On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of 1.0 × 10 −21 . It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1σ. The source lies at a luminosity distance of 410 These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger.

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.

Purkinje cells (PCs) of the cerebellar cortex are necessary for controlling movement with precision, but a mechanistic explanation of how the activity of these inhibitory neurons regulates motor output is still lacking. We used an optogenetic approach in awake mice to show for the first time that transiently suppressing spontaneous activity in a population of PCs is sufficient to cause discrete movements that can be systematically modulated in size, speed, and timing depending on how much and how long PC firing is suppressed. We further demonstrate that this fine control of movement kinematics is mediated by a graded disinhibition of target neurons in the deep cerebellar nuclei. Our results prove a long-standing model of cerebellar function and provide the first demonstration that suppression of inhibitory signals can act as a powerful mechanism for the precise control of behavior.

HRQOL among this multiethnic sample ranged from fair to good. Bivariate analysis suggests that ethnic differences in HRQOL exist. However, regression analyses demonstrated that socio-ecological factors in conjunction with medical characteristics are more salient to HRQOL outcomes, and that ethnic group membership may be a proxy for socio-ecological context. Furthermore, the influence of ethnicity, culture, and social-ecology are complex; research with large, population-based samples are necessary to disentangle the impact of contextual factors on HRQOL.

The aim of this study was to test the potential neurotoxicity of three antiepileptic drugs (AEDs), carbamazepine (5H-dibenzepine-5-carboxamide), topiramate [2,3:4,5-bis-O-(1-methylethylidene)-␤-D-fructopyranose sulfamate], and levetiracetam [2-(2-oxopyrrolidin-1-yl)butanamide], in the developing rat brain, when given alone or in combinations. The extent of cell death induced by AEDs was measured in several brain regions of rat pups (postnatal day 8) by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay 24 h after drug treatment. Carbamazepine alone did not increase neurodegeneration when given in doses up to 50 mg/kg, but it induced significant cell death at 100 mg/kg. When combined with phenytoin, carbamazepine, 50 but not 25 mg/kg, significantly exacerbated phenytoin-induced cell death. Although topiramate (20 -80 mg/ kg) alone caused no neurodegeneration, all doses exacerbated phenytoin-induced neurodegeneration. Levetiracetam (250 -1000 mg/kg) alone did not induce cell death, nor did it exacerbate phenytoin-induced neurodegeneration. Of the combinations examined, only that of levetiracetam (250 mg/kg) with carbamazepine (50 mg/kg) did not induce neurodegeneration. Our data underscore the importance of evaluating the safety of combinations of AEDs given during development and not merely extrapolating from the effects of exposure to single drugs. Although carbamazepine and topiramate alone did not induce neuronal death, both drugs exacerbated phenytoin-induced cell death. In contrast, because cotreatment with levetiracetam and carbamazepine did not enhance cell death in the developing brain, it may be possible to avoid proapoptotic effects, even in polytherapy, by choosing appropriate drugs. The latter drugs, as monotherapy or in combination, may be promising candidates for the treatment of women during pregnancy and for preterm and neonatal infants.