Evaluation of Ablation Patterns Using a Biophysical Model of Atrial Fibrillation

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Surgical/Radiofrequency (RF) ablation is a therapeutic procedure that consists of creating lines of conduction block to interrupt AF. The present study evaluated 13 different ablation patterns by means of a biophysical model of the human atria. In this model, ablation lines were abruptly applied transmurally during simulated sustained AF, and success rate, time to AF termination and average beat-to-beat interval were documented. The gold standard Cox's Maze III procedure was taken as reference. The effectiveness of twelve less invasive patterns was compared to it. In some of these incomplete lines (entailing a gap) were simulated. Finally, the computer simulations were compared to clinical data. The results show that the model reproduces observations made in vivo: (1) the Maze III is the most efficient ablation procedure; (2) less invasive patterns should include lines in both right and left atrium; (3) incomplete ablation lines between the pulmonary veins and the mitral valve annulus lead to uncommon flutter; (4) computer simulations of incomplete lines are consistent with clinical results of non-transumural RF ablation. Biophysical modeling may therefore be considered as a useful tool for understanding the mechanisms underlying AF therapie

CO2 streams containing associated components—A review of the thermodynamic and geochemical properties and assessment of some reactive transport codes

AbstractModelling of the impact on storage of “ CO2-associated components” has rarely been addressed so far. This review, performed within the European research project CO2ReMoVe, exposes a selection of CO2 streams compositions coming from thermal power plants emissions and those injected in pilot sites part of the CO2ReMoVe project. It highlights the lack of data coming from laboratory experiments to describe properly the physical properties of some relevant gas mixtures. The geochemical impact of only 2 components (SO2 and H2S) is evidenced by some geochemical studies. Concerning the numerical modelling, four reactive transport codes (PHREEQC, SCALE2000, TOUGHREACT and COORES) were assessed. Actual limitations lie mainly in the capacity of calculating the physical properties of the whole set of gases (CO2–O2–SO2–N2–Ar–NOx–H2S–COS–CO–H2–HCl–NH3–CH4–C2H6–H2O). The new data acquired within on-going French projects will complete the knowledge of such complex gas mixtures behaviour

On commensurable hyperbolic Coxeter groups

For Coxeter groups acting non-cocompactly but with finite covolume on real hyperbolic space Hn, new methods are presented to distinguish them up to (wide) commensurability. We exploit these ideas and determine the commensurability classes of all hyperbolic Coxeter groups whose fundamental polyhedra are pyramids over a product of two simplices of positive dimensions

The SARAF-LINAC Project for SARAF-PHASE 2

THPF005International audienceSNRC and CEA collaborate to the upgrade of theSARAF accelerator to 5 mA CW 40 MeV deuteron andproton beams (Phase 2). This paper presents the referencedesign of the SARAF-LINAC Project including a fourvane176 MHz RFQ, a MEBT and a superconducting linacmade of four five-meter cryomodules housing 26superconducting HWR cavities and 20 superconductingsolenoids. The first two identical cryomodules house lowbeta($\beta$opt = 0.091), 280 mm long (flange to flange), 176MHz HWR cavities, the two identical last cryomoduleshouse high-beta ($\beta$opt = 0.181), 410 mm long, 176 MHz,HWR cavities. The beam is focused with superconductingsolenoids located between cavities housing steering coils.A BPM is placed upstream each solenoid

Effects of Electrical and Structural Remodeling on Atrial Fibrillation Maintenance: A Simulation Study

Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength - electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely

Contesting language policy for asylum seekers in the Northern periphery: The story of Tailor F

This article is about navigating asylum, employment and language policy in a new country as an asylum seeker. Through the story of one individual, we show that profound inequalities are exacerbated when forced migrants are limited in their choice of language they might study or use. The individual is Tailor F, an Iraqi man seeking asylum, and the country is Finland, officially bilingual, with a majority language (Finnish) and a minority language (Swedish). Finland’s official bilingualism does not extend evenly to language education provided for asylum seekers, who are taught Finnish regardless of the region where they are placed. Upon arrival, Tailor F was housed in a reception centre for asylum seekers located in a Swedish-dominant rural area of the country. Through our linguistic ethnography we examine how he navigates multilingually in his early settlement, his current work and his online life. We relate his story to explicit and implicit official bilingualism in Finland and discuss his lived experiences in relation to the contexts of asylum policy and employment. Tailor F’s story shows how, through his practices, he has contested implicit language policy for asylum seekers in order to gain membership of the local Swedish-dominant community, achieve a sense of belonging, and potentially realise his aspirations for the future

SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras

SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes

Proteome Based Construction of the Lymphocyte Function-Associated Antigen 1 (LFA-1) Interactome in Human Dendritic Cells.

