Exploring factors influencing physiotherapists' perceptions of measuring reactive balance following a theory-based multi-component intervention: a qualitative descriptive study.

Purpose: Reactive balance is a critical consideration for mobility and fall avoidance, but is under-assessed among physiotherapists. The objective of this study was to explore factors influencing physiotherapist perceptions about measuring reactive balance upon completion of a 12-month theory-based, multi-component intervention to increase use of a measure of reactive balance.Methods: A qualitative descriptive approach was used. Semi-structured interviews were conducted with 28 physiotherapists treating adults with balance impairment in three urban Canadian rehabilitation hospitals that participated in the intervention. Interviews explored perceptions of reactive balance measurement and perceived changes in clinical behavior. Thematic analysis involved multiple rounds of coding, review and discussion, theme generation, and interpretation of findings through individual analysis and team meetings.Findings: Participants expressed contrasting views about integrating reactive balance measurement in their practice, despite consistent acknowledgement of the importance of reactive balance for function. Three themes were identified highlighting factors that mediated perceptions about measuring reactive balance: patient characteristics; trust between physiotherapist and patient; and the role of physiotherapist fear.Conclusions: The findings highlight that decision making for measuring reactive balance in rehabilitation settings is complex. There is a need for additional work to facilitate long-term implementation of clinical reactive balance measurement, such as refining patient criteria for administration, ensuring sufficient time to establish a trusting relationship, and developing and testing strategies to address physiotherapist fear.IMPLICATIONS FOR REHABILITATIONReactive balance is important for falls prevention and mobility, but is under-assessed among physiotherapists.This study identified three factors that influenced uptake of reactive balance measurement among physiotherapists in rehabilitation settings: patient characteristics; trust between physiotherapist and patient; and the role of physiotherapist fear.Knowledge of the identified factors may assist with design and use of reactive and other balance measurements.Strategies aimed at developing trusting relationships between physiotherapist and patient along with addressing physiotherapist fear could facilitate the uptake of clinical reactive balance measurement.

Correction: Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single-nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes. We demonstrate that one-quarter of non-coding mutations in regions of kataegis outside the Ig loci are located in genes relevant to CLL. We show that non-coding mutations in ATM may negatively impact on ATM expression and find non-coding and regulatory region mutations in TCL1A, and in IgHVunmut CLL in IKZF3, SAMHD1,PAX5 and BIRC3. Finally, we show that IgHVunmut CLL is dominated by coding mutations in driver genes and an aging signature, whereas IgHVmut CLL has a high incidence of promoter and enhancer mutations caused by aberrant activation-induced cytidine deaminase activity. Taken together, our data support the hypothesis that differences in clinical outcome and biological characteristics between the two subgroups might reflect differences in mutation distribution, incidence and distinct underlying mutagenic mechanisms.

Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

This corrects the article DOI: 10.1038/leu.2017.177.

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. METHODS: We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. RESULTS: We found extensive mutational and copy-number heterogeneity within the primary tumour. We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. CONCLUSION: This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success.

Robust calibration transfer in noninvasive ethanol measurements, Part II: Modification of instrument measurements by incorporation of expert knowledge (MIMIK).

Several calibration transfer methods require measurement of a subset of the calibration samples on each future instrument, which is impractical in some applications. Another consideration is that these methods model inter-instrument spectral differences implicitly rather than explicitly. The present work argues that explicit knowledge of the origins of inter-instrument spectral distortions can benefit calibration transfer during the fabrication and assembly of instrumentation, the formation of the multivariate regression, and its subsequent transfer to future instruments. In Part I of this work, a Fourier transform near-infrared system designed to perform noninvasive ethanol measurements was discussed and equations describing the optical distortions caused by self-apodization, retroreflector misalignment, and off-axis detector field of view were provided and examined using laboratory measurements. The spectral distortions were shown to be nonlinear in the amplitude and wavenumber domains, and thus cannot be compensated by simple wavenumber calibration procedures or background correction. Part II presents a calibration transfer method that combines in vivo data with controlled amounts of optical distortions in order to develop a multivariate regression model that is robust to instrument variation. Evaluation of the method using clinical data showed improved measurement accuracy, outlier detection, and generalization to future instruments relative to simple background correction.

