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Abstract Background Breast cancer is a highly heterogeneous disease with respect to molecular alterations and cellular composition making therapeutic and clinical outcome unpredictable. This diversity creates a significant challenge in developing tumor classifications that are clinically reliable with respect to prognosis prediction. Results This paper describes an unsupervised context analysis to infer context-specific gene regulatory networks from 1,614 samples obtained from publicly available gene expression data, an extension of a previously published methodology. We use the context-specific gene regulatory networks to classify the tumors into clinically relevant subgroups, and provide candidates for a finer sub-grouping of the previously known intrinsic tumors with a focus on Basal-like tumors. Our analysis of pathway enrichment in the key contexts provides an insight into the biological mechanism underlying the identified subtypes of breast cancer. Conclusions The use of context-specific gene regulatory networks to identify biological contexts from heterogenous breast cancer data set was able to identify genomic drivers for subgroups within the previously reported intrinsic subtypes. These subgroups (contexts) uphold the clinical relevant features for the intrinsic subtypes and were associated with increased survival differences compared to the intrinsic subtypes. We believe our computational approach led to the generation of novel rationalized hypotheses to explain mechanisms of disease progression within sub-contexts of breast cancer that could be therapeutically exploited once validated.

Abstract Background The anaerobic spirochaete Brachyspira pilosicoli causes enteric disease in avian, porcine and human hosts, amongst others. To date, the only available genome sequence of B. pilosicoli is that of strain 95/1000, a porcine isolate. In the first intra-species genome comparison within the Brachyspira genus, we report the whole genome sequence of B. pilosicoli B2904, an avian isolate, the incomplete genome sequence of B. pilosicoli WesB, a human isolate, and the comparisons with B. pilosicoli 95/1000. We also draw on incomplete genome sequences from three other Brachyspira species. Finally we report the first application of the high-throughput Biolog phenotype screening tool on the B. pilosicoli strains for detailed comparisons between genotype and phenotype. Results Feature and sequence genome comparisons revealed a high degree of similarity between the three B. pilosicoli strains, although the genomes of B2904 and WesB were larger than that of 95/1000 (~2,765, 2.890 and 2.596 Mb, respectively). Genome rearrangements were observed which correlated largely with the positions of mobile genetic elements. Through comparison of the B2904 and WesB genomes with the 95/1000 genome, features that we propose are non-essential due to their absence from 95/1000 include a peptidase, glycine reductase complex components and transposases. Novel bacteriophages were detected in the newly-sequenced genomes, which appeared to have involvement in intra- and inter-species horizontal gene transfer. Phenotypic differences predicted from genome analysis, such as the lack of genes for glucuronate catabolism in 95/1000, were confirmed by phenotyping. Conclusions The availability of multiple B. pilosicoli genome sequences has allowed us to demonstrate the substantial genomic variation that exists between these strains, and provides an insight into genetic events that are shaping the species. In addition, phenotype screening allowed determination of how genotypic differences translated to phenotype. Further application of such comparisons will improve understanding of the metabolic capabilities of Brachyspira species.

Abstract Background Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is commonly used to identify differentially expressed proteins under two or more experimental or observational conditions. Wu et al (2009) developed a univariate probabilistic model which was used to identify differential expression between Case and Control groups, by applying a Likelihood Ratio Test (LRT) to each protein on a 2D PAGE. In contrast to commonly used statistical approaches, this model takes into account the two possible causes of missing values in 2D PAGE: either (1) the non-expression of a protein; or (2) a level of expression that falls below the limit of detection. Results We develop a global Bayesian model which extends the previously described model. Unlike the univariate approach, the model reported here is able treat all differentially expressed proteins simultaneously. Whereas each protein is modelled by the univariate likelihood function previously described, several global distributions are used to model the underlying relationship between the parameters associated with individual proteins. These global distributions are able to combine information from each protein to give more accurate estimates of the true parameters. In our implementation of the procedure, all parameters are recovered by Markov chain Monte Carlo (MCMC) integration. The 95% highest posterior density (HPD) intervals for the marginal posterior distributions are used to determine whether differences in protein expression are due to differences in mean expression intensities, and/or differences in the probabilities of expression. Conclusions Simulation analyses showed that the global model is able to accurately recover the underlying global distributions, and identify more differentially expressed proteins than the simple application of a LRT. Additionally, simulations also indicate that the probability of incorrectly identifying a protein as differentially expressed (i.e., the False Discovery Rate) is very low. The source code is available at https://github.com/stevenhwu/BIDE-2D.

Abstract Background The immune response has been proposed to be an important factor in determining patient outcome in colorectal cancer (CRC). Previous studies have concentrated on characterizing T cell populations in the primary tumour where T cells with regulatory effect (Foxp3+ Tregs) have been identified as both enhancing and diminishing anti-tumour immune responses. No previous studies have characterized the T cell response in the regional lymph nodes in CRC. Methods Immunohistochemistry was used to analyse CD4, CD8 or Foxp3+ T cell populations in the regional lymph nodes of patients with stage II CRC (n = 31), with (n = 13) or without (n = 18) cancer recurrence after 5 years of follow up, to determine if the priming environment for anti-tumour immunity was associated with clinical outcome. Results The proportions of CD4, CD8 or Foxp3+ cells in the lymph nodes varied widely between and within patients, and there was no association between T cell populations and cancer recurrence or other clinicopathological characteristics. Conclusions These data indicate that frequency of these T cell subsets in lymph nodes may not be a useful tool for predicting patient outcome.

Abstract Background Reliability of real-time PCR (RT-qPCR) data is dependent on the use of appropriate reference gene(s) for normalization. To date, no validated reference genes have been reported for normalizing gene expression in human myocardium. This study aimed to identify validated reference genes for use in gene expression studies of failed and non-failed human myocardium. Methods Bioinformatic analysis of published human heart gene expression arrays (195 failed hearts, 16 donor hearts) was used to identify 10 stable and abundant genes for further testing. The expression stability of these genes was investigated in 28 failed and 28 non-failed human myocardium samples by RT-qPCR using geNorm software. Results Signal recognition particle 14 kDa (SRP14), tumor protein, translationally-controlled 1 (TPT1) and eukaryotic elongation factor 1A1 (EEF1A1) were ranked the most stable genes. The commonly used reference gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was ranked the least stable of the genes tested. The normalization strategy was tested by comparing RT-qPCR data of both normalized and raw expression levels of brain natriuretic peptide precursor (NPPB), a gene known to be up-regulated in heart failure. Non-normalized levels of NPPB exhibited a marginally significant difference between failed and non-failed samples (p = 0.058). In contrast, normalized NPPB expression levels were significantly higher in heart-failed patients compared with controls (p = 0.023). Conclusion This study used publicly available gene array data to identify a strategy for normalization involving two reference genes in combination that may have broad application for accurate and reliable normalization of RT-qPCR data in failed and non-failed human myocardium.

Abstract Background The analysis of gene sets has become a popular topic in recent times, with researchers attempting to improve the interpretability and reproducibility of their microarray analyses through the inclusion of supplementary biological information. While a number of options for gene set analysis exist, no consensus has yet been reached regarding which methodology performs best, and under what conditions. The goal of this work was to examine the performance characteristics of a collection of existing gene set analysis methods, on both simulated and real microarray data sets. Of particular interest was the potential utility gained through the incorporation of inter-gene correlation into the analysis process. Results Each of six gene set analysis methods was applied to both simulated and publicly available microarray data sets. Overall, the various methodologies were all found to be better at detecting gene sets that moved from non-active (i.e., genes not expressed) to active states (or vice versa), rather than those that simply changed their level of activity. Methods which incorporate correlation structures were found to provide increased ability to detect altered gene sets in some settings. Conclusion Based on the results obtained through the analysis of simulated data, it is clear that the performance of gene set analysis methods is strongly influenced by the features of the data set in question, and that methods which incorporate correlation structures into the analysis process tend to achieve better performance, relative to methods which rely on univariate test statistics.

Dietary nitrate (NO 3 - ) supplementation has been shown to reduce blood pressure (BP), improve exercise performance, and alter the oral microbiome. Following a "control" diet (CON), we manipulated dietary NO 3 - intake to examine the effect of a short-term (7-day) low NO 3 - diet (LOW) followed by a 3-day high NO 3 - diet (HIGH), compared to a 7-day standard (STD) NO 3 - diet followed by HIGH, on saliva, plasma, and muscle [NO 3 - ] and nitrite ([NO 2 - ]), BP, and cycling exercise performance in healthy young adults. We also examined the effect of LOW on the oral microbiome. Saliva [NO 3 - ] and [NO 2 - ], and plasma [NO 3 - ] were significantly lower than CON following LOW (all P < 0.05) but there was no change in plasma [NO 2 - ] or muscle [NO 3 - ] and [NO 2 - ] (all P > 0.05). Following HIGH, saliva and plasma [NO 3 - ] and [NO 2 - ], and muscle [NO 3 - ], were significantly elevated above CON, LOW and STD (all P < 0.05), but there was no difference between CON-LOW-HIGH and CON-STD-HIGH (P < 0.05). BP and exercise performance were not altered following LOW (P > 0.05). HIGH significantly reduced systolic and diastolic BP compared to CON when preceded by STD (both P < 0.05) but not when preceded by LOW (P > 0.05). Peak (+4 %) and mean (+3 %) power output during sprint cycling was significantly improved following HIGH (both P < 0.05), with no differences between CON-LOW-HIGH and CON-STD-HIGH (both P > 0.05). LOW altered the oral microbiome composition, including decreases in relative abundances of phylum Proteobacteria and genus Neisseria. The findings indicate that a short-term low NO 3 - diet lowers plasma but not skeletal muscle [NO 3 - ]. The maintenance of plasma [NO 2 - ] and muscle [NO 3 - ] and [NO 2 - ] following LOW may be indicative of their importance to biological functions, including BP regulation and exercise performance., Competing Interests: Declaration of competing interest Alan N. Schechter is listed as a co-inventor on several patents issued to the National Institutes of Health (NIH) for the use of nitrite salts for the treatment of cardiovascular diseases. He receives royalties based on NIH licensing of these patents for clinical development but no other compensation. The other authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dietary nitrate (NO 3 - ) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO 2 - ]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO 3 - , NO 2 - , S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO 3 - supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO 3 - -rich beetroot juice (BR) (∼12.8 mmol NO 3 - ) and NO 3 - -depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5-3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (-2 ± 3 mmHg, P = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0-30 ms (39 ± 57 N m s -1 , P = 0.03) and 0-50 ms (79 ± 99 N m s -1 , P = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO 2 - ] was correlated with lower diastolic BP (r = -0.68, P = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO 3 - ] was correlated with greater RTD at 0-30 ms (r = 0.64, P=0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO 3 - ] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO 3 - ingestion in humans., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dietary nitrate (NO 3 - ) supplementation can enhance nitric oxide (NO) bioavailability and lower blood pressure (BP) in humans. The nitrite concentration ([NO 2 - ]) in the plasma is the most commonly used biomarker of increased NO availability. However, it is unknown to what extent changes in other NO congeners, such as S-nitrosothiols (RSNOs), and in other blood components, such as red blood cells (RBC), also contribute to the BP lowering effects of dietary NO 3 - . We investigated the correlations between changes in NO biomarkers in different blood compartments and changes in BP variables following acute NO 3 - ingestion. Resting BP was measured and blood samples were collected at baseline, and at 1, 2, 3, 4 and 24 h following acute beetroot juice (∼12.8 mmol NO 3 - , ∼11 mg NO 3 - /kg) ingestion in 20 healthy volunteers. Spearman rank correlation coefficients were determined between the peak individual increases in NO biomarkers (NO 3 - , NO 2 - , RSNOs) in plasma, RBC and whole blood, and corresponding decreases in resting BP variables. No significant correlation was observed between increased plasma [NO 2 - ] and reduced BP, but increased RBC [NO 2 - ] was correlated with decreased systolic BP (r s  = -0.50, P = 0.03). Notably, increased RBC [RSNOs] was significantly correlated with decreases in systolic (r s  = -0.68, P = 0.001), diastolic (r s  = -0.59, P = 0.008) and mean arterial pressure (r s  = -0.64, P = 0.003). Fisher's z transformation indicated no difference in the strength of the correlations between increases in RBC [NO 2 - ] or [RSNOs] and decreased systolic blood pressure. In conclusion, increased RBC [RSNOs] may be an important mediator of the reduction in resting BP observed following dietary NO 3 - supplementation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Dietary nitrate (NO 3 - ) supplementation increases nitric oxide bioavailability and can enhance exercise performance. We investigated the distribution and metabolic fate of ingested NO 3 - at rest and during exercise with a focus on skeletal muscle., Methods: In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol 15 N-labeled potassium nitrate (K 15 NO 3 ; NIT) or potassium chloride placebo (PLA). Muscle biopsies were taken at baseline, at 1- and 3-h post-supplement ingestion, and immediately following the completion of 60 maximal intermittent contractions of the knee extensors. Muscle, plasma, saliva, and urine samples were analyzed using chemiluminescence to determine absolute [NO 3 - ] and [NO 2 - ], and by mass spectrometry to determine the proportion of NO 3 - and NO 2 - that was 15 N-labeled., Results: Neither muscle [NO 3 - ] nor [NO 2 - ] were altered by PLA. Following NIT, muscle [NO 3 - ] (but not [NO 2 - ]) was elevated at 1-h (from ~35 to 147 nmol/g, p < 0.001) and 3-h, with almost all of the increase being 15 N-labeled. There was a significant reduction in 15 N-labeled muscle [NO 3 - ] from pre- to post-exercise. Relative to PLA, mean muscle torque production was ~7% greater during the first 18 contractions following NIT. This improvement in torque was correlated with the pre-exercise 15 N-labeled muscle [NO 3 - ] and the magnitude of decline in 15 N-labeled muscle [NO 3 - ] during exercise (r = 0.66 and r = 0.62, respectively; p < 0.01)., Conclusion: This study shows, for the first time, that skeletal muscle rapidly takes up dietary NO 3 - , the elevated muscle [NO 3 - ] following NO 3 - ingestion declines during exercise, and muscle NO 3 - dynamics are associated with enhanced torque production during maximal intermittent muscle contractions., (© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Purpose: This study aimed 1) to examine the accuracy with which W' reconstitution (W' REC ) is estimated by the W' balance (W' BAL ) models after a 3-min all-out cycling test (3MT), 2) to determine the effects of a 3MT on the power-duration relationship, and 3) to assess whether accounting for changes in the power-duration relationship during exercise improved estimates of W' REC ., Methods: The power-duration relationship and the actual and estimated W' REC were determined for 12 data sets extracted from our laboratory database where participants had completed two 3MT separated by 1-min recovery (i.e., control [C-3MT] and fatigued [F-3MT])., Results: Actual W' REC (6.3 ± 1.4 kJ) was significantly overestimated by the W' BAL·ODE (9.8 ± 1.3 kJ; P < 0.001) and the W' BAL·MORTON (16.9 ± 2.6 kJ; P < 0.001) models but was not significantly different to the estimate provided by the W' BAL·INT (7.5 ± 1.5 kJ; P > 0.05) model. End power (EP) was 7% lower in the F-3MT (263 ± 40 W) compared with the C-3MT (282 ± 44 W; P < 0.001), and work done above EP (WEP) was 61% lower in the F-3MT (6.3 ± 1.4 kJ) compared with the C-3MT (16.9 ± 3.2 kJ). The size of the error in the estimated W' REC was correlated with the reduction in WEP for the W' BAL·INT and W' BAL·ODE models (both r > -0.74, P < 0.01) but not the W' BAL·MORTON model ( r = -0.18, P > 0.05). Accounting for the changes in the power-duration relationship improved the accuracy of the W' BAL·ODE and W' BAL·MORTON , but they remained significantly different to actual W' REC ., Conclusions: These findings demonstrate that the power-duration relationship is altered after a 3MT, and accounting for these changes improves the accuracy of the W' BAL·ODE and the W' BAL·MORTON , but not W' BAL·INT models. These results have important implications for the design and use of mathematical models describing the energetics of exercise performance., (Copyright © 2022 by the American College of Sports Medicine.)

Dietary nitrate (NO 3 - ) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO 3 - reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO 3 - concentration ([NO 3 - ]) following the ingestion of dietary NO 3 - . Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of ∼1300 mg (12.8 mmol) potassium nitrate (KNO 3 ), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO 3 - ] and [NO 2 - ] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO 3 - ] or [NO 2 - ] over time. In NIT, muscle [NO 3 - ] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO 2 - ] did not change significantly over time. Following ingestion of a bolus of dietary NO 3 - , skeletal muscle [NO 3 - ] increases rapidly, reaches a peak at ∼3 h and subsequently declines towards baseline values. Following dietary NO 3 - ingestion, human m. vastus lateralis [NO 3 - ] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO 3 - ]., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: We tested the hypotheses that a highly cushioned running shoe (HCS) would 1) improve incremental exercise performance and reduce the oxygen cost (Oc) of submaximal running, and 2) attenuate the deterioration in Oc elicited by muscle damage consequent to a downhill run., Methods: Thirty-two recreationally active participants completed an incremental treadmill test in an HCS and a control running shoe (CON) for the determination of Oc and maximal performance. Subsequently, participants were pair matched and randomly assigned to one of the two footwear conditions to perform a moderate-intensity running bout before and 48 h after a 30-min downhill run designed to elicit muscle damage., Results: Incremental treadmill test performance was improved (+5.7%; +1:16 min:ss; P < 0.01) in the HCS when assessed in the nondamaged state, relative to CON. This coincided with a significantly lower Oc (-3.2%; -6 mL·kg-1·km-1; P < 0.001) at a range of running speeds and an increase in the speed corresponding to 3 mM blood lactate (+3.2%; +0.4 km·h-1; P < 0.05). As anticipated, the downhill run resulted in significant changes in biochemical, histological, and perceptual markers of muscle damage, and a significant increase in Oc (+5.2%; 10.1 mL·kg-1·km-1) was observed 48 h post. In the presence of muscle damage, Oc was significantly lower in HCS (-4.6%; -10 mL·kg-1·km-1) compared with CON., Conclusions: These results indicate that HCS improved incremental exercise performance and Oc in the absence of muscle damage and show, for the first time, that despite worsening of Oc consequent to muscle damage, improved Oc in HCS is maintained., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

The influence of anthropometry and body composition on running economy is unclear, with previous investigations involving small relatively homogeneous groups of runners and limited anthropometric/composition measurements., Purpose: To comprehensively investigate the relationships of anthropometry and body composition with running economy within a large heterogeneous sample of runners., Methods: Eighty-five runners (males [M], n = 45; females [F], n = 40), of diverse competitive standard, performed a discontinuous protocol of incremental treadmill running (4-min stages, 1 km·h increments) to establish locomotory energy cost (LEc) of running at submaximal speeds (averaged across 10-12 km·h; the highest common speed < lactate turnpoint). Measurements of anthropometry, including segment lengths, perimeters, masses and moments of inertia, and body composition were obtained using tape-based measurements and dual-energy x-ray absorptiometry., Results: Absolute LEc (ABSLEc, kcal·km) was positively correlated with 21 (of 27) absolute anthropometric variables in both male and female cohorts. Multiple-regression analyses revealed that one variable (mean perimeter z score) explained 49.4% (M) and 68.9% (F) of the variance in ABSLEc. Relative LEc (RELLEc, kcal·kg·km) was also correlated with five (M) and seven (F) normalized anthropometric variables, and regression analyses explained 31.6% (M; percentage bone mass and normalized hip perimeter) and 33.3% (F, normalized forearm perimeter) of the variance in RELLEc., Conclusions: These findings provide novel and robust evidence that anthropometry and body composition variables, predominantly indicative of relative slenderness, explain a considerable proportion of the variance in running economy (i.e., more slender, lower energy cost). We, therefore, recommend that runners and coaches are attentive to relative slenderness in selecting and training athletes with the aim of enhancing running economy, and improving distance running performance.

