Changes of the Atlantic meridional overturning circulation of the past 30ka recorded in a depth transect at the Blake Outer Ridge

Oceans and climate are a tightly coupled system interacting with each other in various ways such as storage of carbon dioxide in the deep ocean. Within the global conveyor belt the Atlantic Meridional Overturning Circulation (AMOC) holds a key function, transporting warm salty surface waters from the tropical to the northern Atlantic where deep water formation takes place. Following the continental rise of North America this newly formed deep water propagates southward as Western Boundary Undercurrent (WBUC) ventilating the deep Atlantic. In the past (e.g. the last glacial cycle) strength and geometry of the AMOC have changed significantly. This study aims to provide a better understanding of the temporal and spatial (also depth depended) evolution of the AMOC in the western Atlantic sector since the last glacial (∼30 ka). We have investigated four sediment cores of the Blake Outer Ridge (30°N, 74°W; ODP 1059 to 1062) in a depth transect from 3000 to 4700 m water depth in the main flow path of the WBUC. We measured four down-core profiles of neodymium (εNd) and 231Pa/230Th isotopes for the reconstruction of water mass provenance and circulation strength of the last ∼30 ka. In contrast to published Nd isotope and 231Pa/230Th records from the Blake Ridge area our records are of unprecedented resolution, resolving climate key features of the North Atlantic region: Heinrich Stadials (HS) 1 and 2, the Last Glacial Maximum (LGM), the Bølling-Allerød and Younger Dryas (YD). Radiogenic Nd isotope signatures during the LGM reveal AABW to be the prevalent water mass in the deep western North Atlantic. The trend to more unradiogenic signatures during the deglaciation point to an increased formation of NADW which was again replaced by AABW during YD. The Holocene shows the most unradiogenic signatures and therefore established NADW. The circulation strength-proxy 231Pa/230Th indicates reduced LGM deep circulation, a pronounced slowdown during HS1 and a strong and deep circulation during the Holocene. Compared to isotopic records from the Bermuda Rise (ODP 1063) we found depth depended geometry changes of the WBUC which have occurred through the last glacial. Here, we focus on how deep northern sourced water has reached during phases of reduced circulation (indicated by increased 231Pa/230Th ratios) and the timing of this southward progradation of lower NADW

Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals

BACKGROUND: The appropriate evaluation of atrial electrical function is only possible by means of invasive electrophysiology techniques, which are expensive and therefore not suitable for widespread use. Mechanical atrial function is mainly determined from atrial volumes and volume-derived indices that are load-dependent, time-consuming and difficult to reproduce because they are observer-dependent. AIMS: To assess the feasibility of tissue velocity echocardiography (TVE) to evaluate atrial electromechanical function in young, healthy volunteers. SUBJECTS AND METHODS: We studied 37 healthy individuals: 28 men and nine women with a mean age of 29 years (range 20–47). Standard two-dimensional (2-D) and Doppler echocardiograms with superimposed TVE images were performed. Standard echocardiographic images were digitized during three consecutive cardiac cycles in cine-loop format for off-line analysis. Several indices of regional atrial electrical and mechanical function were derived from both 2-D and TVE modalities. RESULTS: Some TVE-derived variables indirectly reflected the atrial electrical activation that follows the known activation process as revealed by invasive electrophysiology. Regionally, the atrium shows an upward movement of its walls at the region near the atrio-ventricular ring with a reduction of this movement towards the upper levels of the atrial walls. The atrial mechanical function as assessed by several TVE-derived indices was quite similar in all left atrium (LA) walls. However, all such indices were higher in the right (RA) than the LA. There were no correlations between the 2-D- and TVE-derived variables expressing atrial mechanical function. Values of measurement error and repeatability were good for atrial mechanical function, but only acceptable for atrial electrical function. CONCLUSION: TVE may provide a simple, easy to obtain, reproducible, repeatable and potentially clinically useful tool for quantifying atrial electromechanical function

A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship

The most common sustained cardiac arrhythmias in humans are atrial tachyarrhythmias, mainly atrial fibrillation. Areas of complex fractionated atrial electrograms and high dominant frequency have been proposed as critical regions for maintaining atrial fibrillation; however, there is a paucity of data on the relationship between the characteristics of electrograms and the propagation pattern underlying them. In this study, a realistic 3D computer model of the human atria has been developed to investigate this relationship. The model includes a realistic geometry with fiber orientation, anisotropic conductivity and electrophysiological heterogeneity. We simulated different tachyarrhythmic episodes applying both transient and continuous ectopic activity. Electrograms and their dominant frequency and organization index values were calculated over the entire atrial surface. Our simulations show electrograms with simple potentials, with little or no cycle length variations, narrow frequency peaks and high organization index values during stable and regular activity as the observed in atrial flutter, atrial tachycardia (except in areas of conduction block) and in areas closer to ectopic activity during focal atrial fibrillation. By contrast, cycle length variations and polymorphic electrograms with single, double and fragmented potentials were observed in areas of irregular and unstable activity during atrial fibrillation episodes. Our results also show: 1) electrograms with potentials without negative deflection related to spiral or curved wavefronts that pass over the recording point and move away, 2) potentials with a much greater proportion of positive deflection than negative in areas of wave collisions, 3) double potentials related with wave fragmentations or blocking lines and 4) fragmented electrograms associated with pivot points. Our model is the first human atrial model with realistic fiber orientation used to investigate the relationship between different atrial arrhythmic propagation patterns and the electrograms observed at more than 43000 points on the atrial surface.This work was partially supported by the Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica, Ministerio de Ciencia e Innovacion of Spain (TEC2008-02090), by the Plan Avanza (Accion Estrategica de Telecomunicaciones y Sociedad de la Informacion), Ministerio de Industria Turismo y Comercio of Spain (TSI-020100-2010-469), by the Programa Prometeo 2012 of the Generalitat Valenciana and by the Programa de Apoyo a la Investigacion y Desarrollo de la Universitat Politecnica de Valencia (PAID-06-11-2002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Tobón Zuluaga, C.; Ruiz Villa, CA.; Heidenreich, E.; Romero Pérez, L.; Hornero, F.; Saiz Rodríguez, FJ. (2013). A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship. PLoS ONE. 8(2):1-13. https://doi.org/10.1371/journal.pone.0050883S11382Ho SY, Sanchez-Quintana D, Anderson RH (1998) Can anatomy define electric pathways? In: International Workshop on Computer Simulation and Experimental Assessment of Electrical Cardiac Function, Lausanne, Switzerland. 77–86.Tobón C (2009) Evaluación de factores que provocan fibrilación auricular y de su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Master Thesis Universitat Politècnica de València.Ruiz C (2010) Estudio de la vulnerabilidad a reentradas a través de modelos matemáticos y simulación de la aurícula humana. Doctoral Thesis Universitat Politècnica de València.Tobón C (2010) Modelización y evaluación de factores que favorecen las arritmias auriculares y su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Doctoral Thesis Universitat Politècnica de València.Henriquez, C. S., & Papazoglou, A. A. (1996). Using computer models to understand the roles of tissue structure and membrane dynamics in arrhythmogenesis. Proceedings of the IEEE, 84(3), 334-354. doi:10.1109/5.486738Grimm, R. A., Chandra, S., Klein, A. L., Stewart, W. J., Black, I. W., Kidwell, G. A., & Thomas, J. D. (1996). Characterization of left atrial appendage Doppler flow in atrial fibrillation and flutter by Fourier analysis. American Heart Journal, 132(2), 286-296. doi:10.1016/s0002-8703(96)90424-xMaleckar, M. M., Greenstein, J. L., Giles, W. R., & Trayanova, N. A. (2009). K+ current changes account for the rate dependence of the action potential in the human atrial myocyte. American Journal of Physiology-Heart and Circulatory Physiology, 297(4), H1398-H1410. doi:10.1152/ajpheart.00411.200

Electrical conduction between the right atrium and the left atrium via the musculature of the coronary sinus

Background-The purpose of this study was to determine whether the coronary sinus (CS) musculature has electrical connections to the right atrium (RA) and left atrium (LA) and forms an RA-LA connection. Methods and Results-Six excised dog hearts were perfused in a Langendorff preparation. A 20-electrode catheter (2-4-2-mm spacing center to center) was placed along the CS, Excision of the pulmonary veins provided access to the LA, and a second 20-electrode catheter was placed along the LA endocardium opposite the CS catheter. An incision opened the CS longitudinally, and microelectrodes were inserted into the CS musculature and adjacent LA myocardium. Continuous CS musculature was visible along a 35+/-9-mm length of the CS beginning at the ostium. During lateral LA pacing, CS electrodes recorded double potentials, a rounded, low-frequency potential followed by a sharp potential. The rounded initial potential propagated in the lateral-to-septal direction and represented "far-field" LA activation (timing coincided with adjacent LA potentials and with action potentials recorded from microelectrodes in adjacent LA cells). The sharp potential represented CS activation (timing coincided with action potentials recorded from CS musculature). A distal LA-CS connection (earliest sharp potential in the CS during lateral LA pacing) was located 26+/-7 mm from the ostium. During RA pacing posterior to the CS ostium, CS electrodes recorded septal-to-lateral activation of the high-frequency potential, with slightly later activation of the rounded potential (LA activation). Incisions surrounding the CS ostium isolating the ostium from the RA had no effect on the CS musculature and LA potentials during RA pacing within the isolated segment containing the CS ostium. RA pacing outside the isolated segment delayed activation of the CS musculature until after LA activation, confirming that the RA-CS connection was located in the region of the CS ostium as well as confirming the presence of the LA-CS connection. Conclusions-In canine hearts, the CS musculature is electrically connected to the RA and the LA and forms an RA-LA connection

NMR structure and functional characteristics of the hydrophilic N terminus of the potassium channel beta-subunit Kvbeta1.1

Rapid N-type inactivation of voltage-dependent potassium (Kv) channels controls membrane excitability and signal propagation in central neurons and is mediated by protein domains (inactivation gates) occluding the open channel pore from the cytoplasmic side. Inactivation domains (ID) are donated either by the pore-forming alpha-subunit or certain auxiliary beta-subunits. Upon coexpression, Kvbeta1.1 was found to endow non-inactivating members of the Kv1alpha family with fast inactivation via its unique N terminus. Here we investigated structure and functional properties of the Kvbeta1.1 N terminus (amino acids 1-62, betaN-(1-62)) using NMR spectroscopy and patch clamp recordings. betaN-(1-62) showed all hallmarks of N-type inactivation: it inactivated non-inactivating Kv1.1 channels when applied to the cytoplasmic side as a synthetic peptide, and its interaction with the alpha-subunit was competed with tetraethylammonium and displayed an affinity in the lower micromolar range. In aequous and physiological salt solution, betaN-(1-62) showed no well defined three-dimensional structure, it rather existed in a fast equilibrium of multiple weakly structured states. These structural and functional properties of betaN-(1-62) closely resemble those of the "unstructured" ID from Shaker B, but differ markedly from those of the compactly folded ID of the Kv3.4 alpha-subunit

Critical atrial site for ablation of pacing-induced atrial fibrillation in the normal dog heart

Site for Ablation of AF in Dogs. Introduction: Radiofrequency catheter ablation (RFA) has been used recently to treat atrial fibrillation (AF). The purpose of this study was to investigate a new approach to preventing AF by RFA. Methods and Results: In open chest, anesthetized dogs, AF (lasting > 30 sec) was induced after burst stimulation, and electrophysiologic parameters were recorded before and after RFA. In group 1 (9 dogs) we performed selective and combined slow and fast pathway RFA, whereas in group 2 (11 dogs) RFA was applied as a linear lesion at the mid-atrial septum between the inferior vena cava and the fossa ovalis. After ablation, the Wenckebach cycle length was significantly prolonged only in group 1 (194 +/- 23 vs 282 +/- 35 msec, P = 0.002), whereas the interval between the stimulus (S) artifact applied at the high right atrium to the His bundle (H) (SH interval) prolonged to the same extent in both groups (162 +/- 14 vs 146 +/- 45 msec, P = NS); group 1 due to an A-H prolongation whereas in group 2 it was due to an intra-atrial conduction delay. In group 1 AF still remained inducible, although with a longer mean R-R interval (215 +/- 16 vs 433 +/- 88 msec, P < 0.05). No instance of complete AV block developed. In group 2, sustained AF was noninducible in 10 dogs and its duration was markedly shorter in the remaining one (8 sec). Gross anatomy and histology did not reveal any damage inside of Koch's triangle, and particularly to the compact AV node. Conclusion: These findings suggest that RFA at the midi-atrial septum prevents AF in the normal dog heart. This approach might also be successful in those clinical settings in which the atrial septum plays a critical role in the maintenance of sustained AF

Electrophysiology of the atrio-AV nodal inputs and exits in the normal dog heart: radiofrequency ablation using an epicardial approach

Ablation of Atrionodal Connections. Introduction: We studied the effects of selective and combined ablation of the fast (FP) and slow pathway (SP) on AV and VA conduction in the normal dog heart using a novel epicardial ablation technique. Methods and Results: For FP ablation, radiofrequency current (RFC) was applied to a catheter tip that was held epicardially against the base of the right atrial wall. SP ablation was performed epicardially at the crux of the heart. Twenty-three dogs were assigned to two ablation protocols: FP/SP ablation group (n = 17) and SP/FP ablation group (n = 6). In 12 of 17 dogs, FP ablation prolonged the PR interval (97 +/- 10 to 149 +/- 22 msec, P < 0.005) with no significant change in anterograde Wenckebach cycle length (WBCL). Subsequent SP ablation performed in 8 dogs further prolonged the PR interval and the anterograde WBCL (117 +/- 22 to 193 +/- 27, P < 0.005). Complete AV block was seen in 1 of 8 dogs, whereas complete or high-grade VA block was seen in 6 of 8 dogs. In the SP/FP ablation group, SP ablation significantly increased WBCL with no PR changes. Combined SP/FP ablation in 6 dogs prolonged the PR interval significantly, but no instance of complete AV block was seen. VA block was found in 50% of these cases. Histologic studies revealed that RFC ablation affected the anterior and posterior atrium adjacent to the undamaged AV node and His bundle. Conclusion: Using an epicardial approach, combined ablation of the FP and SP AV nodal inputs can be achieved with an unexpectedly low incidence of complete AV block, although retrograde VA conduction was significantly compromised

Time for curriculum reform: the case of mathematics

Mathematics education is rarely out of the policy spotlight in England. Over the last ten years, considerable attention has been given to improving 14-19 mathematics curriculum pathways. In this paper we consider some of the challenges of enacting curriculum change by drawing upon evidence from our evaluation of the Mathematics Pathways Project. From 2004-10 this project, which was directed by England’s Qualifications and Curriculum Authority, aimed to improve the engagement, attainment and participation rates of 14-19 year old learners of mathematics. Our particular focus is upon the temporal problems of piloting new curriculum and assessment and we draw on Lemke’s discussion of time-scales, heterochrony and the adiabatic principle to consider the interlocking and interference of various change processes