Prior upper body exercise reduces cycling work capacity but not critical power

Purpose: This study examined whether metabolite accumulation, induced by prior upper body exercise, affected the power–duration relationship for leg cycle ergometry

Investigating the effects of particle shape on normal compression and overconsolidation using DEM

Discrete element modelling of normal compression has been simulated on a sample of breakable two-ball clumps and compared to that of spheres. In both cases the size effect on strength is assumed to be that of real silica sand. The slopes of the normal compression lines are compared and found to be consistent with the proposed equation of the normal compression line. The values of the coefficient of earth pressure at rest K0,nc are also compared and related to the critical state fiction angles for the two materials. The breakable samples have then been unloaded to establish the stress ratios on unloading. At low overconsolidation ratios the values of K0 follow a well-established empirical relationship and realistic Poisson ratios are observed. On progressive unloading both samples head towards passive failure, and the values of the critical state lines in extension in q–p' space are found to be consistent with the critical state angles deduced from the values of K0 during normal compression. The paper highlights the important role of particle shape in governing the stress ratio during both normal compression and subsequent overconsolidation

Response [letter to Editor-in-Chief in response to Chiappa et al.]

We thank Chiappa et al. (4,5) for commending our work (2,3,7), which we reciprocate in light of their thought provoking research that sparked the ensuing trans-Atlantic debate on the effects of inspiratory muscle loading on lactate clearance after exercise. Specifically, despite using similar methodologies, Chiappa et al. (4,5) have twice shown accelerated lactate clearance with inspiratory loading, whereas we have twice shown no effect (2,7). We hypothesized that these discrepancies may be due to interstudy differences in participant endurance training status, as evidenced by higher V˙O2peak and faster blood lactate recovery kinetics in our participants. We were thus intrigued by the authors’ unpublished data showing, in sedentary individuals, no effect of inspiratory loading on lactate clearance. In their accompanying figure, the authors also present novel data showing a significant correlation between maximal inspiratory pressure (MIP) and changes in the area under the blood [Laj] curve with inspiratory loading. This observation informed their hypothesis that the efficacy of inspiratory loading is influenced by inspiratory muscle mass rather than training status

Bond percolation on isoradial graphs: criticality and universality

In an investigation of percolation on isoradial graphs, we prove the criticality of canonical bond percolation on isoradial embeddings of planar graphs, thus extending celebrated earlier results for homogeneous and inhomogeneous square, triangular, and other lattices. This is achieved via the star-triangle transformation, by transporting the box-crossing property across the family of isoradial graphs. As a consequence, we obtain the universality of these models at the critical point, in the sense that the one-arm and 2j-alternating-arm critical exponents (and therefore also the connectivity and volume exponents) are constant across the family of such percolation processes. The isoradial graphs in question are those that satisfy certain weak conditions on their embedding and on their track system. This class of graphs includes, for example, isoradial embeddings of periodic graphs, and graphs derived from rhombic Penrose tilings.Comment: In v2: extended title, and small changes in the tex

A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis

BACKGROUND: Meta-analysis of two randomised controlled trials in severe sepsis performed with recombinant human activated protein C may provide further insight as to the therapeutic utility of targeting the clotting cascade in this syndrome. METHODS: In search for relevant studies published, two randomized clinical trials were found eligible. RESULTS: The studies, PROWESS and ADDRESS, enrolled a total of 4329 patients with risk ratio (RR) and 95% confidence interval (CI) data for effect on 28-day mortality relative to control treatment of 0.92 (0.83–1.02) suggesting that recombinant human activated protein C is not beneficial in severe sepsis. In PROWESS, 873 of 1690 patients presented with low risk, and 2315 of 2639 patients in ADDRESS as defined by APACHE II score < 25. In this low-risk stratum, no effect of recombinant human activated protein C administration on 28-day mortality was observed. This observation appears to be consistent and homogenous. Heterogeneity between the two studies, however, was seen in patients with APACHE II score ≥ 25 in whom recombinant activated protein C was effective in PROWESS (n = 817; RR 0.71, CI 0.59–0.85) whereas a tendency toward harm was present in ADDRESS (n = 324; RR 1.21, CI 0.85–1.74). Even though the overall treatment effect in this high-risk population was still in favour of treatment with recombinant activated protein C (n = 1141; RR 0.80, CI 0.68–0.94), the observed heterogeneity suggests that the efficacy of recombinant human activated protein C is not robust. Not unlikely, the adverse tendency observed could have become significant with higher statistical power would ADDRESS not have been terminated prematurely. CONCLUSION: This meta-analysis, therefore, raises doubts about the clinical usefulness of recombinant activated protein C in patients with severe sepsis and an APACHE II score ≥ 25 which can only be resolved by another properly designed clinical trial

Functional characterization of 8-oxoguanine DNA glycosylase of Trypanosoma cruzi

The oxidative lesion 8-oxoguanine (8-oxoG) is removed during base excision repair by the 8-oxoguanine DNA glycosylase 1 (Ogg1). This lesion can erroneously pair with adenine, and the excision of this damaged base by Ogg1 enables the insertion of a guanine and prevents DNA mutation. In this report, we identified and characterized Ogg1 from the protozoan parasite Trypanosoma cruzi (TcOgg1), the causative agent of Chagas disease. Like most living organisms, T. cruzi is susceptible to oxidative stress, hence DNA repair is essential for its survival and improvement of infection. We verified that the TcOGG1 gene encodes an 8-oxoG DNA glycosylase by complementing an Ogg1-defective Saccharomyces cerevisiae strain. Heterologous expression of TcOGG1 reestablished the mutation frequency of the yeast mutant ogg1-/- (CD138) to wild type levels. We also demonstrate that the overexpression of TcOGG1 increases T. cruzi sensitivity to hydrogen peroxide (H2O2). Analysis of DNA lesions using quantitative PCR suggests that the increased susceptibility to H2O2 of TcOGG1-overexpressor could be a consequence of uncoupled BER in abasic sites and/or strand breaks generated after TcOgg1 removes 8-oxoG, which are not rapidly repaired by the subsequent BER enzymes. This hypothesis is supported by the observation that TcOGG1-overexpressors have reduced levels of 8-oxoG both in the nucleus and in the parasite mitochondrion. The localization of TcOgg1 was examined in parasite transfected with a TcOgg1-GFP fusion, which confirmed that this enzyme is in both organelles. Taken together, our data indicate that T. cruzi has a functional Ogg1 ortholog that participates in nuclear and mitochondrial BER. © 2012 Furtado et al

DEM of triaxial tests on crushable cemented sand

Using the discrete element method, triaxial simulations of cemented sand consisting of crushable particles are presented. The triaxial model used features a flexible membrane, allowing realistic deformation to occur, and cementation is modelled using inter-particle bonds. The effects of particle crushing are explored, as is the influence of cementation on the behaviour of the soil. An insight to the effects that cementation has on the degree of crushing is presented

Pattern Avoidance in Poset Permutations

We extend the concept of pattern avoidance in permutations on a totally ordered set to pattern avoidance in permutations on partially ordered sets. The number of permutations on $P$ that avoid the pattern $\pi$ is denoted $Av_P(\pi)$. We extend a proof of Simion and Schmidt to show that $Av_P(132) \leq Av_P(123)$ for any poset $P$, and we exactly classify the posets for which equality holds.Comment: 13 pages, 1 figure; v2: corrected typos; v3: corrected typos and improved formatting; v4: to appear in Order; v5: corrected typos; v6: updated author email addresse

Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes