The spatial resolution of conventional transcranial direct current stimulation (tDCS) is considered to be relatively diffuse owing to skull dispersion. However, here we show that electric fields may be clustered at distinct gyri/sulci sites due to details in tissue architecture/conductivity notably cerebrospinal fluid (CSF). We calculated the cortical electric field/current density magnitude induced during tDCS using a high spatial resolution (1 mm3) MRI-derived finite element human head model; cortical gyri/sulci were resolved. The spatial focality of conventional rectangular-pad (7 × 5 cm2) and the ring (4 × 1) electrode configurations were compared. The rectangular-pad configuration resulted in diffuse (un-focal) modulation, with discrete clusters of electric field magnitude maxima. Peak induced electric field magnitude was not observed directly underneath the pads, but at an intermediate lobe. The 4 × 1 ring resulted in enhanced spatial focality, with peak induced electric field magnitude at the sulcus and adjacent gyri directly underneath the active electrode. Cortical structures may be focally targeted using ring configurations. Anatomically accurate high resolution MRI-based forward-models may guide the ‘rational’ clinical design and optimization of tDCS.

Transcutaneous electrical stimulation is applied in a range of biomedical applications including Transcranial Direct Current Stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-Definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes.The purpose of this study was to design and optimize "high-definition" electrode-gel parameters for electrode durability, skin safety, and subjective pain. Anode and cathode electrode potential, temperature, pH, and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 minutes on agar gel or subject forearms. A selection of 5 types of solidconductors (Ag pellet, Ag/AgCl pellet, Rubber pellet, Ag/AgCl ring, and Ag/AgCl disc) and 7 conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron, and CCNY-4) were investigated.The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and Rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, Rubber, and Ag/AgCl pellet electrodes across all gels.

In this study, we tested whether estrogen deficiency is associated with oxidative stress and decreased nitric oxide (NO) production, which could be responsible for an increased blood pressure in ovariectomized rats. Hemodynamic studies were performed on conscious, chronically instrumented rats. Chronic estrogen replacement on ovariectomized rats lowered blood pressure approximately 13 mmHg, from 119 +/- 3 mmHg in ovariectomized rats to 106 +/- 3 mmHg in ovariectomized-treated rats; it was also accompanied by an increase in cardiac index and vascular conductance, achieving hemodynamic values similar to those shown by sham-operated rats. N(G)-nitro-L-arginine methyl ester administration lowered significantly less the vascular conductance (0.14 +/- 0.01 vs. 0.22 +/- 0.03 and 0.26 +/- 0.01 ml. min(-1). mmHg(-1)/100 g; P < 0.05) in ovariectomized rats than in the sham-operated and estrogen-treated ovariectomized rats, respectively. Estrogen replacement prevented the lower plasma levels of nitrites/nitrates observed in ovariectomized rats. The lower plasma total antioxidant status and reduced thiol groups and the increase in plasma lipoperoxides presented in ovariectomized animals were reestablished with the estrogen treatment. These results show that estrogen administration decreases blood pressure and increases vascular conductance in ovariectomized rats. This effect may be related to an increase in NO synthesis and/or preventing oxidative stress, then improving endothelial function.

Journal article"Due to the hydrological and socio-economic complexity of water use within river basins and even sub-basins, it is a considerable challenge to manage water resources in an efficient, equitable and sustainable way. This paper shows that multi-agent simulation (MAS) is a promising approach to better understand the complexity of water uses and water users within sub-basins. This approach is especially suitable to take the collective action into account when simulating the outcome of technical innovation and policy change. A case study from Chile is used as an example to demonstrate the potential of the MAS framework. Chile has played a pioneering role in water policy reform by privatizing water rights and promoting trade in such rights, devolving irrigation management authority to user groups, and privatizing the provision of irrigation infrastructure. The paper describes the different components of a MAS model developed for four micro-watersheds in the Maule river basin. Preliminary results of simulation experiments are presented, which show the impacts of technical change and of informal rental markets on household income and water use efficiency. The paper also discusses how the collective action problems in water markets and in small-scale and large-scale infrastructure provision can be captured by the MAS model. To promote the use of the MAS approach for planning purposes, a collaborative research and learning framework has been established, with a recently created multi-stakeholder platform at the regional level (Comisión Regional de Recursos Hidricos) as the major partner. Finally, the paper discusses the potentials of using MAS models for water resources management, such as increasing transparency as an aspect of good governance. The challenges, for example the need to build trust in the model, are discussed as well." -- Publisher's AbstractIFPRI3; Theme 3; Subtheme 3.1; Managing natural resources; DCAEPTD; DSGDP

To cite this article: Roldá n V, Marín F, Díaz J, Gallego P, Jover E, Romera M, Manzano-Ferná ndez S, Casas T, Valdé s M, Vicente V, Lip GYH. High sensitivity cardiac troponin T and interleukin-6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation.J Thromb Haemost 2012; 10: 1500-7.Summary. There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high-sensitivity interleukin-6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0-3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed-up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow-up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS 2 score: HR 2.21 (1.46-3.35, P < 0.001) for high hsTnT and 1.97 (1.29-3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all-cause mortality, the HRs were 1.79 (1.13-2.83, P = 0.013) and 2.48 (1.60-3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS 2 and CHA 2 DS 2 -VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large Ôreal worldÕ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long-term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.

Patients admitted to the intensive care unit with criteria of systemic inflammatory response syndrome had a more severe oxidative stress than patients without this syndrome.

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Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 μA to 2 mA) is applied across the scalp to modulate brain function. tDCS has been applied for therapeutic purposes (e.g., addiction, depression, mood and sleep disorders) as well as cognitive performance enhancement (e.g., memory consolidation, motor learning, language recall). Despite safety and cost advantages, the developments of tDCS therapies have been restricted by spatial targeting concerns using existing two-channel systems. We have developed novel technology for High-Density tDCS (HD-tDCS) that improves spatial focality. To determine optimal stimulation electrode configurations, based on application specific constraints, we developed a HD-tDCS targeting software. High resolution (gyri/sulci precise) MRI derived finite element (FE) human head models are generated by segmenting grey matter, white matter, CSF, skull, muscle, fatty tissue, eyes, blood vessels, scalp, etc. The models comprised >10 million elements with >15 million degrees of freedom. The induced cortical electric field/current density values are calculated; activation of either radially and tangentially oriented neuronal structures are considered. Our HD-tDCS hardware (4×1-C1, 4×4-S1) currently supports the ‘4×1-Ring’ and the ‘4×4-Strip’ electrode configurations. The peak cortical electric field was matched to ‘conventional’ large rectangular-pad tDCS stimulation; however, the spatial focality was significantly enhanced by 4×1 configuration. Using patient specific head models, our software interface allows simple and rapid screening of stimulation electrode configurations. After selecting a target region, clinicians can customize the electrode configuration to balance: 1) cortical surface and brain depth stimulation focality; 2) total applied current/voltage; and 3) electrode/scalp current density. Our HD-tDCS system allows non-invasive, safe, and targeted modulation of selected cortical structures for electrotherapies that are individualized as well as optimized for a range of therapeutic applications.