The β2-integrin lymphocyte function-associated antigen 1 (LFA-1) plays an important role in the migration, adhesion and intercellular communication of dendritic cells (DCs). During the differentiation of human DCs from monocyte precursors, LFA-1 ligand binding capacity is completely lost, even though its expression levels were remained constant. Yet LFA-1-mediated adhesive capacity on DCs can be regained by exposing DCs to the chemokine CCL21, suggesting a high degree of regulation of LFA-1 activity during the course of DC differentiation. The molecular mechanisms underlying this regulation of LFA-1 function in DCs, however, remain elusive. To get more insight we attempted to identify specific LFA-1 binding partners that may play a role in regulating LFA-1 activity in DCs. We used highly sensitive label free quantitative mass-spectrometry to identify proteins co-immunoprecipitated (co-IP) with LFA-1 from ex vivo generated DCs. Among the potential binding partners we identified not only established components of integrin signalling pathways and cytoskeletal proteins, but also several novel LFA-1 binding partners including CD13, galectin-3, thrombospondin-1 and CD44. Further comparison to the LFA-1 interaction partners in monocytes indicated that DC differentiation was accompanied by an overall increase in LFA-1 associated proteins, in particular cytoskeletal, signalling and plasma membrane (PM) proteins. The here presented LFA-1 interactome composed of 78 proteins thus represents a valuable resource of potential regulators of LFA-1 function during the DC lifecycle

Rapid automatic segmentation of abnormal tissue in late gadolinium enhancement cardiovascular magnetic resonance images for improved management of long-standing persistent atrial fibrillation

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder. In order for late Gd enhancement cardiovascular magnetic resonance (LGE CMR) to ameliorate the AF management, the ready availability of the accurate enhancement segmentation is required. However, the computer-aided segmentation of enhancement in LGE CMR of AF is still an open question. Additionally, the number of centres that have reported successful application of LGE CMR to guide clinical AF strategies remains low, while the debate on LGE CMR’s diagnostic ability for AF still holds. The aim of this study is to propose a method that reliably distinguishes enhanced (abnormal) from non-enhanced (healthy) tissue within the left atrial wall of (pre-ablation and 3 months post-ablation) LGE CMR data-sets from long-standing persistent AF patients studied at our centre. Methods: Enhancement segmentation was achieved by employing thresholds benchmarked against the statistics of the whole left atrial blood-pool (LABP). The test-set cross-validation mechanism was applied to determine the input feature representation and algorithm that best predict enhancement threshold levels. Results: Global normalized intensity threshold levels T PRE = 1 1/4 and T POST = 1 5/8 were found to segment enhancement in data-sets acquired pre-ablation and at 3 months post-ablation, respectively. The segmentation results were corroborated by using visual inspection of LGE CMR brightness levels and one endocardial bipolar voltage map. The measured extent of pre-ablation fibrosis fell within the normal range for the specific arrhythmia phenotype. 3D volume renderings of segmented post-ablation enhancement emulated the expected ablation lesion patterns. By comparing our technique with other related approaches that proposed different threshold levels (although they also relied on reference regions from within the LABP) for segmenting enhancement in LGE CMR data-sets of AF patients, we illustrated that the cut-off levels employed by other centres may not be usable for clinical studies performed in our centre. Conclusions: The proposed technique has great potential for successful employment in the AF management within our centre. It provides a highly desirable validation of the LGE CMR technique for AF studies. Inter-centre differences in the CMR acquisition protocol and image analysis strategy inevitably impede the selection of a universally optimal algorithm for segmentation of enhancement in AF studies