Significance of Crypt Atypia in Barrett's Esophagus: A Clinical, Molecular, and Outcome Study.

BACKGROUND & AIMS: The aim of this study was to characterize baseline morphologic features of crypts in nondysplastic Barrett's esophagus and correlate them with DNA content abnormalities and risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS: The morphologic features of nondysplastic crypts in baseline biopsy specimens from 212 BE patients (2956 biopsy specimens) were graded histologically using a 4-point scale (crypt atypia levels, 0-3). DNA content abnormalities were detected using flow cytometry. RESULTS: In patients who had dysplasia in their baseline biopsy specimens, dysplasia was associated significantly with increasing grades of crypt atypia in the background nondysplastic Barrett's esophagus (P < .001). In a subset of patients without dysplasia at baseline (N = 149), a higher grade of crypt atypia was associated with longer Barrett's esophagus segment length (5.5 vs 3.3 cm; P = .0095), and a higher percentage of cells with 4N DNA content (3.67 ± 1.27 vs 2.93 ± 1.22; P = .018). Crypt atypia was associated with the development of any neoplasia (low-grade dysplasia and HGD/EAC). Although no significant association was noted between the grade of crypt atypia and increased 4N, aneuploidy, or progression to HGD/EAC, only patients with grade 2 or 3 crypt atypia showed increased 4N, aneuploidy, or progression to HGD/EAC. CONCLUSIONS: Patients with Barrett's esophagus likely develop dysplasia via a progressive increase in the level of crypt atypia before the onset of dysplasia, and these changes may reflect some alteration of DNA content.

Extrachromosomal DNA in the cancerous transformation of Barrett's oesophagus.

Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer1-6. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett's oesophagus. These data included 206 biopsies in Barrett's oesophagus surveillance and EAC cohorts from Cambridge University. We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case-control study at the Fred Hutchinson Cancer Center. In the Cambridge cohorts, the frequency of ecDNA increased between Barrett's-oesophagus-associated early-stage (24%) and late-stage (43%) EAC, suggesting that ecDNA is formed during cancer progression. In the cohort from the Fred Hutchinson Cancer Center, 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC. In biopsies that were collected before cancer diagnosis, higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not. We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes. Furthermore, ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease. Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer, and that ecDNAs progressively form and evolve under positive selection.

Oxygen uptake and heart rate responses to 4 weeks of RPE-guided handcycle training.

PURPOSE: To investigate the efficacy of using Ratings of Perceived Exertion (RPE) to prescribe and regulate a 4-week handcycle training intervention. METHODS: Thirty active adults, untrained in upper body endurance exercise, were divided into three groups to complete a 4-week intervention: (i) RPE-guided training (n = 10; 2 female), (ii) power output (PO)-guided (n = 10; 2 female) training, or (iii) non-training control (n = 10; 4 female). Training groups performed three sessions of handcycling each week. Oxygen uptake ([Formula: see text]), heart rate (HR), and Feeling Scale (FS) rating were collected during training sessions. RPE-guided training was performed at RPE 13. PO-guided training was matched for percentage of peak PO per session, based upon that achieved by the RPE-guided training group. RESULTS: There were no differences in percentage of peak [Formula: see text] (66 ± 13% vs 61 ± 9%, p = 0.22), peak HR (75 ± 8% vs 71 ± 6%, p = 0.11) or FS rating (1.2 ± 1.9 vs 0.8 ± 1.6, p = 0.48) between RPE- and PO-guided training, respectively. The average coefficient of variation in percentage of peak HR between consecutive training sessions was 2.8% during RPE-guided training, and 3.4% during PO-guided training. CONCLUSION: Moderate-vigorous intensity handcycling exercise can be prescribed effectively using RPE across a chronic training intervention, suggesting utility for practitioners in a variety of rehabilitation settings.

Breakage fusion bridge cycles drive high oncogene copy number, but not intratumoral genetic heterogeneity or rapid cancer genome change.