Comparison of spectroscopically measured finger and forearm tissue ethanol concentration to blood and breath ethanol measurements.

Previous works investigated a spectroscopic technique that offered a promising alternative to blood and breath assays for determining in vivo alcohol concentration. Although these prior works measured the dorsal forearm, we report the results of a 26-subject clinical study designed to evaluate the spectroscopic technique at a finger measurement site through comparison to contemporaneous forearm spectroscopic, venous blood, and breath measurements. Through both Monte Carlo simulation and experimental data, it is shown that tissue optical probe design has a substantial impact on the effective path-length of photons through the skin and the signal-to-noise ratio of the spectroscopic measurements. Comparison of the breath, blood, and tissue assays demonstrated significant differences in alcohol concentration that are attributable to both assay accuracy and alcohol pharmacokinetics. Similar to past works, a first order kinetic model is used to estimate the fraction of concentration variance explained by alcohol pharmacokinetics (72.6-86.7%). A significant outcome of this work was significantly improved pharmacokinetic agreement with breath (arterial) alcohol of the finger measurement (mean k(Art-Fin) = 0.111 min(-1)) relative to the forearm measurement (mean k(Art-For) = 0.019 min(-1)) that is likely due to the increased blood perfusion of the finger.

Phase II study of short-course capecitabine plus oxaliplatin (XELOX) followed by maintenance capecitabine in advanced colorectal cancer: XelQuali study.

PURPOSE: To evaluate the efficacy, safety and quality of life of a short course of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in patients with previously untreated, inoperable, metastatic colorectal cancer. METHODS: Patients received intravenous oxaliplatin 130 mg/m(2) on d1 plus oral capecitabine 1,000 mg/m(2) twice daily (bid) on d1-14 every 21 days for four cycles. Patients achieving stable disease (SD) or better than received capecitabine 1,250 mg/m(2) bid on d1-14 every 21 days until disease progression. The primary endpoint was progression-free survival (PFS). RESULTS: Overall, 21/45 (47%) of patients responded to the initial XELOX chemotherapy whilst SD or better was documented in 76%. Median PFS was 6.7 (95% CI 5.7-9.6) months, and median overall survival (OS) was 20.5 (95% CI 13.1-28.1) months. In the 34 patients who then received capecitabine maintenance therapy, the median PFS was 8.1 (95% CI 6.2-11.8) months and median OS was 23.1 (95% CI 17.8-28.5) months. A marked reduction in the vast majority of all grades of adverse event occurred on switching from initial XELOX to maintenance capecitabine chemotherapy including grades 1-2 (77 vs. 47%) and grade 3 (7 vs. 3%) neuropathy, diarrhoea and lethargy. CONCLUSIONS: Short-course XELOX followed by capecitabine maintenance therapy provides an active and well-tolerated treatment option for patients with previously untreated metastatic colorectal cancer. A median OS of more than 20 months is promising and by limiting the number of oxaliplatin infusions, this approach minimises the risk of unwanted cumulative neurotoxicity, is cheaper and more convenient for both patients and healthcare providers.

Comparison of spectroscopically measured tissue alcohol concentration to blood and breath alcohol measurements.

Alcohol testing is an expanding area of interest due to the impacts of alcohol abuse that extend well beyond drunk driving. However, existing approaches such as blood and urine assays are hampered in some testing environments by biohazard risks. A noninvasive, in vivo spectroscopic technique offers a promising alternative, as no body fluids are required. The purpose of this work is to report the results of a 36-subject clinical study designed to characterize tissue alcohol measured using near-infrared spectroscopy relative to venous blood, capillary blood, and breath alcohol. Comparison of blood and breath alcohol concentrations demonstrated significant differences in alcohol concentration [root mean square of 9.0 to 13.5 mg/dL] that were attributable to both assay accuracy and precision as well as alcohol pharmacokinetics. A first-order kinetic model was used to estimate the contribution of alcohol pharmacokinetics to the differences in concentration observed between the blood, breath, and tissue assays. All pair-wise combinations of alcohol assays were investigated, and the fraction of the alcohol concentration variance explained by pharmacokinetics ranged from 41.0% to 83.5%. Accounting for pharmacokinetic concentration differences, the accuracy and precision of the spectroscopic tissue assay were found to be comparable to those of the blood and breath assays.

