The Influence of Sonographer Experience on Skeletal Muscle Image Acquisition and Analysis

The amount of experience with ultrasonography may influence measurement outcomes while images are acquired or analyzed. The purpose of this study was to identify the interrater reliability of ultrasound image acquisition and image analysis between experienced and novice sonographers and image analysts, respectively. Following a brief hands-on training session (2 h), the experienced and novice sonographers and analysts independently performed image acquisition and analyses on the biceps brachii, vastus lateralis, and medial gastrocnemius in a sample of healthy participants (n = 17). Test–retest reliability statistics were computed for muscle thickness (transverse and sagittal planes), muscle cross-sectional area, echo intensity and subcutaneous adipose tissue thickness. The results show that image analysis experience generally has a greater impact on measurement outcomes than image acquisition experience. Interrater reliability for measurements of muscle size during image acquisition was generally good–excellent (ICC2,1: 0.82–0.98), but poor–moderate for echo intensity (ICC2,1: 0.43–0.77). For image analyses, interrater reliability for measurements of muscle size for the vastus lateralis and biceps brachii was poor–moderate (ICC2,1: 0.48–0.70), but excellent for echo intensity (ICC2,1: 0.90–0.98). Our findings have important implications for laboratories and clinics where members possess varying levels of ultrasound experience

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

The Influence of Sonographer Experience on Skeletal Muscle Image Acquisition and Analysis

The amount of experience with ultrasonography may influence measurement outcomes while images are acquired or analyzed. The purpose of this study was to identify the interrater reliability of ultrasound image acquisition and image analysis between experienced and novice sonographers and image analysts, respectively. Following a brief hands-on training session (2 h), the experienced and novice sonographers and analysts independently performed image acquisition and analyses on the biceps brachii, vastus lateralis, and medial gastrocnemius in a sample of healthy participants (n = 17). Test–retest reliability statistics were computed for muscle thickness (transverse and sagittal planes), muscle cross-sectional area, echo intensity and subcutaneous adipose tissue thickness. The results show that image analysis experience generally has a greater impact on measurement outcomes than image acquisition experience. Interrater reliability for measurements of muscle size during image acquisition was generally good–excellent (ICC2,1: 0.82–0.98), but poor–moderate for echo intensity (ICC2,1: 0.43–0.77). For image analyses, interrater reliability for measurements of muscle size for the vastus lateralis and biceps brachii was poor–moderate (ICC2,1: 0.48–0.70), but excellent for echo intensity (ICC2,1: 0.90–0.98). Our findings have important implications for laboratories and clinics where members possess varying levels of ultrasound experience

The effects of resistance training to near failure on strength, hypertrophy, and motor unit adaptations in previously trained adults

Abstract Limited research exists examining how resistance training to failure affects applied outcomes and single motor unit characteristics in previously trained individuals. Herein, resistance‐trained adults (24 ± 3 years old, self‐reported resistance training experience was 6 ± 4 years, 11 men and 8 women) were randomly assigned to either a low‐repetitions‐in‐reserve (RIR; i.e., training near failure, n = 10) or high‐RIR (i.e., not training near failure, n = 9) group. All participants implemented progressive overload during 5 weeks where low‐RIR performed squat, bench press, and deadlift twice weekly and were instructed to end each training set with 0–1 RIR. high‐RIR performed identical training except for being instructed to maintain 4–6 RIR after each set. During week 6, participants performed a reduced volume‐load. The following were assessed prior to and following the intervention: (i) vastus lateralis (VL) muscle cross‐sectional area (mCSA) at multiple sites; (ii) squat, bench press, and deadlift one‐repetition maximums (1RMs); and (iii) maximal isometric knee extensor torque and VL motor unit firing rates during an 80% maximal voluntary contraction. Although RIR was lower in the low‐ versus high‐RIR group during the intervention (p < 0.001), total training volume did not significantly differ between groups (p = 0.222). There were main effects of time for squat, bench press, and deadlift 1RMs (all p‐values < 0.05), but no significant condition × time interactions existed for these or proximal/middle/distal VL mCSA data. There were significant interactions for the slope and y‐intercept of the motor unit mean firing rate versus recruitment threshold relationship. Post hoc analyses indicated low‐RIR group slope values decreased and y‐intercept values increased after training suggesting low‐RIR training increased lower‐threshold motor unit firing rates. This study provides insight into how resistance training in proximity to failure affects strength, hypertrophy, and single motor unit characteristics, and may inform those who aim to program for resistance‐trained individuals

Perspectives on ENCODE

The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.11Nsciescopu

Membrane protein structure, function, and dynamics: a perspective from experiments and theory

Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.JTD, IA, and MR used the computational resources of the Modeling Facility of the Department of Chemistry, University of California Irvine funded by NSF Grant CHE-0840513 for this work. A-NB was supported in part by the Marie Curie International Reintegration Award IRG-26920.TWA was supported by ARC DP120103548, NSF MCB1052477, DE Shaw Anton (PSCA00061P; NRBSC, through NIH RC2GM093307), VLSCI (VR0200), and NCI (dd7). BA and SV acknowledge the support by ERC advanced Grant No. 268888. ZC and PG would like to acknowledge Reference Framework (NSRF) 2011–2013, National Action ‘‘Cooperation,’’ under grant entitled ‘‘Magnetic Nanoparticles for targeted MRI therapy (NANOTHER),’’ with code ‘‘11RYM-1-1799.’’ The program is cofunded by the European Regional Development Fund and national resources. Part of the calculations presented herein were performed using resources of the LinkSCEEM-2 project, funded by the EC under FP7 through Capacities Research Infrastructure, INFRA-2010-1.2.3 Virtual Research Communities, Combination of Collaborative Project and Coordination and Support Actions (CPCSA) under Grant agreement no. RI-261600. GB was supported in part by NSF grant MCB1330728 from the National Science Foundation and Grant PO1GM55876-14A1 from the National Institutes of Health. LD received funding from EU FP7 (PIOF-GA-2012-329534). LD, and MLK used the computational resources of Temple University, supported by the National Science Foundation through major research instrumentation grant number CNS-09-58854. JS acknowledges support from the Instituto de Salud Carlos III FEDER (CP12/03139