Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.

The Dissociation of Location and Object Working Memory using fMRI and MEG

Visual working memory (VWM) involves maintaining and processing visual information, often for the purpose of making immediate decisions. Neuroimaging experiments of VWM provide evidence in support of a neural system mainly involving a fronto-parietal neuronal network, but the role of specific brain areas is less clear. A proposal that has recently generated considerable debate suggests that a dissociation of object and location VWM occurs within the prefrontal cortex, in dorsal and ventral regions, respectively. However, re-examination of the relevant literature presents a more robust distribution suggestive of a general caudal-rostral dissociation from occipital and parietal structures, caudally, to prefrontal regions, rostrally, corresponding to location and object memory, respectively. The purpose of the present study was to identify a dissociation of location and object VWM across two imaging methods (magnetoencephalography, MEG, and functional magnetic imaging, fMRI). These two techniques provide complimentary results due the high temporal resolution of MEG and the high spatial resolution of fMRI. The use of identical location and object change detection tasks was employed across techniques and reported for the first time. Moreover, this study is the first to use matched stimulus displays across location and object VWM conditions. The results from these two imaging methods provided convergent evidence of a location and object VWM dissociation favoring a general caudal-rostral rather than the more common prefrontal dorsal-ventral view. Moreover, neural activity across techniques was correlated with behavioral performance for the first time and provided convergent results. This novel approach of combining imaging tools to study memory resulted in robust evidence suggesting a novel interpretation of location and object memory. Accordingly, this study presents a novel context within which to explore the neural substrates of WM across imaging techniques and populations.

Sheep wool in Bronze and Iron Age Europe

This study presents the results of a series of wool measurements from Bronze Age and Iron Age skins and textiles from Hallstatt, and Bronze Age textiles from Scandinavia and the Balkans. A new method of classification that was set up and applied on mostly mineralised Iron Age material has now been applied to a large body of non-mineralised material from the Bronze and Iron Ages. Three types of microscopes were used and their advantages and disadvantages assessed. The results of the investigation cast new light on sheep breeding and fibre processing in prehistoric Europe, and suggest that different sheep breeds existed in Bronze Age Europe.

Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department.

BACKGROUND To date, the use of proton pump inhibitors (PPIs) has been associated with a low risk of hypomagnesaemia and associated adverse outcomes. We hypothesised that a better risk estimate could be derived from a large cohort of outpatients admitted to a tertiary emergency department (ED). METHODS A cross-sectional study was performed in 5118 patients who had measurements of serum magnesium taken on admission to a large tertiary care ED between January 2009 and December 2010. Hypomagnesaemia was defined as a serum magnesium concentration < 0.75 mmol/l. Demographical data, serum electrolyte values, data on medication, comorbidities and outcome with regard to length of hospital stay and mortality were analysed. RESULTS Serum magnesium was normally distributed where upon 1246 patients (24%) were hypomagnesaemic. These patients had a higher prevalence of out-of-hospital PPI use and diuretic use when compared with patients with magnesium levels > 0.75 mmol/l (both p < 0.0001). In multivariable regression analyses adjusted for PPIs, diuretics, renal function and the Charlson comorbidity index score, the association between use of PPIs and risk for hypomagnesaemia remained significant (OR = 2.1; 95% CI: 1.54-2.85). While mortality was not directly related to low magnesium levels (p = 0.67), the length of hospitalisation was prolonged in these patients even after adjustment for underlying comorbid conditions (p < 0.0001). CONCLUSION Use of PPIs predisposes patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of the underlying morbidity, posing a critical concern.

Protective role of autophagy and autophagy-related protein 5 in early tumorigenesis.

Autophagy, a fundamental cellular catabolic process, is involved in the development of numerous diseases including cancer. Autophagy seems to have an ambivalent impact on tumor development. While increasing evidence indicates a cytoprotective role for autophagy that can contribute to resistance against chemotherapy and even against the adverse, hypoxic environment of established tumors, relatively few publications focus on the role of autophagy in early tumorigenesis. However, the consensus is that autophagy is inhibitory for the genesis of tumors. To understand this apparent contradiction, more detailed information about the roles of the individual participants in autophagy is needed. This review will address this topic with respect to autophagy-related protein 5 (ATG5), which in several lines of investigation has been ascribed special significance in the autophagic pathway. Furthermore, it was recently shown that an ATG5 deficiency in melanocytes interferes with oncogene-induced senescence, thus promoting melanoma tumorigenesis. Similarly, an ATG5 deficiency resulted in tumors of the lung and liver in experimental mouse models. Taken together, these findings indicate that ATG5 and the autophagy to which it contributes are essential gatekeepers restricting early tumorigenesis in multiple tissues.

