In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).
Hypofunction of N-methyl-D-aspartic acid-type glutamate receptors (NMDAR) induced by the systemic administration of NMDAR antagonists is well known to cause schizophrenia-like symptoms in otherwise healthy subjects. However, the brain areas or cell types responsible for the emergence of these symptoms following NMDAR hypofunction remain largely unknown. One possibility, the so-called "GABAergic origin hypothesis," is that NMDAR hypofunction at GABAergic interneurons, in particular, is sufficient for schizophrenia-like effects. In one attempt to address this issue, transgenic mice were generated in which NMDARs were selectively deleted from cortical and hippocampal GABAergic interneurons, a majority of which were parvalbumin (PV)-positive. This manipulation triggered a constellation of phenotypes-from molecular and physiological to behavioral-resembling characteristics of human schizophrenia. Based on these results, and in conjunction with previous literature, we argue that during development, NMDAR hypofunction at cortical, PV-positive, fast-spiking interneurons produces schizophrenia-like effects. This review summarizes the data demonstrating that in schizophrenia, GABAergic (particularly PV-positive) interneurons are disrupted. PV-positive interneurons, many of which display a fast-spiking firing pattern, are critical not only for tight temporal control of cortical inhibition but also for the generation of synchronous membrane-potential gamma-band oscillations. We therefore suggest that in schizophrenia the specific ability of fast-spiking interneurons to control and synchronize disparate cortical circuits is disrupted and that this disruption may underlie many of the schizophrenia symptoms. We further argue that the high vulnerability of corticolimbic fast-spiking interneurons to genetic predispositions and to early environmental insults-including excitotoxicity and oxidative stress-might help to explain their significant contribution to the development of schizophrenia.
Abstract. We consider the restoration of piecewise constant images where the number of the regions and their values are not fixed in advance, with a good difference of piecewise constant values between neighboring regions, from noisy data obtained at the output of a linear operator (e.g., a blurring kernel or a Radon transform). Thus we also address the generic problem of unsupervised segmentation in the context of linear inverse problems. The segmentation and the restoration tasks are solved jointly by minimizing an objective function (an energy) composed of a quadratic data-fidelity term and a nonsmooth nonconvex regularization term. The pertinence of such an energy is ensured by the analytical properties of its minimizers. However, its practical interest used to be limited by the difficulty of the computational stage which requires a nonsmooth nonconvex minimization. Indeed, the existing methods are unsatisfactory since they (implicitly or explicitly) involve a smooth approximation of the regularization term and often get stuck in shallow local minima. The goal of this paper is to design a method that efficiently handles the nonsmooth nonconvex minimization. More precisely, we propose a continuation method where one tracks the minimizers along a sequence of approximate nonsmooth energies {Jε}, the first of which being strictly convex and the last one the original energy to minimize. Knowing the importance of the nonsmoothness of the regularization term for the segmentation task, each Jε is nonsmooth and is expressed as the sum of an 1 regularization term and a smooth nonconvex function. Furthermore, the local minimization of each Jε is reformulated as the minimization of a smooth function subject to a set of linear constraints. The latter problem is solved by the modified primal-dual interior point method, which guarantees the descent direction at each step. Experimental results are presented and show the effectiveness and the efficiency of the proposed method. Comparison with simulated annealing methods further shows the advantage of our method.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.