SummaryBackground Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebocontrolled randomised trials to show its efficacy.

Objective To investigate whether discrepancies in trials of use of bone marrow stem cells in patients with heart disease account for the variation in reported effect size in improvement of left ventricular function.Design Identification and counting of factual discrepancies in trial reports, and sample size weighted regression against therapeutic effect size. Meta-analysis of trials that provided sufficient information. Data sources PubMed and Embase from inception to April 2013.Eligibility for selecting studies Randomised controlled trials evaluating the effect of autologous bone marrow stem cells for heart disease on mean left ventricular ejection fraction.Results There were over 600 discrepancies in 133 reports from 49 trials. There was a significant association between the number of discrepancies and the reported increment in EF with bone marrow stem cell therapy (Spearman's r=0.4, P=0.005). Trials with no discrepancies were a small minority (five trials) and showed a mean EF effect size of −0.4%. The 24 trials with 1-10 discrepancies showed a mean effect size of 2.1%. The 12 with 11-20 discrepancies showed a mean effect of size 3.0%. The three with 21-30 discrepancies showed a mean effect size of 5.7%. The high discrepancy group, comprising five trials with over 30 discrepancies each, showed a mean effect size of 7.7%.Conclusions Avoiding discrepancies is difficult but is important because discrepancy count is related to effect size. The mechanism is unknown but should be explored in the design of future trials because in the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero.

BackgroundPhotorespiratory carbon metabolism was long considered as an essentially closed and nonregulated pathway with little interaction to other metabolic routes except nitrogen metabolism and respiration. Most mutants of this pathway cannot survive in ambient air and require CO2-enriched air for normal growth. Several studies indicate that this CO2 requirement is very different for individual mutants, suggesting a higher plasticity and more interaction of photorespiratory metabolism as generally thought. To understand this better, we examined a variety of high- and low-level parameters at 1% CO2 and their alteration during acclimation of wild-type plants and selected photorespiratory mutants to ambient air.Methodology and Principal FindingsThe wild type and four photorespiratory mutants of Arabidopsis thaliana (Arabidopsis) were grown to a defined stadium at 1% CO2 and then transferred to normal air (0.038% CO2). All other conditions remained unchanged. This approach allowed unbiased side-by-side monitoring of acclimation processes on several levels. For all lines, diel (24 h) leaf growth, photosynthetic gas exchange, and PSII fluorescence were monitored. Metabolite profiling was performed for the wild type and two mutants. During acclimation, considerable variation between the individual genotypes was detected in many of the examined parameters, which correlated with the position of the impaired reaction in the photorespiratory pathway.ConclusionsPhotorespiratory carbon metabolism does not operate as a fully closed pathway. Acclimation from high to low CO2 was typically steady and consistent for a number of features over several days, but we also found unexpected short-term events, such as an intermittent very massive rise of glycine levels after transition of one particular mutant to ambient air. We conclude that photorespiration is possibly exposed to redox regulation beyond known substrate-level effects. Additionally, our data support the view that 2-phosphoglycolate could be a key regulator of photosynthetic-photorespiratory metabolism as a whole.

Diel (24 h) leaf growth patterns were differently affected by temperature variations and the circadian clock in several plant species. In the monocotyledon Zea mays, leaf elongation rate closely followed changes in temperature. In the dicotyledons Nicotiana tabacum, Ricinus communis, and Flaveria bidentis, the effect of temperature regimes was less obvious and leaf growth exhibited a clear circadian oscillation.These differences were related neither to primary metabolism nor to altered carbohydrate availability for growth. The effect of endogenous rhythms on leaf growth was analysed under continuous light in Arabidopsis thaliana, Ricinus communis, Zea mays, and Oryza sativa. No rythmic growth was observed under continuous light in the two monocotyledons, while growth rhythmicity persisted in the two dicotyledons. Based on model simulations it is concluded that diel leaf growth patterns in mono- and dicotyledons result from the additive effects of both circadian-clock-controlled processes and responses to environmental changes such as temperature and evaporative demand. Apparently very distinct diel leaf growth behaviour of monocotyledons and dicotyledons can thus be explained by the different degrees to which diel temperature variations affect leaf growth in the two groups of species which, in turn, depends on the extent of the leaf growth control by internal clocks.