Varying sediment sources (Hudson Strait, Cumberland Sound, Baffin Bay) to the NW Labrador Sea slope between and during Heinrich events 0 to 4

Core HU97048-007PC was recovered from the continental Labrador Sea slope at a water depth of 945m, 250km seaward from the mouth of Cumberland Sound, and 400km north of Hudson Strait. Cumberland Sound is a structural trough partly floored by Cretaceous mudstones and Paleozoic carbonates. The record extends from ~ 10 to 58k cal a BP. On-board logging revealed a complex series of lithofacies, including buff-colored detrital carbonate-rich sediments [Heinrich (H)-events] frequently bracketed by black facies. We investigate the provenance of these facies using quantitative X-ray diffraction on drill-core samples from Paleozoic and Cretaceous bedrock from the SE Baffin Island Shelf, and on the \u3c 2-mm sediment fraction in a transect of five cores from Cumberland Sound to the NW Labrador Sea. A sediment unmixing program was used to discriminate between sediment sources, which included dolomite-rich sediments from Baffin Bay, calcite-rich sediments from Hudson Strait and discrete sources from Cumberland Sound. Results indicated that the bulk of the sediment was derived from Cumberland Sound, but Baffin Bay contributed to sediments coeval with H-0 (Younger Dryas), whereas Hudson Strait was the source during H-events 1–4. Contributions from the Cretaceous outcrops within Cumberland Sound bracket H-events, thus both leading and lagging Hudson Strait-sourced H-events

Varying sediment sources (Hudson Strait, Cumberland Sound, Baffin Bay) to the NW Labrador Sea slope between and during Heinrich events 0 to 4

Core HU97048-007PC was recovered from the continental Labrador Sea slope at a water depth of 945m, 250km seaward from the mouth of Cumberland Sound, and 400km north of Hudson Strait. Cumberland Sound is a structural trough partly floored by Cretaceous mudstones and Paleozoic carbonates. The record extends from ~ 10 to 58k cal a BP. On-board logging revealed a complex series of lithofacies, including buff-colored detrital carbonate-rich sediments [Heinrich (H)-events] frequently bracketed by black facies. We investigate the provenance of these facies using quantitative X-ray diffraction on drill-core samples from Paleozoic and Cretaceous bedrock from the SE Baffin Island Shelf, and on the \u3c 2-mm sediment fraction in a transect of five cores from Cumberland Sound to the NW Labrador Sea. A sediment unmixing program was used to discriminate between sediment sources, which included dolomite-rich sediments from Baffin Bay, calcite-rich sediments from Hudson Strait and discrete sources from Cumberland Sound. Results indicated that the bulk of the sediment was derived from Cumberland Sound, but Baffin Bay contributed to sediments coeval with H-0 (Younger Dryas), whereas Hudson Strait was the source during H-events 1–4. Contributions from the Cretaceous outcrops within Cumberland Sound bracket H-events, thus both leading and lagging Hudson Strait-sourced H-events

Fast Excitation and Photon Emission of a Single-Atom-Cavity System

We report on the fast excitation of a single atom coupled to an optical cavity using laser pulses that are much shorter than all other relevant processes. The cavity frequency constitutes a control parameter that allows the creation of single photons in a superposition of two tunable frequencies. Each photon emitted from the cavity thus exhibits a pronounced amplitude modulation determined by the oscillatory energy exchange between the atom and the cavity. Our technique constitutes a versatile tool for future quantum networking experiments.Comment: 4 pages, 5 figure

A five-year observance of changes in the cardiovascular risk profile in 505 HIV-positive individuals