Key Points: Nitric oxide (NO), a potent vasodilator and a regulator of many physiological processes, is produced in mammals both enzymatically and by reduction of nitrite and nitrate ions. We have previously reported that, in rodents, skeletal muscle serves as a nitrate reservoir, with nitrate levels greatly exceeding those in blood or other internal organs, and with nitrate being reduced to NO during exercise. In the current study, we show that nitrate concentration is substantially greater in skeletal muscle than in blood and is elevated further by dietary nitrate ingestion in human volunteers. We also show that high-intensity exercise results in a reduction in the skeletal muscle nitrate store following supplementation, likely as a consequence of its reduction to nitrite and NO. We also report the presence of sialin, a nitrate transporter, and xanthine oxidoreductase in human skeletal muscle, indicating that muscle has the necessary apparatus for nitrate transport, storage and metabolism., Abstract: Rodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate. This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO) via its reduction by tissue xanthine oxidoreductase. To explore if this pathway is also active in human skeletal muscle during exercise, and if it is sensitive to local nitrate availability, we assessed exercise-induced changes in muscle nitrate and nitrite concentrations in young healthy humans, under baseline conditions and following dietary nitrate consumption. We found that baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (∼4-fold and ∼29-fold, respectively), and that the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (∼19-fold) and muscle (∼5-fold). Consistent with these observations, and with previous suggestions of active muscle nitrate transport, we present western blot data to show significant expression of the active nitrate/nitrite transporter sialin in human skeletal muscle. Furthermore, we report an exercise-induced reduction in human muscle nitrate concentration (by ∼39%), but only in the presence of an increased muscle nitrate store. Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise. Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans., (© 2019 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

We tested the hypotheses that the parameters of the power-duration relationship, estimated as the end-test power (EP) and work done above EP (WEP) during a 3-min all-out exercise test (3MT), would be reduced progressively after 40 min, 80 min, and 2 h of heavy-intensity cycling and that carbohydrate (CHO) ingestion would attenuate the reduction in EP and WEP. Sixteen participants completed a 3MT without prior exercise (control), immediately after 40 min, 80 min, and 2 h of heavy-intensity exercise while consuming a placebo beverage, and also after 2 h of heavy-intensity exercise while consuming a CHO supplement (60 g/h CHO). There was no difference in EP measured without prior exercise (260 ± 37 W) compared with EP after 40 min (268 ± 39 W) or 80 min (260 ± 40 W) of heavy-intensity exercise; however, after 2 h EP was 9% lower compared with control (236 ± 47 W; P < 0.05). There was no difference in WEP measured without prior exercise (17.9 ± 3.3 kJ) compared with after 40 min of heavy-intensity exercise (16.1 ± 3.3 kJ), but WEP was lower ( P < 0.05) than control after 80 min (14.7 ± 2.9 kJ) and 2 h (13.8 ± 2.7 kJ). Compared with placebo, CHO ingestion negated the reduction of EP following 2 h of heavy-intensity exercise (254 ± 49 W) but had no effect on WEP (13.5 ± 3.4 kJ). These results reveal a different time course for the deterioration of EP and WEP during prolonged endurance exercise and indicate that EP is sensitive to CHO availability. NEW & NOTEWORTHY The parameters of the power-duration relationship [critical power (CP) and the curvature constant (W')] have typically been considered to be static. Here we report the time course for reductions in CP and W', as estimated with the 3-min all-out cycle test, during 2 h of heavy-intensity exercise. We also show that carbohydrate ingestion during exercise preserves CP, but not W', without altering muscle glycogen depletion. These results provide new mechanistic and practical insight into the power-duration curve and its relationship to exercise-related fatigue development.

The maximal lactate steady state (MLSS) and the critical power (CP) are two widely used indices of the highest oxidative metabolic rate that can be sustained during continuous exercise and are often considered to be synonymous. However, while perhaps having similarities in principle, methodological differences in the assessment of these parameters typically result in MLSS occurring at a somewhat lower power output or running speed and exercise at CP being sustainable for no more than approximately 20-30 min. This has led to the view that CP overestimates the 'actual' maximal metabolic steady state and that MLSS should be considered the 'gold standard' metric for the evaluation of endurance exercise capacity. In this article we will present evidence consistent with the contrary conclusion: i.e., that (1) as presently defined, MLSS naturally underestimates the actual maximal metabolic steady state; and (2) CP alone represents the boundary between discrete exercise intensity domains within which the dynamic cardiorespiratory and muscle metabolic responses to exercise differ profoundly. While both MLSS and CP may have relevance for athletic training and performance, we urge that the distinction between the two concepts/metrics be better appreciated and that comparisons between MLSS and CP, undertaken in the mistaken belief that they are theoretically synonymous, is discontinued. CP represents the genuine boundary separating exercise in which physiological homeostasis can be maintained from exercise in which it cannot, and should be considered the gold standard when the goal is to determine the maximal metabolic steady state., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: To determine the accuracy of critical power (CP) and W' (the curvature constant of the power-duration relationship) derived from self-paced time-trial (TT) prediction trials using mobile power meters to predict 16.1-km road cycling TT performance. This study also aimed to assess the agreement between functional threshold power (FTP) and CP., Methods: Twelve competitive male cyclists completed an incremental test to exhaustion, a FTP test and 4-5 self-paced TT bouts on a stationary bike within the lab, and a 16.1 km road TT, using mobile power meters., Results: CP and W' derived from the power-duration relationship closely predicted TT performance. The 16.1-km road TT completion time (26.7 ± 2.2 min) was not significantly different from and was significantly correlated with the predicted time-to-completion (27.5 ± 3.3 min, r = 0.89, P < 0.01). CP and FTP were not significantly different (275 ± 40 W vs. 278 ± 42 W, P > 0.05); however, the limits of agreement between CP and FTP were 30 to -36 W., Discussion: The findings of this study indicate that CP and W' determined using mobile power meters during maximal, self-paced TT prediction trials can be used to accurately predict 16.1-km cycling performance, supporting the application of the CP and W' for performance prediction. However, the limits of agreement were too large to consider FTP and CP interchangeable.