Oncogene amplification is a major driver of cancer pathogenesis. Breakage fusion bridge (BFB) cycles, like extrachromosomal DNA (ecDNA), can lead to high copy numbers of oncogenes, but their impact on intratumoral heterogeneity, treatment response, and patient survival are not well understood due to difficulty in detecting them by DNA sequencing. We describe a novel algorithm that detects and reconstructs BFB amplifications using optical genome maps (OGMs), called OM2BFB. OM2BFB showed high precision (>93%) and recall (92%) in detecting BFB amplifications in cancer cell lines, PDX models and primary tumors. OM-based comparisons demonstrated that short-read BFB detection using our AmpliconSuite (AS) toolkit also achieved high precision, albeit with reduced sensitivity. We detected 371 BFB events using whole genome sequences from 2,557 primary tumors and cancer lines. BFB amplifications were preferentially found in cervical, head and neck, lung, and esophageal cancers, but rarely in brain cancers. BFB amplified genes show lower variance of gene expression, with fewer options for regulatory rewiring relative to ecDNA amplified genes. BFB positive (BFB (+)) tumors showed reduced heterogeneity of amplicon structures, and delayed onset of resistance, relative to ecDNA(+) tumors. EcDNA and BFB amplifications represent contrasting mechanisms to increase the copy numbers of oncogene with markedly different characteristics that suggest different routes for intervention.

Somatic whole genome dynamics of precancer in Barrett's esophagus reveals features associated with disease progression.

While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett's esophagus compared to 40 Barrett's patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett's tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures. The critical distinction between stable Barrett's versus those who progress to cancer is acquisition and expansion of TP53-/- cell populations having complex structural variants and high-level amplifications, which are detectable up to six years prior to a cancer diagnosis. These findings reveal the timing of common somatic genome dynamics in stable Barrett's esophagus and define key genomic features specific to progression to esophageal adenocarcinoma, both of which are critical for cancer prevention and early detection strategies.

Within-patient phylogenetic reconstruction reveals early events in Barrett's Esophagus.

Barrett's Esophagus is a neoplastic condition which progresses to esophageal adenocarcinoma in 5% of cases. Key events affecting the outcome likely occur before diagnosis of Barrett's and cannot be directly observed; we use phylogenetic analysis to infer such past events. We performed whole-genome sequencing on 4-6 samples from 40 cancer outcome and 40 noncancer outcome patients with Barrett's Esophagus, and inferred within-patient phylogenies of deconvoluted clonal lineages. Spatially proximate lineages clustered in the phylogenies, but temporally proximate ones did not. Lineages with inferred loss-of-function mutations in both copies of TP53 and CDKN2A showed enhanced spatial spread, whereas lineages with loss-of-function mutations in other frequently mutated loci did not. We propose a two-phase model with expansions of TP53 and CKDN2A mutant lineages during initial growth of the segment, followed by relative stasis. Subsequent to initial expansion, mutations in these loci as well as ARID1A and SMARCA4 may show a local selective advantage but do not expand far: The spatial structure of the Barrett's segment remains stable during surveillance even in patients who go on to cancer. We conclude that the cancer/noncancer outcome is strongly affected by early steps in formation of the Barrett's segment.

Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.

Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise "chasms" of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis.

Correction to: NSAID use and somatic exomic mutations in Barrett's esophagus.

It was highlighted that in the original article [1] the Availability of data and materials section was incorrect.

Bilateral scapular kinematics, asymmetries and shoulder pain in wheelchair athletes.

BACKGROUND: Shoulder pain is the most common complaint for wheelchair athletes. Scapular orientation and dyskinesia are thought to be associated with shoulder pathology, yet no previous studies have examined the bilateral scapula kinematics of wheelchair athletes during propulsion. RESEARCH QUESTION: To examine bilateral scapular kinematics of highly trained wheelchair rugby (WR) players and any associations with self-reported shoulder pain during everyday wheelchair propulsion. METHODS: Ten WR players (5 with shoulder pain, 5 without) performed 2 × 3-minute bouts of exercise in their everyday wheelchair on a wheelchair ergometer at two sub-maximal speeds (3 and 6 km h-1). During the final minute, 3D kinematic data were collected at 100 Hz to describe scapulothoracic motion relative to each propulsion cycle. Instantaneous asymmetries in scapular orientation between dominant and non-dominant sides were also reported. Differences in scapular kinematics and propulsion asymmetries were compared across shoulders symptomatic and asymptomatic of pain. RESULTS: An internally rotated, upwardly rotated and anteriorly tilted scapula was common during wheelchair propulsion and asymmetries ≤14° did exist, yet minimal changes were observed across speeds. Participants with bilateral shoulder pain displayed a less upwardly rotated scapula during propulsion, however large inter-individual variability in scapular kinematics was noted. SIGNIFICANCE: Scapular asymmetries are exhibited by wheelchair athletes during wheelchair propulsion, yet these were not exacerbated by increased speed and had limited associations to shoulder pain. This suggests that propulsion kinematics of highly trained athletes may not be the primary cause of pain experienced by this population.

NSAID use and somatic exomic mutations in Barrett's esophagus.

BACKGROUND: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to protect against tetraploidy, aneuploidy, and chromosomal alterations in the metaplastic condition Barrett's esophagus (BE) and to lower the incidence and mortality of esophageal adenocarcinoma (EA). The esophagus is exposed to both intrinsic and extrinsic mutagens resulting from gastric reflux, chronic inflammation, and exposure to environmental carcinogens such as those found in cigarettes. Here we test the hypothesis that NSAID use inhibits accumulation of point mutations/indels during somatic genomic evolution in BE. METHODS: Whole exome sequences were generated from 82 purified epithelial biopsies and paired blood samples from a cross-sectional study of 41 NSAID users and 41 non-users matched by sex, age, smoking, and continuous time using or not using NSAIDs. RESULTS: NSAID use reduced overall frequency of point mutations across the spectrum of mutation types, lowered the frequency of mutations even when adjusted for both TP53 mutation and smoking status, and decreased the prevalence of clones with high variant allele frequency. Never smokers who consistently used NSAIDs had fewer point mutations in signature 17, which is commonly found in EA. NSAID users had, on average, a 50% reduction in functional gene mutations in nine cancer-associated pathways and also had less diversity in pathway mutational burden compared to non-users. CONCLUSIONS: These results indicate NSAID use functions to limit overall mutations on which selection can act and supports a model in which specific mutant cell populations survive or expand better in the absence of NSAIDs.

Evolution of Barrett's esophagus through space and time at single-crypt and whole-biopsy levels.

The low risk of progression of Barrett's esophagus (BE) to esophageal adenocarcinoma can lead to over-diagnosis and over-treatment of BE patients. This may be addressed through a better understanding of the dynamics surrounding BE malignant progression. Although genetic diversity has been characterized as a marker of malignant development, it is still unclear how BE arises and develops. Here we uncover the evolutionary dynamics of BE at crypt and biopsy levels in eight individuals, including four patients that experienced malignant progression. We assay eight individual crypts and the remaining epithelium by SNP array for each of 6-11 biopsies over 2 time points per patient (358 samples in total). Our results indicate that most Barrett's segments are clonal, with similar number and inferred rates of alterations observed for crypts and biopsies. Divergence correlates with geographical location, being higher near the gastro-esophageal junction. Relaxed clock analyses show that genomic instability precedes and is enhanced by genome doubling. These results shed light on the clinically relevant evolutionary dynamics of BE.

Altering the Speed Profiles of Wheelchair Rugby Players With Game-Simulation Drill Design.

PURPOSE: To examine the speed profiles of elite wheelchair rugby (WCR) players during game-simulation training drills of differing player number and shot-clock regulations. A secondary aim was to determine whether the profiles were further influenced by player classification. METHODS: Eight elite WCR players (low-point n = 3, high-point n = 5) were monitored using a radio-frequency-based indoor tracking system during training sessions over a 5-mo period. Speed profiles were collected for 3 modified game-simulation drills-3-versus-3 drills (n = 8 observations), 30-s shot clock (n = 24 observations), and 15-s shot clock (n = 16 observations)-and were compared with regular game-simulation drills (4 vs 4, 40-s shot clock; n = 16 observations). Measures included mean and peak speed; exercise-intensity ratios, defined as the ratio of time spent performing at high and low speeds; and the number of high-speed activities performed. RESULTS: Compared with regular game-simulation drills, 3-versus-3 drills elicited a moderate increase in mean speed (6.3%; effect size [ES] = 0.7) and the number of high-speed activities performed (44.1%; ES = 1.1). Minimal changes in speed profiles were observed during the 30-s shot clock, although moderate to large increases in all measures were observed during the 15-s shot-clock drills. Classification-specific differences were further identified, with increased activity observed for high-point players during the 3-versus-3 drill and for low-point players during the 15-s shot clock. CONCLUSION: By reducing the number of players on court and the shot clock to 15 s, coaches can significantly increase elite WCR players' speed profiles during game-simulation drills.

