Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. KEY FINDINGS: In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (/dL) and ESL 1200 mg QD (/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. SIGNIFICANCE: These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations

The Impact of Forensic vs. Social-Science Evidence on Judicial Decisions to Grant a Writ of Habeas Corpus

Wrongful conviction is a serious dilemma for the criminal-justice system. A joint investigation by the Better Government Association and the Center on Wrongful Convictions tracked exonerations from 1989 through 2010 and identified 85 people who were wrongfully incarcerated.1 Not only were those 85 lives unfairly affected in serious ways due to the incarceration, but the actual perpetrators continued on crime sprees that went on to include 14 murders, 11 sexual assaults, 10 kidnappings, and at least 62 other felonies.2 The reversal of false convictions is becoming more frequent.3 However, scholars have asserted that the exonerations that do occur are probably a small fraction of actual wrongful convictions. Gross and colleagues pointed out that “[o]ur legal system places great weight on the finality of criminal convictions. Courts and prosecutors are exceedingly reluctant to reverse judgments or reconsider closed cases; when they do—and it’s rare—it’s usually because of a compelling showing of error.”4 Therefore, in order for a wrongful conviction to be overturned, these cases must undergo a lengthy appeals process

Predictors of contemporary coronary artery bypass grafting outcomes

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Quasar Clustering from SDSS DR5: Dependences on Physical Properties

Using a homogenous sample of 38,208 quasars with a sky coverage of $4000 {\rm deg^2}$ drawn from the SDSS Data Release Five quasar catalog, we study the dependence of quasar clustering on luminosity, virial black hole mass, quasar color, and radio loudness. At $z<2.5$, quasar clustering depends weakly on luminosity and virial black hole mass, with typical uncertainty levels $\sim 10$ for the measured correlation lengths. These weak dependences are consistent with models in which substantial scatter between quasar luminosity, virial black hole mass and the host dark matter halo mass has diluted any clustering difference, where halo mass is assumed to be the relevant quantity that best correlates with clustering strength. However, the most luminous and most massive quasars are more strongly clustered (at the $\sim 2\sigma$ level) than the remainder of the sample, which we attribute to the rapid increase of the bias factor at the high-mass end of host halos. We do not observe a strong dependence of clustering strength on quasar colors within our sample. On the other hand, radio-loud quasars are more strongly clustered than are radio-quiet quasars matched in redshift and optical luminosity (or virial black hole mass), consistent with local observations of radio galaxies and radio-loud type 2 AGN. Thus radio-loud quasars reside in more massive and denser environments in the biased halo clustering picture. Using the Sheth et al.(2001) formula for the linear halo bias, the estimated host halo mass for radio-loud quasars is $\sim 10^{13} h^{-1}M_\odot$, compared to $\sim 2\times 10^{12} h^{-1}M_\odot$ for radio-quiet quasar hosts at $z\sim 1.5$.Comment: Updated version; accepted for publication in Ap

Easing the transition to secondary education for children with autism spectrum disorder: An evaluation of the Systemic Transition in Education Programme for Autism Spectrum Disorder (STEP-ASD)

In mainstream education, the transition from primary to secondary school ('school transition') is difficult for children with autism spectrum disorder, being marked by high levels of emotional and behavioural difficulties. The Systemic Transition in Education Programme for Autism Spectrum Disorder (STEP-ASD) is a new, manualised school transition intervention. We investigated its feasibility and efficacy for children diagnosed with autism spectrum disorder (N = 37; mean age = 11.47 years; mean IQ = 85.24) using an unblinded, non-randomised, controlled design. Teachers found the intervention feasible and acceptable. Children receiving STEP-ASD (n = 17) showed a large (Cohen's d = 0.88) reduction in school-reported emotional and behavioural difficulties, whereas controls (n = 20) showed a slight increase (d = -0.1) (p = 0.010). These encouraging findings suggest the value of STEP-ASD as a low-intensity intervention for reducing problem behaviours and distress in children with autism spectrum disorder as they transition to mainstream secondary school

The UCLA Study of Children with Moderate-to-Severe Traumatic Brain Injury: Event-Related Potential Measure of Interhemispheric Transfer Time

Traumatic brain injury (TBI) frequently results in diffuse axonal injury and other white matter damage. The corpus callosum (CC) is particularly vulnerable to injury following TBI. Damage to this white matter tract has been associated with impaired neurocognitive functioning in children with TBI. Event-related potentials can identify stimulus-locked neural activity with high temporal resolution. They were used in this study to measure interhemispheric transfer time (IHTT) as an indicator of CC integrity in 44 children with moderate/severe TBI at 3-5 months post-injury, compared with 39 healthy control children. Neurocognitive performance also was examined in these groups. Nearly half of the children with TBI had IHTTs that were outside the range of the healthy control group children. This subgroup of TBI children with slow IHTT also had significantly poorer neurocognitive functioning than healthy controls-even after correction for premorbid intellectual functioning. We discuss alternative models for the relationship between IHTT and neurocognitive functioning following TBI. Slow IHTT may be a biomarker that identifies children at risk for poor cognitive functioning following moderate/severe TBI

Publisher Correction: Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma.

The original version of this Article omitted Suzana A. Kahn, Siddhartha S. Mitra &amp; Samuel H. Cheshier as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article

Preliminary Target Selection for the DESI Milky Way Survey (MWS)

International audienceThe DESI Milky Way Survey (MWS) will observe $\ge$8 million stars between $16 < r < 19$ mag, supplemented by observations of brighter targets under poor observing conditions. The survey will permit an accurate determination of stellar kinematics and population gradients; characterize diffuse substructure in the thick disk and stellar halo; enable the discovery of extremely metal-poor stars and other rare stellar types; and improve constraints on the Galaxy's 3D dark matter distribution from halo star kinematics. MWS will also enable a detailed characterization of the stellar populations within 100 pc of the Sun, including a complete census of white dwarfs. The target catalog from the preliminary selection described here is public

Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma

A major limitation of targeted cancer therapy is the rapid emergence of drug resistance, which often arises through mutations at or downstream of the drug target or through intrinsic resistance of subpopulations of tumor cells. Medulloblastoma (MB), the most common pediatric brain tumor, is no exception, and MBs that are driven by sonic hedgehog (SHH) signaling are particularly aggressive and drug-resistant. To find new drug targets and therapeutics for MB that may be less susceptible to common resistance mechanisms, we used a developmental phosphoproteomics approach in murine granule neuron precursors (GNPs), the developmental cell of origin of MB. The protein kinase CK2 emerged as a driver of hundreds of phosphorylation events during the proliferative, MB-like stage of GNP growth, including the phosphorylation of three of the eight proteins commonly amplified in MB. CK2 was critical to the stabilization and activity of the transcription factor GLI2, a late downstream effector in SHH signaling. CK2 inhibitors decreased the viability of primary SHH-type MB patient cells in culture and blocked the growth of murine MB tumors that were resistant to currently available Hh inhibitors, thereby extending the survival of tumor-bearing mice. Because of structural interactions, one CK2 inhibitor (CX-4945) inhibited both wild-type and mutant CK2, indicating that this drug may avoid at least one common mode of acquired resistance. These findings suggest that CK2 inhibitors may be effective for treating patients with MB and show how phosphoproteomics may be used to gain insight into developmental biology and pathology