No reserve in isokinetic cycling power at intolerance during ramp incremental exercise in endurance-trained men.

During whole-body exercise in health, maximal oxygen uptake (V̇O2max) is typically attained at or immediately prior to the limit of tolerance (LoT). At the V̇O2max and LoT of incremental exercise, a fundamental, but unresolved, question is whether maximal evocable power can increase above the task requirement, i.e. whether there is a "power reserve" at the LoT. Using an instantaneous switch from cadence-independent to isokinetic cycle ergometry, we determined maximal evocable power at the limit of ramp-incremental exercise. We hypothesized that in endurance-trained men at LoT, maximal (4s) isokinetic power would not differ from power required by the task. Baseline isokinetic power at 80rpm (PISO; measured at the pedals) and summed integrated EMG from 5 leg muscles (∑iEMG) were measured in 12 endurance-trained men (V̇O2max=4.2±1.0 l•min(-1)). Participants then completed a ramp-incremental exercise test (20-25W•min(-1)), with instantaneous measurement of PISO and ∑iEMG at the LoT. PISO decreased from 788±103W at baseline to 391±72W at LoT, which was not different from the required ramp-incremental flywheel power (352±58W; p>0.05). At LoT, the relative reduction in PISO was greater than the relative reduction in the isokinetic ∑iEMG (50±9 vs. 63±10% of baseline; p<0.05). During maximal ramp incremental exercise in endurance-trained men, maximum voluntary power is not different from the power required by the task, and is consequent to both central and peripheral limitations in evocable power. The absence of a power reserve suggests both the perceptual and physiological limits of maximum voluntary power production are not widely dissociated at LoT in this population

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Arthritis of the base of the thumb

The purpose of this article is to outline the pathophysiology and epidemiology of arthritis of the base of the thumb. The usual presentation and diagnosis will be discussed along with the current conservative treatment options. Surgical treatment options are determined by the stage of the arthritis as well as the demands of the patient. The current standard surgical treatment options will be reviewed along with their results in the literature

Data collection, handling and fitting strategies to optimize accuracy and precision of oxygen uptake kinetics estimation from breath-by-breath measurements.

Phase 2 pulmonary oxygen uptake kinetics (ϕ2 τVO2P) reflect muscle oxygen consumption dynamics and are sensitive to changes in state of training or health. This study identified an unbiased method for data collection, handling and fitting to optimize VO2P kinetics estimation. A validated computational model of VO2P kinetics and a Monte Carlo approach simulated 2 x 10(5) moderate intensity transitions using a distribution of metabolic and circulatory parameters spanning normal health. Effects of averaging (interpolation, binning, stacking or separate fitting of up to 10 transitions) and fitting procedures (bi-exponential fitting, or ϕ2 isolation by time removal, statistical or derivative methods followed by mono-exponential fitting) on accuracy and precision of ϕ2 τVO2P estimation were assessed. The optimal strategy to maximize accuracy and precision of τVO2P estimation was 1-s interpolation of 4 bouts, ensemble averaged, with the first 20 s of exercise data removed. Contradictory to previous advice, we found optimal fitting procedures removed no more than 20 s of ϕ1 data. Averaging method was less critical: interpolation, bin averaging and stacking gave similar results, each with greater accuracy compared to analyzing repeated bouts separately. The optimal procedure resulted in ϕ2 τVO2P estimates for transitions from an unloaded or loaded baseline that averaged 1.97±2.08 and 1.04±2.30 s from true, but were within 2 s of true in only 47-62% of simulations. Optimized 95% confidence intervals for τVO2P ranged from 4.08-4.51 s, suggesting a minimally important difference of ~5 s to determine significant changes in τVO2P during interventional and comparative studies

Working Together with Conversational Agents: the Relationship of Perceived Cooperation with Service Performance Evaluations

Conversational agents are gradually being deployed by organizations in service settings to communicate with and solve problems together with consumers. The current study investigates how consumers’ perceptions of cooperation with conversational agents in a service context are associated with their perceptions about agents’ anthropomorphism, social presence, the quality of the information provided by an agent, and the agent service performance. An online experiment was conducted in which participants performed a service-oriented task with the assistance of conversational agents developed specifically for the study and evaluated the performance and attributes of the agents. The results suggest a direct positive link between perceiving a conversational agent as cooperative and perceiving it to be more anthropomorphic, with higher levels of social presence and providing better information quality. Moreover, the results also show that the link between perceiving an agent as cooperative and the agent’s service performance is mediated by perceptions of the agent’s anthropomorphic cues and the quality of the information provided by the agent

A Factor Graph Nested Effects Model To Identify Networks from Genetic Perturbations

Complex phenotypes such as the transformation of a normal population of cells into cancerous tissue result from a series of molecular triggers gone awry. We describe a method that searches for a genetic network consistent with expression changes observed under the knock-down of a set of genes that share a common role in the cell, such as a disease phenotype. The method extends the Nested Effects Model of Markowetz et al. (2005) by using a probabilistic factor graph to search for a network representing interactions among these silenced genes. The method also expands the network by attaching new genes at specific downstream points, providing candidates for subsequent perturbations to further characterize the pathway. We investigated an extension provided by the factor graph approach in which the model distinguishes between inhibitory and stimulatory interactions. We found that the extension yielded significant improvements in recovering the structure of simulated and Saccharomyces cerevisae networks. We applied the approach to discover a signaling network among genes involved in a human colon cancer cell invasiveness pathway. The method predicts several genes with new roles in the invasiveness process. We knocked down two genes identified by our approach and found that both knock-downs produce loss of invasive potential in a colon cancer cell line. Nested effects models may be a powerful tool for inferring regulatory connections and genes that operate in normal and disease-related processes

Relationship between cardiac deformation parameters measured by cardiovascular magnetic resonance and aerobic fitness in endurance athletes

Background: Athletic training leads to remodelling of both left and right ventricles with increased myocardial mass and cavity dilatation. Whether changes in cardiac strain parameters occur in response to training is less well established. In this study we investigated the relationship in trained athletes between cardiovascular magnetic resonance (CMR) derived strain parameters of cardiac function and fitness. Methods: 35 endurance athletes and 35 age and sex matched controls underwent CMR at 3.0T including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization (SPAMM). CMR data were analysed quantitatively reporting circumferential strain and torsion from tagged images and left and right ventricular longitudinal strain from feature tracking of cine images. Athletes performed a maximal ramp-incremental exercise test to determine the lactate threshold (LT) and maximal oxygen uptake (V̇O2max). Results: LV circumferential strain at all levels, LV twist and torsion, LV late diastolic longitudinal strain rate, RV peak longitudinal strain and RV early and late diastolic longitudinal strain rate were all lower in athletes than controls. On multivariable linear regression only LV torsion (beta=-0.37, P=0.03) had a significant association with LT. Only RV longitudinal late diastolic strain rate (beta=-0.35, P=0.03) had a significant association with V̇O2max. Conclusions: This cohort of endurance athletes had lower LV circumferential strain, LV torsion and biventricular diastolic strain rates than controls. Increased LT, which is a major determinant of performance in endurance athletes, was associated with decreased LV torsion. Further work is needed to understand the mechanisms by which this occurs

Liver Stiffness Measurement and Biochemical Markers in Senegalese Chronic Hepatitis B Patients with Normal ALT and High Viral Load

Despite the high prevalence of chronic hepatitis B (CHB) in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM) and two biochemical scores (FibroTest®, Fibrometer®) to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10) IU/mL and normal alanine aminotransferase (ALT) values.LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB). Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring.225 patients were evaluated (84% male) and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT), and Fibrometer® (FM) using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis) and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively.In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis

Geographical limits to species-range shifts are suggested by climate velocity

The reorganization of patterns of species diversity driven by anthropogenic climate change, and the consequences for humans, are not yet fully understood or appreciated. Nevertheless, changes in climate conditions are useful for predicting shifts in species distributions at global and local scales. Here we use the velocity of climate change to derive spatial trajectories for climatic niches from 1960 to 2009 (ref. 7) and from 2006 to 2100, and use the properties of these trajectories to infer changes in species distributions. Coastlines act as barriers and locally cooler areas act as attractors for trajectories, creating source and sink areas for local climatic conditions. Climate source areas indicate where locally novel conditions are not connected to areas where similar climates previously occurred, and are thereby inaccessible to climate migrants tracking isotherms: 16% of global surface area for 1960 to 2009, and 34% of ocean for the \u27business as usual\u27 climate scenario (representative concentration pathway (RCP) 8.5)8 representing continued use of fossil fuels without mitigation. Climate sink areas are where climate conditions locally disappear, potentially blocking the movement of climate migrants. Sink areas comprise 1.0% of ocean area and 3.6% of land and are prevalent on coasts and high ground. Using this approach to infer shifts in species distributions gives global and regional maps of the expected direction and rate of shifts of climate migrants, and suggests areas of potential loss of species richness