Purpose: To investigate whether oxygen-uptake ([Formula: see text]) kinetics and simulated 4-km cycling performance are synergistically improved by prior "priming" exercise and an all-out starting strategy., Methods: Nine men completed 4 target work trials (114 ± 17 kJ) to assess [Formula: see text] kinetics and cycling performance in a repeated-measures, crossover experimental design. Trials were initiated with either a 12-s all-out start or a self-selected start and preceded by prior severe-intensity (70%Δ) priming exercise or no priming exercise., Results: The [Formula: see text] mean response time (MRT) was lower (indicative of faster [Formula: see text] kinetics) in the all-out primed condition (20 ± 6 s) than in the all-out unprimed (23 ± 6 s), self-paced-unprimed (42 ± 13 s), and self-paced-primed (42 ± 11 s) trials (P < .05), with the [Formula: see text] MRT also lower in the all-out unprimed than the self-paced unprimed and self-paced primed trials (P < .05). Trial-completion time was shorter (performance was enhanced) in the all-out primed trial (402 ± 14 s) than in the all-out unprimed (408 ± 14 s), self-paced unprimed (411 ± 16 s), and self-paced primed (411 ± 19 s) trials (P < .05), with no differences between the latter 3 trials., Conclusions: The findings from this study suggest that combining severe-intensity priming exercise with a short-duration all-out starting strategy can expedite the adjustment of [Formula: see text] and lower completion time during a cycling performance trial to a greater extent than either intervention administered independently. These results might have implications for optimizing performance in short-duration high-intensity competitive events such as a 4-km cycling time trial.

Purpose: To investigate the influence of β-alanine (BA) supplementation on muscle carnosine content, muscle pH and the power-duration relationship (i.e., critical power and W'). Methods: In a double-blind, randomized, placebo-controlled study, 20 recreationally-active males (22 ± 3 y, V°O 2peak 3.73 ± 0.44 L·min -1 ) ingested either BA (6.4 g/d for 28 d) or placebo (PL) (6.4 g/d) for 28 d. Subjects completed an incremental test and two 3-min all-out tests separated by 1-min on a cycle ergometer pre- and post-supplementation. Muscle pH was assessed using 31 P-magnetic resonance spectroscopy (MRS) during incremental (INC KEE) and intermittent knee-extension exercise (INT KEE). Muscle carnosine content was determined using 1 H-MRS. Results: There were no differences in the change in muscle carnosine content from pre- to post-intervention (PL: 1 ± 16% vs. BA: -4 ± 25%) or in muscle pH during INC KEE or INT KEE ( P > 0.05) between PL and BA, but blood pH (PL: -0.06 ± 0.10 vs. BA: 0.09 ± 0.13) during the incremental test was elevated post-supplementation in the BA group only ( P < 0.05). The changes from pre- to post-supplementation in critical power (PL: -8 ± 18 W vs. BA: -6 ± 17 W) and W' (PL: 1.8 ± 3.3 kJ vs. BA: 1.5 ± 1.7 kJ) were not different between groups. No relationships were detected between muscle carnosine content and indices of exercise performance. Conclusions: BA supplementation had no significant effect on muscle carnosine content and no influence on intramuscular pH during incremental or high-intensity intermittent knee-extension exercise. The small increase in blood pH following BA supplementation was not sufficient to significantly alter the power-duration relationship or exercise performance.

The influence of running speed and sex on running economy is unclear and may have been confounded by measurements of oxygen cost that do not account for known differences in substrate metabolism, across a limited range of speeds, and differences in performance standard. Therefore, this study assessed the energy cost of running over a wide range of speeds in high-level and recreational runners to investigate the effect of speed (in absolute and relative terms) and sex (men vs women of equivalent performance standard) on running economy. To determine the energy cost (kcal · kg -1  · km -1 ) of submaximal running, speed at lactate turn point (sLTP), and maximal rate of oxygen uptake, 92 healthy runners (high-level men, n = 14; high-level women, n = 10; recreational men, n = 35; recreational women, n = 33) completed a discontinuous incremental treadmill test. There were no sex-specific differences in the energy cost of running for the recreational or high-level runners when compared at absolute or relative running speeds (P > .05). The absolute and relative speed-energy cost relationships for the high-level runners demonstrated a curvilinear U shape with a nadir reflecting the most economical speed at 13 km/h or 70% sLTP. The high-level runners were more economical than the recreational runners at all absolute and relative running speeds (P < .05). These findings demonstrate that there is an optimal speed for economical running, there is no sex-specific difference, and high-level endurance runners exhibit better running economy than recreational endurance runners.

Despite an intuitive relationship between technique and both running economy (RE) and performance, and the diverse techniques used by runners to achieve forward locomotion, the objective importance of overall technique and the key components therein remain to be elucidated., Purpose: This study aimed to determine the relationship between individual and combined kinematic measures of technique with both RE and performance., Methods: Ninety-seven endurance runners (47 females) of diverse competitive standards performed a discontinuous protocol of incremental treadmill running (4-min stages, 1-km·h increments). Measurements included three-dimensional full-body kinematics, respiratory gases to determine energy cost, and velocity of lactate turn point. Five categories of kinematic measures (vertical oscillation, braking, posture, stride parameters, and lower limb angles) and locomotory energy cost (LEc) were averaged across 10-12 km·h (the highest common velocity < velocity of lactate turn point). Performance was measured as season's best (SB) time converted to a sex-specific z-score., Results: Numerous kinematic variables were correlated with RE and performance (LEc, 19 variables; SB time, 11 variables). Regression analysis found three variables (pelvis vertical oscillation during ground contact normalized to height, minimum knee joint angle during ground contact, and minimum horizontal pelvis velocity) explained 39% of LEc variability. In addition, four variables (minimum horizontal pelvis velocity, shank touchdown angle, duty factor, and trunk forward lean) combined to explain 31% of the variability in performance (SB time)., Conclusions: This study provides novel and robust evidence that technique explains a substantial proportion of the variance in RE and performance. We recommend that runners and coaches are attentive to specific aspects of stride parameters and lower limb angles in part to optimize pelvis movement, and ultimately enhance performance.

