Ventricular tachycardia associated with lacosamide co-medication in drug-resistant epilepsy.

We report a case of sustained ventricular tachycardia following the initiation of lacosamide as adjunctive epilepsy treatment. A 49-year-old male with intractable frontal lobe seizures experienced severe ventricular tachycardia following the addition of 400 mg lacosamide to his existing regimen of carbamazepine, lamotrigine, clonazepam, and valproate. The tachycardia occurred during a cardiac stress test; stress tests prior to initiation of lacosamide were normal. Conduction defects, including QRS prolongation, persisted during hospitalization until lacosamide was discontinued. The patient had no prior history of cardiac arrhythmia but did possess cardiac risk factors, including hypertension, hypercholesterolemia, and low heart rate variability. This case represents one part of a growing body of literature suggesting a link between arrhythmia and use of lacosamide, which enhances slow inactivation of sodium channels in both the brain and the heart. We believe further study may be necessary to assess the safety of lacosamide in epilepsy patients with cardiac risk factors

Momentum Flow Correlations from Event Shapes: Factorized Soft Gluons and Soft-Collinear Effective Theory

The distributions of two-jet event shapes contain information on hadronization in QCD. Near the two-jet limit, these distributions can be described by convolutions of nonperturbative event shape functions with the same distributions calculated in resummed perturbation theory. The shape functions, in turn, are determined by correlations of momentum flow operators with each other and with light-like Wilson lines, which describe the coupling of soft, wide-angle radiation to jets. We observe that leading power corrections to the mean values of event shapes are determined by the correlation of a single momentum flow operator with the relevant Wilson lines. This generalizes arguments for the universality of leading power corrections based on the low-scale behavior of the running coupling or resummation. We also show how a study of the angularity event shapes can provide information on correlations involving multiple momentum flow operators, giving a window to the system of QCD dynamics that underlies the variety of event shape functions. In deriving these results, we review, develop and compare factorization techniques in conventional perturbative QCD and soft-collinear effective theory (SCET). We give special emphasis to the elimination of double counting of momentum regions in these two formalisms.Comment: 25 pages revtex

Second-generation PLINK: rising to the challenge of larger and richer datasets

PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.Comment: 2 figures, 1 additional fil

Computerized Response Inhibition Training For Children With Trichotillomania

Evidence suggests that trichotillomania is characterized by impairment in response inhibition, which is the ability to suppress pre-potent/dominant but inappropriate responses. This study sought to test the feasibility of computerized response inhibition training for children with trichotillomania. Twenty-two children were randomized to the 8-session response inhibition training (RIT; n = 12) or a waitlisted control (WLT; n = 10). Primary outcomes were assessed by an independent evaluator, using the Clinical Global Impression-Improvement (CGI-I), and the NIMH Trichotillomania Severity (NIMH-TSS) and Impairment scales (NIMH-TIS) at pre, post-training/waiting, and 1-month follow-up. Relative to the WLT group, the RIT group showed a higher response rate (55% vs. 11%) on the CGI-I and a lower level of impairment on the NIMH-TIS, at post-training. Overall symptom reductions rates on the NIMH-TSS were 34% (RIT) vs. 21% (WLT) at post-training. The RIT\u27s therapeutic gains were maintained at 1-month follow-up, as indicated by the CGI-I responder status (= 66%), and a continuing reduction in symptom on the NIMH-TSS. This pattern of findings was also replicated by the 6 waitlisted children who received the same RIT intervention after post-waiting assessment. Results suggest that computerized RIT may be a potentially useful intervention for trichotillomania

The Zwitterionic Cell Wall Teichoic Acid of Staphylococcus aureus Provokes Skin Abscesses in Mice by a Novel CD4+ T-Cell-Dependent Mechanism

