61 research outputs found

    Identification of Periostin as a Critical Marker of Progression/Reversal of Hypertensive Nephropathy

    Get PDF
    Progression of chronic kidney disease (CKD) is a major health issue due to persistent accumulation of extracellular matrix in the injured kidney. However, our current understanding of fibrosis is limited, therapeutic options are lacking, and progressive degradation of renal function prevails in CKD patients. Uncovering novel therapeutic targets is therefore necessary

    How Much Rugby is Too Much? A Seven-Season Prospective Cohort Study of Match Exposure and Injury Risk in Professional Rugby Union Players.

    Get PDF
    INTRODUCTION: Numerous studies have documented the incidence and nature of injuries in professional rugby union, but few have identified specific risk factors for injury in this population using appropriate statistical methods. In particular, little is known about the role of previous short-term or longer-term match exposures in current injury risk in this setting. OBJECTIVES: Our objective was to investigate the influence that match exposure has upon injury risk in rugby union. METHOD: We conducted a seven-season (2006/7-2012/13) prospective cohort study of time-loss injuries in 1253 English premiership professional players. Players' 12-month match exposure (number of matches a player was involved in for ≥20 min in the preceding 12 months) and 1-month match exposure (number of full-game equivalent [FGE] matches in preceding 30 days) were assessed as risk factors for injury using a nested frailty model and magnitude-based inferences. RESULTS: The 12-month match exposure was associated with injury risk in a non-linear fashion; players who had been involved in fewer than ≈15 or more than ≈35 matches over the preceding 12-month period were more susceptible to injury. Monthly match exposure was linearly associated with injury risk (hazard ratio [HR]: 1.14 per 2 standard deviation [3.2 FGE] increase, 90% confidence interval [CI] 1.08-1.20; likely harmful), although this effect was substantially attenuated for players in the upper quartile for 12-month match exposures (>28 matches). CONCLUSION: A player's accumulated (12-month) and recent (1-month) match exposure substantially influences their current injury risk. Careful attention should be paid to planning the workloads and monitoring the responses of players involved in: (1) a high (>≈35) number of matches in the previous year, (2) a low (<≈15) number of matches in the previous year, and (3) a low-moderate number of matches in previous year but who have played intensively in the recent past. These findings make a major contribution to evidence-based policy decisions regarding match workload limits in professional rugby union

    Increasing altruistic and cooperative behaviour with simple moral nudges

    Get PDF
    The conflict between pro-self and pro-social behaviour is at the core of many key problems of our time, as, for example, the reduction of air pollution and the redistribution of scarce resources. For the well-being of our societies, it is thus crucial to find mechanisms to promote pro-social choices over egoistic ones. Particularly important, because cheap and easy to implement, are those mechanisms that can change people's behaviour without forbidding any options or significantly changing their economic incentives, the so-called "nudges". Previous research has found that moral nudges (e.g., making norms salient) can promote pro-social behaviour. However, little is known about whether their effect persists over time and spills across context. This question is key in light of research showing that pro-social actions are often followed by selfish actions, thus suggesting that some moral manipulations may backfire. Here we present a class of simple moral nudges that have a great positive impact on pro-sociality. In Studies 1-4 (total N = 1,400), we use economic games to demonstrate that asking subjects to self-report "what they think is the morally right thing to do" does not only increase pro-sociality in the choice immediately after, but also in subsequent choices, and even when the social context changes. In Study 5, we explore whether moral nudges promote charity donations to humanitarian organisations in a large (N = 1,800) crowdfunding campaign. We find that, in this context, moral nudges increase donations by about 44 percent

    Characterization of Arabidopsis FPS isozymes and FPS gene expression analysis provide insight into the biosynthesis of isoprenoid precursors in seeds

    Get PDF
    Arabidopsis thaliana contains two genes encoding farnesyl diphosphate (FPP) synthase (FPS), the prenyl diphoshate synthase that catalyzes the synthesis of FPP from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). In this study, we provide evidence that the two Arabidopsis short FPS isozymes FPS1S and FPS2 localize to the cytosol. Both enzymes were expressed in E. coli, purified and biochemically characterized. Despite FPS1S and FPS2 share more than 90% amino acid sequence identity, FPS2 was found to be more efficient as a catalyst, more sensitive to the inhibitory effect of NaCl, and more resistant to thermal inactivation than FPS1S. Homology modelling for FPS1S and FPS2 and analysis of the amino acid differences between the two enzymes revealed an increase in surface polarity and a greater capacity to form surface salt bridges of FPS2 compared to FPS1S. These factors most likely account for the enhanced thermostability of FPS2. Expression analysis of FPS::GUS genes in seeds showed that FPS1 and FPS2 display complementary patterns of expression particularly at late stages of seed development, which suggests that Arabidopsis seeds have two spatially segregated sources of FPP. Functional complementation studies of the Arabidopsis fps2 knockout mutant seed phenotypes demonstrated that under normal conditions FPS1S and FPS2 are functionally interchangeable. A putative role for FPS2 in maintaining seed germination capacity under adverse environmental conditions is discussed

    Competing risk models to estimate the excess mortality and the first recurrent-event hazards

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>In medical research, one common competing risks situation is the study of different types of events, such as disease recurrence and death. We focused on that situation but considered death under two aspects: "expected death" and "excess death", the latter could be directly or indirectly associated with the disease.</p> <p>Methods</p> <p>The excess hazard method allows estimating an excess mortality hazard using the population (expected) mortality hazard. We propose models combining the competing risks approach and the excess hazard method. These models are based on a joint modelling of each event-specific hazard, including the event-free excess death hazard. The proposed models are parsimonious, allow time-dependent hazard ratios, and facilitate comparisons between event-specific hazards and between covariate effects on different events. In a simulation study, we assessed the performance of the estimators and showed their good properties with different drop-out censoring rates and different sample sizes.</p> <p>Results</p> <p>We analyzed a population-based dataset on French colon cancer patients who have undergone curative surgery. Considering three competing events (local recurrence, distant metastasis, and death), we showed that the recurrence-free excess mortality hazard reached zero six months after treatment. Covariates sex, age, and cancer stage had the same effects on local recurrence and distant metastasis but a different effect on excess mortality.</p> <p>Conclusions</p> <p>The proposed models consider the excess mortality within the framework of competing risks. Moreover, the joint estimation of the parameters allow (i) direct comparisons between covariate effects, and (ii) fitting models with common parameters to obtain more parsimonious models and more efficient parameter estimators.</p
    corecore