The Northwestern Greenland Ice Sheet During The Early Pleistocene Was Similar To Today

The multi-million year history of the Greenland Ice Sheet remains poorly known. Ice-proximal glacial marine diamict provides a direct but discontinuous record of ice sheet behavior; it is underutilized as a climate archive. Here, we present a novel multiproxy analysis of an Early Pleistocene marine diamict from northwestern Greenland. Low cosmogenic nuclide concentrations indicate minimal near-surface exposure, similar to modern terrestrial sediment. Detrital apatite (U-Th-Sm)/He (AHe) ages all predate glaciation by \u3e150 million years, suggesting the northwestern Greenland Ice Sheet had, by 1.9 Ma, not yet incised fjords of sufficient depth to excavate grains with young AHe ages. The diamict contains terrestrial plant leaf wax, likely from land surfaces surrounding the ice sheet. These data indicate that a persistent, dynamic ice sheet existed in northwestern Greenland by 1.9 Ma and that diamict is a useful archive of ice sheet history and process

Scalar soliton quantization with generic moduli

This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credArticle funded by SCOAP3. CP is a Royal Society Research Fellow and partly supported by the U.S. Department of Energy under grants DOE-SC0010008, DOE-ARRA-SC0003883 and DOE-DE-SC0007897. ABR is supported by the Mitchell Family Foundation. We would like to thank the Mitchell Institute at Texas A&M and the NHETC at Rutgers University respectively for hospitality during the course of this work. We would also like to acknowledge the Aspen Center for Physics and NSF grant 1066293 for a stimulating research environment which led to questions addressed in this paper

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in sinus rhythm (SR) via activation of 5-HT<sub>4</sub> receptors, but its effects in atrial cells from patients with atrial fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>), action potential duration (APD) and arrhythmic activity at 37 °C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10 μM) produced an increase in <i>I</i><sub>CaL</sub> of 115 ± 21% above control (<i>n</i> = 10 cells, 6 patients) that was significantly smaller than that in the SR group (232 ± 33%; <i>p</i> 0.05; <i>n</i> = 27 cells, 12 patients). Subsequent co-application of isoproterenol (1 μM) caused a further increase in <i>I</i><sub>CaL</sub> in the AF group (by 256 ± 94%) that was greater than that in the SR group (22 ± 6%; p < 0.05). The APD at 50% repolarisation (APD<sub>50</sub>) was prolonged by 14 ± 3 ms by 5-HT in the AF group (<i>n</i> = 37 cells, 14 patients). This was less than that in the SR group (27 ± 4 ms; <i>p</i> < 0.05; <i>n</i> = 58 cells, 24 patients). Arrhythmic activity in response to 5-HT was observed in 22% of cells in the SR group, but none was observed in the AF group (p < 0.05). Atrial fibrillation was associated with reduced effects of 5-HT, but not of isoproterenol, on <i>I</i><sub>CaL</sub> in human atrial cells. This reduced effect on <i>I</i><sub>CaL</sub> was associated with a reduced APD<sub>50</sub> and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic influence of 5-HT may be suppressed in AF-remodelled human atrium

Cellular bases for human atrial fibrillation

Atrial fibrillation (AF) causes substantial morbidity and mortality. It may be triggered and sustained by either reentrant or nonreentrant electrical activity. Human atrial cellular refractory period is shortened in chronic AF, likely aiding reentry. The ionic and molecular mechanisms are not fully understood and may include increased inward rectifier K<sup>+</sup> current and altered Ca<sup>2+</sup> handling. Heart failure, a major cause of AF, may involve arrhythmogenic atrial electrical remodeling, but the pattern is unclear in humans. Beta-blocker therapy prolongs atrial cell refractory period; a potentially antiarrhythmic influence, but the ionic and molecular mechanisms are unclear. The search for drugs to suppress AF without causing ventricular arrhythmias has been aided by basic studies of cellular mechanisms of AF. It remains to be seen whether such drugs will improve patient treatment

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Pre-hospital management protocols and perceived difficulty in diagnosing acute heart failure

Aim To illustrate the pre-hospital management arsenals and protocols in different EMS units, and to estimate the perceived difficulty of diagnosing suspected acute heart failure (AHF) compared with other common pre-hospital conditions. Methods and results A multinational survey included 104 emergency medical service (EMS) regions from 18 countries. Diagnostic and therapeutic arsenals related to AHF management were reported for each type of EMS unit. The prevalence and contents of management protocols for common medical conditions treated pre-hospitally was collected. The perceived difficulty of diagnosing AHF and other medical conditions by emergency medical dispatchers and EMS personnel was interrogated. Ultrasound devices and point-of-care testing were available in advanced life support and helicopter EMS units in fewer than 25% of EMS regions. AHF protocols were present in 80.8% of regions. Protocols for ST-elevation myocardial infarction, chest pain, and dyspnoea were present in 95.2, 80.8, and 76.0% of EMS regions, respectively. Protocolized diagnostic actions for AHF management included 12-lead electrocardiogram (92.1% of regions), ultrasound examination (16.0%), and point-of-care testings for troponin and BNP (6.0 and 3.5%). Therapeutic actions included supplementary oxygen (93.2%), non-invasive ventilation (80.7%), intravenous furosemide, opiates, nitroglycerine (69.0, 68.6, and 57.0%), and intubation 71.5%. Diagnosing suspected AHF was considered easy to moderate by EMS personnel and moderate to difficult by emergency medical dispatchers (without significant differences between de novo and decompensated heart failure). In both settings, diagnosis of suspected AHF was considered easier than pulmonary embolism and more difficult than ST-elevation myocardial infarction, asthma, and stroke. Conclusions The prevalence of AHF protocols is rather high but the contents seem to vary. Difficulty of diagnosing suspected AHF seems to be moderate compared with other pre-hospital conditions