Reliability and Validity of Subjective Measures of Aerobic Intensity in Adults With Spinal Cord Injury: A Systematic Review.

OBJECTIVE: To systematically synthesize and appraise research regarding test-retest reliability or criterion validity of subjective measures for assessing aerobic exercise intensity in adults with spinal cord injury (SCI). DATA SOURCES: Electronic databases (Pubmed, PsychINFO, SPORTDiscus, EMBASE, and CINAHL) were searched from inception to January 1, 2016. STUDY SELECTION: Studies involving at least 50% of participants with SCI who performed an aerobic exercise test that included measurement of subjective and objective intensity based on test-retest reliability or criterion validity protocols. DATA EXTRACTION: Characteristics were extracted on study design, measures, participants, protocols, and results. Each study was evaluated for risk of bias based on strength of the study design and a quality checklist score (COnsensus-based Standards for the selection of health Measurement INstruments [COSMIN]). DATA SYNTHESIS: The 7 eligible studies (1 for reliability, 6 for validity) evaluated overall, peripheral and/or central ratings of perceived exertion (RPE) on a scale of 6-20 (RPE 6-20). No eligible studies were identified for other subjective intensity measures. The evidence for reliability and validity were synthesized separately for each measure and were assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Overall, very low GRADE confidence ratings were established for reliability and validity evidence generalizable to the entire population with SCI and various upper-body and lower-body modalities. There was low confidence for the evidence showing that overall RPE 6-20 has acceptable validity for adults with SCI and high fitness levels performing moderate to vigorous-intensity upper-body aerobic exercise. CONCLUSIONS: Health care professionals and scientists need to be aware of the very low to low confidence in the evidence, which currently prohibits a strong clinical recommendation for the use of subjective measures for assessing aerobic exercise intensity in adults with SCI. However, a tentative, conditional recommendation regarding overall RPE 6-20 seems applicable, depending on participants' fitness level as well as the exercise intensity and modality used. LEVEL OF EVIDENCE: NA.

Quantification of Multiple Tumor Clones Using Gene Array and Sequencing Data.

Cancer development is driven by genomic alterations, including copy number aberrations. The detection of copy number aberrations in tumor cells is often complicated by possible contamination of normal stromal cells in tumor samples and intratumor heterogeneity, namely the presence of multiple clones of tumor cells. In order to correctly quantify copy number aberrations, it is critical to successfully de-convolute the complex structure of the genetic information from tumor samples. In this article, we propose a general Bayesian method for estimating copy number aberrations when there are normal cells and potentially more than one tumor clones. Our method provides posterior probabilities for the proportions of tumor clones and normal cells. We incorporate prior information on the distribution of the copy numbers to prioritize biologically more plausible solutions and alleviate possible identifiability issues that have been observed by many researchers. Our model is flexible and can work for both SNP array and next-generation sequencing data. We compare our method to existing ones and illustrate the advantage of our approach in multiple datasets.

Assessment of peak oxygen uptake during handcycling: Test-retest reliability and comparison of a ramp-incremented and perceptually-regulated exercise test.

PURPOSE: To examine the reliability of a perceptually-regulated maximal exercise test (PRETmax) to measure peak oxygen uptake ([Formula: see text]) during handcycle exercise and to compare peak responses to those derived from a ramp-incremented protocol (RAMP). METHODS: Twenty recreationally active individuals (14 male, 6 female) completed four trials across a 2-week period, using a randomised, counterbalanced design. Participants completed two RAMP protocols (20 W·min-1) in week 1, followed by two PRETmax in week 2, or vice versa. The PRETmax comprised five, 2-min stages clamped at Ratings of Perceived Exertion (RPE) 11, 13, 15, 17 and 20. Participants changed power output (PO) as often as required to maintain target RPE. Gas exchange variables (oxygen uptake, carbon dioxide production, minute ventilation), heart rate (HR) and PO were collected throughout. Differentiated RPE were collected at the end of each stage throughout trials. RESULTS: For relative [Formula: see text], coefficient of variation (CV) was equal to 4.1% and 4.8%, with ICC(3,1) of 0.92 and 0.85 for repeated measures from PRETmax and RAMP, respectively. Measurement error was 0.15 L·min-1 and 2.11 ml·kg-1·min-1 in PRETmax and 0.16 L·min-1 and 2.29 ml·kg-1·min-1 during RAMP for determining absolute and relative [Formula: see text], respectively. The difference in [Formula: see text] between PRETmax and RAMP was tending towards statistical significance (26.2 ± 5.1 versus 24.3 ± 4.0 ml·kg-1·min-1, P = 0.055). The 95% LoA were -1.9 ± 4.1 (-9.9 to 6.2) ml·kg-1·min-1. CONCLUSION: The PRETmax can be used as a reliable test to measure [Formula: see text] during handcycle exercise in recreationally active participants. Whilst PRETmax tended towards significantly greater [Formula: see text] values than RAMP, the difference is smaller than measurement error of determining [Formula: see text] from PRETmax and RAMP.

Effects of cooling before and during simulated match play on thermoregulatory responses of athletes with tetraplegia.

OBJECTIVES: Athletes with high level spinal cord injuries (tetraplegia) are under greater thermal strain during exercise than the able-bodied. The purpose of this study was to investigate the effectiveness of pre-cooling using an ice vest and the combination of pre-cooling and cooling during play using water sprays in athletes with tetraplegia. DESIGN: Counter-balanced, cross-over design. METHODS: Eight wheelchair rugby players with tetraplegia completed a 60min intermittent sprint protocol (ISP) on a wheelchair ergometer in 20.2°C±0.2°C and 33.0%±3.1% relative humidity. The ISP was conducted on three occasions; no cooling (NC), pre-cooling with an ice vest (P) and pre-cooling with an ice vest and water sprays between quarters (PW). Gastrointestinal (Tgi) temperature, mean skin temperature (Tsk) and perceptual responses were measured throughout. RESULTS: At the end of pre-cooling, the change in Tgi was not significantly different between conditions (P>0.05) but the change in Tsk was significantly greater in P and PW compared to NC (P<0.001). The change in Tgi over the ISP was significantly lower in PW and P compared to NC (P<0.05), whilst the change in Tsk was lower in PW compared to P and NC (P<0.05). Cooling had no effect on performance or perceptual responses (P>0.05). CONCLUSIONS: Water spraying between quarters combined with pre-cooling using an ice vest lowers thermal strain to a greater degree than pre-cooling only in athletes with tetraplegia, but has no effect on simulated wheelchair rugby performance or perceptual responses.

Salivary alpha amylase not chromogranin A reflects sympathetic activity: exercise responses in elite male wheelchair athletes with or without cervical spinal cord injury.

BACKGROUND: Salivary alpha amylase (sAA) and chromogranin A (sCgA) have both been suggested as non-invasive markers for sympathetic nervous system (SNS) activity. A complete cervical spinal cord injury leading to tetraplegia is accompanied with sympathetic dysfunction; the aim of this study was to establish the exercise response of these markers in this in vivo model. METHODS: Twenty-six elite male wheelchair athletes (C6-C7 tetraplegia: N = 8, T6-L1 paraplegia: N = 10 and non-spinal cord injured controls: N = 8) performed treadmill exercise to exhaustion. Saliva and blood samples were taken pre, post and 30 min post exercise and analysed for sAA, sCgA and plasma adrenaline concentration, respectively. RESULTS: In all three subgroups, sAA and sCgA were elevated post exercise (P < 0.05). Whilst sCgA was not different between subgroups, a group × time interaction for sAA explained the reduced post-exercise sAA activity in tetraplegia (162 ± 127 vs 313 ± 99 (paraplegia) and 328 ± 131 U mL-1 (controls), P = 0.005). The post-exercise increase in adrenaline was not apparent in tetraplegia (P = 0.74). A significant correlation was found between adrenaline and sAA (r = 0.60, P = 0.01), but not between adrenaline and sCgA (r = 0.06, P = 0.79). CONCLUSIONS: The blunted post-exercise rise in sAA and adrenaline in tetraplegia implies that both reflect SNS activity to some degree. It is questionable whether sCgA should be used as a marker for SNS activity, both due to the exercise response which is not different between the subgroups and its non-significant relationship with adrenaline.

Spinal Cord Injury Level Influences Acute Plasma Caffeine Responses.

PURPOSE: This study aimed to investigate the absorption curve and acute effects of caffeine at rest in individuals with no spinal cord injury (SCI), paraplegia (PARA), and tetraplegia (TETRA). METHODS: Twenty-four healthy males (eight able-bodied [AB], eight PARA, and eight TETRA) consumed 3 mg·kg caffeine anhydrous (CAF) in a fasted state. Plasma caffeine [CAF], glucose, lactate, free fatty acid, and catecholamine concentrations were measured during a 150-min rest period. RESULTS: Peak [CAF] was greater in TETRA (21.5 µM) compared with AB (12.2 µM) and PARA (15.1 µM), and mean peak [CAF] occurred at 70, 80, and 80 min, respectively. Moderate and large effect sizes were revealed for TETRA compared with PARA and AB (-0.55 and -1.14, respectively) for the total area under the [CAF] versus time curve. Large interindividual responses were apparent in SCI groups. The change in plasma catecholamine concentrations after CAF did not reach significance (P > 0.05); however, both adrenaline and noradrenaline concentrations were lowest in TETRA. Significant increases in free fatty acid were seen over time (P < 0.0005), but there was no significant influence of SCI level. Blood lactate concentration reduced over time (P = 0.022), whereas blood glucose concentration decreased modestly (P = 0.695), and no difference between groups was seen (P > 0.05). CONCLUSION: The level of SCI influenced the caffeine absorption curve, and there was large interindividual variation within and between groups. Individual curves should be considered when using caffeine as an ergogenic aid in athletes with an SCI. The results indicate TETRA should trial low doses in training and PARA may consider consuming caffeine greater than 60 min before exercise performance. The study also supports caffeine's direct effect on adipose tissue, which is not secondary to catecholamine release.

A Comparison of Speed Profiles During Training and Competition in Elite Wheelchair Rugby Players.

PURPOSE: To investigate the speed profiles of individual training modes in comparison with wheelchair rugby (WCR) competition across player classifications. METHODS: Speed profiles of 15 international WCR players were determined using a radio-frequency-based indoor tracking system. Mean and peak speed (m/s), work:rest ratios, and the relative time spent in (%) and number of high-speed activities performed were measured across training sessions (n = 464) and international competition (n = 34). Training was classified into 1 of 4 modes: conditioning (n = 71), skill-based (n = 133), game-related (n = 151), and game-simulation drills (n = 109). Game-simulation drills were further categorized by the structured duration, which were 3-min game clock (n = 44), 8-min game clock (n = 39), and 10-min running clock (n = 26). Players were grouped by their International Wheelchair Rugby Federation classification as either low-point (≤1.5; n = 8) or high-point players (≥2.0; n = 7). RESULTS: Conditioning drills were shown to exceed the demands of competition, irrespective of classification (P ≤ .005; effect size [ES] = 0.6-2.0). Skill-based and game-related drills underrepresented the speed profiles of competition (P ≤ .005; ES = 0.5-1.1). Mean speed and work:rest ratios were significantly lower during 3- and 8-min game-simulation drills in relation to competition (P ≤ .039; ES = 0.5-0.7). However, no significant differences were identified between the 10-min running clock and competition. CONCLUSIONS: Although game-simulation drills provided the closest representation of competition, the structured duration appeared important since the 10-min running clock increased training specificity. Coaches can therefore modify the desired training response by making subtle changes to the format of game-simulation drills.