We hypothesized that 4 wk of dietary nitrate supplementation would enhance exercise performance and muscle metabolic adaptations to sprint interval training (SIT). Thirty-six recreationally active subjects, matched on key variables at baseline, completed a series of exercise tests before and following a 4-wk period in which they were allocated to one of the following groups: 1 ) SIT and [Formula: see text]-depleted beetroot juice as a placebo (SIT+PL); 2 ) SIT and [Formula: see text]-rich beetroot juice (~13 mmol [Formula: see text]/day; SIT+BR); or 3 ) no training and [Formula: see text]-rich beetroot juice (NT+BR). During moderate-intensity exercise, pulmonary oxygen uptake was reduced by 4% following 4 wk of SIT+BR and NT+BR ( P < 0.05) but not SIT+PL. The peak work rate attained during incremental exercise increased more in SIT+BR than in SIT+PL ( P < 0.05) or NT+BR ( P < 0.001). The reduction in muscle and blood [lactate] and the increase in muscle pH from preintervention to postintervention were greater at 3 min of severe-intensity exercise in SIT+BR compared with SIT+PL and NT+BR ( P < 0.05). However, the change in severe-intensity exercise performance was not different between SIT+BR and SIT+PL ( P > 0.05). The relative proportion of type IIx muscle fibers in the vastus lateralis muscle was reduced in SIT+BR only ( P < 0.05). These findings suggest that BR supplementation may enhance some aspects of the physiological adaptations to SIT. NEW & NOTEWORTHY We investigated the influence of nitrate-rich and nitrate-depleted beetroot juice on the muscle metabolic and physiological adaptations to 4 wk of sprint interval training. Compared with placebo, dietary nitrate supplementation reduced the O 2 cost of submaximal exercise, resulted in greater improvement in incremental (but not severe-intensity) exercise performance, and augmented some muscle metabolic adaptations to training. Nitrate supplementation may facilitate some of the physiological responses to sprint interval training., (Copyright © 2017 the American Physiological Society.)

Lactate or gas exchange threshold (GET) and critical power (CP) are closely associated with human exercise performance. We tested the hypothesis that the limit of tolerance (T lim ) during cycle exercise performed within the exercise intensity domains demarcated by GET and CP is linked to discrete muscle metabolic and neuromuscular responses. Eleven men performed a ramp incremental exercise test, 4-5 severe-intensity (SEV; >CP) constant-work-rate (CWR) tests until T lim , a heavy-intensity (HVY; GET) CWR test until T lim , and a moderate-intensity (MOD; lim Muscle biopsies revealed that a similar ( P > 0.05) muscle metabolic milieu (i.e., low pH and [PCr] and high [lactate]) was attained at T lim (approximately 2-14 min) for all SEV exercise bouts. The muscle metabolic perturbation was greater at T lim following SEV compared with HVY, and also following SEV and HVY compared with MOD (all P < 0.05). The normalized M-wave amplitude for the vastus lateralis (VL) muscle decreased to a similar extent following SEV (-38 ± 15%), HVY (-68 ± 24%), and MOD (-53 ± 29%), ( P > 0.05). Neural drive to the VL increased during SEV (4 ± 4%; P < 0.05) but did not change during HVY or MOD ( P > 0.05). During SEV and HVY, but not MOD, the rates of change in M-wave amplitude and neural drive were correlated with changes in muscle metabolic ([PCr], [lactate]) and blood ionic/acid-base status ([lactate], [K + ]) ( P < 0.05). The results of this study indicate that the metabolic and neuromuscular determinants of fatigue development differ according to the intensity domain in which the exercise is performed. NEW & NOTEWORTHY The gas exchange threshold and the critical power demarcate discrete exercise intensity domains. For the first time, we show that the limit of tolerance during whole-body exercise within these domains is characterized by distinct metabolic and neuromuscular responses. Fatigue development during exercise greater than critical power is associated with the attainment of consistent "limiting" values of muscle metabolites, whereas substrate availability and limitations to muscle activation may constrain performance at lower intensities., (Copyright © 2017 the American Physiological Society.)

Highly aerobically trained individuals are unable to achieve maximal oxygen uptake ([Formula: see text]) during exhaustive running lasting ~2 min, instead [Formula: see text] plateaus below [Formula: see text] after ~1 min. Hypoxia offers the opportunity to study the ([Formula: see text]) response to an exhaustive run relative to a hypoxia induced reduction in [Formula: see text]. The aim of this study was to explore whether there is a difference in the percentage of [Formula: see text] achieved (during a 2 min exhaustive run) in normoxia and hypoxia. Fourteen competitive middle distance runners (normoxic [Formula: see text] 67.0 ± 5.2 ml.kg -1 .min -1 ) completed exhaustive treadmill ramp tests and constant work rate (CWR) tests in normoxia and hypoxia (F i O 2 0.13). The [Formula: see text] data from the CWR tests were modeled using a single exponential function. End exercise normoxic CWR [Formula: see text] was less than normoxic [Formula: see text] (86 ± 6% ramp, P < 0.001). During the hypoxic CWR test, hypoxic [Formula: see text] was achieved (102 ± 8% ramp, P = 0.490). The phase II time constant was greater in hypoxia (12.7 ± 2.8 s) relative to normoxia (10.4 ± 2.6 s) ( P = 0.029). The results demonstrate that highly aerobically trained individuals cannot achieve [Formula: see text] during exhaustive severe intensity treadmill running in normoxia, but can achieve the lower [Formula: see text] in hypoxia despite a slightly slower [Formula: see text] response.

