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  • 1
    Publication Date: 2015-02-04
    Description: Nature Geoscience 8, 122 (2015). doi:10.1038/ngeo2349 Authors: Hanno Meyer, Thomas Opel, Thomas Laepple, Alexander Yu Dereviagin, Kirstin Hoffmann & Martin Werner Relative to the past 2,000 years, the Arctic region has warmed significantly over the past few decades. However, the evolution of Arctic temperatures during the rest of the Holocene is less clear. Proxy reconstructions, suggest a long-term cooling trend throughout the mid- to late Holocene, whereas climate model simulations show only minor changes or even warming. Here we present a record of the oxygen isotope composition of permafrost ice wedges from the Lena River Delta in the Siberian Arctic. The isotope values, which reflect winter season temperatures, became progressively more enriched over the past 7,000 years, reaching unprecedented levels in the past five decades. This warming trend during the mid- to late Holocene is in opposition to the cooling seen in other proxy records. However, most of these existing proxy records are biased towards summer temperatures. We argue that the opposing trends are related to the seasonally different orbital forcing over this interval. Furthermore, our reconstructed trend as well as the recent maximum are consistent with the greenhouse gas forcing and climate model simulations, thus reconciling differing estimates of Arctic and northern high-latitude temperature evolution during the Holocene.
    Print ISSN: 1752-0894
    Electronic ISSN: 1752-0908
    Topics: Geosciences
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  • 2
    Publication Date: 2013-06-29
    Description: Background: Multiple solutes are retained in uremia, but it is currently unclear which solutes are toxic. Small studies suggest that protein-bound solutes, such as p-cresol sulfate and indoxyl sulfate and intracellular solutes, such as methylamine (MMA) and dimethylamine (DMA), may be toxic. Our objective was to test whether elevated levels of these solutes were associated with mortality. Methods: We conducted a prospective cohort study in 521 U.S. incident hemodialysis patients to evaluate associations between these solutes and all-cause and cardiovascular mortality. P-cresol sulfate, indoxyl sulfate, MMA and DMA levels were measured from frozen plasma samples obtained 2 to 6 months after initiation of dialysis. Mortality data was available through 2004 using the National Death Index. Results: Elevated (greater than the population median) p-cresol sulfate, MMA or DMA levels were not associated with all-cause or cardiovascular mortality. Elevated indoxyl sulfate levels were associated with all-cause mortality but not cardiovascular mortality (hazard ratio 1.30 (95% confidence interval 1.01, 1.69) p-value 0.043). Conclusions: In this cohort of 521 incident hemodialysis patients, only elevated indoxyl sulfate levels were associated with all-cause mortality. Further research is needed to identify causes of the toxicity of uremia to provide better care for patients with kidney disease.
    Electronic ISSN: 1471-2369
    Topics: Medicine
    Published by BioMed Central
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  • 3
    Publication Date: 2013-10-05
    Description: The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option. This novel model system of AML1-ETO driven acute myeloid leukaemia addresses the concept of ‘oncogene addiction’. Better understanding of AML1-ETO need to maintain leukemia and rewire the transcriptome may help to design future therapies.
    Print ISSN: 1757-4676
    Electronic ISSN: 1757-4684
    Topics: Medicine
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  • 4
    Publication Date: 2018-07-10
    Description: Consistent epidemiological data demonstrate that patients with heart failure with preserved ejection fraction (HFpEF) are more likely to be women than men. Exploring mechanisms behind this sex difference in heart failure epidemiology may enrich the understanding of underlying HFpEF pathophysiology and phenotypes, with the ultimate goal of identifying therapeutic approaches for the broader HFpEF population. In this review we evaluate the influence of sex on the key domains of cardiac structure and function, the systemic and pulmonary circulation, as well as extracardiac factors and comorbidities that may explain the predisposition of women to HFpEF. We highlight the potential role of factors exclusive to or more prevalent in women such as pregnancy, preeclampsia, and iron deficiency. Finally, we discuss existing controversies and gaps in knowledge, as well as the clinical importance of known sex differences in the context of the potential need for sex-specific diagnostic criteria, improved risk stratification models, and targeted therapies.
    Keywords: Pregnancy, Risk Factors, Women, Heart Failure, Remodeling
    Electronic ISSN: 1524-4539
    Topics: Medicine
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  • 5
    Publication Date: 2012-05-26
    Description: Modeling sub-canopy elevation is an important step in the processing of waveform lidar data to measure three dimensional forest structure. Here, we present a methodology based on high resolution discrete-return lidar (DRL) to correct the ground elevation derived from large-footprint Laser Vegetation Imaging Sensor (LVIS) and to improve measurement of forest structure. We use data acquired over Barro Colorado Island, Panama by LVIS large-footprint lidar (LFL) in 1998 and DRL in 2009. The study found an average vertical difference of 28.7 cm between 98,040 LVIS last-return points and the discrete-return lidar ground surface across the island. The majority (82.3%) of all LVIS points matched discrete return elevations to 2 m or less. Using a multi-step process, the LVIS last-return data is filtered using an iterative approach, expanding window filter to identify outlier points which are not part of the ground surface, as well as applying vertical corrections based on terrain slope within the individual LVIS footprints. The results of the experiment demonstrate that LFL ground surfaces can be effectively filtered using methods adapted from discrete-return lidar point filtering, reducing the average vertical error by 15 cm and reducing the variance in LVIS last-return data by 70 cm. The filters also reduced the largest vertical estimations caused by sensor saturation in the upper reaches of the forest canopy by 14.35 m, which improve forest canopy structure measurement by increasing accuracy in the sub-canopy digital elevation model.
    Electronic ISSN: 2072-4292
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by MDPI Publishing
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  • 6
    Publication Date: 2012-10-16
    Description: The Authors Reply: Kidney International 82, 1033 (November (1) 2012). doi:10.1038/ki.2012.291 Authors: Timothy W Meyer & Thomas H Hostetter
    Topics: Medicine
    Published by Elsevier
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