Parkinson's disease may disrupt overlapping subthalamic nucleus and pallidal motor networks.

There is an ongoing debate about differential clinical outcome and associated adverse effects of deep brain stimulation (DBS) in Parkinson's disease (PD) targeting the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). Given that functional connectivity profiles suggest beneficial DBS effects within a common network, the empirical evidence about the underlying anatomical circuitry is still scarce. Therefore, we investigate the STN and GPi-associated structural covariance brain patterns in PD patients and healthy controls. We estimate GPi's and STN's whole-brain structural covariance from magnetic resonance imaging (MRI) in a normative mid- to old-age community-dwelling cohort (n = 1184) across maps of grey matter volume, magnetization transfer (MT) saturation, longitudinal relaxation rate (R1), effective transversal relaxation rate (R2*) and effective proton density (PD*). We compare these with the structural covariance estimates in patients with idiopathic PD (n = 32) followed by validation using a reduced size controls' cohort (n = 32). In the normative data set, we observed overlapping spatially distributed cortical and subcortical covariance patterns across maps confined to basal ganglia, thalamus, motor, and premotor cortical areas. Only the subcortical and midline motor cortical areas were confirmed in the reduced size cohort. These findings contrasted with the absence of structural covariance with cortical areas in the PD cohort. We interpret with caution the differential covariance maps of overlapping STN and GPi networks in patients with PD and healthy controls as correlates of motor network disruption. Our study provides face validity to the proposed extension of the currently existing structural covariance methods based on morphometry features to multiparameter MRI sensitive to brain tissue microstructure

Water-line design and performance of Z

A new set of bi-plate transmission lines have been designed and installed in the water-section of PBFA-II for the Z-pinch experiments. Thirty-six aluminum flat-plate transmission lines submerged in a water dielectric deliver a timed electrical pulse from coaxial tube sections to a ring stack section. Each of the lines are electrically isolated from each other by transit-time effects. The water-lines are configured radially at four vertical levels. Each level has nine sets of bi-plates, with a transition section that is unique to that level. Mechanically, the bi-plate sections are designed to carry both static and dynamic loads. Electrically, the lines are designed to transport electrical pulses that average 200 nanoseconds with peak voltage of 2.5 to 3.0 MV. The peak fields exceed 200kV/cm. All line sections are a series of chromate coated aluminum plates, broken down into short, light weight sections. The design of the plates was meticulously developed using the Electro code for voltage break down, and NISA for mechanical analysis. Electrical losses associated with impedance mismatching and voltage breakdown were carefully reviewed. Changes in the bi-plate gap, surface shapes and electrical path discontinuities (mechanical joints) were precisely calculated to achieve maximum electrical performance and reliability. Several iterations of surface shapes and line gaps were reviewed to achieve the most desirable characteristics possible. Additional criteria required that minimal time and effort be required to remove and install the water-lines. Special hardware was developed to help meet this requirement

Polyphenols journey through blood-brain barrier towards neuronal protection

Age-related complications such as neurodegenerative disorders are increasing and remain cureless. The possibility of altering the progression or the development of these multifactorial diseases through diet is an emerging and attractive approach with increasing experimental support. We examined the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to infuence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for diferential transport, likely related to chemical structure. Moreover, endothelial metabolism of these phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies. Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and infammatory injuries and this attenuation of neuroinfammation was achieved via modulation of NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary (poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated infammation and exert neuroprotective efects, with potential for alleviation of neurodegenerative diseases.info:eu-repo/semantics/publishedVersio

Neutrino masses in R-parity violating supersymmetric models

We study neutrino masses and mixing in R-parity violating supersymmetric models with generic soft supersymmetry breaking terms. Neutrinos acquire masses from various sources: Tree level neutrino--neutralino mixing and loop effects proportional to bilinear and/or trilinear R-parity violating parameters. Each of these contributions is controlled by different parameters and have different suppression or enhancement factors which we identified. Within an Abelian horizontal symmetry framework these factors are related and specific predictions can be made. We found that the main contributions to the neutrino masses are from the tree level and the bilinear loops and that the observed neutrino data can be accommodated once mild fine-tuning is allowed.Comment: 18 pages; minor typos corrected. To be published in Physical Review

Optical nanofibers and spectroscopy

We review our recent progress in the production and characterization of tapered optical fibers with a sub-wavelength diameter waist. Such fibers exhibit a pronounced evanescent field and are therefore a useful tool for highly sensitive evanescent wave spectroscopy of adsorbates on the fiber waist or of the medium surrounding. We use a carefully designed flame pulling process that allows us to realize preset fiber diameter profiles. In order to determine the waist diameter and to verify the fiber profile, we employ scanning electron microscope measurements and a novel accurate in situ optical method based on harmonic generation. We use our fibers for linear and non-linear absorption and fluorescence spectroscopy of surface-adsorbed organic molecules and investigate their agglomeration dynamics. Furthermore, we apply our spectroscopic method to quantum dots on the surface of the fiber waist and to caesium vapor surrounding the fiber. Finally, towards dispersive measurements, we present our first results on building and testing a single-fiber bi-modal interferometer.Comment: 13 pages, 18 figures. Accepted for publication in Applied Physics B. Changes according to referee suggestions: changed title, clarification of some points in the text, added references, replacement of Figure 13

Solar Neutrino Masses and Mixing from Bilinear R-Parity Broken Supersymmetry: Analytical versus Numerical Results

We give an analytical calculation of solar neutrino masses and mixing at one-loop order within bilinear R-parity breaking supersymmetry, and compare our results to the exact numerical calculation. Our method is based on a systematic perturbative expansion of R-parity violating vertices to leading order. We find in general quite good agreement between approximate and full numerical calculation, but the approximate expressions are much simpler to implement. Our formalism works especially well for the case of the large mixing angle MSW solution (LMA-MSW), now strongly favoured by the recent KamLAND reactor neutrino data.Comment: 34 pages, 14 ps figs, some clarifying comments adde

Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban

Background In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients. Objectives To evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. Patients/Methods In this nested case-control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4-week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type. Results Twenty-four cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01-12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5-16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1-1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5-3.5). Conclusion Advanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power.Thrombosis and Hemostasi

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern