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Because either trough or peak concentration at 2 h after administration is measured in routine therapeutic drug monitoring for cyclosporine A (CyA), a quantification method with a wide-range calibration curve capable of simultaneously measuring both concentrations is required. We developed a sensitive, wide-range and high-throughput quantification method for CyA in whole blood using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and compared patients' blood CyA levels measured by UPLC-MS/MS and antibody-conjugated magnetic immunoassay (ACMIA). Whole blood samples were prepared by solid-phase extraction using Oasis HLB μElution plate. The UPLC-MS/MS assay showed excellent linearity over a wide calibration range of 5-2500 ng/mL. Within-batch accuracy and precision as well as batch-to-batch accuracy and precision fulfilled the criteria of US Food and Drug Administration guidelines. The blood CyA concentrations measured by the UPLC-MS/MS assay correlated strongly with those measured by ACMIA. A Bland-Altman plot showed a fixed error between CyA concentrations measured by the two methods, and the concentrations measured by the UPLC-MS/MS method were consistently lower than those measured by ACMIA. We have succeeded to develop a sensitive, wide-range and high-throughput quantification method for CyA in whole blood using UPLC-MS/MS.<br /><br /> Patient-specific surgical simulation allows presurgical planning through three-dimensional (3D) visualization and virtual rehearsal. Virtual reality simulation for otologic surgery can be based on high-resolution cone-beam computed tomography (CBCT). This study aimed to evaluate clinicians' experience with patient-specific simulation of mastoid surgery.<br /><br /> Prospective, multi-institutional study. Preoperative temporal bone CBCT scans of patients undergoing cochlear implantation (CI) were retrospectively obtained. Automated processing and segmentation routines were used. Otologic surgeons performed a complete mastoidectomy with facial recess approach on the patient-specific virtual cases in the institution's temporal bone simulator. Participants completed surveys regarding the perceived accuracy and utility of the simulation.<br /><br /> Twenty-two clinical CBCTs were obtained. Four attending otologic surgeons and 5 otolaryngology trainees enrolled in the study. The mean number of simulations completed by each participant was 16.5 (range 3-22). "Overall experience" and "usefulness for presurgical planning" were rated as "good," "very good," or "excellent" in 84.6% and 71.6% of the simulations, respectively. In 10.7% of simulations, the surgeon reported to have gained a significantly greater understanding of the patient's anatomy compared to standard imaging. Participants were able to better appreciate subtle anatomic findings after using the simulator for 60.4% of cases. Variable CBCT acquisition quality was the most reported limitation.<br /><br /> Patient-specific simulation using preoperative CBCT is feasible and may provide valuable insights prior to otologic surgery. Establishing a CBCT acquisition protocol that allows for consistent segmentation will be essential for reliable surgical simulation.<br /><br /> 3 Laryngoscope, 2021.<br /><br />3 Laryngoscope, 2021.Throughout plant evolution the circadian clock has expanded into a complex signaling network, coordinating physiological and metabolic processes with the environment. Early land plants faced new environmental pressures that required energy-demanding stress responses. Integrating abiotic stress response into the circadian system provides control over daily energy expenditure. Here, we describe the evolution of the circadian clock in plants and the limited, yet compelling, evidence for conserved regulation of abiotic stress. The need to introduce abiotic stress tolerance into current crops has expanded research into wild accessions and revealed extensive variation in circadian clock parameters across monocot and eudicot species. We argue that research into the ancestral links between the clock and abiotic stress will benefit crop improvement efforts.<br /><br /> Moderate-to-vigorous physical activity (MVPA) and breaks in sedentary time (BST) have been proposed as viable solutions to improve an older adult's physical independence, whereas sedentary time (ST) has been associated with detrimental effects. We sought to assess the joint effects of ST, BST, and MVPA on the physical independence of older adults and determine whether and to what extent the ST relationship with physical independence is moderated by MVPA and/or BST.<br /><br /> Cross-sectional.<br /><br /> Laboratory of Exercise and Health, Faculty of Human Kinetics.<br /><br /> Older adults (≥65 years old) from the national surveillance system in Portugal (n = 821).<br /><br /> Physical activity and ST were assessed by accelerometry. Physical independence was assessed using a 12-item composite physical function (CPF) questionnaire. Multiple linear regression was used to model the outcomes.<br /><br /> Higher ST was related to lower CPF score (β = -0.01, p &lt; 0.0001), whereas higher MVPA was related to better CPF score (β = 0.02, p &lt; 0.0001). BST was nnce, such that engaging in at least 36 min/day of MVPA may blunt the negative effects of ST. [https://www.selleckchem.com/TGF-beta.html TGF-beta inhibitor] At high levels of MVPA (≥108 min/day), having some ST may actually provide some benefit to an older adult's ability to maintain physical independence.Methane (CH4 ) exchange in tree stems and canopies and the processes involved are among the least understood components of the global CH4 cycle. Recent studies have focused on quantifying tree stems as sources of CH4 and understanding abiotic CH4 emissions in plant canopies, with the role of microbial in situ CH4 formation receiving less attention. Moreover, despite initial reports revealing CH4 consumption, studies have not adequately evaluated the potential of microbial CH4 oxidation within trees. In this paper, we discuss the current level of understanding on these processes. Further, we demonstrate the potential of novel metagenomic tools in revealing the involvement of microbes in the CH4 exchange of plants, and particularly in boreal trees. We detected CH4 -producing methanogens and novel monooxygenases, potentially involved in CH4 consumption, in coniferous plants. In addition, our field flux measurements from Norway spruce (Picea abies) canopies demonstrate both net CH4 emissions and uptake, giving further evidence that both production and consumption are relevant to the net CH4 exchange.