Topiramate alters the gut microbiome to aid in its anti-seizure effect

IntroductionThere is a growing interest in the role of the gut microbiota in epilepsy, however, it is unclear if anti-seizure medications (ASMs) play a role in the gut-brain axis. To test this, we investigated the impact of the ASM topiramate on the gut microbiome of mice.MethodsC57BL/6J mice were administered topiramate in their drinking water for 5 weeks. 16S ribosomal RNA gene sequencing was performed on fecal samples collected at 5 weeks. Analysis of alpha diversity, beta diversity, and differential abundance were performed. Cecal contents were analyzed for short-chain fatty acids (SCFAs) composition. Pentylenetetrazol (PTZ)-kindling was performed in saline, topiramate, Lactobacillus johnsonii, and topiramate and Lactobacillus johnsonii treated mice. Mice received PTZ injection every other day for a total of twelve injections, seizure activity was video monitored for 30 minutes and scored.Results and discussionOur study revealed that topiramate ingestion significantly increased Lactobacillus johnsonii in the gut microbiome of namice. Treatment with topiramate and Lactobacillus johnsonii together, but not alone, reduced susceptibility to PTZ-induced seizures. Co-treatment also significantly increased the percent of butyrate and the abundance of butyrate-producing family Lachnospiraceae in the gut, and elevated the GABA/glutamate ratio in the cortex. Our results demonstrate that an ASM can alter the gut microbiome to aid in their anti-seizure effect in vivo and suggest the potential of the probiotic Lactobacillus johnsonii as an adjunct therapy with topiramate in reducing seizure susceptibility

Pretend Play and Social Engagement in Toddlers at High and Low Genetic Risk for Autism Spectrum Disorder

Toddlers with an older sibling with autism spectrum disorder (ASD) and low risk (LR) toddlers with typically-developing older siblings were observed during free play with a parent and elicited pretend with an examiner at 22-months. Functional and pretend play, children’s social engagement, and parent sensitivity were assessed during free play. Complexity of play was assessed during the elicited pretend task. Toddlers with an ASD diagnosis showed less pretend play across contexts and less social engagement with parents or the examiner than either LR toddlers or high risk toddlers without a diagnosis (HR-noASD). Lower levels of pretend play and social engagement were associated with symptom severity within the high risk group, reflecting emerging ASD in toddlerhood

Specialized CFD Grid Generation Methods for Near-Field Sonic Boom Prediction

Ongoing interest in analysis and design of low sonic boom supersonic transports re- quires accurate and ecient Computational Fluid Dynamics (CFD) tools. Specialized grid generation techniques are employed to predict near- eld acoustic signatures of these con- gurations. A fundamental examination of grid properties is performed including grid alignment with ow characteristics and element type. The issues a ecting the robustness of cylindrical surface extrusion are illustrated. This study will compare three methods in the extrusion family of grid generation methods that produce grids aligned with the freestream Mach angle. These methods are applied to con gurations from the First AIAA Sonic Boom Prediction Workshop

The long-term impact of folic acid in pregnancy on offspring DNA methylation : follow-up of the Aberdeen folic acid supplementation trial (AFAST)

Funding This work was supported by the NIHR Bristol Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. R.C.R., G.C.S., N.K., T.G., G.D.S. and C.L.R. work in a unit that receives funds from the University of Bristol and the UK Medical Research Council (MC_UU_12013/1, MC_UU_12013/2 and MC_UU_12013/8). This work was also supported by CRUK (grant number C18281/A19169) and the ESRC (grant number ES/N000498/1). C.M.T. is supported by a Wellcome Trust Career Re-entry Fellowship (grant number 104077/Z/14/Z).Peer reviewedPublisher PD

Effects of Deepwater Horizon oil on feather structure and thermoregulation in gulls: Does rehabilitation work?

Impacts of large-scale oil spills on avian species are far-reaching.While media attention often focuses on lethal impacts, sub-lethal effects and the impacts of rehabilitation receive less attention. The objective of our study was to characterize effects of moderate external oiling and subsequent rehabilitation on feather structure and thermoregulation in gulls. We captured 30 wild ring-billed gulls (Larus delawarensis) and randomly assigned each individual to an experimental group: 1) controls, 2) rehabilitated birds (externally oiled, rehabilitated by washing), or 3) oiled birds (externally oiled, not rehabilitated). We externally oiled birds with weathered MC252 Deepwater Horizon oil (water for controls) and collected feathers and thermography imagery (FLIR) approximately weekly for four weeks to investigate feather structure (quantified using a barbule clumping index) and thermoregulatory ability (characterized by internal body temperature and external surface temperature). Post-oiling feather clumping was significantly higher in oiled and rehabilitated birds compared to controls, but steadily declined over time in both groups. However, feather microstructure in rehabilitated birds was indistinguishable from controls within three weeks of washing whereas the feathers of oiled birds were still significantly clumped a month post oiling. Internal body temperatures didn\u27t differ in any of the groups, suggesting birds maintain thermoregulatory homeostasis in spite of moderate external oiling. External temperatures for rehabilitated birds didn\u27t differ from controls within a week of rehabilitation. Overall, rehabilitation procedures were effective and washed birds were in better condition compared to non-rehabilitated, oiled birds. This study provides evidence that the benefits of rehabilitation for moderately oiled birds likely outweigh the costs with regard to feather structure and thermoregulation.While feather preening and time were insufficient to reestablish baseline fine scale feather structure in moderately oiled birds, the significant clumping reduction over time may indicate that rehabilitation of lightly oiled birds may not be necessary and deserves further study

A Strategy for Electronic Dissemination of NASA Langley Technical Publications

To demonstrate NASA Langley Research Center\u27s relevance and to transfer technology to external customers in a timely and efficient manner, Langley has formed a working group to study and recommend a course of action for the electronic dissemination of technical reports (EDTR). The working group identified electronic report requirements (e.g., accessibility, file format, search requirements) of customers in U.S. industry through numerous site visits and personal contacts. Internal surveys were also used to determine commonalities in document preparation methods. From these surveys, a set of requirements for an electronic dissemination system was developed. Two candidate systems were identified and evaluated against the set of requirements: the Full-Text Electronic Documents System (FEDS), which is a full-text retrieval system based on the commercial document management package Interleaf, and the Langley Technical Report Server (LTRS), which is a Langley-developed system based on the publicly available World Wide Web (WWW) software system. Factors that led to the selection of LTRS as the vehicle for electronic dissemination included searching and viewing capability, current system operability, and client software availability for multiple platforms at no cost to industry. This report includes the survey results, evaluations, a description of the LTRS architecture, recommended policy statement, and suggestions for future implementations

Measuring Transit Signal Recovery in the Kepler Pipeline II: Detection Efficiency as Calculated in One Year of Data

The Kepler planet sample can only be used to reconstruct the underlying planet occurrence rate if the detection efficiency of the Kepler pipeline is known, here we present the results of a second experiment aimed at characterising this detection efficiency. We inject simulated transiting planet signals into the pixel data of ~10,000 targets, spanning one year of observations, and process the pixels as normal. We compare the set of detections made by the pipeline with the expectation from the set of simulated planets, and construct a sensitivity curve of signal recovery as a function of the signal-to-noise of the simulated transit signal train. The sensitivity curve does not meet the hypothetical maximum detection efficiency, however it is not as pessimistic as some of the published estimates of the detection efficiency. For the FGK stars in our sample, the sensitivity curve is well fit by a gamma function with the coefficients a = 4.35 and b = 1.05. We also find that the pipeline algorithms recover the depths and periods of the injected signals with very high fidelity, especially for periods longer than 10 days. We perform a simplified occurrence rate calculation using the measured detection efficiency compared to previous assumptions of the detection efficiency found in the literature to demonstrate the systematic error introduced into the resulting occurrence rates. The discrepancies in the calculated occurrence rates may go some way towards reconciling some of the inconsistencies found in the literature.Comment: 13 pages, 7 figures, 1 electronic table, accepted by Ap

Measuring Transit Signal Recovery in the Kepler Pipeline. III. Completeness of the Q1-Q17 DR24 Planet Candidate Catalogue, with Important Caveats for Occurrence Rate Calculations

With each new version of the Kepler pipeline and resulting planet candidate catalogue, an updated measurement of the underlying planet population can only be recovered with an corresponding measurement of the Kepler pipeline detection efficiency. Here, we present measurements of the sensitivity of the pipeline (version 9.2) used to generate the Q1-Q17 DR24 planet candidate catalog (Coughlin et al. 2016). We measure this by injecting simulated transiting planets into the pixel-level data of 159,013 targets across the entire Kepler focal plane, and examining the recovery rate. Unlike previous versions of the Kepler pipeline, we find a strong period dependence in the measured detection efficiency, with longer (>40 day) periods having a significantly lower detectability than shorter periods, introduced in part by an incorrectly implemented veto. Consequently, the sensitivity of the 9.2 pipeline cannot be cast as a simple one-dimensional function of the signal strength of the candidate planet signal as was possible for previous versions of the pipeline. We report on the implications for occurrence rate calculations based on the Q1-Q17 DR24 planet candidate catalog and offer important caveats and recommendations for performing such calculations. As before, we make available the entire table of injected planet parameters and whether they were recovered by the pipeline, enabling readers to derive the pipeline detection sensitivity in the planet and/or stellar parameter space of their choice.Comment: 8 pages, 5 figures, full electronic version of Table 1 available at the NASA Exoplanet Archive; accepted by ApJ May 2nd, 201