Cellular antiseizure mechanisms of everolimus in pediatric tuberous sclerosis complex, cortical dysplasia, and non-mTOR-mediated etiologies.

The present study was designed to examine the potential cellular antiseizure mechanisms of everolimus, a mechanistic target of rapamycin (mTOR) pathway blocker, in pediatric epilepsy cases. Cortical tissue samples obtained from pediatric patients (n = 11, ages 0.67-6.75 years) undergoing surgical resections for the treatment of their pharmacoresistant epilepsy were examined electrophysiologically in ex vivo slices. The cohort included mTOR-mediated pathologies (tuberous sclerosis complex [TSC] and severe cortical dysplasia [CD]) as well as non-mTOR-mediated pathologies (tumor and perinatal infarct). Bath application of everolimus (2 μm) had practically no effect on spontaneous inhibitory postsynaptic activity. In contrast, long-term application of everolimus reduced spontaneous excitatory postsynaptic activity, burst discharges induced by blockade of γ-aminobutyric acid A (GABAA) receptors, and epileptiform activity generated by 4-aminopyridine, a K+ channel blocker. The antiseizure effects were more pronounced in TSC and CD cases, whereas in non-mTOR-mediated pathologies, the effects were subtle at best. These results support further clinical trials of everolimus in mTOR pathway-mediated pathologies and emphasize that the effects require sustained exposure over time

Nav1.7 expression is increased in painful human dental pulp

© 2008 Luo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Better Health While You Wait: A Controlled Trial of a Computer-Based Intervention for Screening and Health Promotion in the Emergency Department

Study objective: We evaluate a computer-based intervention for screening and health promotion in the emergency department and determine its effect on patient recall of health advice. Methods: This controlled clinical trial, with alternating assignment of patients to a computer intervention (prevention group) or usual care, was conducted in a university hospital ED. The study group consisted of 542 adult patients with nonurgent conditions. The study intervention was a self-administered computer survey generating individualized health information. Outcome measures were (1) patient willingness to take a computerized health risk assessment, (2) disclosure of behavioral risk factors, (3) requests for health information, and (4) remembered health advice. Results: Eighty-nine percent (470/542) of eligible patients participated. Ninety percent were black. Eighty-five percent (210/248) of patients in the prevention group disclosed 1 or more major behavioral risk factors including current smoking (79/248; 32%), untreated hypertension (28/248; 13%), problem drinking (46/248; 19%), use of street drugs (33/248; 13%), major depression (87/248; 35%), unsafe sexual behavior (84/248; 33%), and several other injury-prone behaviors. Ninety-five percent of patients in the prevention group requested health information. On follow-up at 1 week, 62% (133/216) of the prevention group patients compared with 27% (48/180) of the control subjects remembered receiving advice on what they could do to improve their health (relative risk 2.3, 95% confidence interval 1.77 to 3.01). Conclusion: Using a self-administered computer-based health risk assessment, the majority of patients in our urban ED disclosed important health risks and requested information. They were more likely than a control group to remember receiving advice on what they could do to improve their health. Computer methodology may enable physicians to use patient waiting time for health promotion and to target at-risk patients for specific interventions

Supplementary materials: Holocene evolution of parabolic dunes, White River Badlands, South Dakota, USA, revealed by high-resolution mapping

The data paper includes supplementary figures from geomorphological analysis of dunes in the White River Badlands. These figures provide additional information to readers of the paper of this name. White River Badlands (WRB) of South Dakota record aeolian activity spanning late Pleistocene through latest Holocene (21 ka to modern), reflecting the effects of the last glacial period and Holocene climate fluctuations (i.e. Holocene Thermal Maximum, Medieval Climate Anomaly, and Little Ice Age). The WRB are important to paleoclimate studies because of the scarcity of climate proxies in the area. The goal of this study is to use 1 m/pixel resolution digital elevation models (DEMs) to distinguish early to middle Holocene parabolic dunes from late Holocene parabolic dunes. Results indicate that dunes are distinguished by slope and terrain ruggedness index or roughness. Differences are attributed to post-depositional wind erosion, soil formation, and mass wasting. Early to middle Holocene and late Holocene paleowind directions, 324˚± 13.1˚ (N=7) and 323˚ ± 3.0˚ (N = 19) respectively, are indistinguishable and like the modern wind regime. Results suggest that the landscape has significant resilience to wind erosion, which resulted in preservation of a mosaic of early and late parabolic dune. Quantification of differences in dune roughness will help refine the chronology of aeolian activity in the WRB, provide insight into drought-driven landscape evolution, and put activity in the WRB in a regional perspective

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Software systems for operation, control, and monitoring of the EBEX instrument

We present the hardware and software systems implementing autonomous operation, distributed real-time monitoring, and control for the EBEX instrument. EBEX is a NASA-funded balloon-borne microwave polarimeter designed for a 14 day Antarctic flight that circumnavigates the pole. To meet its science goals the EBEX instrument autonomously executes several tasks in parallel: it collects attitude data and maintains pointing control in order to adhere to an observing schedule; tunes and operates up to 1920 TES bolometers and 120 SQUID amplifiers controlled by as many as 30 embedded computers; coordinates and dispatches jobs across an onboard computer network to manage this detector readout system; logs over 3~GiB/hour of science and housekeeping data to an onboard disk storage array; responds to a variety of commands and exogenous events; and downlinks multiple heterogeneous data streams representing a selected subset of the total logged data. Most of the systems implementing these functions have been tested during a recent engineering flight of the payload, and have proven to meet the target requirements. The EBEX ground segment couples uplink and downlink hardware to a client-server software stack, enabling real-time monitoring and command responsibility to be distributed across the public internet or other standard computer networks. Using the emerging dirfile standard as a uniform intermediate data format, a variety of front end programs provide access to different components and views of the downlinked data products. This distributed architecture was demonstrated operating across multiple widely dispersed sites prior to and during the EBEX engineering flight.Comment: 11 pages, to appear in Proceedings of SPIE Astronomical Telescopes and Instrumentation 2010; adjusted metadata for arXiv submissio

EBEX: A balloon-borne CMB polarization experiment

EBEX is a NASA-funded balloon-borne experiment designed to measure the polarization of the cosmic microwave background (CMB). Observations will be made using 1432 transition edge sensor (TES) bolometric detectors read out with frequency multiplexed SQuIDs. EBEX will observe in three frequency bands centered at 150, 250, and 410 GHz, with 768, 384, and 280 detectors in each band, respectively. This broad frequency coverage is designed to provide valuable information about polarized foreground signals from dust. The polarized sky signals will be modulated with an achromatic half wave plate (AHWP) rotating on a superconducting magnetic bearing (SMB) and analyzed with a fixed wire grid polarizer. EBEX will observe a patch covering ~1% of the sky with 8' resolution, allowing for observation of the angular power spectrum from \ell = 20 to 1000. This will allow EBEX to search for both the primordial B-mode signal predicted by inflation and the anticipated lensing B-mode signal. Calculations to predict EBEX constraints on r using expected noise levels show that, for a likelihood centered around zero and with negligible foregrounds, 99% of the area falls below r = 0.035. This value increases by a factor of 1.6 after a process of foreground subtraction. This estimate does not include systematic uncertainties. An engineering flight was launched in June, 2009, from Ft. Sumner, NM, and the long duration science flight in Antarctica is planned for 2011. These proceedings describe the EBEX instrument and the North American engineering flight.Comment: 12 pages, 9 figures, Conference proceedings for SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010

Nearby quasar remnants and ultra-high energy cosmic rays

As recently suggested, nearby quasar remnants are plausible sites of black-hole based compact dynamos that could be capable of accelerating ultra-high energy cosmic rays (UHECRs). In such a model, UHECRs would originate at the nuclei of nearby dead quasars, those in which the putative underlying supermassive black holes are suitably spun-up. Based on galactic optical luminosity, morphological type, and redshift, we have compiled a small sample of nearby objects selected to be highly luminous, bulge-dominated galaxies, likely quasar remnants. The sky coordinates of these galaxies were then correlated with the arrival directions of cosmic rays detected at energies $> 40$ EeV. An apparently significant correlation appears in our data. This correlation appears at closer angular scales than those expected when taking into account the deflection caused by typically assumed IGM or galactic magnetic fields over a charged particle trajectory. Possible scenarios producing this effect are discussed, as is the astrophysics of the quasar remnant candidates. We suggest that quasar remnants be also taken into account in the forthcoming detailed search for correlations using data from the Auger Observatory.Comment: 2 figures, 4 tables, 11 pages. Final version to appear in Physical Review