Three-dimensional imaging core laboratory of the endovascular aneurysm repair trials: validation of methodology

OBJECTIVE: The aim of this study was to establish and validate a three-dimensional imaging protocol for the assessment of Computed Tomography (CT) scans of abdominal aortic aneurysms in UK EVAR trials patients. Quality control and repeatability of anatomical measurements is important for the validity of any core laboratory. METHODS: Three different observers performed anatomical measurements on 50 preoperative CT scans of aortic aneurysms using the Vitrea 2 three-dimensional post-imaging software in a core laboratory setting. We assessed the accuracy of intra and inter observer repeatability of measurements, the time required for collection of measurements, 3 different levels of automation and 3 different automated criteria for measurement of neck length. RESULTS: None of the automated neck length measurements demonstrated sufficient accuracy and it was necessary to perform checking of the important automated landmarks. Good intra and limited inter observer agreement were achieved with three-dimensional assessment. Complete assessment of the aneurysm and iliacs took an average (SD) of 17.2 (4.1) minutes. CONCLUSIONS: Aortic aneurysm anatomy can be assessed reliably and quickly using three-dimensional assessment but for scans of limited quality, manual checking of important landmarks remains necessary. Using a set protocol, agreement between observers is satisfactory but not as good as within observers.

Activity of the glycosylating enzyme, core 2 GlcNAc (beta1,6) transferase, is higher in polymorphonuclear leukocytes from diabetic patients compared with age-matched control subjects: relevance to capillary occlusion in diabetic retinopathy

The exact mechanism for capillary occlusion in diabetic retinopathy is still unclear, but increased leukocyte-endothelial cell adhesion has been implicated. We examined the possibility that posttranslational modification of surface O-glycans by increased activity of core 2 transferase (UDP-Glc:Galbeta1-3GalNAcalphaRbeta-N-acetylglucoaminyltr ansferase) is responsible for increased adhesion of leukocytes to vascular endothelium in diabetes. The mean activity of core 2 transferase in polymorphonuclear leukocytes isolated from type 1 and type 2 diabetic patients was higher compared with age-matched control subjects (1,638 +/- 91 [n = 42] vs. 249 +/- 35 pmol x h(-1) x mg(-1) protein [n = 24], P = 0.00013; 1,459 +/- 194 [n = 58] vs. 334 +/- 86 [n = 11], P = 0.01). As a group, diabetic patients with retinopathy had significantly higher mean activity of core 2 transferase compared with individuals with no retinopathy. There was a significant association between enzyme activity and severity of retinopathy in type 1 and type 2 diabetic patients. There was a strong correlation between activity of core 2 transferase and extent of leukocyte adhesion to cultured retinal capillary endothelial cells for diabetic patients but not for age-matched control subjects. Results from transfection experiments using human myelocytic cell line (U937) demonstrated a direct relationship between increased activity of core 2 transferase and increased binding to cultured endothelial cells. There was no relationship between activity of core 2 transferase and HbA(1c) (P = 0.8314), serum advanced glycation end product levels (P = 0.4159), age of the patient (P = 0.7896), and duration of diabetes (P = 0.3307). On the basis that branched O-glycans formed by the action of core 2 transferase participate in leukocyte adhesion, the present data suggest the involvement of this enzyme in increased leukocyte-endothelial cell adhesion and the pathogenesis of capillary occlusion in diabetic retinopathy.

The Southern Hemisphere at glacial terminations: insights from the Dome C ice core

The many different proxy records from the European Project for Ice Coring in Antarctica (EPICA) Dome C ice core allow for the first time a comparison of nine glacial terminations in great detail. Despite the fact that all terminations cover the transition from a glacial maximum into an interglacial, there are large differences between single terminations. For some terminations, Antarctic temperature increased only moderately, while for others, the amplitude of change at the termination was much larger. For the different terminations, the rate of change in temperature is more similar than the magnitude or duration of change. These temperature changes were accompanied by vast changes in dust and sea salt deposition all over Antarctica. Here we investigate the phasing between a South American dust proxy (non-sea-salt calcium flux, nssCa2+), a sea ice proxy (sea salt sodium flux, ssNa+) and a proxy for Antarctic temperature (deuterium, δD). In particular, we look into whether a similar sequence of events applies to all terminations, despite their different characteristics. All proxies are derived from the EPICA Dome C ice core, resulting in a relative dating uncertainty between the proxies of less than 20 years. At the start of the terminations, the temperature (δD) increase and dust (nssCa2+ flux) decrease start synchronously. The sea ice proxy (ssNa+ flux), however, only changes once the temperature has reached a particular threshold, approximately 5°C below present day temperatures (corresponding to a δD value of −420‰). This reflects to a large extent the limited sensitivity of the sea ice proxy during very cold periods with large sea ice extent. At terminations where this threshold is not reached (TVI, TVIII), ssNa+ flux shows no changes. Above this threshold, the sea ice proxy is closely coupled to the Antarctic temperature, and interglacial levels are reached at the same time for both ssNa+ and δD. On the other hand, once another threshold at approximately 2°C below present day temperature is passed (corresponding to a δD value of −402‰), nssCa2+ flux has reached interglacial levels and does not change any more, despite further warming. This threshold behaviour most likely results from a combination of changes to the threshold friction velocity for dust entrainment and to the distribution of surface wind speeds in the dust source region.

Glacial–interglacial dynamics of Antarctic firn columns: comparison between simulations and ice core air-δ15N measurements

Correct estimation of the firn lock-in depth is essential for correctly linking gas and ice chronologies in ice core studies. Here, two approaches to constrain the firn depth evolution in Antarctica are presented over the last deglaciation: outputs of a firn densification model, and measurements of δ15N of N2 in air trapped in ice core, assuming that δ15N is only affected by gravitational fractionation in the firn column. Since the firn densification process is largely governed by surface temperature and accumulation rate, we have investigated four ice cores drilled in coastal (Berkner Island, BI, and James Ross Island, JRI) and semi-coastal (TALDICE and EPICA Dronning Maud Land, EDML) Antarctic regions. Combined with available ice core air-δ15N measurements from the EPICA Dome C (EDC) site, the studied regions encompass a large range of surface accumulation rates and temperature conditions. Our δ15N profiles reveal a heterogeneous response of the firn structure to glacial–interglacial climatic changes. While firn densification simulations correctly predict TALDICE δ15N variations, they systematically fail to capture the large millennial-scale δ15N variations measured at BI and the δ15N glacial levels measured at JRI and EDML – a mismatch previously reported for central East Antarctic ice cores. New constraints of the EDML gas–ice depth offset during the Laschamp event (~41 ka) and the last deglaciation do not favour the hypothesis of a large convective zone within the firn as the explanation of the glacial firn model–δ15N data mismatch for this site. While we could not conduct an in-depth study of the influence of impurities in snow for firnification from the existing datasets, our detailed comparison between the δ15N profiles and firn model simulations under different temperature and accumulation rate scenarios suggests that the role of accumulation rate may have been underestimated in the current description of firnification models.

High-resolution mineral dust and sea ice proxy records from the Talos Dome ice core

In this study we report on new non-sea salt calcium (nssCa2+, mineral dust proxy) and sea salt sodium (ssNa+, sea ice proxy) records along the East Antarctic Talos Dome deep ice core in centennial resolution reaching back 150 thousand years (ka) before present. During glacial conditions nssCa2+ fluxes in Talos Dome are strongly related to temperature as has been observed before in other deep Antarctic ice core records, and has been associated with synchronous changes in the main source region (southern South America) during climate variations in the last glacial. However, during warmer climate conditions Talos Dome mineral dust input is clearly elevated compared to other records mainly due to the contribution of additional local dust sources in the Ross Sea area. Based on a simple transport model, we compare nssCa2+ fluxes of different East Antarctic ice cores. From this multi-site comparison we conclude that changes in transport efficiency or atmospheric lifetime of dust particles do have a minor effect compared to source strength changes on the large-scale concentration changes observed in Antarctic ice cores during climate variations of the past 150 ka. Our transport model applied on ice core data is further validated by climate model data. The availability of multiple East Antarctic nssCa2+ records also allows for a revision of a former estimate on the atmospheric CO2 sensitivity to reduced dust induced iron fertilisation in the Southern Ocean during the transition from the Last Glacial Maximum to the Holocene (T1). While a former estimate based on the EPICA Dome C (EDC) record only suggested 20 ppm, we find that reduced dust induced iron fertilisation in the Southern Ocean may be responsible for up to 40 ppm of the total atmospheric CO2 increase during T1. During the last interglacial, ssNa+ levels of EDC and EPICA Dronning Maud Land (EDML) are only half of the Holocene levels, in line with higher temperatures during that period, indicating much reduced sea ice extent in the Atlantic as well as the Indian Ocean sector of the Southern Ocean. In contrast, Holocene ssNa+ flux in Talos Dome is about the same as during the last interglacial, indicating that there was similar ice cover present in the Ross Sea area during MIS 5.5 as during the Holocene.

Expression and regulation of a hematopoietic proteoglycan core protein gene during hematopoiesis

Factors involved in regulating tissue specific gene expression play a major role in cell differentiation. In order to further understand the differentiation events occurring during hematopoiesis, a myeloid specific gene was characterized, the expression pattern during hematopoiesis was analyzed, and the mechanisms governing its regulation were assessed. Previously, our laboratory isolated an anonymous cDNA clone, pD-D1, which displayed preferential expression in myeloid cells. From nucleotide sequencing of overlapping cDNA clones I determined that the D-D1 message encodes a hematopoietic proteoglycan core protein (HpPG). The expression pattern of the gene was assessed by in situ hybridization of bone marrow and peripheral blood samples. The gene was shown to be expressed, at variable levels, in all leukocytes analyzed, including cells from every stage of neutrophil development. In an attempt to ascertain the differentiation time point in which the HpPG gene is initially expressed, more immature populations of leukemic myeloblasts were assessed by northern blot analysis. Though the initial point of expression was not obtained, an up-regulatory event was discovered corresponding to a time point in which granule genesis occurs. This finding is consistent with prior observations of extensive packaging of proteoglycans into the secretory granules of granule producing hematopoietic cells. The HpPG gene was also found to be expressed at low levels in all stages of lymphocyte development analyzed, suggesting that the HpPG gene is initially expressed before the decision for myeloid-lymphoid differentiation. To assess the mechanism for the up-regulatory event, a K562 in vitro megakaryocytic differentiation system was used. Nuclear run-off analyses in this system demonstrated the up-regulation to be under transcriptional control. In addition, the HpPG gene was found to be down regulated during macrophage differentiation of HL60 cells and was also shown to be transcriptionally controlled. These results indicate that there are multiple points of transcriptional regulation of the HpPG gene during differentiation. Furthermore, the factors regulating the gene at these time points are likely to play an important role in the differentiation of granule producing cells and macrophages. ^

CO(2) Diffusion in Polar Ice: Observations from Naturally Formed CO(2) Spikes in the Siple Dome (Antarctica) Ice Core

One common assumption in interpreting ice-core CO(2) records is that diffusion in the ice does not affect the concentration profile. However, this assumption remains untested because the extremely small CO(2) diffusion coefficient in ice has not been accurately determined in the laboratory. In this study we take advantage of high levels of CO(2) associated with refrozen layers in an ice core from Siple Dome, Antarctica, to study CO(2) diffusion rates. We use noble gases (Xe/Ar and Kr/Ar), electrical conductivity and Ca(2+) ion concentrations to show that substantial CO(2) diffusion may occur in ice on timescales of thousands of years. We estimate the permeation coefficient for CO(2) in ice is similar to 4 x 10(-21) mol m(-1) s(-1) Pa(-1) at -23 degrees C in the top 287 m (corresponding to 2.74 kyr). Smoothing of the CO(2) record by diffusion at this depth/age is one or two orders of magnitude smaller than the smoothing in the firn. However, simulations for depths of similar to 930-950m (similar to 60-70 kyr) indicate that smoothing of the CO(2) record by diffusion in deep ice is comparable to smoothing in the firn. Other types of diffusion (e.g. via liquid in ice grain boundaries or veins) may also be important but their influence has not been quantified.

Atmospheric Soluble Dust Records from a Tibetan Ice Core: Possible Climate Proxies and Teleconnection With the Pacific Decadal Oscillation

In autumn 2005, a joint expedition between the University of Maine and the Institute of Tibetan Plateau Research recovered three ice cores from Guoqu Glacier (33 degrees 34'37.80 '' N, 91 degrees 10'35.3 '' E, 5720 m above sea level) on the northern side of Mt. Geladaindong, central Tibetan Plateau. Isotopes ( delta(18)O), major soluble ions (Na(+), K(+), Mg(2+), Ca(2+), Cl(-), NO(3)(-), SO(4)(2-)), and radionuclide (beta-activity) measurements from one of the cores revealed a 70-year record (1935-2005). Statistical analysis of major ion time series suggests that atmospheric soluble dust species dominate the chemical signature and that background dust levels conceal marine ion species deposition. The soluble dust time series have interspecies relations and common structure (empirical orthogonal function (EOF) 1), suggesting a similar soluble dust source or transport route. Annual and seasonal correlations between the EOF 1 time series and National Centers for Environmental Prediction/National Center for Atmospheric Research reanalysis climate variables (1948-2004) suggest that the Mt. Geladaindong ice core record provides a proxy for local and regional surface pressure. An approximately threefold decrease of soluble dust concentrations in the middle to late 1970s, accompanied by regional increases in pressure and temperature and decreases in wind velocity, coincides with the major 1976-1977 shift of the Pacific Decadal Oscillation (PDO) from a negative to a positive state. This is the first ice core evidence of a potential teleconnection between central Asian atmospheric soluble dust loading and the PDO. Analysis of temporally longer ice cores from Mt. Geladaindong may enhance understanding of the relationship between the PDO and central Asian atmospheric circulation and subsequent atmospheric soluble dust loading.

A Record of Atmospheric Co2 During the Last 40,000 Years from the Siple Dome, Antarctica Ice Core

We have measured the CO2 concentration of air occluded during the last 40,000 years in the deep Siple Dome A ( hereafter Siple Dome) ice core, Antarctica. The general trend of CO2 concentration from Siple Dome ice follows the temperature inferred from the isotopic composition of the ice and is mostly in agreement with other Antarctic ice core CO2 records. CO2 rose initially at similar to 17.5 kyr B. P. ( thousand years before 1950), decreased slowly during the Antarctic Cold Reversal, rose during the Younger Dryas, fell to a local minimum at around 8 kyr B. P., and rose continuously since then. The CO2 concentration never reached steady state during the Holocene, as also found in the Taylor Dome and EPICA Dome C ( hereafter Dome C) records. During the last glacial termination, a lag of CO2 versus Siple Dome isotopic temperature is probable. The Siple Dome CO2 concentrations during the last glacial termination and in the Holocene are at certain times greater than in other Antarctic ice cores by up to 20 ppm (mumol CO2/mol air). While in situ production of CO2 is one possible cause of the sporadic elevated levels, the mechanism leading to the enrichment is not yet clear.

