The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Influence of heavy metal ions on antibodies and immune complexes investigated by dynamic light scattering and enzyme-linked immunosorbent assay

Bauer R, Müller A, Richter M, Schneider K, Frey J, Engelhardt W. Influence of heavy metal ions on antibodies and immune complexes investigated by dynamic light scattering and enzyme-linked immunosorbent assay. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS. 1997;1334(1):98-108.The effect of Cd2+, Pb2+, Hg2+ and Cu2+ on the aggregation behaviour of monoclonal rat-IgG1-anti-mouse antibodies (kappa-light chain specific) and their antibody-antigen complexes with monoclonal mouse-IgG1 is reported. Investigations were done using the dynamic light scattering method. Cd2+ ions affected the hydrodynamic properties of the antibodies and the immune complex formation very little. More than 4 Cu2+ ions per antibody molecule led to large insoluble aggregates. Pb2+ ions also interacted with antibodies and immune complexes. Instead of 'monomeric' antibodies (Ab) or immune complexes (Ab(1)Ag(1)), large soluble aggregates were detectable in the solution. Hg2+ ions induced complex formation with 3-4 antibodies per aggregate. Possible kinds of interaction are discussed. Additionally, we tested the antigen binding activity of metal-treated antibodies in ELISA-tests. The Sandwich ELISA technique was used to investigate the serological activity of the metal-treated antibodies, i.e., the reaction with the specific antigen. For these experiments we used the same monoclonal antibodies, mouse-IgG1 and rat-IgG1-anti-mouse. The influence of the above mentioned heavy metal ions was investigated up to a 10-fold molar excess over the antibody concentration. Even at these 'unphysiological' high metal ion concentrations an inhibition of the antibody-antigen binding activity was not detectable

COMMENT ON THE IMAGING OF IMMUNOGLOBULIN-G BY SCANNING TUNNELING MICROSCOPY

Müller A, Diemann E, BRANDING A, RICHTER M, Frey J, ENGELHARDT W. COMMENT ON THE IMAGING OF IMMUNOGLOBULIN-G BY SCANNING TUNNELING MICROSCOPY. JOURNAL OF VACUUM SCIENCE & TECHNOLOGY B. 1993;11(2):337-338.Scanning tunneling microscopy has been used to image the shape of individual IgG molecules deposited onto a graphite surface. Images of these noncrystalline biological specimens free of the contradictions reported earlier could be obtained under atmospheric conditions. The results are reported including some comments on problems associated with the assignment of the visible features