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KGaA, Weinheim.PURPOSE Single-leg cycling exercise is one of the most potent, but underutilized, stimuli for promoting peripheral muscle respiratory capacity. Special ergometers used to facilitate single-leg cycling, while maintaining biomechanics similar to double-leg cycling, are not widely available. This lack of availability of specialized ergometers may explain why single-leg cycling has not been widely implemented as standard clinical practice. Therefore, we explored the extent to which participants could emphasize one leg and de-emphasize the other to perform “single-leg emphasis cycling” using standard cycle ergometers. METHODS Sixteen athletic participants performed single-leg emphasis cycling, emphasizing each leg in separate trials, and double-leg cycling. Pedal forces and limb kinematics were collected and used to calculate joint-specific work and power at the ankle, knee, and hip. RESULTS Study participants were able to produce approximately three times as much power with their emphasized leg compared to the de-emphasized leg during single-leg emphasis cycling. Ankle plantar flexion, dorsiflexion, knee extension, and hip extension work produced during single-leg emphasis cycling did not differ from those during double-leg cycling (all P > .60). Hip and knee flexion work during single-leg emphasis cycling exhibited small but significant differences (both P  less then  .05) from double-leg cycling. CONCLUSIONS These results demonstrate that single-leg emphasis cycling provides a convenient alternative to single-leg cycling requiring specialized ergometers, therefore, facilitating improved training in clinical and athletic populations using commonly available equipment. Further, biomechanics during single-leg emphasis cycling closely approximated double-leg cycling ensuring that training adaptations are highly applicable to double-leg cycling. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.AIMS To characterize the pharmacokinetics (PK) of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin, in adults with relapsed or refractory hairy cell leukaemia, we examined data from a phase 1 study (Study 1001; n = 49) and from the pivotal clinical study (Study 1053; n = 74). METHODS Data from both studies were pooled (n = 123) to develop a population PK model. Covariates included demographics, disease state, liver and kidney function, prior treatment, and antidrug antibodies (ADAs). Exposure-response and exposure-safety were analysed separately by study. A 1-compartment model with linear elimination from the central compartment and 2 clearance (CL) rates was developed. RESULTS Moxetumomab pasudotox was cleared more rapidly after cycle 1, day 1 (CL1 = 24.7 L/h) than subsequently (CL2 = 3.76 L/h), with high interindividual variability (116 and 109%, respectively). In Study 1053, patients with ADA titres >10 240 showed ~4-fold increase in CL. Higher exposures (≥median) were related to higher response rates, capillary leak syndrome and increased creatinine (Study 1053 only), or grade ≥3 adverse events (Study 1001 only). Clinical benefits were still observed in patients with lower exposure or high ADA titres. CONCLUSION Despite a high incidence of immunogenicity with increased clearance, moxetumomab pasudotox demonstrated efficacy in hairy cell leukaemia. © 2020 The British Pharmacological Society.PURPOSE Physical preparation of competitive surfers includes substantial dry-land training. It is currently unknown, however, how closely these exercises replicate surfing maneuvers performed in the ocean. This study compared the technique features displayed by surfers when landing simulated aerial maneuvers on land to critical features previously established as necessary for surfers to successfully land aerials in the ocean during competition. METHODS Fourteen competitive surfers (age 20.6 ± 5.7 years, height 178.1 ± 9.50 cm, mass 70.6 ± 10.8 kg) were recruited to perform two variations of a simulated aerial task, a Frontside Air (FA) and Frontside Air Reverse (FAR). Joint ranges of motion (ROM), center of pressure, and apparent gaze data were collected during the landing event. Paired t tests or Wilcoxon signed-rank tests were used to identify any significant differences in the outcome variables between the two aerial tasks. RESULTS Participants displayed 100% and 60% of the critical features associated with successfully landing a FA and FAR, respectively. In both the simulated FA and FAR, participants landed in 1.0-3.7° of dorsiflexion, moving through significantly less ankle joint ROM in the lead limb during the FAR (P  less then  .01). Participants also displayed significantly less knee and hip ROM (P = .002-.048) while landing the FAR compared to the FA. CONCLUSION The simulated FA and FAR tasks are appropriate training tools for surfers to replicate most of the critical features that a surfer should display to successfully land aerial maneuvers in the ocean. These tasks therefore enable surfers to practice these complex movements in a controlled environment. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Wastewater treatment plants (WWTPs) are an important source of mercury (Hg) to surface waters, but little is known about temporal variability of efflux to aquatic systems. We found that Hg concentrations in effluent varied by about a factor of two on monthly, weekly, and hourly time scale comparisons. These results suggest that limited sampling can yield a representative concentration with reasonable uncertainty for purposes of estimating environmental significance of Hg from WWTPs. This article is protected by copyright. find more All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVE Inadequate sleep contributes to several adverse systemic health outcomes due to hormonal and metabolic disorders. The purpose of this study was to determine the effect of bedtime on the development of dental caries and the relationship with salivary ghrelin and leptin in a prospective cohort study of Kuwaiti children. METHODS Data were collected from 5456 10-year-old children in 2012 and repeated in 2014. We selected children from 138 middle schools representing the six governorates of Kuwait. We derived data from oral examinations, self-reported sleep interviews, body and weight measurements, and chemical analysis of whole saliva samples. Leptin and ghrelin were determined by salivary assay in a subset of 744. Two separate analyses were performed. a) Using the entire longitudinal data set (n = 5456), multilevel random intercept analysis was conducted to assess the relationship between reported bedtime and dental caries. b) Using data from a subset of the original sample (n = 744), multiple linear regression analysis was conducted to determine the relationship between dental caries and salivary ghrelin and leptin.