Physiological differences between cycling and running: lessons from triathletes.

The purpose of this review was to provide a synopsis of the literature concerning the physiological differences between cycling and running. By comparing physiological variables such as maximal oxygen consumption (V O(2max)), anaerobic threshold (AT), heart rate, economy or delta efficiency measured in cycling and running in triathletes, runners or cyclists, this review aims to identify the effects of exercise modality on the underlying mechanisms (ventilatory responses, blood flow, muscle oxidative capacity, peripheral innervation and neuromuscular fatigue) of adaptation. The majority of studies indicate that runners achieve a higher V O(2max) on treadmill whereas cyclists can achieve a V O(2max) value in cycle ergometry similar to that in treadmill running. Hence, V O(2max) is specific to the exercise modality. In addition, the muscles adapt specifically to a given exercise task over a period of time, resulting in an improvement in submaximal physiological variables such as the ventilatory threshold, in some cases without a change in V O(2max). However, this effect is probably larger in cycling than in running. At the same time, skill influencing motor unit recruitment patterns is an important influence on the anaerobic threshold in cycling. Furthermore, it is likely that there is more physiological training transfer from running to cycling than vice versa. In triathletes, there is generally no difference in V O(2max) measured in cycle ergometry and treadmill running. The data concerning the anaerobic threshold in cycling and running in triathletes are conflicting. This is likely to be due to a combination of actual training load and prior training history in each discipline. The mechanisms surrounding the differences in the AT together with V O(2max) in cycling and running are not largely understood but are probably due to the relative adaptation of cardiac output influencing V O(2max) and also the recruitment of muscle mass in combination with the oxidative capacity of this mass influencing the AT. Several other physiological differences between cycling and running are addressed: heart rate is different between the two activities both for maximal and submaximal intensities. The delta efficiency is higher in running. Ventilation is more impaired in cycling than in running. It has also been shown that pedalling cadence affects the metabolic responses during cycling but also during a subsequent running bout. However, the optimal cadence is still debated. Central fatigue and decrease in maximal strength are more important after prolonged exercise in running than in cycling.

Opera and madness: Britten's Peter Grimes--a case study.

In this paper, Britten's opera Peter Grimes (1945) is used as an illustrative case study through which to examine the depiction of psychiatric disorders in opera. It is argued that Peter Grimes is a powerful example of how opera, in the hands of a great composer, can become an invaluable tool for examining subjective human experience. After a brief discussion of opera as a vehicle to express emotions, various operas are drawn upon to provide a historical perspective and to demonstrate the long interconnection existing between opera and madness. An in-depth analysis of Peter Grimes, its background and central character, is then provided, in order to demonstrate how opera can elicit empathy for individuals affected by mental health problems.

The effects of caffeine ingestion on time trial cycling performance.

AIM: The purpose of this work was to determine the effects of caffeine ingestion on cycling time trial (TT) performance in well trained male subjects. METHODS: Eight males, with the following physical characteristics (Mean +/- SD) age 30.2+/-10.1 years, height 180.3+/-7.1 cm, mass 70.4+/-5.1 kg, VO2max 63.6+/-4.4 mL.kg(-1).min(-1) undertook three 1 h TT performances on a VelotronPro cycle ergometer, in a double blind, random fashion. The trials were Control (C), Placebo (Pl) and Caffeine (CAF). The CAF and Pl were given 60 min prior to exercise in a dose of 6 mg.kg(-1) body mass. Prior to ingestion, 60 min post ingestion, and at the end of the TT, subjects gave 10 mL of venous blood which was analysed for lactate, glucose, and free fatty acids. Expired air was collected throughout each test by indirect calorimetry. RESULTS: The cyclists rode significantly further in CAF trial (28.11+/-1.32 km) than they did in the C (26.69+/-1.5 km, P < 0.03) or Pl (27.0+/-1.5 km, P < 0.03) trials. No significant differences were seen between C and Pl trials (P > 0.88). No differences between C and Pl were seen in heart rate data throughout the TT (p > 0.05). The free fatty acid (FFA) concentrations were significantly higher in the CAF trials both post ingestion (P < 0.005) and post exercise (P < 0.0001) than either C or Pl trials. CONCLUSION: We concluded that performance was improved possibly based upon a greater reliance on fat metabolism, as indicated by increased FFA and a lower respiratory exchange ratio (RER).

The effects of caffeine ingestion on time trial cycling performance.

PURPOSE: The purpose of this work was to determine the effects of caffeine on high intensity time trial (TT) cycling performance in well-trained subjects. SUBJECTS: Six male cyclists with the following physical characteristics (mean +/- SD) age 30.7 +/- 12, height 179.3 +/- 7.5 cm, mass 70.0 +/- 7.5 kg, VO2max 65.0 +/- 6.3 mL.kg-1.min-1 undertook three 1-h TT performances, control (C), placebo (P) and caffeine (CAF), on a Velotron cycle ergometer conducted in a double-blind, random fashion. Subjects rested for 60 min and were then given CAF or P in a dose of 6 mg.kg-1 body mass and then commenced exercise after another 60 min of rest. Before ingestion, 60 min postingestion, and at the end of the TT, finger-prick blood samples were analyzed for lactate. RESULTS: The cyclists rode significantly further in the CAF trial (28.0 +/- 1.3 km) than they did in the C (26.3 +/- 1.5 km, P < .01) or P (26.4 +/- 1.5 km, P < .02) trials. No differences were seen in heart rate data throughout the TT (P > .05). Blood lactate levels were significantly higher at the end of the trials than either at rest or postingestion (P < .0001), but there were no differences between the three trial groups. CONCLUSION: On the basis of the data, we concluded that performance was improved with the use of a caffeine supplement.

Four weeks one-leg training and high fat diet does not alter PPARalpha protein or mRNA expression in human skeletal muscle.

UNLABELLED: Fatty acid metabolism is influenced by training and diet with exercise training mediating this through activation of nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha) in skeletal muscle. This study investigated the effect of training and high fat or normal diet on PPARalpha expression in human skeletal muscle. Thirteen men trained one leg (T) four weeks (31.5 h in total), while the other leg (UT) served as control. During the 4 weeks six subjects consumed high fat (FAT) diet and seven subjects maintained a normal (CHO) diet. Biopsies were obtained from vastus lateralis muscle in both legs before and after training. After the biopsy, one-leg extension exercise was performed in random order with both legs 30 min at 95% of workload max. A training effect was evident as citrate synthase activity increased (P < 0.05) by 15% in the trained, but not the control leg in both groups. During exercise respiratory exchange ratio was lower in FAT (0.86 +/- 0.01, 0.83 +/- 0.01, mean +/- SEM) than CHO (0.96 +/- 0.02, 0.94 +/- 0.03) and in UT than T legs, respectively. The PPARalpha protein (144 +/- 44, 104 +/- 28, 79 +/- 15, 79 +/- 14, % of pre level) and PPARalpha mRNA (69 +/- [2, 2], 78 +/- [7, 6], 92 +/- [22, 18], 106 +/- [21, 18], % of pre level, geometric mean +/- SEM) expression remained unchanged by diet and training in FAT (UT, T) and CHO (UT, T), respectively. After the training and diet CS, HAD, PPARalpha, UCP2, UCP3 and mFABP mRNA content remained unchanged, whereas GLUT4 mRNA was lower in both groups and LDHA mRNA was lower (P < 0.05) only in FAT. IN CONCLUSION: 4 weeks one leg knee extensor training did not affect PPARalpha protein or mRNA expression. Furthermore, higher fat oxidation during exercise after fat rich diet was not accompanied by an increased PPARalpha protein or mRNA expression after 4 weeks.