Zwitterionic polysaccharide (ZPS) components of the bacterial cell envelope have been shown to exert a major histocompatibility complex (MHC) II-dependent activation of CD4+ T cells, which in turn can modulate the outcome and progression of infections in animal models. We investigated the impact of zwitterionic cell wall teichoic acid (WTA) produced by Staphylococcus aureus on the development of skin abscesses in a mouse model. We also compared the relative biological activities of WTA and capsular polysaccharide (CP), important S. aureus pathogenicity factors, in abscess formation. Expression of both WTA and CP markedly affected the ability of S. aureus to induce skin abscess formation in mice. Purified wild-type zwitterionic WTA was more active in inducing abscess formation than negatively charged mutant WTA or purified CP8. To assess the ability of purified native WTA to stimulate T cell proliferation in vitro, we co-cultivated WTA with human T-cells and antigen presenting cells in the presence and absence of various inhibitors of MHC-II presentation. Wild-type WTA induced T cell proliferation to a significantly greater extent than negatively charged WTA. T cell activation was dependent on the presentation of WTA on MHC II, since inhibitors of MHC II-dependent presentation and antibodies to MHC II significantly reduced T cell proliferation. T cells activated in vitro with wild-type WTA, but not negatively charged WTA, induced abscess formation when injected subcutaneously into wild-type mice. CD4−/− mice similarly injected with WTA failed to develop abscesses. Our results demonstrate that the zwitterionic WTA of S. aureus induces CD4+ T-cell proliferation in an MHCII-dependent manner, which in turn modulates abscess formation in a mouse skin infection model. An understanding of this novel T cell-dependent host response to staphylococcal abscess formation may lead to the development of new strategies to combat S. aureus skin and soft tissue infections

Geodatabase Development to Support Hyperspectral Imagery Exploitation

Geodatabase development for coastal studies conducted by the Naval Research Laboratory (NRL) is essential to support the exploitation of hyperspectral imagery (HSI). NRL has found that the remote sensing and mapping science community benefits from coastal classifications that group coastal types based on similar features. Selected features in project geodatabases relate to significant biological and physical forces that shape the coast. The project geodatabases help researchers understand factors that are necessary for imagery post processing, especially those features having a high degree of temporal and spatial variability. NRL project geodatabases include a hierarchy of environmental factors that extend from shallow water bottom types and beach composition to inland soil and vegetation characteristics. These geodatabases developed by NRL allow researchers to compare features among coast types. The project geodatabases may also be used to enhance littoral data archives that are sparse. This paper highlights geodatabase development for recent remote sensing experiments in barrier island, coral, and mangrove coast types

Molecular Line Emission from Gravitationally Unstable Protoplanetary Disks

In the era of high resolution submillimeter interferometers, it will soon be possible to observe the neutral circumstellar medium directly involved in gas giant planet (GGP) formation at physical scales previously unattainable. In order to explore possible signatures of gas giant planet formation via disk instabilities, we have combined a 3D, non-local thermodynamic equilibrium (LTE) radiative transfer code with a 3D, finite differences hydrodynamical code to model molecular emission lines from the vicinity of a 1.4 M_J self-gravitating proto-GGP. Here, we explore the properties of rotational transitions of the commonly observed dense gas tracer, HCO+. Our main results are the following: 1. Very high lying HCO+ transitions (e.g. HCO+ J=7-6) can trace dense planet forming clumps around circumstellar disks. Depending on the molecular abundance, the proto-GGP may be directly imageable by the Atacama Large Millimeter Array (ALMA). 2. HCO+ emission lines are heavily self-absorbed through the proto-GGP's dense molecular core. This signature is nearly ubiquitous, and only weakly dependent on assumed HCO+ abundances. The self-absorption features are most pronounced at higher angular resolutions. Dense clumps that are not self-gravitating only show minor self-absorption features. 3. Line temperatures are highest through the proto-GGP at all assumed abundances and inclination angles. Conversely, due to self-absorption in the line, the velocity-integrated intensity may not be. High angular resolution interferometers such as the Submillimeter Array (SMA) and ALMA may be able to differentiate between competing theories of gas giant planet formation.Comment: 10 pages, 13 figures; Accepted by Ap