Cardiogenic Shock Management and Research: Past, Present, and Future Outlook

Although great strides have been made in the pathophysiological understanding, diagnosis and management of cardiogenic shock (CS), morbidity and mortality in patients presenting with the condition remain high. Acute MI is the commonest cause of CS; consequently, most existing literature concerns MI-associated CS. However, there are many more phenotypes of patients with acute heart failure. Medical treatment and mechanical circulatory support are well-established therapeutic options, but evidence for many current treatment regimens is limited. The issue is further complicated by the fact that implementing adequately powered, randomized controlled trials are challenging for many reasons. In this review, the authors discuss the history, landmark trials, current topics of medical therapy and mechanical circulatory support regimens, and future perspectives of CS management

Spontaneous Degenerative Aortic Valve Disease in New Zealand Obese Mice

Background: Degenerative aortic valve (AoV) disease and resulting aortic stenosis are major clinical health problems. Murine models of valve disease are rare, resulting in a translational knowledge gap on underlying mechanisms, functional consequences, and potential therapies. Naive New Zealand obese (NZO) mice were recently found to have a dramatic decline of left ventricular (LV) function at early age. Therefore, we aimed to identify the underlying cause of reduced LV function in NZO mice. Methods and Results: Cardiac function and pulmonary hemodynamics of NZO and age-matched C57BL/6J mice were monitored by serial echocardiographic examinations. AoVs in NZO mice demonstrated extensive thickening, asymmetric aortic leaflet formation, and cartilaginous transformation of the valvular stroma. Doppler echocardiography of the aorta revealed increased peak velocity profiles, holodiastolic flow reversal, and dilatation of the ascending aorta, consistent with aortic stenosis and regurgitation. Compensated LV hypertrophy deteriorated to decompensated LV failure and remodeling, as indicated by increased LV mass, interstitial fibrosis, and inflammatory cell infiltration. Elevated LV pressures in NZO mice were associated with lung congestion and cor pulmonale, evident as right ventricular dilatation, decreased right ventricular function, and increased mean right ventricular systolic pressure, indicative for the development of pulmonary hypertension and ultimately right ventricular failure. Conclusions: NZO mice demonstrate as a novel murine model to spontaneously develop degenerative AoV disease, aortic stenosis, and the associated end organ damages of both ventricles and the lung. Closely mimicking the clinical scenario of degenerative AoV disease, the model may facilitate a better mechanistic understanding and testing of novel treatment strategies in degenerative AoV disease

Preliminary results from pre-site surveys for deep geological drillingbelow Ekström Ice Shelf (Sub-EIS-Obs)

During field seasons 2016/17 and 2017/18, pre-site seismic surveys were undertaken in the Ekströmisen region of Dronning Maud Land, with the primary goal of building a stratigraphic age framework of sub-ice-shelf sedimentary strata. These sediments cover the Explora Wedge, a syn- or post-rift volcanic deposit. Expected ages range from Late Mesozoic to Quaternary. From new vibroseismic profiles, we selected sites for seafloor sampling with short cores through Hot Water Drill (HWD) holes of the oldest and of the youngest sedimentary sequencesto confine their age time span. There is further potential for drilling deeper sediment cores with the support of international partners. Deep drilling should recover the sediments overlying the Explora Escarpment, in order to discover the context and nature of the Explora Wedge. We expect the overlying sedimentary sequences to reveal the history of polar amplification and climate changes in this part of Antarctica, the build-up of the East AntarcticIce Sheet during past warmer climates and its Cenozoic and future variability. We successfully sampled the sea floor with different tools through HWD holes at two sites selected from the reflection seismic data close to the German Neumayer Station III, and discovered a pebbly sea floor coated with bryozoan skeletons. Present HWD holes penetrating the ice shelf to sample the sea floor will provide the unique opportunity for further piggy back experiments consisting of multi-disciplinary nature. For example, experiments and deploying measuring setup for oceanography, sea and ice shelf physics, geophysics, geology, hydrography, biogeochemistry could be potential future actions in order to characterise the ocean-ice-sediment interactions, processes and ecosystem observations. For season 2018/19 – besides additional geological sampling – it is planned to deploy a multiyear oceanographic mooring beneath the ice shelf. During future campaigns, we will try to launch an Autonomous Underwater Vehicle (AUV) either through a HWD hole, from a ship, or from the fast ice with the necessary power to operate and measure within the sub-ice shelf cavity