Purpose: Since the introduction of antiretroviral therapy (ART) and the extension of life expectancy, HIV-infected persons have shown an increasing number of cardiovascular events. The reduction of cardiovascular risk factors becomes a new challenge in HIV care. One of the main objectives of the HIV&HEART study is to examine the development of cardiovascular risk factors and treatment of cardiovascular diseases. Methods: This study is an on-going, prospective, regional multicentre trial that was conducted to analyse the frequency and clinical course of cardiac disorders as well as cardiovascular risk factors in HIV-infected patients. 505 HIV-infected outpatients were recruited at baseline (BL) and re-examined during 5-year follow up (5YFU). Results: 84% of 505 eligible HIV-infected patients were male. The average age was 44.3±9.5 years at BL. The proportion of ART-treated patients increased from 85.7% at BL to 96.4% at 5YFU. During the 5-year observation period mean cardiovascular risk detected by Framingham score increased from 6% at BL to 10% at 5YFU. Even after adjusting for age there was a difference in the Framingham score of 2%. Between BL and 5YFU systolic blood pressure increased from 128.4±19.8 mmHg to 138.3±19.9 mmHg in spite of an intensified use of antihypertensive drugs, from 11.9% at BL to 24.0% at 5YFU. The rate of participants with adiposity, characterised by a BMI>30, increased from 7.9% at BL to 11.2% at 5YFU. Lipid-lowering therapy was applied in 10.3% of the patients at BL and in 13.9% at 5YFU. Triglycerides (TAG)≥200 mg/dl reduced from 38.9% at BL to 36.8% at 5YFU; in contrast cholesterol values≥200 mg/dl elevated from 57.8% to 61.8%. The same trend was observed in HDL≤40 mg/dl. Here we found a change from 29.2% versus 31.3%. Doing regular sports elevated from 1.9% to 3.3%. The count of smokers increased for 2.8% and also mean pack-years changes from 24 to 26.5 pack-years. Conclusion: During a 5-year period the cardiovascular risk in Framingham score increased disproportionately high in this HIV-infected cohort even after adjusting for age. There was an increasing blood pressure although an elevated use of antihypertensive therapy. There was also a tendency of elevating BMI and an increasing trend in smoking behavior. As protective facts, we found a tendency in doing sports and a decreasing TAG value during intensifying lipid-lowering therapy. Cardiovascular risk was increasing, in spite of interventions

AMS INSIGHT—Absorbable Metal Stent Implantation for Treatment of Below-the-Knee Critical Limb Ischemia: 6-Month Analysis

Endoluminal treatment of infrapopliteal artery lesions is a matter of controversy. Bioabsorbable stents are discussed as a means to combine mechanical prevention of vessel recoil with the advantages of long-term perspectives. The possibility of not having a permanent metallic implant could permit the occurrence of positive remodeling with lumen enlargement to compensate for the development of new lesions. The present study was designed to investigate the safety of absorbable metal stents (AMSs) in the infrapopliteal arteries based on 1- and 6-month clinical follow-up and efficacy based on 6-month angiographic patency. One hundred seventeen patients with 149 lesions with chronic limb ischemia (CLI) were randomized to implantation of an AMS (60 patients, 74 lesions) or stand-alone percutaneous transluminal angioplasty (PTA; 57 patients, 75 lesions). Seven PTA-group patients “crossed over” to AMS stenting. The study population consisted of patients with symptomatic CLI (Rutherford categories 4 and 5) and de novo stenotic (>50%) or occlusive atherosclerotic disease of the infrapopliteal arteries who presented with a reference diameter of between 3.0 and 3.5 mm and a lesion length of <15 mm. The primary safety endpoint was defined as absence of major amputation and/or death within 30 days after index intervention and the primary efficacy endpoint was the 6-month angiographic patency rate as confirmed by core-lab quantitative vessel analysis. The 30-day complication rate was 5.3% (3/57) and 5.0% (3/60) in patients randomized for PTA alone and PTA followed by AMS implantation, respectively. On an intention-to-treat basis, the 6-month angiographic patency rate for lesions treated with AMS (31.8%) was significantly lower (p = 0.013) than the rate for those treated with PTA (58.0%). Although the present study indicates that the AMS technology can be safely applied, it did not demonstrate efficacy in long-term patency over standard PTA in the infrapopliteal vessels

Intracoronary Brachytherapy, a Promising Treatment Option for Diabetic Patients: Results from a European Multicenter Registry (RENO)

Despite advances in the interventional treatment of coronary disease, diabetics still have double the case fatality rate as nondiabetics. The purpose of this an

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P &lt; 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

NMR Analysis of the Dynamic Exchange of the NS2B Cofactor between Open and Closed Conformations of the West Nile Virus NS2B-NS3 Protease

Dengue and West Nile virus infections put an estimated 2.5 billion people at risk. Neither drugs nor vaccines are currently available against these diseases. The non-structural protein NS3 is a protease that, together with the cofactor NS2B, is essential for viral maturation. The NS2B-NS3 proteases of dengue and West Nile viruses are highly homologous and present promising drug targets. Crystal structures of the West Nile virus protease with and without bound inhibitor revealed large structural differences in NS2B, while no crystal structure of the dengue virus protease could be determined with a bound inhibitor. We investigated the structural change in solution and found that the C-terminal segment (CTS) of the NS2B cofactor is prone to dissociation from NS3. In the case of the West Nile virus protease, the CTS of NS2B is mostly associated with NS3, especially in the presence of inhibitors. In the case of the dengue virus protease and in the absence of inhibitors, the CTS of NS2B is mostly dissociated from NS3. Finding drug candidates to inhibit the association of the NS2B cofactor may thus be easier for the dengue virus protease

Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults