The role of cardiopulmonary exercise testing (CPET) in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis (Protocol)

This is the final version. Available from BMC via the DOI in this record.Background Numerous studies have measured the prognostic associations between cardiorespiratory fitness and patient outcomes in congenital heart disease, but no systematic review has assessed these associations for all types of congenital heart disease. It is therefore a timely opportunity to syntheses all available data using a systematic review methodology. The aim of this study is to detail the protocol for a systematic review and meta-analysis. Objectives Within this paper we have developed a protocol for a prognostic factors systematic review and meta-analysis, to assess the role of cardiopulmonary exercise testing/cardiorespiratory fitness, in the prognosis of mortality and morbidity in congenital heart disease. Methods We have outlined, in detail, the process for this systematic review using the latest accepted methodological guidelines for prognostic factors research, such as the PICOTS system, CHARMS-PF data extraction, QUIPS risk of bias assessments and the prognostic GRADE guidelines (see list of abbreviations). Conclusion The implications of this review will aid future treatments, interventions and individual patient risk prediction. The publication of this protocol aims to improve scientific rigour by ensuring transparency in the systematic review and meta-analysis process.Canon Medical Systems UK Ltd.University of ExeterQUEX instituteMedical Research Counci

Validity of the Supramaximal Test to Verify Maximal Oxygen Uptake in Children and Adolescents

This is the author accepted manuscript. The final version is available from Human Kinetics via the DOI in this record.Purpose: This study had 2 objectives: (1) to examine whether the validity of the supramaximal verification test for maximal oxygen uptake ( formula presented ) differs in children and adolescents when stratified for sex, body mass, and cardiorespiratory fitness and (2) to assess sensitivity and specificity of primary and secondary objective criteria from the incremental test to verify formula presented . Methods: In total, 128 children and adolescents (76 male and 52 females; age: 9.3-17.4 y) performed a ramp-incremental test to exhaustion on a cycle ergometer followed by a supramaximal test to verify formula presented . Results: Supramaximal tests verified formula presented in 88% of participants. Group incremental test peak formula presented was greater than the supramaximal test (2.27 [0.65] L·min-1 and 2.17 [0.63] L·min-1; P  .18). Supramaximal test time to exhaustion predicted supramaximal test formula presented verification (P = .04). Primary and secondary objective criteria had insufficient sensitivity (7.1%-24.1%) and specificity (50%-100%) to verify formula presented . Conclusion: The utility of supramaximal testing to verify formula presented is not affected by sex, body mass, or cardiorespiratory fitness status. Supramaximal testing should replace secondary objective criteria to verify formula presented

Perceptual Responses to High- and Moderate-Intensity Interval Exercise in Adolescents

This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this record.PURPOSE: High-intensity continuous exercise is proposed to evoke unpleasant sensations as predicted by the dual mode theory (DMT), and may negatively impact on future exercise adherence. Previous studies support unpleasant sensations in affective responses during continuous high-intensity exercise, but the affect experience during high-intensity interval exercise (HIIE) involving brief bursts of high-intensity exercise separated by low-intensity activity is poorly understood in adolescents. We examined the acute affective, enjoyment and perceived exertion responses to HIIE compared to moderate-intensity interval exercise (MIIE) in adolescents. METHODS: Thirteen adolescent boys (mean±SD; age 14.0±0.5 years) performed two counterbalanced exercise conditions: 1) HIIE: 8 x 1-minute work intervals at 90% maximal aerobic speed; and 2) MIIE: between 9-12 x 1-minute work intervals at 90% ventilatory threshold where the number of intervals performed were distance-matched to HIIE. HIIE and MIIE intervals were interspersed with 75 s active recovery at 4 km·h. Affect, enjoyment and rating of perceived exertion (RPE) were recorded before, during and after exercise. RESULTS: Affect responses declined in both conditions but the fall was greater in HIIE than MIIE (P0.64). CONCLUSIONS: Despite elevated RPE, HIIE did not elicit prominent unpleasant feelings as predicted by DMT and was associated with greater post-exercise enjoyment responses than MIIE. This study demonstrates the feasibility of the application of HIIE as an alternative form of PA in adolescents.Adam Abdul Malik is financially supported by the Government of Malaysia for the funding under the academic staff training scheme (USM/PPSP(Pent)/L2/bJld.XV)

Validation and calibration for embedding rating of perceived exertion into high-intensity interval exercise in adolescents: a lab-based study

This is the author accepted manuscript. The final version is available from Human Kinetics via the DOI in this recordPURPOSE: Rating of perceived exertion (RPE) is a convenient and cost-effective tool that can be used to monitor high-intensity interval exercise (HIIE). However, no methodological study has demonstrated the validity of RPE in this context. Therefore, the aim of this study was to validate and calibrate RPE for monitoring HIIE in adolescents. METHODS: RPE, heart rate (HR), and oxygen uptake (V˙O2) data were retrospectively extracted from 3 lab-based crossover studies, with a pooled sample size of 45 adolescents, performing either cycling-based or running-based HIIE sessions. Within-participant correlations were calculated for RPE-HR and RPE-V˙O2, and receiver operator characteristic curve analysis was used to establish RPE cut points. RESULTS: The results showed that RPE-HR demonstrated acceptable criterion validity (r = .53-.74, P < .01), while RPE-V˙O2 had poor validity (r = .40-.48, P < .01), except for HIIE at 100% peak power (r = .59, P < .01). RPE cut points of 4 and 5 were established in corresponding to HR/V˙O2 based thresholds. CONCLUSION: RPE has some utility in evaluating intensity during lab-based running or cycling HIIE in adolescents. Future studies should expand the validation and calibration of RPE for prescribing and monitoring HIIE in children and adolescents in field-based contexts

Agreement between left and right middle cerebral artery blood velocity responses to incremental and constant work-rate exercise in healthy males and females

This is the author accepted manuscript. The final version is available from IOP Publishing via the DOI in this recordObjective: To quantify the agreement between left and right middle cerebral artery blood velocity (MCAv) responses to incremental and constant work-rate exercise in adults. Approach: Seventeen healthy adults (23.8±2.4 years, 9 females) completed a ramp incremental test to exhaustion on a cycle ergometer, three 6-minute transitions at a moderate-intensity, and three at a heavy-intensity, all on separate days. Bilateral MCAv was measured throughout using transcranial Doppler ultrasonography, with left and right MCAv data analysed separately. Data were analysed at baseline, gas exchange threshold, respiratory compensation point and exhaustion during ramp incremental exercise. MCAv responses to constant work-rate exercise were analysed using a mono-exponential model, to determine time- and amplitude-based kinetic response parameters. Main Results: Left and right MCAv responses to incremental and constant work-rate exercise were significantly, strongly and positively correlated (r≥0.61, P<0.01). Coefficient of variation (left vs right) ranged from 7.3-20.7%, 6.4-26.2% and 5.9-22.5% for ramp, moderate and heavy 33 intensity exercise, respectively. The relative change in MCAv from baseline was higher in the right compared to left MCAv during ramp, moderate and heavy-intensity exercise (all P<0.05), but the effect sizes were small (d≤0.4). Small mean left-right differences were present during ramp incremental exercise at all time-points (<6 cm/s; <4%), and for all kinetic parameters during moderate and heavy-intensity exercise (<3 cm/s, <3%, <4 s). Significance: These findings demonstrate similarities between left and right MCAv responses to incremental and constant-work rate exercise in adults on a group-level, but also highlight individual variation in the agreement between left and right MCAv exercise responsesQUEX Institut

The reliability of a breath‐hold protocol to determine cerebrovascular reactivity in adolescents

This is the published version. Available on open access from Wiley via the DOI in this recordPurpose Cerebrovascular reactivity (CVR) is impaired in adolescents with cardiovascular disease risk factors. A breath‐hold test is a noninvasive method of assessing CVR, yet there are no reliability data of this outcome in youth. This study aimed to assess the reliability of a breath‐hold protocol to measure CVR in adolescents. Methods Twenty‐one 13 to 15 year old adolescents visited the laboratory on two separate occasions, to assess the within‐test, within‐day and between‐day reliability of a breath‐hold protocol, consisting of three breath‐hold attempts. CVR was defined as the relative increase from baseline in middle cerebral artery mean blood velocity following a maximal breath‐hold of up to 30 seconds, quantified via transcranial Doppler ultrasonography. Results Mean breath‐hold duration and CVR were never significantly correlated (r  .08). The within‐test coefficient of variation for CVR was 15.2%, with no significant differences across breath‐holds (P = .88), so the three breath‐hold attempts were averaged for subsequent analyses. The within‐ and between‐day coefficients of variation for CVR were 10.8% and 15.3%, respectively. Conclusions CVR assessed via a three breath‐hold protocol can be reliably measured in adolescents, yielding similar within‐ and between‐day reliability. Analyses revealed that breath‐hold length and CVR were unrelated, indicating the commonly reported normalization of CVR to breath‐hold duration (breath‐hold index) may be unnecessary in youth

The role of cardiopulmonary exercise testing in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis

This is the final version. Available on open access from Oxford University Press via the DOI in this recordBackground: The role of cardiopulmonary exercise testing (CPET) in predicting major adverse cardiovascular events (MACE) in people with congenital heart disease (ConHD) is unknown. Design: A systematic review with meta-analysis was conducted to report the associations between CPET parameters and MACE in people with ConHD. Methods: Electronic databases were systematically searched on the 30th of April 2020 for eligible publications. Two authors independently screened publications for inclusion, extracted study data, and performed risk of bias assessment. Primary meta-analysis pooled univariate hazard ratios (HR) across studies. Results: A total of 34 studies (18,335 participants; 26.2 ± 10.1 years; 54% ± 16% male) were pooled into a meta-analysis. More than 20 different CPET prognostic factors were reported across 6 ConHD types. Of the 34 studies included in the meta-analysis, 10 (29%), 23 (68%), and 1 (3%) were judged as a low, medium, and high risk of bias, respectively. Primary univariate meta-analysis showed consistent evidence that improved peak and submaximal CPET measures are associated with a reduce risk of MACE. This association was supported by a secondary meta-analysis of multivariate estimates and individual studies that could not be numerically pooled. Conclusion: Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well conducted prospective multicentre cohort studies are needed to confirm these findings.Canon Medical Systems UK Ltd.University of ExeterQUEX instituteMedical Research Council (MRC

The acute and postprandial effects of sugar moiety on vascular and metabolic health outcomes in adolescents

This is the author accepted manuscript. The final version is available from Canadian Science Publishing via the DOI in this recordThis study explored the cardiometabolic responses to sugar moieties acutely, and following a subsequent mixed meal tolerance test (MMTT). Twenty-one healthy adolescents (N=10 female, 14.3±0.4 years) completed three experimental and one control condition, in a counterbalanced order. These consisted of different drinks to compare the effect of 300 mL of water (control), or 300 mL of water mixed with 60 g of glucose, fructose or sucrose, on vascular function (flow-mediated dilation; FMD, microvascular reactivity (total hyperaemic response; TRH); and cerebrovascular reactivity; CVR), and blood samples for [uric acid], [glucose], [triglycerides] and [lactate]. FMD increased 1 hour after glucose and sucrose (P<0.001, ES≥0.92) but was unchanged following fructose and water (P>0.19, ES>0.09). CVR and TRH were unchanged 1 hour following all conditions (P>0.57, ES>0.02). Following the MMTT, FMD was impaired in all conditions (P0.40) with no differences between conditions (P>0.13, ES<0.39). Microvascular TRH was increased in all conditions (P=0.001, ES=0.88), and CVR was preserved in all conditions post MMTT (P=0.87, ES=0.02). Blood [uric acid] was elevated following fructose consumption and the MMTT (P0.40). Consumption of a sugar sweetened beverage did not result in vascular dysfunction in healthy adolescents, however the vascular and metabolic responses were dependent on sugar moiety

On the electromagnetic inverse scattering problem

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46179/1/205_2004_Article_BF00282681.pd

Detecting Remote Evolutionary Relationships among Proteins by Large-Scale Semantic Embedding

Virtually every molecular biologist has searched a protein or DNA sequence database to find sequences that are evolutionarily related to a given query. Pairwise sequence comparison methods—i.e., measures of similarity between query and target sequences—provide the engine for sequence database search and have been the subject of 30 years of computational research. For the difficult problem of detecting remote evolutionary relationships between protein sequences, the most successful pairwise comparison methods involve building local models (e.g., profile hidden Markov models) of protein sequences. However, recent work in massive data domains like web search and natural language processing demonstrate the advantage of exploiting the global structure of the data space. Motivated by this work, we present a large-scale algorithm called ProtEmbed, which learns an embedding of protein sequences into a low-dimensional “semantic space.” Evolutionarily related proteins are embedded in close proximity, and additional pieces of evidence, such as 3D structural similarity or class labels, can be incorporated into the learning process. We find that ProtEmbed achieves superior accuracy to widely used pairwise sequence methods like PSI-BLAST and HHSearch for remote homology detection; it also outperforms our previous RankProp algorithm, which incorporates global structure in the form of a protein similarity network. Finally, the ProtEmbed embedding space can be visualized, both at the global level and local to a given query, yielding intuition about the structure of protein sequence space