer. In the continuous performance test, vigilance was impaired by both doses of scopolamine. The span of apprehension test showed differing results (only the high dose of scopolamine showed a performance decrement only in the three-character version of the span of apprehension test). Significant impairment by both doses of scopolamine was seen in immediate and delayed free recall, continuous visual recognition, running word recognition and running picture recognition. While scopolamine caused a significant slowing in average reaction times for simultaneous matching as well as for delayed matching, subjects made more errors under scopolamine compared to placebo only in delayed matching, not in simultaneous matching. Also, the main outcome of matching to sample showed significant effects only in delayed matching, not in simultaneous matching. Notable in this study is the incongruity between the simultaneous matching test and the span of apprehension test on the one hand and the other cognitive tests used on the other. These results demonstrated that scopolamine has a greater effect on memory than on attention. Thus, the scopolamine-induced effects in the present study seem to be more relevant to Alzheimer's disease in an advanced phase than to normal aging. Copyright (C) 2003 S. Karger AG, Basel

A classical reactive potential for molecular clusters of sulphuric acid and water

We present a two-state empirical valence bond (EVB) potential describing interactions between sulphuric acid and water molecules and designed to model proton transfer between them within a classical dynamical framework. The potential has been developed in order to study the properties of molecular clusters of these species, which are thought to be relevant to atmospheric aerosol nucleation. The particle swarm optimisation method has been used to fit the parameters of the EVB model to density functional theory (DFT) calculations. Features of the parametrised model and DFT data are compared and found to be in satisfactory agreement. In particular, it is found that a single sulphuric acid molecule will donate a proton when clustered with four water molecules at 300 K and that this threshold is temperature dependent

Molecular simulations of heterogeneous ice nucleation. I. Controlling ice nucleation through surface hydrophilicity

Ice formation is one of the most common and important processes on earth and almost always occurs at the surface of a material. A basic understanding of how the physicochemical properties of a material's surface affect its ability to form ice has remained elusive. Here, we use molecular dynamics simulations to directly probe heterogeneous ice nucleation at a hexagonal surface of a nanoparticle of varying hydrophilicity. Surprisingly, we find that structurally identical surfaces can both inhibit and promote ice formation and analogous to a chemical catalyst, it is found that an optimal interaction between the surface and the water exists for promoting ice nucleation. We use our microscopic understanding of the mechanism to design a modified surface in silico with enhanced ice nucleating ability.Comment: 5 pages; 3 figures; Title changed from previous version on arXi

Individual Differences in Goal Pursuit Despite Interfering Aversion, Temptation, and Distraction

Self-control can be defined as the ability to exert control over ones impulses. Currently, most research in the area relies on self-report. Focusing on attentional control processes involved in self-control, we modified a spatial selective attentional cueing task to test three domains of self- control experimentally in one task using aversive, tempting, and neutral picture-distractors. The aims of the study were (1) to investigate individual differences in the susceptibility to aversive, tempting, and neutral distraction within one paradigm and (2) to test the association of these three self-control domains to conventional measures of self-control including self- report. The final sample consisted of 116 participants. The task required participants to identify target letters “E” or “F” presented at a cued target location while the distractors were presented. Behavioral and eyetracking data were obtained during the performance of the task. High task performance was encouraged via monetary incentives. In addition to the attentional self- control task, self-reported self-control was assessed and participants performed a color Stroop task, an unsolvable anagram task and a delay of gratification task using chocolate sweets. We found that aversion, temptation, and neutral distraction were associated with significantly increased error rates, reaction times and gaze pattern deviations. Overall task performance on our task correlated with self-reported self-control ability. Measures of aversion, temptation, and distraction showed moderate split-half reliability, but did not correlate with each other across participants. Additionally, participants who made a self-controlled decision in the delay of gratification task were less distracted by temptations in our task than participants who made an impulsive choice. Our individual differences analyses suggest that (1) the ability to endure aversion, resist temptations and ignore neutral distractions are independent of each other and (2) these three domains are related to other measures of self-control

Acquired resistance of human T cells to sulfasalazine: stability of the resistant phenotype and sensitivity to non-related DMARDs.

2.5 weeks) resumption of SSZ resistance and ABCG2 expression as in the original CEM/SSZ cells. CEM/SSZ cells displayed diminished sensitivity to the DMARDs leflunomide (5.1-fold) and methotrexate (1.8-fold), were moderately more sensitive (1.6-2.0 fold) to cyclosporin A and chloroquine, and markedly more sensitive (13-fold) to the glucocorticoid dexamethasone as compared with parental CEM cells. CONCLUSION: The drug efflux pump ABCG2 has a major role in conferring resistance to SSZ. The collateral sensitivity of SSZ resistant cells for some other (non-related) DMARDs may provide a further rationale for sequential mono- or combination therapies with distinct DMARDs upon decreased efficacy of SSZ

International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies. In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

High performance computations using dynamical nucleation theory

Chemists continue to explore the use of very large computations to perform simulations that describe the molecular level physics of critical challenges in science. In this paper, we describe the Dynamical Nucleation Theory Monte Carlo (DNTMC) model - a model for determining molecular scale nucleation rate constants - and its parallel capabilities. The potential for bottlenecks and the challenges to running on future petascale or larger resources are delineated. A \u27master-slave\u27 solution is proposed to scale to the petascale and will be developed in the NWChem software. In addition, mathematical and data analysis challenges are described