The effects of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performance in trained male subjects.

AIM: The aim of this work was to determine the ergogenic effects of a nucleotide supplement on the metabolic and immune responses to short term high intensity exercise in volunteer, trained, male subjects. METHODS: Thirty moderately trained male subjects were randomly divided into 3 equal sized groups, control (C), placebo (P) or experimental (E). Each subject undertook a 2 min maximal exercise test prior to, and after 60 days, on either a nucleotide (E) or placebo supplement. Prior to exercise testing unstimulated saliva samples and blood samples were taken. Saliva was analysed for cortisol and IgA, while blood was analysed for lactate, lactate dehydrogenase and creatine kinase. RESULTS: The postexercise C value was significantly higher than the pre-exercise concentration (P<0.0001; for C, P, and E). In the postsupplement C analysis, the E postexercise group was significantly lower than either the C (P<0.005) or the P group (P<0.05). In the pre- and postsupplementation periods, the pre-exercise SIgA values were significantly higher than the postexercise values (P<0.0001). However, in the postsupplementation period, the SIgA value in the E group was significantly higher than either the P (P<0.05) or C (P<0.05) groups. There were no significant changes in blood lactate, lactate dehydrogenase, or creatine kinase concentrations post supplementation. CONCLUSIONS: We concluded that a chronically ingested nucleotide supplement blunts the response of the hormones associated with physiological stress.

Arthritic pain is processed in brain areas concerned with emotions and fear.

OBJECTIVE: Functional neuroimaging studies have shown that experimentally induced acute pain is processed within at least 2 parallel networks of brain structures collectively known as the pain matrix. The relevance of this finding to clinical pain is not known, because no direct comparisons of experimental and clinical pain have been performed in the same group of patients. The aim of this study was to compare directly the brain areas involved in processing arthritic pain and experimental pain in a group of patients with osteoarthritis (OA). METHODS: Twelve patients with knee OA underwent positron emission tomography of the brain, using (18)F-fluorodeoxyglucose (FDG). Scanning was performed during 3 different pain states: arthritic knee pain, experimental knee pain, and pain-free. Significant differences in the neuronal uptake of FDG between different pain states were investigated using statistical parametric mapping software. RESULTS: Both pain conditions activated the pain matrix, but arthritic pain was associated with increased activity in the cingulate cortex, the thalamus, and the amygdala; these areas are involved in the processing of fear, emotions, and in aversive conditioning. CONCLUSION: Our results suggest that studies of experimental pain provide a relevant but quantitatively incomplete picture of brain activity during arthritic pain. The search for new analgesics for arthritis that act on the brain should focus on drugs that modify this circuitry.

Implantation of pure cultured olfactory ensheathing cells in an animal model of parkinsonism.

BACKGROUND: Implantation of neural cells has been proposed as a therapeutic strategy for repairing the injured or diseased brain. In the present study we have examined the potential of olfactory ensheathing cells (OEC) to promote brain repair after surgical implantation in a rodent model of parkinsonism. METHODS: Neonatal OECs were implanted in the striatum after a 6-hydroxydopamine lesion of the ipsilateral substantia nigra. Amphetamine-induced rotational asymmetry scores were determined 48 hours before and 4, 6 and 8 weeks after OEC implantation. The density of immunostaining for tyrosine hydroxylase and synaptophysin in the striatum and the number of tyrosine hydroxylase-positive cells remaining in the substantia nigra were also determined. RESULTS: Rotational asymmetry scores were similar in OEC-implanted and vehicle-treated groups at all time points examined, and at each time were similar to those observed prior to implantation. Levels of striatal tyrosine-hydroxylase and synaptophysin immunoreactivity were similar in OEC- and vehicle-treated groups. The number of tyrosine-hydroxylase-positive cells in the substantia nigra was similar in both groups indicating that severity of the lesion was similar. Visualisation of GFP-labelled OECs one week after implantation in a separate group of animals revealed the cells to be located in the area immediately surrounding the needle tract. CONCLUSION: This study demonstrates that implantation of OECs alone is not sufficient to promote tissue repair and functional recovery in a rodent model of parkinsonism. The results add to a growing number of studies that propose a caveat for the use of pure OECs as a neurosurgical strategy for the treatment of brain disease or injury.

Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both: randomised trial.

OBJECTIVE: To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both. DESIGN: Multicentre, prospective, randomised study with follow-up for one year. SETTING: 46 hospitals in United Kingdom. PARTICIPANTS: Patients aged > or =18 with deep vein thrombosis or pulmonary embolism, or both. INTERVENTIONS: Three (n=369) or six months (n=380) of anticoagulation with heparin for five days accompanied and followed by warfarin, with a target international normalised ratio of 2.0-3.5. MAIN OUTCOME MEASURES: Death from deep vein thrombosis or pulmonary embolism; failure to resolve, extension, recurrence of during treatment; recurrence after treatment; and major haemorrhage during treatment. RESULTS: In the patients allocated to three months' treatment two died from deep vein thrombosis or pulmonary embolism during or after treatment, compared with three in the six month group. During treatment deep vein thrombosis or pulmonary embolism failed to resolve, extended, or recurred in six patients in the three month group without fatal consequences, compared with 10 in the six month group. After treatment there were 23 non-fatal recurrences in the three month group and 16 in the six month group. Fatal and non-fatal deep vein thrombosis or pulmonary embolism during treatment, and after treatment thus occurred in 31(8%) of those who had received three months' anticoagulation compared with 29 (8%) of those who had received six months' (P=0.80, 95% confidence interval for difference -3.1% to 4.7%). There were no fatal haemorrhages during treatment but there were eight major haemorrhages in those treated for six months and none in those treated for three months (P=0.008, -3.5% to -0.7%). Thus 31 (8%) of the patients receiving three months' anticoagulation experienced adverse outcomes as a result of deep vein thrombosis or pulmonary embolism or its treatment compared with 35 (9%) of those receiving six months' (P=0.79, -4.9% to 3.2%). CONCLUSION: For patients in the UK with deep vein thrombosis or pulmonary embolism and no known risk factors for recurrence, there seems to be little, if any, advantage in increasing the duration of anticoagulation from three to six months. Any possible advantage would be small and would need to be judged against the increased risk of haemorrhage associated with the longer duration of treatment with warfarin. TRIAL REGISTRATION: Clinical Trials NCT00365950 [ClinicalTrials.gov].

Lactate threshold does not influence metabolic responses during exercise in cyclists.

The purpose of this study was to compare plasma markers of metabolic stress and other physiological parameters during prolonged endurance exercise of different intensity in trained subjects possessing a "high" or "low" lactate threshold (LT) expressed as a percentage (%) of peak power output (PPO). Fifteen trained male cyclists completed an incremental exercise test for determination of PPO and the LT (% PPO). Each subject then completed a 90-min and 20-min exercise trial at an intensity representing 75 and 85 % of PPO, respectively. Blood lactate (La), as well as plasma hypoxanthine (Hx) and uric acid (UA) were measured during each exercise trial. The responses in two groups, one (n = 8) with a LT approximately 65 % PPO (LT (low)), the other group (n = 7) with a LT approximately 75 % (LT (high)) (p < 0.01), were then compared. With the exception of UA, La and Hx increased significantly (p < 0.01) throughout each exercise trial compared to rest. However, there were no significant differences in each trial between the two groups of cyclists. There were also no significant differences in the other physiological parameters in each exercise trial between the subjects in LT (low) and LT (high). This study demonstrates that in trained cyclists homogeneous in terms of PPO, plasma markers of metabolic demand during prolonged exercise are not influenced by the LT when measured in an incremental exercise test.