BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

No abstract

Experimental demethylation of plant DNA enables testing for epigenetic effects in a simple and straightforward way without the use of expensive and laborious DNA sequencing. Plants are commonly demethylated during their germination with the application of agents such as 5‐azacytidine (5‐azaC). However, this approach can cause unwanted effects such as underdeveloped root systems and high mortality of treated plants, hindering a full comparison with untreated plants, and can be applied only on plant reproducing by seeds. Here we test a simple alternative method of plant demethylation designed to overcome the shortcomings of the germinating method. We compared a novel method of demethylating plants, based on periodical spraying of 5‐azaC aqueous solution on established seedlings, with the previous method in which seeds were germinated directly in 5‐azaC solution. We quantified the amount of methylated DNA and measured various aspects of plant performance. Also, we demonstrated its applicability in ecological epigenetic experiments by testing transgenerational effects of plant–plant competition. We found that the spray application had similar DNA‐demethylating efficiency than the germination method, particularly in the earlier phases of plant development, but without unwanted effects. The spray application method did not reduce plant growth and performance compared to untreated plants, as opposed to the traditional method which showed reduced growth. Also, the spray application method equalized the epigenetically modified plant features of seedlings coming from plants grown under competition and plants growing without competition, demonstrating its application in ecological epigenetic experiments. We conclude that regular spraying of 5‐azaC solution onto established seedlings surpassed the germination‐in‐solution method in terms of vigour and fitness of treated plants. This novel method could thus be better suited for experimental studies seeking valuable insights into ecological epigenetics. Furthermore, the spray method can be suitable for clonal species reproducing asexually, and most importantly, it opens the possibility of community‐level experimental demethylation of plants.

Secular trends of adiposity and motor development in preschool children since the fifties of the last century up to the beginning of this millennium were analyzed so as to reveal possible changes due to continuously differentiating lifestyle. In preschool children (n = 3678) height, weight, skinfold thickness over triceps, subscapular, and suprailiac were measured by Harpenden caliper in 1957, 1977, 1980, 1985, 1990, and 2012. Simultaneously, motor performance was tested by evaluating the achievements in broad jump and throwing a ball, as a marker of adaptation to changing level of physical activity, free games, and exercise. Along the period of five decades the values of skinfold thickness increased significantly until 2012, mainly on the trunk. Simultaneously, the level of motor performance significantly decreased. Modifications of the way of life during the mentioned five decades characterized by sedentarism and inadequate food intake as related to energy output influenced negatively both adiposity and motor performance already in preschool children. Mostly increased deposition of fat on the trunk which is considered as a marker of possible development of metabolic syndrome was apparent already in preschool age, indicating the importance of early intervention concerning also physical activity and availability for exercise since early life.

No abstract

Phenotypic plasticity, within and across generations (transgenerational plasticity), allows organisms and their progeny to adapt to the environment without modification of the underlying DNA. Recent findings suggest that epigenetic modifications are important mediators of such plasticity. However, empirical studies have, so far, mainly focused on plasticity in response to abiotic factors, overlooking the response to competition. We tested for within-generation and transgenerational phenotypic plasticity triggered by plant-plant competition intensity, and we tested whether it was mediated via DNA methylation, using the perennial, apomictic herb Taraxacum brevicorniculatum in four coordinated experiments. We then tested the consequences of transgenerational plasticity affecting competitive interactions of the offspring and ecosystem processes, such as decomposition. We found that, by promoting differences in DNA methylation, offspring of plants under stronger competition developed faster and presented more resource-conservative phenotypes. Further, these adjustments associated with less degradable leaves, which have the potential to reduce nutrient turnover and might, in turn, favour plants with more conservative traits. Greater parental competition enhanced competitive abilities of the offspring, by triggering adaptive phenotypic plasticity, and decreased offspring leaf decomposability. Our results suggest that competition-induced transgenerational effects could promote rapid adaptations and species coexistence and feed back on biodiversity assembly and nutrient cycling.

No abstract

Functional and phylogenetic diversity (FD and PD respectively) of the resident community are expected to exert a key role in community resistance to colonization by surrounding species, and their establishment success. However, few studies have explored this topic experimentally or evaluated the interactive effects of these diversity measures. We implemented a diversity experiment to disentangle the role of FD and PD by sowing mixtures of 6 species, drawn from a pool of 19 species naturally coexisting in central European mesic meadows. The mixtures were designed to cover four independent combinations of high and low FD and PD. Species covers were estimated in spring and late summer over two growing seasons. We then assessed the establishment success of colonizers as a function of their mean traits and phylogenetic distance to the resident (i.e. sown) communities, as well as the resistance of the resident communities to natural colonizers as a function of their functional and phylogenetic structure. Results generally indicated a temporal shift regarding which trait values made a colonizer successful, from an acquisitive strategy in early stages to a more conservative trait syndrome in later stages. FD decreased community resistance to natural colonization. However, PD tempered this effect: with high PD, FD was not significant, suggesting complementary information between these two components of biodiversity. On average, colonizing species were more functionally distant from the resident species in sown communities with high functional diversity, i.e. those that were more colonized. Synthesis. Our results confirm an interplay between FD and PD during community assembly processes, namely resistance to colonizers, suggesting that these two descriptors of biodiversity only partially overlap in their contribution to the overall ecological structure of a community. The hypothesis that higher FD increases resistance through a more complete use of resources was challenged. Results rather suggested that greater FD could provide an unsaturated functional trait space allowing functionally unique species to occupy it.