The genetics of reproductive organ morphology in two Petunia species with contrasting pollination syndromes

Main conclusion Switches between pollination syndromes have happened frequently during angiosperm evolution. Using QTL mapping and reciprocal introgressions, we show that changes in reproductive organ morphology have a simple genetic basis. In animal-pollinated plants, flowers have evolved to optimize pollination efficiency by different pollinator guilds and hence reproductive success. The two Petunia species, P. axillaris and P. exserta, display pollination syndromes adapted to moth or hummingbird pollination. For the floral traits color and scent, genetic loci of large phenotypic effect have been well documented. However, such large-effect loci may be typical for shifts in simple biochemical traits, whereas the evolution of morphological traits may involve multiple mutations of small phenotypic effect. Here, we performed a quantitative trait locus (QTL) analysis of floral morphology, followed by an in-depth study of pistil and stamen morphology and the introgression of individual QTL into reciprocal parental backgrounds. Two QTLs, on chromosomes II and V, are sufficient to explain the interspecific difference in pistil and stamen length. Since most of the difference in organ length is caused by differences in cell number, genes underlying these QTLs are likely to be involved in cell cycle regulation. Interestingly, conservation of the locus on chromosome II in a different P. axillaris subspecies suggests that the evolution of organ elongation was initiated on chromosome II in adaptation to different pollinators. We recently showed that QTLs for pistil and stamen length on chromosome II are tightly linked to QTLs for petal color and volatile emission. Linkage of multiple traits will enable major phenotypic change within a few generations in hybridizing populations. Thus, the genomic architecture of pollination syndromes in Petunia allows for rapid responses to changing pollinator availability.

The Restructuring in the Post-Crisis Korean Economy

The current paper evaluates the restructuring measures implemented in the post-crisis Korean economy. Its policies taken after the economic crisis were quite successful in terms of economic recovery. The financial and corporate sector reforms undertaken by the Korean government contributed to strengthening the banking and corporate sectors, attracting FDI inflows. However, most indicators show worsening of income inequalities and workers. situation regarding job security. The strengths as well as the weaknesses of the development strategy of Korea and its reform measures undertaken since the occurrence of the economic crisis need to be differentiated.

Recent distribution and accumulation of organic carbon on the continental margin west off Spitsbergen

The study compiles the controlling factors for organic matter sedimentation patterns from a suite of organogeochemical parameters in surface sediments off Spitsbergen and direct seabed observations using a Remotely Operated Vehicle (ROV). In addition we assess its storage rates as well as the potential of carbon sinks on the northwestern margin of the Barents Sea with short sediment cores from a selected fjord environment (Storfjord). While sedimentation in the fjords is mainly controlled by river/meltwater discharge and coastal erosion by sea ice/glaciers resulting in high supply of terrigenous organic matter, Atlantic water inflow, and thus enhanced marine organic matter supply, characterizes the environment on the outer shelf and slope. Local deviations from this pattern, particularly on the shelf, are due to erosion and out washing of fine-grained material by bottom currents. Spots dominated by marine productivity close to the island have been found at the outer Isfjord and west off Prins Karls Forland as well as off the Kongsfjord/Krossfjord area and probably reflect local upwelling of nutrient-rich Atlantic water-derived water masses. Accumulation rates of marine organic carbon as well as reconstructed primary productivities decreased since the middle of the last century. Negative correlation of the Isfjord temperature record with reconstructed productivities in the Storfjord could be explained by a reduced annual duration of the marginal ice zone in the area due to global warming. Extremely high accumulation rates of marine organic carbon between 5.4 and 17.2 g/m**2/yr mark the Storfjord area, and probably high-latitude fjord environments in general, as a sink for carbon dioxide.