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

New details about the LGM extent and subsequent retreat of the West Antarctic Ice Sheet from the easternmost Amundsen Sea Embayment shelf

In recent years several previously undiscovered grounding-zone wedges (GZWs) have been described within the Abbot-Cosgrove palaeo-ice stream trough on the easternmost Amundsen Sea Embayment shelf. These GZWs document both the Last Glacial Maximum (LGM; 26.5-19 cal. ka BP) grounding-line extent and the subsequent episodic retreat within this trough that neighbors the larger Pine Island-Thwaites trough to the west. Here we combine bathymetric, seismic, and geologic data showing that 1) the grounding line in Abbot Trough did not reach the continental shelf break at any time during the last glacial period, and 2) a prominent stacked GZW constructed from six individual wedges lying upon another was deposited 100 km upstream from the LGM grounding-line position. The available data allow for calculating volumes for most of these individual GZWs and for the entire stack. Sediment cores were recovered seawards from the outermost GZW in the trough, and from the individual wedges of the stacked GZW in order to define the LGM grounding-line extent, and provide minimum grounding-line retreat ages for the respective positions on the stacked GZW. We present implications of a grounded-ice free outer shelf throughout the last glacial period. Furthermore, we assess the significance of the grounding-line stillstand period recorded by the stacked GZW in Abbot Trough for the timing of post-LGM retreat of the West Antarctic Ice Sheet from the Amundsen Sea Embayment shelf

Subglacial lakes, seafloor geomorphology, and deglaciation history in Pine Island Bay, West Antarctica during the last glacial termination

Subglacial meltwater largely facilitates rapid but nonlinear ice flow beneath concurrent ice streams, and there is widespread evidence for a dynamic subglacial water system beneath the Antarctic Ice Sheet. It steers and affects the pattern of ice flow and is a direct result of boundary processes acting at the ice sheet bed, i.e. pressure-induced basal melting. Consequently, the occurrence of subglacial meltwater plays an important role in bedrock erosion, subsequent re-deposition, and in shaping the topography of ice-sheet beds. Here we present new geological, geophysical, and geochemical data from sediment cores recovered from the continental shelf in Pine Island Bay. We interpret the data as reliably indicating palaeo-subglacial lake deposition beneath the formerly expanded West Antarctic Ice Sheet, presumably during and/or subsequent to the Last Glacial Maximum (LGM) (Kuhn et al. 2017). Characteristic changes of sedimentary facies and geochemical profiles within these cores that were recovered on RV Polarstern expeditions ANT-XXIII/4 (2006) and ANT-XXVI/3 (2010), support the presence of an active and expanded subglacial lake system in at least five basins. The basins, which also have been targeted by sediment coring during the recent RV Polarstern cruise PS104 (2017), had been carved into bedrock over previous glacial cycles and were then filled with several meters of sediments. These findings have important implications for palaeo ice-sheet dynamics, suggesting the presence of considerable amounts of water lubricating the ice-bed interface, eventually leading to the subglacial deposition of lake sediments and water-saturated soft tills. Based on our recent findings, we conclude that the transition from the subglacial lake to an ocean-influenced environment took place during deglaciation at the transition from the LGM to the Holocene. We suggest that the ice sheet thinned and the subglacial lake basins successively transformed to sub-ice cavities, flushed by tidal currents at this time. We will present estimates of ice thickness for buoyancy at the grounding line for the time when the grounding line retreated landward across the rim of the subglacial lake. These estimates are based on the bathymetric setting, a glacial isostatic adjustment model, a global sea level curve, and the available chronological information. Our findings have implications for ice sheet models, which need to consider the predominantly non-linear effects related to subglacial hydrology. Keywords: West Antarctic Ice Sheet (WAIS), Sub-Ice processes, Deglaciation processes References Kuhn, G., Hillenbrand, C.-D., Kasten, S., Smith, J. A., Nitsche, F. O., Frederichs, T., Wiers, S., Ehrmann, W., Klages, J. P., Mogollón, J. M., 2017. Evidence for a palaeo-subglacial lake on the Antarctic continental shelf. Nature Communications, 8, 15591