Although a number of algorithms exist for estimating ground contact events (GCEs) from kinematic data during running, they are typically only applicable to heelstrike running, or have only been evaluated at a single running speed. The purpose of this study was to investigate the accuracy of four kinematics-based algorithms to estimate GCEs over a range of running speeds and footstrike types. Subjects ran over a force platform at a range of speeds; kinetic and kinematic data was captured at 1000Hz, and kinematic data was downsampled to 250Hz. A windowing process initially identified reduced time windows containing touchdown and toe-off. Algorithms based on acceleration and jerk signals of the foot markers were used to estimate touchdown (2 algorithms), toe-off (2 algorithms), and ground contact time (GCT) (4 algorithms), and compared to synchronous 'gold standard' force platform data. An algorithm utilising the vertical acceleration peak of either the heel or first metatarsal marker (whichever appeared first) for touchdown, and the vertical jerk peak of the hallux marker for toe-off, resulted in the lowest offsets (+3.1ms, 95% Confidence Interval (CI): -11.8 to +18.1ms; and +2.1ms, CI: -8.1 to +12.2ms respectively). This method also resulted in the smallest offset in GCT (-1.1ms, CI: -18.6 to +16.4ms). Offsets in GCE and GCT estimates from all algorithms were typically negatively correlated to running speed, with offsets decreasing as speed increased. Assessing GCEs and GCT using this method may be useful when a force platform is unavailable or impractical., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: The parameters of the power-duration relationship (i.e., the critical power, CP, and the curvature constant, W') may theoretically predict maximal performance capability for exercise above the CP. The CP and W' are associated with the parameters of oxygen uptake ([Formula: see text]O 2 ) kinetics, which can be altered by manipulation of the work-rate forcing function. We tested the hypothesis that the CP and W' derived from constant work-rate (CWR) prediction trials would overestimate ramp incremental exercise performance., Methods: Thirty subjects (males, n = 28; females, n = 2) performed a ramp incremental test, and 3-5 CWR prediction trials for the determination of the CP and W'. Multiple ramp incremental tests and corresponding CP and W' estimates were available for some subjects such that in total 51 ramp test performances were predicted., Results: The ramp incremental test performance (729 ± 113 s) was overestimated by the CP and W' estimates derived from the best (751 ± 114 s, P < 0.05) and worst (749 ± 111 s, P < 0.05) individual fits of CWR prediction trial data. The error in the prediction was inversely correlated with the magnitude of the W' for the best (r = -0.56, P < 0.05) and worst individual fits (r = -0.36, P < 0.05)., Conclusions: The overestimation of ramp incremental performance suggests that the CP and W' derived from different work-rate forcing functions, thus resulting in different [Formula: see text]O 2 kinetics, cannot be used interchangeably. The present findings highlight a potential source of error in performance prediction that is of importance to both researchers and applied practitioners., Competing Interests: The authors declare that they have no conflict of interest.

Key Points: The power-asymptote (critical power; CP) of the hyperbolic power-time relationship for high-intensity exercise defines a threshold between steady-state and non-steady-state exercise intensities and the curvature constant (W') indicates a fixed capacity for work >CP that is related to a loss of muscular efficiency. The present study reports novel evidence on the muscle metabolic underpinnings of CP and W' during whole-body exercise and their relationships to muscle fibre type. We show that the W' is not correlated with muscle fibre type distribution and that it represents an elevated energy contribution from both oxidative and glycolytic/glycogenolytic metabolism. We show that there is a positive correlation between CP and highly oxidative type I muscle fibres and that muscle metabolic steady-state is attainable CP. Our findings indicate a mechanistic link between the bioenergetic characteristics of muscle fibre types and the power-time relationship for high-intensity exercise., Abstract: We hypothesized that: (1) the critical power (CP) will represent a boundary separating steady-state from non-steady-state muscle metabolic responses during whole-body exercise and (2) that the CP and the curvature constant (W') of the power-time relationship for high-intensity exercise will be correlated with type I and type IIx muscle fibre distributions, respectively. Four men and four women performed a 3 min all-out cycling test for the estimation of CP and constant work rate (CWR) tests slightly >CP until exhaustion (Tlim ), slightly CP Tlim isotime to test the first hypothesis. Eleven men performed 3 min all-out tests and donated muscle biopsies to test the second hypothesis. Below CP, muscle [PCr] [42.6 ± 7.1 vs. 49.4 ± 6.9 mmol (kg d.w.)(-1) ], [La(-) ] [34.8 ± 12.6 vs. 35.5 ± 13.2 mmol (kg d.w.)(-1) ] and pH (7.11 ± 0.08 vs. 7.10 ± 0.11) remained stable between ∼12 and 24 min (P > 0.05 for all), whereas these variables changed with time >CP such that they were greater [[La(-) ] 95.6 ± 14.1 mmol (kg d.w.)(-1) ] and lower [[PCr] 24.2 ± 3.9 mmol (kg d.w.)(-1) ; pH 6.84 ± 0.06] (P < 0.05) at Tlim (740 ± 186 s) than during the

Purpose: To assess whether combining prior "priming" exercise with an all-out pacing strategy is more effective at improving oxygen-uptake (VO2) kinetics and cycling performance than either intervention administered independently., Methods: Nine men completed target-work cycling performance trials using a self-paced or all-out pacing strategy with or without prior severe-intensity (70%Δ) priming exercise. Breath-by-breath pulmonary VO2 and cycling power output were measured during all trials., Results: Compared with the self-paced unprimed control trial (22 ± 5 s), the VO2 mean response time (MRT) was shorter (VO2 kinetics were faster) with all-out pacing (17 ± 4 s) and priming (17 ± 3 s), with the lowest VO2 MRT observed when all-out pacing and priming were combined (15 ± 4 s) (P < .05). However, total O2 consumed and end-exercise VO2 were only higher than the control condition in the primed trials (P < .05). Similarly, cycling performance was improved compared with control (98 ± 11 s) in the self-paced primed (93 ± 8 s) and all-out primed (92 ± 8 s) trials (P < .05) but not the all-out unprimed trial (97 ± 5 s; P > .05)., Conclusions: These findings suggest that combining an all-out start with severe-intensity priming exercise additively improves VO2 MRT but not total O2 consumption and cycling performance since these were improved by a similar magnitude in both primed trials relative to the self-paced unprimed control condition. Therefore, these results support the use of priming exercise as a precompetition intervention to improve oxidative metabolism and performance during short-duration high-intensity cycling exercise, independent of the pacing strategy adopted.

Unlabelled: It is possible that dietary nitrate (NO3 (-)) supplementation may improve both physical and cognitive performance via its influence on blood flow and cellular energetics., Purpose: To investigate the effects of dietary NO3 (-) supplementation on exercise performance and cognitive function during a prolonged intermittent sprint test (IST) protocol, which was designed to reflect typical work patterns during team sports., Methods: In a double-blind randomised crossover study, 16 male team-sport players received NO3 (-)-rich (BR; 140 mL day(-1); 12.8 mmol of NO3 (-)), and NO3 (-)-depleted (PL; 140 mL day(-1); 0.08 mmol NO3 (-)) beetroot juice for 7 days. On day 7 of supplementation, subjects completed the IST (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out" sprint, 100-s active recovery and 20 s of rest), on a cycle ergometer during which cognitive tasks were simultaneously performed., Results: Total work done during the sprints of the IST was greater in BR (123 ± 19 kJ) compared to PL (119 ± 17 kJ; P < 0.05). Reaction time of response to the cognitive tasks in the second half of the IST was improved in BR compared to PL (BR first half: 820 ± 96 vs. second half: 817 ± 86 ms; PL first half: 824 ± 114 vs. second half: 847 ± 118 ms; P < 0.05). There was no difference in response accuracy., Conclusions: These findings suggest that dietary NO3 (-) enhances repeated sprint performance and may attenuate the decline in cognitive function (and specifically reaction time) that may occur during prolonged intermittent exercise.

