Thalamocortical relationship in epileptic patients with generalized spike and wave discharges — A multimodal neuroimaging study

AbstractUnlike focal or partial epilepsy, which has a confined range of influence, idiopathic generalized epilepsy (IGE) often affects the whole or a larger portion of the brain without obvious, known cause. It is important to understand the underlying network which generates epileptic activity and through which epileptic activity propagates. The aim of the present study was to investigate the thalamocortical relationship using non-invasive imaging modalities in a group of IGE patients. We specifically investigated the roles of the mediodorsal nuclei in the thalami and the medial frontal cortex in generating and spreading IGE activities. We hypothesized that the connectivity between these two structures is key in understanding the generation and propagation of epileptic activity in brains affected by IGE. Using three imaging techniques of EEG, fMRI and EEG-informed fMRI, we identified important players in generation and propagation of generalized spike-and-wave discharges (GSWDs). EEG-informed fMRI suggested multiple regions including the medial frontal area near to the anterior cingulate cortex, mediodorsal nuclei of the thalamus, caudate nucleus among others that related to the GSWDs. The subsequent seed-based fMRI analysis revealed a reciprocal cortical and bi-thalamic functional connection. Through EEG-based Granger Causality analysis using (DTF) and adaptive DTF, within the reciprocal thalamocortical circuitry, thalamus seems to serve as a stronger source in driving cortical activity from initiation to the propagation of a GSWD. Such connectivity change starts before the GSWDs and continues till the end of the slow wave discharge. Thalamus, especially the mediodorsal nuclei, may serve as potential targets for deep brain stimulation to provide more effective treatment options for patients with drug-resistant generalized epilepsy

Lifshitz-like space-time from intersecting branes in string/M theory

We construct 1/4 BPS, threshold F-D$p$ bound states (with $0\leq p \leq 5$) of type II string theories by applying S- and T-dualities to the D1-D5 system of type IIB string theory. These are different from the known 1/2 BPS, non-threshold F-D$p$ bound states. The near horizon limits of these solutions yield Lifshitz-like space-times with varying dynamical critical exponent $z=2(5-p)/(4-p)$, for $p\neq 4$, along with the hyperscaling violation exponent $\theta = p - (p-2)/(4-p)$, showing how Lifshitz-like space-time can be obtained from string theory. The dilatons are in general non-constant (except for $p=1$). We discuss the holographic RG flows and the phase structures of these solutions. For $p=4$, we do not get a Lifshitz-like space-time, but the near horizon limit in this case leads to an AdS$_2$ space.Comment: 20 pages, no figure, v2: proper identification of hyperscaling violation exponent has been made, abstract and the text has been changed accordingly, note added, v3: minor changes, refs added, version to appear in JHE

Three geographically separate domestications of Asian rice

Domesticated rice (Oryza sativa L.) accompanied the dawn of Asian civilization(1) and has become one of world's staple crops. From archaeological and genetic evidence various contradictory scenarios for the origin of different varieties of cultivated rice have been proposed, the most recent based on a single domestication(2,3). By examining the footprints of selection in the genomes of different cultivated rice types, we show that there were three independent domestications in different parts of Asia. We identify wild populations in southern China and the Yangtze valley as the source of the japonica gene pool, and populations in Indochina and the Brahmaputra valley as the source of the indica gene pool. We reveal a hitherto unrecognized origin for the aus variety in central India or Bangladesh. We also conclude that aromatic rice is a result of a hybridization between japonica and aus, and that the tropical and temperate versions of japonica are later adaptations of one crop. Our conclusions are in accord with archaeological evidence that suggests widespread origins of rice cultivation(1,4). We therefore anticipate that our results will stimulate a more productive collaboration between genetic and archaeological studies of rice domestication, and guide utilization of genetic resources in breeding programmes aimed at crop improvement.European Research Council [339941]info:eu-repo/semantics/publishedVersio

The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study (ANA-LIS): 5 year results of a Randomized Controlled Trial

PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in subjects diagnosed as primary angle closure suspects (PACS) DESIGN: Prospective, randomized controlled trial PARTICIPANTS: This multi-center, randomized controlled trial (NCT00347178, Clinical trials.gov) enrolled 480 subjects over the age of 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each subject underwent prophylactic LPI in one randomly selected eye, while the fellow eye served as control. Subjects were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC, defined as presence of peripheral anterior synechiae, and/or intraocular pressure>21 mmHg or acute angle closure [AAC]) or PACG over 5 years. RESULTS: Of the 480 randomized subjects, the majority were Chinese (92.7%) and female (75.8%) with mean age of 62.8±6.9 years. LPI-treated eyes reached endpoint less frequently after five years (24, 5.0%, incidence rate [IR]=11.65 per 1000 eye-years) compared to control eyes (45, 9.4%, IR=21.84 per 1000 eye-years, p=0.001). The adjusted hazards ratio (HR) for progression to PAC was 0.55 (95%CI: 0.37-0.83, p=0.004) in LPI-treated eyes compared to control eyes. Older subjects (per year, HR=1.06, 95%CI: 1.03-1.10, p<0.001) and eyes with higher baseline IOP (per mm Hg, HR=1.35, 95%CI: 1.22-1.50, p<0.0001) were more likely to reach an endpoint. The number needed to treat in order to prevent an endpoint was 22 (95%CI: 12.8-57.5). CONCLUSIONS: In subjects with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI had significantly fewer endpoints compared to control eyes over 5 years. However, the overall incidence of PAC or PACG was low

Δ\Delta-scaling and Information Entropy in Ultra-Relativistic Nucleus-Nucleus Collisions

The $\Delta$-scaling method has been applied to ultra-relativistic p+p, C+C and Pb+Pb collision data simulated using a high energy Monte Carlo package, LUCIAE 3.0. The $\Delta$-scaling is found to be valid for some physical variables, such as charged particle multiplicity, strange particle multiplicity and number of binary nucleon-nucleon collisions from these simulated nucleus-nucleus collisions over an extended energy ranging from $E_{lab}$ = 20 to 200 A GeV. In addition we derived information entropy from the multiplicity distribution as a function of beam energy for these collisions.Comment: 4 pages, 4 figures, 1 table; to appear in the July Issue of Chin. Phys. Lett.. Web Page: http://www.iop.org/EJ/journal/CP

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

In Situ Ambient Pressure X-ray Photoelectron Spectroscopy Studies of Lithium-Oxygen Redox Reactions

The lack of fundamental understanding of the oxygen reduction and oxygen evolution in nonaqueous electrolytes significantly hinders the development of rechargeable lithium-air batteries. Here we employ a solid-state Li4+xTi5O12/LiPON/LixV2O5 cell and examine in situ the chemistry of Li-O2 reaction products on LixV2O5 as a function of applied voltage under ultra high vacuum (UHV) and at 500 mtorr of oxygen pressure using ambient pressure X-ray photoelectron spectroscopy (APXPS). Under UHV, lithium intercalated into LixV2O5 while molecular oxygen was reduced to form lithium peroxide on LixV2O5 in the presence of oxygen upon discharge. Interestingly, the oxidation of Li2O2 began at much lower overpotentials (~240 mV) than the charge overpotentials of conventional Li-O2 cells with aprotic electrolytes (~1000 mV). Our study provides the first evidence of reversible lithium peroxide formation and decomposition in situ on an oxide surface using a solid-state cell, and new insights into the reaction mechanism of Li-O2 chemistry.National Science Foundation (U.S.) (Materials Research Science and Engineering Center (MRSEC) Program, Award DMR-0819762)United States. Dept. of Energy (Assistant Secretary for Energy Efficiency and Renewable Energy, Office of FreedomCAR and Vehicle Technologies of the U. S. Department of Energy under contract no. DE-AC03-76SF00098)Lawrence Berkeley National LaboratoryUnited States. Dept. of Energy (Office of Basic Energy Sciences, Materials Sciences and Engineering

Solving monotone stochastic variational inequalities and complementarity problems by progressive hedging

The concept of a stochastic variational inequality has recently been articulated in a new way that is able to cover, in particular, the optimality conditions for a multistage stochastic programming problem. One of the long-standing methods for solving such an optimization problem under convexity is the progressive hedging algorithm. That approach is demonstrated here to be applicable also to solving multistage stochastic variational inequality problems under monotonicity, thus increasing the range of applications for progressive hedging. Stochastic complementarity problems as a special case are explored numerically in a linear two-stage formulation

Benchmarking the Self-Assembly of Surfactin Biosurfactant at the Liquid–Air Interface to those of Synthetic Surfactants

The adsorption of surfactin, a lipopeptide biosurfactant, at the liquid–air interface has been investigated in this work. The maximum adsorption density and the nature and the extent of lateral interaction between the adsorbed surfactin molecules at the interface were estimated from surface tension data using the Frumkin model. The quantitative information obtained using the Frumkin model was also compared to those obtained using the Gibbs equation and the Langmuir–Szyszkowski model. Error analysis showed a better agreement between the experimental and the calculated values using the Frumkin model relative to the other two models. The adsorption of surfactin at the liquid–air interface was also compared to those of synthetic anionic, sodium dodecylbenzenesulphonate (SDBS), and nonionic, octaethylene glycol monotetradecyl ether (C14E8), surfactants. It has been estimated that the area occupied by a surfactin molecule at the interface is about 3- and 2.5-fold higher than those occupied by SDBS and C14E8 molecules, respectively. The interaction between the adsorbed molecules of the anionic biosurfactant (surfactin) was estimated to be attractive, unlike the mild repulsive interaction between the adsorbed SDBS molecules

Focus on vulnerable populations and promoting equity in health service utilization ––an analysis of visitor characteristics and service utilization of the Chinese community health service

Background Community health service in China is designed to provide a convenient and affordable primary health service for the city residents, and to promote health equity. Based on data from a large national study of 35 cities across China, we examined the characteristics of the patients and the utilization of community health institutions (CHIs), and assessed the role of community health service in promoting equity in health service utilization for community residents. Methods Multistage sampling method was applied to select 35 cities in China. Four CHIs were randomly chosen in every district of the 35 cities. A total of 88,482 visitors to the selected CHIs were investigated by using intercept survey method at the exit of the CHIs in 2008, 2009, 2010, and 2011. Descriptive analyses were used to analyze the main characteristics (gender, age, and income) of the CHI visitors, and the results were compared with that from the National Health Services Survey (NHSS, including CHIs and higher levels of hospitals). We also analyzed the service utilization and the satisfactions of the CHI visitors. Results The proportions of the children (2.4%) and the elderly (about 22.7%) were lower in our survey than those in NHSS (9.8% and 38.8% respectively). The proportion of the low-income group (26.4%) was apparently higher than that in NHSS (12.5%). The children group had the lowest satisfaction with the CHIs than other age groups. The satisfaction of the low-income visitors was slightly higher than that of the higher-income visitors. The utilization rate of public health services was low in CHIs. Conclusions The CHIs in China appears to fulfill the public health target of uptake by vulnerable populations, and may play an important role in promoting equity in health service utilization. However, services for children and the elderly should be strengthened