Intelligence functions disorders in patients with complex partial epilepsy

Objective: To compare the performance of patients with complex partial epilepsy with the normal controls in the subtests of an instrument used to assess intelligence function. Method: Fifty epileptic patients, whose ages ranged from 19 to 49 years and 20 normal controls without any neuropsychiatric disorders. The Wechsler-Bellevue adult intelligence test was applied in groups, epileptic patients and control subjects. This test is composed of several subtests that assess specific cognitive functions. A statistical analysis was performed using non-parametric tests. Results: All the Wechsler-Bellevue subtests revealed that the intelligence functions of the patients were significantly inferior to that of the controls (p<0.05). This performance was supported by the patient's complaints in relation to their cognitive performance. Conclusion: Patients with complex partial epilepsy presented poorer results in the intelligence test when compared with individuals without neuropsychiatric disorders.62498398

An Optical Counterpart to the Anomalous X-ray Pulsar 4U 0142+61

The energy source of the anomalous X-ray pulsars is not well understood, hence their designation as anomalous. Unlike binary X-ray pulsars, no companions are seen, so the energy cannot be supplied by accretion of matter from a companion star. The loss of rotational energy, which powers radio pulsars, is insufficient to power AXPs. Two models are generally considered: accretion from a large disk left over from the birth process, or decay of a very strong magnetic field (10^15 G) associated with a 'magnetar'. The lack of counterparts at other wavelengths has hampered progress in our understanding of these objects. Here, we present deep optical observations of the field around 4U 0142+61, which is the brightest AXP in X-rays. We find an object with peculiar optical colours at the position of the X-ray source, and argue that it is the optical counterpart. The optical emission is too faint to admit the presence of a large accretion disk, but may be consistent with magnetospheric emission from a magnetar.Comment: 16 pages, 3 figures, accepted by Nature. Press embargo until 1900 hrs London time (GMT) on 6 December 200

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.&lt;/p&gt

Effects of intermediate scales on renormalization group running of fermion observables in an SO(10) model

In the context of non-supersymmetric SO(10) models, we analyze the renormalization group equations for the fermions (including neutrinos) from the GUT energy scale down to the electroweak energy scale, explicitly taking into account the effects of an intermediate energy scale induced by a Pati--Salam gauge group. To determine the renormalization group running, we use a numerical minimization procedure based on a nested sampling algorithm that randomly generates the values of 19 model parameters at the GUT scale, evolves them, and finally constructs the values of the physical observables and compares them to the existing experimental data at the electroweak scale. We show that the evolved fermion masses and mixings present sizable deviations from the values obtained without including the effects of the intermediate scale.Comment: Comments: 20 pages, 3 figures. Final version published in JHE

Fluid-structure interaction simulation of prosthetic aortic valves : comparison between immersed boundary and arbitrary Lagrangian-Eulerian techniques for the mesh representation

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results

Systemic delivery and SPECT/CT in vivo imaging of 125I-labelled oncolytic adenoviral mutants in models of pancreatic cancer.

Early phase clinical trials have demonstrated good therapeutic index for oncolytic adenoviruses in patients with solid tumours when administered intratumorally, resulting in local tumour elimination. Entrapment and binding of adenovirus to erythrocytes, blood factors, and neutralising antibodies have prevented efficient systemic delivery and targeting of distant lesions in the clinic. We previously generated the novel replication-selective Ad-3∆-A20T to improve tumour targeting by increasing the viral dose at distant sites. Here, we developed a protocol to directly radiolabel the virus for rapid and sensitive detection by single-photon emitted computed tomography (SPECT/CT) providing a convenient method for determining biodistribution following intravenous administration in murine models. Longitudinal whole-body scans, demonstrated efficient viral uptake in pancreatic Suit-2 and Panc04.03 xenografts with trace amounts of 125I-Ad-3∆-A20T up to 48 h after tail vein delivery. Hepatic and splenic radioactivity decreased over time. Analysis of tissues harvested at the end of the study, confirmed potency and selectivity of mutant viruses. Ad-3∆-A20T-treated animals showed higher viral genome copy numbers and E1A gene expression in tumors than in liver and spleen compared to Ad5wt. Our direct radiolabeling approach, allows for immediate screening of novel oncolytic adenoviruses and selection of optimal viral genome alterations to generate improved mutants

Ergodic properties of quasi-Markovian generalized Langevin equations with configuration dependent noise and non-conservative force

We discuss the ergodic properties of quasi-Markovian stochastic differential equations, providing general conditions that ensure existence and uniqueness of a smooth invariant distribution and exponential convergence of the evolution operator in suitably weighted $L^{\infty}$ spaces, which implies the validity of central limit theorem for the respective solution processes. The main new result is an ergodicity condition for the generalized Langevin equation with configuration-dependent noise and (non-)conservative force

Accreting Black Holes

This chapter provides a general overview of the theory and observations of black holes in the Universe and on their interpretation. We briefly review the black hole classes, accretion disk models, spectral state classification, the AGN classification, and the leading techniques for measuring black hole spins. We also introduce quasi-periodic oscillations, the shadow of black holes, and the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin note: substantial text overlap with arXiv:1711.1025

Enhancement of Naringenin Bioavailability by Complexation with Hydroxypropoyl-β-Cyclodextrin

The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβCD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and Cmax increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (K01DK080241)Harvard Clinical Nutrition Research Center (P30-DK040561)European Research Council (Starting Grant (TMIHCV 242699))Massachusetts General Hospital (BioMEMS Resource Center (P41 EB-002503))Alexander Silberman Institute of Life Science

N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease

BACKGROUND: Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory. METHODS: We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects. RESULTS: Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12–1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9–1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well. CONCLUSION: We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD