Eclipse Ice Core Accumulation and Stable Isotope Variability as an Indicator of North Pacific Climate

The high accumulation rate and negligible amount of melt at Eclipse Icefield (3017 m) in the Saint Elias Range of Yukon, Canada, allows for the preservation of a high-resolution isotopic and glaciochemical records valuable for reconstruction of climatic variables. Each of the three Eclipse ice cores have a well-constrained depth–age scale with dozens of reference horizons over the twentieth century that permits an exceptional level of confi- dence in the results of the current calibration exercise. Stacked time series of accumulation and stable isotopes were divided into cold and warm seasons and seasons of extreme high and extreme low accumulation and stable isotope values (eight groups). For each group, season-averaged composites of 500-hPa geopotential height grids, and the individual seasons that constitute them, were analyzed to elucidate common anomalous flow patterns. This analysis shows that the most fractionated isotopes and lowest accumulation cold seasons reflect a more zonal height pattern in the North Pacific associated with negative Pacific–North American (PNA) and Pacific decadal oscillation (PDO) indices. Conversely, the least fractionated isotopes and highest accumulation cold seasons are associated with a positive PNA pattern. Although only a maximum of approximately 20% of the total number of accumulation and stable isotope seasons exhibit a relatively consistent relationship with 500-hPa geopotential height patterns, these results support the hypothesis that the most extreme accumulation and extreme isotope cold-season values in the Saint Elias Mountains are related to consistent atmospheric circulation and oceanic sea surface temperature patterns

Seasonal deuterium excess in a Tien Shan ice core: Influence of moisture transport and recycling in Central Asia

Stable water isotope (δ18O, δD) data from a high elevation (5100 masl) ice core recovered from the Tien Shan Mountains, Kyrgyzstan, display a seasonal cycle in deuterium excess (d = δD − 8*δ18O) related to changes in the regional hydrologic cycle during 1994–2000. While there is a strong correlation (r2 = 0.98) between δ18O and δD in the ice core samples, the regression slope (6.9) and mean d value (23.0) are significantly different than the global meteoric water line values. The resulting time-series ice core d profile contains distinct winter maxima and summer minima, with a yearly d amplitude of ∼15–20‰. Local-scale processes that may affect d values preserved in the ice core are not consistent with the observed seasonal variability. Data from Central Asian monitoring sites in the Global Network of Isotopes in Precipitation (GNIP) have similar seasonal d changes. We suggest that regional-scale hydrological conditions, including seasonal changes in moisture source, transport, and recycling in the Caspian/Aral Sea region, are responsible for the observed spatial and temporal d variability

Ice core paleovolcanic records from the St. Elias Mountains, Yukon, Canada

We previously reported a record of regionally significant volcanic eruptions in the North Pacific using an ice core from Eclipse Icefield (St. Elias Mountains, Yukon, Canada). The acquisition of two new ice cores from Eclipse Icefield, along with the previously available Eclipse Icefield and Mount Logan Northwest Col ice cores, allows us to extend our record of North Pacific volcanism to 550 years before present using a suite of four ice cores spanning an elevation range of 3–5 km. Comparison of volcanic sulfate flux records demonstrates that the results are highly reproducible, especially for the largest eruptions such as Katmai (A.D. 1912). Correlation of volcanic sulfate signals with historically documented eruptions indicates that at least one-third of the eruptions recorded in St. Elias ice cores are from Alaskan and Kamchatkan volcanoes. Although there are several moderately large (volcanic explosivity index (VEI) ≥ 4) eruptions recorded in only one core from Eclipse Icefield, the use of multiple cores provides signals in at least one core from all known VEI ≥ 4 eruptions in Alaska and Kamchatka since A.D. 1829. Tephrochronological evidence from the Eclipse ice cores documents eruptions in Alaska (Westdahl, Redoubt, Trident, and Katmai), Kamchatka (Avachinsky, Kliuchevoskoi, and Ksudach), and Iceland (Hekla). Several unidentified tephra-bearing horizons, with available geochemical evidence suggesting Alaskan and Kamchatkan sources, were also found. We present a reconstruction of annual volcanic sulfate loading for the North Pacific troposphere based on our ice core data, and we provide a detailed assessment of the atmospheric and climatic effects of the Katmai eruption

Ice core evidence for a second volcanic eruption around 1809 in the Northern Hemisphere

A volcanic signal observed in ice cores from both polar regions six years prior to Tambora is attributed to an unknown tropical eruption in 1809. Recovery of dacitic tephra from the 1809 horizon in a Yukon ice core (Eclipse) that is chemically distinct from andesitic 1809 tephra found in Antarctic ice cores indicates a second eruption in the Northern Hemisphere at this time. Together with the similar magnitude and timing of the 1809 volcanic signal in the Arctic and Antarctic, this could suggest a large tropical eruption produced the sulfate and Antarctic tephra and a minor Northern Hemisphere eruption produced the Eclipse tephra. Nonetheless, the possibility that there were coincidental eruptions of similar magnitude in both hemispheres, rather than a single tropical eruption, should not be discounted. Correctly attributing the source of the 1809 volcanic signal has important implications for modeling the magnitude and latitudinal distribution of volcanic radiative forcing

Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genes and Genetic Variants

Direct oral anticoagulants (DOAC) have shown an upward prescribing trend in recent years due to favorable pharmacokinetics and pharmacodynamics without requirement for routine coagulation monitoring. However, recent studies have documented inter-individual variability in plasma drug levels of DOACs. Pharmacogenomics of DOACs is a relatively new area of research. There is a need to understand the role of pharmacogenomics in the interpatient variability of the four most commonly prescribed DOACs, namely dabigatran, rivaroxaban, apixaban, and edoxaban. We performed an extensive search of recently published research articles including clinical trials and in-vitro studies in PubMed, particularly those focusing on genetic loci, single nucleotide polymorphisms (SNPs), and DNA polymorphisms, and their effect on inter-individual variation of DOACs. Additionally, we also focused on commonly associated drug-drug interactions of DOACs. CES1 and ABCB1 SNPs are the most common documented genetic variants that contribute to alteration in peak and trough levels of dabigatran with demonstrated clinical impact. ABCB1 SNPs are implicated in alteration of plasma drug levels of rivaroxaban and apixaban. Studies conducted with factor Xa, ABCB1, SLCOB1, CYP2C9, and VKORC1 genetic variants did not reveal any significant association with plasma drug levels of edoxaban. Pharmacokinetic drug-drug interactions of dabigatran are mainly mediated by p-glycoprotein. Strong inhibitors and inducers of CYP3A4 and p-glycoprotein should be avoided in patients treated with rivaroxaban, apixaban, and edoxaban. We conclude that some of the inter-individual variability of DOACs can be attributed to alteration of genetic variants of gene loci and drug-drug interactions. Future research should be focused on exploring new genetic variants, their effect, and molecular mechanisms that contribute to alteration of plasma levels of DOACs

Flow dynamics of an accumulation basin: a case study of upper Kahiltna Glacier, Mount McKinley, Alaska

We interpreted flow dynamics of the Kahiltna Pass Basin accumulation zone on Mount McKinley, Alaska, USA, using 40, 100 and 900 MHz ground-penetrating radar profiles and GPS surface velocity measurements. We found dipping, englacial surface-conformable strata that experienced vertical thickening as the glacier flowed westward from a steep, higher-velocity (60 m a–1) region into flat terrain associated with a 908 bend in the glacier and lower velocities (15 m a–1) to the south. Stratigraphy near the western side of the basin was surface-conformable to 170 m depth and thinned as flow diverged southward, down-glacier. We found complex strata beneath the conformable stratigraphy and interpret these features as buried crevasses, avalanche debris and deformed ice caused by up-glacier events. We also suggest that basin dimensions, bed topography and the sharp bend each cause flow extension and compression, significantly contributing to conformable and complex strata thickness variations. Our findings show that surface-conformable stratigraphy continuous with depth and consistent strata thicknesses cannot be assumed in accumulation basins, because local and upglacier terrain and flow dynamics can cause structural complexities to occur under and within surfaceconformable layers

Caffeine Consumption and Heart Rate and Blood Pressure Response to Regadenoson

BACKGROUND: Current guidelines recommend that caffeinated products should be avoided for at least 12 hours prior to regadenoson administration. We intended to examine the effect of caffeine consumption and of timing of last dose on hemodynamic effects after regadenoson administration for cardiac stress testing. METHODS: 332 subjects undergoing regadenoson stress testing were enrolled. Baseline characteristics, habits of coffee/caffeine exposure, baseline vital signs and change in heart rate, blood pressure, percent of maximal predicted heart rate, and percent change in heart rate were prospectively collected. RESULTS: Non-coffee drinkers (group 1) (73 subjects) and subjects who last drank coffee >24 hours (group 3) (139 subjects) prior to regadenoson did not demonstrate any difference in systolic blood pressure, heart rate change, maximal predicted heart rate and percent change in heart rate. Systolic blood pressure change (15.2±17.1 vs. 7.2±10.2 mmHg, p = 0.001), heart rate change (32.2±14 vs. 27.3±9.6 bpm, p = 0.038) and maximal predicted heart rate (65.5±15.6 vs. 60.7±8.6%, p = 0.038) were significantly higher in non-coffee drinkers (group 1) compared to those who drank coffee 12-24 hours prior (group 2) (108 subjects). Subjects who drank coffee >24 hours prior (group 3) exhibited higher systolic blood pressure change (13±15.8 vs. 7±10.2, p = 0.007), and heart rate change (32.1±15.3 vs. 27.3±9.6, p = 0.017) as compared to those who drank coffee 12-24 hours prior to testing (group 2). CONCLUSIONS: Caffeine exposure 12-24 hours prior to regadenoson administration attenuates the vasoactive effects of regadenoson, as evidenced by a blunted rise in heart rate and systolic blood pressure. These results suggest that caffeine exposure within 24 hours may reduce the effects of regadenoson administered for vasodilatory cardiac stress testing

Melt regimes, internal stratigraphy, and flow dynamics of three glaciers in the Alaska Range

We used ground-penetrating radar (GPR), GPS and glaciochemistry to evaluate melt regimes and ice depths, important variables for mass-balance and ice-volume studies, of Upper Yentna Glacier, Upper Kahiltna Glacier and the Mount Hunter ice divide, Alaska. We show the wet, percolation and dry snow zones located below 2700 m a.s.l., at 2700 to 3900 m a.s.l. and above 3900 m a.s.l., respectively. We successfully imaged glacier ice depths upwards of 480 m using 40–100 MHz GPR frequencies. This depth is nearly double previous depth measurements reached using mid-frequency GPR systems on temperate glaciers. Few Holocene-length climate records are available in Alaska, hence we also assess stratigraphy and flow dynamics at each study site as a potential ice-core location. Ice layers in shallow firn cores and attenuated glaciochemical signals or lacking strata in GPR profiles collected on Upper Yentna Glacier suggest that regions below 2800 m a.s.l. are inappropriate for paleoclimate studies because of chemical diffusion, through melt. Flow complexities on Kahiltna Glacier preclude ice-core climate studies. Minimal signs of melt or deformation, and depth–age model estimates suggesting 4815 years of ice on the Mount Hunter ice divide (3912 m a.s.l.) make it a suitable Holocene-age ice-core location

Constraining recent lead pollution sources in the North Pacific using ice core stable lead isotopes

Trends and sources of lead (Pb) aerosol pollution in the North Pacific rim of North America from 1850 to 2001 are investigated using a high-resolution (subannual to annual) ice core record recovered from Eclipse Icefield (3017 masl; St. Elias Mountains, Canada). Beginning in the early 1940s, increasing Pb concentration at Eclipse Icefield occurs coevally with anthropogenic Pb deposition in central Greenland, suggesting that North American Pb pollution may have been in part or wholly responsible in both regions. Isotopic ratios (208Pb/207Pb and 206Pb/207Pb) from 1970 to 2001 confirm that a portion of the Pb deposited at Eclipse Icefield is anthropogenic, and that it represents a variable mixture of East Asian (Chinese and Japanese) emissions transported eastward across the Pacific Ocean and a North American component resulting from transient meridional atmospheric flow. Based on comparison with source material Pb isotope ratios, Chinese and North American coal combustion have likely been the primary sources of Eclipse Icefield Pb over the 1970–2001 time period. The Eclipse Icefield Pb isotope composition also implies that the North Pacific mid-troposphere is not directly impacted by transpolar atmospheric flow from Europe. Annually averaged Pb concentrations in the Eclipse Icefield ice core record show no long-term trend during 1970–2001; however, increasing 208Pb/207Pb and decreasing 206Pb/207Pb ratios reflect the progressive East Asian industrialization and increase in Asian pollutant outflow. The post-1970 decrease in North American Pb emissions is likely necessary to explain the Eclipse Icefield Pb concentration time series. When compared with low (lichen) and high (Mt. Logan ice core) elevation Pb data, the Eclipse ice core record suggests a gradual increase in pollutant deposition and stronger trans-Pacific Asian contribution with rising elevation in the mountains of the North Pacific rim

Platelet Factor XIIIa Release During Platelet Aggregation and Plasma Clot Strength Measured by Thrombelastography in Patients with Coronary Artery Disease Treated with Clopidogrel.

It has been estimated that up to half of circulating Factor XIIIa (FXIIIa) is stored in platelets. The release of FXIIIa from platelets upon stimulation with ADP in patients with coronary artery disease treated with dual antiplatelet therapy has not been previously examined. Samples from 96 patients with established coronary artery disease treated with aspirin and clopidogrel were examined. Platelet aggregation was performed by light transmittance aggregometry (LTA) in platelet rich plasma (PRP) with platelet poor plasma (PPP) as reference and ADP 5μM as agonist. Kaolin activated TEG was performed in citrate PPP. PRP after aggregation was centrifuged and plasma supernatant (PSN) collected. FXIIIa was measured in PPP and PSN.Platelet aggregation after stimulation with ADP 5μM resulted in 24% additional FXIIIa release in PSN as compared to PPP (99.3 ± 27 vs. 80.3 ± 24 %, p<0.0001). FXIIIa concentration in PSN correlated with maximal plasma clot strength (TEG-G) (r=0.48, p<0.0001), but not in PPP (r=0.15, p=0.14). Increasing quartiles of platelet derived FXIIIa were associated with incrementally higher TEG-G (p=0.012). FXIIIa release was similar between clopidogrel responders and non-responders (p=0.18). In summary, platelets treated with aspirin and clopidogrel release a significant amount of FXIIIa upon aggregation by ADP. Platelet derived FXIIIa may contribute to differences in plasma TEG-G, and thus in part provide a mechanistic explanation for high clot strength observed as a consequence of platelet activation. Variability in clopidogrel response does not significantly influence FXIIIa release from platelets