A 700-Year Record of Atmospheric Circulation Developed from the Law Dome Ice Core, East Antarctica

A 700-year, high-resolution, multivariate ice core record from Dome Summit South (DSS) (66degrees46'S, 112degrees48'E; 1370 m), Law Dome, is used to investigate sea level pressure (SLP) variability in the region of East Antarctica. Empirical orthogonal function (EOF) analysis reveals that the first EOF (LDEOF1) of the combined glaciochemical, oxygen isotope ratio, and accumulation rate record from DSS represents most of the variability in sea salt seen in the record. LDEOF1 is positively correlated (at least 95% confidence level) to instrumental June mean SLP across most of East Antarctica. Over the last 700 years, LDEOF1 levels at Law Dome were the highest during the nineteenth century, suggesting an increase in intensification of winter circulation during this period. The Law Dome DSS oxygen isotope ratio series also indicates that the nineteenth century had the coldest winters of any century in the record. In contrast, LDEOF1 levels were the lowest at Law Dome during the eighteenth century, suggesting a significant shift in the patterns and/or intensity of East Antarctic atmospheric circulation between the eighteenth and the nineteenth centuries. The LDEOF1 sea salt record is characterized by significant decadal-scale variability with a strong 25-year periodic structure.

Changes of coronary plaque composition correlate with C-reactive protein levels in patients with ST-elevation myocardial infarction following high-intensity statin therapy.

OBJECTIVES Levels of inflammatory biomarkers associate with changes of coronary atheroma burden in statin-treated patients with stable coronary artery disease. This study sought to determine changes of plaque composition in vivo in relation to high-sensitivity C-reactive protein (hs-CRP) levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy. METHODS The IBIS-4 study performed serial (baseline and 13-month), 2-vessel intravascular ultrasound (IVUS) and radiofrequency-IVUS of the non-infarct-related arteries in patients with STEMI treated with high-intensity statin therapy. The present analysis included 44 patients (80 arteries) with serial measurements of hs-CRP. RESULTS At follow-up, median low-density lipoprotein cholesterol (LDL-C) levels decreased from 126 to 77 mg/dl, HDL-C increased from 44 to 47 mg/dl, and hs-CRP decreased from 1.6 to 0.7 mg/L. Regression of percent atheroma volume (-0.99%, 95% CI -1.84 to -0.14, p = 0.024) was accompanied by reduction of percent fibro-fatty (p = 0.04) and fibrous tissue (p < 0.001), and increase in percent necrotic core (p = 0.006) and dense calcium (p < 0.001). Follow-up levels of hs-CRP, but not LDL-C, correlated with changes in percent necrotic core (p = 0.001) and inversely with percent fibrous tissue volume (p = 0.008). Similarly, baseline-to-follow-up change of hs-CRP correlated with the change in percent necrotic core volume (p = 0.02). CONCLUSIONS In STEMI patients receiving high-intensity statin therapy, stabilization of VH-IVUS-defined necrotic core was confined to patients with lowest on-treatment levels and greatest reduction of hs-CRP. Elevated CRP levels at follow-up may identify progression of high-risk coronary plaque composition despite intensive statin therapy and overall regression of atheroma volume.

Deep-sea sediment core PS2644 record from the southern Greenland Sea

The PS2644 deep-sea core sequence, retrieved from the northwestern margin of Iceland and covering the last 86 ka, exhibits high sedimentation rates during the last glacial cycle that allow the clear distinction of Greenland stadial (GS)/ interstadial (GI) cycles in the various proxy records. Abundance records of rhyolitic, basaltic and tachylytic tephra grains reveal several maxima. Tephra grains of all types were geochemically analyzed in 44 levels. A total of 92 tephras with a distinctive character have been defined within the glacial sequence of gravity core PS2644-5, whereas the Holocene record is dominated by reworked Vedde Ash grains and not suitable for tephra stratigraphic work. Of the 92 tephras only 19 geochemical populations have been linked with confidence to previously defined tephras such as from the Vedde Ash, Faeroe Marine Ash Zones (FMAZ) II and III and North Atlantic Ash Zone (NAAZ) II. For the glacial period informal names were given to 78 new tephras, most of which are basaltic tephras. Several of these layers have a unique geochemical character and might become new chronostratigraphic markers in the North Atlantic region. Linking the tephra populations to the volcanic system producing them, respectively, revealed that Icelandic eruptions dominate with 83 tephra geochemical populations and Jan Mayen with 9. Around 48% of the informal tephra layers linked to the Icelandic volcanic province are produced from either the Grimsvötn or the Veidivötn-Bardarbunga volcanic systems. The intervals spanning from Greenland Stadial (GS) 3 to Greenland Interstadial (GI) 4 (24.5-29 ka BP), from GI 8 to GS 10 (36.9-40.5 ka BP) and from GI 14 to GI 15.2 (50-56 ka BP) are the periods with the highest number of eruptions, all of which are associated with known tephra zones.

Chemical analysis with regard to global and local climatic forcing measured on sediment core GeoB3711-1, GeoB3711-3 and GeoB4917-8

Global and local climatic forcing, e.g. concentration of atmospheric CO2 or insolation, influence the distribution of C3 and C4 plants in southwest Africa. C4 plants dominate in more arid and warmer areas and are favoured by lower pCO2 levels. Several studies have assessed past and present continental vegetation by the analysis of terrestrial n-alkanes in near-coastal deep sea sediments using single samples or a small number of samples from a given climatic stage. The objectives of this study were to evaluate vegetation changes in southwest Africa with regard to climatic changes during the Late Pleistocene and the Holocene and to elucidate the potential of single sample simplifications. We analysed two sediment cores at high resolution, altogether ca. 240 samples, from the Southeast Atlantic Ocean (20°S and 12°S) covering the time spans of 18 to 1 ka and 56 to 2 ka, respectively. Our results for 20°S showed marginally decreasing C4 plant domination (of ca. 5%) during deglaciation based on average chain length (ACL27-33 values) and carbon isotopic composition of the C31 and C33 n-alkanes. Values for single samples from 18 ka and the Holocene overlap and, thus, are not significantly representative of the climatic stages they derive from. In contrast, at 12°S the n-alkane parameters show a clear difference of plant type for the Late Pleistocene (C4 plant domination, 66% C4 on average) and the Holocene (C3 plant domination, 40% C4 on average). During deglaciation vegetation change highly correlates with the increase in pCO2 (r² = 0.91). Short-term climatic events such as Heinrich Stadials or Antarctic warming periods are not reflected by vegetation changes in the catchment area. Instead, smaller vegetation fluctuations during the Late Pleistocene occur in accordance with local variations of insolation.

High-resolution carbon dioxide concentration records from the EPICA Dome C ice core (EDC99)

Changes in past atmospheric carbon dioxide concentrations can be determined by measuring the composition of air trapped in ice cores from Antarctica. So far, the Antarctic Vostok and EPICA Dome C ice cores have provided a composite record of atmospheric carbon dioxide levels over the past 650,000 years. Here we present results of the lowest 200 m of the Dome C ice core, extending the record of atmospheric carbon dioxide concentration by two complete glacial cycles to 800,000 yr before present. From previously published data and the present work, we find that atmospheric carbon dioxide is strongly correlated with Antarctic temperature throughout eight glacial cycles but with significantly lower concentrations between 650,000 and 750,000 yr before present. Carbon dioxide levels are below 180 parts per million by volume (p.p.m.v.) for a period of 3,000 yr during Marine Isotope Stage 16, possibly reflecting more pronounced oceanic carbon storage. We report the lowest carbon dioxide concentration measured in an ice core, which extends the pre-industrial range of carbon dioxide concentrations during the late Quaternary by about 10 p.p.m.v. to 172-300 p.p.m.v.