The parameters of the power-duration relationship for severe-intensity exercise (i.e., the critical power (CP) and the curvature constant (W')) are related to the kinetics of pulmonary O2 uptake, which may be altered by pacing strategy. We tested the hypothesis that the CP would be higher when derived from a series of self-paced time-trials (TT) than when derived from the conventional series of constant work-rate (CWR) exercise tests. Ten male subjects (age, 21.5 ± 1.9 years; mass, 75.2 ± 11.5 kg) completed 3-4 CWR and 3-4 TT prediction trial protocols on a cycle ergometer for the determination of the CP and W'. The CP derived from the TT protocol (265 ± 44 W) was greater (P < 0.05) than the CP derived from the CWR protocol (250 ± 47 W), while the W' was not different between protocols (TT: 18.1 ± 5.7 kJ, CWR: 20.6 ± 7.4 kJ, P > 0.05). The mean response time of pulmonary O2 uptake was shorter during the TTs than the CWR trials (TT: 34 ± 16, CWR: 39 ± 19 s, P < 0.05). The CP was correlated with the total O2 consumed in the first 60 s across both protocols (r = 0.88, P < 0.05, n = 20). These results suggest that in comparison with the conventional CWR exercise protocol, a self-selected pacing strategy enhances CP and improves severe-intensity exercise performance. The greater CP during TT compared with CWR exercise has important implications for performance prediction, suggesting that TT completion times may be overestimated by CP and W' parameters derived from CWR protocols.

It has been shown that the critical power (CP) in cycling estimated using a novel 3-min all-out protocol is reliable and closely matches the CP derived from conventional procedures. The purpose of this study was to assess the predictive validity of the all-out test CP estimate. We hypothesised that the all-out test CP would be significantly correlated with 16.1-km road time-trial (TT) performance and more strongly correlated with performance than the gas exchange threshold (GET), respiratory compensation point (RCP) and VO2 max. Ten club-level male cyclists (mean±SD: age 33.8±8.2 y, body mass 73.8±4.3 kg, VO2 max 60±4 ml·kg(-1)·min(-1)) performed a 10-mile road TT, a ramp incremental test to exhaustion, and two 3-min all-out tests, the first of which served as familiarisation. The 16.1-km TT performance (27.1±1.2 min) was significantly correlated with the CP (309±34 W; r = -0.83, P<0.01) and total work done during the all-out test (70.9±6.5 kJ; r = -0.86, P<0.01), the ramp incremental test peak power (433±30 W; r = -0.75, P<0.05) and the RCP (315±29 W; r = -0.68, P<0.05), but not with GET (151±32 W; r = -0.21) or the VO2 max (4.41±0.25 L·min(-1); r = -0.60). These data provide evidence for the predictive validity and practical performance relevance of the 3-min all-out test. The 3-min all-out test CP may represent a useful addition to the battery of tests employed by applied sport physiologists or coaches to track fitness and predict performance in atheletes.

Recent studies have suggested that dietary inorganic nitrate (NO₃(-)) supplementation may improve muscle efficiency and endurance exercise tolerance but possible effects during team sport-specific intense intermittent exercise have not been examined. We hypothesized that NO₃(-) supplementation would enhance high-intensity intermittent exercise performance. Fourteen male recreational team-sport players were assigned in a double-blind, randomized, crossover design to consume 490 mL of concentrated, nitrate-rich beetroot juice (BR) and nitrate-depleted placebo juice (PL) over ~30 h preceding the completion of a Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1). Resting plasma nitrite concentration ([NO₂(-)]) was ~400% greater in BR compared to PL. Plasma [NO₂(-)] declined by 20% in PL (P < 0.05) and by 54 % in BR (P < 0.05) from pre-exercise to end-exercise. Performance in the Yo-Yo IR1 was 4.2% greater (P < 0.05) with BR (1,704 ± 304 m) compared to PL (1,636 ± 288 m). Blood [lactate] was not different between BR and PL, but the mean blood [glucose] was lower (3.8 ± 0.8 vs. 4.2 ± 1.1 mM, P < 0.05) and the rise in plasma [K(+)] tended to be reduced in BR compared to PL (P = 0.08). These findings suggest that NO₃(-) supplementation may promote NO production via the nitrate-nitrite-NO pathway and enhance Yo-Yo IR1 test performance, perhaps by facilitating greater muscle glucose uptake or by better maintaining muscle excitability. Dietary NO₃(-) supplementation improves performance during intense intermittent exercise and may be a useful ergogenic aid for team sports players.

Patients with acute oesophageal obstruction, either due to a foreign body or food bolus, present to any of the specialties of Otorhinolaryngology, General Surgery, Cardiothoracic Surgery or Gastroenterology. To review current routine management of this condition, we conducted a postal survey of all the consultants in the aforementioned specialties in the South Thames region. The aims of the survey were to assess current practice and to produce a standardized management plan for these patients.

The effects of mesothermic anaerobic or aerobic sludge digestion on survival of eggs from the roundworms Ascaris suum, toxocara canis, Trichuris vulpis, and Trichuris suis and from the rat tapeworm Hymenolepis diminuta were studied. Destruction of eggs throughout a 15-day treatment period, as well as their viabilities after reisolation, was analyzed. The laboratory model digesters used in this study were maintained at a 15-day retention schedule, partially simulating a continuously operating system. Ascaris eggs were destroyed in the anaerobic (23%) or aerobic (38%) digesters, and 11% Trichuris eggs were destroyed in the aerobic digesters. Trichuris eggs in anaerobic digesters and Toxocara eggs in either anaerobic or aerobic digesters were not destroyed. Destruction of eggs in digesters was correlated with the state of the eggs before subjection to the treatment processes; i.e., some Ascaris and Trichuris eggs were already embryonated in host intestinal contents or feces and hence past their most resistant stage. The viabilities of Ascaris and Toxocara eggs that survived the digestion processes were greater in anaerobically treated than in aerobically treated material. Eggs from Hymenolepis were nonviable before use in the experiments. However, they were more effectively destroyed in aerobic digesters than in anaerobic digesters.